Search

The experience with immune tolerance (IT) induction therapy for haemophilia patients with inhibitors, instituted during 1990-97 at 17 haemophilia treatment centres in the western United States, was reviewed. IT was instituted in 104 of 139 (75%) of all identified haemophilia A and haemophilia B patients with inhibitors. Doses and schedules for IT varied but most patients were treated with a daily administration of 25-200 units kg-1 day-1. Successful immune tolerance (defined as Bethesda Unit titres < 1.0) was achieved in 57 of 81 (78%) patients who completed therapy. IT success was significantly greater for those patients with historic titres < 100 BU (P < 0.0003) and those with titres of < 10 BU at initiation of IT (P < 0.0001). IT success was uniformly achieved in 16 patients with low to moderate responding inhibitors. IT in infants < 2 years of age was problematic due to the presence of high titre inhibitors and complications of venous access. Frequent complications of IT included increased bleeding during intravenous access device insertion (20%) and infections associated with venous access devices (64%). IT is widely accepted as a treatment modality for haemophilia patients with inhibitors. Patient participation in IT regimens and management during therapy is facilitated greatly by the efforts of treatment centre nurse coordinators who are knowledgeable about haemophilia and its complications. Additional clinical trials will be necessary to define better initial dose, schedule, dose adjustment and success/failure criteria for IT.

Hepatitis C is a major cause of liver disease leading to cirrhosis. Although interferon (IFN) is the only approved therapy, treatment is characterized by low response rates and dose-limiting side effects. We evaluated the addition of thymosin alpha1 (TA1), an immunomodulatory peptide, to the standard treatment regimen for hepatitis C to determine if combination therapy shows biological activity using outcome measures including normalization of alanine aminotransferase levels, histological activity, and viral load during treatment. We performed a randomized, double-blind, placebo-controlled trial to compare the biological activity of a combination TA1 and IFN with that seen for IFN alone in patients with chronic hepatitis C infection. One hundred nine patients were randomized for intention to treat and received 1.6 mg of TA1 subcutaneously twice weekly and 3 MU of IFN three times weekly; 3 MU of IFN three times weekly and placebo TA1; or placebo for both agents. All patients had chronic HCV infection with confirmation of chronic hepatitis on liver biopsy. Biochemical responders were followed up until alanine aminotransferase (ALT) levels became abnormal or for 26 weeks, and relapsers were retreated for 26 weeks in the same treatment arm. One hundred three patients completed treatment for 26 weeks, and six patients dropped out. The groups were similar with regard to sex, gender distribution, baseline histological activity index (HAI) score, risk factors, and viral titers. End-of-treatment biochemical response was seen in 37.1% of patients treated with combination therapy, 16.2% of patients treated with IFN alone, and 2.7% of untreated controls by intent-to-treat analysis (IFN/TA1 vs. IFN, chi2 = 4.05, P = .04). HCV RNA clearance was seen in 37.1% of IFN/TA1-treated patients and 18.9% of IFN-treated subjects. Mean HCV RNA titers were significantly lower than baseline at weeks 8, 16, and 24 after drug initiation among patients treated with IFN/TA1 but not in the other treatment arms. Histological improvement, as evidenced by a decrease in HAI of more than two points, occurred in the combination therapy arm more frequently than in comparison groups. Cumulative sustained biochemical responses were 14.2% and 8.1% in the IFN/TA1 and IFN arms, respectively, based on an intention-to-treat model. The combination of TA1 and standard IFN treatment for chronic hepatitis C showed evidence of biological activity at the completion of treatment by biochemical, histological, and virological outcome measures. Further research involving longer duration and varied dosing is needed.

Background: Patients with abdominal aortic aneurysm often are followed up with serial ultrasound examinations, but published studies usually describe rupture risk according to the diameter of the abdominal aortic aneurysm at diagnosis rather than by most recent ultrasound. Information in this form is misleading when used to predict prognosis., Methods: We used data from the population-based cohort of residents of Rochester, Minn, diagnosed as having abdominal aortic aneurysm who have had at least 1 ultrasound measurement. Of the 181 patients who were enrolled in this cohort between January 1, 1974, and December 31, 1988, 5 had clinical evidence of rupture at entry. Analysis of a cohort defined by size category at "last ultrasound" was undertaken to assess rupture risk and growth rate., Results: Median overall aneurysmal growth rate was 0.21 cm/y. Initial growth rate did not correlate with subsequent growth rate (r = 0.18; P = .14) or with initial size (r = -0.12; P = .22). Only 1 aneurysm ruptured when last ultrasound was less than 5 cm, and this occurred 3 1/2 years after this ultrasound. Estimated rupture risk by last ultrasound was 0% per year (95% confidence interval [CI], 0%-5%) when less than 4.00 cm, 1.0% per year (95% CI, 0%-5%) when 4.00 to 4.99 cm, and 11% per year (95% CI, 1%-21%) when 5.00 to 5.99 cm., Conclusions: The most clinically useful approach to estimating the risk of abdominal aortic aneurysm rupture is according to size at last ultrasound. Aneurysm growth rate is predicted neither by size nor by initial growth rate.

The follow up of pacemaker and defibrillator dependent patients has a significant role for both the evaluation of pacing effectiveness and check of hemodynamic advantages about patient's quality of life. The bulky paper archives are often inaccurate, hampering the consultation. At present the paper card is the only document which can be utilized to record some data concerning the implant and patient clinical story. Therefore, there is the necessity for a card that can include all patient's data, and the implant and programming pacemaker/defibrillator data during follow up. This new pacemaker card has portable file or data-base including shared data with safety mechanism, which can be utilized in several controls by different users (physicians, hospital ward, primary care units, insurance companies). The pacemaker card includes a chip that permits to store a considerable amount of data; it can be update in every further medical control, in observance of laws. The card Chip Operating System (C.O.S.) consists of a microchip with a memory completely managed by the operating system inside the chip itself. The card can be read by means of a GCR-200 modem linked with a PC IBM-compatible computer and the data can be updated during the follow up. The pacemaker-defibrillator card will appear immediately on screen, and it can be printed, updated and/or modified by a Microsoft Windows operating programme. With this pacemaker card we are able to ensure serviceable medical work, particularly in terms of cost/benefit ratio giving to patient more and more reasoning and safe service.

Objectives: We compared the efficacy of two different mapping techniques in identifying the ablation site for atrial tachycardia. Moreover, we evaluated the additive positive predictive value of mechanical interruption of atrial tachycardia to reduce the number of ineffective radiofrequency applications., Background: Radiofrequency catheter ablation has been suggested as a highly effective technique to treat drug-resistant atrial tachycardia. However, irrespective of the mapping technique utilized, success was most often achieved with a large number of radiofrequency applications., Methods: Forty-five patients with atrial tachycardia underwent radiofrequency catheter ablation. Mapping techniques included identification of earliest atrial activation and pace-mapping concordant sequence., Results: Atrial tachycardia was successfully treated in 42 (93.3%) of 45 patients with a mean of 3.9 radiofrequency pulses/patient. An interval between the onset of the intracavitary atrial deflection and the onset of the P wave during atrial tachycardia (AP interval) > or = 30 ms (p < 0.001) and pace-mapping concordant sequence (p = 0.01) were all significant predictors of outcome. An AP interval > or = 30 ms and a pace-mapping concordant sequence were highly sensitive (92.8%, 95% confidence interval [CI] 80.5% to 98.5%; 85.7%, 95% CI 71.5% to 94.6%, respectively) but less specific (47.8%, 95% CI 37.9% to 58.2%, 36.8%, 95% CI 27.6% to 47.2%, respectively) in identifying the site of ablation. By using atrial tachycardia mechanical interruption combined with the AP interval >30 ms or the pace-mapping concordant sequence, we obtained a specifically of 76.5% (95% CI 66.4% to 84.0%) and 73.5% (95% CI 63.2% to 81.4%), respectively, and a positive predictive value of 49.2% and 44.6%, respectively., Conclusions: An AP interval > or = 30 ms and a pace-mapping concordant sequence were reliable mapping features for predicting the outcome of the ablation procedure. Mechanical interruption of atrial tachycardia improved the specificity and positive predictive value of these two mapping techniques.

Background: The observation of low levels of weed pollens following a freeze and an early autumn snowfall in Denver, Colorado led to this analysis of meteorologic variables and pollen counts., Objective: The purpose of this study was to examine, in depth, the relationship between observed pollen counts and a selection of independent meteorologic variables., Methods: We prospectively studied in 1991 daily high and low temperature, relative humidity, precipitation, barometric pressure, percent sunshine, wind velocity and direction, tree, grass, and weed pollen, as well as dates of the first frost/freeze. Similar data were retrospectively analyzed for 1987-1990., Results: Correlation coefficients for the prospective data were as high as .611 for high temperature and cottonwood and .718 for high temperature and maple (P < .001). High and low temperature showed strong correlations with the combined weed counts (.598 and .628, respectively, P < .001)., Conclusions: Denver weed pollens appear impacted more by temperature and less by precipitation and humidity, while the converse is true for tree and grass pollen. However, weed pollen, especially sage, may appreciably rebound after freezing temperatures. While separate meteorologic variables may have high correlations with specific pollen counts in a given year, such effect is not consistent and varies from year to year.

Objective: To determine the clinical usefulness of skin temperature patterns for tracking reflex sympathetic dystrophy (RSD) by assessing (a) long-term relationships between changes in pain due to RSD and patterns of near surface blood flow and (b) relationships between site of pain and site of greatest asymmetries in near surface blood flow patterns., Design: Multiple videothermographic evaluations of near surface blood flow patterns were performed on subjects diagnosed as having RSD. At each session, subjects filled in an outline of the body to show the location, intensity, and description of their pain. The thermograms were evaluated independently by two raters for location and intensity of pain, as well as location and degree of temperature asymmetries., Setting: Two Army Medical Centers., Subjects: Thirteen male and 16 female subjects were subsequently diagnosed as having RSD., Outcome Measures: Ratings of pain and videothermograms of the lower limbs were used as outcome measures., Results: All but one subject were usually cooler on the most painful side by at least 0.5 degrees C. The amount of relative coolness was not proportional to pain intensity. There were no consistent overlaps between exact location of pain and greatest thermal asymmetry. Seven subjects were thermally symmetrical on at least one recording. Six subjects were warmer on the affected side on at least one recording. One subject was always warmer on the affected side., Conclusions: Videothermography is not an appropriate tool to use alone for either single session diagnosis or multi-session tracking of RSD.

To assess the impact of a quality improvement program on the occurrence of serious complications related to endotracheal tube misplacement and to identify risk factors, we did a before and after comparison in the adult intensive care units of a military referral hospital. All adult patients requiring endotracheal intubation during two 12-month periods comprised the study population. After the identification of a sentinel case, a retrospective review identified 278 adult patients requiring endotracheal intubation over a 12-month period. Twenty-two of these patients had at least one significant endotracheal tube misplacement; five of these misplacements (23%) were associated with serious complications (anoxic encephalopathy, atelectasis and respiratory failure, gastric aspiration, pneumothorax, and hypoxemia). In four of these patients the complications directly contributed to patient morbidity and mortality. During a subsequent 12-month period, after the initiation of a quality improvement program, 246 patients requiring tracheal intubation were prospectively studied. Of these 246 patients, 113 (46%) were identified as having at least one endotracheal tube misplacement requiring immediate repositioning. The incidence of serious complications related to endotracheal tube misplacement was significantly less during the implementation of the quality improvement program (0 of 246 patients) than during the retrospective period (5 of 278 patients). Multivariate analysis showed that a longer duration of endotracheal intubation, the lack of chemical paralysis, and the occurrence of cardiac arrest were independently predictive of endotracheal tube misplacement. These results suggest that a specific ICU quality improvement program can have a favorable impact on patient outcome.

An interview system was used to survey 56,199 students in Avellaneda between the ages of 3 and 20 years, representing 60.6% of the population of that age group in the census. The study covered 178 of the 201 pre-schools, grade schools, high schools and special schools in the area. Thirty three diabetic children were identified (18 girls, 15 boys), with a mean of 12.5 years of age. This represents a prevalence of diabetes in the school age population of 0.45/1000 in the 3-12 year old group, 1.25/1000 in the 13-20 year old group, with 0.59/1000 for the total of children surveyed. (93.82 of ascertainement, 95% CI 0.34 to 0.42/1000). Similar figures have resulted from studies in developed countries. The most frequent initial symptoms were the typical ones, with only 15% showing acidosis or diabetic coma as the initiation of the illness. Viral infections and stress appeared to be related to the onset of the disease. Diabetes was in the family history of 48.5% of the diabetic children, and 24.5% of the non-diabetics. The most common diabetic relative was the paternal grandfather. The maternal side showed a higher number of diabetic relatives with preponderance of males. No socio-economic differences were found between diabetics and non-diabetics.

Purpose: Although intracranial hemorrhage remains a leading cause of death in hemophilia, spinal epidural hematoma is seen rarely. Decompressive laminectomy has a high associated morbidity, and recent reports have suggested that patients can be treated conservatively without surgical intervention., Patients and Methods: We present a case of spontaneous spinal epidural hematoma diagnosed by MRI scan in a 6-month-old hemophilic infant. Immediate treatment with factor VIII replacement was instituted., Results: There was rapid and complete clinical and radiographic resolution., Conclusion: This case shows that selected hemophilic patients with spinal epidural hematoma can be spared surgical decompression by prompt medical attention.

It is very difficult to evaluate the ability of carrying out physical exercise in patients with rate responsive (RR) pacemaker (PM). However, the anaerobic threshold (AT) proved to be a useful parameter in the evaluation of cardiac function. The AT can be easily reproduced and not influenced from emotional aspects of both the patient and the physician, moreover being under maximum and then easy to achieve. Aims of our study were: to evaluate if the cardiopulmonary stress test can represent a method to be used for a more correct rate responsive pacemaker programming; to compare the data obtained of 3 rate responsive pacemakers steered by different sensors. We have studied 24 patients, of whom 10 with Activitrax (A), 8 with Meta (M), and 6 with Phymos MPT (P) pacemakers. Patients were submitted to symptoms limited cycloergometer stress test at 2 different settings: fixed rate at 70 b/min; increasing rate at until 85% of maximum heart rate for each patient, with range 0 + 10 W/min. Gas exchange data were continuously collected using an automated system (Medical Graphic System 2001) based on Whipp and Wasserman's method.(ABSTRACT TRUNCATED AT 250 WORDS)

One hundred twenty-eight patients were examined prospectively to determine the significance of mucosal thickening seen in the paranasal sinuses during routine MR imaging of the brain. On the basis of responses to a questionnaire, each patient was categorized as symptomatic (n = 60) or asymptomatic (n = 68) for paranasal sinus disease. Patients were categorized further on the basis of the maximal mucosal thickening seen by MR in any paranasal sinus. A modified t test was used to compare the prevalence of various degrees of mucosal thickening between symptomatic and asymptomatic groups. Statistically significant differences between the groups were seen only in those patients with normal sinuses and in those with 4 mm or more of mucosal thickening. We conclude that mucosal thickening of up to 3 mm is common and lacks clinical significance in asymptomatic patients. An ancillary finding is that 1- to 2-mm areas of mucosal thickening in the ethmoidal sinuses occur in 63% of asymptomatic patients. This minimal mucosal thickening in the ethmoidal sinuses is thought to be a normal variant, possibly a function of the physiologic nasal cycle.

Radiographic contrast media (CM) (meglumine/sodium diatrizoate-76%; 1650 mOsm/kg) and other hypertonic solutions induce renal vasoconstriction by an unknown mechanism. In anesthetized dogs, renal blood flow (RBF) was measured with an electromagnetic flowmeter and filtration fraction (FF) and glomerular filtration rate (GFR) by the renal extraction of technetium-99m tin chelate. Ureteral pressure (UP) and wedged renal venous pressure (VP) were measured as indices of intrarenal pressure. Measurements of renal length (L), along with pressures, made it possible to examine the compliance of the system. A 4-cc intrarenal bolus of CM caused a 59% reduction in GFR (control: 0.63 +/- 0.04 to 0.26 +/- 0.04 ml/min X g, mean +/- SEM), in association with a 23% reduction in RBF (control: 3.10 +/- 0.11 to 2.39 +/- 0.26 ml/min X g) and a 44% decrease in FF (control: 0.32 +/- 0.01 to 0.18 +/- 0.03). These responses were compared with a 3-microgram intrarenal bolus of norepinephrine (NOREPI) which resulted in a 79.0 +/- 7.5% reduction in RBF, 68.3 +/- 7.3% reduction in GFR and 42.6 +/- 15.6% increase in FF. The NOREPI-induced vasoconstriction caused transient decreases in renal L, UP, and VP, whereas the CM-induced decrease in renal blood flow was associated with increases in these parameters. In studies employing ureteral occlusion to elevate intrarenal pressure, the magnitude (area, cm2) of the CM-induced decrease in renal perfusion was accentuated with increased UP (r = 0.79, n = 24, P less than 0.001). The CM-induced increase in renal L, UP, and VP must reflect osmotic forces and an increase in intrarenal pressure. The decreases in FF and GFR probably reflect Starling forces in the glomerular capillaries, with osmotic transients dominating. The results suggest a mechanical mechanism for the CM-induced decrease in RBF.

A group of 13 patients on Continous Ambulatory Peritoneal Dialysis up to 18 months was studied. During the study period, Peritoneal Urea Clearance was stable. In all but 2 cases peritonitis did not depress the efficiency in clearing urea. When Peritoneal Urea Clearance was corrected for 1.73 m2 surface area, there was on the average an 11.8% increase over not corrected clearance rates. This increase was statistically significant.

The effects of three calcium antagonists, verapamil, lanthanum, and 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB-8) were studied on the release of slow-reacting substance of anaphylaxis (SRS-A) from ovalbumin-sensitized chopped guinea pig lung parenchyma in calcium-containing and calcium-free media. The SRS-A levels (mean +/- SEM) obtained from tissues incubated in normal and calcium-free Krebs-bicarbonate buffer were 51 +/- 8 (N = 19) and 21 +/- 4 (N = 14) U/mL, respectively. TMB-8 (0.1-10 microM), a reported intracellular calcium antagonist, reduced antigen-stimulated SRS-A release from lung tissue incubated in calcium-containing, but not calcium-free, medium; A23187-induced SRS-A release from normal guinea pig lung was not significantly altered by TMB-8 at concentrations up to 10 microM. Verapamil and lanthanum consistently reduced SRS-A release only at high concentrations (100 microM and 1mM, respectively). The quantities of SRS-A released from lung tissue incubated in the presence of verapamil in normal medium were similar to those obtained in calcium-free medium. Tissues incubated in the presence of potassium chloride (60 and 100 mM) did not release significant quantities of SRS-A, and release which did occur was not blocked by verapamil, suggesting that antigen-induced SRS-A release is not dependent on membrane depolarization and that verapamil was not exerting inhibition via blockade of voltage-dependent calcium channels. These data suggest that although intracellular calcium is important for the regulation of SRS-A secretion from guinea pig lung tissue, extracellular calcium is necessary for optimal release of SRS-A.

The equilibrium between plasma and peritoneal dialysis fluid has been studies for 23 amino acids during peritoneal exchanges at dwell times up to 8 hours in patients on CAPD. It is demonstrated that equilibration is a particular process typical for each amino acid which after 8 hour is nearly complete only for Glycine, Alanine and Asparagine.

To study the cost-effectiveness of fecal culture in the detection of enteropathogenic or enteroinvasive bacteria, a review and analysis was done of fecal cultures from ambulatory or hospitalized patients treated for acute diarrhea at a Buenos Aires sanatorium during 1985. Of 1,295 fecal cultures performed, pathogens were isolated in 369 cases (28.5%), of which 79 corresponded to Shigella sp. (S. flexnerii, 49; S. sonnei, 29; S. dysenteriae, 2), 25 to Salmonella sp., and 270 to enteropathogenic Escherichia coli (EPEC) of the infant. There was no statistically significant difference between the ambulatory patients and the hospitalized patients in the proportion of positive fecal cultures. The cost of each positive fecal culture was US$ 60.36, while the cost of diagnosing invasion of the mucous membrane (isolation of Shigella sp. or detection of leukocytes in feces) was US$ 109.74. These costs are excessive and could be greatly reduced if the test were applied in only selected cases. Many of the strains of Shigella sp., Salmonella sp., and EPEC that were found were resistant to ampicillin, chloramphenicol, and cotrimoxazole. These cases of resistance suggest that fosfomycin may be one of the antibiotics of choice for the treatment of diarrhea caused by invasive organisms.

Danazol, a synthetic androgen reported to increase factor VIII and IX activity levels, was given to 6 hemophiliacs. With danazol therapy (600 mg/da) the APTTs shortened by 30-45% of pre-treatment times. However, the activity levels of the deficient factors did not increase significantly nor consistently with the APTT change. The prothrombin times and activity levels of factors XI and XII also did not change during the study period. Addition of plasma from danazol-treated patients to plasma with a known factor VIII inhibitor and to plasma from an untreated severe hemophilia A patient caused a similar shortening of the respective APTTs. Absorption of the danazol plasma with precipitating antibody against factor VIII and IX did not remove the APTT correcting principal. The data suggest that danazol may cause the de novo appearance of an intrinsic coagulation pathway activator having factor VIII and IX bypassing activity.

Current medical management programs for established joint diseases in hemophiliacs are unsatisfactory and do not modify the eventual outcome. D-penicillamine, a drug effective in the proliferative synovitis of rheumatoid arthritis, was evaluated in a rabbit model of hemarthroses-induced arthritis and in four hemophiliacs with chronic synovitis. The animals had intra-articular injections of citrate (left knees) and autologous citrated whole blood (right knees). Eight weeks later, the rabbits were divided into two groups: no treatment and D-penicillamine (50 mg/kg/day, IM) until sacrificed at 6 months. The saline-injected joints showed no inflammation and no iron deposition. The blood-injected knees showed iron deposition in both groups, the D-penicillamine animals had marked suppression of chronic inflammation. Of the four patients treated, three had clinical responses (reduction in synovial thickness, reduction in number of bleeds in the affected joint). One patient, who did not respond, developed mild-moderate proteinuria. Those patients who responded received between 5.3 and 7.1 mg/kg/day of the drug. Mild abnormalities in platelet aggregation were seen in the responders. This preliminary study suggests that D-penicillamine is beneficial in the chronic synovitis/arthritis induced by hemarthroses. Further trials are recommended.

Danazol was given orally at a dose of 600 mg/day to six hemophiliacs for eight to 14 weeks. All patients showed a significant decrease in activated partial thromboplastin time (APTT) beginning with the first measurement (two weeks) and persisting until use of the drug was discontinued. However, a corresponding increase in the deficient factor activity could not be consistently demonstrated. Despite the shortened APTT, bleeding episodes continued in the severe hemophiliacs and the patient with Christmas disease. In four patients, bleeding appeared to increase in severity or change in pattern, and in two cases the bleeding manifestations did not respond to usual factor infusions but responded to discontinuation of the drug therapy and further factor replacement. Euglobulin lysis times were measured in five patients (one hemophiliac and four with nonhemophilic conditions) who were receiving danazol. The lysis times were markedly shortened. Increased fibrinolytic activity may be responsible for the increased bleeding manifestations in danazol-treated hemophiliacs.

A sensitive, rapid high-pressure liquid chromatographic assay was developed to compare the disposition of an intravenous dose of 14C-nicotine in normal, carefully matched smokers and nonsmokers. The elimination half-lifes of nicotine and cotinine were shorter in smokers than in nonsmokers. Also consistent with an inductive effect of smoking was the increased nicotine elimination rate constant in smokers, but smoking induced more complex kinetic changes: nicotine volume of distribution was diminished in smokers, whereas nicotine clearance and area under the concentration-time curve were unchanged. The presence of nicotine and its principal metabolites in a morning specimen of urine obtained from nonsmokers before 14C-nicotine administration suggests ubiquitous, passive exposure to and absorption of chemicals present in cigarette smoke.

Amino acid losses in peritoneal dialyzate during CAPD were less than 2 g a day (15, 128 micrometers). CAPD does not correct the tyrosine/phenylalanine ratio in plasma and does not prevent accumulation of 3-methylhistidine.