The cascade of HIV care among refugees and nationals in Nakivale Refugee Settlement in Uganda.

OBJECTIVES: Refugees living in Uganda come from HIV-endemic countries, and many remain in refugee settlements for over a decade. Our objective was to evaluate the HIV care cascade in Nakivale Refugee Settlement and to assess correlates of linkage to care. METHODS: We prospectively enrolled individuals accessing clinic-based HIV testing in Nakivale Refugee Settlement from March 2013 to July 2014. Newly HIV-diagnosed clients were followed for 3 months post-diagnosis. Clients underwent a baseline survey. The following outcomes were obtained from HIV clinic registers in Nakivale: clinic attendance ('linkage to HIV care'), CD4 testing, antiretroviral therapy (ART) eligibility, and ART initiation within 90 days of testing. Descriptive data were reported as frequency with 95% confidence interval (CI) or median with interquartile range (IQR). The impact of baseline variables on linkage to care was assessed with logistic regression models. RESULTS: Of 6850 adult clients tested for HIV, 276 (4%; CI: 3-5%) were diagnosed with HIV infection, 148 (54%; CI: 47-60%) of those were linked to HIV care, 54 (20%; CI: 15-25%) had a CD4 test, 22 (8%; CI: 5-12%) were eligible for ART, and 17 (6%; CI: 3-10%) initiated ART. The proportions of refugees and nationals at each step of the cascade were similar. We identified no significant predictors of linkage to care. CONCLUSIONS: Less than a quarter of newly HIV-diagnosed clients completed ART assessment, considerably lower than in other reports from sub-Saharan Africa. Understanding which factors hinder linkage to and engagement in care in the settlement will be important to inform interventions specific for this environment.

The effect of age on fitness among female firefighters.

BACKGROUND: The physical demands of firefighting require both cardiovascular and muscular fitness, which both decline with age. While much has been published on age-related changes among male firefighters (FFs), data on female FFs are lacking. AIMS: To describe cardiorespiratory fitness (CRF) and muscular fitness in a sample of female career FFs ranging in age from 25 to 60 years and determine whether ageing affects their achievement of the current recommended professional CRF standards of 12 metabolic equivalents (METs). METHODS: Data were collected on female FFs over an 11-year period. A cross-sectional analysis using one-way analysis of variance with Bonferroni post hoc comparisons was used to compare age groups. RESULTS: There were 96 study participants. Maximum METs was significantly higher (P < 0.01) in the 25- to 34-year age group (14.6 ± 2.1) compared with the 35-44 age group (12.9 ± 2.0 METs) and the 45-54 age group (12.2 ± 1.8 METs, P < 0.001). While the mean values of all measured age groups met or exceeded the 12-MET profession standard, as many as one-third of FFs <45 years of age and 43% of FFs >45 years of age fell below the benchmark of 12 METs. Muscular fitness as measured by maximum number of push-ups, sit-ups and back endurance was not significantly different between age groups. CONCLUSIONS: Fire departments should recognize and take steps to ensure all female FFs maintain CRF and muscular fitness throughout their careers.

When one becomes more: minimum renal artery length in laparoscopic live donor nephrectomy.

BACKGROUND: Laparoscopic donor nephrectomy may convert short main arteries into multiple arteries, increasing the technical challenge of implantation. We evaluated our experience to identify factors predictive of multiple arteries after laparoscopic nephrectomy. METHODS: All laparoscopic nephrectomies from the start of our program in November 2002 until June 2013 were studied, and preoperative imaging reviewed for donor artery length and multiplicity together with operative findings. RESULTS: A total of 287 consecutive laparoscopic live donor nephrectomies (64 right and 223 left nephrectomies) were studied. Renal artery length was measured from preoperative donor magnetic resonance or computed tomography angiogram and nephrectomy performed using a laparoscopic stapling device. Nine left kidneys with a single artery (6, 7, 9, 10, 11, 12, 13, 14, and 16 mm in length) and five right kidneys with a single artery (5, 13, 15, 20, and 26 mm) on imaging resulted in multiple renal arteries at implantation. Complex renal vein anatomy was associated with multiple arteries following retrieval. CONCLUSION: A main renal artery length of more than 16 mm on the left and 26 mm on the right is unlikely to result in multiple arteries to implant. The possibility of multiple arteries should be borne in mind when the donor renal artery is short.

Quantification and comparison of psychiatric distress in African patients with albinism and vitiligo: a 5-year prospective study.

BACKGROUND: Vitiligo and albinism are two disorders of pigmentation that make the affected African highly visible and strikingly different from their peers. Both pose considerable management challenges, attract significant stigma and profound impairment of quality of life. OBJECTIVE AND METHODS: To determine and compare psychiatric distress in vitiligo and albinism using the Hospital Anxiety and Depression Scale (HADS). Participants were 87 albinos and 102 vitiligo adult patients seen at an urban tertiary hospital in Nigeria between 2004 and 2009. RESULTS: Prevalence of psycho morbidity was 59% (60/102) in vitiligo compared with 26% (23/87) in the albinos. The mean anxiety score was estimated to be 2.55 points lower for albino patients (95% CI: 1.47 to 3.64), and the mean depression score 2.76 points lower (95% CI: 1.84 to 3.68), after adjustment for age, sex and marital status. However, significant differences were not observed when comparing the vitiligo patients with the subset of albino patients with skin cancer. Older patients had significantly higher anxiety and depression scores. Females had significantly higher anxiety scores (but not depression scores) compared to males. Genital involvement in vitiligo was significantly associated with anxiety but not depression. CONCLUSIONS: We found that the African with vitiligo suffers significantly higher psychiatric distress than the African albino on average. Clinical evaluation of these patients would be incomplete without assessment of their psycho morbidity. There is need for increased focus on cancer prevention strategies in the African albino.

Accuracy of hepatocellular carcinoma detection on multidetector CT in a transplant liver population with explant liver correlation.

AIM: To evaluate the diagnostic accuracy of multidetector computed tomography (MDCT) for hepatocellular carcinoma (HCC) in cirrhotic patients undergoing liver transplantation. Secondary aims were to examine the effect of radiologist experience and lesion size on diagnostic accuracy. MATERIALS AND METHODS: Thirty-nine patients (72% male with a mean age of 56.5 years) underwent liver transplantation following preoperative triple-phase MDCT examination of the liver. MDCT examinations were retrospectively independently reviewed by three radiologists for the presence and location of suspected HCCs, with the diagnostic confidence recorded using a five-point confidence scale. MDCT examinations were compared with explant specimens for histopathological correlation. RESULTS: Histopathological results demonstrated 46 HCCs in 29 of the 39 patients. Analysis demonstrated a sensitivity of 65-75% and specificity of 47-88% for detection of HCC lesions. The sensitivity dropped to 48-57% for lesions of size ≤20mm. As the diagnostic confidence increased, there was a further decrease in the sensitivity (4-26%). The radiologist with the greatest number of years experience was found to have a significantly higher accuracy of detection of HCC lesions compared with the least experienced radiologist. CONCLUSION: Larger lesion size of HCC and greater number of years experience of the radiologist resulted in significantly higher accuracy of HCC lesion detection. The overall sensitivity and specificity results for MDCT detection of HCC are comparable to previous helical CT imaging.

Quantitative evaluation of subchondral bone injury of the plantaro-lateral condyles of the third metatarsal bone in Thoroughbred horses identified using nuclear scintigraphy: 48 cases.

REASONS FOR PERFORMING STUDY: Increased radio-isotope uptake (IRU) in the subchondral bone of the plantaro-lateral condyle of the third metatarsus (MTIII) is a commonly reported scintigraphic finding and potential cause of lameness in UK Thoroughbred racehorses in training and has not been fully documented. OBJECTIVES: To characterise lameness attributable to IRU of the subchondral bone of MTIII, compare the scintigraphic findings of these horses with a normal population and evaluate the use of scintigraphy as an indicator of prognosis. HYPOTHESIS: IRU will be in significantly higher in horses with subchondral bone injury and will be related to prognosis and future racing performance. METHODS: Data were analysed from 48 horses in which subchondral bone injury of the plantaro-lateral condyle of MTIII had been diagnosed using nuclear scintigraphy and that met the inclusion criteria. Data recorded included age, sex, trainer, racing discipline, lameness assessment, treatment regimes, radiographic and scintigraphic findings, response to diagnostic analgesia where performed and racing performance pre- and post diagnosis. Region of interest (ROI) counts were obtained for the plantar condyle and the mid diaphysis from the latero-medial view, the ratio calculated and then compared with a control group of clinically unaffected horses. RESULTS: The mean condyle mid-diaphysis ROI ratio was significantly (P<0.001) higher in the affected population and with positively correlation (P = 0.024) with the level of lameness. The presence of radiographic findings had no significant effect on the ROI ratio. CONCLUSION: Subchondral bone injury of the plantar lateral condyles of MTIII is a significant cause of lameness in UK Thoroughbred racehorses. Nuclear scintigraphy is a useful diagnostic imaging modality in the detection of affected horses but is a poor indicator of prognosis for the condition. POTENTIAL RELEVANCE: Better understanding of the clinical manifestations, diagnosis of and prognosis for subchondral bone injury will benefit the Thoroughbred industry in the UK.

Chondromalacia of the cranial medial femoral condyle; its occurrence and association with clinical outcome in a population of adult horses with stifle lameness.

BACKGROUND: Chondromalacia of the cranial medial femoral condyle (CMFC) is a potential cause of stifle lameness in adult horses. However, there is scant published evidence of either its occurrence or its clinical significance. OBJECTIVES: To document the occurrence of CMFC seen during diagnostic arthroscopy in adult horses with stifle lameness and to investigate its prognostic significance. STUDY DESIGN: Retrospective cohort study. METHODS: The records were reviewed of all horses with unilateral or bilateral lameness localised to the stifle that underwent diagnostic arthroscopy of the cranial medial femorotibial joint at a UK equine hospital. The surgical findings were noted from each. Case outcomes were determined by unstructured telephone discussions with owners. A satisfactory outcome was defined as a horse that was in ridden work without ongoing anti-inflammatory medication. Multivariable logistic regression was used to create a model with an outcome time point at 12-month post-operatively. RESULTS: One hundred and four horses were included in the study. CMFC was found in 79. In 25 CMFC was the only finding, 54 horses had CMFC plus other pathology and 25 had other pathology, but no CMFC. At 12 months, horses with CMFC were 9.9 (95% CI 2.2-45.0, P<0.01) times more likely to have an unsatisfactory outcome than horses without CMFC. MAIN LIMITATIONS: The study relied on retrospective analysis of clinical notes and archived arthroscopy videos. Assessment of outcome was determined by unstructured telephone interview and therefore there is potential for reporting errors to exist. CONCLUSIONS: CMFC is a common arthroscopic finding in horses with stifle lameness and is significantly associated with an increased likelihood of the horse not being in ridden work at long-term follow-up.

NAA is a Marker of Disability in Secondary-Progressive MS: A Proton MR Spectroscopic Imaging Study.

BACKGROUND AND PURPOSE: The secondary progressive phase of multiple sclerosis is characterised by disability progression due to processes that lead to neurodegeneration. Surrogate markers such as those derived from MRI are beneficial in understanding the pathophysiology that drives disease progression and its relationship to clinical disability. We undertook a 1H-MRS imaging study in a large secondary progressive MS (SPMS) cohort, to examine whether metabolic markers of brain injury are associated with measures of disability, both physical and cognitive. MATERIALS AND METHODS: A cross-sectional analysis of individuals with secondary-progressive MS was performed in 119 participants. They underwent 1H-MR spectroscopy to obtain estimated concentrations and ratios to total Cr for total NAA, mIns, Glx, and total Cho in normal-appearing WM and GM. Clinical outcome measures chosen were the following: Paced Auditory Serial Addition Test, Symbol Digit Modalities Test, Nine-Hole Peg Test, Timed 25-foot Walk Test, and the Expanded Disability Status Scale. The relationship between these neurometabolites and clinical disability measures was initially examined using Spearman rank correlations. Significant associations were then further analyzed in multiple regression models adjusting for age, sex, disease duration, T2 lesion load, normalized brain volume, and occurrence of relapses in 2 years preceding study entry. RESULTS: Significant associations, which were then confirmed by multiple linear regression, were found in normal-appearing WM for total NAA (tNAA)/total Cr (tCr) and the Nine-Hole Peg Test (ρ = 0.23; 95% CI, 0.06-0.40); tNAA and tNAA/tCr and the Paced Auditory Serial Addition Test (ρ = 0.21; 95% CI, 0.03-0.38) (ρ = 0.19; 95% CI, 0.01-0.36); mIns/tCr and the Paced Auditory Serial Addition Test, (ρ = -0.23; 95% CI, -0.39 to -0.05); and in GM for tCho and the Paced Auditory Serial Addition Test (ρ = -0.24; 95% CI, -0.40 to -0.06). No other GM or normal-appearing WM relationships were found with any metabolite, with associations found during initial correlation testing losing significance after multiple linear regression analysis. CONCLUSIONS: This study suggests that metabolic markers of neuroaxonal integrity and astrogliosis in normal-appearing WM and membrane turnover in GM may act as markers of disability in secondary-progressive MS.

Payload crew members' view of spacelab operations.

Various operational aspects of the Spacelab 1 mission are reviewed by the four payload crew members. Two-shift operations, voice communication with ground investigators, joint participation in experiment activity, Spacelab performance, and recent advances are discussed.

The Prostate Health Index adds predictive value to multi-parametric MRI in detecting significant prostate cancers in a repeat biopsy population.

Both multi-parametric MRI (mpMRI) and the Prostate Health Index (PHI) have shown promise in predicting a positive biopsy in men with suspected prostate cancer. Here we investigated the value of combining both tests in men requiring a repeat biopsy. PHI scores were measured in men undergoing re-biopsy with an mpMRI image-guided transperineal approach (n = 279, 94 with negative mpMRIs). The PHI was assessed for ability to add value to mpMRI in predicting all or only significant cancers (Gleason ≥7). In this study adding PHI to mpMRI improved overall and significant cancer prediction (AUC 0.71 and 0.75) compared to mpMRI + PSA alone (AUC 0.64 and 0.69 respectively). At a threshold of ≥35, PHI + mpMRI demonstrated a NPV of 0.97 for excluding significant tumours. In mpMRI negative men, the PHI again improved prediction of significant cancers; AUC 0.76 vs 0.63 (mpMRI + PSA). Using a PHI≥35, only 1/21 significant cancers was missed and 31/73 (42%) men potentially spared a re-biopsy (NPV of 0.97, sensitivity 0.95). Decision curve analysis demonstrated clinically relevant utility of the PHI across threshold probabilities of 5-30%. In summary, the PHI adds predictive performance to image-guided detection of clinically significant cancers and has particular value in determining re-biopsy need in men with a negative mpMRI.

Anti-stunning and anti-infarct effects of adenosine-enhanced ischemic preconditioning.

BACKGROUND: Adenosine-enhanced ischemic preconditioning (APC) extends the protection afforded by ischemic preconditioning (IPC) by both significantly decreasing infarct size and significantly enhancing post-ischemic functional recovery. In this study, the anti-infarct effects and the anti-stunning effects of APC in contributing to enhanced post-ischemic functional recovery were determined and compared with IPC. METHODS AND RESULTS: Sheep (n=96) were subjected to 15, 30, 45, or 60 minutes of regional ischemia and 120 minutes of reperfusion. IPC hearts received 5 minutes of regional ischemia and 5 minutes of reperfusion before ischemia/reperfusion. APC hearts received a bolus injection of adenosine coincident with IPC. Adenosine hearts (ADO) received a bolus injection of adenosine before ischemia/reperfusion. Regional ischemia (RI) hearts received no pretreatment. Infarct size/area at risk was determined by tetrazolium staining. Regional myocardial function was determined by sonomicrometry. Segment shortening after 15 minutes of ischemia in which no infarct was incurred was 32. 1+/-10.6% in RI, 70.6+/-8.5% in IPC, and 77.4+/-6.0% in APC hearts. Segment shortening after 30 minutes of ischemia was 60.7+/-6.3% in APC hearts (P:<0.05 versus RI, ADO, IPC) but was <37% in all other groups. Infarct size/area at risk after 30 and 60 minutes of ischemia was, respectively, 25.8+/-5.7% and 49.8+/-6.0% in RI, 12. 9+/-3.0% and 29.2+/-5.0% in ADO, 11.6+/-2.4% and 24.6+/-2.7% in IPC, and 5.1+/-1.6% and 12.4+/-2.0% in APC hearts (P:<0.05 versus RI, ADO, IPC). CONCLUSIONS: APC and IPC exhibit anti-infarct and anti-stunning effects in the ovine heart, but these effects are rapidly diminished with IPC. APC significantly extends these effects, providing for significantly enhanced infarct size reduction and post-ischemic functional recovery (P:<0.05 versus IPC).

Altered insulin secretion associated with reduced lipolytic efficiency in aP2-/- mice.

Recent studies have shown that genetic deficiency of the adipocyte fatty acid-binding protein (aP2) results in minor alterations of plasma lipids and adipocyte development but provides significant protection from dietary obesity-induced hyperinsulinemia and insulin resistance. To identify potential mechanisms responsible for this phenotype, we examined lipolysis and insulin secretion in aP2-/- mice. Beta-adrenergic stimulation resulted in a blunted rise of blood glycerol levels in aP2-/- compared with aP2+/+ mice, suggesting diminished lipolysis in aP2-/- adipocytes. Confirming this, primary adipocytes isolated from aP2-/- mice showed attenuated glycerol and free fatty acid (FFA) release in response to dibutyryl cAMP. The decreased lipolytic response seen in the aP2-/- mice was not associated with altered expression levels of hormone-sensitive lipase or perilipin. The acute insulin secretory response to beta-adrenergic stimulation was also profoundly suppressed in aP2-/- mice despite comparable total concentrations and only minor changes in the composition of systemic FFAs. To address whether levels of specific fatty acids are different in aP2-/- mice, the plasma FFA profile after beta-adrenergic stimulation was determined. Significant reduction in both stearic and cis-11-eicoseneic acids and an increase in palmitoleic acid were observed. The response of aP2-/- mice to other insulin secretagogues such as arginine and glyburide was similar to that of aP2+/+ mice, arguing against generally impaired function of pancreatic beta-cells. Finally, no aP2 expression was detected in isolated pancreatic islet cells. These results provide support for the existence of an adipo-pancreatic axis, the proper action of which relies on the presence of aP2. Consequently, aP2's role in the pathogenesis of type 2 diabetes might involve regulation of both hyperinsulinemia and insulin resistance through its impact on both lipolysis and insulin secretion.

Importance of imaging method over imaging modality in noninvasive determination of left ventricular volumes and ejection fraction: assessment by two- and three-dimensional echocardiography and magnetic resonance imaging.

OBJECTIVES: This study sought to determine the concordance between biplane and volumetric echocardiography and magnetic resonance imaging (MRI) strategies and their impact on the classification of patients according to left ventricular (LV) ejection fraction (EF) (LVEF). BACKGROUND: Transthoracic echocardiography and MRI are noninvasive imaging modalities well suited for serial evaluation of LV volume and LVEF. Despite the accuracy and reproducibility of volumetric methods, quantitative biplane methods are commonly used, as they minimize both scanning and analysis times. METHODS: Thirty-five adult subjects, including 25 patients with dilated cardiomyopathies, were evaluated by biplane and volumetric (cardiac short-axis stack) cine MRI and by biplane and volumetric (three-dimensional) transthoracic echocardiography. Left ventricular volume, LVEF and LV function categories (LVEF > or =55%, >35% to <55% and < or =35%) were then determined. RESULTS: Biplane echocardiography underestimated LV volume with respect to the other three strategies (p < 0.01). There were no significant differences (p > 0.05) between any of the strategies for quantitative LVEF. Volumetric MRI and volumetric echocardiography differed by a single functional category for 2 patients (8%). Six to 11 patients (24% to 44%) differed when comparing biplane and volumetric methods. Ten patients (40%) changed their functional status when biplane MRI and biplane echocardiography were compared; this comparison also revealed the greatest mean absolute difference in estimates of EF for those subjects whose EF functional category had changed. CONCLUSIONS: Volumetric MRI and volumetric echocardiographic measures of LV volume and LVEF agree well and give similar results when used to stratify patients with dilated cardiomyopathy according to systolic function. Agreement is poor between biplane and volumetric methods and worse between biplane methods, which assigned 40% of patients to different categories according to LVEF. The choice of imaging method (volumetric or biplane) has a greater impact on the results than does the choice of imaging modality (echocardiography or MRI) when measuring LV volume and systolic function.

Early changes in biochemical markers of bone turnover predict the long-term response to alendronate therapy in representative elderly women: a randomized clinical trial.

Although the antiresorptive agent alendronate has been shown to increase bone mineral density (BMD) at the hip and spine and decrease the incidence of osteoporotic fractures in older women, few data are available regarding early prediction of long-term response to therapy, particularly with regard to increases in hip BMD. Examining short-term changes in biochemical markers incorporates physiologic response with therapeutic compliance and should provide useful prognostic information for patients. The objective of this study was to examine whether early changes in biochemical markers of bone turnover predict long-term changes in hip BMD in elderly women. The study was a double-blind, placebo-controlled, randomized clinical trial which took place in a community-based academic hospital. One hundred and twenty community-dwelling, ambulatory women 65 years of age and older participated in the study. Intervention consisted of alendronate versus placebo for 2.5 years. All patients received appropriate calcium and vitamin D supplementation. The principal outcome measures included BMD of the hip (total hip, femoral neck, trochanter, and intertrochanter), spine (posteroanterior [PA] and lateral), total body, and radius. Biochemical markers of bone resorption included urinary N-telopeptide cross-linked collagen type I and free deoxypyridinoline; markers of bone formation included serum osteocalcin and bone-specific alkaline phosphatase. Long-term alendronate therapy was associated with increased BMD at the total hip (4.0%), femoral neck (3.1%), trochanter (5.5%), intertrochanter (3.8%), PA spine (7.8%), lateral spine (10.6%), total body (2.2%), and one-third distal radius (1.3%) in elderly women (all p < 0.01). In the placebo group, bone density increased 1.9-2.1% at the spine (p < 0.05) and remained stable at all other sites. At 6 months, there were significant decreases in all markers of bone turnover (-10% to -53%, p < 0.01) in women on alendronate. The changes in urinary cross-linked collagen at 6 months correlated with long-term bone density changes at the hip (r = -0.35, p < 0.01), trochanter (r = -0.36, p < 0.01), PA spine (r = -0.41, p < 0.01), and total body (r = -0.34, p < 0.05). At 6 months, patients with the greatest drop in urinary cross-linked collagen (65% or more) demonstrated the greatest gains in total hip, trochanteric, and vertebral bone density (all p < 0.05). A 30% decrease in urinary cross-linked collagen at 6 months predicted a bone density increase of 2.8-4.1% for the hip regions and 5.8-6.9% for the spine views at the 2.5-year time point (p < 0.05). There were no substantive associations between changes in biochemical markers and bone density in the placebo group. Alendronate therapy was associated with significant long-term gains in BMD at all clinically relevant sites, including the hip, in elderly women. Moreover, these improvements were associated with early decreases in biochemical markers of bone turnover. Early dynamic decreases in urinary cross-linked collagen can be used to monitor and predict long-term response to bisphosphonate therapy in elderly women. Future studies are needed to determine if early assessment improves long-term patient compliance or uncovers poor compliance, thereby aiding the physician in maximizing the benefits of therapy.

Early changes in serum N-telopeptide and C-telopeptide cross-linked collagen type 1 predict long-term response to alendronate therapy in elderly women.

The aim of this study was to determine whether early changes in serum markers of bone resorption could predict long-term responses in bone mineral density (BMD) after alendronate therapy in elderly women. One hundred and twenty women (mean age, 70 yr) were randomized to alendronate or placebo in this double blind, placebo-controlled clinical trial for 2.5 yr. Outcome measures were hip and spine BMD and biochemical markers of bone resorption, including serum N-telopeptide and C-telopeptide cross-linked collagen type I (NTx and CTx, respectively). Serum NTx and CTx were highly correlated at baseline (r = 0.73; P < 0.001) and remained so throughout the study (range, r = 0.36-0.56; all P < 0.05). After treatment with alendronate, serum NTx decreased 30.4+/-16.0% at 6 months, reaching a nadir of -36.7+/-18.0% by 24 months (P < 0.001). Serum CTx decreased 43.5+/-67.0% at 6 months and continued to decrease to 67.3+/-19.3% at 2.5 yr (P < 0.001). Moreover, decreases in serum NTx and CTx at 6 months were correlated with long-term improvements in vertebral BMD at 2.5 yr in patients receiving alendronate therapy (NTx: r = -0.42; CTx: r = -0.31; both P < 0.05). We conclude that early changes in serum NTx and CTx, markers of bone resorption, predict long-term changes in vertebral BMD in elderly women receiving alendronate therapy and provide a useful tool to assess skeletal health.

Bone loss in men with prostate cancer treated with gonadotropin-releasing hormone agonists.

Prostate cancer is the most common visceral malignancy in men. As the tumor is testosterone dependent, a frequent treatment modality involves therapy with GnRH agonists (GnRH-a) resulting in hypogonadism. Because testosterone is essential for the maintenance of bone mass in men, we postulated that GnRH-a therapy would negatively impact skeletal integrity. We compared bone mineral density (BMD), biochemical markers of bone turnover, and body composition in 60 men with prostate cancer (19 men receiving GnRH-a therapy and 41 eugonadal men) and BMD in 197 community-living healthy controls of similar age. BMD was assessed by dual energy x-ray absorptiometry and ultrasound. Biochemical markers of bone turnover, included markers of bone resorption (urinary N-telopeptide) and bone formation markers (bone-specific alkaline phosphatase and osteocalcin). Body composition (total body fat and lean body mass) was assessed by dual energy x-ray absorptiometry. Significantly lower BMD was found at the lateral spine (0.69 +/- 0.17 vs. 0.83 +/- 0.20 g/cm(2); P < 0.01), total hip (0.94 +/- 0.14 vs. 1.05 +/- 0.16 g/cm(2); P < 0.05), and forearm (0.67 +/- 0.11 vs. 0.78 +/- 0.07 g/cm(2); P < 0.01) in men receiving GnRH-a compared with the eugonadal men with prostate cancer. Significant differences were also seen at the total body, finger, and calcaneus (all P < 0.01). BMD values in eugonadal men with prostate cancer and healthy controls were similar. Markers of bone resorption (urinary N-telopeptide) and bone formation (bone-specific alkaline phosphatase) were elevated in men receiving GnRH-a therapy compared with those in eugonadal men with prostate cancer. Men receiving GnRH-a also had a higher percent total body fat (29 +/- 5% vs. 25 +/- 5%; P < 0.01) and lower percent lean body weight (71 +/- 5% vs. 75 +/- 5%; P < 0.01) compared with eugonadal men with prostate cancer. In conclusion, men with prostate cancer receiving androgen deprivation therapy have a significant decrease in bone mass and increase in bone turnover, thus placing them at increased risk of fracture.

Flecainide enantiomers: disposition in human subjects and electrophysiologic actions in vitro.

The antiarrhythmic agent flecainide is administered as a racemate. The disposition of the individual enantiomers and their electrophysiologic actions are unknown. We therefore determined through plasma levels of S-(+)-flecainide and R-(-)-flecainide in 13 patients who were receiving long-term oral flecainide therapy. In addition, the effects of the enantiomers on action potential characteristics in canine cardiac Purkinje fibers were assessed. Plasma concentrations of R-(-)flecainide were significantly higher than those of the S-(+)-enantiomer (-/+ ratio, 1.10 +/- 0.13,mean +/- SD; range, 0.89 to 1.32, p less than 0.01), suggesting that the drug undergoes enantioselective disposition. In the in vitro experiments, both enantiomers reduced phase 0 action potential Vmax (an index of the fast inward sodium current) and shortened action potential duration at 50% and 90% repolarization, but no differences between the enantiomers were detected. The time constants for development of Vmax depression were significantly longer for S-(+)-flecainide (13.4 +/- 1.5 seconds) compared with R-(-)-flecainide (8.9 +/- 0.6 seconds, p less than 0.001). Thus, although S-(+)-flecainide and R-(-)-flecainide undergo modest enantioselective disposition, they exert similar electrophysiologic effects. These studies have provided no evidence to indicate that administration of a single enantiomer, rather that the racemic drug, would offer any advantage.

Adrenal medullary transplantation to the caudate nucleus in Parkinson's disease. Initial clinical results in 18 patients.

Results from a pilot study of adrenal medullary autotransplantation for Parkinson's disease are presented. Eighteen patients were studied; 12 were followed up for 1 year, and 6 were followed up for 6 months. Four of 12 patients showed distinct improvement in the signs and symptoms of their disease, as assessed using the Columbia Rating Scale, at 1 year; none showed distinct deterioration. The 6 patients who were followed up for only 6 months were an average of 20 years older and generally more severely affected. None distinctly improved. Morbidity was considered to be minor and transient among the first 12 patients, while 4 of the last 6 patients experienced alteration in mental status lasting as long as several months. This problem has led us to conclude that older patients with preexisting cognitive impairment should not be included in future studies until the benefits are more clearly established. However, we believe that the distinct and persistent improvement seen in some of the younger patients warrants the initiation of a well-designed, randomized, and controlled trial of adrenal medullary autotransplantation for the purpose of confirming these results and assessing the effect of the procedure on the natural progression of Parkinson's disease.

The course of seizure disorders in patients with malignant gliomas.

OBJECTIVE: To describe the morbidity associated with seizures and the efficacy of anticonvulsant therapy in adult patients with malignant gliomas (MGs). STUDY DESIGN: A retrospective review of charts was performed to determine the occurrence of seizures at diagnosis, the frequency and character of subsequent seizures, and the use and toxic side effects of anticonvulsants. PATIENTS: Sixty-five consecutive adult patients with supratentorial MGs who were examined in the neurooncology clinic at a university medical center were studied. The diagnosis was glioblastoma in 47 of the patients, and it was anaplastic astrocytoma in 18 patients. The mean age of the patients was 49.5 years. The median Karnofsky status score was 80. The median survival was 18 months. RESULTS: Twenty-nine patients presented with seizures, and 21 of these had subsequent (eg, "recurrent") seizures while they were receiving anticonvulsant therapy. Ten of 36 patients who were free of seizures at diagnosis experienced seizures after diagnosis (eg, "late onset") while they were being treated with anticonvulsants, including five patients who had single seizures. Long-term seizure frequency in excess of one per month was observed in 13 patients. Ten patients had episodes of partial motor status epilepticus. Most recurrent and late-onset seizures occurred despite therapeutic anticonvulsant levels, and without evidence of tumor progression. Rash associated with anticonvulsants was observed in 26% of the patients. Other clinically important toxic side effects were observed in 14% of the patients who were receiving long-term anticonvulsant therapy. CONCLUSIONS: Seizures contributed substantially to the neurologic morbidity of MGs in at least 25% of these patients. The occurrence of seizures at diagnosis was a strong predictor of subsequent seizures, and in many patients, seizures proved to be refractory to standard anticonvulsant therapy. Long-term anticonvulsant toxic side effects are relatively common in patients with MGs. The use of long-term seizure prophylaxis for patients with MGs who are free of seizures at presentation is not clearly beneficial and should be studied in a prospective trial.