The longitudinal study of adrenal maturation during gonadal suppression: evidence that adrenarche is a gradual process.

The physical changes that herald the onset of puberty result from the combination of adrenarche and gonadarche. To examine adrenal maturation and associated changes in growth without the confounding effects of changes in the gonadal steroid milieu, we performed a longitudinal study in 14 young girls with idiopathic central precocious puberty during long-term pituitary-gonadal suppression. Beginning at the mean age of 2.

Efficacy of low tidal volume ventilation in patients with different clinical risk factors for acute lung injury and the acute respiratory distress syndrome.

In patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), a recent ARDS Network randomized controlled trial demonstrated that a low tidal volume (VT) mechanical ventilation strategy (6 ml/kg) reduced mortality by 22% compared with traditional mechanical ventilation (12 ml/kg). In this study, we examined the relative efficacy of low VT mechanical ventilation among 902 patients with different clinical risk factors for ALI/ARDS who participated in ARDS Network randomized controlled trials. The clinical risk factor for ALI/ARDS was associated with substantial variation in mortality.

Tryptophan depletion in SSRI-recovered depressed outpatients.

Rationale: Recently, a number of studies have challenged the finding that acute tryptophan depletion (TD) increases depressive symptoms in medicated, formerly depressed patients. The present study examined the effects of acute nutritional TD on remitted depressed patients currently treated with selective serotonin reuptake inhibitors. In an attempt to clarify conflicting earlier findings, the effects of a number of clinical variables on outcome were also investigated.

Idiopathic hypereosinophilic syndrome in 3 Rottweilers.

Three Rottweilers with marked peripheral eosinophilia and infiltration of the liver, spleen, lungs, and bone marrow with eosinophils were diagnosed with idiopathic hypereosinophilic syndrome (IHES). Mean serum immunoglobulin E concentrations were markedly high. On cytogenetic analysis, no evidence of karyotypic abnormalities was found in bone marrow aspirates.

Effects of growth hormone (GH) administration on homocyst(e)ine levels in men with GH deficiency: a randomized controlled trial.

GH deficiency is associated with increased cardiovascular mortality and early manifestations of atherosclerosis. Elevated serum homocyst(e)ine levels have been found to be associated with increased cardiovascular risk. The effect of GH replacement on homocyst(e)ine has not been investigated to date.

Hypogonadism in patients with acromegaly: data from the multi-centre acromegaly registry pilot study.

Objective: Because acromegaly is an uncommon disorder, epidemiological data regarding the demographics of the disease such as the prevalence of hypogonadism have been limited. In order to derive clinical and epidemiological information, including underlying hormonal factors, regarding hypogonadism in patients with acromegaly, we performed a pilot study designed to develop a multi-centre acromegaly patient registry.

Design And Measurements: Medical records of patients with acromegaly seen between 1976 and 1996 at three Institutions were reviewed, and data were entered into a database using a secure internet website.

Risperidone-associated hyperprolactinemia.

Objective: To compare the prolactogenic effects of risperidone, clozapine, and typical antipsychotic agents in an outpatient community-based psychiatric population.

Methods: Prolactin and thyroid-stimulating hormone (TSH) concentrations were measured in 68 outpatients with schizophrenia who were receiving antipsychotic medications and were recruited from a community mental health clinic.

Results: The percentage of women with increased prolactin concentrations was significantly greater in the risperidone group (100%, 12 of 12 patients) than in the clozapine group (25%, 1 of 4) (P = 0.

Intra-laboratory reproducibility of human papillomavirus identification in cervical specimens by a polymerase chain reaction-based assay.

Background: polymerase chain reaction (PCR)-based assays for human papillomavirus (HPV) sequences are in wide use in clinical and epidemiological studies. The reproducibility of these assays is not extensively studied.

Objectives: to estimate the intra-laboratory reproducibility of generic and type-specific HPV diagnoses by the MY09/MY11/HMB01 consensus L1 primer-based PCR assay.

Increased oxidative damage to DNA in ALS patients.

Although the cause of amyotrophic lateral sclerosis (ALS) is unknown, substantial evidence indicates that oxidative toxicity is associated with neuronal death in this disease. We examined levels of a well-established marker of oxidative damage to DNA, 8-hydroxy-2'-deoxyguanosine (8OH2'dG) in plasma, urine, and cerebrospinal fluid (CSF) at a single time point from subjects with ALS, other neurological diseases, or no known disorders. We also measured the rate of change of 8OH2'dG levels in plasma and urine from ALS and in urine from control subjects over 9 months and examined the relationship to disease severity.

Effects of testosterone and progressive resistance training in eugonadal men with AIDS wasting. A randomized, controlled trial.

Background: Substantial loss of muscle mass occurs among men with AIDS wasting.

Objective: To investigate the independent effects of testosterone therapy and progressive resistance training in eugonadal men with AIDS wasting.

Design: Randomized, controlled trial.

Effects of growth hormone administration on inflammatory and other cardiovascular risk markers in men with growth hormone deficiency. A randomized, controlled clinical trial.

Background: Growth hormone-deficient adults have increased cardiovascular mortality. Growth hormone replacement may affect cardiovascular risk. Inflammation plays an important role in atherosclerosis, and inflammatory markers are predictive of cardiovascular events.

Clozapine, diabetes mellitus, weight gain, and lipid abnormalities: A five-year naturalistic study.

Objective: The goal of this 5-year naturalistic study of patients treated with clozapine was to examine the incidence of treatment-emergent diabetes mellitus in relation to other factors, including weight gain, lipid abnormalities, age, clozapine dose, and treatment with valproate.

Method: Data on age, gender, race, diagnosis, family history of diabetes, and age at clozapine initiation were collected from medical records of 82 outpatients with schizophrenia or schizoaffective disorder. Clozapine dose, data on use of valproate, and laboratory test results were recorded at 6-month intervals.

Withdrawal of long-term physiological growth hormone (GH) administration: differential effects on bone density and body composition in men with adult-onset GH deficiency.

Adults with acquired GH deficiency (GHD) have been shown to have osteopenia associated with a 3-fold increase in fracture risk and exhibit increased body fat and decreased lean mass. Replacement of GH results in decreased fat mass, increased lean mass, and increased bone mineral density (BMD). The possible differential effect of withdrawal of GH replacement on body composition compartments and regional bone mass is not known.

Hepatoblastoma with erythrocytosis in a young female horse.

A 2.5-year-old female Thoroughbred was examined because of lethargy, anorexia, and weight loss. Analysis of a CBC revealed erythrocytosis and an increase in PCV.

Donepezil therapy in clinical practice: a randomized crossover study.

Objective: To determine the efficacy of donepezil hydrochloride for the treatment of Alzheimer disease in patients drawn from clinical practice.

Design: Two-center, randomized, placebo-controlled, double-masked crossover study.

Setting: Memory disorders units at Massachusetts General and Brigham and Women's hospitals, Boston.

The pharmacokinetics and pharmaco-dynamics of Procysteine in amyotrophic lateral sclerosis.

In 13 subjects with ALS, we studied the safety and pharmacokinetic properties of Procysteine, a cysteine prodrug that increases levels of intracellular glutathione. We found that oral administration of Procysteine was safe. Procysteine enters CSF after both IV and oral dosing and accumulates to significant levels in CSF.

Riluzole therapy in Huntington's disease (HD).

We conducted a 6-week open-label trial of riluzole (50 mg twice a day) in eight subjects with Huntington's disease. Subjects were evaluated before riluzole treatment, on treatment, and off treatment with the chorea, dystonia, and total functional capacity (TFC) scores from the Unified Huntington's Disease Rating Scale and magnetic resonance spectroscopy measurements of occipital cortex and basal ganglia lactate levels. Adverse events and safety blood and urine tests were assessed throughout the study.

A placebo-controlled trial of D-cycloserine added to conventional neuroleptics in patients with schizophrenia.

Background: In a preliminary dose-finding study, D-cycloserine, a partial agonist at the glycine modulatory site of the glutamatergic N-methyl-D-aspartate (NMDA) receptor, improved negative symptoms and cognitive function when added to conventional neuroleptics at a dose of 50 mg/d.

Methods: Forty-seven patients with schizophrenia meeting criteria for deficit syndrome were randomized to D-cycloserine, 50 mg/d (n=23) or placebo (n=24) added to their conventional neuroleptic for an 8-week, double-blind trial. Clinical assessments were performed at baseline and at weeks 1, 2, 4, 6, and 8.

Altered p53 is associated with aggressive behavior of chondrosarcoma: a long term follow-up study.

Background: p53 is a major tumor suppressor gene that has been implicated in the biology of a variety of human neoplasms, including some that affect the skeleton. Recent studies based on small numbers of cases have shown that overexpression or alteration of the p53 gene is frequently present in high grade, clinically aggressive chondrosarcomas of bone. In this study, the authors addressed the relation between overexpression and alteration of the p53 gene and the clinical aggressiveness of chondrosarcoma in a large series of patients for whom long term follow-up data were available.

Randomized controlled trial of doxorubicin versus dactinomycin in a multiagent protocol for treatment of dogs with malignant lymphoma.

Objective: To compare efficacy and toxicity of 2 multiagent chemotherapeutic protocols similar in all respects except that 1 incorporated dactinomycin and the other incorporated doxorubicin for treatment of dogs with malignant lymphoma.

Design: Randomized controlled trial.

Animals: 45 dogs with malignant lymphoma.

Effects of physiological growth hormone (GH) therapy on cognition and quality of life in patients with adult-onset GH deficiency.

GH replacement of adults with acquired GH deficiency (GHD) results in body composition changes including increases in lean mass and bone mineral density. However, the effects of long-term GH therapy on cognitive function are largely unknown, and there are conflicting data regarding quality of life. We performed a randomized, double-blind, placebo-controlled study of GH replacement in adults with GHD and measured cognition and sense of well-being using standardized psychometric tests before and after therapy.

Analysis in Drosophila melanogaster of the interaction between sex combs reduced and extradenticle activity in the determination of tarsus and arista identity.

Sex Combs Reduced (SCR) activity is proposed to be required cell nonautonomously for determination of tarsus identity, and Extradenticle (EXD) activity is required cell autonomously for determination of arista identity. Using the ability of Proboscipedia to inhibit the SCR activity required for determination of tarsus identity, we found that loss-of-EXD activity is epistatic to loss-of-SCR activity in tarsus vs. arista determination.