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Biomedical subjects

D Hayden

Publications and source records attributed to D Hayden.

At least 19 recordsLinked to original sources

Effect of airway pressure display on interobserver agreement in the assessment of vascular pressures in patients with acute lung injury and acute respiratory distress syndrome.

BACKGROUND: Previous investigations have identified significant interobserver variability in the measurements of central venous pressure and pulmonary artery occlusion pressure in critically ill patients. Large interobserver variability in the measurement of vascular pressures could potentially lead to inappropriate treatment decisions. OBJECTIVE: We postulated that adding an airway pressure signal (Paw) to pressure tracings of central venous pressure and pulmonary artery occlusion pressure would improve interobserver agreement by facilitating identification of end-expiration. DESIGN: To test this hypothesis, six independent experts used a standard protocol to interpret strip-chart recordings of central venous pressure and pulmonary artery occlusion pressure with or without Paw. Two observers were said to agree if their measurements were within 2 mm Hg of each other. SETTING/SUBJECTS/INTERVENTIONS: A total of 459 strip-chart recordings (303 without Paw and 156 with Paw) were obtained from 121 patients enrolled in the ARDSnet Fluids and Catheters Treatment Trial (FACTT) in 16 different hospitals. RESULTS: Agreement within 2 mm Hg between two measurements was 79% for central venous pressure strips without Paw vs. 86% with Paw. For pulmonary artery occlusion pressure, agreement increased from 71% without Paw to 83% with Paw. The increase in agreement with the addition of Paw was greater for strips demonstrating >8 mm Hg phasic respiratory variation compared with strips demonstrating less phasic respiratory variation. CONCLUSION: Paw display is a simple, inexpensive method to facilitate the identification of end-expiration that can significantly improve interobserver agreement.

Airway Resistance↗

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. The risk of death (before discharge home with unassisted breathing) was highest in patients with sepsis (43%); intermediate in subjects with pneumonia (36%), aspiration (37%), and other risk factors (35%); and lowest in those with trauma (11%) (p < 0.0001). Despite these differences in mortality, there was no evidence that the efficacy of the low VT strategy varied by clinical risk factor (p = 0.76, for interaction between ventilator group and risk factor). There was also no evidence of differential efficacy of low VT ventilation in the other study outcomes: proportion of patients achieving unassisted breathing (p = 0.59), ventilator-free days (p = 0.58), or development of nonpulmonary organ failure (p = 0.44). Controlling for demographic and clinical covariates did not appreciably affect these results. After reclassifying the clinical risk factors as pulmonary versus nonpulmonary predisposing conditions and infection-related versus non-infection-related conditions, there was still no evidence that the efficacy of low VT ventilation differed among clinical risk factor subgroups. In conclusion, we found no evidence that the efficacy of the low VT ventilation strategy differed among clinical risk factor subgroups for ALI/ARDS.

Adult↗

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. METHODS: Ten patients underwent TD in a double-blind, controlled, balanced crossover fashion. The control session followed the procedure of Krahn et al. (1996 Neuropsychopharmacology 15:325-328). Sessions were 5-8 days apart. RESULTS: TD was significantly related to increased scores on clinician-rated depression and anxiety scales, and on self-rated depression, anxiety, and somatic symptoms. The control challenge had no effect, despite the fact that the reductions in plasma tryptophan during the control session were unexpectedly high. Some evidence was found for a threshold in the relationship between reduction of plasma tryptophan and mood response. CONCLUSIONS: The mood effect of TD in medicated, formerly depressed patients was confirmed. A threshold may exist for mood effects following TD, implying that recent negative findings may have been caused by insufficient depletion. No other predicting or mediating factors were identified, although the variable "history of response pattern to medication" deserves further study.

Adolescent↗

Clinical and cost outcomes of medical nutrition therapy for hypercholesterolemia: a controlled trial.

OBJECTIVE: To compare the results and cost-effectiveness of a cholesterol lowering protocol implemented by registered dietitians with cholesterol lowering advice by physicians. DESIGN: Six month randomized controlled trial, cost-effectiveness analysis. Subjects included 90 ambulatory care patients (60 men, 30 women), age range 21 to 65 years, with hypercholesterolemia and not taking hypolipidemic drugs. Patients were randomly assigned to receive medical nutrition therapy (MNT) from dietitians using a NCEP based lowering protocol or usual care (UC) from physicians. Outcome measures were plasma lipid profiles, dietary intake, weight, activity, patient satisfaction, and costs of MNT. Changes from baseline for each variable of interest were compared between treatment groups using analysis of covariance controlling for baseline value of the variable and gender. RESULTS: MNT achieved a 6% decrease in total and LDL cholesterol levels at 3 and 6 months compared with a 1% increase and a 2% decrease in both values at 3 and 6 months with UC (P<.001 and P<.05, respectively). Weight loss (1.9 vs 0 kg, P<.001) and dietary intake of saturated fat (7% of energy vs 10%, P<.001) were better in the MNT than the UC group. The additional costs of MNT were $217 per patient to achieve a 6% reduction in cholesterol and $98 per patient to sustain the reduction. The cost-effectiveness ratio for MNT was $36 per 1% decrease in cholesterol and LDL level. APPLICATIONS/CONCLUSIONS: MNT from registered dietitians is a reasonable investment of resources because it results in significantly better lipid, diet, activity, weight, and patient satisfaction outcomes than UC.

Adult↗

Inflammatory cardiovascular risk markers in women with hypopituitarism.

Patients with hypopituitarism have increased cardiovascular mortality. A high prevalence of conventional cardiovascular risk factors, including obesity, central fat distribution, insulin resistance, and dyslipidemia, have been described in these patients. The inflammatory markers C-reactive protein (CRP) and IL-6 are predictors of cardiovascular events, and high levels of CRP have been reported in men with hypopituitarism and GH deficiency. However, little is known about inflammatory cardiovascular risk markers in women with hypopituitarism. We therefore investigated whether inflammatory and traditional cardiovascular risk markers are elevated in women with hypopituitarism. Fifty-three women with hypopituitarism and 111 healthy control women were included in this cross-sectional study. Morning blood samples were drawn after an overnight fast. Serum was assayed for CRP, IL-6, glucose, insulin, IGF-I, triglycerides, total cholesterol, low density lipoprotein cholesterol, high density lipoprotein (HDL) cholesterol, lipoprotein(a), E2, total testosterone (total T) and free testosterone (free T), and dehydroepiandrosterone sulfate. IL-6 and CRP levels were higher in women with hypopituitarism than in healthy controls (P < 0.0001 for comparison between groups). In a multivariate model, CRP levels depended on hypopituitarism, body mass index (BMI), and estrogen use. There was an interaction between the effect of BMI and hypopituitarism on CRP levels, such that the importance of hypopituitarism in determining CRP levels disappeared at high BMIs. In a similar multivariate model, IL-6 levels depended on hypopituitarism and BMI. Total cholesterol, the total to HDL cholesterol ratio, and triglycerides were higher in hypopituitary patients, but only triglycerides and the total to HDL cholesterol ratio depended on hypopituitarism when controlling for BMI. There was no significant difference in lipoprotein(a) levels between hypopituitary women and control subjects. However, when controlling for estrogen use, lipoprotein(a) levels showed a trend toward being lower in the hypopituitary group (P = 0.075). In patients with hypopituitarism, CRP correlated negatively with IGF-I (r = -0.35; P = 0.010), total T (r = -0.42; P = 0.0020), and free T (r = -0.30; P = 0.031). Similarly, IL-6 correlated negatively with total T (r = -0.39; P = 0.0040) and androstenedione (r = -0.27; P = 0.048) in hypopituitary patients. In conclusion, hypopituitary women have increased levels of IL-6 and CRP, both of which are inflammatory markers of atherosclerosis. GH deficiency and androgen deficiency may contribute to these findings. Chronic inflammation may contribute to the high cardiovascular risk seen in this population.

Biomarkers↗

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. We evaluated the effect of GH replacement on fasting homocyst(e)inemia in a group of men with adult-onset GH deficiency in a randomized, single blind, placebo-controlled trial. Forty men with adult-onset GH deficiency were randomized to GH or placebo for 18 months, with dose adjustments made according to serum insulin-like growth factor I (IGF-I) levels. Fasting serum homocyst(e)ine, folate, vitamin B12, and total T(3) levels were determined at baseline and 6 and 18 months. Anthropometry, IGF-I levels, insulin, and glucose were measured at 1, 3, 6, 12, and 18 months. Nutritional assessment, body composition, total T(4), thyroid hormone binding index, and free T(4) index were assessed every 6 months. Homocyst(e)ine decreased in the GH-treated group compared with that in the placebo group (net difference, -1.2 +/- 0.6 micromol/L; confidence interval, -2.4, -0.02 micromol/L; P = 0.047). Homocyst(e)ine at baseline was negatively correlated with plasma levels of folate (r = -0.41; P = 0.0087). Total T(3) increased in the GH-treated group vs. that in the placebo group (net difference, 0.17 +/- 0.046 ng/dL; confidence interval, 0.071, 0.26 nmol/L; P = 0.0012). Folate and vitamin B12 levels did not significantly change between groups. Changes in homocyst(e)ine were negatively correlated with changes in IGF-I. For each 1 nmol/L increase in IGF-I, homocyst(e)ine decreased by 0.04 +/- 0.02 micromol/L (P = 0.029). In contrast, changes in homocyst(e)ine did not correlate with changes in folate, vitamin B12, total T(3), C-reactive protein, interleukin-6, or insulin levels. This study shows that GH replacement decreases fasting homocyst(e)ine levels compared with placebo. This may be one of the mechanisms involved in the putative modulation of atherosclerosis and cardiovascular risk by GH replacement.

Adult↗

Clinicians' approaches to mechanical ventilation in acute lung injury and ARDS.

STUDY OBJECTIVES: To examine clinicians' approaches to mechanical ventilation in patients with acute lung injury (ALI; PaO(2)/fraction of inspired oxygen [FIO(2)] 35 cm H(2)O in 26% of patients. Seventy-eight percent of patients with ARDS received <or= 10 cm H(2)O of positive end-expiratory pressure. CONCLUSIONS: Physicians in ARDS Network centers caring for patients early in the course of ALI/ARDS used volume-targeted ventilation and selected tidal volumes that resulted in Pplats generally < 35 cm H(2)O. The average tidal volume was similar for patients with ARDS vs those with milder oxygenation deficits.

Airway Resistance↗

Risperidone added to clozapine: impact on serum prolactin levels.

BACKGROUND: Several years ago, we reported that the addition of risperidone to clozapine improved response in some patients with schizophrenia. Risperidone, in general, is well tolerated when administered as monotherapy, but has been linked to a persistent elevation of serum prolactin and associated symptoms. The goal of this study was to determine whether the addition of risperidone to clozapine results in an elevation of serum prolactin levels in patients with chronic schizophrenia or schizoaffective disorder. METHOD: Twenty patients on clozapine-risperidone combination therapy were matched for age and gender with 20 patients treated with clozapine monotherapy. Demographic information was gathered along with clozapine and risperidone dose and the length of time on risperidone. Serum prolactin levels were measured from a single blood sample. RESULTS: The 2 groups did not differ in age, race, gender, diagnosis, age at clozapine initiation, age at onset, Abnormal Involuntary Movement Scale scores, or clozapine dose. The mean +/- SD serum prolactin level was 8.42+/-4.17 ng/mL for clozapine monotherapy patients and 35.76+/-17.43 ng/mL for combination therapy patients. The 2 medication categories showed a significant difference in log prolactin values (t = -7.97, df = 38, p < or = .0001). Sixteen combination therapy patients (80%) exhibited elevated prolactin levels (range for entire group, 9.7-69.8 ng/mL) while only 2 clozapine monotherapy patients (10%) exhibited prolactin elevation levels (range for entire group, 2.4-20.2 ng/mL; df = 1, p < .0001). CONCLUSION: The combination of risperidone and clozapine appears to result in a moderate elevation of serum prolactin levels. Additionally, controlled prospective studies are needed to clarify the risks of long-term elevations of serum prolactin level.

Adult↗

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. In each fluid, 8OH2'dG levels were significantly elevated in the ALS group as compared to control subjects. In all subjects, the plasma and CSF 8OH2'dG levels increased with age, providing further evidence for a role of oxidative damage in normal aging. Plasma and urine 8OH2'dG levels increased significantly with time in the ALS group only. The rate of increase in urine 8OH2'dG levels with time was significantly correlated with disease severity. These findings are consistent with the hypothesis that oxidative pathology accompanies the neurodegenerative process in ALS and suggest that 8OH2'dG may provide a useful tool for monitoring therapeutic interventions in this disease.

8-Hydroxy-2'-Deoxyguanosine↗

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. SETTING: University hospital. PATIENTS: 54 eugonadal men with AIDS wasting (weight < 90% ideal body weight or weight loss > 10%). INTERVENTION: In a 2 x 2 factorial design, patients were assigned to receive testosterone enanthate (200 mg/wk) or placebo injections and progressive resistance training (three times weekly) or no training for 12 weeks. MEASUREMENTS: Cross-sectional muscle area and other indices of muscle mass. RESULTS: Cross-sectional muscle area increased in response to training compared with nontraining (change in arm muscle mass, 499 +/- 349 mm2 vs. 206 +/- 264 mm2 [P = 0.004]; change in leg muscle mass, 1106 +/- 854 mm2 vs. 523 +/- 872 mm2 [P = 0.045]) and in response to testosterone therapy compared with placebo (change in arm muscle mass, 512 +/- 371 mm2 vs. 194 +/- 215 mm2 [P< 0.001]; change in leg muscle mass, 1,236 +/- 881 mm2 vs. 399 +/- 729 mm2 [P = 0.002]). Levels of high-density lipoprotein cholesterol decreased in response to testosterone therapy compared with placebo (-0.03 +/- 0.13 mmol/L vs. 0.05 +/- 0.13 mmol/L [-1 +/- 5 mg/dL vs. 2 +/- 5 mg/dL]; P= 0.011) and increased in response to training compared with nontraining (0.05 +/- 0.13 mmol/L vs. 0.00 +/- 0.16 mmol/L [2 +/- 5 mg/dL vs. 0 +/- 6 mg/dL]; P = 0.052). CONCLUSIONS: In contrast to anabolic therapies that may have adverse effects on metabolic variables, supervised exercise effectively increases muscle mass and is associated with significant positive health benefits in eugonadal men with AIDS wasting.

Arm↗

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. OBJECTIVE: To investigate the effect of growth hormone replacement on inflammatory and other cardiovascular risk factors. DESIGN: Randomized, single-blind, placebo-controlled trial. PATIENTS: 40 men with adult-onset growth hormone deficiency. INTERVENTION: Growth hormone or placebo given for 18 months at a dose adjusted for normal serum insulin-like growth factor I level. MEASUREMENTS: Anthropometric, hemoglobin A1c, and central fat values were assessed every 6 months. Levels of glucose, insulin, insulin-like growth factor I, and lipids were measured at 1, 3, 6, 12, and 18 months. C-reactive protein, serum amyloid polypeptide A, inteleukin-6, and lipoprotein(a) levels were determined at baseline and 6 and 18 months. RESULTS: C-reactive protein and inteleukin-6 levels decreased in growth hormone recipients compared with placebo recipients (differences between groups, -1.9 +/- 0.6 mg/L [P = 0.0027] and -1.3 +/- 0.5 ng/L [P = 0.013], respectively). Changes in serum amyloid polypeptide A levels between groups did not reach statistical significance (difference between groups, -2.4 +/- 1.2 mg/L; P = 0.056). Serum cholesterol levels, low-density lipoprotein cholesterol levels, and ratios of total cholesterol to high-density lipoprotein cholesterol decreased in growth hormone recipients in the first 3 months compared with placebo recipients (differences between groups, -0.86 +/- 0.17 mmol/L [-33.2 +/- 6.6 mg/dL] [P < 0.001], -0.63 +/- 0.20 mmol/L [-24.5 +/- 5.9 mg/dL] [P < 0.001], and -0.56 +/- 0.26 [P = 0.040], respectively), but the decrease was not maintained from month 6 to month 18. Lipoprotein(a) levels increased (difference between groups, 22.0 +/- 8.0 mg/L; P = 0.0096). Short-term increases occurred in glucose levels, insulin levels, and insulin-to-glucose ratios (differences between groups, 0.54 +/- 0.16 mmol/L [9.6 +/- 2.8 mg/dL] [P = 0.0018], 37.9 +/- 9.6 pmol/L [P < 0.001], and 6.0 +/- 1.8 [P = 0.0025], respectively), but only the increase in glucose level was maintained over the long term (difference between groups, 0.56 +/- 0.17 mmol/L [10.0 +/- 3.1 mg/dL]; P = 0.0026). Hemoglobin A1c values did not change. Truncal fat-to-total fat ratios decreased (difference between groups, -0.018 +/- 0.007; P = 0.0087). CONCLUSIONS: Long-term growth hormone replacement in men reduces levels of inflammatory cardiovascular risk markers, decreases central fat, and increases lipoprotein(a) and glucose levels without affecting lipid levels.

Adipose Tissue↗

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. STUDY DESIGN: systematically collected specimens (n=207) were masked and retested. RESULTS: when specimens negative in both initial and repeat assays were excluded from analysis, the diagnostic reproducibility was 98. 6% for beta-globin, 90.7% for generic HPV (any HPV type), and 76.9% for type-specific HPVs. The reproducibility of type-specific diagnosis increased with increase in signal strength in the hybridization reaction of the initial assay. When a specimen contained five or more HPV types in the initial assay, it was rare to identify all of the HPV types in the repeat assay. CONCLUSIONS: the degree of reproducibility of the PCR diagnosis should be taken into account in the interpretation of HPV data in clinical and epidemiological studies.

Cervix Uteri↗

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. We performed a randomized, single blind, placebo-controlled 36-month cross-over study of GH vs. placebo (PL) in adults with GHD and now report the effect of withdrawal of GH on percent body fat, lean mass, and bone density, as measured by dual energy x-ray absorptiometry. Forty men (median age, 51 yr; range, 24-64 yr) with pituitary disease and peak serum GH levels under 5 microg/L in response to two pharmacological stimuli were randomized to GH therapy (starting dose, 10 microg/kg x day, final dose 4 microg/kg x day) vs. PL for 18 months. Replacement was provided in a physiological range by adjusting GH doses according to serum insulin-like growth factor I levels. After discontinuation of GH, body fat increased significantly (mean +/- SEM, 3.18 +/- 0.44%; P = 0.0001) and returned to baseline. Lean mass decreased significantly (mean loss, 2133 +/- 539 g; P = 0.0016), but remained slightly higher (1276 +/- 502 g above baseline; P = 0.0258) than at study initiation. In contrast to the effect on body composition, BMD did not reverse toward pretreatment baseline after discontinuation of GH. Bone density at the hip continued to rise during PL administration, showing a significant increase (0.0014 +/- 0.00042, g/cm2 x month; P = 0.005) between months 18-36. Every bone site except two (radial BMD and total bone mineral content), including those without a significant increase in BMD during the 18 months of GH administration, showed a net increase over the entire 36 months. Therefore, there is a critical differential response of the duration of GH action on different body composition compartments. Physiological GH administration has a persistent effect on bone mass 18 months after discontinuation of GH.

Absorptiometry, Photon↗

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. METHODS: The authors analyzed the expression and/or alteration of the p53 gene in 158 cases of chondrosarcoma of bone using immunohistochemistry, single-strand conformation polymorphism, and direct sequencing. They then related the findings to various clinicopathologic parameters and long term follow-up data. RESULTS: The presence of overexpression and/or structural alterations of the p53 gene was documented in 38.1% of chondrosarcomas of bone. A statistically significant correlation was observed between overexpression or alteration of the p53 gene and both the histologic grade of the tumor and the presence of metastasis. The probability of local recurrence free, metastasis free, and overall survival was significantly higher for patients with no overexpression or alteration of p53 than for patients with p53 overexpression or alteration. CONCLUSIONS: Overexpression or alteration of the p53 gene is an important predictor of aggressive clinical behavior in chondrosarcoma of bone.

Adolescent↗

Effects of androgen administration in men with the AIDS wasting syndrome. A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Development of successful anabolic strategies to reverse the loss of lean body mass is of critical importance to increase survival in men with the AIDS wasting syndrome. Hypogonadism, an acquired endocrine deficiency state characterized by loss of testosterone, occurs in more than half of all men with advanced HIV disease. It is unknown whether testosterone deficiency contributes to the profound catabolic state and loss of lean body mass associated with the AIDS wasting syndrome. OBJECTIVE: To investigate the effects of physiologic testosterone administration on body composition, exercise functional capacity, and quality of life in androgen-deficient men with the AIDS wasting syndrome. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: University medical center. PATIENTS: 51 HIV-positive men (age 42 +/- 8 years) with wasting (body weight < 90% of ideal body weight or weight loss > 10% of baseline weight) and a free testosterone level less than 42 pmol/L (normal range for men 18 to 49 years of age, 42 to 121 pmol/L [12.0 to 35.0 pg/mL]). INTERVENTION: Patients were randomly assigned to receive testosterone enanthate, 300 mg, or placebo intramuscularly every 3 weeks for 6 months. MEASUREMENTS: Change in fat-free mass was the primary end point. Secondary clinical end points were weight, lean body mass, muscle mass, exercise functional capacity, and change in perceived quality of life. Virologic variables were assessed by CD4 count and viral load. RESULTS: Compared with patients who received placebo, testosterone-treated patients gained fat-free mass (-0.6 kg and 2.0 kg; P = 0.036), lean body mass (0.0 kg and 1.9 kg; P = 0.041), and muscle mass (-0.8 kg and 2.4 kg; P = 0.005). The changes in weight, fat mass, total-body water content, and exercise functional capacity did not significantly differ between the groups. Patients who received testosterone reported benefit from the treatment (P = 0.036), feeling better (P = 0.033), improved quality of life (P = 0.040), and improved appearance (P = 0.021). Testosterone was well tolerated in all patients. CONCLUSIONS: Physiologic testosterone administration increases lean body mass and improves quality of life among androgen-deficient men with the AIDS wasting syndrome.

Adolescent↗

Intrasubject reliability of high-frequency (9-14 kHz) thresholds: tested separately vs. following conventional-frequency testing.

Retrospective analysis of hearing-threshold data from a multisite ototoxicity monitoring study identified an individualized range of predominantly high frequencies (> 8 kHz) that appeared to be highly sensitive to early threshold changes caused by ototoxicity. This suggested the potential for a limited-frequency monitoring protocol that could be conducted rapidly without compromising sensitivity to ototoxicity. Such testing would require high-frequency thresholds to be obtained independently, that is, without prior testing at conventional frequencies (0.25-8 kHz). This study was conducted to determine the test-retest reliability of isolated threshold testing in a "target" frequency range of high frequencies (9, 10, 11.2, 12.5, and 14 kHz) that represented a shortened ototoxicity monitoring test. Twenty normal-hearing subjects were evaluated over five sessions. During each session, subjects were tested in each of two conditions: (1) conventional frequencies (0.25-8 kHz) tested first, followed by target frequencies; and (2) target frequencies tested alone (isolation condition). Depending on test frequency, reliability of high-frequency thresholds was either unchanged or improved in the isolation condition. Although these results cannot be generalized to ill hospitalized patients, who may also have pre-existing hearing loss, they lay the groundwork for development of a time-saving limited-frequency test to monitor for ototoxicity in these patients.

Adult↗

Pupil dilation to tropicamide is not specific for Alzheimer disease.

BACKGROUND: The extent of pupil dilation after instillation of a dilute tropicamide solution was proposed as a noninvasive neurobiological diagnostic test for Alzheimer disease (AD). Pupils in patients with AD dilated 23% vs only 5% in control subjects. OBJECTIVE: To determine whether pupil dilation in response to tropicamide distinguishes patients with AD from control subjects without dementia. METHODS: There were 50 patients with AD and 51 control subjects; no participant had primarily ocular pathological conditions or took drugs that affected cholinergic tone. All participants received 1 drop of 0.01% tropicamide in 1 eye and 1 drop of 0.9% saline solution in the other eye in random order. Pupil measurements were obtained using a pupil and corneal reflection tracking system (RK-426 PC system, ISCAN Inc, Burlington, Mass) that illuminated the eye with a low-level infrared source and measured pupil diameters, fixation, and light level every 16.7 milliseconds during each 30-second-measurement. Pupil measurements were obtained from each eye at baseline and 5, 10, 15, and 30 minutes after drop instillation. RESULTS: The increase in pupil size after tropicamide instillation was equal between patients with AD and control subjects. The mean (+/- SD) pupil diameter increased from 4.5 +/- 1.1 to 5.5 +/- 1.1 mm after 30 minutes in patients with AD and from 4.7 +/- 0.9 to 5.8 +/- 0.9 mm in control subjects. Anisocoria and the mean rate of dilation did not differ between patients with AD and control subjects. Eye color and corneal moisture did not affect these results. The extent of pupil dilation in patients with AD was not related to clinical estimates of dementia severity. CONCLUSION: Pupil dilation in response to instillation of 0.01% tropicamide is not useful as an antemortem diagnostic test for AD.

Aged↗