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Background: Resource-based relative value scale is an objective estimate of physician work that allows comparisons of physician productivity, yet few studies have explored its use to compare the productivity between teaching faculty and nonteaching hospitalists., Methods: Demographic and billing data of patients assigned either to a resident-staffed teaching service or a hospitalist service, the number of encounters per provider, relative value units (RVUs) generated, and total charges were obtained from billing records (November 2006-April 2007). Age, race, sex, insurance status, case mix index, and length of stay were also analyzed., Results: The mean RVUs generated per unit of encounter and the mean charges generated per unit of encounter were not significantly different between the 2 services. However, mean RVUs generated per full-time equivalent provider and mean charges generated per clinical full-time equivalent were significantly higher in the teaching service., Conclusions: Based on a resource-based relative value scale analysis, the clinical productivity of teaching faculty was superior to that of nonteaching hospitalists. The difference may be attributable to lower time requirements of the teaching attendings compared with full-time hospitalists.

Darier's disease is a rare disorder of keratinization of the epidermis, nails, and mucous membranes. Patients usually present with pruritus and pain along with multiple small, red-brown papules on the seborrheic areas. Other cutaneous signs include punctate keratotic pits of the palms and soles and dystrophy of the nails. Darier's disease is the result of a mutation in the ATP2A2 gene. A case which was difficult to diagnose because its presentation resembled more commonly seen skin conditions is reported. The patient was misdiagnosed with acne, eczema, and seborrheic dermatitis, and was treated without improvements. This case highlights the fact that skin disorders that do not respond to conventional therapy should lead physicians to suspect an uncommon or even serious cutaneous disorder. The diagnosis of Darier's disease, based on family history, clinical appearance, and histopathology, expedited the appropriate treatment.

Background: The realization that angiotensin-converting enzyme (ACE) inhibitors do not provide complete blockade of angiotensin II synthesis has resulted in an increased use of combinations of ACE inhibitors and angiotensin receptor blockers (ARBs). This study examines the characteristics of patients in whom this combination was prescribed., Methods: Seventy-two patients diagnosed with primary hypertension and receiving an ACE inhibitor, an ARB, or their combinations were included. A retrospective review using outcome variables of mean arterial pressure (MAP), and changes between pretreatment MAP and post-treatment MAP were compared between groups. Statistical analysis was performed with SPSS statistical software. Analysis of variance (ANOVA) with Tukey's post hoc analysis was performed on continuous variables. Chi-square analysis was performed on categorical variables. Multivariate linear regression was performed to determine the best predictors of post-treatment MAP., Results: There were no significant differences between the groups in pre- or post-treatment MAP. Patients on combination therapy with an ACE and ARB agent tended to be on more antihypertensive medications and tended to be diabetic., Conclusion: All treatment groups had similar blood pressure control and changes in MAP regardless of treatment. These findings suggest that combination ARB and ACE inhibitor therapy is a strategy being used for diabetics with difficult-to-control hypertension, although we cannot determine from our study whether this is primarily for blood pressure control or for renal protection. Whether combining an ACE inhibitor and ARB for blood pressure control alone is supported by the literature may be debatable. Further studies should evaluate the efficacy of such intervention to control hypertension., Key Points: 1. Antihypertensive therapies using ACE inhibitors with ARBs are gaining popularity. 2. This retrospective chart review was completed to examine the characteristics of patients on monotherapy and of patients on combination therapy with ACE inhibitors and ARB agents. 3. This study suggests a tendency toward combined ARB and ACE inhibitor therapy in patients with diabetes who are on multiple antihypertensive medications.

The incidence, methods and risk factors for suicide may vary among the different cultures, which makes necessary to study the risk factors for suicide in specific settings in order to design adequate intervention strategies. This study aims to determine the risk factors for suicide in Medellín (Colombia). It is a case-control study conducted among 108 individuals who committed suicide and 108 deceased in accidents, matched for age and gender. Both cases and controls were examined by means of psychological autopsy. Conditional logistic regression analysis identified the following factors: Adverse life events in the last six months (OR=11.81, 95% CI: 4.29-32.52), family history of suicide (OR=10.82, 95% CI: 2.23-52.47), major depressive episode (OR=4.58, 95% CI: 1.53-13.67) and expression of a wish to die (OR=3.54, 95% CI: 1.25-10.06). These findings may suggest that risk factors for suicide are similar across cultures.

We performed a whole genome microsatellite marker scan in six multiplex families with bipolar (BP) mood disorder ascertained in Antioquia, a historically isolated population from North West Colombia. These families were characterized clinically using the approach employed in independent ongoing studies of BP in the closely related population of the Central Valley of Costa Rica. The most consistent linkage results from parametric and non-parametric analyses of the Colombian scan involved markers on 5q31-33, a region implicated by the previous studies of BP in Costa Rica. Because of these concordant results, a follow-up study with additional markers was undertaken in an expanded set of Colombian and Costa Rican families; this provided a genome-wide significant evidence of linkage of BPI to a candidate region of approximately 10 cM in 5q31-33 (maximum non-parametric linkage score=4.395, P<0.00004). Interestingly, this region has been implicated in several previous genetic studies of schizophrenia and psychosis, including disease association with variants of the enthoprotin and gamma-aminobutyric acid receptor genes.

Metastatic spread of prostate adenocarcinoma to the temporal bone is very rare. Involvement of the jugular foramen may result in Collet-Sicard syndrome. This syndrome is characterized by paralysis of the lower four cranial nerves. A case of metastatic prostate adenocarcinoma involving the temporal bone causing Collet-Sicard syndrome is presented. This case highlights an uncommon manifestation of prostate adenocarcinoma causing symptoms referable to the occipital condyle of the temporal bone. Few cases have been reported in the literature of Collet-Sicard syndrome due to metastatic prostate cancer. This case reminds readers that awareness of atypical presentations may reduce diagnostic delay and expedite appropriate treatment.

Recent reports have implicated polymorphisms in the brain derived neurotrophic factor (BDNF) gene region in the etiology of several psychiatric phenotypes, including bipolar disorder. Significant disease association has been reported for the G allele at SNP rs6265, which encodes for Valine at position 66 of BDNF (Val66Met), an apparently functional variant of this key BDNF. Here we examined a sample of 224 bipolar type I patients and available parents (comprising a total of 212 nuclear families) ascertained in a South American population isolate (Antioquia, Colombia). We tested for transmission distortion to bipolar patients of alleles at the rs6265 polymorphism and at a microsatellite marker 1.3 kb away from this SNP. Significant excess transmission of the rs6265 G allele to cases was observed (chi(2) = 10.77, d.f. = 1, P = 0.001). Two-locus haplotype analysis showed a significant global transmission distortion (chi(2) = 16.059, d.f. = 7, P = 0.025) with an excess transmission of a haplotype comprising the rs6265 G allele and microsatellite allele 227. These results are consistent with previous studies pointing to a role for BDNF in susceptibility to mood disorders., ((c) 2006 Wiley-Liss, Inc.)

This article addresses the increasing use of electronic medical records and supporting clinical information systems in US hospitals. It also addresses the current barriers to implementation of digital technology, which include cost, cultural factors, and the reluctance to embrace new technology. However, despite the barriers, there is evidence from the Veteran's Administration, Partners' HealthCare, Kaiser Permanente, and other organizations that electronic medical records and clinical information systems are a worthwhile investment. The benefits of the electronic medical records include the reduction of errors, improvement in clinical decision making during patient encounters, and universal access to information in real time. From a managerial perspective, health care organizations should adopt such systems to improve quality of care and to stay competitive in the marketplace. From a policy perspective, the electronic medical record provides an opportunity for integration of patient information and improves efficiency and quality of care across a wide range of patient populations.

Background: Aspirin has been routinely prescribed following transcatheter closure of secundum atrial septal defects (ASDs) but its rationale has not been clinically or biologically evaluated; and despite aspirin, thrombotic complications occur following transcatheter ASD closure. We therefore evaluated the presence, degree and timing of the activation of the coagulation and platelet systems following transcatheter closure of ASDs., Methods and Results: Fourteen consecutive patients (9 females, mean age 41+/-22 years) who underwent successful transcatheter closure of an ASD defect with the Amplatzer septal occluder were prospectively studied. Measurements of the prothrombin fragment 1+2 (F1+2) levels and the percentage of activated platelets (determined by P-selectin expression detected by flow cytometry) were taken at baseline just before the procedure, and at 1, 7, 30 and 90 days following device implantation. F1+2 levels increased from 0.85+/-0.29 nmol/l at baseline to a maximal value of 1.20+/-0.52 nmol/l at 7 days, gradually returning to the baseline levels at 90 days (0.79+/-0.54 nmol/l) (p<0.001). F1+2 levels at 7 days were also significantly higher than those obtained in a control group of 20 healthy subjects (p=0.016). A greater increase in coagulation activation was observed in cases of residual shunt following ASD closure (r=0.53, p=0.050). No significant variations in the percentage of platelets expressing P-selectin were detected at any time., Conclusions: Transcatheter closure of ASDs with the Amplatzer septal occluder was associated with a significant increase in F1+2 levels during the first week after device implantation, but there was no detectable effect on platelet system activation. These findings raise the question whether the optimal prophylactic approach following transcatheter ASD closure should be anticoagulant instead of antiplatelet therapy.

The mammalian kidney bumetanide-sensitive Na(+)-K(+)-2Cl(-) and thiazide-sensitive Na(+)-Cl(-) cotransporters are the major pathways for salt reabsorption in the thick ascending limb of Henle's loop and distal convoluted tubule, respectively. These cotransporters serve as receptors for the loop- and thiazide-type diuretics, and inactivating mutations of corresponding genes are associated with development of Bartter's syndrome type I and Gitleman's disease, respectively. Structural requirements for ion translocation and diuretic binding specificity are unknown. As an initial approach for analyzing structural determinants conferring ion or diuretic preferences in these cotransporters, we exploited functional differences and structural similarities between Na(+)-K(+)-2Cl(-) and Na(+)-Cl(-) cotransporters to design and study chimeric proteins in which the NH(2)-terminal and/or COOH-terminal domains were switched between each other. Thus six chimeric proteins were produced. Using the heterologous expression system of Xenopus laevis oocytes, we observed that four chimeras exhibited functional activity. Our results revealed that, in the Na(+)-K(+)-2Cl(-) cotransporter, ion translocation and diuretic binding specificity are determined by the central hydrophobic domain. Thus NH(2)-terminal and COOH-terminal domains do not play a role in defining these properties. A similar conclusion can be suggested for the Na(+)-Cl(-) cotransporter.

The thiazide-sensitive Na+:Cl- cotransporter is the major salt transport pathway in the distal convoluted tubule of the kidney, and a role of this cotransporter in blood pressure homeostasis has been defined by physiological studies on pressure natriuresis and by its involvement in monogenic diseases that feature arterial hypotension or hypertension. Data base analysis revealed that 135 single nucleotide polymorphisms along the human SLC12A3 gene that encodes the Na+:Cl- cotransporter have been reported. Eight are located within the coding region, and one results in a single amino acid change; the residue glycine at the position 264 is changed to alanine (G264A). This residue is located within the fourth transmembrane domain of the predicted structure. Because Gly-264 is a highly conserved residue, we studied the functional properties of this polymorphism by using in vitro mutagenesis and the heterologous expression system in Xenopus laevis oocytes. G264A resulted in a significant and reproducible reduction ( approximately 50%) in (22)Na+ uptake when compared with the wild type cotransporter. The affinity for extracellular Cl- and for thiazide diuretics was increased in G264A. Western blot analysis showed similar immunoreactive bands between the wild type and the G264A cotransporters, and confocal images of oocytes injected with enhanced green fluorescent protein-tagged wild type and G264A cotransporter showed no differences in the protein surface expression level. These observations suggest that the G264A polymorphism is associated with reduction in the substrate translocation rate of the cotransporter, due to a decrease in the intrinsic activity. Our study also reveals a role of the transmembrane segment 4 in defining the affinity for extracellular Cl- and thiazide diuretics.

Soy intake reduces cholesterol levels, but neither the exact component in soy causing this reduction nor the mechanism by which cholesterol is reduced is known with certainty. In this study, a genetic screen was performed to identify hepatic mRNA in gerbils regulated by soy or soy isoflavones. Gerbils were fed casein, an alcohol-washed soy-based diet (containing low levels of isoflavones), and the soy-based diet supplemented with an isoflavone-containing soy extract. After feeding for 28 d, gerbils were killed, hepatic RNA was isolated, and genes that were differentially expressed in any of the three dietary conditions were identified. Fifteen different mRNA were originally selected, including two mRNA that were studied further and shown to be highly regulated. Messenger RNA levels for both cytochrome P450-2A and phosphoribosylpyrophosphate synthetase-associated protein were up-regulated in a dose-dependent manner when soy replaced casein in the diet at 0, 33, 67 and 100% of original casein levels. A subsequent experiment used purified amino acid mixtures resembling the percentage amino acid composition of soy and casein to ensure that isoflavone-free protein sources could be tested. Using these mixtures, a 2 x 2 x 2 design tested: natural vs. synthetic protein sources, casein- vs. soy-based diets, and isoflavone extract-supplemented or supplement-free diets. This design demonstrated that these two mRNA were again significantly up-regulated more than twofold (P < 0.05) in gerbils fed all diets containing isoflavones. Induction of these two mRNA by soy may be due to the aryl hydrocarbon receptor element in the promoter region of both genes.

Background and Objectives: Bone marrow biopsies are routinely performed in the staging of patients with lymphoma. Despite the lack of evidence for its usefulness, many institutions include flow cytometry (FC) of bone-marrow aspirates in an attempt to increase sensitivity and specificity. The aim of this study is to evaluate the usefulness of FC for the assessment of bone-marrow involvement by lymphoma in follicular (FL) and diffuse large B-cell lymphomas (DLBCL)., Design and Methods: Seventy-nine bone marrow biopsies from 65 patients diagnosed with FL or DLBCL were examined to compare histology and FC for the assessment of bone-marrow involvement by lymphoma., Results: Bone marrow histology showed involvement (BM+) in 16 cases (20.3%), lack of infiltration (BM(-)) in 52 cases (65.8%) and undetermined or undiagnosed for involvement (BMu) in 11 cases (13.9%). FC was positive for involvement in 28 cases (35.4%) and negative in 51 cases (64.6%). 65 cases (95%) showed concordance between the results of morphology and FC (BM(+)/FC(+) or BM(-)/FC(-)). No BM(+)/FC(-) cases were observed. 3 cases showed discrepant results (BM(-)/FC(+)). In these 3 cases the molecular studies (PCR) demonstrated clonal rearrangement of the heavy immunoglobulin chain (IgH) and/or bcl2-IgH in agreement with the flow results. Among the 11 cases with BMu, all but 2 were FC(+) and concordance with the PCR results was seen in 9 cases (81.9%)., Interpretation and Conclusions: We conclude that FC is just as sensitive or perhaps slightly more sensitive than histology in the detection of bone marrow involvement in FL and DLBCL. FC studies may be warranted in those cases in which the morphology is not diagnosed. The clinical relevance of the small clonal B-cell population in patients without histologic bone marrow involvement (BM(-)/FC(+) cases) remains an open question.

The short variant of a functional length polymorphism in the promoter region of the serotonin transporter has been associated with several behavioural and psychiatric traits, including bipolar mood disorder. The same short allele has also been implicated as a modifier of the bipolar phenotype. Here we evaluate the etiologic/modifier role of this polymorphism in a case (N=103) / control (N=112) sample for bipolar mood disorder (type I) collected from an isolated South American population. We did not detect an association between bipolar disorder and the 5-HTT promoter polymorphism in this sample. However, an excess of the short allele was seen in younger cases and in cases with psychotic symptoms. When combined with data from the literature, the increased frequency of the short allele in patients with psychotic symptoms was statistically significant.

Background: Thrombotic Thrombocytopenic Purpura (TTP) is an uncommon clinical syndrome with high mortality rate in the absence of treatment. Despite the therapeutic efficacy of plasma exchange, patients often relapse even after long periods of time in remission. Over the last few years, late relapses in previously diagnosed patients have been seen in our hospital., Patients and Methods: We analyzed retrospectively 22 episodes of TTP in 16 patients diagnosed during a four-year period. We reviewed the clinical features at diagnosis as well as the therapeutic results. In all but one, the treatment included daily plasma exchange. Other treatments, including vincristine, were also used in addition to plasma exchange, in 18 of 21 episodes., Results: A complete remission was obtained in eighty-two percent of the episodes treated by plasma exchange. The median number of plasma exchange to achieve a complete remission was 6. In 4 episodes, 20 or more plasma exchange were required before achieving a satisfactory response. A complete remission was obtained in 78% of episodes where vincristine was used, versus 84% response rate in episodes where vincristine was not used. In four patients the cause death was directly related to TTP, while a fifth patients died of progressive lymphoma without evidence of TTP. Five of the eleven surviving patients relapsed with a median time to relapse of 24.6 months. Relapsing episodes presented with a less severe clinical picture including less clear signs of microangiopathic hemolytic anemia (MAHA), when compared with the initial ones. All patients in relapse responded promptly to treatment. The variables analyzed failed to predict either the response to treatment or the probability of relapse., Conclusions: The therapeutic efficacy of plasma exchange in the treatment of TTP has been demonstrated in our series as previously observed by many other groups. We have observed some slow responders where the prolongation of treatment by plasma exchange succeeded in achieving a complete remission. The use of vincristine did not show any therapeutical advantage in our experience.

Invasive aspergillosis is a severe complication in the immunocompromised patient. Despite antifungal treatment the mortality rate is higher than 90% if the immunity deficiency is not corrected. The use and dosage of conventional amphotericin B (deoxycholate-suspended formulation) is limited by its toxicity, especially nephrotoxicity. To reduce these untoward effects, amphotericin B has been formulated in liposomes. Better tolerance and lower nephrotoxicity in the liposomal formulations allow higher doses to be given safely, even in the presence of renal failure. Liposomal encapsulated amphotericin B (LAmB) is a safe and effective alternative to conventional formulations for antifungal therapy. We present a case of a 60-year-old man affected by chronic lymphocytic leukaemia. In the course of his disease and after chemotherapy treatment, he presented an invasive aspergillosis of the lung and paransal sinuses. The rhino-sinusal lesion had progressed despite surgical debridement and treatment with amphotericin B in a dosage of 50 mg per day. Moreover, renal impairment caused by conventional amphotericin was detected. Then, LAmB was started at a dose of 150 mg per day. Treatment with LAmB has resulted in clinical recovery and radiologic ressolution.