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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.

Objective— To determine the effects of intraarticular administration of Samarium-153 (153Sm) bound to hydroxyapatite microspheres (153SmM) on an osteochondral chip–Ninduced synovitis. Study Design— Sixty days after implantation of autogenous osteochondral fragments in the middle carpal and metacarpophalangeal joints, 153SmM was administered into 1 joint of each type. The contralateral joints were used as untreated controls. Animals or Sample Population— Fifteen horses without preexisting joint disease were randomly divided into 2 groups (7 in the carpal group, 8 in the metacarpophalangeal group). Methods— Horses had osteochondral fragments that were harvested from the lateral ridge of the trochlea of the talus and implanted bilaterally into a middle carpal joint and a metacarpophalangeal joint; the opposite joint type served as a control. Sixty days later, 10 to 15 mCi of 153SmM (20 to 50 μm diam) was injected into the fragment-implanted joints. Three horses were treated with nonradioactive hydroxyapatite fragments. Horses were examined clinically until they were killed 14 or 30 days later. Control and treated joints were examined grossly and microscopically to determine the effects of 153SmM on synovial membrane and cartilage. Results— Intraarticular 153SmM caused a transient flare with lameness, effusion, and edema for 48 to 72 hours. Implanted osteochondral chips induced a synovitis characterized by variable degrees of joint damage and synovial infiltrate. Use of 153SmM resulted in synovectomy of variable depth and extent. Conclusions— Intraarticular 153SmM may be a useful method for synovectomy of inflamed synovial membrane. Clinical Relevance— With further testing, radioactive pharmaceuticals might become useful clinical treatments for persistent synovitis not responsive to conventional techniques.

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.

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.

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.

Maternal cocaine injection causes fetal hypoxemia, hypertension, and increased cerebral blood flow (CBF) in sheep. To test the hypothesis that increased fetal CBF is not due solely to fetal hypoxemia, we injected cocaine directly into a fetal vein. A single dose of cocaine [1 (group 1; n = 7) or 2 (group 2; n = 8) mg/kg i.v.] was administered to chronically catheterized, unanesthetized, near-term fetal sheep. Fetal CBF (microspheres), arterial blood pressure (BP), O2 content, and cerebral O2 consumption (CMRo2) were measured at baseline, 30 s, and 2, 5, and 15 min after fetal cocaine injection. Fetal CBF increased 27 +/- 9% (SE) at 5 min in group 1 and returned to baseline by 15 min, whereas fetal CBF increased 57 +/- 8% at 5 min and remained elevated at 15 min in group 2. Fetal BP increased at 30 min in both groups and remained increased at 2 min in group 1 and at 5 min in group 2. Cerebrovascular resistance increased at 30 s in both groups and then decreased at 5 min only in group 2. Fetal hypoxemia was observed in group 2 5 min after cocaine injection (arterial PO2 decreased 24 +/- 5%), whereas no hypoxemia was noted in group 1. CMRO2 was unchanged in group 1 but increased in group 2 at 5 min (41 +/- 10%) and was associated with an increase in cerebral O2 extraction. Increases in myocardial and adrenal blood flows and reductions in both small and large intestinal blood flows were noted at 5 min in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Tumors have heterogeneous properties, which could be explained by the existence of hierarchically and biologically distinct tumor cells such as tumor-initiating cells (TICs). This model is clinically important, as TICs are promising targets for cancer therapies. However, TICs in spontaneous B-cell lymphoma have not been conclusively identified.Tumor cells with a progenitor phenotype exist in B-cell lymphoma, reflecting a hierarchical organization.Twenty-eight client-owned dogs with previously untreated B-cell lymphoma and 6 healthy dogs.This was a prospective study. Flow cytometry was used to identify lymphoid progenitor cells (LPCs) that coexpressed hematopoietic progenitor antigens CD34, CD117, and CD133, with lymphoid differentiation markers CD21 and/or CD22 in B-cell lymphoma. The polymerase chain reaction for antigen receptor rearrangements was used to analyze clonality and relatedness of tumor populations. A xenograft model with NOD/SCID/IL-2Rγ(-/-) mice was adapted to expand and serially transplant primary canine B-cell lymphoma.LPCs were expanded in lymph nodes from 28 dogs with B-cell lymphoma compared with 6 healthy dogs (P= .0022). LPCs contained a clonal antigen receptor gene rearrangement identical to that of the bulk of tumor cells. Canine B-cell lymphoma xenografts in recipient mice that maintained LPCs in the tumors were recurrently observed.These results suggest the presence of a hierarchy of tumor cells in B-cell lymphoma as has been demonstrated in other cancers. These findings have the potential to impact not only the understanding of lymphoma pathogenesis but also the development of lymphoma therapies by providing novel targets for therapy.

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.

Summary Complete thoracic radiographic examinations were performed on 7 horses ranging in age from 24 to 60 months, followed by in-situ lung fixation. Radiographs were examined by 3 radiologists for the presence, degree and distribution of generalised pulmonary patterns within a region of interest in the caudodorsal lung. Pulmonary tissue was obtained from 12 sites within a designated volume of interest in the caudodorsal lung, corresponding to the area of interest evaluated radiographically, and examined for the presence, character and severity of microscopic lesions. Radiographic findings within the volume of interest consisted of mild to moderate bronchial, bronchointerstitial, or interstitial pulmonary patterns. Interstitial and bronchointerstitial radiographic findings were related to severity of peribronchiolar mononuclear cell infiltrates, the degree of bronchiolar mucosal plication, and alveolar capillary and peribronchial blood vessel erythrocyte content. The severity of the interstitial radiographic pattern was inversely associated with the perceived diagnostic quality of the radiographic examinations. There was no evidence of spatial variation in the severity of the microscopic changes examined in this limited pulmonary region. Inter-rater reliability between radiologists was good in the assessment of diagnostic quality of the radiographic examinations but poor in assessing severity of the primary generalised pulmonary patterns within the radiographic region of interest.

The distal phalanx and metacarpal physis of both forelimbs of 32 Thoroughbred foals 3-32 weeks of age were radiographed to identify those limbs with osseous bodies at a palmar process (PP) of the distal phalanx. Osseous bodies (ossicles) were identified radiographically in 19% of the foals. Sixteen of the 32 foals were selected for microradiographic and histological evaluation: 6 foals with radiographic evidence of ossicles and 10 foals without. Fourteen ossicles of the PP were observed radiographically. Ossicles were either a triangular bone fragment at the palmar aspect of the distal angle of the PP, or an oblong bone fragment separated from P3 by a radiolucent line extending 1-3 cm from the incisure of the PP to the solar margin. One foal had radiographic evidence of bilateral distal metacarpal physitis. Seventeen of 35 PPs examined microradiographically were considered normal, in that the dorsal and solar cortices were thin with trabecular bone orientated parallel to the cortical surfaces, and there was a depression in the dorsal cortical surface (i.e. parietal sulcus). Abnormal microradiographic findings in the other 18 PPs included a fracture line extending from the dorsal cortical surfaces and trabecular bridging of the fracture gap. The fracture line was often continuous with the parietal sulcus. Microradiographic evidence of a fracture was found in 75% of foals evaluated. Normal histological findings in 16 PPs included thin dorsal and solar cortices with trabeculae orientated parallel to the cortical surfaces, parallel-fibred dense connective tissue attachments of the deep digital flexor tendon to the solar cortical surfaces, and a neurovascular bundle associated with the parietal sulcus.(ABSTRACT TRUNCATED AT 250 WORDS)

Maternal cocaine abuse has been associated with neonatal neurological and neurobehavioral problems of unknown pathogenesis. We administered a single intravenous dose of cocaine (2 mg/kg) to 12 unanesthetized pregnant sheep; their fetuses had been catheterized in utero 2 days before the study. We measured fetal cerebral blood flow (CBF), cerebral metabolic rate of O2 (CMRO2), mean arterial blood pressure (MAP), and blood gases before and 2, 5, 15, and 30 min after maternal cocaine injection. Fetal CBF increased by 37 +/- 33% (mean +/- SD) at 5 min and returned to baseline by 15 min. Regional brain blood flow changes paralleled CBF changes with the greatest increases occurring in cerebellum (54 +/- 43%) and brain stem (54 +/- 52%). Cerebral vascular resistance was decreased for cerebellum (22%) and brain stem (19%) but was unchanged for cerebral hemispheres and caudate. Increased CBF at 5 min was associated with a 20 +/- 9% increase in fetal MAP and a 38 +/- 13% decrease in fetal arterial O2 content. Fetal CMRO2 was unchanged. There was a decrease in fetal intestinal blood flow at 2 min, an increase in myocardial, adrenal, and renal blood flow at 5 min, and no change in placental blood flow. Maternal cocaine injection causes fetal hypoxemia, hypertension, and increased CBF. Possible mechanisms for cerebral vasodilation (in some areas) include hypoxemia, impaired autoregulatory response to increased blood pressure, and/or direct or indirect vascular effects of cocaine or its metabolites.

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.

The aim of this study was to examine inhibin production in granulosa-theca cell tumours (GTCT). The experimental aims were: (i) to determine GTCT cell types that produce inhibin alpha- and betaA-subunits; (ii) to determine whether alpha- and betaA-subunit forms differ in GTCT fluid and normal equine follicular fluid (eFF); and (iii) to determine whether dimeric inhibin (alpha betaA) is present in GTCT plasma and tumour fluid. Plasma, tumour fluid and tumour tissue were collected from mares (n=6) with GTCT. Plasma and eFF were collected during the follicular phase from mares (n=4) undergoing normal cycles. Immunohistochemical examination of GTCT tumour sections showed strong inhibin alpha- and betaA-Subunit immunostaining in granulosa cells and polyhedral-shaped cells in the thecal-stromal layer. The presence of polyhedral-shaped cells was related to testosterone concentration in tumour fluid. Low molecular weight alpha-subunit forms were less abundant in tumour fluid than in eFF, whereas the amounts of betaA-subunit forms were similar in tumour fluid and eFF. Concentrations of betaA were increased in plasma from mares with GTCT and similar in tumour fluid and eFF. In summary, lower molecular weight alpha-subunit forms were less prominent in GTCT fluid than in eFF and concentrations of betaA were higher in GTCT plasma than in control plasma.

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.

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.

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.

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.

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.

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.

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.

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.

A high human immunodeficiency virus (HIV) load may increase the probability of HIV transmission by sexual contact, but the association of virus load of hepatitis C virus (HCV) with risk of HCV transmission is uncertain. HIV and HCV virus loads were examined in hemophilic men, as were risks of HIV and HCV transmission to their female partners in a hemophilia cohort in which most subjects are dually infected. A higher HIV load was associated with an increased risk of HIV transmission (odds ratio [OR], 1.31 per log10 increase in virus load). A higher HCV load was associated, although not significantly, with an increased risk of HCV transmission (OR, 1. 42 per log10). HCV load was higher among dually infected men than in those infected with HCV alone (P=.001). However, much larger studies are needed to clearly show whether HIV/HCV coinfection significantly increases the risk of HCV transmission to female partners.

In 1997 CA 125 celebrated its 15th anniversary. Since the discovery of OC 125, an antibody that recognizes CA 125, by Bob Bast and his colleagues, considerable progress has been made toward the development of more sensitive and more precise assay systems. However, a great deal of mystery still remains about the CA 125 molecule and further enlightenment will probably not come until the gene for CA 125 is cloned and the complete open reading frame for the peptide core identified. In the meantime, we have learned some structural features of the CA 125 molecule as well as a little about its regulation and the requirements for its secretion or release from epithelial derived cells in cultures. The CA 125 molecule is almost certainly a glycoprotein with a predominance of O-linkages. It is heterogeneous with regard to both size and charge, most likely due to continuous deglycosylation of side chains during its life-span in bodily fluids. It exists as a very large complex (perhaps as much as 4 million daltons) under natural conditions. The core CA 125 subunit is in excess of 200,000 daltons and it retains the capacity to bind both OC 125 class antibodies and M 11 class antibodies. As a denatured purified subspecies the CA 125 molecule appears to autoproteolyse presumably due to an endogenous protease activity inherent to the molecule. Release or secretion of CA 125 appears directly linked to the epithelial growth factor receptor signal transduction pathway. Prior to its release from cultured cells, CA 125 is phosphorylated (at either/both serine and threonine) and dephosphorylated when released. To stimulate discussion on the regulation of CA 125 synthesis, its secretion and its structural configuration, we have presented a model of a theoretical CA 125 molecule. Perhaps it will provide a focus of attention until the CA 125 gene is cloned and the real molecule is described.

This study sought to determine if extensive trimming of the front hooves of foals results in a higher incidence of palmar process fractures compared to untrimmed foals, and to characterise the clinical course of foals with palmar process fractures with physical findings, hoof measurements and radiography. Twenty foals age 4-8 weeks of multiple breeds were examined every 2 weeks over a 12 week period. Ten foals had both front hooves extensively trimmed every 4 weeks, while 10 foals remained untrimmed. Palmar process fractures occurred in 4 trimmed and 3 untrimmed foals. Four foals with fractures had brief lameness (Grades I-II/V) and hoof tester sensitivity was found inconsistently with fractures. All foals with fractures were sound at the end of the study. Fractures healed based on radiographic evaluations in an average of 8.4 weeks. Two of 3 foals with fractures developed club-footed conformation. None of the measured hoof parameters significantly differed between foals with and without fractures. We conclude that extensive trimming of the heels did not appear to affect the occurrence of palmar process fractures in this group of foals.

Population surveys of Sulawesi crested black macaques (Macaca nigra) were conducted on the Indonesian islands of Sulawesi and Bacan in 1992-1994 to assess the status of natural populations and determine habitat and anthropogenic factors affecting their population densities. We surveyed five sites for primates, including undisturbed and disturbed habitats. Data were collected on habitat structure and composition at two undisturbed and one disturbed forest site in which the primates were surveyed. The highest density of macaques was found in primary forest at Gunung Sibela Nature Reserve on Bacan (170.3 individuals/km2). Population density in logged forest on Bacan was high but significantly less than primary forest (133.4 individuals/km2). The high density of crested black macaques in primary forest on Bacan is best explained by the high carrying capacity found in primary forest. The lower food quantity and quality of food resources found in logged forest correlated with lower primate densities compared to primary forest. However, the large population of macaques in logged forest demonstrates the conservation value of such forest. Densities on Sulawesi at Tangkoko-Batuangas-DuaSudara Nature Reserve (TBDS) showed a continuing decline since earlier surveys. Primate densities were highest near the protected center of Tangkoko Reserve (66.7 individuals/km2). The peripheral areas of Batuangas and DuaSudara, even though adjacent and continuous, showed lower population densities of 46.4 and 23.5 individuals/km2, respectively. The best explanation for the continued decline of Macaca nigra populations at TBDS is hunting. Unless conservation measures are implemented immediately, M. nigra on Sulawesi risks extinction in the near future.

This study prospectively evaluates the likelihood of a return of military personnel to full duty after anterior cruciate ligament reconstruction. We report the results of 120 active duty military patients who underwent anterior cruciate ligament reconstruction with autogenous patella tendon. Mean follow-up was 29 months (range, 24-65 months). Time from injury to reconstruction was6 months in 90% of patients. Final Lysholm scores averaged 89 (range, 29-100). We found that 77% of patients returned to full duty, whereas 23% of patients were medically discharged from military service. The patient age, military rank, time from injury to surgery, and KT-1000 measurements did not correlate with either the Lysholm score or return to duty (p = 0.05). Severe chondromalacia (Outerbridge III or IV) did correlate with poor result (p = 0.043), and Lysholm score did correlate with return to duty (p = 0.003). Anterior cruciate ligament reconstruction offers a higher likelihood of return to full military duty than nonoperative treatment in a similar study.

Sixteen patients with cerebral palsy causing equinovarus deformity were treated surgically. All of these patients underwent preoperative gait analysis by using a CODA-3 motion analyzer. The equinus deformity was assessed by using sagittal kinematics, and in particular, the range of movement of the ankle during stance phase and the maximal dorsiflexion during swing. The varus deformity was assessed by the degree of varus of the foot at prepositioning. The degree of varus was obtained by measuring the angle generated between the plane of progression and a line joining a marker on the heel to a marker on the fifth metatarsal in the transverse plane. All patients underwent split tibialis posterior tendon transfer and, in 13, this was combined with tendo calcaneus lengthening. Clinical assessment and gait analysis repeated 1 year postoperatively confirmed good outcome after split tibialis posterior tendon transfer in combination with gastrocnemius lengthening. This was confirmed by using sagittal kinematic analysis and quantitative assessment of the degree of varus of the foot at the time of prepositioning.

The recently cloned gene p16 (MST1) has been identified as a putative tumor suppressor gene that binds to CDK4 and CDK6 (cyclin-dependent kinases), preventing their interaction with cyclin D1 and thereby preventing cell cycle progression at the G1 stage. In addition, the p16 gene has been shown to have a high frequency of mutation in some tumor cell lines; however, it has also been shown that a much lower frequency of mutation occurs in primary tumors. This study investigated the mRNA expression level and mutation status of the p16 gene in ovarian tumors.We performed quantitative polymerase chain reaction and direct cDNA sequencing analysis. To confirm the p16 protein level in ovarian tumors, Western blotting and immunohistochemical staining were performed. Expression levels of mRNA for the p16 gene relative to the beta-tubulin gene were examined in 32 ovarian tumors (24 carcinomas, six low malignant potential tumors, and two benign tumors) and six normal ovaries.The mRNA expression level of p16 was significantly elevated in 28 ovarian tumors (22 carcinomas, five low malignant potential tumors, and one benign tumor) compared with that of normal ovaries. Western blotting analysis and immunohistochemical staining confirmed elevated p16 protein levels in ovarian tumor samples. Among 32 ovarian tumors, cDNA sequencing of the p16 gene showed no p16 mutation resulting in a coding error, although one silent mutation and three polymorphisms were found.Although p16 is seldom mutated in ovarian tumors, the overexpression of p16 in most ovarian tumor cases indicates a dysfunction in the regulatory complex for G1 arrest. Therefore, overexpression of p16 may be an important early event in the neoplastic transformation of the ovarian epithelium.

Anesthetic induction and maintenance with propofol are associated with decreased blood pressure that is, in part, due to decreased peripheral resistance. Several possible mechanisms whereby propofol could reduce peripheral resistance include a direct action of propofol on vascular smooth muscle, an inhibition of sympathetic activity to the vasculature, or both. This study examined these two possibilities in humans by measuring the forearm vascular responses to infusions of propofol into the brachial artery (study 1) and by determining the forearm arterial and venous responses to systemic (intravenous) infusions of propofol after sympathetic denervation of the forearm by stellate blockade (study 2).Bilateral forearm venous occlusion plethysmography was used to examine forearm vascular resistance (FVR) and forearm vein compliance (FVC). Study 1 used infusion of intralipid (time control) and propofol at rates between 83 and 664 micrograms/min into the brachial artery of 11 conscious persons and compared responses to arterial infusions of sodium nitroprusside (SNP) at 0.3, 3.0, and 10 micrograms/min. Venous blood from the infusion arm was assayed for plasma propofol concentrations. In study 2, after left stellate block (12 ml 0.25% bupivacaine + 1% lidocaine), six participants were anesthetized and maintained with propofol infusions of 125 and 200 micrograms.kg-1.min-1. Simultaneous right forearm (unblocked) blood flow dynamics served as the time control. In three additional conscious participants, intrabrachial artery infusions of SNP and nitroglycerin, both at 10 micrograms/min, were performed before and after stellate blockade of the left forearm to determine whether the sympathetically denervated forearm vessels could dilate beyond the level produced by denervation alone.In study 1, infusion of intralipid or propofol into the brachial artery did not change FVR or FVC. Sodium nitroprusside significantly decreased FVR in a dose-dependent manner by 22 +/- 5%, 65 +/- 3%, and 78 +/- 2% (mean +/- SEM) but did not change FVC. During the incremental propofol infusions, plasma propofol concentrations increased from 0.2 to 10.1 micrograms/ml and averaged 7.4 +/- 1.1 micrograms/ml during the highest infusion rate. In study 2, stellate ganglion blockade decreased FVR by 50 +/- 6% and increased FVC by 58 +/- 10%. Propofol anesthesia at 125 and 200 micrograms.kg-1.min-1 progressively reduced mean arterial pressure. In the arm with sympathetic denervation, FVR and FVC showed no further changes during propofol anesthesia, whereas in the control arm FVR significantly decreased by 41 +/- 9% and 42 +/- 7%, and FVC increased significantly by 89 +/- 27% and 85 +/- 32% during 125 and 200 micrograms.kg-1.min-1 infusions of propofol, respectively. In the three additional conscious participants, intraarterial infusion of SNP and nitroglycerin (TNG) after the stellate blockade resulted in a further decrease of FVR and a further increase of FVC.In contrast to SNP infusions, propofol infusions into the brachial artery of conscious persons caused no significant vascular responses, despite the presence of therapeutic plasma concentrations of propofol within the forearm. The effects of propofol anesthesia on FVR and FVC are similar to the effects of sympathetic denervation by stellate ganglion blockade. Thus the peripheral vascular actions of propofol appear to be due primarily to an inhibition of sympathetic vasoconstrictor nerve activity.

We wished to ascertain whether the measurement of maternal serum human chorionic gonadotropin (MShCG) in the serum of pregnant women with unexplained elevations of maternal serum alpha-fetoprotein (MSAFP) would more precisely define those women at risk of adverse pregnancy outcomes. MShCG was measured in samples of serum obtained from women in the second trimester of pregnancy who had elevated MSAFP, normal Level II ultrasounds, and normal fetal karyotypes. Based on the characteristics of a receiver-operator curve for MShCG and birth weight, patients were divided into two groups and pregnancy outcomes were compared. Pregnant women with an unexplained elevation in MSAFP, who also had an abnormal MShCG (or = 0.5 MoMor = 2.5) were at significantly greater risk of delivering a low-birth-weight infant compared to women with a normal MShCG (43% and 15%, respectively; P = 0.013). They were also more likely to deliver a preterm infant (48% and 11.9%), respectively; P = 0.001). In the prediction of low birth weight, an abnormal MShCG had a sensitivity of 50%, a specificity of 81%, and a positive predictive value of 43%; in the detection of preterm delivery the values were 59%, 88%, and 48%, respectively. These findings suggest that in pregnant women with a second trimester unexplained elevation in MSAFP, abnormal MShCG levels may identify a group of women at high risk of preterm delivery or delivery of a low-birth-weight infant.

To determine the potential clinical usefulness of duplex Doppler estimation of arcuate artery resistive index (a measure of intrarenal blood flow impedance) for diagnosis of aminoglycoside-induced nephrotoxicosis.30 adult, female, mixed-breed dogs, allotted to 3 groups of 10 dogs each as: toxic dosage of gentamicin, therapeutic dosage of gentamicin, and saline solution sham equivalent in volume to that of the toxic dosage of gentamicin.After baseline screening to establish normalcy (serum biochemical analysis, endogenous creatinine clearance determination, urinalysis, urine protein-to-creatinine ratio, urine culture, gray-scale sonography, and percutaneous ultrasound-guided renal biopsy), results of arcuate artery resistive index determination were compared with serum creatinine and urine specific gravity values on a Monday-Wednesday-Friday data collection schedule for 10 days. Endogenous creatinine clearance determination, ultrasound-guided renal biopsy, and urine culture were repeated at the end of data collection in all 3 groups.Significant differences in resistive index measurements were not observed, despite clinicopathologic and renal biopsy results compatible with severe acute tubular necrosis in dogs of the toxic dosage group.Duplex Doppler sonography of arcuate artery blood flow impedance, expressed as the resistive index, appears to have poor clinical usefulness as a diagnostic tool in this disorder.Normal arcuate artery resistive index values obtained in dogs for which aminoglycoside-induced nephrotoxicosis is suspected do not exclude the disorder. If abnormal arcuate artery resistive index values are obtained for such dogs, further evaluation for nephropathies other than aminoglycoside-induced nephrotoxicosis may be considered.

Thymidine phosphorylase (TP), also known as platelet-derived endothelial cell growth factor, has been implicated in bladder cancer angiogenesis. To examine its role more clearly, we have quantified and localized its expression using Western analysis and immunohistochemistry in a series of 105 bladder cancers. We have also assessed the relationship between TP expression and other tumor parameters including quantitative angiogenesis, p53 status, ploidy, and survival. By Western analysis, TP expression was 5-fold higher in tumors than in normal bladder samples (P0.02). Expression was 15-fold higher in invasive tumors than in normal bladder (P0.001) and 8-fold higher than in superficial tumors (P0.005). Immunohistochemistry of the tumors showed TP was present in the neoplastic epithelium in 27% of the tumors, in the inflammatory cells in 72% of the tumors, in stromal cells in 30% of the tumors, and in tumor-associated endothelium in 11% of the tumors. Expression by Western blotting and immunohistochemistry was significantly up-regulated in tumors compared with normal bladder (P0.05). Tumor cell TP expression correlated with tumor grade (P0.02), but there was no correlation between tumor cell TP expression and tumor stage (P = 0.46), ploidy (P = 0.52), p53 expression (P = 0.9), tumor vascularity (P = 0.8), relapse-free survival (P = 0.57), or overall survival (P = 0.94). TP protein is expressed in bladder cancers, and expression is associated with an aggressive phenotype. Because TP can activate a number of cytotoxic agents, it provides a potential therapeutic target in bladder cancer.

Background The speed, quality, and cost of mask induction of anesthesia and laryngeal mask airway insertion or tracheal intubation were studied in young non-premedicated volunteers given high inspired concentrations of sevoflurane (6 to 7%). Methods Twenty healthy persons who were 19 to 32 years old participated three times, received 6 l/min fresh gas flow, and were randomized to receive 6 to 7% sevoflurane in 66% nitrous oxide/28% oxygen by face mask until tracheal intubation (treatment 1) or until laryngeal mask airway insertion (treatment 3), or 6 to 7% sevoflurane without nitrous oxide to tracheal intubation (treatment 2). Participants exhaled to residual volume and took three vital capacity breaths of the gas mixture; thereafter ventilation was manually assisted. The time of exposure to the inhaled gas was varied for consecutive participants. It was either increased or decreased by 30-sec increments based on the failure or success of the preceding volunteer's response to laryngoscopy and intubation after a preselected exposure time. Failure was defined as poor jaw relaxation, coughing or bucking, or inadequate vocal cord relaxation. Results Loss of the lid-lash reflex in unpremedicated young volunteers was achieved in 1 min and did not differ among groups. Average time (and 95% confidence interval) for acceptable conditions for LMA insertion was achieved in 1.7 (0.7 to 2.7) min, and all participants had an immediate return of spontaneous ventilation. The time for acceptable tracheal intubating conditions after manual hyperventilation by mask was 4.7 (3.7 to 5.7) min and 6.4 (5.1 to 7.7) min in treatments 1 and 2, respectively. There were no cases of increased secretions or laryngospasm. The incidence of breath holding and expiratory stridor ("crowing") was 7.5% and 25%, respectively, during treatment 1 and 15% and 40%, respectively, during treatment 2. Conclusions The induction of anesthesia to loss of lid reflex in young non-premedicated adults approaches the speed of intravenous induction techniques. No untoward airway responses were noted during mask induction of anesthesia with a three-breath technique. In response to intubation, no adverse airway responses, including jaw tightness, laryngospasm, and excessive coughing or bucking, occurred in participants whose duration of mask administration of sevoflurane met the appropriate times (as determined in this study).

A prospective study of the bicycle spoke injury over a 1-year period included a total of 71 spoke injuries. Of these, 67 injuries occurred on an adult bicycle and four occurred on a child's bicycle. All children sustained ankle and foot injuries, which consisted of contusion and superficial abrasion (N = 45), skin loss (N = 10), skin laceration (N = 4), and undisplaced fractures (N = 12). A biomechanical study was conducted to investigate the use of a protective cover over the wheel to prevent the foot from slipping between the spokes. Wind resistance studies showed that a cover with a mesh size of 10 mm hexagonal could prevent this and at the same time stop the cover from acting as a sail if a flat cover without holes was used instead. The mesh cover, however, will prevent the toes from entering between the spokes but will not prevent the foot from becoming jammed between the wheel and the fork. To prevent this, a plastic shield to bridge the gap between the fork and the horizontal upright has been designed. With these modifications, the bicycle spoke injury can become an injury of the past.

Six 15- to 20-year-old obese cynomolgus monkeys were determined to have diabetes mellitus. These monkeys were hyperglycemic and hypertriglyceridemic, yet remained nonketotic for several years before requiring clinical intervention. A significant decrease in glucose disappearance and an increased area under the glucose disappearance curve were found in response to intravenous glucose tolerance testing. Basal hyperinsulinemia was found in three animals that, in response to glucose stimulation, had a blunted insulin response, resulting in an overall decrease in the area under the insulin curve. Two animals died during the study and had extensive amyloid infiltration of pancreatic islets. The combined findings of old age, obesity, hyperinsulinemia, improvement in response to caloric restriction, and islet amyloidosis are consistent with type 2 diabetes mellitus.

Cardiac transplantation has become the treatment of choice for end stage heart disease. In 1990 2,000 transplants were performed worldwide. Orthopaedic Surgeons will be asked with increasing frequency to evaluate and treat bone and soft tissue problems with these patients. Orthopaedic service at the Mater Hospital has been involved in the follow-up treatment of orthopaedic complications in 46 transplant patients over a six year period. Thirty eight were male and eight were female. The ages were between 12 years and 65 years (mean 44.3). Nine (20%) of these patients developed thirteen orthopaedic complications: A vascular Necrosis of the hip (AVN) (4), Soft tissue infections (3), Osteoporosis (2), Stress Fractures (2), Osteomyelitis (1) and Ostomalacia (1). The mode of presentation, investigation and management of orthopaedic problems particular to these patients is described. Most patients who develop bony complications have had increased doses of steroids for episodes of rejection. This study highlights the special features of this patient population that require modification of the treatment approach such as the need to avoid the drug Erythromycin and the increased risk of AVN of the hip in patients who require high dose steroids.