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Purpose The force–velocity relationship of muscular contraction has been extensively studied. However, previous research has focussed either on isolated muscle or single-joint movements, whereas human movement consists of multi-joint movements (e.g. squatting). Therefore, the purpose of this study was to investigate the force–velocity relationship of isovelocity squatting. Methods Fifteen male participants (24 ± 2 years, 79.8 ± 9.1 kg, 177.5 ± 6 cm) performed isovelocity squats on a novel motorised isovelocity device (Kineo Training System) at three concentric (0.25, 0.5, and 0.75 m s−1) and three eccentric velocities (− 0.25, − 0.5, and − 0.75 m s−1). Peak vertical ground reaction forces, that occurred during the isovelocity phase, were collected using dual force plates (2000 Hz) (Kistler, Switzerland). Results The group mean squat force–velocity profile conformed to the typical in vivo profile, with peak vertical ground reaction forces during eccentric squatting being 9.5 ± 19% greater than isometric (P = 0.037), and occurring between − 0.5 and − 0.75 m s−1. However, large inter-participant variability was identified (0.84–1.62 × isometric force), with some participants being unable to produce eccentric forces greater than isometric. Sub-group analyses could not identify differences between individuals who could/could not produce eccentric forces above isometric, although those who could not tended to be taller. Conclusions These finding suggest that variability exists between participants in the ability to generate maximum eccentric forces during squatting, and the magnitude of eccentric increase above isometric cannot be predicted solely based on a concentric assessment. Therefore, an assessment of eccentric capabilities may be required prior to prescribing eccentric-specific resistance training.

To analyze the records of the pregnancies of 2283 Australian women with epilepsy in the Australian Register of Antiepileptic Drugs in Pregnancy database to identify neurological factors relevant to the Cesarean sections carried out in these pregnancies.The Cesarean section rate in Australian women overall increased by an average of 0.59% annually over 20 years, from 26.0% to its calculated 2020 value of 37.3%. For the operations in women with epilepsy, the corresponding figures were 0.71% annually, and 34.4% and 48.7%. The average annual rate of increase for pre-labor operations was 0.89% to a 2020 value of 39.1%, the annual rate for operations during labor showing no statistically significant change. Multivariate regression analysis identified a number of characteristics of women with epilepsy that were statistically significantly associated with an increased likelihood of Cesarean section, but of these only seizures continuing to occur in the third trimester and having chronic illness, in particular migraine, were neurological ones. In 70 migraine-affected women, the Cesarean section rate was 51.4%, compared with 39% in the remaining pregnancies (P 0.05).Having seizures in the final trimester of pregnancy and having chronic neurological illness, especially migraine, favored Cesarean section being carried out in Australian women with epilepsy, but did not adequately account for the increasing rates of occurrence of the operation over the past 20 years.

Maternal smoking during pregnancy (MSDP) has been robustly associated with externalizing problems and their developmental precursors in offspring in studies using behavioral teratologic designs (Wakschlag et al., Am J Public Health 92(6):966-974, 2002; Espy et al., Dev Psychol 47(1):153-169, 2011). In contrast, the use of behavior genetic approaches has shown that the effects commonly attributed to MSDP can be explained by family-level variables (D'Onofrio et al., Dev Psychopathol 20(01):139-164, 2008). Reconciling these conflicting findings requires integration of these study designs. We utilize longitudinal data on a preschool proband and his/her sibling from the Midwest Infant Development Study-Preschool (MIDS-P) to test for teratologic and family level effects of MSDP. We find considerable variation in prenatal smoking patterns both within and across pregnancies within families, indicating that binary smoking measures are not sufficiently capturing exposure. Structural equation models indicate that both conduct disorder and oppositional defiant disorder symptoms showed unique effects of MSDP over and above family level effects. Blending high quality exposure measurement with a within-family design suggests that it is premature to foreclose the possibility of a teratologic effect of MSDP on externalizing problems. Implications and recommendations for future studies are discussed.

Prenatal smoking cessation has been described as an empathic action “for the baby,” but this has not been empirically demonstrated. We capitalized on a genetically-characterized extant dataset with outstanding measurement of prenatal smoking patterns and maternal face processing data (as an indicator of empathy) to test this hypothesis, and explore how empathy and smoking patterns may be moderated by a genetic substrate of empathy, the oxytocin receptor gene (OXTR). Participants were 143Caucasian women from the East Boston family study with repeated prospective reports of smoking level, adjusted based on repeated cotinine bioassays. Salivary DNA and face processing (Diagnostic Analysis of Nonverbal Accuracy-2) were assessed 14 years later at an adolescent follow-up of offspring. Two-thirds of participants reported smoking prior to pregnancy recognition. Of these, 21% quit during pregnancy; 56% reduced smoking, and 22% smoked persistently at the same level. A significant interaction between face processing and OXTR variants previously associated with increased sensitivity to social context, rs53576GG and rs2254298A, was found (β = −.181; p = .015); greater ability to identify distress in others was associated with lower levels of smoking during pregnancy for rs53576(GG)/rs2254298(A) individuals (p = .013), but not for other genotypes (p = .892). Testing this “empathy hypothesis of prenatal smoking cessation” in larger studies designed to examine this question can elucidate whether interventions to enhance empathy can improve prenatal smoking cessation rates.

Population-based evidence on second cancer risk following autologous haematopoietic SCT (HCT) is lacking. We quantified second cancer risk for a national, population-based cohort of adult Australians receiving autologous HCT for cancer and notified to the Australasian Bone Marrow Transplant Recipient Registry 1992-2007 (n=7765). Cancer diagnoses and deaths were ascertained by linkage with the Australian Cancer Database and National Death Index. Standardized incidence ratios (SIRs) were calculated and Cox regression models were used to estimate within-cohort risk factors treating death as a competing risk. During a median 2.5 years follow-up, second cancer risk was modestly increased compared with the general population (SIR 1.4, 95% confidence interval 1.2-1.6); significantly elevated risk was also observed for AML/myelodysplastic syndrome (SIR=20.6), melanoma (SIR=2.6) and non-Hodgkin lymphoma (SIR=3.3). Recipients at elevated risk of any second cancer included males, and those transplanted at a younger age, in an earlier HCT era, or for lymphoma or testicular cancer. Male sex, older age (>45 years) and history of relapse after HCT predicted melanoma risk. Transplantation for Hodgkin lymphoma and older age were associated with lung cancer risk. Second malignancies are an important late effect and these results inform and emphasize the need for cancer surveillance in autologous HCT survivors.

Preconception care (PCC) and strict periconceptional glycemic control are both used to minimize the risk of congenital birth defects in offspring of women with type 1 or type 2 diabetes mellitus (DM). These malformations are ascribed in large measure to poor periconceptional control. This study evaluated PCC by a meta-analysis of published studies of PCC in women with DM, published from 1970 to 2000. Two reviewers independently abstracted the data, and the rate and relative risk (RR) of major and minor malformations were pooled from eligible studies using a random effects model. Early first-trimester values of glycosylated hemoglobin were recorded. Eight retrospective and eight prospective cohort studies were included; they were carried out in Europe, the United Kingdom, the United States, and Israel. Most participants had type 1 DM, but three studies included women with type 2 DM. Women given PCC tended to be about 2 years older on average than the others. Methods of PCC were quite variable, although most centers provided some maternal education about the pregnancy risks associated with poor glycemic control. In seven studies reporting early gestational glycosylated hemoglobin values, mean levels were consistently lower in PCC patients. Among 2104 offspring, the pooled rate for major and minor anomalies was 2.4% in the PCC group and 7.7% in non-PCC recipients, for a pooled RR of 0.32. Among 2651 offspring, major malformations were less prevalent in the PCC group (2.1 vs. 6.5%; pooled RR = 0.36). Comparable results were obtained when only prospective studies were analyzed and in studies where the infant examiners were unaware of the mothers' PCC status. The lowest risk of major anomalies was in a study that administered folic acid periconceptionally to its PCC recipients; the RR was 0.11. This meta-analysis, which included both retrospective and prospective studies, demonstrates an association of PCC with a significantly lower risk of congenital anomalies in the offspring of women with established DM. The lowered risk was accompanied by significantly lower glycosylated hemoglobin values in the first trimester in recipients of PCC.

Sera from 516 participants enrolled in a population-based cross-sectional study in northwest Tanzania were tested for antibodies to hepatitis C virus (HCV). The mean age of study subjects was 29 years (range = 16-49 years); 43% were men, 6% reported a history of blood transfusion, and 4% were infected with human immunodeficiency virus-1 (HIV-1). Although 53 of 516 sera (10.3%, 95% confidence interval [CI] = 7.8-13.2%) were repeatedly reactive by a third-generation enzyme immunoassay (EIA-3), only 6 of the 53 were positive when tested with a third-generation recombinant immunoblot assay (confirmed HCV seroprevalence = 1.2%, 95% CI = 0.4-2.5%). The positive predictive value of the HCV EIA-3 in this population was 18.8% (95% CI = 7.0-36.4%). False positivity was not correlated with EIA-3 optical density values, age, sex, infection with HIV-1, or a history of blood transfusion, but it was marginally associated with increased serum IgG levels. We conclude that the prevalence of HCV is low in this region and that the HCV EIA-3 has a higher false-positivity rate in this population than has been reported among U.S. blood donors.

Externalizing behaviors (encompassing antisocial, impulsive, and substance use behaviors) are pervasive and impairing across a multitude of settings and developmental contexts. These behaviors, though often investigated separately, are highly comorbid. Prenatal tobacco exposure in interaction with various genetic influences has predicted later externalizing behavior, and recent evidence supports investigating sex differences in these patterns. In the current study, we extend this work by (a) examining two functional genetic markers in the dopamine system: the transporter gene ( DAT1 ) and the dopamine receptor D 4 gene ( DRD4 ) in interaction with prenatal tobacco exposure to predict a latent composite of externalizing behavior and (b) testing whether these patterns differ by sex of youth in a community sample of adolescents (n = 176). The relatively small sample is partially offset by high quality, multi-method prospective measurement. We assessed prenatal tobacco exposure using prospective repeated cotinine-corrected reports and externalizing behaviors were assessed utilizing multiple measures across three waves. The interaction between DAT1 (but not DRD4 ) and prenatal tobacco exposure was statistically significant in boys, and patterns appeared to differ by sex. Risk for externalizing behaviors for exposed boys increased linearly as a function of the 10r DAT1 allele. For exposed girls, there was a trend such that DAT1 heterozygotes had a marginally higher risk than homozygotes. This pattern was not explained by passive gene-environment correlation. Elucidating sex-specific pathways through which early adverse exposures and genetic susceptibilities contribute to externalizing behavior can inform early targeted prevention efforts for those children at highest risk.

The Arizona Twin Project is an ongoing longitudinal study designed to elucidate the genetic and environmental influences underlying the development of early competence and resilience to common mental and physical health problems during infancy and childhood. Participants are a sample of 600 twins (25% Hispanic) recruited from birth records in the state of Arizona, United States. Primary caregivers were interviewed on twins’ development and early social environments when twins were 12 and 30 months of age. Measures include indices of prenatal and obstetrical risk coded from hospital medical records, as well as primary caregiver-report questionnaires assessing multiple indicators of environmental risk and resilience (e.g., parental warmth and control, family and social support), twins’ developmental maturity, temperament, health, behavior problems, and competencies. Preliminary findings highlight the importance of the early environment for infant and toddler health and well-being, both directly and as a moderator of genetic influences. Future directions include a third longitudinal assessment in middle childhood examining daily bidirectional relations between sleep, health behaviors, stress, and mood.

With the FACSCount TM flow cytometer, counts of CD4, CD8 and CD3 lymphocytes and CD4/CD8 ratios were performed in a rural hospital in Tanzania. A total of 168 subjects (21 HIV-1 seropositive and 147 HIV-1 seronegative) were tested as part of a population-based serosurvey and AIDS education programme; 134 other subjects were hospitalized patients who had signs and symptoms suggestive of AIDS (69 HIV-1 seropositive and 65 HIV-seronegative). Mean values for the 147 HIV-1 seronegative subjects from the local population were 980 CD4 cells (95% CI 930, 1031), 598 CD8 cells (560, 635) and CD4/CD8 ratio 1.78 (1.68, 1.89). Seropositive subjects from the local population had significantly lower CD4 cell counts, higher CD8 counts and a lower CD4/CD8 ratio. CD4 cells were significantly lower and CD8 cells significantly higher in HIV-1 seropositive hospital patients compared to HIV-1 seronegative patients. However, 23 (35%) seronegative hospital patients had CD4 counts lower than 600. These results establish baseline values for the lymphocyte subsets in this population and indicate that this technique can be used in remote areas to monitor progress of HIV-infected individuals.

To evaluate the frequency, pattern, and severity of liver function test abnormalities in patients with Lyme disease associated with erythema migrans (EM), 115 individuals with no other identifiable cause for liver function test abnormalities who presented with EM between July 1990 and September 1993 were prospectively evaluated. For individuals with abnormal liver function tests, common causes of hepatitis, including hepatitis A, B, and C, were excluded. A local control group was used for comparison. Forty-six (40%) patients had at least one liver test abnormality, and 31 (27%) had more than 1 abnormality compared with 19 (19%) and 4 (4%) of controls, respectively (P < .01 for each comparison). gamma-Glutamyl transpeptidase (28%) and alanine transaminase (ALT) (27%) were the most frequently elevated liver function tests among Lyme disease patients. Anorexia, nausea, or vomiting was reported by 30% of patients, but did not occur more frequently in patients with elevated liver function tests compared with those with normal values. Patients with early disseminated Lyme disease were more likely to have elevated liver function studies (66%) compared with patients with localized disease (34%) (P = .002). After antibiotic treatment, elevated liver function tests improved or resolved in most patients. Liver function test abnormalities are common in patients with EM but were mild, most often not associated with symptoms, and improved or resolved by 3 weeks after the onset of antibiotic therapy in most patients.

We report the clinical outcome of arthroscopic labral reconstruction using a transglenoid suture technique in a young, active-duty military population. Forty-eight patients (49 shoulders) with varying degrees of gleno humeral instability underwent arthroscopic labral re construction using a transglenoid suture technique. All patients had traumatic injuries to their shoulders and all patients had magnetic resonance imaging scans dem onstrating anterior labral tears. Postoperatively, the patients' shoulders were immobilized for up to 6 weeks. At a mean followup of 30 months (range, 12 to 49), 17 of the 41 patients (41%) with preoperative dislocation or subluxation had recurrent instability. Nine of these patients subsequently underwent open reconstruction procedures for recurrent instability. On the basis of the Rowe rating system, 53% had excel lent or good results and 47% had fair or poor results. The overall perioperative complication rate was 14%. Suprascapular nerve palsy occurred in three cases (6%). Using the Fisher exact test, we determined that immobilization for 6 weeks postoperatively correlated with a lower recurrence rate in the patients with a history of glenohumeral dislocation (P = 0.007). The results of arthroscopic labral reconstruction using transglenoid sutures in the military patient are inferior to the reported 3% to 5% recurrence rate with open Bankart procedures, and the transglenoid pin tech nique jeopardizes the suprascapular nerve.

Objectives: The aim of the paper is to present data on the first year of all appeals lodged with a Mental Health Review Tribunal against compulsory treatment orders of psychiatric inpatients. Method: Two tribunals have been in operation in New Zealand since the introduction of a new Mental Health (Compulsory Assessment and Treatment) Act in 1992. The case records of all patients who had appeals heard by either the Northern or Southern regional tribunal from 16/12/92 to 7/12/93 inclusive were examined. Results: 145 appeals were heard by the tribunals: 14.5% of appeal hearings resulted in the discharge of a patient from their compulsory treatment status. Discharge rates for the Southern Tribunal were found to be significantly higher at 22%, compared with 10% for the Northern Tribunal (p Conclusions: Ambiguities within the Act need to be addressed in order that criteria used to judge a patient's fitness for discharge may be standardised. In addition, the Act stipulates a maximum delay of 14 days in reviewing a patient's case; however in practice a mean of 22 days elapses, indicating that this stipulation requires review.

Intra-articular morphine has been shown to provide prolonged analgesia after arthroscopic knee surgery; the addition of local anaesthetic agents has been reported to improve this analgesic effect. Pethidine possesses local anaesthetic properties, and therefore this study was designed to evaluate its analgesic efficacy after arthroscopic meniscectomy. Sixty patients were allocated randomly to receive intra-articular injections of pethidine 50 mg, morphine 5 mg or saline after elective arthroscopic meniscectomy. Postoperative pain was assessed using an interval visual analogue scale and measuring analgesic requirements. Both treatment groups had significantly lower pain scores compared with the control group. Patients in the pethidine group had lower pain scores than those in the morphine group at 0.5, 1 and 2 h, but significantly higher scores at 12 and 24 h. These observations suggest that the local anaesthetic effect of pethidine may be responsible for the improved early analgesia, but its duration of action appears to be less than that of morphine.

✓ Tenascin is an extracellular matrix glycoprotein expressed during both normal development and neoplastic growth in both neural and nonneural tissues. During development of the central nervous system (CNS), tenascin is synthesized by glial cells, in particular by immature astrocytes, and is concentrated in transient boundaries around emerging groups of functionally distinct neurons. In the mature CNS, only low levels of the glycoprotein can be detected. The present study demonstrates that following trauma to the adult human cerebral cortex, discrete populations of reactive astrocytes upregulate their expression of tenascin and dramatically increase their transcription of the tenascin gene. The enhanced expression of tenascin may be involved in CNS wound healing, and may also affect neurite growth within and around a brain lesion.

This study aimed to evaluate and validate chemical shift imaging (CSI) for in vivo glutamate (Glu) quantification in patients with supratentorial gliomas. If validated, CSI could become an extremely useful tool to investigate metabolic dysfunction of Glu in excitotoxic neuropathologies. Quantitative CSI estimates of Glu concentrations were compared with known concentrations of Glu in aqueous phantom solutions. Forty-one patients with known or likely supratentorial gliomas underwent preoperative CSI. The spectra obtained were analyzed for Glu concentrations and Glu to creatine (Cr) ratios. These in vivo measurements were correlated against ex vivo Glu content quantified by high performance liquid chromatography (HPLC) measured in 65 resected brain tumor and peritumoral brain specimens. For the phantom solutions the CSI estimates of Glu concentration and the Glu/Cr ratios were highly correlated with known Glu concentration (r² = 0.95, p = 0.002, and r² = 0.97, p 0.0001, respectively). There was a modest, but statistically significant, correlation between the ex vivo measured Glu and in vivo spectroscopic Glu concentration (r² = 0.22, p = 0.04) and ratios of Glu to Cr (r² = 0.30, p = 0.002). Quantitative measurement of Glu content is feasible in patients with supratentorial gliomas using CSI. The in vitro and in vivo results suggest that this has the potential to be a reliable quantitative imaging assay for brain tumor patients. This may have wide clinical research applications in a number of neurological disorders where Glu excitotoxicity and metabolic dysfunction are known to play a role in pathogenesis, including tumor associated epilepsy, epilepsy, stroke and neurotrauma.

To estimate the prevalence and demographic distribution of treated epilepsy in a community-based population.We surveyed all residents in Tasmania, Australia, who were supplied at least one antiepileptic drug prescription between July 1, 2001 and June 30, 2002, recorded on the national prescription database. We adjusted for the effect of disease-related non-response bias by imputation methods.After three mail contacts, 54.0% (4072/7541) responded, with 1774 (43.6%) indicating treatment for epilepsy, representing 86.0% of the estimated total possible cases in Tasmania. The adjusted treated epilepsy prevalence was 4.36 per 1000 (95% CI 4.34, 4.39); lower in women (prevalence ratio 0.92 (95% CI 0.84, 1.00)); greater with increasing age (P0.001); similar in the three main geographic regions; and similar with socioeconomic status of postcode of residence.Although our estimates are likely to be affected by access to health services, overall treated epilepsy prevalence of 4.4 per 1000 is similar to previous studies. Our finding of high elderly prevalence has been reported in a few recent studies in developed countries and has important clinical and public health implications in populations with similar aging demographics.

Longitudinal epiphyseal bracket (LEB) is a rare ossification anomaly in which an epiphysis brackets the diaphysis of a phalanx, metacarpal, or metatarsal. This abnormal epiphysis tethers longitudinal growth, resulting in a shortened and oval-shaped bone. Four patients with five LEBs were treated by central physiolysis and followed for a mean of 6 years. The patients had significant hallux varus deformity. Three patients had duplicated great toes, and two had tibia hemimelia significant enough to require epiphysiodesis as they neared adolescence. Resection of the LEB allowed the proximal and distal epiphysis to resume untethered growth. Silastic or methyl methacrylate was placed over the resected physis to prevent bony rebridging. The associated hallux varus deformity was corrected by capsulorrhaphy and K-wire fixation. In all patients, the metatarsal resumed longitudinal growth and correction of the hallux varus was maintained.

In studies investigating foetal malformations associated with antiepileptic drug exposure during pregnancy, the common practice has been to assess the incidence and nature of the malformations at, or soon after, birth. The adequacy of this approach to determine the true incidence of the malformations has received little attention.To compare the incidence and natures of the foetal malformations recognized by, or soon after, birth with similar data for malformations recognized in the first post-natal year.Analysis of data from the Australian Register of Antiepileptic Drugs in Pregnancy.Up to 25% of the malformations recognized by the end of the first post-natal year had not been detected by, or soon after, birth. There was a tendency for the late-recognized malformations to differ from the early-recognized ones in relation to the body parts involved.Early assessment and delayed assessment of infants for the presence of foetal malformations are complementary, with the latter resulting in finding a higher incidence of malformations. However, omission of an early post-natal assessment may result in biases because of loss of subjects to follow-up.

Glycogen Synthase Kinase 3 beta (GSK3β) is a serine-threonine kinase originally identified for its role in the conversion of glucose to glycogen. Pharmacological inhibition can be achieved by drug binding to ATP or magnesium binding sites on the enzyme. Pharmaceutical companies have developed several small molecule GSK3β inhibitors for diabetes research. Additionally, GSK3β inhibitors are being clinically tested as therapeutics for neurological diseases, however, the mechanisms of involvement are unclear. Several studies have shown that the therapeutic effect of GSK3β inhibition is associated with the inhibition of inflammation. Similarly, the mechanisms underlying the anti-inflammatory function of GSK3β inhibition are not well understood. GSK3β inhibition attenuates activation of the pro-inflammatory transcription factor NFκB, and activates the immuno-modulatory transcription factor β-catenin. GSK3β inhibition has also been shown to induce secretion of the anti-inflammatory cytokine IL-10. In addition, pharmacological inhibition of GSK3β suppressed alloreactive T-cell responses. The combined anti-proliferative and anti-inflammatory properties of small molecule inhibitors of GSK3β make them an attractive treatment modality towards the control of inflammation.

Twenty-four-hour ambulatory blood pressure measurements (ABPM) are likely to eliminate the stress of visits and observer bias in office blood pressure (BP) recordings, allow consideration of the circadian variability in BP, and correlate well with target organ damage. To define the prevalence of "white coat" hypertension in a rural community to a nonacademic setting, and to assess age and sex related differences, we studied 131 patients who had more than two prior office diastolic BP measurements greater than 90 mm Hg and less than 115 mm Hg. Blood pressure was measured every 10 to 60 min for 24 h using the SpaceLabs 90207 device. Office BP readings were higher than ABPM in the group as a whole, in individual age groups, and in both sexes. The differences were more pronounced at night. Average differences between office and ambulatory BP ranged between 14.4 +/- 1.7/2.9 +/- 2.0 (ABPM at 10:00), and 33.8 +/- 2.3/22.8 +/- 1.5 mm Hg (systolic/diastolic +/- SE) (ABPM at 01:00). The nighttime drop in systolic BP was not apparent in subjects more than 65 years old. Women had a proportionately higher mean office BP than men (115.0 +/- 0.9 office v 110.2 +/- 1.3 mm Hg ABPM in women and 112.3 +/- 0.9 v 104.3 +/- 1.1 mm Hg in men) (P = .013), and the elderly did not display the relationship between ambulatory and office mean BP seen in younger subjects (r = 0.15, P = .30 v r = 0.36, P = .0004, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Two hundred eighty-one patients underwent magnetic resonance (MR) imaging of the shoulder over a 2-year period. Eighty-eight patients underwent arthroscopic surgery, and their surgical results were correlated with the findings at MR imaging. MR imaging enabled accurate prediction of anterior labral tears, with a sensitivity of 95%, a specificity of 86%, and an accuracy of 92%. MR imaging was less effective in the prediction of tears of the superior labrum, with a sensitivity of 75%, a specificity of 99%, and an accuracy of 95%. These two categories accounted for the majority of the surgically correctable disease. MR imaging was found to be unreliable in the prediction of posterior (sensitivity, 7.7%) or inferior (sensitivity, 40%) labral tears, isolated cases of which occurred in only two (2%) of those undergoing surgery. MR imaging proved to be a highly accurate, noninvasive technique for the clinical evaluation of shoulder instability.

Although levels of high density lipoprotein (HDL) cholesterol in males decrease during adolescence and after treatment with testosterone derivatives, several studies have reported that levels of HDL cholesterol are positively associated with endogenous levels of testosterone in men. This association was further examined using data collected during 1985 and 1986 from 3,562 white and 500 black men who ranged in age from 31 to 45 years. Black men had higher mean levels of both HDL cholesterol (8 mg/dl) and total testosterone (33 ng/dl) than white men, and positive associations were observed between testosterone and HDL cholesterol levels (r = 0.22, whites; r = 0.26, blacks). In addition, levels of testosterone were related positively to alcohol consumption and cigarette smoking and negatively to age, Quetelet index, and use of beta-blockers. We used stratification and regression analyses to determine if any of these characteristics could account for the positive association between levels of HDL cholesterol and total testosterone. Although controlling for most factors had little influence, adjusting for Quetelet index reduced the strength of the association between levels of testosterone and HDL cholesterol by approximately 30%. These findings suggest that the positive association between levels of testosterone and HDL cholesterol may not be causal. Multivariable analyses that control for obesity and other potentially confounding characteristics should be used in studies that assess the relation of testosterone levels to coronary heart disease.

Available techniques for determining age from human cranial remains are limited. This study examines the efficacy of Meindl and Lovejoy's (1985) method of determining age based on ectocranial suture closure patterns as compared to a baseline of ages developed from a multifactorial approach employing various age determining factors from across the skull. What makes this study different is that the sample upon which this comparison is performed contains a large number of artificially deformed crania. Our hypothesis is that aging techniques that rely on suture closure patterns as markers are complicated by the results of artificial modification of the cranial vault. The study is conducted on adult, human crania from prehispanic archaeological sites in South America. Results demonstrate a significant difference between the two aging methods, more particularly when applied to deformed skulls. We conclude that when a skull is deformed age should be estimated utilizing multiple factors that exclude Meindl and Lovejoy's ectocranial suture aging technique.

Glycogen synthase kinase 3 beta (GSK-3beta) was one of the first kinases identified and studied, initially for its role in the regulation of glycogen synthesis. Over the past decade, interest in GSK-3beta has grown far beyond glycogen metabolism, and this is due in large measure to the critical role that GSK-3beta plays in the regulation of many other cellular processes, particularly cell proliferation and apoptosis. GSK-3beta has been shown to regulate the proteolysis and sub-cellular compartmentalization of a number of proteins directly involved in the regulation of cell cycling, proliferation, differentiation and apoptosis. GSK-3beta also regulates the degradation of proteins that regulate gene expression and thus affects a variety of important cell functions. Specifically, GSK-3beta controls the degradation of beta-catenin, the main effector of Wnt that regulates haematopoiesis and stem cell function. In this case GSK-3beta is a negative regulator of Wnt. In contrast, GSK-3beta positively regulates NF-kappaB, another important biochemical pathway also involved in the regulation of multiple aspects of normal and aberrant haematopoiesis. GSK-3beta regulates degradation of IkappaB, a central inhibitor of NF-kappaB. In this way, GSK-3beta acts to control the resistance of leukaemic cells to chemotherapy through the modulation of NF-kappaB, a critical factor in maintaining leukaemic cell growth. In addition, GSK-3beta regulates the pro-inflammatory activity of NF-kappaB. As GSK-3beta is a pleiotropic regulator, inhibitors may increase the range of novel anti-leukaemic and anti-inflammatory drugs that control immune response.

Vulvovaginitis in the prepubertal child may present with itch, irritation, pain, dysuria or discharge as a result of poor hygiene, contact irritants, sexual abuse or skin disease involving the genital area. Common infectious causes include threadworms, group A beta-haemolytic streptococci and Haemophilus influenzae. A full history and examination are essential. Investigations may include swabs, midstream urine, biopsy, ultrasound and examination under anaesthesia.

Management of bacterial keratitis: beyond exorcism towards consideration of organism and host factors

To assess the significance of ultrasonographically detected hypoechoic lesions of the testis when the clinical examination is normal, and to highlight the management difficulties thereafter.Over a 2-year period four patients underwent radical orchidectomy where the sole indication for surgery was a hypoechoic lesion detected on ultrasonography (US). The indications for US were persistent scrotal discomfort in two men, contralateral orchitis, and the follow-up of testicular microlithiasis. The lesions were 4-11 mm in size and one man had several. None of the lesions were palpable; the tumour markers were normal in all patients.Three of the testes contained seminoma; in one there were two foci of seminoma and in all intratubular germ cell neoplasia was also identified. The remaining case was a Leydig-cell tumour. All tumours were staged as pT1 after radical inguinal orchidectomy.Impalpable lesions of the testis are likely to be malignant if they are hypoechoic on US and should be considered as seminoma until proved otherwise. The management thereafter is not straightforward, but must ensure an adequate histological diagnosis if the US appearances do not resolve.

To estimate the likelihood of poor surgical results being explained by chance rather than under-performance.The 30-day mortality rates after radical cystectomy for bladder cancer were analysed theoretically. Surgical competence was defined as a mortality rate of 4%, excellence as 2% and under-performance as 8%, 12%, 20% or 40%. Four scenarios were explored for surgeons of different competence: first, the sample size required to show that a given level of under-performance is very unlikely to be due to chance; second, the likelihood of two or more consecutive deaths in a series of cases; third, the likelihood of clustering of deaths, defined as two deaths in five or in 10 cases; and last, the likelihood of outstanding surgical results (i.e. no deaths) being achieved in small cohorts by surgeons of differing competence.For surgeons with a mortality rate of 8%, 12%, 20% or 40%, the sample sizes needed to prove under-performance are 211, 65, 21 and seven, respectively. For consecutive deaths, 0.4% of excellent, 1.4% of competent and 21% of surgeons with a mortality rate of 12% will experience two or more consecutive deaths in the next 10 cases. For clustered deaths, 1% of excellent, 5% of competent and 23% of seriously under-performing surgeons (mortality ratesor = 12%) will experience two deaths in their next 10 cases. Lastly, for the likelihood of outstanding results, only 3.6% of surgeons with an 8% mortality rate and1% of surgeons with a mortality rateor = 12% will experience no deaths over 40 consecutive cases.Very large cohorts are needed to confirm even significant under-performance. Consecutive deaths are very unlikely events for competent surgeons. Clustered deaths (two deaths in 10 cases) are very unlikely events for excellent surgeons but plausible for competent ones. Analysis of consecutive/clustered deaths is limited by low statistical sensitivity; only up to a quarter of seriously under-performing surgeons are identified. No deaths in 40 consecutive cases implies competence.

We have previously described an indicator dilution technique of measuring cardiac output in which lithium chloride is injected as a bolus via a central venous catheter and cardiac output derived from the arterial lithium dilution curve recorded from a lithium-selective electrode, which we have developed for this purpose. It would be an advantage if the lithium could be injected via the basilic vein (in the antecubital fossa) in those patients who do not need central venous catheterisation for other reasons. We have therefore compared cardiac output measurements made using these two routes of lithium chloride administration.Lithium dilution cardiac output was measured 10 times in each of 10 patients, injecting the lithium chloride alternately via the basilic or central venous catheter.The mean difference was 0.8 +/- 5.2% (SD) (range -8.5 to +7.0%) over a range of cardiac output of 4.5-13 l/min.Injection of lithium chloride via the basilic vein in the antecubital fossa allows accurate lithium dilution cardiac output measurements to be made in patients who do not have central venous catheters in place.

Previous angiographic and radiological studies have suggested that the peroneal artery is the best preserved of the calf vessels in peripheral vascular disease and should be a site of preference for a femorodistal bypass graft. Calf vessel run-off assessed by pulse generated run-off (PGR) provides a more accurate prediction of graft success or failure than angiography and may therefore give a better functional picture of vessel patency than angiography. This study compares the presence and degree of preservation of the three calf vessels in patients with severe peripheral vascular disease using both intra-arterial digital subtraction angiography (IADSA) and PGR. Thirty-four limbs in patients with either ischaemic rest pain, ulceration or gangrene were studied and the results were scored according to the extent and severity of disease in the peroneal, posterior tibial and anterior tibial arteries. On IADSA, the peroneal artery was patent significantly more often (79%) than the posterior tibial artery (47%) or the anterior tibial artery (38%). Conversely, PGR examination showed no difference in patency between the three vessels (peroneal 91%, posterior tibial 88%, anterior tibial 79%). The peroneal artery was also significantly better preserved on IADSA (65%) compared to the posterior tibial artery (38%) and the anterior tibial artery (23%). PGR studies again showed no difference in the best preserved vessel between peroneal (47%), posterior tibial (50%) and anterior tibial (50%) arteries. Thus, the peroneal artery appears the better preserved vessel on angiography but this appearance may be misleading because the more functional PGR studies show no significant difference in the patency or degree of preservation of the three calf vessels.

When there is a genetic mutation in a major cardiac protein, SCD is often an unfortunate part of the clinical phenotype. In the majority of common cardiac diseases, even though the nature or degree of genetic influence is not understood their importance cannot be denied. Although advancing by one gene or gene interaction at a time is arduous, it is the only apparent way to begin to unravel as complex a clinic syndrome as SCD.

The cellular responses to carcinogen exposure influence cellular fate, which in turn modulates the neoplastic response. Certain hexavalent chromium [Cr(VI)] compounds are implicated as occupational respiratory carcinogens at doses that are both genotoxic and cytotoxic. We examined the mechanism of Cr(VI)-induced apoptosis in normal human fibroblasts (BJ) immortalized by human telomerase gene transfection (BJ-hTERT), and we assessed the spectrum of cumulative cellular fates [(a) regaining of replicative potential; (b) terminal growth arrest; or (c) apoptosis] for a narrow range of increasingly genotoxic doses of Cr(VI). Exposure of BJ-hTERT cells to Cr(VI) resulted in a dose-dependent increase in apoptosis that involved mitochondrial disruption as evidenced by mitochondrial membrane depolarization and cytochrome c release. The initial response to Cr(VI) exposure was inhibition of cell cycle progression. At the lowest dose tested (1 microM; 32% clonogenic survival), the cell cycle inhibition led to terminal growth arrest but no apoptosis. The fraction of terminally growth arrested cells increased as the dose was increased to 3 microM but then decreased at 4, 5, and 6 microM as apoptosis became the predominant cell fate. Our results suggest that cell populations exposed to Cr(VI) have a different spectrum of responses, depending on the extent of DNA damage, and that the regaining of replicative potential after relatively higher genotoxic exposures may be attributable to either escape from, or resistance to, terminal growth arrest or apoptosis.

We investigated the relationship between cyclin E mRNA overexpression and p53 protein accumulation in epithelial ovarian cancers.mRNA was isolated and cDNA was prepared from 36 epithelial ovarian tumors (three adenomas, three low malignant potential tumors, and 30 carcinomas), and six normal ovaries. The cyclin E mRNA expression levels relative to an internal control, beta-tubulin, were determined by semiquantitative polymerase chain reaction (PCR). Cyclin E and p53 protein expression in ovarian cancer tissues were examined by immunohistochemistry using the same series of samples. Fisher exact test of significance and an unpaired t test were used for statistical analysis.Considerable levels of cyclin E mRNA were detected in all normal ovaries and ovarian tumor samples examined by semiquantitative PCR amplification. mRNA levels of cyclin E were significantly higher in nine of 30 (30%) ovarian cancers compared with those in normal ovaries. The immunohistochemical expression of cyclin E protein was confirmed in the nuclei of tumor cells in 13 of 30 (43%) ovarian cancers. p53 protein accumulation was detected in 12 of 30 (40%) ovarian cancers examined. There was a significant inverse correlation between cyclin E mRNA overexpression and p53 protein accumulation (P.01, Fisher exact test).Cyclin E mRNA overexpression frequently occurs in ovarian cancers without p53 protein accumulation. Cyclin E might have an important effect on the development of a limited number of ovarian cancers.

Objective: To compare the results of cardiac output measurements obtained by lithium dilution and transpulmonary thermodilution in paediatric patients. Design: A prospective study.¶Setting: Paediatric intensive care unit in a university teaching hospital.¶Patients: Twenty patients (age 5 days–9 years; weight 2.6–28.2 kg) were studied.¶Interventions: Between two and four comparisons of lithium dilution cardiac output (LiDCO) and transpulmonary thermodilution (TPCO) were made in each patient.¶Measurements and results: Results from three patients were excluded: in one patient there was an unsuspected right-to-left shunt, in two patients there was a problem with blood sampling through the lithium sensor. There were 48 comparisons of LiDCO and TPCO in the remaining 17 patients over a range of 0.4–6 l/min. The mean of the differences (LiDCO–TPCO) was –0.1 ± 0.3 (SD) l/min. Linear regression analysis gave LiDCO = 0.11 + 0.90 × TPCO l/min (r 2 = 0.96). There were no adverse effects in any patient.¶Conclusions: These results suggest that the LiDCO method can be used to provide safe and accurate measurement of cardiac output in paediatric patients. The method is simple and quick to perform, requiring only arterial and venous catheters, which will already have been inserted for other reasons in these patients.

In a continued effort to identify and characterize secreted proteases that are overexpressed in ovarian carcinomas, we discovered the testisin protease as such a candidate. When this discovery was originally made, no data existed in the literature or in the GenBank database that identified such a gene. Our main objective was to determine whether this gene was overexpressed exclusively in ovarian tumor tissues compared with normal ovary and whether it was expressed in any other normal tissues.mRNA was isolated and cDNA was prepared from 34 ovarian tumors (four adenomas, three low malignant potential tumors, and 27 carcinomas) and seven normal ovaries. The testisin mRNA expression level relative to internal control, beta-tubulin, was determined by Northern blot analysis and semiquantitative polymerase chain reaction (PCR).Northern blot hybridization showed that the testisin transcript was abundant in ovarian carcinoma but was not detected in normal ovary. On examination of Northern blots from normal fetal and adult tissues, only adult testis showed abundant transcripts of testisin. Semiquantitative PCR examination showed that the testisin mRNA levels in ovarian tumors of low malignant potential and in ovarian carcinomas were significantly higher than in normal ovaries (P.01). Testisin mRNA level in ovarian carcinomas was also significantly higher than in ovarian adenomas (P.05). Testisin overexpression rates in advanced stage (stage 2 or 3) diseases were significantly higher than that in early stage diseases (stage 1) in ovarian carcinoma samples (P.05).The induction of the testisin transcript might contribute to the development, progression, and invasive or metastatic capacity of ovarian carcinomas.

It has been known for10 years that there are two alleles of the human ornithine decarboxylase (ODC) gene, defined by a polymorphic PstI RFLP in intron 1. We have sequenced a large portion of each of the two alleles, including some of the 5' promoter region, exon 1, intron 1, and exon 2, and determined that a single nucleotide polymorphism at base +317 (relative to transcription start site) is responsible for the presence or absence of the PstI restriction site. We have developed two genotyping assays, a PCR-RFLP assay and a high-throughput TaqMan-based method, and determined the ODC genotype distribution in900 North American DNA samples. On the basis of its location between two closely spaced Myc/Max binding sites (E-boxes), we speculated that the single nucleotide polymorphism at base +317 could have functional significance. Results of transfection assays with allele-specific reporter constructs support this hypothesis. The promoter/regulatory region derived from the minor ODC allele (A allele) was more effective in driving luciferase expression in these assays than the identical region from the major allele (G allele). Our results suggest that individuals homozygous for the A allele may be capable of greater ODC expression after environmental exposures, especially those that up-regulate c-MYC expression.

Objective To determine the functional and radiographic outcome of low Weber C ankle fractures and to evaluate the contribution of the syndesmotic screw in their outcome. Design Prospective evaluation of a consecutive series. Setting Level I trauma center. Patients Forty-five patients divided into two groups matched for age, sex, and severity of injury. Twenty-six patients were treated with open reduction, internal fixation, and a supplemental syndesmotic screw, and nineteen patients were treated without a syndesmotic screw. Minimum time to follow-up was three years. Methods A subjective, objective, and radiographic ankle scoring system was used. Logistical regression analysis was performed to determine whether the presence or absence of a syndesmotic screw was a predictor of a poor outcome. The likelihood ratio test was used to evaluate the significance of each variable in both univariate and multivariate analyses. Results There was no statistically significant difference between either group, either using subjective outcome criteria (p = 0.86) or in ankle range of motion (p = 0.94). Logistical regression analysis indicated that fracture dislocation could be used as a predictor of a poor outcome for either group. Inadequate reduction and advancing age were also found to be significant predictors of a poorer outcome regardless of the use of a syndesmotic screw (p = 0.003, p = 0.004). Conclusions Judicious fixation of Weber C type injuries within five centimeters of the ankle joint, with or without a syndesmotic screw, gives similar results. Obligatory fixation of these fractures with syndesmotic screws appears to have no benefit and creates the need for an additional procedure.

Wide use of a succession of different manufactured antimicrobial agents during the past 60 years has prompted the eventual emergence and progressive spread through the world's interconnecting bacterial populations of a growing variety of genes expressing resistance to those agents. The complex processes that spread and link resistance genes into different distributions at different times and places are driven by antimicrobial selection and by contagion. Management of resistance by reducing selection and contagion in a coordinated way requires better information. Most of the information about the spread of resistance exists in laboratory files of isolates at medical centers, and the information about patient antimicrobial use is found in pharmacy files at the same centers. Putting these in a combined database at each center would give a valuable tool to each center's antimicrobial resistance management team. Merging such databases from multiple centers would provide a public health resource for benchmarking, overview surveillance, and general resistometrics.

Patients with medically intractable partial epilepsy and well-defined symptomatic MRI lesions were studied using phase-encoded frequency spectral analysis (PEFSA) combined with low-resolution electromagnetic tomography (LORETA). Ten patients admitted to the epilepsy monitoring unit with MRI-identified lesions and intractable partial epilepsy were studied using 31-electrode scalp EEG. The scalp electrodes were located in three-dimensional space using a magnetic digitizer and coregistered with the patient's MRI. PEFSA was used to obtain a phase-encoded scalp map for the ictal frequencies. The ictal generators were obtained from the scalp map using LORETA. In addition, the generators of interictal epileptogenic spikes were identified using time-domain LORETA. The LORETA generators were rostral to the MRI lesion in 87% (7/8) of patients with temporal lobe lesions, but all were located in the mesial temporal lobe in concordance with the patients' MRI lesions. In patients with frontal lobe epilepsy, the ictal generators at the time that the spectral power was maximal localized to the MRI lesions. Eight of 10 patients had interictal spikes, of which 4 were bilateral independent temporal lobe spikes. Only generators of the interictal spikes that were ipsilateral to seizure onset correlated with the ictal generators. LORETA combined with PEFSA of the ictal discharge can localize ictal EEG discharges accurately and improve correlation with brain anatomy by allowing coregistration of the ictal generator with the MRI. Analysis of interictal spikes was less useful than analysis of the ictal discharge.

Mitochondrial ribosomal proteins (MRPs) are required for the translation of all 13 mitochondrial encoded genes in humans. It has been speculated that mutations and polymorphisms in the human MRPs may be a primary cause of some oxidative phosphorylation disorders or modulate the severity and tissue specificity of pathogenic mitochondrial DNA mutations. Although the sequences of most of the yeast MRPs are known, only very few mammalian and nearly no human MRPs have been completely characterized. MRPs differ greatly in sequence, and sometimes biochemical properties, between different species, not allowing easy recognition by sequence homology. Therefore, the Mammalian Mitochondrial Ribosomal Consortium is using a direct approach of purifying individual mammalian (bovine) MRPs, determining their N-terminal and/or internal peptide sequences using different protein sequencing techniques, and using the resulting sequence information for screening expressed sequence tags and genomic data bases to determine human, mouse, and rat homologues of the bovine proteins. Two proteins of the large and three proteins of the small ribosomal subunit have been analyzed in this manner. Three of them represent "new," i.e. formerly unknown mammalian mitochondrial ribosomal protein classes. Only one of these three different MRPs shows significant sequence similarities to known ribosomal proteins. In one case, the corresponding human genomic DNA sequences were found in the data bases, and the exon/intron structure was determined.

To characterize the distribution of male and female ophthalmologists with regard to practice type, subspecialty training, rural-urban distribution, and regional distribution.Ophthalmology Matching Program files containing the records of residents who began their second year at accredited programs between 1986 and 1990 (inclusive), were compared to membership files of the American Academy of Ophthalmology. Practice locations for each individual were classified according to region, stage, and Rural-Urban Continuum County Code, as defined by the US Department of Agriculture.This cohort comprised 2,494 individuals, 77.1% (1922) of whom were male and 22.9% (572) of whom were female. Group practice was most common (55.9% for women and 61.3% for men). More women were in salaried positions associated with health maintenance organizations (p = 0.006) and academic settings (p0.001) than were men. Notable differences in subspecialty choice were restricted to pediatric ophthalmology, chosen three times more frequently by women, and vitreoretinal diseases/surgery, chosen twice as often by men. Only 5.6% of women selected nonmetropolitan practice locales compared to approximately twice that percentage of men. The Middle Atlantic and New England regions attracted more women, while the South Atlantic attracted more men.

Four different classes of mammalian mitochondrial ribosomal proteins were identified and characterized. Mature proteins were purified from bovine liver and subjected to N-terminal or matrix-assisted laser-desorption mass spectroscopic amino acid sequencing after tryptic in-gel digestion and high pressure liquid chromatography separation of the resulting peptides. Peptide sequences obtained were used to virtually screen expressed sequence tag data bases from human, mouse, and rat. Consensus cDNAs were assembled in silico from various expressed sequence tag sequences identified. Deduced mammalian protein sequences were characterized and compared with ribosomal protein sequences of Escherichia coli and yeast mitochondria. Significant sequence similarities to ribosomal proteins of other sources were detected for three out of four different mammalian protein classes determined. However, the sequence conservation between mitochondrial ribosomal proteins of mammalian and yeast origin is much less than the sequence conservation between cytoplasmic ribosomal proteins of the same species. In particular, this is shown for the mammalian counterparts of the E. coli EcoL2 ribosomal protein (MRP-L14), that do not conserve the specific and functional highly important His(229) residue of E. coli and the corresponding yeast mitochondrial Rml2p.

Proteases play essential roles in the process of tumor invasion and metastasis. The serine protease stratum corneum chymotryptic enzyme (SCCE) has been purified from human stratum corneum and is known to contribute to the cell shedding process by catalyzing the degradation of intercellular cohesive structures at the skin surface. The presence of SCCE on the surface of tumor cells suggests it also may contribute to the process of tumor cell shedding, resulting in early metastasis of carcinoma.Gene expression of SCCE was investigated in 44 ovarian tumors (12 low malignant potential tumors and 32 carcinomas) and 10 normal ovaries by quantitative polymerase chain reaction (PCR). The PCR product was labeled with (32)P and a phosphoimager was used to determine the relative expression of SCCE compared with an internal control Beta-tubulin. mRNA transcripts were studied by Northern blot hybridization and protein expression and localization was examined by Western blot analysis and immunohistochemistry.mRNA expression levels of SCCE were elevated significantly in 66.7% of 12 low malignant potential tumors and 78.1% of 32 carcinomas. Furthermore, SCCE protein was abundant in tumor cells and tumor cell lines that overexpressed the mRNA transcript.The results of the current study suggest that SCCE frequently is overexpressed in ovarian tumors and therefore may contribute to tumor cell growth, tumor spread, and the metastatic potential of ovarian tumor cells.

As blockade of CC-chemokine receptor 5 (CCR5) has been proposed as therapy for HIV-1, we examined whether the CCR5-delta32/delta32 homozygous genotype has phenotypic expressions other than those related to HIV-1.Study subjects were white homosexual men or men with hemophilia who were not infected with HIV-1. In this study, 15 CCR5-delta32/delta32 homozygotes were compared with 201 CCR5 wild-type (+/+) subjects for a wide range of clinical conditions and laboratory assay results ascertained during prospective cohort studies and routine clinical care. CCR5-delta32 genotype was determined by polymerase chain reaction, followed by single-stranded conformational polymorphism analysis.Hypertension and conditions attributable to hemophilia were the only diagnoses frequently found in clinical records of CCR5-delta32/delta32 study subjects. Based on blood pressure measurement and treatment history, CCR5-delta32/delta32 homozygotes had a 2.8-fold higher prevalence of hypertension than age-matched CCR5-+/+ study subjects (95% confidence interval [CI], 1.2-6.4; p = .01); none of the homozygotes had severe hypertension. Hematologic measures were generally similar across the genotypes, but total lymphocyte counts were approximately 20% higher in CCR5-delta32/delta32 study subjects than in CCR5-+/+ study subjects (p.05). Among patients with hemophilia who were infected with hepatitis C virus (HCV), mean alanine aminotransferase levels were 117% higher among CCR5-delta32/delta32 homozygotes (p.05), but serum HCV levels did not differ by CCR5-delta32 genotype. CCR5-delta32/delta32 homozygous study subjects had a lower prevalence of antibodies to measles virus than those with other genotypes, but this association was not confirmed in a group of blood donors. The prevalence of antibodies to nine other common viruses, HBV, and HCV was not related to CCR5 genotype.CCR5-delta32/delta32 homozygotes are generally similar to wild-type persons. Confirmatory investigations are required to determine whether hypertension, increased lymphocyte counts, and higher hepatic enzyme levels in the presence of HCV infection represent true phenotypic expressions of this genotype. CCR5-delta32/delta32 homozygosity does not provide broad protection against viral infections.