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Coronary artery calcification (CAC) is a well-known marker of subclinical coronary atherosclerosis, which is always detectable in non ECG-gated routine chest CT examinations, and its visual estimation is correlated to clinical outcomes. Agatston scoring is not routinely performed on these examinations. We sought to validate a visual scoring scheme we derived against ECG-gated CT’s and compare our system with another previously published visual scoring scheme in a different cohort of lung cancer screening participants. 50 COPDGene participants received, regular dose full inspiration (non-gated high mA), and low dose expiration CT (non-gated low mA) and ECG-gated CT’s at the same time. CAC was visually scored by 3 readers using our total visual scoring (TVS) method and compared to the Agatston score. The second portion of the study involved visual and Agatston scoring of a larger sample of 198 lung cancer screening patients, comparing visual scoring described by Shemesh et. al. and our TVS method. For the COPDGene participants, scores were highly correlated among readers (all ICC≥0.92), between the ECG-gated CT, non-gated high mA CT, and the non-gated low dose CT (all p

PURPOSE This study aimed to determine if a single-source rapid kilovolt (peak)-switching dual-energy (RSDE) multidetector computed tomography (CT) can differentiate high lipid content (HLC) from low lipid content (LLC) incidental adrenal lesions. METHODS A retrospective intrapatient study of 40 consecutive adults with known hepatic or pancreatic pathology who underwent multiphasic abdominal RSDE for nonadrenal-related clinical indications and had adrenal lesions was done. Arterial phase was acquired with RSDE, conventional unenhanced (CU) images with standard MDCT. RSDE measurements included lesion attenuation in Hounsfield units on simulated monochromatic 140-keV images and density (in milligrams per milliliter) on material decomposition images, using water-iodine and fat-iodine basis pairs. Each variable was correlated with CU Hounsfield units (Pearson coefficient). RSDE lesion values were compared with analysis of variance and Tukey HSD test. Receiver operating characteristic (ROC) analysis was performed to identify RSDE thresholds comparable to 10 HU on unenhanced MDCT. RESULTS Twenty-nine HLC and 18 LLC lesions were evaluated in 40 subjects (21 men; mean age, 66.5 years). RSDE variables correlated with CU Hounsfield units, r = 0.90-0.92, P < 0.001. Myelolipomas, HLC, and LLC lesions were different by analysis of variance, P < 0.001 for all dual-energy variables. Excluding myelolipomas from ROC curve analysis, ROC areas for Hounsfield unit 140-keV images, fat(-iodine), and water(-iodine) were 0.929 (0.039), 0.917 (0.046), and 0.912 (0.048), respectively (P < 0.001); using a specificity of 94.4%, 64% of adenomatous lesions had 140 keV values of less than 9.5 HU, 59% had fat(-iodine) values of less than 987 mg/mL, and 50% had water(-iodine) values of less than 994 mg/mL. CONCLUSIONS There is a strong correlation between RSDE measures and accepted MDCT attenuation values for HLC and LLC adrenal lesions. In some patients undergoing postcontrast RSDE who are found to have incidental adrenal nodules, further unenhanced CT or adrenal-protocol CT or magnetic resonance imaging may not be necessary.

An electrohydraulic lithotripter has been designed that mimics the behavior of the Dornier HM3 extracorporeal shock wave lithotripter. The key mechanical and electrical properties of a clinical HM3 were measured and a design implemented to replicate these parameters. Three research lithotripters have been constructed on this design and are being used in a multi-institutional, multidisciplinary research program to determine the physical mechanisms of stone fragmentation and tissue damage in shock wave lithotripsy. The acoustic fields of the three research lithotripters and of two clinical Dornier HM3 lithotripters were measured with a PVDF membrane hydrophone. The peak positive pressure, peak negative pressure, pulse duration, and shock rise time of the focal waveforms were compared. Peak positive pressures varied from 25 MPa at a voltage setting of 12 kV to 40 MPa at 24 kV. The magnitude of the peak negative pressure varied from -7 to -12 MPa over the same voltage range. The spatial variations of the peak positive pressure and peak negative pressure were also compared. The focal region, as defined by the full width half maximum of the peak positive pressure, was 60 mm long in the axial direction and 10 mm wide in the lateral direction. The performance of the research lithotripters was found to be consistent at clinical firing rates (up to 3 Hz). The results indicated that pressure fields in the research lithotripters are equivalent to those generated by a clinical HM3 lithotripter. © 2000 American Institute of Physics.

To measure reader variability related to the evaluation of screening chest radiographs (CXRs) for findings of primary lung cancer.From the National Lung Screening Trial (NLST), 100 cases were randomly selected from baseline CXR examinations for retrospective interpretation by 9 NLST radiologists; images with noncalcified lung nodules (NCNs) or other abnormalities suspicious for lung cancer as determined by the original NLST reader were oversampled. Agreement on the presence of pulmonary nodules and abnormalities suspicious for cancer and recommendations for follow-up were assessed by the multirater κ statistic.The multirater κ statistic for interreader agreement on the presence of at least 1 NCN was 0.38. Rates at which readers reported the presence of at least 1 NCN ranged from 32% to 63% (mean, 41%); among 16 subjects with NCN and a cancer diagnosis within 1 year of the CXR examination, an average of 87% (range, 81% to 94%) of cases were classified as suspicious for cancer across all readers. The multirater κ for agreement on follow-up recommendations was 0.34; pairwise κ values ranged from 0.15 to 0.64 (mean, 0.36). For all subjects, readers recommended a follow-up procedure classified as high level (computed tomography, fluorodeoxyglucose-positron emission tomography, or biopsy) 42% of the time on average (range, 30% to 67%); this increased to 84% (range, 52% to 100%) when readers reported an NCN and 88% (range, 82% to 94%) for subjects with cancer.Reader agreement for screening CXR interpretation and follow-up recommendations is fair overall but is high for malignant lesions.

The purpose of the study was to determine whether a difference in patient preference exists between iohexol (Omnipaque) and diatrizoate sodium (Gastroview) as oral contrast medium for abdominal-pelvic CT. A secondary objective was to evaluate whether there are significant differences in bowel opacification and adverse effect profile for the two agents.From August 2007 through March 2009, 300 patients were enrolled in this prospective study after informed consent was obtained. Eligible patients were identified from those scheduled for outpatient abdominal-pelvic CT. Subjects were randomly assigned to receive one of two oral contrast agents in a double-blinded fashion. Subjects graded the taste using a 5-point scale, and data regarding demographics, total volume, and adverse effects were collected. A direct comparison of 30 mL of each of the two diluted agents in randomized order was then performed. CT images were graded for bowel opacification by two blinded abdominal radiologists.Of 287 subjects who expressed a preference, 233 patients (81%) preferred dilute iohexol compared with 54 patients (19%) who preferred dilute diatrizoate sodium (p0.001). Ten patients had no preference, and three patients did not complete the taste comparison study. No difference in bowel opacification was identified between the oral contrast agents (p = 0.27), nor was there a significant difference in adverse effects (p = 0.352).Patents preferred dilute iohexol over dilute diatrizoate sodium for oral contrast for abdominal-pelvic CT. There was no significant difference in bowel opacification or adverse effect profile.

The objective of our study was to examine the correlation between CT-based and radionuclide renography-based measures of split renal function in a healthy population of live potential kidney donors using 3D models generated from CT angiography.The records of 173 renal donor candidates who had undergone CT and radionuclide renography between March 1, 2005, and February 28, 2006, were retrospectively evaluated; of those 173 patients, 152 met study inclusion criteria. A blinded investigator using 3D models that were created semiautomatically from the unenhanced, arterial, and excretory phase data made measurements of CT renal volumes and attenuations. The mean renal attenuation and volume were used to calculate the net accumulation of contrast material and split renal function for comparison with radionuclide renography. Split function from CT was calculated in the arterial and excretory phases as well as based on split renal volume and the Patlak method.All four CT-based methods for the calculation of split renal function showed correlation with no significant difference from radionuclide renography (p0.05, Student's t test). Pearson's correlation coefficients varied from 0.36 to 0.63 (p0.001 for each). Difference scores revealed that the excretory and renal volume splits had the narrowest range and showed a linear, nonzero relationship to the renography splits. Bland-Altman analysis confirmed that the majority of difference scores between each CT method and the radionuclide renography were within the 95% CI of the differences.Split renal function based on 3D CT models can provide a "one-stop" evaluation of both the anatomic and the functional characteristics of the kidneys of living potential kidney donors. The excretory phase data and the split renal volume data show the best correlation and the smallest difference scores compared with radionuclide renography data.

Cholelithiasis is a frequent complication in pediatric sickle cell disease (SCD). Though it is standard practice to perform a cholecystectomy in pediatric SCD patients with symptoms of cholelithiasis, the use of elective cholecystectomy for asymptomatic patients remains controversial.Records of 191 pediatric sickle cell patients with cholelithiasis who underwent cholecystectomy were retrospectively reviewed. Patients classified as follows: (i) elective-no preoperative symptoms, cholelithiasis on screening ultrasound, comprehensive preoperative plan; (ii) symptomatic-preoperative symptoms of cholelithiasis on diagnostic ultrasound, comprehensive preoperative plan; or (iii) emergent-hospitalization for acute cholecystitis symptoms, cholelithiasis on diagnostic ultrasound, limited preoperative preparation. We compared the morbidity of cholecystectomy by examining pre- and post-cholecystectomy hospital admission days, length of stay for cholecystectomy, and surgical complications.Patients with SCD underwent a total of 191 cholecystectomies over a 10-year period: 51 elective, 110 symptomatic, and 30 emergent. Patients who required emergent cholecystectomy had a longer postoperative hospitalization time than elective or symptomatic cholecystectomy (7.3 vs 4.3, P0.001). Baseline values for total bilirubin and aspartate aminotransferase (AST) were significantly elevated (P0.02 and P0.07, respectively) in patients requiring emergent cholecystectomy.This represents the largest reported retrospective review of pediatric cholelithiasis and cholecystectomy in SCD to date. These data strongly suggest that elective cholecystectomy decreases morbidity associated with emergent cholecystectomy. The overall outcomes for symptomatic and elective patients are favorable. However, our study indicates the need for prospective studies to identify clinical indicators for those emergent patients.

The purpose of this study was to evaluate the sensitivity and specificity of seven CT signs in the diagnosis of internal hernia after laparoscopic Roux-en-Y gastric bypass.With institutional review board approval, the CT scans of 18 patients (17 women, one man) with surgically proven internal hernia after laparoscopic Roux-en-Y gastric bypass were retrieved, as were CT studies of a control group of 18 women who had undergone gastric bypass but did not have internal hernia at reoperation. The scans were reviewed by three radiologists for the presence of seven CT signs of internal hernia: swirled appearance of mesenteric fat or vessels, mushroom shape of hernia, tubular distal mesenteric fat surrounded by bowel loops, small-bowel obstruction, clustered loops of small bowel, small bowel other than duodenum posterior to the superior mesenteric artery, and right-sided location of the distal jejunal anastomosis. Sensitivity and specificity were calculated for each sign. Stepwise logistic regression was performed to ascertain an independent set of variables predictive of the presence of internal hernia.Mesenteric swirl was the best single predictor of hernia; sensitivity was 61%, 78%, and 83%, and specificity was 94%, 89%, and 67% for the three reviewers. The combination of swirled mesentery and mushroom shape of the mesentery was better than swirled mesentery alone, sensitivity being 78%, 83%, and 83%, and specificity being 83%, 89%, and 67%, but the difference was not statistically significant.Mesenteric swirl is the best indicator of internal hernia after laparoscopic Roux-en-Y gastric bypass, and even minor degrees of swirl should be considered suspicious.

We assessed the value of positron emission tomography to predict long-term outcome in patients with diabetes and ischemic left ventricular (LV) dysfunction. Circumferential profiles of nitrogen-13 ammonia (NH3) and fluorine-18 fluorodeoxyglucose uptakes were obtained in 61 patients who had diabetes and ischemic LV dysfunction. Patient profiles were compared with those from a normal database. NH3 and fluorine-18 fluorodeoxyglucose defect sizes and extent of perfusion-metabolism mismatch (percentage of myocardium with fluorine-18 fluorodeoxyglucose uptake minus NH3 uptake2 SD above the normal difference) were determined. Patients were followed every 6 months. Over a mean follow-up of 4.3 years, cardiac death occurred in 52% of patients who underwent revascularization and 61% of those who underwent medical therapy (p = 0.69). No clinical or imaging variables predicted cardiac death in patients who underwent revascularization. In those who received medical therapy, mismatch inor =3% of the left ventricle (risk ratio 4.0, p = 0.01) was the only multivariate predictor of cardiac death. Revascularization improved survival of patients who had mismatch ofor =3% at 4 years (p = 0.003) and at 8 years (p = 0.012) of follow-up. Patients who had mismatchor =3% and ejection fraction30% had the greatest improvement in survival with revascularization compared with medical therapy (p0.0001). Revascularization also improved 4-year survival of patients who had NH3 perfusion defects ofor =25% of the left ventricle (p = 0.02). In conclusion, mismatch identifies medically treated patients who have diabetes and LV dysfunction, who are at high risk for cardiac death. Intermediate- and long-term survival of patients who have diabetes and mismatch may be improved with revascularization, and those who have significant mismatch and severe LV dysfunction have the greatest benefit.

We conducted an institutional review of patients with locally advanced esophageal cancer who had complete pretreatment and surgical staging to identify variables predictive of outcome.From 1993 through 2002, 286 patients presented for surgical therapy of esophageal cancer. Of these, 176 patients met criteria for review including pretreatment endoscopic ultrasound stages IIA through IVA and a transthoracic surgical approach with "two-field" lymph node dissection. This cohort was primarily male (84.7%, n = 149) with adenocarcinoma (88.6%, n = 156), and 101 patients (57.3%) demonstrated endoscopic ultrasound stage III or IVA.Eighty-five (48.3%) patients presented to surgery after receiving neoadjuvant chemoradiation therapy, and 91 (51.7%) underwent surgery alone. Both groups were well matched with respect to comorbidities and pretreatment stage. Patients receiving neoadjuvant chemoradiation demonstrated a nonsignificant trend toward increased operative mortality and nonfatal morbidity. The overall median survival was 16.8 months, and there was no survival difference comparing patients treated with neoadjuvant chemoradiation followed by surgery or surgery alone (p = 0.82). The subset of 25 patients (29.4%) demonstrating a complete pathologic response after neoadjuvant chemoradiation therapy however had superior survival (median survival = 57.6 months, p0.01) as compared with neoadjuvant chemoradiation patients demonstrating partial downstaging (n = 36, 42.3%), no downstaging (n = 24, 28.2%), and surgery alone patients. Multivariate analysis identified a complete pathologic response, endoscopic ultrasound stage, and number of pathologically positive lymph nodes as independent predictors of survival.These data support the use of neoadjuvant chemoradiation for locally advanced esophageal cancer as the subset of patients who demonstrate a complete pathologic response experienced significantly better survival.

We tested the hypothesis that the presence of a CYP3A5 * 1 allele is associated with increases in blood pressure in 2 studies of subjects with a total of 683 participants. The first study involving 271 subjects was part of a longitudinal study conducted at Indiana University Medical Center that consisted of 2 phases. The first phase studied the relationship of salt sensitivity with blood pressure, whereas the second phase, conducted ≈26 years later, studied the relationship between blood pressure, carbohydrate intolerance, and vascular compliance in the same subjects. The second study was a cross-sectional evaluation of 412 normotensive and hypertensive subjects conducted at the University of California San Diego. The second study (Mantel–Haenszel χ 2 test; P =0.05) showed that a greater proportion of black participants with poor blood pressure control had CYP3A5 * 1 /* 1 genotype. Evaluation of the untreated blood pressure from phase 1 of the first study showed that the blacks with CYP3A5 * 3 /* 3 (146±35 mm Hg) had a higher systolic blood pressure than those with the * 1 /* 3 (119±14.1 mm Hg; P =0.0006) and * 1 /* 1 (125±17.4 mm Hg; P =0.009) genotypes. For blacks in study 2, the CYP3A5 * 1 allele was more common in hypertensives (Fisher exact test; P =0.025) than normotensives. In whites there was no association between CYP3A5 genotype and blood pressure in either study. We conclude that although untreated blood pressure may be higher in blacks with the CYP3A5 * 3 /* 3 genotype, the CYP3A5 * 1 allele may be associated with hypertension that is more refractory to treatment in this ethnic group.

Shockwave lithotripsy (SWL) predictably damages renal tissue and transiently reduces function in both kidneys. This study characterized the effects on renal function of a supraclinical dose of shockwaves (SWs) (8000) in porcine kidneys and tested the hypothesis that such excessive treatment would intensify and prolong the resulting renal impairment.Pigs aged 6 to 7 weeks were anesthetized and assigned to one of three groups. Groups 1 (N=8) and 2 (N=6) each received 8000 SWs at 24 kV (Dornier HM3) to the lower-pole calix of one kidney. Group 3 (7 pigs) received sham treatment. Renal function was monitored for the first 4 hours after SW treatment in Group 1 and for 24 hours in Group 2. Plasma renin activity was measured in Groups 2 and 3.The renal lesions produced by 8000 SWs comprised 13.8%+/-1.4% of the renal mass. In the 4-hour protocol, this injury was associated with marked reduction of the glomerular filtration rate (GFR), renal plasma flow (RPF), and urinary sodium excretion in both kidneys, although fractional sodium excretion was reduced only in the shocked kidneys. In the 24-hour protocol, GFR and RPF remained below baseline in shocked kidneys at 24 hours. Evidence of progressive ischemic injury was noted in shocked tissue at 24 hours after SW treatment.These findings support the hypothesis that the severity of the renal injury caused by SWL is related to the number of SWs administered and demonstrate the connection in this relation between renal structure and function.

Progressive disease is the major cause of treatment failure after autologous hematopoietic stem cell transplantation for relapsed or refractory non-Hodgkin's lymphoma. An augmented high-dose regimen of cyclophosphamide 7,200 mg/m2, carmustine 300 - 400 mg/m2, and etoposide 2,400 mg/m2 (CBV) was developed in an attempt to improve disease control post-transplant. Sixty-seven adult patients received augmented CBV followed by infusion of unpurged autologous peripheral blood stem cells. Thirty seven patients had relapsed after standard chemotherapy, 28 patients had primary refractory disease, and 2 patients had transformed lymphoma in first partial response. Treatment-related mortality was 4%. Actuarial four year overall survival and progression-free survival were 46+/-8% and 36+/-6%, respectively. Risk factors for disease progression were histologic involvement of marrow by lymphoma and infusion of increased numbers of CD34 + cells per kg in the stem cell autograft. The outcome for patients with relatively chemorefractory disease (defined as 25 - 49% reduction in tumor volume after salvage chemotherapy) was no different than that for patients with chemosensitive disease. Compared to standard high-dose CBV regimens, augmented CBV does not appear to have substantially improved disease control. Prospective study of the association between inferior progression-free survival and infusion of higher CD34 + cell doses in stem cell autografts is warranted.

Pre-formed HLA antibodies (Ab), reported as panel-reactive antibody (PRA), prolong transplant waiting time. We hypothesized that rituximab (RIT) could reduce PRA via B-cell depletion. As part of a Phase I study of single RIT dose, we studied in vivo and ex vivo effects on T-cell immune responses. Nine subjects (n = 3) were treated at 50, 150, and 375 mg/m(2). Serum interleukin-1alpha (IL-1alpha), IL-6, IL-12, tumor necrosis factor beta (TNF-beta), and interferon-gamma (IFN-gamma) were measured by enzyme-linked immunosorbent assay (ELISA). T-cell function was monitored with T-cell proliferation assays. IL-6 levels rose in eight patients (7.15 +/- 4.38 pg/mL to 86.22 +/- 77.08, p = 0.021). The high-dose group had detectable TNF-betapost rituximab infusion (874.7 +/- 1466.5 pg/mL). There was no decline in T-cell proliferation in response to phytohemagglutinin or allogeneic lymphocyte stimuli. Stimulation indices in the presence of both concentrations of tetanus toxoid rose significantly at 4 weeks.

Background Preformed HLA antibodies (Ab), reported as panel-reactive antibody (PRA), prolong patient waiting time for kidney transplantation. We hypothesized that rituximab (RTX) could reduce PRA via B-cell depletion. This initial study reports the safety, pharmacokinetics, and pharmacodynamics of RTX in patients with end-stage renal failure. Methods The study was an investigator-initiated single-dose, dose-escalation phase I trial of RTX in chronic dialysis patients (PRA >50%). It was approved by the Institutional Review Board and the Food and Drug Administration. Nine subjects were treated with a single dose of RTX (n=3 per group) at 50, 150, or 375 mg/m. Peripheral lymphocyte cell surface markers and HLA Ab levels (%PRA and titers) were tested using flow cytometry. Results There were four significant adverse events: a suspected histoplasmosis infection; two Tenchkoff dialysis catheter infections; and fever (38.7 degrees C) during infusion. At 2 days after RTX therapy, there was depletion of CD19 cells (pre-RTX 181+/-137 vs. post-RTX 12+/-5.6, P =0.006). In 2 (22%) of 9 subjects, there was no appreciable change in PRA. Among the other seven patients, one had a decrease in PRA from 87% to 51% with a concurrent decrease in fluorescence intensity; five patients had changes in histogram architecture suggesting loss of antibody specificity; and one patient had a fourfold decrease in PRA titer from 1:64 to 1:16 at 6 months after treatment. In addition, one of the seven patients converted a donor-specific crossmatch to negative and underwent a successful living donor kidney transplantation. Conclusions RTX can be safely administered and may be an effective agent to reduce high-titer anti-HLA Abs in subjects awaiting kidney transplantation.

Renal blood flow falls in both kidneys following delivery of a clinical dose of shockwaves (SW) (2000 SW, 24 kV, Dornier HM3) to only one kidney. The role of renal nerves in this response was examined in a porcine model of renal denervation. Six-week-old pigs underwent unilateral renal denervation. Nerves along the renal artery of one kidney were identified, sectioned and painted with 10% phenol. Two weeks later the pigs were anesthetized and baseline renal function was determined using inulin and PAH clearances. Animals then had either sham-shockwave lithotripsy (SWL) (group 1), SWL to the innervated kidney (group 2) or SWL to the denervated kidney (group 3). Bilateral renal function was again measured 1 and 4 h after SWL. Both kidneys were then removed for analysis of norepinephrine content to validate the denervation. Renal plasma (RPF) flow was significantly reduced in shocked innervated kidneys (group 2) and shocked denervated kidneys (group 3). RPF was not reduced in the unshocked denervated kidneys of group 2. These observations suggest that renal nerves play a pivotal role in modulating the vascular response of the contralateral unshocked kidney to SWL, but only a partial role, if any, in modulating that response in the shocked kidney.

Objectives: The purpose of this study was to determine the pattern of mediastinal dissemination of nonseminomatous germ cell tumors of testicular origin and evaluate variables that may influence survival with mediastinal dissection in patients with metastatic nonseminomatous germ cell tumors. Methods: From 1981 to 2000, a total of 421 patients were seen at our institution for extirpation of residual lung or mediastinal disease after cisplatin-based chemotherapy for metastatic testicular nonseminomatous germ cell tumors. We reviewed 268 of these patients, with a mean age of 26.8 years, who required at least one surgical procedure to remove residual mediastinal disease. Pathologic types of resected residual mediastinal disease were necrosis (15%), teratoma (59%), persistent nonseminomatous germ cell cancer (15%), and non-germ cell carcinomatous degeneration (11%). Twelve variables were evaluated by univariate analyses, and four variables potentially statistically significant at P

Purpose: The current trend toward ungated shock wave lithotripsy means that more patients are being treated with shock waves delivered at a rapid rate (120 shock waves per minute or greater). However, no benefit of an increased shock wave rate has been shown and in vitro studies indicate that slowing the shock wave rate actually improves stone fragmentation. We tested the effect of the shock wave rate on stone comminution in a new animal model.Materials and Methods: Gypsum model stones were inserted via upper pole percutaneous access into the lower pole calix of the kidneys of female pigs weighing approximately 100 pounds. Shock wave lithotripsy was performed (400 shock waves uninterrupted at 20 kV. and 30 or 120 shock waves per minute) 2 hours later using an unmodified HM3 lithotriptor (Dornier Medical Systems, Marietta, Georgia). After en bloc excision of the urinary tract stone fragments were collected and sieved through 2 mm. mesh. The particles were weighed and surface area was determined.Res...

Purpose: In studies to understand better the role of cavitation in kidney trauma associated with shock wave lithotripsy we assessed structural and functional markers of kidney injury when animals were exposed to modified shock waves (pressure release reflector shock pulses) that suppress cavitation. Experiments were also performed in isolated red blood cells, an in vitro test system that is a sensitive indicator of cavitation mediated shock wave damage. Materials and Methods: We treated 6-week-old anesthetized pigs with shock wave lithotripsy using an unmodified HM3 lithotriptor (Dornier Medical Systems, Marietta, Georgia) fitted with its standard brass ellipsoidal reflector (rigid reflector) or with a pressure release reflector insert. The pressure release reflector transposes the compressive and tensile phases of the lithotriptor shock pulse without otherwise altering the positive pressure or negative pressure components of the shock wave. Thus, with the pressure release reflector the amplitude of the incident shock wave is not changed but cavitation in the acoustic field is stifled. The lower pole of the right kidney was treated with 2,000 shocks at 24 kV. Glomerular filtration rate, renal plasma flow and tubular extraction of para-aminohippurate were measured in the 2 kidneys 1 hour before and 1 and 4 hours after shock wave lithotripsy, followed by the removal of each kidney for morphological analysis. In vitro studies assessed shock wave induced lysis to red blood cells in response to rigid or pressure release reflector shock pulses. Results: Sham shock wave lithotripsy had no significant effect on kidney morphology, renal hemodynamics or para-aminohippurate extraction. Shock waves administered with the standard rigid reflector induced a characteristic morphological lesion and functional changes that included bilateral reduction in renal plasma flow, and unilateral reduction in the glomerular filtration rate and para-aminohippurate extraction. When the pressure release reflector was used, the morphological lesion was limited to hemorrhage of vasa recta vessels near the tips of renal papillae and the only change in kidney function was a decrease in the glomerular filtration rate at the 1 and 4-hour periods in shock wave treated kidneys. Red blood cell lysis in vitro was significantly lower with the pressure release reflector than with the rigid reflector. Conclusions: These data demonstrate that shock wave lithotripsy damage to the kidney is reduced when cavitation is suppressed. This finding supports the idea that cavitation has a prominent role in shock wave lithotripsy trauma.

OBJECTIVE—To determine, for individuals with type 2 diabetes and microalbuminuria, the effects of 6 weeks of meals containing plant-based protein (PP) versus meals with predominantly animal-based protein (AP) on renal function and secondarily on glycemia, lipid levels, and blood pressure. RESEARCH DESIGN AND METHODS—In a randomized crossover trial, we compared 6 weeks of meals containing only PP with meals containing primarily AP (60% animal, 40% plant) in 17 subjects with type 2 diabetes and microalbuminuria treated with diet and/or oral antidiabetic agents. Protein content was equivalent to the average American diet, and calories provided weight maintenance. Nutrients were equivalent between the two diets. Meals were prepared and packaged by a metabolic kitchen staff and were sent home weekly. At the beginning and end of each 6-week period, subjects were studied for 36 h on a metabolic unit. RESULTS—There were no significant differences between diets for glomerular filtration rate, renal plasma flow, albumin excretion rate, total cholesterol, HDL cholesterol, triglyceride area under the curve (AUC), glucose and insulin AUC, HbA1c, blood pressure, or serum amino acids. For both diets, at the end of the treatment periods as compared with baseline, total cholesterol was significantly lower (PP and AP: from 4.75 to 4.34 mmol/l, P < 0.01), HbA1c had significantly improved (PP: from 8.1 to 7.5%, P < 0.01; AP: from 7.9 to 7.4%, P < 0.01), and diastolic blood pressure was significantly lower (PP: from 83 to 80 mmHg, P < 0.02; AP: from 82 to 78, P < 0.02). CONCLUSIONS—There is no clear advantage for the recommendation of diets containing only PP rather than diets containing protein that is primarily animal-based for individuals with type 2 diabetes and microalbuminuria. There are, however, potential lipid, glycemic, and blood pressure benefits for following a carefully constructed, weight-maintaining, healthy diet, regardless of protein source.

We conducted noninvasive measures of vascular compliance and glucose tolerance in 275 normotensive and hypertensive subjects. Of the total, 194 (70.5%) were hypertensive, 73 (26%) diabetic, 7 (2.5%) normotensive and diabetic and 66 (24%) both hypertensive and diabetic, and 74 (27%) normotensive and nondiabetic. In addition, 57 of the nondiabetic subjects had impaired glucose tolerance based on the results of blood glucose levels 2 h after a glucose challenge. For the entire population, large artery compliance was correlated with systolic (P.001), diastolic (P = .041), and pulse (P.001) pressures, whereas small artery compliance correlated significantly (P.001) only with systolic and pulse pressures. Among hypertensives, a significant decrease in large and small vessel compliance was seen, which was reduced further in the case of small vessel compliance by the presence of diabetes. When the population was separated on the basis of glucose tolerance into normal, impaired, and diabetic groups, a progressive reduction (P.001) in small artery compliance was seen that was independent of age. Similar significant (P.001) progressive increases in body mass index and systolic pressure were seen with progression of carbohydrate intolerance. These findings confirm the close relationship between elevated blood pressure (BP) and carbohydrate intolerance and indicate that the vascular effects of both are separate, additive, and primarily on small blood vessel compliance. These findings have important implications for the preclinical detection and potential prevention of hypertension, diabetes, and associated vascular disease.

Background — Nitric oxide (NO) is a potent vasodilator and antiplatelet agent that suppresses vascular smooth muscle cell proliferation. Hypothesizing that generating NO in the pericardial space would reduce luminal narrowing after coronary angioplasty without affecting systemic hemodynamics, we have determined the effect of a novel NO donor on vascular healing after balloon overstretch. Methods and Results — Diazeniumdiolated bovine serum albumin (D-BSA; molecular weight 74 kDa, half-life for NO release 20 days) was radioiodinated and found by intravital γ-imaging to have a longer residence time in pig pericardium than a low-molecular-weight (0.5 kDa) analogue (22 versus 4.6 hours, respectively). Intrapericardial injection of D-BSA immediately before 30% overstretch of normal left anterior descending and left circumflex coronary arteries dose dependently reduced the intimal/medial area ratio by up to 50% relative to controls treated with underivatized albumin when measured 2 weeks after intervention. Positive remodeling was also noted, which increased luminal area relative to control. Conclusions — Perivascular exposure of coronary arteries to NO via intrapericardial D-BSA administration reduced flow-restricting lesion development after angioplasty in pigs without causing significant systemic effects. The data suggest that intrapericardial delivery of NO donors for which NO release rates and pericardial residence times are matched and optimized might be a beneficial adjunct to coronary angioplasty.

Medial artery calcification in ESRD patients is associated with deposition of bone matrix proteins. Background In non-ESRD patients, recent studies have demonstrated that the process of vascular calcification resembles developmental osteogenesis. Patients with ESRD are known to have excessive vascular calcification, but this has previously been attributed to the non-cell-mediated process of metastatic calcification. Methods To determine if the calcification observed in patients with ESRD is related to a cell-mediated process, we removed a piece of inferior epigastric artery at the time of renal transplant. Calcium content of the entire vessel was quantified with spiral computed tomography (CT). The vessel was then examined histologically for calcification and the presence of bone matrix proteins by immunohistochemistry, and medial and intimal thickness quantified by histomorphometry. These findings were correlated with demographic, clinical and laboratory values. Results The proximal inferior epigastric artery was obtained from 41 patients undergoing renal transplantation, but two were inadequate for histologic examination. Twenty-seven of the remaining vessels had no evidence of calcification by MacNeal's or Alizarin red pH 4.2 staining, five vessels had mild/moderate calcification, and seven had severe calcification, all in the medial layer. Calcification assessed histologically was closely correlated with calcification score as assessed by spiral CT, normalized for vessel weight ( P = 0.027). Positive immunostaining for the bone matrix proteins osteopontin, type I collagen, bone sialoprotein, and alkaline phosphatase was strongly correlated with calcification (all P ≤ 0.001), as was a history of coronary artery disease ( P P = 0.034). The calcification score by spiral CT correlated with these same factors and the serum phosphorus and calcium × phosphorus product ( P = 0.032 and 0.037). The location of immunostaining for the bone proteins was strongly associated with the presence of calcification. However, positive immunostaining also was observed in association with disorganization of the vascular smooth muscle cells in the medial layer due to deposition of a matrix-like substance, prior to overt calcification. Conclusions In patients with ESRD undergoing renal transplantation, vascular calcification of the medial layer of the inferior epigastric artery is common (44%), can be detected by spiral CT, and is associated with deposition of bone matrix proteins. This implies an active cell-mediated process, raising hope that directed intervention can arrest this process.

Sequential analysis of kidney stone formation in the Aprt knockout mouse. Background We have previously shown that, as in human adenine phosphoribosyltransferase (APRT) deficiency, Aprt knockout mice form 2,8-dihydroxyadenine (DHA) renal stones. The disease develops earlier and is more severe in male than in female mice. To examine the biological bases for these differences, the area occupied by DHA crystals was quantified in kidney sections from male and female mice (strain 129) aged one day to eight months and this parameter was correlated with changes in renal histopathology. Aprt heterozygous and wild-type mice were used as controls. Methods Following anesthesia, the left kidney was removed and immediately frozen in dry ice. Unstained cryosections were examined by polarized light to determine total area of birefringent particles. The right kidney was perfused and embedded in plastic, and stained sections were viewed by light microscopy to examine the histopathology and to determine the location of the birefringent particles. A pathological score was assigned to the histological findings. The scores from the right kidney were compared with crystal/particle area in the left kidney, and the data were analyzed using two-way analysis of variance. The chemical composition of the particles was determined by x-ray diffraction analysis. Several stone fragments from the bladder were also examined by scanning electron microscopy (SEM). Results Crystals were detected in kidney sections from one- to two-day-old Aprt knockout mice. The crystal burden remained low in both sexes throughout the study except in males at the 120- to 240-day period. Furthermore, there was a substantial degree of renal pathology, primarily seen as interstitial fibrosis, in those males with a very high level of stone formation. The crystalline material was identified as 6-amino-2,8(3,9)-purine dione, a tautomeric form of DHA. SEM indicated that the crystals were spherical, with a diameter of 10 to 20 μm. Tissue staining and fixation procedures dramatically reduced the amount of birefringent material in kidney sections. Aprt heterozygotes of both sexes had low levels of crystalline material in the kidneys and no pathology. Birefringent material or pathological changes were not seen in kidneys from wild-type mice. Conclusions Both male and female Aprt knockout mice accumulate DHA. However, the area occupied by DHA crystals was significantly greater in 120- to 240-day-old males compared with the females of similar age. Also, substantial renal pathology was detected in kidneys of male mice that had very high levels of stone material.

Objective: To assess the out-of-hospital cardiac arrest (OHCA) survival advantage after providing police with automated external defibrillators (AEDs) in rural and suburban Indiana. Methods: An observational evaluation was conducted in six Indiana counties (population: 464,741) before (retrospective) and after (prospective) training and equipping police with AEDs. The primary outcome evaluated was survival to hospital discharge for all cases of ventricular tachycardia/ventricular fibrillation (VT/VF) OHCA. Other factors evaluated include age, gender, race, arrest location, witnessed arrest, bystander cardiopulmonary resuscitation, response intervals, and survival to discharge for all OHCAs. Results are reported using chi-square, Student's t-test, and logistic regression. Results: Police were equipped with 112 AEDs, increasing total defibrillator capability by 43.2%. During the study period, AED-equipped police responded prior to emergency medical services (EMS) in 26 of 388 cases (6.7%). The time intervals from 911 call-to-scene and 911 call-to-shock were shortened by 1.6 minutes (95% confidence interval [95% CI] = 0.0 to 3.1, p = 0.05) and 4.8 minutes (95% CI = 1.3 to 8.3, p = 0.008), respectively, with police response as compared with EMS response. Survival to hospital discharge for VT/VF OHCA was 15.0% (3/20) in cases in which police responded first and 10.0% (16/160) in cases in which EMS responded first (relative risk [RR] 0.63, 95% CI = 0.17 to 2.39, p = 0.45). Survival to hospital discharge for VT/VF OHCA did not improve from the prestudy period (16/204, 7.8%) to after police AED availability (19/180, 10.6%) (RR 0.72, 95% CI = 0.36 to 1.45, p = 0.38). Conclusions: Out-of-hospital cardiac arrest survival in suburban and rural Indiana did not improve after police were equipped with AEDs, likely related to poor police response.

OBJECTIVE—Whereas new diagnostic criteria based on a fasting plasma glucose (FPG) of >126 mg/dl (7.8 mmol/l) have improved the detection of diabetes, multiple reports indicate that many people with diabetes diagnosed by 2-h oral glucose tolerance test (OGTT) glucose measurements of ≥11.1 mmol/l (200 mg/dl) would remain undiagnosed based on this FPG criteria. Thus, improved methods to detect diabetes are particularly needed for high-risk individuals. We evaluated whether the combination of FPG and HbA1c measurements enhanced detection of diabetes in those individuals at risk for diabetes with nondiagnostic or minimally elevated FPG. RESEARCH DESIGN AND METHODS—We analyzed FPG, OGTT, and HbA1c data from 244 subjects screened for participation in the Early Diabetes Intervention Program (EDIP). RESULTS—Of 244 high-risk subjects studied by FPG measurements and OGTT, 24% of the individuals with FPG levels of 5.5–6.0 mmol/l (100–109 mg/dl) had OGTT-diagnosed diabetes, and nearly 50% of the individuals with FPG levels of 6.1–6.9 mmol/l (110–125 mg/dl) had OGTT-diagnosed diabetes. In the subjects with OGTT-diagnosed diabetes and FPG levels between 5.5 and 8.0 mmol/l, detection of an elevated HbA1c (>6.1% or mean + 2 SDs) led to a substantial improvement in diagnostic sensitivity over the FPG threshold of 7.0 mmol/l (61 vs. 45%, respectively, P = 0.002). Concordant FPG levels ≥7.0 mmol/l (currently recommended for diagnosis) occurred in only 19% of our cohort with type 2 diabetes. CONCLUSIONS—Diagnostic criteria based on FPG criteria are relatively insensitive in the detection of early type 2 diabetes in at-risk subjects. HbA1c measurement improves the sensitivity of screening in high-risk individuals.

A survey was mailed to a probability sample of primary care physicians in Indiana to assess their use of and barriers to nutritional therapy for patients with type 2 diabetes. Most (62%) primary care physicians reported referring their type 2 diabetes patients for nutrition counseling, while 38% reported providing counseling themselves. Patient-centered barriers were most frequently cited as reasons for poor effectiveness of nutrition therapy. This differs from previous research that cites system-level factors as barriers.

Background —Although thrombus formation plays a major role in acute coronary syndromes, few studies have evaluated a thrombus marker in risk stratification of patients with chest pain. Furthermore, the relation between markers that reflect myocardial injury and thrombus formation that may predict events in a heterogeneous patient population is unknown. This study correlated markers of thrombus and myocardial injury with early and late ischemic events in consecutive patients with chest pain. Methods and Results —Serum troponin I (TnI), myoglobin, and myosin light chain levels were obtained from 247 patients and urinary fibrinopeptide A (FPA) from 178 of the 247. By multivariate analysis, patients with an elevated FPA level were 4.82 times more likely to die or have myocardial infarction, unstable angina, and coronary revascularization at 1 week ( P =0.002, 95% CI 1.78, 13.03), whereas those with an elevated TnI (>0.2 ng/mL) were 9.41 times more likely ( P P P Conclusions —Elevated FPA and TnI correlated with cardiac events during the initial week in patients presenting to the Emergency Department with chest pain. FPA predicted adverse events and a shorter event-free survival at 6 months.

Electrical Remodeling of the Heart due to Rate. Introduction: We previously demonstrated in dogs that a transient rate increase superimposed on bradycardia causes prolongation of ventricular refractoriness that persists for hours after resumption of bradycardia. In this study, we examined changes in membrane currents that are associated with this phenomenon. Methods and Results: The whole cell, patch clamp technique was used to record transmembrane voltages and currents, respectively, in single mid-myocardial left ventricular myocytes from dogs with 1 week of complete AV block; dogs either underwent 1 hour of left ventricular pacing at 120 beats/min or did not undergo pacing. Pacing significantly heightened mean phase 1 and peak plateau amplitudes by ∼6 and ∼3 mV, respectively (P < 0.02). and prolonged action potential duration at 90% repolarization from 235 ± 8 msec to 278 ± 8 msec (1 Hz; P = 0.02). Rapid pacing-induced changes in transmembrane ionic currents included (1) a more pronounced cumulative inactivation of the 4-aminopyridine-sensitive transient outward K+ current, I to over the range of physiologic frequencies, resulting from a ∼30% decrease in the population of quickly reactivating channels; (2) increases in peak density of L-type Ca2+ currents, Ica.I.' by 15% to 35% between +10 and +60 mV; and (3) increases in peak density of the Ca2+-activated chloride current, ICl.Ca' by 30% to 120% between +30 and +50 mV. Conclusion: Frequency-dependent reduction in Ito combined with enhanced ICa.I. causes an increase in net inward current that may he responsible for the observed changes in ventricular repolarization. This augmentation of net cation influx is partially antagonized by an increase in outward ICa.Cl.

Background Intravenous amiodarone is effective for the acute suppression of recurrent hemodynamically destabilizing ventricular arrhythmias. There are no follow-up data on patients undergoing long-term therapy with intravenous amiodarone. The objective of this investigation was to evaluate long-term outcome. Methods and Results We reviewed the clinical courses of 245 patients given intravenous amiodarone for sustained ventricular tachyarrhythmias. Of the 107 survivors (84% men; mean age 64 years) released from the hospital taking oral amiodarone, 41 were discharged with an empiric prescription for oral amiodarone. For 64 patients a decision regarding further therapy was based on results of an electrophysiologic study. Two patients were treated empirically with oral amiodarone and an implantable cardioverter defibrillator. Clinical variables and survival curves were the same for the empirically treated group and the group whose treatment was based on electrophysiologic findings ( P = .89). Survival at 6, 12, and 18 months was 88%, 81% and 71%, respectively, for empirically treated patients, and 83%, 80% and 73%, respectively, for patients whose therapy was directed with an electrophysiologic study. Of the 64 patients who underwent electrophysiologic studies, 33 received an implantable cardioverter defibrillator. The Kaplan-Meier survival curves for patients with and patients without an implantable cardioverter defibrillator were similar ( P = .46). Conclusions Patients for whom recurrent ventricular tachycardia and fibrillation are suppressed with intravenous amiodarone and who are discharged receiving oral amiodarone have an 80% 1-year survival rate. Although not randomized, our data suggested that among such patients, electrophysiologic testing, implantation of a cardioverter defibrillator, or both may not be necessary. Ascertaining the best management strategy for these patients will require a prospective randomized trial.

We reviewed the clinicopathologic and immunophenotypic profiles of 7 pediatric and 11 adult minimally differentiated acute myelogenous leukemias (AML-M0). We also compared and evaluated myeloperoxidase in leukemic blasts using standard cytochemical and polyclonal antibody immunohistochemical stains. No distinctive clinical findings were noted in either patient group; however, thrombocytopenia typically was more prominent in adults. Adult AML-M0 also was associated with an immature myeloid profile (CD34+, terminal deoxynucleotidyl transferase positive, CD13+, and CD33+), in contrast with pediatric AML-M0, which usually lacked terminal deoxynucleotidyl transferase or CD34 but expressed bright CD33 with weak or negative CD13. Coexpression of the T-cell-associated antigen CD7 was observed in both groups. Antibody immunohistochemical stains were more sensitive than cytochemical stains for detection of myeloperoxidase activity and a useful adjunct for establishing a diagnosis of myeloid leukemia in paraffin-embedded marrow tissues.

The present study was designed to determine the effects of shock wave voltage (kV) on lesion size and renal function induced by shock wave lithotripsy (SWL) in the 6- to 8-wk-old pig. Each SWL-treated pig received 2000 shock waves at 12, 18, or 24 kV to the lower pole calyx of one kidney. A group of sham SWL pigs served as time controls. Bilateral GFR, renal plasma flow (RPF), and para-aminohippurate (PAH) extraction were measured 1 h before and 1 and 4 h after SWL in all treated and sham animals. The kidneys were removed at the end of each experiment for morphometric analysis. The SWL-induced lesion increased significantly in size as shock wave energy was increased from 12 to 24 kV. PAH extraction, a measure of tubular function, was not significantly affected at 12 kV, was transiently reduced at 18 kV, and was reduced for the duration of the experiment at 24 kV. GFR and RPF, however, were significantly and similarly reduced at the 1 h post-SWL period at all three kilovolt levels. At the 4-h post-SWL period, both GFR and RPF had returned to baseline levels. Lesion size and tubular injury were correlated with changes in kilovoltage, while changes in renal hemodynamics were already maximal at the lowest discharge voltage. These findings suggest that renal microvessels are highly sensitive to shock waves and that frank injury to tubules and vessels may be more closely related to discharge energy than is renal blood flow.

The present study tested the hypothesis that renal disease potentiates the structural/functional changes induced by a clinical dose of shockwaves.Experimental pyelonephritis was induced in 6- to 8-week-old pigs before treatment with 2,000 shocks at 24 kV. These pigs were divided into two groups according to whether they were infected with a highly virulent (Group 1) or less virulent (Group 2) inoculation of E. coli. All animals were imaged by MR prior to SWL as a means of documenting the extent of pyelonephritis and immediately after SWL to examine the lesion produced by the shockwaves. The glomerular filtration rate (GFR), renal plasma flow (RPF) and para-aminohippurate (PAH) extraction were determined bilaterally on day 30 (Group 1) or day 80 (Group 2).In group 2, urine flow and sodium excretion were reduced by 50% from baseline in the shocked kidneys at both 1 and 4 hours post-SWL. A sustained reduction in RPF through 4 hours post-SWL was noted in the shocked kidneys in Group 1, but RPF was significantly reduced only at the 1-hour determination in Group 2. Large, consistent reductions in GFR were evident at 1 and 4 hours post-SWL in shocked and unshocked kidneys of Group 2 and in the shocked kidneys of Group 1. No significant changes were noted in PAH extraction.Acute pyelonephritis exaggerated the effect of a clinical dose of shockwaves on renal hemodynamics. This effect suggests that renal disease may be risk factor for SWL-induced injury.

The relationship between kidney size and impaired renal function induced by shock-wave lithotripsy (SWL) was examined in 6- and 10-wk-old anesthetized pigs. Each pig received 2000 shock waves, 24 kV, or sham SWL to the lower pole calyx of one kidney. Bilateral GFR, renal plasma flow (RPF), and para-aminohippurate extraction was measured 1 h before and 1 and 4 h after SWL. The kidneys were then removed for morphometric analysis. Mean kidney weights were 66.1 ± 2.7 g ( n = 9) and 103.1 ± 3.3 g ( n = 8) in the SWL groups, and 60.1 ± 2.6 g ( n = 9) and 82.3 ± 4.0 g ( n = 9) in the sham-SWL groups. SWL-induced lesions occupied a significantly greater volume of the small kidneys (6.1 ± 1.7 vol % versus 1.5 ± 0.2 vol % in the large kidneys). RPF was significantly reduced by SWL in small and large kidneys, but to a significantly greater extent in small kidneys. RPF was also significantly reduced in the contralateral kidneys of both groups, but only at 1 h after SWL. SWL significantly reduced GFR to similar degrees in both kidneys of both groups, regardless of kidney size. Para-aminohippurate extraction was likewise reduced to similar degrees in both groups, but this effect was evident only in the SWL-treated kidneys, and only in the pole to which the shock waves had been applied. The injury induced by SWL affected a larger fraction of small kidneys than large ones, and the renal vasoconstriction induced by SWL was greatest in small kidneys.

Objective: To compare glycemic responses of isocaloric mixed meals containing 2% and 17% sucrose in children with type 1 diabetes who had fasting euglycemia. Study design: Nine children (11 to 16 years) with type 1 diabetes were randomized in a crossover design to receive 2 isocaloric diets (2% or 17% sucrose) in the Clinical Research Center. In the 2% sucrose diet, starch isocalorically replaced sucrose. Results: Fasting euglycemia was comparable on both study days (mean ± SEM: 2% sucrose, 5.0 ± 0.3 mmol/L or 90 ± 5 mg/dL; 17% sucrose, 5.0 ± 0.3 mmol/L or 91 ± 6 mg/dL). The 17% sucrose diet resulted in a lower glycemic response than the 2% sucrose diet over the 4-hour study period (area under glucose response curve: mean ± SEM, 37 ± 3.5 mmol/L·4 h vs 42 ± 4.7 mmol/L·4 h, P = .01). Peak blood glucose response was earlier and lower (2.2 to 2.8 mmol/L, 40 to 50 mg/dL) with the 17% sucrose diet. Conclusions: Sucrose in moderate amounts, isocalorically exchanged for starch, lowered glycemic response between breakfast and lunch in children who were euglycemic before breakfast. These data refute concerns about adverse glycemic effects of sucrose and support the use of sucrose-containing foods in the context of a healthy meal plan. (J Pediatr 1998;133:429-34)

OBJECTIVE The significance of gestational diabetes mellitus (GDM) results from its short-term detrimental effects on the fetus and its long-term prediction of NIDDM in the mother. We compared several variables associated with insulin resistance between GDM and non-GDM pregnant women to show the similarities between GDM and NIDDM (and thus insulin resistance). RESEARCH DESIGN AND METHODS On the basis of a 3-h oral glucose tolerance test (OGTT), 52 GDM patients and 127 non-GDM patients were recruited from pregnant, non-diabetic women who had a nonfasting 1-h-50-g glucose screening test ≥ 7.2 mmol/l (130 mg/dl) performed between 16 and 33 weeks of gestation (a total of 518 of 3,041 women drawn from six community health care prenatal clinics were screened positive). During the OGTT, several potential markers of insulin resistance were measured at fasting and 2-h time points, in addition to the standard glucose measurements. The relationship of these variables with the diagnosis of GDM was studied. RESULTS GDM patients, compared with non-GDM patients, had 1) higher prepregnancy weight (P = 0.011), prepregnancy BMI (P = 0.006), C-peptide at fasting (P = 0.002) and at 2 h (P < 0.001), insulin at fasting (P = 0.001) and at 2 h (P < 0.001), triglycerides at fasting (P = 0.005) and at 2 h (P = 0.003), free fatty acids at fasting (P = 0.017), β-hydroxybutyrate at fasting (P = 0.007); and 2) lower HDL cholesterol at fasting (P = 0.029). These variables were all predictive of GDM (P < 0.036) individually. Using stepwise logistic regression with all of these variables available, fasting (P = 0.019) and 2-h (P < 0.001) insulin levels, fasting free fatty acids (P = 0.031), and fasting β-hydroxybutyrate (P = 0.036) were statistically significant as jointly predictive of GDM. Comparisons between GDM patients and non-GDM patients matched by BMI confirmed that the metabolic abnormalities persisted when difference in BMI was taken into account. Concomitant blood pressure measurements in women with GDM did not differ significantly from those without GDM. CONCLUSIONS Our results show that many of the known metabolic components of the syndrome of insulin resistance (syndrome X) are predictive of GDM. These results are in keeping with the argument that GDM is one phase of the syndrome of insulin resistance. We suggest that GDM be looked upon as a component of the syndrome of insulin resistance that provides an excellent model for the study and prevention of NIDDM in a relatively young age-group.

This study tested the hypothesis that the effects of SWL on hemodynamics in solitary kidneys differ from those in kidneys of binephric animals. Five female miniature pigs (Pitman-Moore, 6 months of age, 30-35 kg) were anesthetized for unilateral nephrectomy. Seven pigs served as binephric controls. Two weeks later, each pig was anesthetized, prepared for unilateral or bilateral urine collections, and subjected to SWL (Dornier HM3, 2000 shocks, 24 kV). Clearances of inulin (glomerular filtration rate; GFR) and para-aminohippurate (renal plasma flow; RPF) were measured 1 hour prior to and 1, 4, and 24 hours after SWL. The GFR and RPF were higher in uninephrectomized than in intact pigs at all time points. In both groups, SWL reduced GFR and RPF. In the binephric pigs, RPF was reduced at all times post-SWL, but in the uninephrectomized pigs, RPF was returning toward baseline by 4 hours post-SWL and was not different from baseline at 24 hours. A comparison of whole-animal GFR and RPF (righ plus left clearances in binephric pigs v solitary renal clearances in uninephrectomized pigs) showed that whole-animal GFR and RPF did not differ between the groups before or after SWL. Compensatory renal hypertrophy and improved hemodynamics in solitary kidneys may acutely attenuate the renal vasoconstrictive effect of SWL. The long-term consequences of the compensatory changes are unknown.

Objectives. We investigated the patterns of perfusion and metabolism in dysfunctional myocardium whose contractility improved with dobutamine.Background. Clinical studies have suggested that dobutamine echocardiography can identify hibernating myocardium, but laboratory studies suggest that reduced perfusion limits the response to dobutamine.Methods. Twenty-five patients with coronary disease and ventricular dysfunction underwent low (5 and 10 μg/kg body weight per min) and high dose (maximum of 50 μg/kg per min) dobutamine echocardiography and positron emission tomography (PET) using nitrogen-13 (N-13) ammonia and fluorine-18 fluorodeoxyglucose (FDG) for imaging of perfusion and metabolism. Wall motion and tracer uptake were scored in 16 left ventricular segments.Results. Perfusion and metabolism were normal in 56.4%, mildly reduced in 29.1% and mismatched (reduced perfusion, preserved FDG uptake) in 14.5% of dysfunctional segments viable on PET. Wall motion improved with dobutamine in 89 dysfunctional segments (62 at low dose, 27 only at peak dose), and 86 of these (97%) were viable on PET. Improvement in wall motion with dobutamine was more common in segments with normal perfusion and metabolism (56.5%) than in those with mildly reduced tracer uptake (28.5%, p < 0.001) and those with mismatch (32%, p = 0.03). All the segments with a biphasic response were supplied by vessels with ≥70% stenosis, and 88% had normal perfusion and metabolism.Conclusions. The majority of viable segments with rest dysfunction had normal perfusion and metabolism, suggesting that myocardial stunning was common. Improvement of wall motion at low and high doses of dobutamine was highly correlated with myocardial viability on PET and was more common in myocardium with normal perfusion. A biphasic response to dobutamine identified segments with normal perfusion and metabolism supplied by severely diseased vessels.(J Am Coll Cardiol 1997;29:55–61)>

PURPOSE The purpose of this study was to evaluate intravenous (IV) contrast-enhanced single-source rapid kilovolt (peak)-switching dual-energy (RSDE) multidetector computed tomography (CT) material density assessment of hepatic steatosis compared to conventional unenhanced (CU) Multidetector computed tomography (MDCT). MATERIALS AND METHODS This is an institutional review board-approved intrapatient study of 363 consecutive adults (189 men, 174 women; mean age, 59 years) evaluated with multiphasic IV abdominal RSDE. Material density virtual unenhanced water and fat hepatic parenchymal values were measured and correlated to Hounsfield units (HUs) on CU CT using linear regression. Study population was dichotomized into steatotic or nonsteatotic liver parenchyma on the basis of CU liver-spleen (L-S) difference. The RSDE fat(-iodine) values (in milligram per milliliter) were compared (t test), correlated to the L-S difference in HU, and a milligram-per-milliliter fat threshold for clinically significant steatosis was calculated using receiver operator curve (ROC) analysis. RESULTS Regression analysis revealed r value of 0.86 for mg/mL water (P < 0.001) and 0.87 for milligram-per-milliliter fat (P < 0.001). Twenty-seven participants were excluded from the L-S analysis (splenectomy). A total of 107 (32%) had steatosis (mean L-S, - 6.3; mean fat(-iodine) milligram per milliliter, 1018.4); 229 (68%) had no steatosis (mean L-S, 9.4; milligram per milliliter, 1028.4 [P < 0.001]). The RSDE fat material density measurement correlated to L-S less than 1 with r value of 0.74 (P < 0.001), with an area under receiver operator curve of 0.847. A threshold of 1023-mg/mL fat had 71% sensitivity and 80% specificity, and a threshold of 1027-mg/mL fat had 90% sensitivity and 61% specificity for steatosis. CONCLUSIONS The RSDE milligram-per-milliliter fat values correlate well with hepatic steatosis defined by the L-S difference less than 1 on conventional MDCT. A threshold of 1027 mg/mL can identify 90% of steatotic livers when post-IV contrast RSDE is used, without obtaining additional CU scans. However, regression equations were not helpful to convert an individual participant's milligram-per-milliliter fat or milligram-per-milliliter water-derived from RSDE material density images to CU MDCT HU for the estimation of liver fat content.

Insulin lispro [Lys (B28), Pro (B29) human insulin] is a rapidly absorbed analog that has diminished tendency to self-associate. In four open-label, 1-year-long international randomized trials, we contrasted the immunogenicity of insulin lispro versus regular human insulin (RHI) in patients previously treated with insulin who had IDDM or NIDDM. Using a self-blank subtraction assay, we assessed sera for the presence of insulin-specific antibodies (ISA), insulin lispro-specific antibodies (LSA), and cross-reactive antibodies (CRA). Basal insulin needs were provided either with human ultralente (UL) or NPH insulins. After 2 to 4 weeks of therapy with RHI plus UL or RHI plus NPH, 50% of patients were randomly assigned to begin insulin lispro or continue on RHI. At baseline, few pretreated patients had LSA (0–4%) and ∼ 10% had ISA, whereas 41–45% of patients with IDDM and 23–27% of patients with NIDDM had CRA (IDDM vs. NIDDM, P < 0.001). Within studies, no significant differences were noted over time in ISA, LSA, or CRA attributable to the type of short-acting insulin. When data were pooled, inconsistent changes were noted in ISA and LSA (LSA were greater in NIDDM vs. IDDM at baseline, P = 0.001, and ISA were greater in IDDM vs. NIDDM at 6 months, P = 0.007). Significant levels of CRA were more common in IDDM at all times (P < 0.001, P = 0.022, and P = 0.002 at baseline, 6 months, and 12 months, respectively). For patients receiving insulin lispro, no significant changes occurred in antibody status among IDDM and NIDDM patients throughout the study (became positive, remained positive, became negative, or remained negative). IDDM patients were more likely to develop or maintain CRA levels (P = 0.008 vs. NIDDM), whereas antibody levels were comparable among positive individuals. No evidence was noted that insulin lispro differs in immunogenicity from RHI in previously treated IDDM and NIDDM patients.

Purpose: This study examined the acute time course of effects of extracorporeal shock wave lithotripsy (ESWL)1 1Dornier Medical Systems, Marietta, Georgia. on renal hemodynamics in anesthetized minipigs with and without pretreatment with verapamil.Materials and Methods: We applied ESWL (2000 shocks, 24 kV, unmodified Dornier HM3), to the right kidneys of isoflurane-anesthetized female pigs. Urine flow and renal hemodynamics were monitored from each kidney via ureteral balloon catheters. Arterial blood pressure and bilateral urine flow, glomerular filtration rate (GFR, inulin clearance) and renal plasma flow (RPF, para-aminohippurate clearance) were monitored for 45 minutes before ESWL, and at 1, 4 and 24 hours after ESWL.Results: Treatment with ESWL consistently caused unilateral hematuria and subcapsular renal hematomas in the shocked kidneys and significantly reduced GFR and RPF in those kidneys at 1 and 4 hours after ESWL. Urine flow was reduced through 24 hours in the shocked kidneys. Renal pl...

We prospectively compared digital echocardiographic images, by a minimal digital-acquisition strategy, with videotape images to determine the diagnostic utility of digital imaging in patients admitted to the emergency department with chest pain. Digital acquisition has many potential advantages for evaluating echocardiographic images, especially in the acute-care setting. It is not yet known how much the imaging study can be condensed with digital technology and still provide the necessary information needed for clinical echocardiographic diagnosis. One hundred seventeen patients with diagnoses consisting of coronary artery disease, pericardial disease, and valvular disease were studied. Overall agreement between videotape and digital recordings with regard to normal versus abnormal wall motion was 94% (p < 0.001). The wall motion score index, a semiquantitative measure of global function, also correlated well (r = 0.94). Complete concordance was noted in all patients with aortic stenosis and pericardial effusion. Digital echocardiographic imaging, by a minimal-acquisition strategy, is an accurate summary of the complete echocardiographic examination and provides the relevant diagnostic data needed for the assessment of patients with chest pain in the emergency department.

Objective To quantify the cervical dilation achieved from multiple medium-thick laminaria tents used for 16–26 hours in single applications before abortion. Methods In a practice setting, cervical dilation was studied from all abortions done at greater than 8 weeks in which one or more medium-thick laminaria tents were used in a single application for 16–26 hours. Multiple regression analysis was used to quantify results. Results There was a positive linear regression of dilation against weeks of gestation for all numbers of tents. The more tents, the greater the dilation; the more weeks, the greater the dilation. Conclusion Approximate cervical circumferential dilation from medium-thick laminaria tents under the constraints listed is provided by the formula: Pratt dilation = 12.36 + (2.35 × tents) + (1.79 × weeks).

Objective to determine metabolic responses to commercially sweetened flaked corn cereal, unsweetened flaked corn cereal, glucose, and sucrose in teenagers and young adults with insulin-dependent diabetes mellitus (IDDM). Design A crossover design in which each subject consumed test meals in random order on 4 separate days at least 72 hours apart. Setting The inpatient setting of the General Clinical Research Center of the Indiana University Medical Center Hospital. Subjects Sixteen males and eight females, aged 14 to 25 years, with IDDM. Interventions After fasting overnight, each subject underwent challenge tests with 50g carbohydrate per 1.73m 2 of body surface area from sweetened flaked corn cereal, unsweetened flaked corn cereal, sucrose, and glucose. All subjects were maintained on continuous intravenous infusion of insulin overnight (euglycemic goal=3.9 to 6.7mmol/L), with a constant basal insulin dose infused before and throughout a 3-hour postprandial period. Main outcome measures Plasma glucose, free insulin, triglycerides, and free fatty acid levels measured at baseline and 15, 30, 45, 60, 90, 120, 150, and 180 minutes after meals. Statistical analyses performed Comparisons among the four meals were made using two-way repeated measures analyses of variance followed by the Newman-Keuls multiple comparison procedure to identify specific differences among meals. The areas under the response curves were compared using one-way repeated measures analysis of covariance, adjusted for baseline values. Results The response to glucose for the area under the 3-hour blood glucose response curve was significantly greater than the response to sucrose ( P =.006 by repeated measures analysis of variance); the areas for the two cereals (not significantly different from one another) were between the glucose and sucrose areas. At 3 hours, glycemia differed significantly among three of the meals: unsweetened flaked corn cereal>sweetened flaked corn cereal>sucrose ( P P Applications Equivalent gram amounts of carbohydrate as presweetened breakfast cereals are not detrimental to persons with IDDM compared with unsweetened cereals. Therefore, presweetened cereals can be used in the correct portion sizes and based on the number of carbohydrate or starch servings in a person's diabetic meal plan. J Am Diet Assoc. 1996; 96:458-463 .

Purpose: To describe glycemic control among older adolescents with insulin dependent diabetes mellitus (IDDM) as they move from pediatric to adult-focused health care. Methods: Prospective cohort study conducted in a university medical center. Participants included 82 consecutive adolescents (50 males and 32 females) with IDDM transferred from a pediatric to an adolescent/young adult diabetes clinic. Main outcome measures were the levels of total stable glycosylated hemoglobin (HbA 1 ) obtained at each visit for up to one year before and after the transfer. Results: The average age of transfer to the young adult clinic was 17.3 ± 0.8 years. Mean age at onset of IDDM was 9.6 ± 4.2 years (1.2 to 17.3) with duration of 7.7 ± 3.9 years (0.7 to 16.1). Glycemic control remained unchanged following transfer (9.9% ± 1.8 vs 10.2% ± 1.9; t = 1.6; p = 0.125). Following transfer, both males and females maintained similar levels of glycemic control (9.8% ± 1.7 and 10.7% ± 1.8 respectively); although the difference between males and females was significant ( t = −2.0; p = 0.048) following transfer, there was no difference in the degree of change by gender ( t = −0.2; p = 0.8). In both pediatric and young adult clinics, there was no relationship between duration of IDDM ( I . Conclusions: Transfer to an adult-focused diabetes program appears to have no negative impact on glycemic control.

Objectives. This study attempted to determine the safety and accuracy of dobutamine stress echocardiograpby for detection of coronary artery disease in patients with dilated cardiomyopathy. Background. Detection of regional wall motion abnormalities at rest does not reliably distinguish ischemic front nonischemic cardiomyopathy. Previous studies have shown that dobutamine stress echocardiography safely and accurately identifies coronary artery disease in patients without dilated cardiomyopathy. Methods. Seventy patients with dilated cardiomyopathy under-went dobutamine stress echocardiography. Echocardiograms were obtained at baseline and at low (5 to 10 μg/kg body weight per min) and peak doses of dobutamine. Rest and stress left ventricular wall motion scores were derived from analysis of regional wall motion. Fifty-four subjects underwent coronary angiography. Results. Dobutamine infusion was terminated after achievement of the target heart rate or maximal protocol dose in 49 patients (70%), ischemia in 12 (17%), arrhythmia in 4 (6%) and side efects in 5 (7%). No patient had prolonged ischemia or sustained arrhythmia. Of those with angiographic studies, 40 had significant coronary artery disease (≥50% diameter stenosis). Use of the change in global wall motion score index from low to peak dose resulted in a sensitivity of 83% for dobutamine stress echocardiography and a specificity of 71% for detection of coronary artery disease. Sensitivity for detection of triple-,double-and single-vessel disease was 100%, 83% and 69%, respectively. Conclusions. Dobutamine stress echocardiography safely provides diagnostic information in patients with dilated cardiomyopathy. This technique has high sensitivity for multivessel coronary artery disease but only moderate specificity.

The purpose of this study was to examine whether insulin's effect to vasodilate skeletal muscle vasculature is mediated by endothelium-derived nitric oxide (EDNO). N-monomethyl-L-arginine (L-NMMA), a specific inhibitor of NO synthase, was administered directly into the femoral artery of normal subjects at a dose of 16 mg/min and leg blood flow (LBF) was measured during an infusion of saline (NS) or during a euglycemic hyperinsulinemic clamp (HIC) designed to approximately double LBF. In response to the intrafemoral artery infusion of L-NMMA, LBF decreased from 0.296 +/- 0.032 to 0.235 +/- 0.022 liters/min during NS and from 0.479 +/- 0.118 to 0.266 +/- 0.052 liters/min during HIC, P < 0.03. The proportion of NO-dependent LBF during NS and HIC was approximately 20% and approximately 40%, respectively, P < 0.003 (NS vs. HIC). To elucidate whether insulin increases EDNO synthesis/release or EDNO action, vasodilative responses to graded intrafemoral artery infusions of the endothelium-dependent vasodilator methacholine chloride (MCh) or the endothelium-independent vasodilator sodium nitroprusside (SNP) were studied in normal subjects during either NS or HIC. LBF increments in response to intrafemoral artery infusions of MCh but not SNP were augmented during HIC versus NS, P < 0.03. In summary, insulin-mediated vasodilation is EDNO dependent. Insulin vasodilation of skeletal muscle vasculature most likely occurs via increasing EDNO synthesis/release. Thus, insulin appears to be a novel modulator of the EDNO system.

To evaluate the effect of salt responsiveness of blood pressure to the antihypertensive effect of calcium channel blockade, we studied 15 essential hypertensive patients who had previously been characterized with respect to salt sensitivity or resistance of blood pressure. After a placebo period, titration with verapamil in doses of 180 to 480 mg/day was begun until goal blood pressure responses were reached. The study population exhibited a significant (P < or = .007) reduction in systolic and diastolic blood pressure with treatment. There were no significant differences in the response to calcium channel blockade when the subjects were separated into salt-sensitive (n = 8) and salt-resistant (n = 7) subgroups. A significant (P < or = .05) correlation was observed between the age of the subjects and the blood pressure response. In this study verapamil lowered blood pressure in all subjects. We conclude that calcium channel blockade reduces blood pressure in essential hypertensive subjects during a normal sodium intake, independent of salt-sensitivity status.

Early pancreatic cancer response following cetuximab and/or irinotecan therapies was measured by serial dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) before and during therapy. Groups 1 to 4 (n = 6/group) of SCID mice bearing orthotopic pancreatic adenocarcinoma xenografts expressing luciferase were treated with phosphate-buffered saline, cetuximab, irinotecan, or cetuximab combined with irinotecan, respectively, twice weekly for 3 weeks. DCE-MRI was performed on days 0, 1, 2, and 3 after therapy initiation, whereas anatomic magnetic resonance imaging was performed on days 0, 1, 2, 3, 6, and 13. Bioluminescence imaging was performed on days 0 and 21. At day 21, all tumors were collected for further histologic analyses (Ki-67 and CD31 staining), whereas tumor dimensions were measured by calipers. The Ktrans values in the 0.5 mm-thick peripheral tumor region were calculated, and the changes in Ktrans during the 3 days posttherapy were compared to tumor volume changes, bioluminescent signal changes, and histologic findings. The Ktrans changes in the peripheral tumor region after 3 days of therapy were linearly correlated with 21-day decreases in tumor volume (p.001), bioluminescent signal (p = .050), microvessel densities (p = .002), and proliferating cell densities (p = .001). This study supports the clinical use of DCE-MRI for pancreatic cancer patients for early assessment of an anti-epidermal growth factor receptor therapy combined with chemotherapy.