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Biomedical subjects

S Fowler

Publications and source records attributed to S Fowler.

At least 55 records · Page 3Linked to original sources
PubMed1996

Regulation of the steps of angiogenesis by human head and neck squamous cell carcinomas.

Human head and neck squamous cell carcinoma (HNSCC) cell cultures were established to identify the angiogenic factors they produced and how these factors contribute to two steps of the angiogenic process: endothelial cell proliferation and migration. The HNSCC cells secreted vascular endothelial cell growth factor (VEGF), transforming growth factor-beta (TGF-beta) and prostaglandin E2 (PGE2), but only low levels of basic fibroblast growth factor. Both proliferation-stimulatory and -inhibitory cytokines were produced by the HNSCC cells, with VEGF promoting endothelial cell proliferation, prostaglandins having no effect and TGF-beta downregulating proliferation. Two methods were used to measure endothelial cell migration: migration into a wound in the endothelial cell monolayer and migration across a filter into lower compartments. HNSCC cell supernatants stimulated endothelial cell migration in both migration models. VEGF had no effect on the motility of endothelial cells. However, when TGF-beta activity in the HNSCC supernatants was neutralized with antibody or the production of prostaglandins by HNSCC cells was blocked with indomethacin, the migration-stimulatory activity in the HNSCC cell supernatants was diminished. Adding authentic PGE2 or TGF-beta 1 to endothelial cells mimicked the migration-stimulatory activity of the HNSCC supernatants. Thus, HNSCC-derived VEGF is important in stimulating endothelial cell proliferation, while the antiproliferative effect of TGF-beta and the migration-stimulatory activity of TGF-beta and PGE2 suggest their having a role in the morphogenic processes of angiogenesis.

Carcinoma, Squamous Cell↗
PubMed1996

Yttrium-90-labeled anti-CD20 monoclonal antibody therapy of recurrent B-cell lymphoma.

A Phase I/II dose escalation study of 90Y-murine anti-CD20 monoclonal antibody (mAb) in patients with recurrent B-cell lymphoma was performed. The primary objectives of the study were: (a) to determine the effect of the preinfusion of unlabeled anti-CD20 mAb on the biodistribution of 111In-anti-CD20 mAb; (b) to determine the maximal tolerated dose of 90Y-anti-CD20 mAb that does not require bone marrow transplantation; and (c) to evaluate the safety and antitumor effect of 90Y-anti-CD20 mAb in patients with recurrent B-cell lymphoma. Eighteen patients with relapsed low- or intermediate-grade non-Hodgkin's lymphoma were treated. Biodistribution studies with 111In-anti-CD20 mAb were performed prior to therapy. Groups of three or four patients were treated at dose levels of approximately 13.5, 20, 30, 40, and 50 mCi 90Y-anti-CD20 mAb. Three patients were retreated at the 40-mCi dose level. The use of unlabeled antibody affected the biodistribution favorably. Nonhematological toxicity was minimal. The only significant toxicity was myelosuppression. The overall response rate following a single dose of 90Y-anti-CD20 mAb therapy was 72%, with six complete responses and seven partial responses and freedom from progression of 3-29+ months following treatment. Radioimmunotherapy with </=50 mCi 90Y-anti-CD20 mAb resulted in minimal nonhematological toxicity and durable clinical responses in patients with recurrent B-cell lymphoma. Doses of </=40 mCi 90Y-anti-CD20 mAb were not myeloablative.

Adult↗
PubMed1996

Treatment of hormone-refractory prostate cancer with 90Y-CYT-356 monoclonal antibody.

A Phase I dose-escalation study using 90Y-CYT-356 monoclonal antibody was performed in 12 patients with hormone-refractory prostate carcinoma. Biodistribution studies using 111In-CYT-356 were performed 1 week before 90Y-CYT-356 administration. Of the 12 patients, 58% had at least one site of disease imaged after administration of 111In-CYT-356. The dose of 90Y ranged from 1.83-12 mCi/m2. Both 111In and 90Y-CYT-356 were tolerated well, without significant nonhematological toxicity. Myelosuppression was the dose-limiting toxicity and occurred at dose levels of 4.5-12 mCi/m2. Of the patients receiving </=9 mCi/m2, 55% had grade 1 or 2 leukopenia and/or thrombocytopenia. Two of three patients treated with 12 mCi/m2 experienced grade 3 thrombocytopenia and leukopenia. One patient treated with 12 mCi/m2 had grade 4 neutropenia. The maximum tolerated dose of 90Y-CYT-356 was 9 mCi/m2. Only one patient developed a human anti-mouse antibody 4 weeks after treatment. No patient attained a complete or partial response based on prostate-specific antigen and/or radiological criteria. Three patients had transient subjective improvement in the symptomatology of their disease. In addition, patients treated with 12 mCi/m2 of 90Y-CYT-356 had a slightly longer freedom from disease progression than patients treated with doses of 90Y-CYT-356 </=9 mCi/m2.

Aged↗
PubMed1995

Presentation of comparative audit data.

The Royal College of Surgeons of England organizes a voluntary comparative audit service for its general surgical fellows. To date, the information from the audit has been presented purely descriptively, which does not take account of statistical variability and the effects of differences in case mix between the participants. A new approach to the presentation of these data, based on statistical modelling of the effects of case mix, is presented. The approach is illustrated in an application based on data relating to 136203 admissions reported by 110 surgeons. The result of adjusting for case mix is a substantial change in the relative performance of the participating surgeons, which demonstrates the folly of attempting to compare surgical performance on the basis of a measure as crude as the unadjusted mortality rate. Further development of the statistical modelling is required, but this new statistical approach appears to enhance greatly the credibility of the audit data, by quantifying its strengths and limitations.

Age Distribution↗
PubMed1995

Contrast sensitivity and coherent motion detection measured at photopic luminance levels in dyslexics and controls.

Development dyslexics perform differently from controls on a number of low level visual tasks. We carried out three experiments to explore some of these differences. Dyslexics have been found to have reduced luminance contrast sensitivity at mesopic luminance levels. We failed to replicate this finding at photopic luminance levels. We also compared the (photopic) coherent motion detection thresholds of groups of child and adult dyslexics with those of age matched controls. Dyslexics were significantly less sensitive to motion. The results are discussed in relation to a recent suggestion that developmental dyslexia may be associated with a magnocellular visual deficit.

Adolescent↗
PubMed1995

A confidential comparative audit of stapedectomies: results of the Royal College of Surgeons of England Comparative Audit of ENT surgery 1994.

This paper presents the results of a national confidential comparative audit of stapedectomy: 185 operations by 28 consultants over a two-year period were retrospectively analysed. This included 10 revision procedures. Small fenestra stapedectomies accounted for 63 per cent of the total. Thirty-nine per cent of consultants operated on the second ear. Of the 168 stapedectomies in which the hearing change was known at six months, 87 per cent achieved improved hearing, eight per cent had no change and five per cent were worse. The overall complication rate was 30 per cent with a 'dead ear' rate of two per cent.

Bone Conduction↗
PubMed1995

Mastoidectomy audit: results of the Royal College of surgeons of England comparative audit of ENT surgery.

This paper presents the results of a national comparative audit of mastoid surgery, retrospectively analysing 611 operations by 55 consultants. Confidentiality for both patient and surgeon was assured. For cholesteatoma 80% of mastoidectomies performed were open cavity procedures and for other middle ear disease 58% used an intact canal wall technique. Thirty-two surgeons used only an open cavity mastoidectomy for cholesteatoma during the period of the audit. There was a statistically significantly greater number of wet ears with open cavities than with closed cavities, but the frequency of the operator did not correlate with the dry ear rate. Ten serious complications (facial palsy and dead ear) were recorded. All occurred in open cavity mastoidectomies. The post-operative hearing status was unknown in 40% of patients.

Cholesteatoma↗
PubMed1995

Damage to cerebellocortical pathways after closed head injury: a behavioural and magnetic resonance imaging study.

The objective was to investigate the anatomical substrate of ataxia seen after severe head injury. Five patients were recruited from present and former inpatients at Rivermead Rehabilitation Centre. All patients had had a closed head injury and all had cerebellar type ataxia. Four normal controls were also studied. Brain MRI, clinical examination, computer based recording, and analysis of visuomotor tracking were carried out. Focal damage was found in the superior cerebellar peduncle in all five ataxic patients. The patients' tracking movements showed profound tremor, and unusual reliance on visual feedback. Ataxia seen after severe head injury can arise from damage to the superior cerebellar peduncle, which may interfere with the cerebellocortical circuits involved in coordinated movement.

Adult↗
PubMed1994

Effect of filgrastim (G-CSF) in Hodgkin's disease patients treated with radiation therapy.

PURPOSE: To evaluate the effect of filgrastim (recombinant human G-CSF) on radiation-induced neutropenia in a well defined, homogenous patient population. METHODS AND MATERIALS: Seven patients who were to receive large field subdiaphragmatic irradiation after thoracic "mantle" fields for treatment of Hodgkin's disease entered this study. They received daily subcutaneous (SC) injections of filgrastim during subdiaphragmatic irradiation. Total white blood cell (WBC) and absolute neutrophil cell (ANC) counts were measured and compared to a historical series of patients, and hematological toxicity was assessed. The endpoints of the study were nadir WBC and ANC counts and time to WBC and ANC recovery. RESULTS: Compared to the historical series, filgrastim significantly increased the WBC and ANC throughout the period of subdiaphragmatic irradiation. Nadir WBC (5.98 +/- 1.24/mm3) and ANC (4.71 +/- 1.07/mm3) in the Filgrastim group were approximately two times those of the historical series (3.32 +/- 1.06/mm3 and 2.39 +/- 0.97/mm3 respectively; p < 0.002). Nadir platelet counts were not affected by filgrastim therapy. Three of seven patients reported mild musculoskeletal pain, but there was no other apparent toxicity. CONCLUSION: Compared to the historical series, filgrastim therapy significantly increased WBC and ANC during extended field radiation therapy and was well tolerated. It may be clinically useful in other groups of patients who are likely to develop profound neutropenia during large field irradiation.

Adult↗
PubMed1994

What children see affects how they spell.

The authors predicted that children who have experienced frequent visual confusion of text during their development because of unstable binocular control may be prevented from discovering the rules and patterns of English orthography. The authors compared the spelling errors made by children who had unstable binocular vision with those of children who had stable binocular vision and the same spelling ability. The subjects were drawn from a clinical population of children referred because of suspected reading difficulties; though they were of mixed abilities, they were generally poor spellers and readers. Children with unstable binocular control made spelling errors which were more phonologically plausible than those made by the control group with normal binocular vision.

Child↗
PubMed1994

Laparoscopic cholecystectomy in England and Wales: results of an audit by the Royal College of Surgeons of England.

The results of an audit of open and laparoscopic cholecystectomy conducted by the Comparative Audit Service of The Royal College of Surgeons of England are presented. Data were submitted by 124 consultant surgeons on 3319 attempted laparoscopic and by 227 consultant surgeons on 8035 open cholecystectomies performed in England and Wales during the 2 years 1990 and 1991. These were contrasted with 9322 attempted laparoscopic cholecystectomies reported in 21 series reported in the world literature between 1991 and 1992, and with five other nations' audit studies. Among attempted laparoscopic cases, conversion to an open procedure was necessary in 175/3319 (5.2%) of cases and overall mortality was 0.15% (5/3319). Major complications were reported in 2.1% and minor complications in 5.9% of cases. Bile duct injury was reported to be significantly more common after attempted laparoscopic cholecystectomy (11/3319, 0.33%) than after open cholecystectomy (4/8035, 0.06%) (95% confidence intervals -0.48 to 0.08), but it was not significantly different from that reported for laparoscopic cholecystectomy in the combined world literature (28/9322, 0.3%) (95% confidence intervals -0.19 to 0.25). Most systemic complications were significantly more common after open cholecystectomy. For open cholecystectomy, the mortality was 55/8035 (0.76%), with major complications reported in 3.2% and minor complications in 9.8% of patients. Adoption of the laparoscopic approach was associated with a four-fifths reduction in the mortality of cholecystectomy, and a 40% reduction in the overall complication rate when compared with the open operation. While laparoscopic cholecystectomy has an impressively low mortality and morbidity profile during the first 2 years of its introduction into the UK, prevention of bile duct injury is the most important issue to be addressed in all laparoscopic cholecystectomy training programmes.

Bile Ducts↗