Rapid suppression of bone formation marker in response to sleep restriction and circadian disruption in men.

We describe the time course of bone formation marker (P1NP) decline in men exposed to ~ 3 weeks of sleep restriction with concurrent circadian disruption. P1NP declined within 10 days and remained lower with ongoing exposure. These data suggest even brief exposure to sleep and circadian disruptions may disrupt bone metabolism. INTRODUCTION: A serum bone formation marker (procollagen type 1 N-terminal, P1NP) was lower after ~ 3 weeks of sleep restriction combined with circadian disruption. We now describe the time course of decline. METHODS: The ~ 3-week protocol included two segments: "baseline," ≥ 10-h sleep opportunity/day × 5 days; "forced desynchrony" (FD), recurring 28 h day (circadian disruption) with sleep restriction (~ 5.6-h sleep per 24 h). Fasted plasma P1NP was measured throughout the protocol in nine men (20-59 years old). We tested the hypothesis that PINP would steadily decline across the FD intervention because the magnitude of sleep loss and circadian misalignment accrued as the protocol progressed. A piecewise linear regression model was used to estimate the slope (ß) as ΔP1NP per 24 h with a change point mid-protocol to estimate the initial vs. prolonged effects of FD exposure. RESULTS: Plasma P1NP levels declined significantly within the first 10 days of FD ([Formula: see text] = - 1.33 µg/L per 24 h, p < 0.0001) and remained lower than baseline with prolonged exposure out to 3 weeks ([Formula: see text] = - 0.18 µg/L per 24 h, p = 0.67). As previously reported, levels of a bone resorption marker (C-telopeptide (CTX)) were unchanged. CONCLUSION: Sleep restriction with concurrent circadian disruption induced a relatively rapid decline in P1NP (despite no change in CTX) and levels remained lower with ongoing exposure. These data suggest (1) even brief sleep restriction and circadian disruption can adversely affect bone metabolism, and (2) there is no P1NP recovery with ongoing exposure that, taken together, could lead to lower bone density over time.

The growing ubiquity of algorithms in society: implications, impacts and innovations.

The growing ubiquity of algorithms in society raises a number of fundamental questions concerning governance of data, transparency of algorithms, legal and ethical frameworks for automated algorithmic decision-making and the societal impacts of algorithmic automation itself. This article, an introduction to the discussion meeting issue of the same title, gives an overview of current challenges and opportunities in these areas, through which accelerated technological progress leads to rapid and often unforeseen practical consequences. These consequences-ranging from the potential benefits to human health to unexpected impacts on civil society-are summarized here, and discussed in depth by other contributors to the discussion meeting issue.This article is part of a discussion meeting issue 'The growing ubiquity of algorithms in society: implications, impacts and innovations'.

24-hour profile of serum sclerostin and its association with bone biomarkers in men.

The osteocyte's role in orchestrating diurnal variations in bone turnover markers (BTMs) is unclear. We identified no rhythm in serum sclerostin (osteocyte protein). These results suggest that serum sclerostin can be measured at any time of day and the osteocyte does not direct the rhythmicity of other BTMs in men. INTRODUCTION: The osteocyte exerts important effects on bone remodeling, but its rhythmicity and effect on the rhythms of other bone cells are not fully characterized. The purpose of this study was to determine if serum sclerostin displays rhythmicity over a 24-h interval, similar to that of other bone biomarkers. METHODS: Serum sclerostin, FGF-23, CTX, and P1NP were measured every 2 h over a 24-h interval in ten healthy men aged 20-65 years. Maximum likelihood estimates of the parameters in a repeated measures model were used to determine if these biomarkers displayed a diurnal, sinusoidal rhythm. RESULTS: No discernible 24-h rhythm was identified for sclerostin (p = 0.99) or P1NP (p = 0.65). CTX rhythmicity was confirmed (p < 0.001), peaking at 05:30 (range 01:30-07:30). FGF-23 levels were also rhythmic (p < 0.001), but time of peak was variable (range 02:30-11:30). The only significant association identified between these four bone biomarkers was for CTX and P1NP mean 24-h metabolite levels (r = 0.65, p = 0.04). CONCLUSIONS: Sclerostin levels do not appear to be rhythmic in men. This suggests that in contrast to CTX, serum sclerostin could be measured at any time of day. The 24-h profiles of FGF-23 suggest that a component of osteocyte function is rhythmic, but its timing is variable. Our results do not support the hypothesis that osteocytes direct the rhythmicity of other bone turnover markers (CTX), at least not via a sclerostin-mediated mechanism.

Loss of bone strength in response to exercise-induced weight loss in obese postmenopausal women: results from a pilot study.

OBJECTIVE: Exercise-induced weight loss (WL) can lead to decreased areal bone mineral density (aBMD). It is unknown whether this translates into decreased volumetric BMD (vBMD) or bone strength. The purpose of this pilot study was to determine whether exercise-induced WL results in decreased vBMD and bone strength in postmenopausal women. METHODS: Fourteen subjects participated in a 4-month endurance exercise WL intervention. A weight stable (WS) control group (n=10) was followed for 4 months. Proximal femur aBMD was measured by DXA. Femoral neck vBMD and estimates of bone strength (cross-sectional moment of inertia (CSMI) and section modulus (SM)) were measured by quantitative CT. RESULTS: Women were 54.6±2.4 years, BMI 32.1±5.9 kg/m(2) and 54.4±2.9 years, BMI 27.9±3.6 kg/m(2) in the WL and WS groups, respectively. The WL group lost 3.0±2.6 kg which was predominately fat mass. There was a significant decrease in SMmax. Changes in CSMImax and total hip aBMD were not significant. Total hip vBMD did not decrease significantly in response to WL. There were no significant changes in the WS group. CONCLUSIONS: WL may lead to decreased bone strength before changes in BMD are detected. Further studies are needed to determine whether bone-targeted exercise can preserve bone strength during WL.

Defining vitamin D status by secondary hyperparathyroidism in the U.S. population.

BACKGROUND: Vitamin D is associated with a variety of health outcomes, but the exact definition of vitamin D sufficiency remains controversial. AIM: We sought to define skeletal-related vitamin D sufficiency by estimating maximum PTH suppression in the U.S. population. METHODS: We performed a cross-sectional analysis of the National Health and Nutrition Examination Survey (NHANES), 2003-2006. We examined the association between serum 25-hydroxyvitamin D (25OHD) level and serum PTH level in 14,681 participants aged ≥6 yr. We also evaluated the 25OHD-PTH association using 2 thresholds of hyperparathyroidism: PTH≥45 pg/ml and ≥75 pg/ml. RESULTS: The mean 25OHD level was 24 ng/ml and mean PTH was 42 pg/ml. PTH≥45 pg/ml was present in 35% of the population, while PTH≥75 pg/ml was present in 7%. The prevalence of 25OHD levels <40 ng/ml and <30 ng/ml was 95% and 77%, respectively. In both unadjusted and adjusted models, there was a strong inverse relationship between 25OHD and PTH. Compared to 25OHD≥40 ng/ml, the 25OHD-PTH association was 2.36 [95% confidence interval (CI), 2.08-2.67] times greater for 25OHD<5 ng/ml and 1.12 (95%CI, 1.07-1.17) times greater for 25OHD 30-39.9 ng/ml. Compared to 25OHD≥40 ng/ml, 25OHD levels of 20- 29.9 ng/ml [odds ratio (OR) 2.0 (95%CI, 1.4-2.8)] but not 30- 39.9 ng/ml [OR 1.1 (95%CI, 0.8-1.6)] were independently associated with PTH≥45 pg/ml. CONCLUSIONS: Optimal vitamin D status, defined by estimated maximum PTH suppression, does not occur until at least 25OHD levels ≥40 ng/ml. Using these thresholds, most of the U.S. population needs more vitamin D. Large, prospective studies are needed to determine optimal vitamin D supplementation.

Timing of Estradiol Treatment After Menopause May Determine Benefit or Harm to Insulin Action.

CONTEXT: Type 2 diabetes (T2D) is reduced in postmenopausal women randomized to estrogen-based hormone therapy (HT) compared with placebo. Insulin sensitivity is a key determinant of T2D risk and overall cardiometabolic health, and studies indicate that estradiol (E2) directly impacts insulin action. OBJECTIVE: We hypothesized that the timing of E2 administration after menopause is an important determinant of its effect on insulin action. DESIGN: We performed a randomized, crossover, placebo-controlled study. PARTICIPANTS: Study participants were early postmenopausal (EPM; ≤ 6 years of final menses; n = 22) and late postmenopausal (LPM; ≥ 10 years since last menses; n = 24) women naive to HT. INTERVENTION: Study interventions included short-term (1 week) transdermal E2 and placebo. MAIN OUTCOMES AND MEASURES: The study's main outcome was insulin-mediated glucose disposal (glucose disposal rate [GDR]) via hyperinsulinemic-euglycemic clamp. RESULTS: Compared to EPM women, LPM women were older (mean ± SD; 63 ± 3 vs 56 ± 4 years, P < .05) and more years past menopause (12 ± 2 vs 3 ± 2 years, P < .05). Body mass index (24 ± 3 vs 25 ± 7 kg/m(2)) and fat mass (25 ± 7 vs 23 ± 6 kg) did not differ between groups, but fat-free mass (FFM) was lower in LPM women compared to EPM women (40 ± 4 vs 43 ± 5 kg, P < .05). Baseline GDR did not differ between groups (11.7 ± 2.8 vs 11.5 ± 2.9 mg/kg FFM/min). In support of our hypothesis, 1 week of E2 decreased GDR in LPM women compared to an increase in EPM women (+0.44 ± 1.7 vs - 0.76 ± 2.1 mg/kg FFM/min, P < .05). CONCLUSIONS: There was not an apparent decline in GDR with age or time since menopause per se. However, E2 action on GDR was dependent on time since menopause, such that there was an apparent benefit early (≤ 6 years) compared to harm later (≥ 10 years) in menopause. E2-mediated effects on insulin action may be one mechanism by which HT reduces the incidence of T2D in early postmenopausal women.

Type 2 diabetes exaggerates exercise effort and impairs exercise performance in older women.

OBJECTIVE: Type 2 diabetes mellitus (T2DM) is associated with high levels of disability and mortality. Regular exercise prevents premature disability and mortality, but people with T2DM are generally sedentary for reasons that are not fully established. We previously observed that premenopausal women with T2DM report greater effort during exercise than their counterparts without diabetes, as measured by the Rating of Perceived Exertion (RPE) scale. We hypothesized that RPE is greater in older women with T2DM versus no T2DM. RESEARCH DESIGN AND METHODS: We enrolled overweight, sedentary women aged 50-75 years with (n=26) or without T2DM (n=28). Participants performed submaximal cycle ergometer exercise at 30 W and 35% of individually-measured peak oxygen consumption (35% VO2peak). We assessed exercise effort by RPE (self-report) and plasma lactate concentration. RESULTS: VO2peak was lower in T2DM versus controls (p=0.003). RPE was not significantly greater in T2DM versus controls (30 W: Control, 10.4±3.2, T2DM, 11.7±2.3, p=0.08; 35% VO2peak: Control, 11.1±0.5, T2DM, 12.1±0.5, p=0.21). However, lactate was greater in T2DM versus controls (p=0.004 at 30 W; p<0.05 at 35% VO2peak). Greater RPE was associated with higher lactate, higher heart rate, and a hypertension diagnosis (p<0.05 at 30 W and 35% VO2peak). CONCLUSIONS: Taken together, physiological measures of exercise effort were greater in older women with T2DM than controls. Exercise effort is a modifiable and thereby targetable end point. In order to facilitate regular exercise, methods to reduce exercise effort in T2DM should be sought. TRIAL NUMBER: NCT00785005.

Fungal sinusitis in patients with AIDS: report of 4 cases and review of the literature.

We report here 3 cases of aspergillus sinusitis in patients with AIDS and the 1st fully described case, to our knowledge, of sinusitis associated with Pseudallescheria boydii in a patient with AIDS. We review the microbiology and pathology of fungal sinusitis in patients with AIDS and the morphologic and clinical features and treatment of P. boydii infection and aspergillus sinusitis. Fungal sinusitis in patients with HIV or AIDS generally occurs later in the course of primary disease with low CD4+ lymphocyte counts (< 50/mm3), unlike bacterial sinusitis which may occur at any time. Differentiation between invasive and noninvasive forms is likely not important, in contrast to fungal sinusitis in noncompromised patients. The number of cases is likely to increase as the number of patients with AIDS increases, patients survive longer, and other opportunistic infections are prevented or treated. Causative agents are likely to be resistant to fluconazole, which is in widespread use. Aspergillus sinusitis in patients with HIV or AIDS occurs in both those with and without traditional risk factors. Fungal sinusitis may present vexing management problems and be relentlessly progressive in the face of therapy. Ideal therapy has yet to be defined but an early combined surgical and medical approach in these compromised patients is preferred.

Plasma xanthophyll carotenoids correlate inversely with indices of oxidative DNA damage and lipid peroxidation.

Post hoc analysis of data obtained from a study designed to modulate oxidative damage by dietary intervention revealed consistently strong inverse correlations between plasma xanthophyll carotenoids and oxidative damage indices. Thirty-seven women participated in a 14-day dietary intervention that increased mean vegetable and fruit (VF) consumption to approximately 12 servings/day. An additional 10 subjects participated in an intervention that limited VF consumption to less than four servings per day. 8-Hydroxy-2'-deoxyguanosine (8-OHdG) in DNA isolated from peripheral lymphocytes and 8-OHdG excreted in urine were measured as indices of oxidative DNA damage. Lipid peroxidation was assessed by measuring 8-epiprostaglandin F2alpha (8-EPG) in urine. Plasma levels of selected carotenoids were also determined, with the intention of using a-carotene as a biochemical index of VF consumption. Urinary 8-OHdG and 8-EPG were measured by ELISA, and plasma carotenoids were measured by high performance liquid chromatography. Lymphocyte 8-OHdG was measured by reverse phase high performance liquid chromatography with electrochemical detection. We observed that the structurally related xanthophyll carotenoids, lutein and beta-cryptoxanthin, which occur in dissimilar botanical families, were consistently inversely associated with these oxidative indices. Statistically significant inverse correlations were observed between plasma lutein and/or beta-cryptoxanthin levels and lymphocyte 8-OHdG and urinary 8-EPG. Moreover, an inverse correlation was observed between change in plasma xanthophylls and change in lymphocyte 8-OHdG concentration that occurred during the course of the study. These data lead us to hypothesize that lutein and beta-cryptoxanthin serve as markers for the antioxidant milieu provided by plants from which they are derived. Whether these carotenoids are directly responsible for the observed antioxidant phenomena merits further investigation.

Immunogenicity of the 23-valent pneumococcal polysaccharide vaccine in Alaska Native chronic alcoholics compared with nonalcoholic Native and non-Native controls.

PURPOSE: This study was designed to evaluate the immunogenicity of the 23-valent pneumococcal polysaccharide vaccine in Alaska Native chronic alcoholics and compare these responses with those in age- and sex-matched nonalcoholic, Native and non-Native control subjects. PATIENTS AND METHODS: Native alcoholic patients were recruited from the inpatient medical service and outpatient clinics. Healthy age- and sex-matched Alaska Native and non-Native nonalcoholics were recruited from hospital employees. At the initial visit, a standardized questionnaire, the Alcohol Dependency Scale, was administered to all participants. Participants were examined for liver diseases; blood was drawn for liver function tests and prevaccination pneumococcal antibody levels. Charts of all Native participants were reviewed for alcohol-related diseases. Participants received one dose of the 23-valent pneumococcal vaccine at the time of the initial visit and returned 20 to 55 days after immunization for liver function tests and pneumococcal antibody level measurement. Serotype-specific pneumococcal antibody levels were measured by radioimmunoassay. Logistic regression analysis was used to examine the proportion of persons whose serotype-specific antibody level doubled following vaccination. A model including adjustments for age, sex, and initial antibody level was used to examine the effect of alcohol status and ethnicity on response to the vaccine. Eighty-five persons completed the study. Of these, 41 were chronic alcoholics and 44 were nonalcoholic. Of these, 21 were Alaska Natives and 23 were non-Natives. RESULTS: Before vaccination, the geometric mean titers (GMTs) were similar in all 3 groups but were slightly higher in Native alcoholic participants for 11 of 12 serotypes tested. For 11 or more serotypes tested, 46% of alcoholics and 27% of nonalcoholics had total antibody levels at or above 500 nanograms of antibody nitrogen per milliliter (p = 0.11). After vaccination, the GMTs were higher in nonalcoholic than in alcoholic participants for serotypes 3, 7F, and 19F (p < 0.05). When Natives and non-Natives were compared, non-Natives had higher antibody levels than Native participants for 10 of 12 serotypes. After vaccination, 83% of alcoholics and 91% of nonalcoholics had pneumococcal antibody levels of more than 500 nanograms of antibody nitrogen per milliliter for at least 11 serotypes. When responses consisting of a twofold or greater increase in antibody level were compared, a greater proportion of nonalcoholics than alcoholics responded to serotypes 3, 4, 7F, 8, and 19F. This difference was significant for types 3 and 19F only (p < 0.05). In alcoholics there was a direct correlation between pneumococcal antibody level and age both before and after vaccination. This was significant before vaccination for serotypes 4, 6B, 18C, and 23F, and after vaccination for these types and for types 1 and 19F. In nonalcoholics there was a correlation between age and antibody response, following vaccination, for serotype 9N and 18C. Alcoholic males had antibody levels higher than that in females for most serotypes, but significantly so only for serotype 12F before vaccination, and for type 14 after vaccination. There were no sex differences seen among nonalcoholics, and no differences in response to vaccine could be detected in patients with or without liver dysfunction. CONCLUSION: In this study of Alaska Natives with chronic alcoholism, Native and non-Native participants responded adequately to immunization with the 23-valent pneumococcal vaccine, although significant differences in some serotypes were evident.

Lack of response to suramin in patients with AIDS and AIDS-related complex.

Forty-one homosexual men with the acquired immune deficiency syndrome (AIDS) or AIDS-related complex were treated with 0.5, 1.0, or 1.5 g of suramin weekly for up to six months. In no patient was evidence of symptomatic improvement or regression of Kaposi's sarcoma shown. Opportunistic infections developed in 16 patients during therapy. Only six patients (15 percent) became human immunodeficiency virus (HIV) culture-negative during treatment, despite documentation of adequate serum suramin levels. All but one of these six have had disease progression. Decreases in the numbers of total T4 cells with time were observed in both AIDS and AIDS-related complex subgroups. Toxicity was significant and consisted of fatigue, fever, and hepatic and renal dysfunction, all of which were observed most frequently with the 1.0 or 1.5 g dosages. Fatal hepatic failure developed in two patients, and adrenal insufficiency was documented in eight patients. Suramin is a toxic agent that shows no virologic, immunologic, or clinical benefit in patients with HIV-related disease.

Response of AIDS-related thrombocytopenia to intravenous and oral azidothymidine (3'-azido-3'-deoxythymidine).

A patient with AIDS-related thrombocytopenia (ART) was treated with the new anti-retroviral agent azidothymidine (AZT, Retrovir, zidovudine) by the intravenous and oral routes for a period of 20 weeks. After a 6 week period of initial treatment, the platelet count rose from 38,000 to 140,000/mm3. AZT was intentionally discontinued for three weeks over which the platelet count declined to 70,000/mm3. After reinstitution of AZT, the platelet count rose once again and remained near normal levels for over one year. We conclude that AZT may have efficacy against the thrombocytopenia observed in some patients infected with human immunodeficiency virus (HIV). The pathogenesis of ART and the mechanisms of action of AZT in this condition remain unknown.

Physician perspectives on increasing minorities in cancer clinical trials: an Eastern Cooperative Oncology Group (ECOG) Initiative.

PURPOSE: This paper describes the ECOG-NMA Minority Accrual Initiative to assure minority participation in cancer clinical trials. METHODS: Focus groups were held to identify physician-reported barriers to the enrollment of minority patients in Cleveland, OH, Indianapolis, IN, Santa Clara County, CA, and Philadelphia, PA. Community physicians affiliated with the National Medical Association (NMA), and Eastern Cooperative Oncology Group (ECOG) investigators participated in the focus groups. A four-step process consisting of focus group workshops were conducted to (i) identify barriers, (ii) develop potential solutions to the barriers, (iii) define solutions to barriers involving specific clinical trials, and (iv) implement the solutions. RESULTS: Focus group participants identified physician lack of information, patient fears and suspicion, the fear of losing patients, and distrust of the health care system as the major barriers to enrollment of African Americans. We found significant differences between community physicians and cancer program physicians in several areas. Community physicians emphasized personal contacts to address the lack of information and to overcome patient fears and suspicions, while the cancer program physicians emphasized printed materials. There was no difference by region in the barriers identified in the focus group workshops; however, the proposed solutions to overcoming the barriers were specific to each site. CONCLUSION: The four-step process developed by the ECOG and the NMA used the focus group methodology to identify and overcome barriers to participation of African Americans in cancer clinical trials. Outreach efforts to educate patients, their families, and community physicians about cancer clinical trials should be directed at overcoming patient suspicions and providing practical information to physicians about specific trials and how to enroll patients.

Videokeratography of keratoconus in monozygotic twins.

PURPOSE: To determine the corneal topographic appearance in a pair of monozygotic twins and family members of the twins because one of the twins had keratoconus and the other appeared normal by clinical examination. METHODS: Clinical examination and videokeratography (Topographic Modeling System, Tomey) of the patient, his monozygotic twin brother, an older brother, and his parents were performed. The I-S values (difference in the average dioptric powers of symmetrical points between the inferior and superior cornea) were calculated. RESULTS: The patient, a 28-year-old man, had clinical keratoconus confirmed with videokeratography. Clinical examination of family members including a twin brother, an older brother and both parents revealed no corneal abnormalities. Videokeratography of the clinically normal twin brother showed inferior steepening with progression over time. The I-S value of the clinically normal brother was 1.36 (right eye) (greater than 2.00 SD of normal controls), which progressed to 1.69 (right eye), 1.32 (left eye) 5 months later and to 1.87 (right eye), 1.43 diopters (D) (left eye) 14 months later. Minimal asymmetric inferior steepening was noted in an older brother who had an I-S value of 0.81 (right eye), 1.27 (left eye). The mother appeared topographically normal. CONCLUSIONS: This study lends support to the existence of subclinical keratoconus detectable by videokeratography only.

The effect of diurnal and menstrual cyclicity and menopausal status on estrogen metabolites: implications for disease-risk assessment.

It has been proposed that the ratio of two estrogen metabolites, 2-hydroxyestrone (2-OHE1) and 16alpha-hydroxyestrone (16alpha-OHE1), may represent a marker to predict a woman's risk for developing breast cancer and other estrogen-related disease. The present studies evaluated the potential confounders of type of sample, diurnal rhythm, menstrual cycle phase, and menopausal status on the ratio of 2/16alpha-OHE1 using an urine-based monoclonal antibody enzyme immunoassay. Two initial studies to compare a 24-h urine collection with a first-morning void and to evaluate diurnal variation were performed. Subsequently, urine samples were collected every other day for 2 months from five premenopausal subjects to assess the impact of the menstrual cycle. Spot urine samples were then obtained from a total of 67 pre, peri-, early post-, and late post-menopausal women to assess the effect of menopausal status. No significant difference in the ratio of 2/16alpha-OHE1 was found between a 24-h and first-morning void or over a 24-h period. No significant difference in the mean ratio of 2/16alpha-OHE1 was found with the menstrual phase. Intra-individual variability was observed in the ratio of 2/16alpha-OHE1, which was attributable to small fluctuations in the small denominator, 16alpha-OHE1. No difference in the ratio of 2/16alpha-OHE1 was observed in groups of women of different menopausal status. The data suggest that a first-morning void is representative of a 24-h collection and that the 2/16alpha-OHE1 ratio is constant throughout a 24-h period. Moreover, menstrual phase and menopausal status do not appear to significantly influence the ratio of 2/16alpha-OHE1.

Global budgeting in the OECD countries.

Many of the Organization for Economic Cooperation and Development countries use global budgeting to control all or certain portions of their health care expenditures. Although the use of global budgets as a cost-containment tool has not been implemented in the United States in any comprehensive way, recent health care reform initiatives have increased the need for research into such tools. In general, the structure, process, and effectiveness of global budgets vary enormously from country to country, in part because the underlying social welfare system of each country is unique.

Total parathyroidectomy and autotransplantation.

Total parathyroidectomy and autotransplantation of tissue to the forearm was practiced in 50 chronic renal failure patients as treatment for secondary hyperparathyroidism. Four hyperplastic glands were removed in all cases. Followup observation ranged from 3 to 42 months. Serum parathyroid hormone, alkaline phosphatase, calcium and phosphorus levels decreased significantly following the procedure (P less than 0.005) and remained stable during the period of observation. Significant bone pain present in 26 patients improved or ceased in 19; pruritus, present in 39 patients, universally improved. Strong radiographic suggestion of secondary hyperparathyroidism, present in 38 patients, improved or disappeared in 17. Three patients remained functionally hyperparathyroid, requiring further tissue removal. Autograft function 3 to 7 days after transplantation was demonstrated in 3 cases by differential parathyroid hormone concentration determinations. Essentially all patients experienced symptomatic improvement after surgery and most showed objective evidence of improved calcium-phosphorus metabolism and bone healing.

Fatigue rate during anaerobic and aerobic exercise in insulin-dependent diabetics and nondiabetics.

This study was designed to determine whether insulin-dependent diabetics fatigue at a different rate than nondiabetics during anaerobic and aerobic exercise. The rate of fatigue during cycle ergometer exercise at 90 percent (anaerobic) and 60 percent (aerobic) of predicted maximum oxygen consumption in eight men who were insulin-dependent diabetics and eight nondiabetic men was determined. For the insulin-dependent diabetics, performance at 90 percent was a significantly better predictor (p less than .05) of performance at 60 percent than it was for the nondiabetics. The rate of fatigue during cycle ergometer exercise for insulin-dependent diabetics may be predictable, and this may be important in evaluating exercise tolerance for these patients.

Further investigation of traumatic brain injury versus insufficient effort with the California Verbal Learning Test.

The present study replicates and attempts to extend previous research using the California Verbal Learning Test (CVLT) to identify malingerers. Documented moderate and severe traumatic brain injury patients (n = 42) were compared with clinical malingerers identified by criteria other than the CVLT (n = 21), malingering simulators instructed in realistic potential injury sequelae (n = 25), and normal controls (n = 21). Results of discriminant function analyses for high and low base rates are reported, showing similar results. Also, the four individual cutoff scores (Recognition Hits, Discriminability, Total Words Recalled, Long Delay Cued Recall) from Millis, Putnam, Adams, and Ricker (1995) were evaluated with these groups. Similar specificity rates were found with all four variables, while sensitivity rates were slightly lower than that of Millis. Adjusted cutoffs derived from the new samples resulted in slightly improved overall classification rates. Overall, present findings support those of Millis et al. (1995) with regard to the use of the CVLT in detection of malingering. Exploratory use of Total Intrusions and Recognition Hits Compared to Long Delay Free Recall was not promising. Simulators were found to be fairly comparable in performance to actual malingerers, affirming their use in malingering research.

Response to luteinizing hormone releasing hormone in postpubertal boars with large testes.

The objective of the present study was to determine if postpubertal boars (12-13 months of age; 156 +/- 8 kg) with large testes had altered hypothalamic control of secretion of luteinizing hormone (LH). Seven boars with the highest estimated 150 d, paired testis weights from a line selected for large testes (769 +/- 60 g = mean weight of excised testes) and 8 boars from a control group (control, 544 +/- 20 g) were tethered in stalls and fitted with indwelling jugular catheters. Males were bled when they were intact, 14 days after castration and during administration of sodium pentobarbital anesthetic (subsequent to castration) to block secretion of endogenous LH-releasing hormone (LHRH). Blood samples were collected at 12-min intervals for 6 hr before and 1 hr after intravenous injection of LHRH in intact and castrated males. During anesthesia, LHRH was administered 4 times at 1-hr intervals and blood samples were collected every 6 min. All samples were analyzed for concentrations of LH and pooled samples were analyzed for concentrations of 17-beta estradiol (E2) and testosterone (T). In intact and castrated males, mean concentrations of LH, frequency and amplitude of pulses of LH, and concentrations of E2 and T were not different between boars of the two groups (P greater than .10). Response to exogenous LHRH was less (P less than .05) in intact males with large testes than in corresponding males from the control group (P less than .05). Fourteen days after castration, males that had larger testes before castration had less of a response to LHRH than males from the control group (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)