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S Williams

Publications and source records attributed to S Williams.

At least 127 records · Page 7Linked to original sources

Plasma transforming growth factor beta(1) and platelet activation: implications for studies in transplant recipients.

BACKGROUND: Evidence from animal models supports the hypothesis that dysregulated transforming growth factor beta(1) (TGF beta(1)) expression plays a role in chronic allograft rejection, the progression of diabetic nephropathy and fibrotic glomerulopathies. However, more evidence is required to support this hypothesis in man, and the current literature concerning blood TGF beta(1) levels in clinical studies is highly confused. We have investigated: (i) the hypothesis that the widespread practice of activating clinical samples prior to measurement of TGF beta(1) is detecting the platelet-released pool of TGF beta(1), artefactually generated on venepuncture and unrepresentative of the real circulating in vivo TGF beta(1) pool; and (ii) the effect of different immunosuppressive drugs on apparent TGF beta(1) plasma levels. METHODS: The effect of two different venepuncture procedures on plasma TGF beta(1) was compared in 10 healthy volunteers, one procedure designed to minimize platelet activation and the other representing standard venepuncture practice in a clinic situation. Blood samples from 52 renal transplant recipients on either cyclosporine or tacrolimus immunosuppression were taken by standard venepuncture to investigate the effect of immunosuppressive drugs on plasma TGF beta(1). Plasma TGF beta(1) and beta thromboglobulin were measured by ELISA. RESULTS: Among 10 healthy volunteers who underwent two different methods of venepuncture, eight of 10 had undetectable levels of TGF beta(1) (<100 pg/ml) under conditions that minimize platelet activation. In contrast, all 10 paired plasma samples collected by vacutainer had measurable TGF beta(1) (median 7.70 ng/ml, interquartile range 5.87-13.64 ng/ml) following acid/ urea activation. The median beta TG level (a measure of platelet degranulation) was 0.71 microg/ml (interquartile range 0.53-1.19 microg/ml) in the special collections compared with 3.39 microg/ml (interquartile range 2.27-4.33 microg/ml) in the vacutainer samples (P=0.0029). Among 52 allograft recipients there was a significantly higher mean TGF beta(1) level in plasma from patients on cyclosporine therapy compared with patients on tacrolimus (28,090+/-26,860 pg/ml vs 7173+/-10 610 pg/ml, respectively; P<0.002). Mean plasma beta TG levels were also significantly higher during cyclosporine therapy compared with tacrolimus (8.14+/-5.54 microg/ml vs 3.66+/-3.32 microg/ml, respectively; P<0.002). However, when TGF beta(1) values were corrected for the degree of platelet activation (by factoring with beta TG) there was no significant difference between TGF beta(1) levels on cyclosporine or tacrolimus (4117+/-2993 pg/microg beta TG vs 2971+/-658 pg/microg beta TG, respectively; P=0.294). CONCLUSIONS: To avoid erroneous hypotheses concerning TGF beta(1) and perpetuating confusion in the literature over levels in health and disease, it is imperative that proper internal controls for platelet activation are used. The effects of experimental treatments and drugs on platelet biology must be rigorously controlled when attempting to measure and interpret plasma levels of TGF beta(1) in clinical practice.

Adult↗

Effects of perceptions and mentorship on pursuing a career in academic medicine in obstetrics and gynecology.

PURPOSE: To understand the perceptions of residents and Fellows in obstetrics and gynecology about the impacts of race or ethnicity, gender, and mentorship experiences on pursuing careers in academic medicine. METHOD: Two surveys were administered: one to a sample of 2,000 Fellows of the American College of Obstetricians and Gynecologists, and one to the 4,814 obstetrics and gynecology residents taking the 1998 in-training examination. The questionnaires asked about demographics, perceptions about careers in academic medicine, and residents' experiences with mentorship. RESULTS: Response rates were 96.8% for residents and 40.6% for FELLOWS: Of the residents, 26.1% indicated they would not consider a career in academic medicine. First-year women residents were more inclined to pursue careers in academic medicine than were first-year men (p =.042), but their interest declined during residency. Women residents (43%)-especially minorities-felt that men were mentored and recruited more for faculty positions, while men (38%) felt that women were mentored and recruited more. Fellows' reports of recruitment did not differ by gender. Most white residents did not perceive racial or ethnic bias in mentoring or recruiting, while most non-white residents did. Almost one third of non-white women residents felt that supervisors were more likely to condescend to women and minority individuals. CONCLUSIONS: It is likely that neither men nor women residents in obstetrics and gynecology receive adequate mentorship for careers in academic medicine. Perceptions of bias are a serious barrier to developing racial, ethnic, and gender diversity in leadership positions.

Attitude of Health Personnel↗

Independent AVA?

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Animals↗

Magnetic resonance markers of ischaemia: their correlation with vasodilatory reserve in patients with carotid artery stenosis and occlusion.

OBJECTIVES: Better methods of identifying patients with asymptomatic carotid artery stenosis who are at high risk of stroke are required. It has been suggested that proton magnetic resonance spectroscopy (MRS) may allow the identification of ongoing ischaemia in this patient group by the detection of a potentially reversible reduction of N-acetyl aspartate (NAA), a presumed marker of neuronal integrity, and the presence of lactate, a marker of anaerobic metabolism. Previous studies have reported metabolite ratios rather than absolute concentrations. This study was performed to determine if NAA was reduced ipsilateral to carotid stenosis or occlusion, and if its concentration was related to carbon dioxide reactivity, a marker of cerebrovascular reserve. METHODS: Twenty one patients with unilateral carotid stenosis (>70%) or occlusion were studied. Single voxel proton MRS was performed in the ipsilateral and contralateral hemispheres, with the voxel positioned in the arterial borderzone region between the middle and anterior cerebral artery territories. Absolute quantification of metabolite concentrations was performed. Cerebrovascular reactivity to 6% carbon dioxide was determined in both middle cerebral artery territories using transcranial Doppler ultrasonography. RESULTS: Mean (SD) cerebrovascular reactivity was significantly lower in the stenosed compared with the contralateral hemisphere (13.3 (7.7) v 19.2 (8.2)%/kPa, p=0.002). There were no significant differences in the absolute concentrations of NAA, choline, or creatine between the ipsilateral and contralateral hemispheres (for example, NAA 10.1 (1.1) v 10.5 (1.1) mmol/l, p=0.1). No lactate peak was seen in any spectra. For each metabolite measured, there was no correlation between the absolute concentration and cerebrovascular reactivity for either hemisphere. CONCLUSIONS: In patients with carotid stenosis and occlusion we found no evidence that chronic hypoperfusion is associated with a reduction in NAA or the presence of lactate. Magnetic resonance spectroscopy is unlikely to help in the selection of patients with asymptomatic carotid stenosis for endarterectomy.

Aged↗

Audiometric notch as a sign of noise induced hearing loss.

OBJECTIVES: To investigate the relation between different types of exposure to noise and a classic sign of noise induced hearing loss (NIHL), the audiometric notch. METHODS: The study sample had exposure to both continuous and impulse noise and was drawn from a population of electrical transmission workers. Audiograms, taken as part of a hearing conservation programme, were read by three clinicians experienced in the assessment of NIHL. Working independently and using their clinical judgment, they were asked to identify localised increases in the threshold of hearing (audiometric notches) which they would attribute to noise, had a suitable history of exposure been elicited. Prevalent cases of NIHL were identified by the presence of a notch in either ear. Risk factors for NIHL were assessed by a questionnaire which sought information about exposure to air blast circuit breaker noise; firearms; explosions, and continuous noise. The odds of exposure to these factors in those with and without hearing loss were calculated, and odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated by logistic regression. RESULTS: Of the 648 questionnaires sent out 357 were returned, a response rate of 55%. Of these, at least two out of the three assessors identified 175 (49%) people with a notch at any audiometric frequency. There was no association between these cases and the NIHL risk factors identified by the questionnaire, but a further frequency specific analysis showed a small proportion of people (15 (4%)) with notches at 4 kHz who had the expected associations with exposure to noise and a significant OR for firearms of 4.25 (95% CI 1.28 to 14.1). The much larger proportion of people with 6 kHz notches (110 (31%)) did not show these associations. CONCLUSIONS: To diagnose NIHL it is important to elicit a detailed and accurate history of exposure to noise: although the notch at 4 kHz is a well established clinical sign and may be valuable in confirming the diagnosis, the 6 kHz notch is variable and of limited importance.

Audiometry↗

Structural abnormalities in frontal, temporal, and limbic regions and interconnecting white matter tracts in schizophrenic patients with prominent negative symptoms.

OBJECTIVE: Imaging studies of schizophrenia have repeatedly demonstrated global abnormalities of cerebral and ventricular volumes. However, pathological changes at more local levels of brain organization have not yet been so clearly characterized because of the few brain regions of interest heretofore included in morphometric analyses as well as heterogeneity of patient samples. METHOD: Dual echo magnetic resonance imaging (MRI) data were acquired at 1.5 T from 27 right-handed patients who met DSM-IV criteria for schizophrenia with enduring negative symptoms and from 27 healthy comparison subjects. Between-group differences in gray and white matter volume were estimated at each intracerebral voxel after registration of the images in standard space. The relationship between clinical symptom scores and brain structure was also examined within the patient group. Spatial statistics and permutation tests were used for inference. RESULTS: Significant deficits of gray matter volume in the patient group were found at three main locations: 1) the left superior temporal gyrus and insular cortex, 2) the left medial temporal lobe (including the parahippocampal gyrus and hippocampus), and 3) the anterior cingulate and medial frontal gyri. The volume of these three regions combined was 14% lower in the patients relative to the comparison subjects. White matter deficits were found in similar locations in the left temporal lobe and extended into the left frontal lobe. The patient group showed a relative excess of gray matter volume in the basal ganglia. Within the patient group, basal ganglia gray matter volume was positively correlated with positive symptom scores. CONCLUSIONS: Anatomical abnormalities in these schizophrenic patients with marked negative symptoms were most evident in left hemispheric neocortical and limbic regions and related white matter tracts. These data are compatible with models that depict schizophrenia as a supraregional disorder of multiple, distributed brain regions and the axonal connections between them.

Adult↗

Superior temporal gyrus abnormalities in early-onset schizophrenia: similarities and differences with adult-onset schizophrenia.

OBJECTIVE: The superior temporal gyrus is associated with developmental mechanisms of brain lateralization and the pathogenesis of language-related schizophrenic symptoms. It therefore lends itself to investigation of developmental deviance in the early onset of schizophrenia. METHOD: Using stereological methods, the authors obtained bilateral measurements of the superior temporal gyrus (total, gray matter, and white matter volumes) from 40 adolescents with recent-onset schizophrenia and an equal number of matched healthy volunteers. Symptoms were rated by using the Positive and Negative Syndrome Scale. RESULTS: The total and gray matter volume of the right superior temporal gyrus was significantly lower in patients with early-onset schizophrenia than in the healthy volunteers, even after differences in whole brain volume were controlled. Bilateral superior temporal gyrus volumes were positively correlated with the age at onset of psychosis, while severity of thought disorder and hallucinations were inversely related to right superior temporal gyrus volume. CONCLUSIONS: In patients with early-onset schizophrenia, the predominantly right-sided volumetric abnormalities found in the superior temporal gyrus may reflect a particularly early neurodevelopmental disruption. The relationship between language-related symptoms and superior temporal gyrus volume is similar to that seen in adult-onset cases but not as lateralized.

Adolescent↗

Obturator dislocation of the hip.

We describe two patients with obturator dislocation of the hip which was irreducible by described techniques of closed reduction. The first required open reduction using the iliofemoral approach with release of rectus femoris. The second was treated on a traction table which allowed disengagement of the head and, when combined with simultaneous lateral traction, adduction and gradual release of the longitudinal traction, facilitated a smooth reduction. Since the hip is stable in flexion, early mobilisation in an extension-limiting brace avoids the prolonged bed rest traditionally recommended for this injury.

Adult↗

Randomized controlled trial of home-based exercise training to evaluate cardiac functional gains.

There is evidence that multiple benefits can be obtained through exercise training that leads to increases in peak oxygen consumption (V(O(2))). It is unclear whether significant improvements can also be achieved through unsupervised low-budget home-based training regimes, especially in terms of cardiac functional gains. A randomized cross-over trial was conducted to investigate the effects of a home-based unsupervised exercise training programme of moderate intensity on aerobic capacity, cardiac reserve and peak cardiac power output in healthy middle-aged volunteers. Nine subjects with no known cardiovascular diseases performed symptom-limited treadmill cardiopulmonary exercise tests after an 8-week period of exercise training, and results were compared with those obtained after a similar 'non-exercising' control period. Cardiac output was measured non-invasively during exercise tests using the CO(2)-rebreathing method. With exercise training, resting heart rate decreased significantly from 88.3+/-3.4 to 78.7+/-3.2 beats.min(-1) (P<0.05), heart rate at a submaximal workload (V(O(2))=1.5 litres.min(-1)) decreased from 125.5+/-2.4 to 115.5+/-1.6 beats.min(-1), and peak V(O(2)) increased by 9% from 2.62+/-0.19 to 2.85+/-0.18 litres.min(-1) (P<0.01). Baseline cardiac power output was 1.11+/-0.05 W, and this remained unchanged with training. Peak cardiac power output increased by 16% from 4.1+/-0.3 to 4.7+/-0.3 W (P<0.001), and cardiac reserve increased by 21% (P<0.01). A major contribution to these increases was from the 11% increase in stroke volume, from 100.1+/-5.3 to 111.2+/-6.2 ml (P<0.001). All subjects reported more positive perceptions of their health (P<0.05), fitness (P<0.01) and levels of activity (P<0.01) after the training period. These results show that motivated subjects undergoing low-budget unsupervised home-based exercise training of moderate intensity can derive benefit in terms of symptoms, aerobic capacity and cardiac functional reserve.

Analysis of Variance↗

Identifying, educating the pre-ESRD patient.

Clinicians want the best for their patients, including more timely and thorough education on RRT to help patients cope with and adjust to their chronic disease. The predicted patient growth over the next decade will place an even greater demand on these health care professionals. Supplementary methods to support patient education must be found. Associations, including the NKF, AKF, and the AAKP have created ways to identify and educate patients earlier. Industry, associations, and clinicians must come together as a renal community to coordinate their efforts, keeping the interest of the patients foremost. This will ensure that patients are identified early enough to have timely access to complete information and are taking an active role in their own care. This integrated and collaborative approach will result in more prepared and empowered pre-ESRD patients and, ultimately, improved quality of care and quality of life.

Humans↗

It's just different in the country: postnatal depression and group therapy in a rural setting.

The treatment of postnatal depression (PND) via group therapy is an accepted practice in Sydney and other metropolitan areas throughout Australia. This article analyses the difficulties faced in the importation of this urban-developed treatment model into a rural setting. In 1995, this program was established in a major rural centre of New South Wales (NSW) and drew participants from the regional centre, surrounding rural properties, towns and villages. Participation in the program resulted in significant lowering or absences of depressive episodes following treatment. But beyond this significant aspect of a positive response to this treatment program is a fascinating aspect of differences between the rural and urban groups in this population. The differences occurred in group formation, group process and attitudes of the participants. We would suggest that group leaders in rural PND programs face more resistance to the idea of groups for therapeutic intervention, need to draw different lines between personal and professional boundaries from their urban counterparts and are confronted with participants who adhere more strongly to the prevailing mythology of motherhood. This mythology may increase the likelihood and intensity of postnatal depression and cause greater resistance to cognitive restructuring skills, which are essential for challenging thoughts that enhance depression.

Depression, Postpartum↗

Inhibitory role for dual specificity phosphatase VHR in T cell antigen receptor and CD28-induced Erk and Jnk activation.

The 21-kDa dual specific protein phosphatase VH1-related (VHR) is one of the smallest known phosphatases, and its function has remained obscure. We report that this enzyme is expressed in lymphoid cells and is not induced by T cell antigen receptor like other dual specificity phosphatases. Introduction of exogenous VHR into Jurkat T cells caused a marked decrease in the transcriptional activation of a nuclear factor of activated T cells and an activator protein-1-driven reporter gene in response to ligation of T cell antigen receptors. The inhibition was dose-dependent and was similar at different doses of anti-receptor antibody. Catalytically inactive VHR mutants caused an increase in gene activation, suggesting a role for endogenous VHR in this response. In contrast, the activation of a nuclear factor kappaB-driven reporter was not affected. The inhibitory effects of VHR were also seen at the level of the mitogen-activated kinases Erk1, Erk2, Jnk1, Jnk2, and on reporter genes that directly depend on these kinases, namely Elk, c-Jun, and activator protein-1. In contrast, p38 kinase activation was not affected by VHR, and p38-assisted gene activation was less sensitive. Our results suggest that VHR is a negative regulator of the Erk and Jnk pathways in T cells and, therefore, may play a role in aspects of T lymphocyte physiology that depend on these kinases.

CD28 Antigens↗

Radiation exposure to the spine surgeon during fluoroscopically assisted pedicle screw insertion.

STUDY DESIGN: In vitro study to determine occupational radiation exposure during lumbar fluoroscopy. OBJECTIVES: To assess radiation exposure to the spine surgeon during fluoroscopically assisted thoracolumbar pedicle screw placement. SUMMARY OF BACKGROUND DATA: Occupational radiation exposure during a variety of fluoroscopically assisted musculoskeletal procedures has been previously evaluated. No prior study has assessed fluoroscopy-related radiation exposure to the spine surgeon. METHODS: Bilateral pedicle screw placement (T11-S1) was performed in six cadavers using lateral fluoroscopic imaging. Radiation dose rates to the surgeon's neck, torso, and dominant hand were measured with dosimeter badges and thermolucent dosimeter (TLD) rings. Radiation levels were also quantified at various distances from the dorsal lumbar surface using an ion chamber radiation survey meter. RESULTS: The mean dose rate to the neck was 8.3 mrem/min. The dose rate to the torso was greatest when the surgeon was positioned ipsilateral to the beam source (53.3 mrem/min, compared with 2.2 mrem/min on the contralateral side). The average hand dose rate was 58.2 mrem/min. A significant increase in hand dose rate was associated with placement of screws ipsilateral to the beam source (P = 0.0005) and larger specimens (P = 0.0007). Radiation levels significantly decreased as distance from the beam source and dorsal body surface increased. The greatest levels of radiation were noted on the side where the primary radiograph beam entered the cadaver. CONCLUSION: Fluoroscopically assisted thoracolumbar pedicle screw placement exposes the spine surgeon to significantly greater radiation levels than other, nonspinal musculoskeletal procedures that involve the use of a fluoroscope. In fact, dose rates are up to 10-12 times greater. Spine surgeons performing fluoroscopically assisted thoracolumbar procedures should monitor their annual radiation exposure. Measures to reduce radiation exposure and surgeon awareness of high-exposure body and hand positions are certainly called for.

Bone Screws↗

Body Mass Index reference curves derived from a New Zealand birth cohort.

AIM: To construct reference curves for body mass index (BMI) and estimate the prevalence of obesity or being overweight at ages eighteen and 21 years. METHODS: Smoothed BMI curves were derived from data from a birth cohort born in Dunedin in 1972-73, followed up at two yearly intervals from age three to fifteen years, and then at ages eighteen, 21 and 26 years. RESULTS: Nine curves 0.67 SD apart, corresponding to the 0.4, 2, 9, 25, 50, 75, 91, 98, 99.6 centiles are provided. The prevalence of obesity, a BMI of 30 kg/m2 or more, was 2.7% for men and 2.6% for women at age eighteen years, and 5.8% for men and 5% for women at age 21 years. At age eighteen years, 14.9% men and 16.8% of women were overweight, with a BMI between 25 kg/m2 and 30 kg/m2. The prevalence increased to 24.7% for men and 24.2% for women at age 21 years. CONCLUSION: At age eighteen years, the value of the 98th centile was close to WHO criteria defining obesity in adults. This suggests that it could be used to describe obese children and adolescents. The 75th centile could be used in a similar way to delineate those regarded as overweight.

Adolescent↗

Methods for detection of haematogenous dissemination of brain tissue after stunning of cattle with captive bolt guns.

Because of concern that the stunning of cattle with captive bolt guns (CBGs) could, if used on an animal with bovine spongiform encephalopathy (BSE), cause embolism of infective brain tissue and carcass contamination, the Ministry of Agriculture, Food and Fisheries commissioned research to assess the risk of haematogenous dissemination of CNS material after stunning. We have devised two methods to investigate this risk. The first involves the concentration of embolic tissue in buffy coat Cytoblocks that can be embedded for sectioning, microscopy and immunocytochemistry. The second method is an ELISA for the presynaptic protein, syntaxin 1B. The methods were validated by analysis of several bovine tissues, including blood samples deliberately contaminated with brain. We then studied jugular venous blood obtained before and after the stunning of 60 cattle with CBGs. Samples obtained, after stunning, from five of the cattle contained CNS tissue within the Cytoblocks and yielded positive syntaxin assays. Syntaxin was also detected in samples from one other animal that had been stunned with a pneumatically operated CBG. The described methods should allow an assessment of the risk of neuroembolism associated with different types of CBG and may also be useful in other contexts.

Abattoirs↗