Perspectives of Hospitalists in an Academic Health System.

Objectives: The primary outcome of this study is to assess the perspectives of Hospitalists on their workload and their perceived effects on patient care. The secondary outcomes are to evaluate the satisfaction of the Hospitalists with their compensation, quality of life, scholarship activity and promotion in their department and the support received to achieve this. Methodology: We developed a 49-question questionnaire. The questionnaire was based on (a) Oldenburg Burnout Inventory and (b) topics specific to census, compensation, academic support with desire for promotion, and the effects of workload on patient care and teaching. All questions were formatted with a 4-point Likert-type response scale. The questionnaires were distributed electronically using an online survey platform to all 32 of the Hospitalists at our institution. Conclusion: Each institution needs to do a self-assessment based on clinician feedback: Hospitalists workload, burn-out and satisfaction to reduce the high turnover rates and brevity of this role. From this study in this academic institution, the perspectives of Hospitalists revealed a high level of burn out (exhaustion and disengagement) and high assigned patient censuses that negatively impact their ability to deliver optimal patient care. Most Hospitalists reported lack of mentorship and inadequate time allocated for scholarly activity. The majority reported not having their input on decisions made by the administration that directly affect them. Most were unsatisfied with their compensation and the lack of PTO (paid time off). The majority would like to be promoted in this academic institution but feel unsupported to achieve this goal.

A review of the HIV-infected homeless sub-population at the Centre for HIV/AIDS Research, Education and Services, Department of Medicine, University Hospital of the West Indies.

OBJECTIVE: The twin epidemics of HIV and homelessness present several challenging aspects to the development of programmes for the provision of treatment and care. This paper describes the characteristics of this population being managed by a collaborative effort between the Centre for HIV/AIDS Research, Education and Services, Department of Medicine, University Hospital of the West Indies and the National Council on Drug Abuse. SUBJECTS AND METHODS: A retrospective descriptive study was conducted via review of patients'medical files. Demographic and clinical data of the HIV-infected homeless population were summarized, highlighting issues related to the provision of care, rates of antiretroviral therapy (ART) uptake and subsequent adherence to treatment and known factors associated with HIV transmission. RESULTS: A total of 12 cases were included in the analysis. There was an average age of 38.0 years (IQR 32.5-49.25) with the majority being female, nine (75.0%). Late stage diagnosis was a common feature. The majority of cases were eligible for ART on first contact, with CD4 counts on average being 284.4 (95% CI 10.9.0, 459.8). Significant risk factors for HIV transmission were also identified as all cases reported being sexual active with limited condom use reported and high reported numbers of lifetime partners, 30 (IQR 25.0-100.0). Other factors identified include eight (66.6%) cases reporting sexually transmitted infection (STI) symptoms, 10 (83.3%) reporting substance abuse and nine (75.0%) reporting sex work. CONCLUSION: The implementation of combination interventions providing a comprehensive package of services that address the multitude of issues facing the HIV-infected homeless population is required in order to appropriately manage this population.

The prevalence of personality disorder in a general medical hospital population in Jamaica.

OBJECTIVE: To determine the prevalence of personality disorders in patients admitted to the general medical wards of the University Hospital of the West Indies (UHWI). METHOD: Patients (n = 100) sequentially admitted to the general medical wards of the UHWI were assessed for the diagnosis of personality disorder using the gold standard of a consultant assessment based on the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision (DSM IV-TR) diagnostic criteria for personality disorder, the International Personality Disorder Examination Screening questionnaire (IPDE-S) and the Jamaica Personality Disorder Inventory (JPDI). RESULTS: The three assessment instruments identified a prevalence of personality disorder in the cohort of patients of 21% consultant DSM IV-TR assessment, 28% JPDI and 70% IPDE-S. The prevalence rate identified by the IPDE-S was significantly higher than the local instruments used (p < 0.000). CONCLUSIONS: The prevalence of personality disorder assessed by the JPDI and the IPDE-S and the consultant DSM IV-TR instruments in Jamaica is significantly higher than the prevalence rate of studies in other countries.

Transient cortical blindness post angiography--a case report.

A 56-year old female reported having had a fall two weeks prior to presentation. Computed Tomography (CT) scan showed an acute right-sided convexity subdural haematoma. A computed tomography angiogram revealed no vascular anomaly. One hour post procedure she had bilateral cortical blindness. Her vision subsequently was fully restored. A diagnosis of transient cortical blindness was made. Transient cortical blindness is a rare but recognized complication ofintra-arterial injection of iodinated contrast agents.

The importance of bone biomarkers in the diagnosis of renal osteodystrophy.

OBJECTIVE: To evaluate the association of serum biochemical markers in patients with chronic kidney disease (CKD) in Jamaica for early detection of renal osteodystrophy (ROD). METHODS: The study contained two groups: CKD group (221) which consisted of adult patients, from dialysis units and renal clinics, with stage III to V CKD. The control group (237) had adult individuals, from the medical outpatient clinics, with mild and controlled chronic diseases and absence of renal failure. The patients in the study were between 18-80 years of age and gave informed consent to participate in the study. The differences in distribution of demographic, clinical and pathologic variables between the two groups were evaluated. Pearson's chi-squared test and Spearman' rho correlation coefficient test was used, with p < 0.01 considered statistically significant. Data analysis was conducted using the statistical package for the social sciences (SPSS) version 17.0. RESULTS: Among the 221 CKD patients in the study, 174 (78.7%) had ROD based on serum intact parathyroid hormone (iPTH) levels. The majority of patients in the control group did not have bone disease ie 95-96%. The majority of CKD patients (70.0%) had high-turnover (HTO) bone disease compared to 29.3% of patients with low-turnover (LTO) bone disease. Dialysis patients who had HTO bone disease compared with those with LTO had significantly higher levels of iPTH and total serum alkaline phosphatase (ALP). A similar relationship was observed among CKD patients not on dialysis. There was a significant individual variation in bone turnover biochemical markers. A total of 237 patients were recruited in the control group. Based on the levels of iPTH and tALP six of them were found to have bone disease. The majority of these patients with bone disease were diabetic (83.3%) while the other patient had cancer (16.7%). The six patients in the control group with bone disease were within the age cohort of 64-80 years, most of whom were 78 years old. CONCLUSION: A combination of serum biochemical markers might predict underlying renal osteodystrophy better that would individual biochemical markers. A predictive model using bone histology and biochemical markers can be developed in the future.

Depression among persons attending a HIV/AIDS outpatient clinic in Kingston, Jamaica.

OBJECTIVES: To determine the prevalence of depression among persons attending a HIV/AIDS clinic in Kingston, Jamaica, and to explore the possible role of patient-specific clinical and social issues as intermediary factors in the relationship between HIV/AIDS and depression. SUBJECTS AND METHODS: Over a three-month period, all eligible and consenting patients from a HIV/ AIDS clinic in Kingston, Jamaica, were invited to participate in the study. They were interviewed using the Patient Health Questionnaire (PHQ-9), an instrument validated for the detection of depression in primary care settings. Clinical and socio-demographic data were retrieved for all participating patients from a pre-existing clinic database. Depression prevalence rates were calculated and the association between depression and age, gender, antiretroviral treatment, CD4 count, living arrangement, marital status and major stressors explored. RESULTS: Sixty-three patients participated in the study and 43% (n = 36) of them were depressed. No significant differences in depression rates were found with respect to any of the sociodemographic or clinicalfactors explored (p > 0.05). CONCLUSION: The relatively high prevalence of depression among attendees at the HIV/AIDS clinic underscores the need for depression screening in these patients.

Validation of the Beck Depression Inventory II in HIV-positive patients.

OBJECTIVE: Research on depression among HIV-positive patients has been limited by the lack of a valid and reliable measure of depression. This project addresses this problem by exploring the internal consistency reliability and the concurrent and discriminant validity of the Beck Depression Inventory-II (BDI-II) using HIV-positive patients in Jamaica. METHOD: Patients from three HIV clinics in Jamaica (n = 191 patients; 61% female, 39% male, mean age 40.5-10 years) were administered the BDI-II along with the Centre for Epidemiological Studies -Depression Scale (CES-D) and the Social Provisions Scale. RESULTS: Overall, the BDI-II was found to have a high degree of reliability (alpha = 0.89). The scale also had good concurrent validity as evidenced by a high correlation with scores on the CES-D (r = 0.74) and acceptable discriminant validity as demonstrated through a moderate correlation with the Social Provisions Scale (r = -0.42). This pattern of scores suggests that the majority of the variance underlying the BDI-II assesses depression (55%) while a smaller degree of the variability (18%) measures a conceptually similar but distinct concept. CONCLUSION: The BDI-II is a sufficiently reliable and valid measure for assessing depression in HIV-positive patients.

Patterns of depressive symptoms among patients with HIV infection.

OBJECTIVE: To identify the level of depressive symptoms among patients with HIV infection and to examine the reported patterns of depressive symptoms not confounded by the physical manifestations of HIV-infection. METHOD: A total of 191 patients with HIV infection (75 males (39%) and 116 females (61%), mean age 40.48 +/- 10 years), from three HIV clinics were administered the Beck Depression Inventory-II as well as a demographic questionnaire as part of a larger study. RESULTS: Moderate to severe depressive symptoms were reported by 17.3% of the HIV-infected patients with females reporting significantly higher levels of depressive symptoms than males. A principal components analysis identified three clusters of depressive symptoms: cognitive-affective, negative cognitions and somatic symptoms. The HIV-infected patients were found to display mainly cognitive-affective symptoms of depression. CONCLUSION: HIV-infected patients, especially female patients, may be at an increased risk of experiencing high levels of depressive symptoms. It is recommended that HIV-infected patients be routinely screened for depression, particularly cognitive-affective symptoms of depression.

An analysis of three opportunistic infections in an outpatient HIV clinic in Jamaica.

OBJECTIVES: To determine the occurrence of opportunistic infection (OI) in HIV-positive patients and to identify any risk factors which may be associated with such. METHODS: A cross-sectional study of all patients attending the HIV out-patient clinic was conducted. Their hospital notes were examined between January 1 and December 31, 2007 inclusive, to identify any occurrence of opportunistic infection. In addition, the patient list was also cross-referenced with all patients hospitalized on the medical wards during the same time period. Clinical and demographic data were collected for all participants. The occurrence of opportunistic infections and the variables of age, gender CD4 counts and viral loads: (first ever last in 2007 and at diagnosis of OI [or within six months]), the use of primary and secondary prophylaxis, the discontinuation of prophylactic regimens and the HAART regime at diagnosis of an OI and the diagnostic and treatment protocols of these infections were calculated. RESULTS: Six hundred and three patients participated in the study and 4.7% (n = 28) were found to have experienced at least one opportunistic infection in 2007. Significant associations were found between first and last CD4 cell count, viral load in 2007, year of entry into the clinic and death (p < 0.05). CONCLUSIONS: Opportunistic infections continue to cause significant morbidity and mortality in the HIV-patient population in this study. Earlier entry to treatment facilities and the use of HAART and appropriate prophylaxis can reduce this impact and lead to improved quality of life for HIV-positive individuals.

Sociodemographics and clinical presentation of HIV in Jamaica over 20 years. A comparative analysis of surveillance data.

OBJECTIVE: To delineate changes in the epidemiology of HIV including morbidity and mortality patterns based on three key time points in Jamaica's HIV response. METHOD: Surveillance data from Jamaica's HIV/AIDS Tracking system (HATS) were analysed and distribution of cases by age, gender sexual practice, risk factors and clinical features were determined for three time periods (1988-1994: formal establishment of HIV surveillance at the national level, 1995-2003: introduction of HAART globally; 2004-June 2008: introduction of HAART and HIV rapid testing in Jamaica). Factors that predicted late stage diagnosis (AIDS or AIDS death) were also determined RESULTS: 22 603 persons with HIV were reported to the Ministry of Health, Jamaica, between 1988 and June 2008. Between the first and last time blocks, the modal age category remained constant (25-49 years) and the proportion of women reported with HIV non-AIDS increased from 32.5% to 61.4% (p < 0.001). However the male:female ratio for persons reported with AIDS remained at 1.3:1 between 1995 and 2008. Although heterosexual transmission was the most frequent mode of transmission in each time period, sexual behaviour was consistently under-reported (4769 persons or 21% of all cases ever reported). Late stage diagnosis (AIDS or AIDS death) decreased significantly between the first and last time blocks (16% decline, p < 0.0001) with men, older persons and persons with unknown risk history being more likely to be diagnosed at AIDS or AIDS death. CONCLUSION: HIV testing and treatment programmes have improved timely diagnosis and reduced morbidity associated with HIV infection in Jamaica. However new strategies must be developed to target men and older persons who are often diagnosed at a late stage of disease. Surveillance systems must be strengthened to improve understanding of persons reported with unknown risk behaviours and unknown sexual practices.

HIV seroprevalence among hospital inpatients with neuropsychiatric and other central nervous system disorders.

OBJECTIVE: To determine the seroprevalence of HIV among inpatients with neuropsychiatric and other central nervous system (CNS) disorders at the University Hospital of the West Indies (UHWI). METHODS: Sera and data of hospital inpatients with disorders of the CNS were prospectively investigated and reviewed at the Virology Laboratory, UHWI, over the period January 1 to December 31, 2007. The study population included inpatients with a principal diagnosis of a neuropsychiatric or other CNS disorder and for whom a serological analysis for HIV had been requested. The CNS disorders were categorized as follows: neuropsychiatric disorder (eg schizophrenia), CNS infection (eg viral, bacterial), motor and psychogenic dysfunction not included in other categories (eg seizures), gross structural brain lesion (eg tumours) and other HIV prevalence rates were calculated and compared according to age, gender and diagnostic category. RESULTS: Eighty-two patients were included. Sixty-one per cent were males and 39% females. The mean age in years (+/- SD) was 37.6 (+/- 16.3). There were significant differences in prevalence rates according to diagnostic category (p = 0.026). All of the patients with psychiatric disorders (n = 40) were HIV-negative and 25% (3 out of 12) of patients with CNS infection were HIV-positive. There were no statistically significant associations demonstrated between HIV and age or gender (p > 0.05). CONCLUSION: Clinicians should have a high index of suspicion for HIV infection when faced with patients with CNS infection. Further research is needed to clearly identify the reasons for the comparatively low prevalence of HIV among the psychiatric patients included in this study.

Response to first line HAART using CD4 cell counts experience in a university hospital in Kingston.

OBJECTIVES: To assess the extent to which the current practice for first line therapy concurs with the recommended guidelines and to examine the response of treatment naïve patients to first line Highly Active Antiretroviral Therapy (HAART) at the University Hospital of the West Indies, using CD4 cell counts. METHODS: Over a three-month period, a cross-sectional study design was instituted and data were collected on all patients on HAARTat the University Hospital of the West Indies (UHWI) outpatient HIV clinic. Information was collected by reviewing patient medical records using data collection sheets. The data obtained from the medical records included: age, gender date of diagnosis of HIV date at which HAART was commenced, CD4 cell counts prior to the commencement of antiretrovirals, the initial HAART regimes and subsequent CD4 cell counts. RESULTS: A total of 165 persons who met the criteria of being on HAART therapy were enrolled in the study The average time span between diagnosis of HIV and commencement of antiretroviral therapy was 1.92 years and the range for this was 0 to 12.29 years. The average CD4 count prior to initiation of HAART was 186 cells/mm3. The most common regime used at the UHWI for first line therapy was combivir and efavirenz, n = 78 (47.3%), followed by combivir and nevirapine, n = 29 (17.6%). The average difference between the initial CD4 count prior to the initiation of HAART and first repeated CD4 count was 102 cells/mm3. The mean time between the first and repeated CD4 cell counts was 376 days. CONCLUSION: The recommended guidelines were adhered to for the majority of patients initiated on antiretrovirals at the UHWI. The treatment outcomes achieved at the UHWI were similar to those achieved in developed countries. This gives substantial evidence in support of international efforts to make antiretroviral therapy available in developing countries.

Disclosure of HIV status among HIV clinic attendees in Jamaica.

OBJECTIVE: This study aimed to examine factors related to disclosure of HIV serostatus among clinic attendees in an outpatient HIV clinic at the University Hospital of the West Indies (UHWI). METHODS: This was a cross-sectional survey of 107 attendees to a HIV clinic at the University Hospital of the West Indies. Participants were selected on a convenience basis. The instrument was developed for this study and covered socio-demographic data and self-report of disclosure and other variables related to HIV experience such as perceptions of family support. Data were analysed using nonparametric tests. RESULTS: Findings demonstrate a 49% disclosure rate among males and 60% among females. The results further indicate that age, sexual orientation, mode of transmission, and perception of family support were significantly associated with disclosure. Age and perception of family support were found to be significantly associated with consistent condom use. Age and perception of family support were the factors demonstrating the most significant correlations with age being significantly associated with disclosure to partner. Perception of family support was significantly associated with disclosure to family. CONCLUSION: Findings from this study demonstrate a low disclosure rate among HIV clinic attendees. Given that disclosure of HIV serostatus is critical in the control of the spread of HIV this report highlights the need for the development of prevention interventions focussed on de-stigmatization for both infected and non-infected persons.

Müllerian inhibiting substance signaling uses a bone morphogenetic protein (BMP)-like pathway mediated by ALK2 and induces SMAD6 expression.

Signal reception of Müllerian inhibiting substance (MIS) in the mesenchyme around the embryonic Müllerian duct in the male is essential for regression of the duct. Deficiency of MIS or of the MIS type II receptor, MISRII, results in abnormal reproductive development in the male due to the maintenance of the duct. MIS is a member of the transforming growth factor-beta (TGFbeta) superfamily of secreted protein hormones that signal through receptor complexes of type I and type II serine/threonine kinase receptors. To investigate candidate MIS type I receptors, we examined reporter construct activation by MIS. The bone morphogenetic protein (BMP)-responsive Tlx2 and Xvent2 promoter-driven reporter constructs were stimulated by MIS but the TGFbeta/activin-induced p3TP-lux or CAGA-luc reporter constructs were not. The induction of Tlx2-luc was dependent upon the kinase activity of MISRII and was blocked by a dominant negative truncated ALK2 (tALK2) receptor but not by truncated forms of the other BMP type I receptors ALK1, ALK3, or ALK6. MIS induced activation of a Gal4DBD-Smad1 but not a Gal4DBD-Smad2 fusion protein. This activation could also be blocked by tALK2. The BMP-induced inhibitory Smad, Smad6, was up-regulated by MIS endogenously in Leydig cell-derived lines and is expressed in male but not female Müllerian duct mesenchyme. ALK6 has been shown to function as an MIS type I receptor. Investigation of the pattern of ALK2, MISRII, and ALK6 in the developing urogenital system demonstrated overlapping expression of ALK2 and MISRII in the mesenchyme surrounding the duct while ALK6 was observed only in the epithelium. Examination of ALK6 -/- male animals revealed no defect in duct regression. The reporter construct analysis, pattern of expression of the receptors, and analysis of ALK6-deficient animals suggest that ALK2 is the MIS type I receptor involved in Müllerian duct regression.

Human Müllerian-inhibiting substance promoter contains a functional TFII-I-binding initiator.

Müllerian-inhibiting substance (MIS) plays an essential role in mammalian male sexual development; thus, it is important to determine how the tightly regulated expression of the MIS gene is transcriptionally controlled. Transcription of eukaryotic genes is dependent on regulatory elements in the enhancer and one or both distinct elements in the core promoter: the TATA box, and the initiator (Inr) element. Because the human MIS gene does not contain a consensus TATA and has not been reported to contain an Inr element, we hypothesized that the initiator region of the core promoter was essential for promoter activity. Transient transfection assays were conducted using an immortalized Embryonic Day 14.5 male rat urogenital ridge cell line (CH34) that expresses low levels of MIS. These studies revealed that promoter activity is dependent on the region around the start site (-6 to +10) but not on the nonconsensus TATA region. Electrophoretic mobility shift assays demonstrated that the human MIS initiator sequence forms a specific DNA-protein complex with CH34 cell nuclear extract, HeLa cell nuclear extract, and purified TFII-I. This complex could be blocked or supershifted by the addition of antibodies directed against TFII-I. These data suggest that the human MIS gene contains a functional initiator that is specifically recognized by TFII-I.

Mullerian inhibiting substance inhibits ovarian cell growth through an Rb-independent mechanism.

Müllerian inhibiting substance (MIS), a transforming growth factor-beta family member, causes regression of the Müllerian duct in male embryos. MIS overexpression in transgenic mice ablates the ovary, and MIS inhibits the growth of ovarian cancer cell lines in vitro, suggesting a key role for this hormone in postnatal development of the ovary. This report describes a mechanism for MIS-mediated growth inhibition in both a human epithelial ovarian cancer cell line and a cell line derived from normal ovarian surface epithelium, which is the origin of human epithelial ovarian cancers. MIS-treated cells accumulated in the G(1) phase of the cell cycle and subsequently underwent apoptosis. MIS up-regulated the cyclin-dependent kinase inhibitor p16 through an MIS type II receptor-mediated mechanism and inhibited growth in the absence of detectable or inactive Rb protein. Prolonged treatment with MIS down-regulated the Rb-related protein p130 and increased the Rb family-regulated transcription factor E2F1, overexpression of which inhibited growth. These findings demonstrate that p16 is required for MIS-mediated growth inhibition in ovarian epithelial cells and tumor cells and suggest that up-regulation of E2F1 also plays a role in this process.

Endogenous expression of Müllerian inhibiting substance in early postnatal rat sertoli cells requires multiple steroidogenic factor-1 and GATA-4-binding sites.

Müllerian inhibiting substance (MIS) is a key element required to complete mammalian male sex differentiation. The expression pattern of MIS is tightly regulated in fetal, neonatal, and prepubertal testes and adult ovaries and is well conserved among mammalian species. Although several factors have been shown to be essential to MIS expression, its regulatory mechanisms are not fully understood. We have examined MIS promoter activity in 2-day postnatal primary cultures of rat Sertoli cells that continue to express endogenous MIS mRNA. Using this system, we found that the region between human MIS-269 and -192 is necessary for full MIS promoter activity. We identified by DNase I footprint and electrophoretic mobility-shift analyses a distal steroidogenic factor-1 (SF-1)-binding site that is essential for full promoter activity. Mutational analysis of this new distal SF-1 site and the previously identified proximal SF-1 site showed that both are necessary for transcriptional activation. Moreover, the proximal promoter also contains multiple GATA-4-binding sites that are essential for functional promoter activity. Thus multiple SF-1- and GATA-4-binding sites in the MIS promoter are required for normal tissue-specific and developmental expression of MIS.

The multiple murine 3 beta-hydroxysteroid dehydrogenase isoforms: structure, function, and tissue- and developmentally specific expression.

The enzyme 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) is essential for the biosynthesis of all active steroid hormones. To date five distinct isoforms have been identified in the mouse. The different isoforms are indicated by roman numerals (I-V) in the chronological order in which they have been isolated. The different isoforms are expressed in a tissue- and developmentally specific manner and fall into two functionally distinct groups. 3 beta-HSD I, II, and III function as NAD(+)-dependent dehydrogenaselisomerases, and IV and V function as NADPH-dependent 3-keto steroid reductases. These latter two isoforms, therefore, are not involved in the biosynthesis of steroid hormones, but most likely in the inactivation of steroid hormones. In the adult mouse 3 beta-HSD I is expressed in the classical steroidogenic tissues, the adrenal glands and the gonads. 3 beta-HSD II and III are expressed in the liver and kidney, with III being the major isoform expressed in the adult liver. 3 beta-HSD IV is expressed almost exclusively in the kidney of both sexes, and expression of 3 beta-HSD V is observed only in the male liver starting late in puberty. In the fetal liver of both sexes, 3 beta-HSD I is the major or only isoform expressed at 13.5 days postconception and remains the major isoform until the day of birth, after which 3 beta-HSD III becomes the major isoform. Expression of 3 beta-HSD I in the liver decreases after birth and ceases by day 20 postnatally. Thus the liver expresses four distinct isoforms of 3 beta-HSD, I, II, III, and V, at different times during development. The mouse 3 beta-HSD genes, Hsd3b, have been mapped to a small region on mouse chromosome 3. Analysis of two yeast artificial chromosome (YAC) libraries identified one clone that contains the entire Hsd3b locus within a 1400-kb insert. Hybridization by Southern blot analysis of restriction-enzyme-digested YAC DNA using an 18-base oligonucleotide that hybridizes without mismatch to all known Hsd3b sequences indicates that there are a total of seven Hsd3b genes or pseudogenes in the mouse genome. Further analysis of mouse genomic DNA by pulse field gel electrophoresis suggests that all of the Hsd3b gene family is found within a 400-kb fragment.

Isolation and characterization of several members of the murine Hsd3b gene family.

The enzyme 3 beta-hydroxysteroid dehydrogenase (3 betaHSD) is essential for all steroid hormone biosynthesis. Six distinct 3 betaHSD cDNAs in the mouse (3 betaHSD I-VI) have been isolated previously. This study reports the isolation of genes or partial genes encoding the 3 betaHSDI, II, III, and IV isoforms. Characterization of the genes revealed that they consist of four exons, the same structure that has been observed for characterized human 3 betaHSD genes. Primer extension and nuclease S1 analysis identified the start sites of transcription of Hsd3b -1 and -4. The proximal promoter regions of Hsd3b-1 and -4 were sequenced and putative cis-acting sequences were determined. Previously, we reported that the then known 3 betaHSD genes (3 betaHSD I-IV) were located in a small region of mouse chromosome 3. To analyze this locus further, six yeast artificial chromosome clones containing the 3 betaHSD sequence were identified. One clone appears to contain the complete 3 betaHSD locus within its 1,400-kbp insert. Further analysis of this YAC, along with analysis of mouse genomic DNA by pulsed-field gel electrophoresis, suggests all members of the 3 betaHSD gene family may be contained on a 400-kbp fragment.