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Biomedical subjects

M Williams

Publications and source records attributed to M Williams.

At least 361 records · Page 20Linked to original sources

The effect of protoporphyrin on the susceptibility of human erythrocytes to oxidative stress: exposure to hydrogen peroxide.

Binding of protoporphyrin caused a perturbation of the erythrocyte membrane, as reflected by a change in cell shape from discoid to echinocyte, and a concomitant increase in mean cellular volume and K(+)-loss. Protoporphyrin-induced changes could be prevented by the presence of BaCl2, whereas binding of protoporphyrin was not affected. Exposure of erythrocytes to hydrogen peroxide leads to K(+)-leakage and lipid peroxidation. In de presence of protoporphyrin, H2O2-induced K(+)-leakage was enhanced, whereas lipid peroxidation was inhibited. The increase in H2O2-induced K(+)-leakage by protoporphyrin was not affected by diamide or various K+ channel blockers, but could be prevented by the addition of BaCl2. The inhibition of lipid peroxidation, on the other hand, was not affected by BaCl2. These results indicate that the enhancement of H2O2-induced K(+)-leakage was most likely caused by the change in cell shape. Addition of chlorpromazine and promethazine, positively charged molecules that induce stomatocytosis, did not cause an enhancement of H2O2-induced K(+)-leakage.

Cell Size↗

Partial purification of a novel mitogen for oligodendroglia.

A protein with a MWapp of 50-70 kDa isolated from the salt extract of crude membranes from neonatal rat brain increases the numbers of oligodendroglia in mixed glial cultures prepared from neonatal rat cerebral white matter. After partial purification by ion exchange and gel exclusion chromatography, and elution from an SDS-polyacrylamide gel, this protein ("oligodendroglial trophic factor," OTF) elicited half-maximal oligodendroglial recruitment at a concentration of 5 ng/mL. OTF is a mitogen for oligodendroglia, and to a lesser extent, for oligodendroglial progenitor (O2A) cells, but does not stimulate proliferation of astroglia, Schwann cells, or endoneurial fibroblasts. OTF, unlike platelet-derived growth factor (PDGF), is not an oligodendroglial survival factor. Antibodies against PDGF and basic fibroblast growth factor (bFGF) do not interfere with the accumulation of oligodendroglia induced by OTF. When OTF is given simultaneously with either PDGF or bFGF, there is an additive increase in the numbers of cells of the oligodendroglial lineage.

Animals↗

Prevalence of smoking among adult American Indian clinic users in northern California.

BACKGROUND: The American Indian Cancer Control Project is a 5-year program funded by the National Cancer Institute designed to promote smoking cessation among adult Indians living in Northern California. This article describes the result of our smoking prevalence survey. Our Indian-specific program combines the physician's anti-smoking message with the efforts of Indian Community Health Representatives, who have access to the Indian patients' families and communities. The study sites consist of 4 urban and 14 rural American Indian clinics in Northern California. This article reports on the results of the smoking prevalence study conducted in the first phase of the project. METHODS: A total of 1,369 adult Northern California Indian patients at 18 Indian health clinics completed a questionnaire designed to assess smoking rates and patterns as well as health problems. Participants were adult American Indians attending 1 of 18 Indian health care clinics in Northern California during 1991. The participants included patients waiting for appointments with the clinic physician, dentist, and nurses. RESULTS: Forty percent (37.35, 42.64; 95% confidence interval) of the adult population in the sample smoke cigarettes; they hold lenient attitudes toward smoking and began smoking at an early age. These patients rate obesity as the No. 1 health problem, followed by high blood pressure, arthritis/rheumatism, and problems with alcohol. The survey also found that the highest smoking rate was among the Sioux (62%), a non-California tribe. This was followed by high rates among native California tribes: Maidu (46%), Pit River (39%), Pomo (38%), Hupa (37%), and Yurok (32%).

Adult↗

Dual-energy X-ray absorptiometry of the calcaneus: comparison with vertebral dual-energy X-ray absorptiometry and quantitative computed tomography.

The purpose of this study was to determine the efficacy of using bone mineral measurements of the calcaneus to evaluate osteoporosis. Dual energy X-ray absorptiometry (DXA) of the calcaneus was compared with posteroanterior lumbar absorptiometry (DXA) and vertebral quantitative computed tomography (QCT) measurements in 171 white women (78 normal and 93 osteoporotic). DXA measurement of os calcis mineralization decreased significantly in osteoporosis, but to a lesser extent than in vertebral sites. In normal subjects, good correlations were observed between calcaneal and lumbar DXA (0.69) and QCT (0.56). In subjects with vertebral fractures, there was also good correlation between calcaneal DXA and QCT (0.59-0.69). This suggests that trabecular bone in calcaneus and vertebrae have related involution in cases of vertebral osteoporosis. However, the extent of bone loss is less marked in the calcaneus than in the vertebrae and is not sufficient to be accurately measured over time. We conclude, therefore, that although the global densitometric measurement at this site is not sufficiently sensitive for general use, it can be useful as a epidemiological research tool.

Absorptiometry, Photon↗

Morbid risk of schizophrenia for relatives of patients with cannabis-associated psychosis.

Twenty-three patients admitted with acute psychosis who were cannabis positive on urinary screening were each matched, with respect to sex, with two psychotic controls who screened negatively for all substances. The lifetime morbid risk of psychiatric disorder was estimated among the first degree relatives of cases and controls, using RDC-FH criteria to define diagnoses, and Weinberg's shorter method of age correction. The cases had a significantly greater familial morbid risk of schizophrenia (7.1%) than the controls (0.7%), while the risks of other psychoses, and of non-psychotic conditions were similar. The same pattern of familial risk was evident when the analysis was restricted to patients with DSM-III schizophrenia. The data suggest that the development or recurrence of acute psychosis in the context of cannabis use may be associated with a genetic predisposition to schizophrenia.

Adult↗

Ureteropelvic junction obstruction in upper and lower moiety of duplex renal systems.

OBJECTIVES: To review our experience with ureteropelvic junction obstruction in a duplicated renal collecting system. METHODS: The records of 7 patients with ureteropelvic junction obstruction in a duplex collecting system were reviewed. In addition to routine demographics, each case was reviewed for presenting symptoms, site of obstruction, and type of surgical treatment. RESULTS: Three of the 7 cases involved obstruction of the upper pole moiety, and the remaining 4 involved the lower pole segment of a duplex system. Obstruction of the upper and lower pole segments was found in both incomplete and complete duplicated collecting systems. CONCLUSIONS: Careful preoperative evaluation of patients with ureteropelvic junction obstruction will usually identify segmental obstruction in a duplicated system. Treatment should be individualized based on site of obstruction and degree of function remaining in the affected segment.

Abnormalities, Multiple↗

Phase I study of accelerated FEC with granulocyte colony-stimulating factor (Lenograstim) support.

With the aim of increasing the dose intensity of chemotherapy in breast cancer, 14 patients with stage II-IV breast cancer were treated with FEC chemotherapy at 2 week intervals together with granulocyte colony-stimulating factor (G-CSF) 5 micrograms kg-1 s.c. on days 2-14. Five of six patients completed six courses of 5-fluorouracil 600 mg m-2, epirubicin 60 mg m-2 and cylcophosphamide 600 mg m-2 within 11 weeks. Eight patients were treated with 5-fluorouracil 700 mg m-2, epirubicin 70 mg m-2 and cyclophosphamide 700 mg m-2 and four had dose-limiting toxicity with sepsis, thrombocytopenia or mucositis. All patients who received G-CSF had satisfactory neutrophil counts by day 15 of each course. Cumulative anaemia and thrombocytopenia were observed, but treatment at the first dose was tolerable. Seven of eight patients with measurable disease had partial responses. This regimen permits a 50% increase in dose intensity compared with conventional treatment at 3 week intervals and warrants further evaluation.

Adolescent↗

Final results from a meta-analysis of remedial interventions with drink/drive offenders.

A meta-analysis of the efficacy of remediation with drinking/driving offenders included 215 independent evaluations identified through a comprehensive literature search. Study characteristics, including dimensions of methodological quality were coded using scales and protocols developed by expert panels. Better methodological quality (as indicated by group equivalence) was associated with smaller effect size and less variation in effect size. Among studies with adequate methods (as determined empirically through examination of effect size variation with quality), the average effect of remediation on drinking/driving recidivism was an 8-9% reduction over no remediation. A similar effect size was found for alcohol involved crashes. However, licensing actions tended to be associated with reduction in occurrence of non-alcohol events (e.g. non-alcohol crashes). Exploratory regression analysis and confirmatory within study analysis suggested that combinations of modalities--in particular those including education, psychotherapy/counseling and follow-up contact/probation--were more effective than other evaluated modes for reducing drinking/driving recidivism. Treatment effects are probably underestimated in the literature due to overemphasis on education as a treatment for all offenders and drinking/driving recidivism as the most frequent measure of outcome. Limitations of the primary literature and future research needs are discussed.

Accidents, Traffic↗

Staff perceptions of organization change of treatment delivery on an addiction unit.

The Work Environment Scale was used to assess staff perceptions of a change in a treatment programme for problem drinkers. A more cost-effective 2-week research-based day-patient programme, which included the concept of matching, replaced a 5-week cognitive behavioural in-patient programme. The maintenance of a positive work environment was attributed to the meeting of staff expectations, a cognitive behavioural ideology, and the establishment of a research culture. The study highlights the importance of the thorough preparation of staff for change, and their active involvement in the process in settings where work satisfaction is already above the average level for mental health facilities.

Alcoholism↗

Beta 3-endonexin, a novel polypeptide that interacts specifically with the cytoplasmic tail of the integrin beta 3 subunit.

The adhesive and signaling functions of integrins are regulated through their cytoplasmic domains. We identified a novel 111 residue polypeptide, designated beta 3-endonexin, that interacted with the cytoplasmic tail of the beta 3 integrin subunit in a yeast two-hybrid system. This interaction is structurally specific, since it was reduced by 64% by a point mutation in the beta 3 cytoplasmic tail (S752-->P) that disrupts integrin signaling. Moreover, this interaction is integrin subunit specific since it was not observed with the cytoplasmic tails of the alpha IIb, beta 1, or beta 2 subunits. beta 3-Endonexin fusion proteins bound selectively to detergent-solubilized beta 3 from platelets and human umbilical vein endothelial cells, and beta 3-endonexin mRNA and protein were detected in platelets and other tissues. A related mRNA encoded a larger polypeptide that failed to bind to beta integrin tails. The apparent specificity of beta 3-endonexin for the beta 3 integrin subunit suggests potential mechanisms for selective modulation of integrin functions.

Amino Acid Sequence↗

Correlation between fragment size at D4F104S1 and age at onset or at wheelchair use, with a possible generational effect, accounts for much phenotypic variation in 4q35-facioscapulohumeral muscular dystrophy (FSHD)

In facioscapulohumeral muscular dystrophy (FSHD), the wide range of clinical severity observed both within and between families has obscured past attempts to identify any phenotypic differences between families from which phenotype-genotype correlation could proposed, although it is noted that age at onset is youngest and severity greatest in isolated cases. From 14/16 large 4q35-linked FSHD families, and 25/34 isolated cases exhibiting a de novo D4F104S1 DNA fragment, we find a significant correlation between proband age at onset and FSHD-associated D4F104S1 fragment size (r = 0.56; p < 0.001), with the smallest fragments occurring in isolated cases. A similar correlation (r = 0.70; p < 0.01) with fragment size is observed for age to loss of ambulation in 16 subjects using a wheelchair. We find also that age at onset appears younger with successive generations in the 4q35 families. We propose that fragment size at D4F104S1, together with a possible generational effect, accounts for a significant part of the wide phenotypic variation in FSHD. Our results predict a more limited range for severity within families, and in one family with a 4q35-linked 38kb fragment support scapulohumeral presentation without facial involvement as a late onset variant of FSHD. We propose that in FSHD, quantitative variation in a uniform mutation mechanism influences age at onset, but by deletion rather than expansion of DNA.

Adolescent↗

Cervical assessment.

The relationship between the clinical state of the cervix and spontaneous onset of labor has long been known. The cervix can be characterized by evaluating five parameters: effacement, dilatation, firmness, position, and level of the presenting part. The relative associations between successful labor induction and these factors appears to vary, with the strongest correlation observed with cervical dilation, whereas the association with cervical station and position is less robust. By its nature, cervical examination is somewhat subjective, but the use of objective criteria and numerical scoring of this information has substantially reduced this source of error. The Bishop score and it variations have been used widely and accepted in clinical practice. Its advantage lies in its simplicity, reproducibility, and predictability in successful inductions. Although criticized for the equal weight given to each of the five elements, none of the modifications to the original score has been shown to improve predictability. Although the Bishop score was initially evaluated only in multiparous women, it has been extended to nulliparous women with an equal degree of predictive value. To date, the Bishop score remains as the best and simplest method available to determine the duration and safety of induced labor.

Cervix Uteri↗

Outpatients revisited: subjective views and clinical decisions in the management of general surgical outpatients in south west England.

STUDY OBJECTIVE: To assess the scope for reducing unnecessary outpatient reattendances, using a benchmark an acute specialty at a site recognised to have an especially low ratio of repeat to new attendances. DESIGN: This was a survey of the re-attendance workload at general surgery outpatient clinics over a three month period. Patient re-booking and discharge rates for different grades of staff; clinicians' perception of the ability of the GP to have managed the patient; perception of the value of individual re-attendances; reason given for discharging/re-booking; and outcome of attendance for patients in relation to diagnostic category were determined. SETTING: General surgery outpatients clinics with re-attendance rates that were 50% below average, in Taunton and Somerset Hospital, a non-teaching district general hospital. PATIENTS: Altogether 454 patients who made 470 second or subsequent visits (re-attendances) within the same episode of outpatient care. MAIN RESULTS: Thirty eight percent (178/470) of visits were perceived as manageable by the GP, 45% (79, 17% of total re-attendances) of which were also thought to have been of marginal or little value. A substantial group of patients was being followed up largely for reasons of convention and traditional policy. Re-booking rates were higher among junior staff. Subjective views of the value of attendance at the hospital outpatient clinic and the ability of the GP to have seen the patient varied systematically between consultants and junior staff. Judgements varied to some extent according to the diagnostic group. CONCLUSION: The numbers of patients being followed up equivocally at most general surgical outpatient departments will be 50% more an average than those in this benchmark department. A department seeing 2000 new patients per annum will have 3600 reattendances, 25.5% (918) of which may be avoidable on the basis of these results. A variety of approaches can be used to increase the proportion of patients seen appropriately by GPs. In some cases this might be achieved without the intensive commitment required to plan and develop shared care protocols or new formal discharge guidelines, but by encouraging GPs to manage some patients, increasing of hospital clinicians' access to knowledge of local general practices, and internal clinic review of 'routine' follow up policies as shown in this study. This type of review of outpatient practice can also help prioritise conditions likely to repay the effort of developing and implementing clinical management guidelines and local protocols.

Delivery of Health Care↗