Biomedical subjects
Publications and source records attributed to S Fowler.
Families of head-injured patients may respond to the critical nature of the situation with anxiety and cognitive dissociation. This reaction may be classified as an acute stress disorder (ASD). Symptoms may occur 2-28 days after exposure to a traumatic event. Understanding this problem allows nurses to target assessment and interventions that focus on decreasing stress and facilitating coping.
Increases in high density lipoprotein cholesterol (HDL-C) levels have previously been reported after moderate exercise bouts lasting less than two hours in men. Little information exists, however, on HDL-C responses after moderate duration exercise in women. Post-exercise HDL-C modifications may appear differently in women because of higher baseline HDL-C concentrations and differences in lipolytic activity. To determine the influence of exercise on acute HDL-C responses in women, 12 trained premenopausal women (22 (4) years old; mean (SD)) who ran 24-48 km a week exercised on a motor driven treadmill at 75% VO2MAX until 3.34 MJ (800 kcal) were expended (72 (9) min). Subjects were all tested during the early follicular phase of their menstrual cycle. Fasting blood samples were obtained before exercise (baseline), immediately after (IPE), one hour after (1 h PE), 24 hours after (24 h PE), and 48 hours after (48 h PE) exercise. Plasma was analysed for HDL-C, HDL2-C, and HDL3-C. A significant increase in HDL-C was observed 48 h PE (p<0.05). HDL3-C increased IPE (p<0.01) but returned to baseline at 1 h PE. In contrast, HDL2-C was not significantly different from baseline at any time point. The rise in HDL-C, however, was attributed to an increase in both HDL2 and HDL3. Moreover, at 48 h PE, the increase in HDL-C correlated highly with changes in HDL2-C (r = 0.92). Thus it appears that exercise of moderate duration can elicit similar post-exercise increases in HDL-C in women to those previously reported in men. However, the changes in HDL subfractions leading to the rise in HDL-C may be different in women.
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BACKGROUND: Tumor growth is dependent on the expansion and proliferation of the host vascular system into the primary neoplasm (angiogenesis). The development of an intact vascular system requires migration and proliferation of endothelial cells and assembly into microvessels. Previous studies in our laboratory demonstrated that head and neck squamous cell carcinomas (HNSCC) are angiogenic in vivo. To clarify the mechanism of HNSCC-induced angiogenesis, the present study sought to determine if HNSCCs produced endothelial cell mitogens in vitro. METHODS: Production of PGE-2, TGF-beta, FGF-2 (basic-FGF [fibroblast growth factor]), and vascular endothelial cell growth factor (VEGF) were quantitated by enzyme-linked immunoabsorbant assay (ELISA) in five HNSCC lines. Cell free supernatants of 5 HNSCC lines were tested in a nonradioactive proliferation assay using human umbilical vein endothelial cells (HUVECs). RESULTS: All lines demonstrated enhanced endothelial cell proliferation in a dose-dependent fashion. Fractionation of these supernatants by heparin column chromatography significantly reduced endothelial cell proliferation in the five lines tested (range, 31.7% to 46.23% reduction; mean, 38.14+/-6.02%). Pretreatment with antibody to VEGF but not transforming growth factor (TGF)-beta inhibited endothelial cell proliferation. CONCLUSIONS: These studies indicate HNSCCs produce factor(s) which stimulate endothelial cell proliferation and that VEGF may be involved in HNSCC-induced endothelial cell mitogenesis.
The results of a national audit of sinus surgery are presented. Forty-six consultant ENT surgeons reported on over 2500 sinus procedures. There has been an exponential rise in the number of surgeons in England and Wales performing functional endoscopic sinus surgery (FESS) in recent years. Sixty-five per cent of surgeons in our study used the FESS technique and 81% had formal or other training. Outpatient sinus endoscopy and CT scans have become more routine pre-operative investigations, whilst the use of plain films has waned. There was a wide variation in the numbers of FESS procedures performed by individual surgeons in the 6-month period (between 5 and 85). The overall complication rate was 0.75% for conventional surgery and 1.41% for functional surgery but no major complications were recorded. The primary symptom of blockage was most successfully treated by both conventional and functional surgery (70% and 84% asymptomatic or improved at 6 months). Pain was relieved in 75% of functional procedures and 47% of conventional procedures and discharge relieved in 76% of FESS procedures and 47% of conventional procedures.
BACKGROUND: The Comparative Audit Service of the Royal College of Surgeons of England studied laparoscopic cholecystectomy in England and Wales during 1990-1991. The follow-on study undertaken during 1994 provides data to assess progress. METHODS: Pro formas were sent to consultant surgeons, requesting data on open and laparoscopic cholecystectomies performed in their units during 1994 with data on mean stay, mortality, complications, and the use of peroperative cholangiography and bile duct exploration. The identity of the consultants was treated confidentially. RESULTS: Data were provided by 110 surgeons on 4823 cholecystectomies (1019 open and 3804 laparoscopic) and outcome was compared with that of 3319 attempted laparoscopic and 8035 open cholecystectomies carried out during 1990-1991. The proportion of cases attempted laparoscopically rose from 27.2 per cent in 1990-1991 to 78.9 per cent in 1994, and conversion to open cholecystectomy rose from 5.3 to 6.7 per cent respectively. During 1994 peroperative cholangiography was undertaken in 22.9 per cent of laparoscopic and 44.6 per cent of open cases. Complication rates were similar in the two study periods, except the number of reported haemorrhagic complications was reduced by 40 per cent and bile duct injuries by fivefold (from 0.33 to 0.07 per cent). CONCLUSION: During 1994 the audit sampled approximately 10 per cent of all cholecystectomies performed in England and Wales. The results suggest progress in surgical techniques compared with findings in 1990-1991.
This system for interdepartmental collection of data on surgical complications should, though designed for otolaryngology, be applicable to any surgical specialty. The system under which data are collected prospectively on a coded proforma has been shown to document considerably higher complication rates than retrospective, uncoded data collection and, as consultants are unlikely to report non-existent complications, we assume that the higher rates are more valid. The system also provides a list of factors which must be standardised before data on complication rates from different units can usefully be pooled or comparisons made between them.
Chimeric anti-CD4 monoclonal antibody was administered intravenously as a single dose to eight patients with mycosis fungoides. The dose was escalated throughout the study between patients groups, and individual patients received 50, 100, or 200 mg per dose. Seven of eight patients responded to treatment with an average freedom from progression of 25 weeks (range, 6 to 52 weeks). The treatment was well tolerated, and there was no clinical evidence of immunosuppression. Following treatment, there was significant suppression of peripheral blood CD4 counts in all patients for 1 to 22+ weeks. Only one patient made a very low titer human antichimeric antibody response. All but two patients made primary antibody and T-cell proliferative responses to a foreign antigen administered 24 hours after antibody infusion. However, there was generally marked, but temporary suppression of T-cell proliferative responses in vitro to phytohemagglutinin (PHA), tetanus toxoid, and normal donor lymphocytes. We conclude that at the dose levels studied, this antibody (1) had clinical efficacy against mycosis fungoides; (2) was well tolerated; (3) had a low level of immunogenicity; (4) decreased T-cell proliferative responses in vitro, and (5) did not induce tolerance to a foreign antigen.
In order to compare the influence of a single bout of exercise on HDL-C metabolism with normal variability, 12 male runners (mean age: 24.9 +/- 4 yr) who ran 15-30 miles per week underwent exercise (E) and control (C) experimental conditions. During the E trial subjects ran on a motor driven treadmill at 75% (42.5 +/- 4.7 ml.kg-1.min-1) VO2max until 800 Kcals were expended. The C trial consisted of no exercise. Subjects were instructed to follow the same diet and keep a four d food diary during each experimental condition. Fasted blood samples were obtained at the same time of day in each condition at time points corresponding to 24 h pre-exercise (24 PRE), 6 h post- (6 h) and 24 h post-exercise (24 h). Plasma was analyzed for HDL-C, HDL2-C and HDL3-C (mg.dl-1). In addition post-heparin plasma samples were analyzed for lipoprotein lipase (LPL) and hepatic lipase (HL) activity (mumol.FFA-1.ml-1). All values were adjusted for changes in plasma volume and compared to Baseline. HDL-C levels were unaltered following the C trial. However, following the E trial, HDL-C increased (p < 0.01) above baseline values at 24 h. The increase in HDL-C was reflected in the HDL3-C subfraction (p < 0.05). Analysis of lipolytic activity revealed an overall greater LPL activity (p < 0.05) in the E trial vs the C trial. In addition, a decrease in HL was observed at 24 h (p < 0.05) but was not different between experimental conditions. These data suggest that exercise and not normal variability are responsible for alterations in lipolytic activity and corresponding increases in HDL-C levels.
Expression of a major thyroid autoantigen, thyroid peroxidase (TPO) was studied using the baculovirus-insect cell expression system. Human TPO cDNA modified so as to code for the extracellular fragment of the protein was placed under the control of the strong polyhedrin promoter in baculovirus transfer vector pBlueBacIII and cotransfected with linearized AcMNPV viral DNA. Expression in two insect cell lines Spodoptera frugiperda (Sf9) and Tricoplusia ni (High Five) was investigated and levels of recombinant TPO (rTPO) monitored by RIA and SDS-PAGE followed by Western blotting. Both insect cell lines expressed rTPO, but higher levels (30 mg/l culture medium) were obtained with High Five cells. Culture medium rTPO was purified and its glycosylation and immunoreactivity analysed. Lectin-affinity blotting and treatment with glycosidases indicated that both high mannose and complex-type sugar residues were associated with the recombinant protein. Studies with an ELISA based on biotinlabelled rTPO and an immunoprecipitation assay based on 125I-labelled rTPO indicated that the rTPO and native TPO showed similar reactivity to TPO autoantibodies (r = 0.96, P < 0.001, n = 50 and r = 0.99, P < 0.001, n = 80 respectively). In addition, rTPO expressed in High Five cells showed enzyme activity comparable with that of native TPO when the heme biosynthesis precursor delta-aminolevulinic acid was included in the culture medium. Overall, our studies indicate that the High Five insect cell line provides a useful system for the expression of relatively high levels of rTPO which should be suitable for structural analysis of TPO and TPO-TPO autoantibody complexes.
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A survey to assess variations in management and outcome of patients admitted with epistaxis was conducted. A questionnaire was sent to all consultant otolaryngologists working at NHS hospitals in England and Wales requesting information about management of patients admitted with epistaxis over a 3 month period. Data analysis of information provided by 102 consultants for a total of 933 patients was performed. The average number of patients admitted with epistaxis over a period of 3 months per consultant was 10.2. More than 70% of the patients were aged 60 years or over. Approximately 75% of the patients required nasal packing; the most common pack used was BIPP (Bismuth Iodine Paraffin Paste). Of the patients, 5.6% required general anaesthesia, with less than 1% requiring formal arterial ligation. The mean duration of stay in hospital was 2.9 days. Few complications were reported. Patients admitted with epistaxis were generally managed conservatively, with very few requiring surgical intervention. There was remarkable consensus in various aspects of management of patients admitted with epistaxis.
The 1990s has been heralded as the Decade of the Brain. The National Stroke Association refers to stroke as a brain attack. Medical and nursing interventions are aimed at limiting the extent of brain injury, promoting early reperfusion, and preventing complications as a result of secondary injury or hazards of immobility. Medical-surgical nurses play a key role in facilitating collaborative rehabilitation in the acute care setting to achieve expected outcomes for the patient and family.
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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.
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.
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.