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Biomedical subjects

J Williams

Publications and source records attributed to J Williams.

At least 289 records · Page 16Linked to original sources
PubMed1999

Prospective study of external cephalic version in Glasgow: patient selection, outcome and factors associated with outcome.

Data were collected prospectively on all 67 women who underwent an attempt at external cephalic version (ECV) over 1 year in the four Glasgow maternity hospitals. Ultrasonography was used in all women. However, tocolytics were used in only two (6%) nulliparous women despite published evidence of their efficacy. Only 25 (37%) women undergoing ECV had a free presenting part which is known to be associated with success. Seventeen (25%) women were less than 37 weeks pregnant despite spontaneous version being common at this stage. ECV was successful in only 26 (39%) women and only 18 (27%) had a vaginal cephalic delivery. These results compare unfavourably with published results of around two-thirds for both end-points. Although publication bias is likely, patient selection, under-usage of tocolytics and lack of experience may also be factors. Consideration should be given to a reduced number of operators who can maximise their throughput and expertise.

Journal Article↗
PubMed1999

Home-based multidisciplinary diagnosis and treatment of inner-city elders with dementia.

The Memory and Aging Project Satellite (MAPS) of the Washington University Alzheimer's Disease Research Center was developed to meet the medical, social, and housing needs of minority and medically underserved elders with cognitive impairments. MAPS is located in the offices of the St. Louis Area Agency on Aging (AAA). This program provides multidisciplinary outreach, as well as home-based diagnosis, treatment, and case management. It differs from most other satellite programs in that it seeks to provide service to individuals who do not voluntarily seek help for dementia. Cognitively impaired clients had numerous, unmanaged medical conditions and social problems. Few clients were adequately served by health and social service systems. Despite recent contact, only 10% of clients received a formal diagnosis of dementia from a physician. Treatment was hampered by the absence or limitations of caregivers. Despite the complexities of these cases, the MAPS staff have been generally successful in addressing client problems.

Aged↗
PubMed1999

A full genome scan for late onset Alzheimer's disease.

We have genotyped 292 affected sibling pairs (ASPs) with Alzheimer's disease (AD) according to NINCDS-ADRDA diagnostic criteria and with onset ages of >/=65 years using 237 microsatellite markers separated by an average distance of 16.3 cM. Data were analysed by SPLINK and MAPMAKER/SIBS on the whole sample of 292 ASPs and subsets of 162 ASPs where both members possessed an apolipoprotein E (APOE)straightepsilon4 allele and 63 pairs where neither possessed anstraightepsilon4 allele. Sixteen peaks with a multipoint lod score (MLS) >1 either in the whole sample, the straightepsilon4-positive or -negative subgroups were observed on chromosomes 1 (two peaks), 2, 5, 6, 9 (two peaks), 10 (two peaks), 12, 13, 14, 19, 21 and X (two peaks). Simulation studies revealed that these findings exceeded those expected by chance, although many are likely to be false positives. The highest lod scores on chromosomes 1 (MLS 2.67), 9 (MLS 2.38), 10 (MLS 2.27) and 19 (MLS 1.79) fulfilLander and Kruglyak's definition of 'suggestive' in that they would be expected to occur by chance once or less per genome scan. Several other peaks were only marginally less significant than this, in particular those on chromosomes 14 (MLS 2.16), 5 (MLS 2.00), 12, close to alpha2-macroglobulin (MLS 1.91), and 21, close to amyloid precursor protein (MLS 1.77). This is the largest genome scan to date in AD and shows for the first time that this is a genetically complex disorder involving several, perhaps many, genes in addition to APOE. Moreover, our data will be of interest to those hoping to identify positional candidate genes using information emerging from neurobiological studies of AD.

Age of Onset↗
PubMed1999

Systemic sclerosis (scleroderma) in two iron ore mines.

Six males with systemic sclerosis were observed in the work forces of two iron ore mines. The usual spectrum of clinical features encountered in systemic sclerosis patients were present. Histologic examination of pulmonary tissue was performed on three of the cases and showed features of both silicosis and scleroderma but to different degrees and stages of development. Exposure to high levels of silica-containing dusts had occurred in all six cases.

Adult↗
PubMed1999

SF-36 scores vary by method of administration: implications for study design.

BACKGROUND: Previous research suggests that people respond differently to health status measures when data are collected by interview or self completion of a questionnaire. The objective of this study was to determine whether SF-36 health status scores differ systematically by method of administration. METHOD: A randomized cross-over study was carried out on 210 new attenders at general medicine, endocrinology, gastroenterology and urological out-patient departments. The outcome was the difference in SF-36 profiles comparing clinic based interviews with self completion at home by the same subjects. RESULTS: For seven of the eight variables of the SF-36 scores were lower in the self assessment, the differences being statistically significant in four of the eight comparisons. The largest differences were in role limitations due to emotional problems (difference 14.74, 95 per cent confidence interval (CI) 7.76-21.7) and social function (difference 7.21, 95 per cent CI 3.19-11.23). CONCLUSIONS: Clinic based interviews systematically exaggerate health status compared with self assessment. The difference is sufficiently large to underestimate the effectiveness of health service interventions when a clinic based pre-intervention and postal self completed follow-up design is used, unless adjustment is made for this systematic bias.

Analysis of Variance↗
PubMed1999

Expression of eIF4E during head and neck tumorigenesis: possible role in angiogenesis.

OBJECTIVE: The translation initiation factor eIF4E (4E) when overexpressed in mammalian cells results in their oncogenic transformation. 4E facilitates the synthesis of two powerful tumor angiogenic factors (VEGF and FGF-2) by selectively enhancing their translation. 4E is overexpressed not only in all head and neck squamous cell cancers but also in some dysplastic margins. Tumorigenesis in the head and neck is proposed to be a multistep process preceded by clinically evident precancerous lesions. Molecular events underlie the histological changes that herald transformation. We wanted to study the role of 4E in tumorigenesis and further elucidate its causal role in angiogenesis. METHODS: An immunohistochemical analysis with antibodies to 4E, VEGF, and basic (b)-FGF was performed on 115 specimens of the head and neck representing various stages of histological progression of malignancy. This was correlated with mean vessel density (MVD) using factor VIII. RESULTS: There were 41 cases of hyperplasia and low-grade dysplasia, 40 cases of high-grade dysplasia and 34 cases of cancer. There was a significant increase in the percent of cases expressing 4E from low-grade dysplasia through tumor. However, for VEGF and b-FGF the significant increase was only seen between the tumor group and dysplastic groups and no significant increase was noted between low-grade and high-grade dysplasia There was a significant increase in MVD from low- (10.7+/-1) to high-grade grade dysplasia (18.0+/-2.3). This increase was even more striking for the 4E positive cases. CONCLUSION: 4E elevation is correlated with progressive cell transformation in the head and neck. Its correlation with VEGF, b-FGF, and MVD potentiates its possible role in angiogenesis.

Antibodies, Neoplasm↗
PubMed1999

The effects of cisplatinum and vincristine on peripheral nerve regeneration.

Current treatment modalities for extremity sarcoma often include tumor extirpation plus neoadjuvant therapy. Limb-sparing surgery may require reconstruction of critical nerve defects. Neurotoxic side effects from adjuvant chemotherapy have been reported and raise concerns regarding the effects of chemotherapy on nerve regeneration. In an attempt to define the effects of adjuvant chemotherapy on peripheral nerve regeneration, cisplatin and vincristine were administered to rats following isografting of the posterior tibial nerve. Parameters used to assess peripheral nerve regeneration included walking track analysis and histomorphology. Sixty 250-g Sprague-Dawley rats were randomly allocated into one of three treatment groups. Each animal underwent a 15-mm reversed interposition nerve isograft from 30 donor rats into the right posterior tibial nerve. Ten animals served as control. The remaining animals were divided into two groups of 25 animals each. One group received cisplatin (75 mg/m2) and the other group received vincristine (1 mg/m2). Chemotherapy was administered at 4-week cycles for a total of six cycles (24 weeks). Walking track analysis was performed monthly. Nerve specimens were harvested from the grafted segment and the distal posterior tibial nerve for histomorphology. Walking track analysis demonstrated no statistical difference in print length between the control and chemotherapeutic groups at the conclusion of the study. The number of axons per square millimeter and nerve fiber density were not statistically different between control and chemotherapeutic groups. In the rodent posterior tibial nerve model, postoperative adjuvant therapy does not significantly alter functional outcome in peripheral nerve regeneration. The practice of immediate nerve grafting after tumor extirpation, despite planned postoperative chemotherapy, is supported.

Animals↗
PubMed1999

The endurance shuttle walk: a new field test for the assessment of endurance capacity in chronic obstructive pulmonary disease.

BACKGROUND: The purpose of this study was to develop an externally controlled, constant paced field walking test to assess endurance capacity in patients with chronic obstructive pulmonary disease (COPD). There were four objectives: (1) to develop a protocol; (2) to compare treadmill and shuttle walk tests of endurance capacity; (3) to examine the repeatability of the endurance shuttle walk test; and (4) to compare the sensitivity to pulmonary rehabilitation of endurance and incremental shuttle walk tests. METHODS: The test was designed to complement the incremental shuttle walk test (ISWT) using the same 10 m shuttle course and an audio signal to control pace. The intensity of the field endurance test was related to a percentage of each patient's maximum field exercise performance assessed by the ISWT. A number of cassette tapes were pre-recorded with a range of audio signal frequencies to dictate walking speeds between 1.80 and 6.00 km/h. In the first limb of the study 10 patients with COPD (mean (SD) forced expiratory volume in one second (FEV1) 1.0 (0.36) 1, 35% predicted) performed three endurance shuttle walk tests (ESWTs) and three treadmill endurance tests. The walking speeds were calculated to elicit 75%, 85%, and 95% of each patient's maximum ISWT performance for the field tests and measured peak oxygen consumption for the treadmill tests. In a separate group of patients the repeatability of the ESWT at an intensity of 85% of the ISWT performance was evaluated. Finally, the ESWT (at the 85% intensity) and the ISWT were performed at the start of a five week control period and at the start and end of a seven week pulmonary rehabilitation programme in 21 patients with COPD (mean FEV1 0.80 (0.18) 1). RESULTS: The mean (SE) times achieved during the ESWT were 13.1 (2.3), 10.2 (2.5), and 5.3 (1.7) min for the walks at 75%, 85%, and 95% intensities, respectively. Patients tended to walk for longer on the treadmill than during the field tests at all intensities, but there were no significant differences between the end of test heart rates or Borg ratings of breathlessness or perceived exertion. Following one practice ESWT at the 85% intensity, the mean difference and limits of agreement (2SD) between tests 2 and 3 was +15 (42) s (p > 0.05). There was no significant change in performance on either test following the five week control period prior to rehabilitation. Following rehabilitation the ESWT duration increased by 160 (24)% and the ISWT distance increased by 32 (11)% (effect sizes 2.90 and 0.41, respectively). CONCLUSIONS: The ESWT was simple to perform, acceptable to all patients, and exhibited good repeatability after one practice walk. The test showed major improvement following rehabilitation and was more sensitive to change than the field test of maximal capacity.

Exercise Test↗
PubMed1999

Squalamine, a novel cationic steroid, specifically inhibits the brush-border Na+/H+ exchanger isoform NHE3.

Squalamine, an endogenous molecule found in the liver and other tissues of Squalus acanthias, has antibiotic properties and causes changes in endothelial cell shape. The latter suggested that its potential targets might include transport proteins that control cell volume or cell shape. The effect of purified squalamine was examined on cloned Na+/H+ exchanger isoforms NHE1, NHE2, and NHE3 stably transfected in PS120 fibroblasts. Squalamine (1-h pretreatment) decreased the maximal velocity of rabbit NHE3 in a concentration-dependent manner (13, 47, and 57% inhibition with 3, 5, and 7 micrograms/ml, respectively) and also increased K'[H+]i. Squalamine did not affect rabbit NHE1 or NHE2 function. The inhibitory effect of squalamine was 1) time dependent, with no effect of immediate addition and maximum effect with 1 h of exposure, and 2) fully reversible. Squalamine pretreatment of the ileum for 60 min inhibited brush-border membrane vesicle Na+/H+ activity by 51%. Further investigation into the mechanism of squalamine's effects showed that squalamine required the COOH-terminal 76 amino acids of NHE3. Squalamine had no cytotoxic effect at the concentrations studied, as indicated by monitoring lactate dehydrogenase release. These results indicate that squalamine 1) is a specific inhibitor of the brush-border NHE isoform NHE3 and not NHE1 or NHE2, 2) acts in a nontoxic and fully reversible manner, and 3) has a delayed effect, indicating that it may influence brush-border Na+/H+ exchanger function indirectly, through an intracellular signaling pathway or by acting as an intracellular modulator.

Animals↗
PubMed1999

Disruption of p53 in human cancer cells alters the responses to therapeutic agents.

We have examined the effects of commonly used chemotherapeutic agents on human colon cancer cell lines in which the p53 pathway has been specifically disrupted by targeted homologous recombination. We found that p53 had profound effects on drug responses, and these effects varied dramatically depending on the drug. The p53-deficient cells were sensitized to the effects of DNA-damaging agents as a result of the failure to induce expression of the cyclin-dependent kinase inhibitor p21. In contrast, p53 disruption rendered cells strikingly resistant to the effects of the antimetabolite 5-fluorouracil (5-FU), the mainstay of adjuvant therapy for colorectal cancer. The effects on 5-FU sensitivity were observed both in vitro and in vivo, were independent of p21, and appeared to be the result of perturbations in RNA, rather than DNA, metabolism. These results have significant implications for future efforts to maximize therapeutic efficacy in patients with defined genetic alterations.

Animals↗
PubMed1999

Amphiregulin is coordinately expressed with heparin-binding epidermal growth factor-like growth factor in the interstitial smooth muscle of the human prostate.

Peptide growth factors have been proposed as mediators of smooth muscle-epithelial cell interactions in the human prostate; however, the identity of these molecules has not been established. In this study, we compared expression levels of messenger RNAs (mRNAs) encoding the epidermal growth factor (EGF) receptor-related receptor tyrosine kinases (ErbB1 through 4), the six EGF receptor ligands, EGF, transforming growth factor (TGF)-alpha, amphiregulin (ARG), HB-EGF, betacellulin, and epiregulin, and the related molecule heregulin-alpha, in a series of 10 prostate tissue specimens. Only EGF showed a disease-specific association, with increased mRNA levels in four of five PCa specimens in comparison to matched normal tissue from the same subject. In contrast, ARG and HB-EGF mRNAs showed a coordinate pattern of expression in 7/10 specimens that was distinct from all other growth factor or receptor genes examined and from mRNAs for prostate specific antigen, the androgen receptor and GAPDH, a house-keeping enzyme. Analysis of an additional series of benign prostatic hyperplasia and prostate cancer specimens from 60 individuals confirmed that ARG and HB-EGF mRNA levels varied in a highly coordinate manner (r = 0.93; P < 0.0001) but showed no association with disease. ARG was immunolocalized largely to interstitial smooth muscle cells (SMC), previously identified as the site of synthesis of HB-EGF in the prostate, while the cognate ARG and HB-EGF receptor, ErbB1, was localized exclusively to ductal epithelial cells and carcinoma cells. Although ARG was a relatively poor mitogen for Balb/c3T3 cells in comparison to HB-EGF, it was similar in potency to HB-EGF in stimulating human prostate epithelial cell growth, suggesting that prostate epithelia may be a physiologic target for ARG in vivo. Expression of both ARG and HB-EGF mRNAs was induced in cultured prostate SMC by fibroblast growth factor-2, a human prostate SMC mitogen linked to prostate disease. These findings indicate that ARG and HB-EGF are likely to be key mediators of directional signaling between SMC and epithelial cells in the human prostate and appear to be coordinately regulated.

Amphiregulin↗
PubMed1999

Staff grade doctors and the consultant ladder: falling off or stepping off?

The majority of the doctors in staff grade posts surveyed had qualified overseas and a substantial proportion were dissatisfied with their posts. Very few doctors had received adequate careers counselling before starting their post and many were concerned at the lack of opportunities for career development.

Career Mobility↗
PubMed1999

Alcohol and drug use of inter-city versus rural school age children.

The purpose of this study of seventy-nine children was to determine: 1) the prevalence and type of substance use in inter-city and rural eight to twelve-year-old children; and 2) the relationships between child substance use, self-esteem, peer substance use, and family climate. The conceptual framework for the study was a modification of Kumpfer and Turner's Social Ecology Model (1991). Nineteen percent of the children had used alcohol or drugs. Thirty-three percent of the children acknowledged having friends who used substances. Inter-city children reported more alcohol and marijuana use, while the rural children reported more use of inhalants. The responses of both inter-city and rural children also indicated that there were problems with substance use and family violence in the home. Self-esteem and affiliation with drug using peers were significantly correlated with substance use of the child.

Alcoholism↗
PubMed1999

Propofol in the treatment of moderate and severe head injury: a randomized, prospective double-blinded pilot trial.

OBJECT: Sedation regimens for head-injured patients are quite variable. The short-acting sedative-anesthetic agent propofol is being increasingly used in such patients, yet little is known regarding its safety and efficacy. In this multicenter double-blind trial, a titratable infusion of 2% propofol accompanied by low-dose morphine for analgesia was compared with a regimen of morphine sulfate in intubated head-injured patients. In both groups, other standard measures of controlling intracranial pressure (ICP) were also used. METHODS: Forty-two patients from 11 centers were evaluated to assess both the safety and efficacy of propofol: 23 patients in the propofol group (mean time of propofol usage 95+/-87 hours) and 19 patients in the morphine group (mean time of morphine usage 70+/-54 hours). There was a higher incidence of poor prognostic indicators in the propofol group than in the morphine group: patient age older than 55 years (30.4% compared with 10.5%, p < 0.05), initial Glasgow Coma Scale scores of 3 to 5 (39.1% compared with 15.8%, p < 0.05), compressed or absent cisterns on initial computerized tomography scanning (78.3% compared with 57.9%, p < 0.05), early hypotension and/or hypoxia (26.1% compared with 10.5%, p = 0.07). During treatment there was a trend toward greater use of vasopressors in the propofol group. However, the mean daily ICP and cerebral perfusion pressure were generally similar between groups and, on therapy Day 3, ICP was lower in the propofol group compared with the morphine group (p < 0.05). Additionally, there was less use of neuromuscular blocking agents, benzodiazepines, pentobarbital, and cerebrospinal fluid drainage in the propofol group (p < 0.05). At 6 months postinjury, a favorable outcome (good recovery or moderate disability) was observed in 52.1% of patients receiving propofol and in 47.4% receiving morphine; the mortality rates were 17.4% and 21.1%, respectively. Patients who received the highest doses of propofol for the longest duration tended to have the best outcomes. There were no significant differences between groups in terms of adverse events. CONCLUSIONS: Despite a higher incidence of poor prognostic indicators in the propofol group, ICP therapy was less intensive, ICP was lower on therapy Day 3, and long-term outcome was similar to that of the morphine group. These results suggest that a propofol-based sedation and an ICP control regimen is a safe, acceptable, and, possibly, desirable alternative to an opiate-based sedation regimen in intubated head-injured patients.

Adult↗
PubMed1999

Immunohistochemical staining for Ber-EP4, p53, proliferating cell nuclear antigen, Ki-67, bcl-2, CD34, and factor XIIIa in nevus sebaceus.

Increased expression of p53 has been found in the majority of basal cell carcinomas (BCCs). The pattern and intensity of this staining, as well as staining for proliferation antigens, seems to correlate with behavior of histologic subtypes of BCC. Nevus sebaceus (NS) is considered a hamartoma. Multiple epithelial neoplasms do arise in NS, and, rarely, they show an aggressive biologic behavior. Significant numbers of these neoplasms, however, have areas of basaloid hyperplasia that are often reported as BCC. Although morphologically similar to BCC, the mechanism underlying the development of these areas has not been investigated, so we sought to evaluate the expression of Ber-EP4, p53, proliferating cell nuclear antigen, Ki-67, bcl-2, Factor XIIIa, and CD34 in areas showing basaloid hyperplasia, arising in NS. We performed immunohistochemical stains for Ber-EP4, p53, proliferating cell nuclear antigen, Ki-67, bcl-2, Factor XIIIa, and CD34 on seven cases of NS with areas of basaloid hyperplasia. All of the eight cases of NS showed diffuse positive membrane staining for Ber-EP4 and negative nuclear staining for p53. Proliferating cell nuclear antigen and Ki-67 staining was only slightly increased in the areas of basaloid hyperplasia, compared with the surrounding epidermis and with areas of the epidermis peripheral to the hamartomatous proliferation, and bcl-2 was only focally positive. Factor XIIIa-positive cells and CD34-positive vascular endothelial cells were increased within the subjacent dermis, a pattern suggestive of follicular differentiation. Our findings suggest that even though areas of basaloid hyperplasia in NS are morphologically similar to BCC, they are induced by different stimulatory and molecular mechanisms. These different mechanisms result in expression of immunohistochemical markers more characteristic of benign follicular tumors than of BCC.

Adolescent↗