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Temporary expatriation is related to HIV-1 infection in rural Senegal.

OBJECTIVES: To assess temporary expatriation as a risk factor for HIV infection in a rural area of Senegal and to examine the transmission of HIV from expatriates to their families. DESIGN: Cross-sectional study in identified expatriates and in a representative cluster sample of the general population from the same geographical area in northern Senegal. METHODS: In 1989, a survey (including questionnaire and serological tests for HIV-1 and HIV-2) was conducted in all expatriates currently living in 11 villages in northern Senegal and spouses of all expatriates (present or not) from this area ('expatriate' group, n = 258). In parallel, a cluster sample of 600 adults was drawn from eight villages of the same area, of whom 414 were selected as the control group since they and their spouses had not travelled outside Senegal in the last 10 years. RESULTS: In the 'expatriate' group, sera from 39 subjects were confirmed as HIV-positive by Western blot [17 out of 63 men (27.0%) and 22 out of 195 women (11.3%)]. Of these subjects, 33 were infected by HIV-1, four by HIV-2 and two had a dual HIV-1/2 profile. In contrast, only two subjects (one man and one woman) from the control group were infected by HIV-2 and none by HIV-1. In men, HIV-1 seroprevalence was associated with age < 40 years [odds ratio (OR), 7.4; P = 0.03] and previous sexually transmitted disease (STD) symptoms (OR, 13.5; P = 0.03), whereas the risk factors in women were age < 25 years (OR, 3.7; P = 0.04), being a widow (OR, 30.4; P < 0.01) and presence of sexual activity over the last 2 years (OR, 21.3; P < 0.01). CONCLUSIONS: Penetration of HIV-1 infection in a country where HIV-2 is endemic shows that the HIV-1 epidemic is currently spreading to rural West Africa. Migrant workers appear to play a major role in this epidemic.

Acquired Immunodeficiency Syndrome↗

Hypothyroid patients showing shortened responsiveness to oral iodized oil have paradoxically low serum thyroglobulin and low thyroid reserve. Thyroglobulin/thyrotropin ratio as a measure of thyroid damage.

In Central Africa, all of northern Zaire is very severely deficient in iodine. A peculiar feature of this endemia is that iodine deficiency and the ensuing thyroid gland stimulation not only leads to goitre formation but also to progressive thyroid involution and to myxoedematous cretinism. An iodine supplementation trial based on oral administration of small doses of iodine was made in 81 schoolchildren. All of them received a small dose of iodine (0.1 ml containing 48 mg) per os and the thyroid status was followed during 4 months. Blood and urine samples were collected at the start of the study, then 2 weeks, 2 months and 4 months after iodine administration. Before iodine supplementation the mean urinary iodine level was 0.18 +/- 0.02 micromol/l, and 10% of the subjects had a urinary iodine level below 0.08 micromol/l. Fifty-two percent of the subjects had a serum thyrotropin (TSH) level above 10 mU/l. All the subjects responded to the administration of iodine. and all of them recovered a euthyroid status. Most of them were still euthyroid at the end of the study. However. within 4 or even 2 months, some subjects (15 % of the total) reverted to hypothyroidism. At the entry of the study these subjects were all hypothyroid and had elevated TSH and paradoxically low serum thyroglobulin (TG) values. In myxoedematous cretins living in the same area, even lower serum TG levels were found. Together with the absence of goitre, a paradoxically low serum TG Suggests a low thyroid reserve, and in the present case a reduced amount of functional thyroid tissue. We show that the serum TG/TSH ratio may be used as a predictive index of thyroid reserve and of positive response to iodine administration. These data further suggest that thyroid damage is not confined to myxoedematous cretins. but is widely distributed in the phenotypically normal population. Widely distributed thyroid damage may render iodine prophylaxis based on oral administration unpredictable.

Administration, Oral↗

Widespread assessment of risk-adjusted outcomes: lessons from local initiatives.

BACKGROUND: Controlling costs while maintaining quality is a crucial element of national health care reform. Prompted generally by concerns of local businesses, states and regions around the country have already initiated such dual efforts. The central component of these activities is the examination of risk-adjusted outcomes. ISSUES: Publicizing comparisons across providers and using these data for payer contracting have prompted several concerns among many providers, primarily involving reservations about the validity of the risk-adjustment methodologies and the fairness of the outcomes data reports. In contrast, business leaders recognize potential limitations in the data but argue that some information is better than none. They believe that these efforts have already saved money by forcing providers to compete and to justify unusually high costs. Troubling questions arise about whether publicizing their outcomes may prompt providers to avoid especially sick and high-risk patients. Although common themes emerge, each of these initiatives to monitor risk-adjusted outcomes has had to address specific local concerns. The form that these local initiatives take is influenced particularly by relationships between the business and provider communities and their respective visions of how to motivate change in the health care sector. SUMMARY: In some regions, businesses and providers have worked collaboratively, whereas in others relationships have been strained. One major problem in making objective decisions about risk-adjusted outcomes methods is the lack of clear evidence about whether such information truly measures quality of care. Whether a standard national quality monitoring program will satisfy local demands remains unclear.

Consumer Advocacy↗

Preliminary estimates of human immunodeficiency virus prevalence and incidence among cocaine abusers of Porto Alegre, Brazil.

A sample of 193 southern Brazilian inner-city cocaine abusers was studied to assess the prevalence of human immunodeficiency virus (HIV) infection. Following the exclusion of those who were seropositive from the intake sample, a cohort of 138 HIV-negative cocaine abusers was followed for 18 months to assess seroincidence rates and the associated characteristics. HIV status, drug use, sexual risk behaviors, and presence and severity of medical and psychiatric symptoms were collected at intake using a Brazilian version of the Risk Assessment Battery, the Addiction Severity Index (ASI), Symptom Check List-90 (SCL-90), and Beck Depression Inventory (BDI); this was repeated at 6-, 12-, and 18-month intervals. The overall seroprevalence was 28.5%, and the variables associated with HIV seropositivity were age older than 25 years, being single, having less than 8 years of education, and having injected cocaine at least once. Although follow-up procedures were difficult to implement due to sample characteristics, we obtained data from 82.6% of the participants for at least one follow-up and for 57% at all follow-up windows. Most participants showed high scores on the Beck Depression Inventory (mean of 20.6 +/- 13.9) and Symptom Check List-90 (mean of 106.4 +/- 91.9). There were 8 seroconversions in the 18-month period, yielding an incidence rate of 5.03/100 (confidence interval [CI] 2.2-9.7) person-years at risk. None of the seroconverters reported recent cocaine injection, and only 14.5% of the overall sample reported ever injecting cocaine, which suggests that another significant mode of transmission via sexual behavior should be considered as well. Each of these findings has important implications for the design of preventive interventions.

Adult↗

Use of pharmacy data to assess quality of pharmacotherapy for schizophrenia in a national health care system: individual and facility predictors.

OBJECTIVES: This paper presents a profile of the use of antipsychotic medications in the treatment of schizophrenia in a national health system. METHODS: Prescription drug records written for antipsychotic medications between June 1999 and September 1999 were collected for patients diagnosed with schizophrenia in the Department of Veteran Affairs (VA). Indicators were constructed describing whether patients received multiple antipsychotic medications and whether the total weekly dose was outside of the range specified in the treatment recommendations developed by the schizophrenia Patient Outcomes Research Team (PORT). Generalized estimation equations were used to identify patient and facility characteristics that are associated with adherence to PORT recommendations. RESULTS: Of the 34,925 patients in the final sample, 2,383 (6.8%) received prescriptions for more than one antipsychotic (polypharmacy). A higher number of patients (4,554 or 13.0%) were dosed above the PORT recommendations on an antipsychotic medication and even more (8,148 or 23.3%) were dosed below the recommended PORT dosage. Older patients, minorities, and those with comorbid depression or substance abuse were generally less likely to receive multiple antipsychotics or be dosed above PORT recommendations. Neither academic emphasis (the percentage of the mental health budget spent on research and education) nor fiscal stress was significantly associated with adherence to recommendations. CONCLUSIONS: In the nation's largest mental health system, a relatively small number of patients were prescribed multiple antipsychotic medications, but more than a third were dosed outside of the PORT recommended range.

Academic Medical Centers↗

Patterns and correlates of contacting clergy for mental disorders in the United States.

OBJECTIVE: To present nationally representative data on the part played by clergy in providing treatment to people with mental disorders in the United States. DATA SOURCES: The National Comorbidity Survey (NCS), a nationally representative general population survey of 8,098 respondents ages 15-54. STUDY DESIGN: Cross-sectional survey. DATA COLLECTION: A modified version of the Composite International Diagnostic Interview was used to assess DSM-III-R mental disorders. Reports were obtained on age of onset of disorders, age of first seeking treatment, and treatment in the 12 months before interview with each of six types of professionals (clergy, general medical physicians, psychiatrists, other mental health specialists, human services providers, and alternative treatment providers). PRINCIPAL FINDINGS: One-quarter of those who ever sought treatment for mental disorders did so from a clergy member. Although there has been a decline in this proportion between the 1950s (31.3 percent) and the early 1990s (23.5 percent), the clergy continue to be contacted by higher proportions than psychiatrists (16.7 percent) or general medical doctors (16.7 percent). Nearly one-quarter of those seeking help from clergy in a given year have the most seriously impairing mental disorders. The majority of these people are seen exclusively by the clergy, and not by a physician or mental health professional. CONCLUSIONS: The clergy continue to play a crucial role in the U.S. mental health care delivery system. However, interventions appear to be needed to ensure that clergy members recognize the presence and severity of disorders, deliver therapies of sufficient intensity and quality, and collaborate appropriately with health care professionals.

Adolescent↗

Transplantation of pediatric en bloc cadaver kidneys into adult recipients.

BACKGROUND: To maximize the renal donor pool, cadaveric pediatric en bloc kidneys have been transplanted as a dual unit by some transplant centers. We compared the short- and long-term outcomes of adult recipients of cadaveric pediatric en bloc renal transplants versus those of matched recipients of cadaveric adult kidneys. METHODS: Thirty-three adults who received pediatric en bloc kidney transplants between April 1990 and September 1997 were retrospectively identified and were compared with 33 matched adults who received adult cadaveric kidney transplants. The groups were identical for transplantation era, immunosuppression, recipient sex, race, cause of renal failure, mean weight, and follow-up duration (37.8 vs. 37.5 months). The mean recipient age study versus control was lower (36.3 vs. 48.9 years, P=0.0003). Results. There was no difference between the en bloc and adult donor groups in the 3-year patient survival rates (95% vs. 87%, P=0.16) or the 3-year graft survival rates (87.3% vs. 84.2%, P=0.35). Further, there was no difference in en bloc patient or en bloc graft survival time stratified by recipient age (14-44 vs. >45 years, P=0.11), en bloc donor age (<24 vs. >24 months, P=0.39), or recipient weight (<60, 61-75, >75 kg; P=0.60). Differences in serum creatinine (mg/dl) for the en bloc versus the control group at the time of discharge (3.0 vs. 7.8 mg/dl, P=0.06), at 1 year (1.4 vs. 2.0 mg/dl, P=0.06), and at 2 years (1.1 vs. 1.6 mg/dl, P=0.14) had dissipated by the time of the 5-year follow-up examination (1.1 vs. 1.6 mg/dl, P=0.14). Vascular complications were more prevalent in the en bloc group: renal vein thrombosis (one case), thrombosis of donor aorta (two cases), arterial thrombosis of one renal moiety (two cases), and renal artery stenosis (two cases). There were no differences between groups in delayed graft function, acute or chronic rejection, posttransplant hypertension, posttransplant protein-uria, or long-term graft function. CONCLUSIONS: Collectively, these data indicate that transplanting pediatric en bloc kidneys into adult recipients results in equivalent patient and graft survival compared with adult cadaveric kidneys. Further, the data also suggest that pediatric en bloc kidneys need not be strictly allocated based on recipient weight or age criteria.

Adolescent↗

Mouse leukotriene A4 hydrolase is expressed at high levels in intestinal crypt cells and splenic lymphocytes.

LTA4 hydrolase (EC 3.3.2.6) is a dual-function enzyme that is essential for the conversion of leukotriene A4 (LTA4) to leukotriene B4 (LTB4) and also possesses an aminopeptidase activity. To characterize the expression of this unusual enzyme, we have cloned the mouse LTA4 hydrolase cDNA. The deduced amino acid sequence revealed 92% identity with the human sequence. Cloning and analysis of genomic sequences of mouse LTA4 hydrolase indicated that it is a single-copy gene spanning over 40kb and containing 20 exons. LTA4 hydrolase is widely expressed, with the highest levels of expression occurring in the small intestine, followed by the spleen. In situ hybridization revealed that LTA4 hydrolase is localized in the crypt cells of the small intestine, white pulp of the spleen, bronchiolar epithelium of the lung, myocardium, adrenal cortex, epithelium of the seminal vesicles, proximal tubules and the collecting ducts of the kidney, and occasional hepatocytes. Thus the widespread distribution of LTA4 hydrolase in various cell types in the tissues suggests that LTB4 may possess biological activities other than those known at present. It is also plausible that the widespread occurrence of LTA4 hydrolase in various tissues may correspond more with its function as an aminopeptidase than its function as an LTA4 hydrolase.

Amino Acid Sequence↗

A Canadian survey on the management of corticosteroid induced osteoporosis by rheumatologists.

OBJECTIVE: To survey the practice pattern of Canadian rheumatologists (CR) on their management of corticosteroid induced osteoporosis in their premenopausal (PrM) and postmenopausal (PoM) female patients. METHODS: The practice pattern was surveyed using a 17 item questionnaire probing the diagnosis, prevention, treatment, and monitoring of osteoporosis in PrM and PoM women receiving longterm oral systemic corticosteroid therapy. RESULTS: Most CR investigated and treated osteoporosis themselves, 13% referred to other specialists for investigation, and 22% referred for treatment. Eighty-two percent of CR used dual energy x-ray absorptiometry (DEXA) to confirm a diagnosis of osteoporosis. Most CR initiated investigation for osteoporosis at the start or within the first year of starting longterm systemic corticosteroid therapy: PrM 87% and PoM 93%. The most frequently used initial strategy for the prevention of osteoporosis was as follows. PrM: calcium and vitamin D3 (53%); PoM: hormone replacement therapy (HRT) and calcium (29%). The most common initial choice for treatment of established osteoporosis was as follows: PrM: etidronate (53%); PoM: bisphosphonates +/- HRT (53%). Ninety-six percent of CR used only bone mineral density (BMD) measurement to monitor therapy for corticosteroid induced osteoporosis. Most CR monitored BMD every 12 to 24 months for PrM (81%) and PoM (84%). The BMD parameter(s) (T and Z scores as measured by DEXA) used to initiate therapy for corticosteroid induced osteoporosis was variable. CONCLUSION: It appears that, while certain trends are evident, there is still considerable variability in the management of corticosteroid induced osteoporosis.

Absorptiometry, Photon↗

Relative frequency of human rotavirus VP4 (P) genotypes recovered over a ten-year period from South African children with diarrhea.

The relative frequency and distribution of the VP4 (P) genotypes of 227 human rotavirus field strains were investigated in South Africa. The stool samples were collected between 1984-1993 from infants and young children with diarrhea at Ga-Rankuwa Hospital, Pretoria, South Africa. The RNA was extracted from stools, heat denatured, and dot blotted onto nylon membranes. The blots were hybridized to PCR-generated, 32P radio-labelled VP4-specific probes (corresponding to the hyperdivergent region of the VP4 gene) of the following human rotavirus VP4 genotypes: P4, P6, P8, P9, P10, and P12. Of the 157 rotavirus strains typed by the probes, the P8 genotype was identified most frequently in 63.7% (n = 100) of the samples. The P4 and P6 genotypes were detected less frequently in 22.3% (n = 35) and 8.3% (n = 13) of the samples, respectively. Five cases of dual infection between P8 and P4 genotypes occurred, indicating the potential for reassortment between members of different rotavirus genogroups. The P9 genotype could not be confirmed in 3 cases (1.9%), while the P10 genotype was not observed at all, indicating the scarcity or absence of these VP4 genotypes in this region. Interestingly, we identified the newly-described P12 VP4 genotype in 6 cases (3.8%), suggesting a wide geographical distribution. Furthermore, several samples with sufficient RNA by gel electrophoresis remained untyped by the probes used in this study, and may represent putative "new" human VP4 genotype(s).

Base Sequence↗

Identification of myotubularin as the lipid phosphatase catalytic subunit associated with the 3-phosphatase adapter protein, 3-PAP.

Myotubularin is a dual-specific phosphatase that dephosphorylates phosphatidylinositol 3-phosphate and phosphatidylinositol (3,5)-bisphosphate. Mutations in myotubularin result in the human disease X-linked myotubular myopathy, characterized by persistence of muscle fibers that retain an immature phenotype. We have previously reported the identification of the 3-phosphatase adapter protein (3-PAP), a catalytically inactive member of the myotubularin gene family, which coprecipitates lipid phosphatidylinositol 3-phosphate-3-phosphatase activity from lysates of human platelets. We have now identified myotubularin as the catalytically active 3-phosphatase subunit interacting with 3-PAP. A 65-kDa polypeptide, coprecipitating with endogenous 3-PAP, was purified from SDS/PAGE, subjected to trypsin digestion, and analyzed by collision-induced dissociation tandem MS. Three peptides derived from human myotubularin were identified. Association between 3-PAP and myotubularin was confirmed by reciprocal coimmunoprecipitation of both endogenous and recombinant proteins expressed in K562 cells. Recombinant myotubularin localized to the plasma membrane, causing extensive filopodia formation. However, coexpression of 3-PAP with myotubularin led to attenuation of the plasma membrane phenotype, associated with myotubularin relocalization to the cytosol. Collectively these studies indicate 3-PAP functions as an "adapter" for myotubularin, regulating myotubularin intracellular location and thereby altering the phenotype resulting from myotubularin overexpression.

Amino Acid Sequence↗

Comparative evaluation of local and international reference databases for forearm densitometry: different impacts on diagnostic decisions.

Reference databases play a key role in the management of osteoporosis. The aim of this preliminary study was to compare the diagnostic consequences of using either an international or a local reference database in peripheral densitometry. For this purpose, standard curves for bone mineral density (measured by dual-energy X-ray absorptiometry at the distal and proximal forearm) were generated for healthy Hungarian men and women. In total, 303 healthy volunteers of both sexes (age range: 20-94 yr) were recruited from four osteoporosis centers. Subjects with medical conditions or taking medication affecting the bone metabolism were excluded. Bone densitometry was performed with pDEXA (Norland-Stratec, Fort Atkinson, WI) devices in each center after cross-calibration of the machines. The precision error of the forearm measurement was also determined (<1% in vitro, and 1.2-2.5% in vivo). In females, the peak forearm density was detected in the 30-39-yr group. The density decreased by 8% per 5 yr in early postmenopausal females, and by 10% per 10 yr in late postmenopausal females. In males, the highest bone mineral density was found in the 30-39-yr group for the distal forearm, but 1 decade later for the proximal site. Subsequently, a 5% decrease in density occurred per 10 yr, except in the 8th decade, in which a 20% decrease was demonstrated. One thousand four hundred thirty-four patients with suspected osteoporosis were classified according to the forearm density T-scores using both the new Hungarian reference database and the international database provided by the manufacturer. Comparison of the results measured at the distal forearm with the two different databases led to similar outcomes. However, at the proximal site, one fifth of the female patients were reclassified from the low-density group to the normal group using the domestic normative database. An opposite difference was observed for the males: use of the Hungarian reference data resulted in 40% more men being categorized in the low-density group than when the international normal database was applied. Our results suggest that not only geographic differences, but also the reference database used, can influence the prevalence of the diagnosis of osteoporosis. Further data are currently being collected to increase the statistical power of the study.

Absorptiometry, Photon↗

Substance use disorder trajectory classes: diachronic integration of onset age, severity, and course.

BACKGROUND: Substance use disorders (SUDs) may be characterized by onset age, severity, substance type, course, and outcomes. SUD phenotypes in the literature typically consider each of these features in isolation. Conceptual frameworks and data collection procedures for assessing SUD phenotypes are increasingly "diachronic" in approach, providing for characterizations "throughout time". The recent availability of statistical procedures for the identification of latent classes offers the possibility of developing SUD phenotypes integrating these developmental features. This article illustrates the utilization of SAS-TRAJ mixture modeling to characterize variations in SUD symptom trajectories to define phenotypes. METHODS: The subjects were 332 adult males with SUDs. Their course of symptoms from early adolescence through middle adulthood was retrospectively determined. Symptom trajectories were defined by the number of DSM-IV SUD symptoms by year of age. SAS-TRAJ mixture models identified trajectory classes. Model development, evaluation, and selection using this approach are discussed. RESULTS: Among these men with SUDs, six trajectory classes were identified, including groups characterized by early-onset and severe SUD symptoms persisting into adulthood, an early-onset group similar in adolescence but improving in adulthood, and other groups with symptoms emerging later with varying degrees of severity and persistence. The SUD trajectory classes were significantly different on comorbid psychopathology, particularly childhood disruptive behavior disorders. CONCLUSION: The results present a new method for the comprehensive depiction of heterogeneity in SUD symptoms. Future studies may determine the extent to which SUDs phenotypes based on the course of symptom development inform etiology, prevention and treatment research.

Adolescent↗

The relevance of psychosocial variables and working conditions in predicting nurses' coping strategies during the SARS crisis: an online questionnaire survey.

OBJECTIVES: The purpose of this investigation was to examine the relationship between psychosocial variables and working conditions, and nurses' coping methods and distress in response to the severe acute respiratory syndrome (SARS) crisis in Canada. PARTICIPANTS AND PROCEDURE: The sample consisted of 333 nurses (315 women, 18 men) who completed an Internet-mediated questionnaire that was posted on the Registered Nurses' Association of Ontario (RNAO) website between March and May 2004. The questionnaire was restricted to respondents who had to authenticate their RNAO membership with a valid username and password before accessing the questionnaire. This served a dual purpose: to ensure that only RNAO nurses completed the questionnaire and thereby safeguarding the generalizability of the findings; and second, to prevent any one nurse from contributing more than once to the overall sample. RESULTS: Correlational analysis yielded several significant relationships between psychosocial variables and working conditions, and the traditional correlates of burnout and stress. Three multiple regression analysis revealed that the model we evolved--including higher levels of vigor, organizational support, and trust in equipment/infection control initiative; and lower levels of contact with SARS patients, and time spent in quarantine--predicted to lower levels of avoidance behavior, emotional exhaustion, and state anger. CONCLUSIONS: By employing models of stress and burnout that combine psychosocial variables and working conditions, researchers can account for significant amounts of variance in outcomes related to burnout. These findings highlight the importance of vigor and perceived organizational support in predicting nurses' symptoms of burnout. For healthcare administrators, this means that a likely strategy for assuaging the negative outcomes of stress should address nurses' psychosocial concerns and the working conditions that they face during novel times of crisis.

Adaptation, Psychological↗

A picture archiving and communications system featuring multiple monitors using Windows98.

We present an effective approach to manage, review, and distribute Digital Imaging and Communications in Medicine (DICOM) images with multiple monitors using Windows98 (Microsoft Corp, Redmond, WA) that can be implemented in an office-based setting. Computed tomography (CT), magnetic resonance imaging (MRI), and angiographic DICOM images were collected, compressed, and stored using Medweb (Medweb, Inc, San Francisco, CA) software. The Medweb server used the Linux/UNIX operating system on a Pentium 333-MHz processor with 128 MB of RAM. Short-term storage capacity was about 2 weeks with routine usage of an 11-GB hard drive. Images were presented for reading on a dual-monitor Windows98 Pentium display station with 160 MB of RAM using a Medweb/Netscape (Netscape Communications Corp, Mountain View, CA) viewer. There was no significant discrepancy in diagnosis between electronic and conventional film images. Mean reading time for 32 cases was 118 seconds. The Medweb JAVA plug-in viewer loaded the first image within 30 seconds of selecting the case for review. Full uncompressed 16-bit images allowed different window settings to better assess for pathology. Multiple monitors allowed viewing various hanging protocols. Cine viewing was also possible. Key diagnostic images were electronically transmitted to referring physicians. On-call radiologists were able to access images through the Internet. By combining Medweb, DICOM, and web-browser software using desktop personal computers (PCs), an easily accessible picture archiving and communications system (PACS) is available to radiologists and referring physicians. Multiple monitors are easily configured and managed using Windows98. This system can sustain changes and can be extended to provide variable functions using inexpensive PCs.

Angiography↗

Does recovery from substance use disorder matter in patients with bipolar disorder?

OBJECTIVE: To examine the potential impact of recovery from substance use disorder (SUD) on the course of bipolar disorder among patients diagnosed with both bipolar and substance use disorders according to DSM-IV criteria. METHOD: As part of the multicenter Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), we examined bipolar disorder status (i.e., whether the patient is recovering or recovered), role functioning, and quality of life in the first 1000 patients to enter the STEP-BD study. We compared patients with no history of SUD, current SUD, and past SUD (i.e., lifetime SUD, but no current SUD) on these parameters. Data were collected between November 1999 and April 2001. RESULTS: A current clinical status of recovering or recovered from bipolar disorder was less likely among patients with current or past SUD compared to patients with no SUD (p < .002). Recovering/recovered status did not differ significantly between patients with current SUD versus past SUD. All 3 groups differed significantly on measures of role functioning as assessed by the Longitudinal Interval Follow-Up Evaluation-Range of Impaired Functioning Tool (LIFE-RIFT), with poorest role functioning among patients with current SUD, followed by patients with past SUD (p = .0002). Patients with current or past SUD reported significantly lower quality of life as measured by the LIFE-RIFT and the Quality of Life Enjoyment and Satisfaction Questionnaire and more lifetime suicide attempts (p < .001) than patients without an SUD; patients with past versus current SUD did not differ significantly on these measures. CONCLUSION: The results suggest that patients with bipolar disorder who experience sustained remission from an SUD fare better than patients with current SUD, but not as well as subjects with no history of SUD; differences among the 3 groups appear greatest in the area of role functioning.

Adult↗

Bone mineralization in children and adolescents with a milk allergy.

To evaluate the correlation between dietary calcium intake and mineralization of the immature skeleton 55 children and adolescents aged 5-14 years (mean, 9.5 years) with a positive radioallergosorbent test (RAST) for serum antibodies to cow's milk protein were evaluated. Bone mineral density (BMD) in the lumbar spine and proximal femurs were measured by dual energy X-ray absorptiometry. BMD at each site for each subject was converted to an age-adjusted Z score based on our own series of 95 normal pediatric controls. Calcium intake was determined using a detailed food frequency questionnaire administered by a nutritionist during a 30-40-min interview. Dietary adjustments to the condition varied and resulted in a wide range of calcium intakes. Calcium supplements were taken by 22% of the subjects and were included in the determination of daily calcium intake. The group of 55 subjects was divided into quartiles based on calcium intake (mean +/- S.E mg calcium/day): Group 1, 409 +/- 21, Group 2, 663 +/- 16, Group 3, 950 +/- 32, Group 4, 1437 +/- 124. Bone density Z scores in the proximal femur serially increased across the calcium intake groups (mean +/- S.E.): Group 1, -0.16 +/- 0.31; Group 2, 0.05 +/- 0.33; Group 3, 0.44 +/- 0.24; Group 4, 0.79 +/- 0.41 (P = 0.03). A similar pattern was found with lumbar spine BMD Z scores: Group 1, -0.16 +/- 0.27; Group 2, 0.10 +/- 0.21; Group 3, 0.18 +/- 0.20; Group 4, 0.30 +/- 0.25 (P = 0.05). These data add further to the evidence that dietary calcium intake is important for optimal mineralization of the growing skeleton.

Absorptiometry, Photon↗

Endocrine and metabolic effects of long-term administration of [Nle27]growth hormone-releasing hormone-(1-29)-NH2 in age-advanced men and women.

Attenuation of the GH and insulin-like growth factor I (IGF-I) axis in aging may be responsible for changes in body composition and metabolism. This relationship has been confirmed by studies of recombinant human GH replacement in aging men and women, but the adverse effects encountered limit its clinical utility. The use of GHRH or its analogs may be an alternative mode for restoring the GH-IGF-I axis in aging individuals. Here we report the endocrine-metabolic changes in response to a GHRH analog in age-advanced men and women. A single blind, randomized, placebo-controlled trial of 5 months duration was conducted. Ten women and 9 men between the ages of 55-71 yr self-injected placebo (saline) s.c. nightly for 4 weeks followed by 16 weeks of [Nle27]GHRH-(1-29)-NH2 at a dose of 10 microg/kg. Subjects underwent 12-h nocturnal (2000-0800 h) frequent blood sampling (10-min intervals) and 24-h urine collection at baseline, after 4 weeks of placebo injections, and after 16 weeks of GHRH analog administration. GH responses to GHRH analog and spontaneous GH pulsatility were assessed. Subjects were also monitored 2, 4, 8, and 12 weeks after commencement of GHRH analog treatment. Blood pressure, body weight, and fasting insulin and glucose levels were recorded at each visit. Serum concentrations of IGF-I, IGF binding protein-1 (IGFBP-1), IGFBP-3, GH-binding protein (GHBP), lipids, and safety laboratory tests (complete blood count and chemistry profile) were measured in fasting samples (0800-0900 h). Body composition was determined by dual energy x-ray absorptiometry scan, and skin thickness was measured at four sites, including the right and left hand and volar forearm, by Harpenden skin calipers. Insulin sensitivity was assessed by a frequently sampled i.v. glucose tolerance test. Quality of life parameters, including sleep, were evaluated through self-administered questionnaires. Nightly GHRH analog administration at 2100 h induced, within 10 min, an acute release of GH, which lasted for 2 h. The GH-releasing effect of GHRH analog was sustained during the course of the study. Compared with placebo, GHRH analog induced a significant increase in 12-h integrated nocturnal GH levels in women (P < 0.01) and men (P < 0.05). This was accompanied, within 2 weeks, by increased serum levels of IGF-I (P < 0.05) and IGFBP-3 (P < 0.001), but not IGFBP-1, which remained elevated for 12 weeks, returning toward baseline by 16 weeks in both genders. Within 4 weeks, GHBP concentrations were significantly increased (P < 0.01) in women, but not in men. Although blood pressure and body weight were unaffected, GHRH analog treatment resulted in a significant increase in skin thickness (P < 0.05) in both genders and increased lean body mass in men only (P < 0.05), with no other changes in body composition or bone mineral density in either gender. There was a trend for a positive nitrogen balance in both genders, which became significant (P = 0.03) when the data were combined. Fasting insulin and glucose levels were unaltered, but a significant increase in insulin sensitivity occurred in men (P < 0.05), but not in women. Assessment of quality of life parameters revealed a significant improvement in general well-being (P < 0.05) and libido (P < 0.01) in men, but not in women, and sleep quality was unaffected in both genders. The only adverse side-effect was transient hyperlipidemia, which resolved by the end of the study. We conclude that nightly administration of GHRH analog for 4 months in age-advanced men and women activated the somatotropic axis. Although an increase in skin thickness was found in both genders, increases in lean body mass, insulin sensitivity, general well-being, and libido occurred in men but not in women. These observations suggest that GHRH analog administration induced anabolic effects favoring men more than women. Further studies are needed to define the gender differences observed in response to GHRH analog administration.

Aged↗