Physical Frailty: ICFSR International Clinical Practice Guidelines for Identification and Management.

OBJECTIVE: The task force of the International Conference of Frailty and Sarcopenia Research (ICFSR) developed these clinical practice guidelines to overview the current evidence-base and to provide recommendations for the identification and management of frailty in older adults. METHODS: These recommendations were formed using the GRADE approach, which ranked the strength and certainty (quality) of the supporting evidence behind each recommendation. Where the evidence-base was limited or of low quality, Consensus Based Recommendations (CBRs) were formulated. The recommendations focus on the clinical and practical aspects of care for older people with frailty, and promote person-centred care. Recommendations for Screening and Assessment: The task force recommends that health practitioners case identify/screen all older adults for frailty using a validated instrument suitable for the specific setting or context (strong recommendation). Ideally, the screening instrument should exclude disability as part of the screening process. For individuals screened as positive for frailty, a more comprehensive clinical assessment should be performed to identify signs and underlying mechanisms of frailty (strong recommendation). Recommendations for Management: A comprehensive care plan for frailty should address polypharmacy (whether rational or nonrational), the management of sarcopenia, the treatable causes of weight loss, and the causes of exhaustion (depression, anaemia, hypotension, hypothyroidism, and B12 deficiency) (strong recommendation). All persons with frailty should receive social support as needed to address unmet needs and encourage adherence to a comprehensive care plan (strong recommendation). First-line therapy for the management of frailty should include a multi-component physical activity programme with a resistance-based training component (strong recommendation). Protein/caloric supplementation is recommended when weight loss or undernutrition are present (conditional recommendation). No recommendation was given for systematic additional therapies such as cognitive therapy, problem-solving therapy, vitamin D supplementation, and hormone-based treatment. Pharmacological treatment as presently available is not recommended therapy for the treatment of frailty.

Impact of frailty on outcomes in surgical patients: A systematic review and meta-analysis.

IMPORTANCE: Age has historically been used to predict negative post-surgical outcomes. The concept of frailty was introduced to explain the discrepancies that exist between patients' chronological and physiological age. The efficacy of the modified frailty index (mFI) to predict surgical risk is not clear. OBJECTIVE: We sought to synthesize the current literature to quantify the impact of frailty as a prognostic indicator across all surgical specialties. DATA SOURCES: Pubmed and Cochrane databases were screened from inception to 1 January 2018. STUDY SELECTION: Studies utilizing the modified Frailty Index (mFI) as a post-operative indicator of any type of surgery. The mFI was selected based on a preliminary search showing it to be the most commonly applied index in surgical cohorts. DATA EXTRACTION AND SYNTHESIS: Articles were selected via a two-stage process undertaken by two reviewers (AP and DS). Statistical analysis was performed in Revman (Review manager V5.3). The random-effects model was used to calculate the Risk Ratios (RR). MAIN OUTCOME(S) AND MEASURE(S): The primary outcomes: post-operative complications, re-admission, re-operation, discharge to a skilled care facility, and mortality. RESULTS: This meta-analysis of 16 studies randomizes 683,487 patients, 444,885 frail, from gastrointestinal, vascular, orthopedic, urogenital, head and neck, emergency, neurological, oncological, cardiothoracic, as well as general surgery cohorts. Frail patients were more likely to experience complications (RR 1.48, 95%CI 1.35-1.61; p < 0.001), major complications (RR 2.03, 95%CI 1.26-3.29; p = 0.004), and wound complications (RR 1.52, 95%CI 1.47-1.57; p < 0.001). Furthermore, frail patients had higher risk of readmission (RR 1.61, 95%CI 1.44-1.80; p < 0.001) and discharge to skilled care (RR 2.15, 95%CI 1.92-2.40; p < 0.001). Notably, the risk of mortality was 4.19 times more likely in frail patients (95% CI 2.96-5.92; p < 0.001). CONCLUSIONS: and Relevance: This study is the first to synthesize the evidence across multiple surgical specialties and demonstrates that the mFI is an underappreciated prognostic indicator that strongly correlates with the risk of post-surgical morbidity and mortality. This supports that formal incorporation of pre-operative frailty assessment improves surgical decision-making.

Diabetes self care activities among adults 20 years and above residing in a resettlement colony in East Delhi.

BACKGROUND: Self-care activities are the cornerstone of diabetes care that ensures patients participation to achieve optimal glycemic control and to prevent complications. OBJECTIVE: The aim of this study is to find the level of self-care activities among diabetics aged ≥20 years residing in a resettlement colony in East Delhi and its association with sociodemographic factors, disease, and treatment profile. METHODS: Using cross-sectional survey, 168 known diabetic patients were selected from Nand Nagri, a resettlement colony in East Delhi. Data were collected using Hindi translation of revised version-Summary of Diabetic Self Care Activities along with a pretested semi-open-ended questionnaire. Self-care was assessed on six parameters as follows: (a) general diet, (b) specific diet, (c) exercise, (d) blood sugar testing, (e) foot-care, and (f) smoking. The study period was from November 2014 to April 2016. RESULTS: Nearly 35.1% of respondents belonged to 60-69 years age group. About 52.4% of respondents were female. Fifty-two diabetics (31%) reported having practised diet control on all 7 days in the past 1 week. Nearly 39.3% of patients did not perform any physical activity. The blood test was not practised by 92.3% of respondents. Foot-care was practised by only 19% of patients. There was a significant association between general diet among diabetics with family support (P = 0.020), place of diagnosis (P = 0.033), and treatment funds (P = 0.017). The exercise score among diabetics who were below the poverty line was higher than those above poverty line (P = 0.029). Younger age (P = 0.005) and treatment with insulin (P = 0.008) were positively associated with blood glucose testing. The foot-care practice was better in patients aware of complications and foot-care practices (P < 0.001). CONCLUSION: Self-care activities among diabetic patients were very poor. Self-management educational programs at hospitals along with information, education, and communication activities at the community level and one-to-one counseling are recommended.

Does the volume of supplemental intraligamentary injections affect the anaesthetic success rate after a failed primary inferior alveolar nerve block? A randomized-double blind clinical trial.

AIM: To investigate the efficacy of 0.2 mL vs. 0.6 mL of 2% lidocaine when given as a supplementary intraligamentary injection after a failed inferior alveolar nerve block (IANB). METHODOLOGY: Ninety-seven adult patients with symptomatic irreversible pulpits received an IANB and root canal treatment was initiated. Pain during treatment was recorded using a visual analogue scale (Heft-Parker VAS). Patients with unsuccessful anaesthesia (n = 78) randomly received intraligamentary injection of either 0.2 mL or 0.6 mL of 2% lidocaine with 1 : 80 000 epinephrine. Root canal treatment was reinitiated. Success after primary injection or supplementary injection was defined as no or mild pain (HP VAS score ≤54 mm) during access preparation and root canal instrumentation. Heart rate was monitored using a finger pulse oximeter. The anaesthetic success rates were analysed with Pearson chi-square test at 5% significance levels. The heart rate changes were analysed using t-tests. RESULTS: The intraligamentary injections with 0.2 mL solution gave an anaesthetic success rate of 64%, whilst the 0.6 mL was successful in 84% of cases with failed primary IANB. (χ2  = 4.3, P = 0.03). There was no significant effect of the volume of intraligamentary injection on the change in heart rate. CONCLUSIONS: Increasing the volume of intraligamentary injection improved the success rates after a failed primary anaesthetic injection.

Contributors to the substantial variation in on-treatment testosterone levels in men receiving transdermal testosterone gels in randomized trials.

There is substantial inter-individual variability in serum testosterone levels in hypogonadal men treated with testosterone gels. We aimed to elucidate participant-level factors that contribute to inter-individual variability in testosterone levels during testosterone therapy. An exploratory aim was to determine whether polymorphisms in genes encoding testosterone-metabolizing enzymes could explain the variation in on-treatment testosterone concentrations in men who were randomized to testosterone arm in TOM Trial. We used data from three randomized trials that used 1% transdermal testosterone gels and had testosterone levels measured 2-4 weeks after randomization for dose adjustment: Testosterone in Older Men with Mobility Limitation (TOM), Effects of Testosterone on Pain Perception (TAP), and Effects of Testosterone on Atherosclerosis Progression (TEAAM). Forty-seven percent, 38%, and 9% of participants in TAP, TEAAM, and TOM trials, respectively, failed to raise testosterone levels >400 ng/dL; 6, 8, and 30% of participants had on-treatment testosterone levels >1000 ng/dL. Even after dose adjustment, there was substantial variation in on-treatment levels at subsequent study visits. Baseline characteristics (age, height, weight, baseline testosterone, SHBG, hematocrit, and creatinine) accounted for only a small fraction of the variance (<8%). Polymorphisms in SHBG and AKR1C3 genes were suggestively associated with on-treatment testosterone levels. To conclude, baseline participant characteristics account for only a small fraction of the variance in on-treatment testosterone levels investigated. Multiple dose titrations are needed to maintain on-treatment testosterone levels in the target range. The role of SHBG and AKR3C1 polymorphisms as contributors to variations in on-treatment testosterone levels should be investigated.

Sarcopenia Trials in Specific Diseases: Report by the International Conference on Frailty and Sarcopenia Research Task Force.

Muscle atrophy occurs as a consequence of a number of conditions, including cancer, chronic obstructive pulmonary disease (COPD), diabetes mellitus, heart failure, and other chronic diseases, where it is generally a predictor of poor survival. It also occurs as a consequence of disuse and an age-related loss of muscle mass and strength (sarcopenia). The aims of the 2016, International Conference on Frailty and Sarcopenia Research (ICFSR) Task Force were to examine how these specific chronic conditions have been employed in treatment trials thus far and how future trials using these patient groups might be designed for efficient identification of effective sarcopenia interventions. Functional limitations assessed as gait speed, distance walked over a set time period, or other attributes of physical performance have been suggested as outcome measures in sarcopenia trials. Indeed, such measures have already been used successfully in a number of trials aimed at preventing disability in older adults.

Sleep Quality of Call Handlers Employed in International Call Centers in National Capital Region of Delhi, India.

BACKGROUND: Call center sector in India is a relatively new and fast growing industry driving employment and growth in modern India today. Most international call centers in National Capital Region (NCR) of Delhi operate at odd work hours corresponding to a time suitable fortheir international customers. The sleep quality of call handlers employed in these call centers is in jeopardy owing to their altered sleep schedule. OBJECTIVE: To assess the sleep quality and determine its independent predictors among call handlers employed in international call centers in NCR of Delhi. METHODS: A cross-sectional questionnaire-based study was conducted on 375 call handlers aged 18-39 years employed in international call centers in NCR of Delhi. Sleep quality was assessed using Athens Insomnia scale along with a pre-tested, structured questionnaire. RESULTS: The mean age of respondents was 24.6 (SD 2.4) years. 78% of participants were male. 83.5% of respondents were unmarried. 44.3% of call handlers were cigarette smokers. Physical ailments were reported by 37% call handlers. 77.6% of call handlers had somesuspicion of insomnia or suspected insomnia; the rest had no sleep problem. Smoking, poor social support, heavy workload, lack of relaxation facility at office, and prolonged travel time to office were independent predictors of sleep quality (p<0.05). CONCLUSION: Call handlers have to compromise upon their sleep owing to the contemporary work settings in call centers. Safeguarding their health becomes an occupational health challenge to public health specialists.

TSPAN5, ERICH3 and selective serotonin reuptake inhibitors in major depressive disorder: pharmacometabolomics-informed pharmacogenomics.

Millions of patients suffer from major depressive disorder (MDD), but many do not respond to selective serotonin reuptake inhibitor (SSRI) therapy. We used a pharmacometabolomics-informed pharmacogenomics research strategy to identify genes associated with metabolites that were related to SSRI response. Specifically, 306 MDD patients were treated with citalopram or escitalopram and blood was drawn at baseline, 4 and 8 weeks for blood drug levels, genome-wide single nucleotide polymorphism (SNP) genotyping and metabolomic analyses. SSRI treatment decreased plasma serotonin concentrations (P<0.0001). Baseline and plasma serotonin concentration changes were associated with clinical outcomes (P<0.05). Therefore, baseline and serotonin concentration changes were used as phenotypes for genome-wide association studies (GWAS). GWAS for baseline plasma serotonin concentrations revealed a genome-wide significant (P=7.84E-09) SNP cluster on chromosome four 5' of TSPAN5 and a cluster across ERICH3 on chromosome one (P=9.28E-08) that were also observed during GWAS for change in serotonin at 4 (P=5.6E-08 and P=7.54E-07, respectively) and 8 weeks (P=1.25E-06 and P=3.99E-07, respectively). The SNPs on chromosome four were expression quantitative trait loci for TSPAN5. Knockdown (KD) and overexpression (OE) of TSPAN5 in a neuroblastoma cell line significantly altered the expression of serotonin pathway genes (TPH1, TPH2, DDC and MAOA). Chromosome one SNPs included two ERICH3 nonsynonymous SNPs that resulted in accelerated proteasome-mediated degradation. In addition, ERICH3 and TSPAN5 KD and OE altered media serotonin concentrations. Application of a pharmacometabolomics-informed pharmacogenomic research strategy, followed by functional validation, indicated that TSPAN5 and ERICH3 are associated with plasma serotonin concentrations and may have a role in SSRI treatment outcomes.

Effects of testosterone administration on cognitive function in hysterectomized women with low testosterone levels: a dose-response randomized trial.

PURPOSE: To determine the dose-dependent effects of testosterone administration on cognition in women with low testosterone levels. METHODS: 71 hysterectomized women with or without oophorectomy with total testosterone <31 ng/dl and/or free testosterone <3.5 pg/ml received a standardized transdermal estradiol regimen during the 12-week run-in period and were then randomized to receive weekly intramuscular injections of placebo, 3, 6.25, 12.5, or 25 mg testosterone enanthate for 24 weeks. Total testosterone was measured in serum by LC-MS/MS, and free testosterone levels were measured by equilibrium dialysis. Cognitive function was evaluated using a comprehensive battery of standardized neuropsychological tests at baseline and 24 weeks. RESULTS: 46 women who had baseline and end-of-treatment cognitive function data constituted the analytic sample. The five groups were similar at baseline. Mean on-treatment nadir total testosterone concentrations were 15, 89, 98, 134, and 234 ng/dl in the placebo, 3, 6.25, 12.5, and 25 mg groups, respectively. No significant changes in spatial ability, verbal fluency, verbal memory, or executive function were observed in any treatment arm compared to placebo even after adjustment for baseline cognitive function, age, and education. Multiple regression analysis did not show any significant relation between changes in testosterone concentrations and change in cognitive function scores. CONCLUSION: Short-term testosterone administration over a wide range of doses for 24 weeks in women with low testosterone levels was neither associated with improvements nor worsening of cognitive function.

Family caregivers' burden: A hospital based study in 2010 among cancer patients from Delhi.

BACKGROUND: A large number of patients with chronic diseases like, cancer are cared for in homes by the family members in India. The vital role that these family members play as "caregivers" is well recognized, however, the burden on them is poorly understood. AIMS: To assess burden and to determine the predictors of burden on family caregivers of cancer patients. SETTING AND DESIGN: A cross-sectional, hospital based study conducted in National Capital Territory of Delhi. MATERIALS AND METHODS: 200 family caregivers of cancer patients were selected by systematic random sampling and interviewed using standard, validated Hindi version of Zarit Burden Interview. STATISTICAL ANALYSIS: Univariate analysis and multivariable logistic regression were carried out using Statistical Package for the Social Sciences software (version 17.0). RESULTS: The study population consisted of 90 (45%) males and 110 (55%) female caregivers aged 18-65 years. 113 (56.5%) caregivers reported no or minimal burden while 75 (37.5%) caregivers reported mild to moderate burden. Using logistic regression marital status, education and type of family of caregivers, occupation of cancer patients and type of treatment facility were found to be the predictors of burden on caregivers. CONCLUSION: In view of the substantial burden on family caregivers coupled with lack of adequate number of cancer hospitals, there is a public-health imperative to recognize this important group. All levels of health-staff in cancer hospitals in developing countries should be sensitized to the various burdens faced by family caregivers.

The heritability of circulating testosterone, oestradiol, oestrone and sex hormone binding globulin concentrations in men: the Framingham Heart Study.

OBJECTIVE: Circulating testosterone, oestradiol and oestrone concentrations vary considerably between men. Although a substantial proportion of this variation may be attributed to morbidity and behavioural factors, these cannot account for its entirety, suggesting genetic inheritance as a potential additional determinant. The analysis described here was intended to estimate the heritability of male circulating total testosterone (TT), calculated free testosterone (cFT), oestrone (E1), oestradiol (E2) and sex hormone binding globulin (SHBG), along with the genetic correlation between these factors. DESIGN: Cross-sectional, observational analysis of data from male members of the Offspring and Generation 3 cohorts of the Framingham Heart Study. Data were collected in the years 1998-2005. PARTICIPANTS: A total of 3367 community-dwelling men contributed to the analysis, including 1066 father/son and 1284 brother pairs among other family relationships. MEASUREMENTS: Levels of serum sex steroids (TT, E1 and E2) were measured by liquid chromatography-tandem mass spectrometry, SHBG by immunofluorometric assay and cFT by mass action equation. Heritability was obtained using variance components analysis with adjustment for covariates including age, diabetes mellitus, body mass index and smoking status. RESULTS: Age-adjusted heritability estimates were 0·19, 0·40, 0·40, 0·30 and 0·41 for cFT, TT, E1, E2 and SHBG, respectively. Adjustment for covariates did not substantially attenuate these estimates; SHBG-adjusted TT results were similar to those obtained for cFT. Genetic correlation coefficients (ρG ) indicated substantial genetic association between TT and cFT (ρG = 0·68), between TT and SHBG (pG = 0·87), between E1 and E2 (ρG = 0·46) and between TT and E2 (ρG = 0·48). CONCLUSION: Circulating testosterone, oestradiol and oestrone concentrations exhibit substantial heritability in adult men. Significant genetic association between testosterone and oestrogen levels suggests shared genetic pathways.

Sildenafil increases serum testosterone levels by a direct action on the testes.

Phosphodiesterase-5-inhibitors, such as sildenafil, increase intracavernosal cyclic guanosine monophosphate levels, which results in corporal smooth muscle relaxation and penile erection. Here, we determined the effects of sildenafil administration on the hypothalamic-pituitary-gonadal axis in men with erectile dysfunction and low testosterone levels. The Testosterone and Erectile Dysfunction trial (ClinicalTrials.gov # NCT00512707) initially administered an optimized dose of sildenafil to 140 men, aged 40-70 years with erectile dysfunction, low serum total testosterone (<11.4 nmol/L; 330 ng/dL) and/or free testosterone (<173 pmol/L; 50 pg/mL) over 3-7 weeks. Sex steroids and gonadotropins were measured at baseline and after sildenafil optimization in a longitudinal study without a separate control group. Serum testosterone, dihydrotestosterone (DHT) and oestrogens were measured using liquid chromatography-tandem mass spectrometry. Administration of an optimized dose of sildenafil was associated with mean increases of 3.6 nmol/L (103 ng/dL; p < 0.001) and 110 pmol/L (31.7 pg/mL; p < 0.001) in total and free testosterone levels respectively. This was accompanied by parallel increases in serum DHT (0.17 nmol/L; 4.9 ng/dL; p < 0.001) and oestradiol (14 pmol/L; 3.7 pg/mL; p < 0.001) and significant suppression of luteinizing hormone (change -1.3 units/L; p = 0.003) levels, suggesting a direct effect at the testicular level. Androstenedione and oestrone increased by 1.3 nmol/L (38 ng/dL; p = 0.011) and 10.7 pmol/L (2.9 pg/mL; p = 0.012), respectively, supporting a possible effect of sildenafil on adrenal steroidogenesis. In conclusion, sildenafil administration was associated with increased testosterone levels likely ascribable to a direct effect on the testis.

Conservative management of morbidly adherant placenta - a case report and review of literature.

Placenta accreta is a condition when the placenta is abnormally adherent to the uterus. This can result in complications like severe haemorrhage, injuries to pelvic organs, possible need for Caesarian hysterectomy. There is always high risk of maternal morbidity and mortality. Over the last decade there has been gradual shift towards conservative management of placenta accreta involving uterine and placental conservation, with the main aim to reduce pelvic injury and to achieve haemostasis with the aid of intervention radiology by means of Uterine Artery embolisation and use of medical chemotherapeutic agents like Methotrexate. This strategy has previously been shown to reduce morbidity and mortality in carefully selected cases of Placenta accreta. We have successfully managed a case of Placenta percreta conservatively using Uterine Artery embolisation followed by Injection methotrexate.

Circulating testosterone and SHBG concentrations are heritable in women: the Framingham Heart Study.

CONTEXT: Many factors influence the concentration of circulating testosterone and its primary binding protein, SHBG. However, little is known about the genetic contribution to their circulating concentrations in women, and their heritability in women is not well established. OBJECTIVE: Our objective was to estimate the heritability of circulating total testosterone (TT), free testosterone (FT), and SHBG in women in families from the Framingham Heart Study. METHODS: Women in the Framingham Heart Study who were not pregnant, had not undergone bilateral oophorectomy, and were not using exogenous hormones were eligible for this investigation. TT was measured using liquid chromatography tandem mass spectrometry and SHBG using an immunofluorometric assay (Delfia-Wallac), and FT was calculated. Heritability estimates were calculated using variance-components methods in Sequential Oligogenic Linkage Analysis Routines (SOLAR) and were adjusted for age, age(2), body mass index (BMI), BMI(2), diabetes, smoking, and menopausal status. Bivariate analyses were done to assess genetic correlation between TT, FT, and SHBG. RESULTS: A total of 2685 women were studied including 868 sister pairs and 688 mother-daughter pairs. Multivariable adjusted heritability estimates were 0.26 ± 0.05 for FT, 0.26 ± 0.05 for TT, and 0.56 ± 0.05 for SHBG (P < 1.0 × 10(-7) for all). TT was genetically correlated with SHBG [genetic correlation coefficient (ρG) = 0.31 ± 0.10] and FT (ρG = 0.54 ± 0.09), whereas SHBG was inversely correlated with FT (ρG = -0.60 ± 0.08). CONCLUSION: Circulating TT, FT, and SHBG concentrations in women are significantly heritable, underscoring the importance of further work to identify the specific genes that contribute significantly to variation in sex steroid concentrations in women. The strong shared genetic component among pairs of TT, FT, and SHBG concentrations suggests potential pleiotropic effects for some of the underlying genes.

Role of the androgen receptor CAG repeat polymorphism in prostate cancer, and spinal and bulbar muscular atrophy.

Androgens are involved in the development of several tissues, including prostate, skeletal muscle, bone marrow, hair follicles, and brain. Most of the biological effects of the androgens are mediated through an intracellular transcription factor, the androgen receptor (AR) at the level of gene regulation. Several types of mutations in the AR gene have been linked to endocrine dysfunctions. The expansion of CAG codon repeat, coding for a polyglutamine (PolyQ) tract in the N-terminal domain is one such mutation. The polyQ chain length impacts AR's ability to interact with critical coregulators, which in turn modulates its transcriptional efficacy. Pathologic manifestations of variations in polyQ chain length have been associated with prostate cancer susceptibility, and the Spinal and Bulbar Muscular Atrophy (SBMA), a neurodegenerative disease. In this review article, we discuss multiple aspects of the role of polyQ chain length in the actions of the AR, their importance in prostate cancer development and progression, and SBMA with an aim to understand the underlying mechanisms involved in these diseases, which can be targeted for future therapeutic approaches.

Chemotherapy-induced palmer planter erythrodysesthesia.

We report a case of palmar plantar erythrodysesthesia (PPE) in a case of acute lymphoblastic leukemia treated with VALP regime. The treating physician must be aware of this uncommon complication of chemotherapeutic agents to avoid unnecessary investigations.

Disseminated histoplasmosis with reactive haemophagocytosis presenting as PUO in an immunocompetent host.

Disseminated histoplasmosis (DH) with reactive haemophagocytosis has been described in literature mainly in immunocompromised hosts. Only sporadic case reports exist in immunocompetent hosts. Here, we present a rare case of DH with reactive haemophagocytosis in an immunocompetent host presenting as PUO.

Testosterone dose-response relationships in healthy young men.

Testosterone increases muscle mass and strength and regulates other physiological processes, but we do not know whether testosterone effects are dose dependent and whether dose requirements for maintaining various androgen-dependent processes are similar. To determine the effects of graded doses of testosterone on body composition, muscle size, strength, power, sexual and cognitive functions, prostate-specific antigen (PSA), plasma lipids, hemoglobin, and insulin-like growth factor I (IGF-I) levels, 61 eugonadal men, 18-35 yr, were randomized to one of five groups to receive monthly injections of a long-acting gonadotropin-releasing hormone (GnRH) agonist, to suppress endogenous testosterone secretion, and weekly injections of 25, 50, 125, 300, or 600 mg of testosterone enanthate for 20 wk. Energy and protein intakes were standardized. The administration of the GnRH agonist plus graded doses of testosterone resulted in mean nadir testosterone concentrations of 253, 306, 542, 1,345, and 2,370 ng/dl at the 25-, 50-, 125-, 300-, and 600-mg doses, respectively. Fat-free mass increased dose dependently in men receiving 125, 300, or 600 mg of testosterone weekly (change +3.4, 5.2, and 7.9 kg, respectively). The changes in fat-free mass were highly dependent on testosterone dose (P = 0.0001) and correlated with log testosterone concentrations (r = 0.73, P = 0.0001). Changes in leg press strength, leg power, thigh and quadriceps muscle volumes, hemoglobin, and IGF-I were positively correlated with testosterone concentrations, whereas changes in fat mass and plasma high-density lipoprotein (HDL) cholesterol were negatively correlated. Sexual function, visual-spatial cognition and mood, and PSA levels did not change significantly at any dose. We conclude that changes in circulating testosterone concentrations, induced by GnRH agonist and testosterone administration, are associated with testosterone dose- and concentration-dependent changes in fat-free mass, muscle size, strength and power, fat mass, hemoglobin, HDL cholesterol, and IGF-I levels, in conformity with a single linear dose-response relationship. However, different androgen-dependent processes have different testosterone dose-response relationships.

Neuroendocrine abnormalities associated with HIV infection.

Functional derangement of every endocrine organ system has been reported in association with HIV infection. The changes in endocrine function may be related to the viral infection of the gland, to systemic effects of HIV or an opportunistic infection, to infiltration by a neoplasm such as Kaposi's sarcoma, to a complication of treatment, or generation of cytokines. A wide spectrum of endocrine abnormalities is observed in HIV-infected patients. Some of these abnormalities are similar to those seen in other systemic illness, whereas others are unique to HIV infection. The clinical significance of many of these endocrine abnormalities is not well understood.

Specific localization of RBM1a in the nuclei of all cell types except elongated spermatids within seminiferous tubules of the human.

Recent studies have indicated that at least three regions (AZF a-c) on the long arm of the Y-chromosome code for factors are involved in spermatogenesis. One of the candidate genes in the AZFb region is RBM1a, coding for a protein with an RNA binding motif. In this study, poly clonal antibodies raised against a 15 amino acid peptide, corresponding to residues 263-304 of the deduced amino acid sequence of RBM1a, has been used to localize the RBM1a protein in the human testis. Immunohistochemistry on normal human testis using this RBM1a antibody, localized the antigen to the nuclei of spermatogonia, primary spermatocytes, and round spermatids but not to the nuclei of elongated spermatids. The antibody also specifically identified the nuclei of Sertoli cells, although the fluorescence was not as strong as in the germ cell nuclei it identified. No specific fluorescence was seen in the nuclei of either peritubular, endothelial or Leydig cells. Western blot of normal human testicular tissue using the anti-RBM1a antibody gave rise to a single specific band of approximately 55 kDa, corresponding to the expected size of RBM1a. In view of its expression in germ cells, and because RBM1a has an RNA binding domain, RBM1a may be involved in RNA processing, such as RNA splicing or RNA export which are events necessary for normal spermatogenesis.