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Biomedical subjects

J Eaton

Publications and source records attributed to J Eaton.

At least 19 recordsLinked to original sources

Coxsackie B and adenovirus receptor, integrin and major histocompatibility complex class I expression in human prostate cancer cell lines: implications for gene therapy strategies.

Gene therapy strategies based on modifying tumour cells using high efficiency adenoviral vectors have shown promise in the clinic. Recently the Coxsackie and adenovirus receptor (CAR) has been shown to mediate adenoviral entry into tumour cells, although previous studies also suggested a role for MHC class I heavy chain. Detailed evaluation of the expression of both CAR and MHC class I in prostate cancer cell lines would have important implications for therapeutic strategies. We have found that, unlike cell lines derived from other malignancies, in human and murine prostate cancer loss of CAR expression appears to be relatively infrequent and does not correlate with loss of MHC class I expression. These findings, together with the demonstration of appreciable levels of cell-surface expression of integrins, suggest that cancer vaccine strategies based on modifying whole prostate cancer cells should be feasible using the current generation of recombinant adenoviral vectors, without deleterious effects on either the virus vector or the target cell.

Adenoviridae↗

A pilot study of recombinant insulin-like growth factor-1 in seven multiple sderosis patients.

The purpose of this open-label, crossover study was to determine the safety and efficacy of recombinant insulin-like growth factor-1 (rhIGF-1) using magnetic resonance imaging (MRI) and clinical measures of disease activity in seven multiple sderosis (MS) patients. Monthly clinical and MPI examinations were performed during a 24-week baseline and a 24-week treatment period with rhIGF-1. The primary outcome measure was contrast enhancing lesion (CEL) frequency on treatment compared to baseline. Secondary outcome measures included dinical and MRI measures of disease activity including: white matter lesion load (WMLL), magnetization transfer ratio (MTR), T1-Hypointensity volume, cervical spine cross-sectional area and proton magnetic resonance spectroscopic (MRS) imaging for determining regional metabolite ratios. rhIGF-1 (Cephalon) was administered at a dose of 50 mg subcutaneously twice a day for 6 months. rhIGF-1 was safe and well tolerated with no severe adverse reactions. There was no significant difference between baseline and treatment periods for any MRI or clinical measures of disease activity. Although rhIGF-1 did not alter the course of disease in this small cohort of MS patients, the drug was well tolerated. Further studies using rhIGF-1 alone or in combination with other therapies may be of value because of the proposed mechanism of action of this growth factor on the oligodendrocyte and remyelination.

Aged↗

Encephalitogenic potential of the myelin basic protein peptide (amino acids 83-99) in multiple sclerosis: results of a phase II clinical trial with an altered peptide ligand.

Myelin-specific T lymphocytes are considered essential in the pathogenesis of multiple sclerosis. The myelin basic protein peptide (a.a. 83-99) represents one candidate antigen; therefore, it was chosen to design an altered peptide ligand, CGP77116, for specific immunotherapy of multiple sclerosis. A magnetic resonance imaging-controlled phase II clinical trial with this altered peptide ligand documented that it was poorly tolerated at the dose tested, and the trial had therefore to be halted. Improvement or worsening of clinical or magnetic resonance imaging parameters could not be demonstrated in this small group of individuals because of the short treatment duration. Three patients developed exacerbations of multiple sclerosis, and in two this could be linked to altered peptide ligand treatment by immunological studies demonstrating the encephalitogenic potential of the myelin basic protein peptide (a.a. 83-99) in a subgroup of patients. These data raise important considerations for the use of specific immunotherapies in general.

Adolescent↗

Recent changes in the workload and clinical experience of pre-registration house officers: experiences over four years in south-west England.

We aimed to measure changes in the training and workload of pre-registration house officers using a postal questionnaire. Two hundred and six pre-registration house officers in the south-western region of England were surveyed and asked to report on the education, training and workload of their posts. Results were compared with a survey conducted four years earlier. Since the previous survey, the number of hours on duty had reduced from a median of 80 h week-1 in 1992/3 to 72 h week-1 in 1996/7 (P < 0.0001). There were no statistically significant changes in the number of patients admitted or clerked in an average week, but house officers' clinical experience had fallen. All but five of 26 marker conditions showed a decline, which was statistically significant in seven cases. House officers were keener to include four months of general practice in the pre-registration year and were less adverse to extending the pre-registration year to two years. The reduction in hours of work for house officers has been accompanied by a decline in their clinical exposure to common medical and surgical emergencies. The long-term effects of these changes are unknown.

Emergency Medicine↗

Low prevalence of psychoses among the Hutterites, an isolated religious community.

OBJECTIVE: The authors estimated the prevalence of psychoses among the Hutterites in Manitoba, Canada, who lived in 102 communal farms or colonies. The study stemmed from an earlier epidemiological survey of North American Hutterite colonies (1950-1953), in which a low prevalence of psychoses was documented. METHOD: Psychiatrically ill individuals identified during the previous survey were rediagnosed with DSM-IV criteria. A current provincial health insurance claims database was queried anonymously for the period June 1992-May 1997, and the prevalence rate of disease among Hutterites, identified by distinctive surnames and unique postal addresses, was compared with the rate in the entire population of the province of Manitoba and in a comparison group of persons with Hutterite surnames but with addresses outside the Hutterite colonies. RESULTS: The annual prevalence of schizophrenia among the communal Hutterites, estimated from the database search by using ICD-9 criteria, was consistent with the prevalence found in the prior epidemiological survey (annual mean of 1.2/1,000 population, compared with 1.3/1,000 in the prior survey). The database search yielded a significantly lower prevalence for schizophrenia and other functional psychoses among communal Hutterites as well as among the comparison group, compared to the total Manitoba population. There was also lower prevalence for affective psychoses and adjustment reaction disorders among the communal Hutterites, compared to the total Manitoba population. Rates for neurotic disorders were elevated both among the communal Hutterites and the comparison group. CONCLUSIONS: The prevalence of specific psychoses was reduced among the Hutterites, although neurotic disorders were more prevalent. These findings suggest some specificity, although possible artifacts such as ascertainment bias must be considered. Further research is needed to examine genetic and environmental factors that may contribute to reduced prevalence of specific psychoses among the Hutterites.

Age of Onset↗

Teaching vaginal breech delivery and external cephalic version. A survey of faculty attitudes.

OBJECTIVE: To ascertain current faculty attitudes regarding teaching of vaginal breech delivery (VBD) and external cephalic version (ECV). STUDY DESIGN: A questionnaire was sent to obstetrics and gynecology residency programs. Respondents were queried regarding demographic parameters, resident and practice experience, and attitudes toward teaching these procedures. RESULTS: Fifty-four (96%) surveys were returned. Sixteen (30%) respondents were female and 38 (70%) male. Sixteen (30%) completed residency prior to 1980, 17 (32%) during the 1980s and 21 (48%) during the 1990s. Nineteen (35%) trained locally. Forty-seven (87%) received training in VBD during residency. Thirty-five (65%) received training in ECV. Thirty-two (60%) had performed VBDs in practice. However, only 18 (33%) continued to perform this procedure. During the proceeding three years, they reported performing an average of five VBDs per chief resident per year. Thirty-seven (69%) performed ECV in clinical practice. The 17 who did not indicated that they referred to others. They reported performing an average of 15 ECVs per chief resident per year. Fifty-two (96%) thought residents should still be taught VBD. All faculty thought that residents should be taught ECV. None of the above parameters exerted a statistically significant effect on these opinions. CONCLUSION: There was nearly universal faculty support for continuing to teach VBD to residents. However, only one-third of faculty members currently perform this procedure. There do not appear to be sufficient numbers of VBDs to teach this procedure utilizing a "hands on" approach. There is universal support for teaching ECV. There appear to be both enough individuals with experience and enough procedures to accomplish this education.

Attitude↗

Gasless laparoscopy using a planar lifting technique.

In clinical use, the mechanical lifting technique has demonstrated the ability to displace the abdominal wall and create a useful cavity for visualization and surgical manipulation. By forming a planar ceiling, as opposed to the domed ceiling of conventional pneumoperitoneum, the abdominal organs are brought into closer proximity of the surgeon. Instrument length may be shortened, imparting greater surgical control. Without the necessity for gas sealing, entry portals are simplified. Conventional instruments (right angle clamps) may be introduced through the fan retractor insertion sites or by way of separate stab incisions. The planar lifting technique has the potential for simplifying laparoscopy and restoring instrument control to the operating surgeon.

Abdominal Muscles↗

A multiyear study of blood cholinesterase activity in urban pesticide applicators.

This article is a review of blood cholinesterase activity in a cohort of urban pesticide applicators ranging from 1680 to over 3800 workers. During the period 1981-1991, 208, 788 blood samples were taken for measurement of cholinesterase activity with an average of 6 samples per year from each worker. A total of 150 workers or 0.44% of the cohort was removed from exposure to cholinesterase-inhibiting insecticides because of decreased cholinesterase activity. No worker required treatment for signs of cholinesterase inhibition.

Adult↗

Kohl: a lead-hazardous eye makeup from the Third World to the First World.

Kohl is a widely used traditional cosmetic. It is mainly worn around the eyes in Asia, Africa, and the Middle East. It may be a pervasive source of lead poisoning in those areas and among individuals from those areas who have immigrated to developed nations. Samples of kohl were purchased in Morocco, Mauritania, Great Britain, and the United States. Some of these samples originated from Pakistan, India, and Saudi Arabia. Kohl is widely believed to consist of antimony, but analysis consistently revealed only trace amounts of antimony. Nine of the twenty-two samples tested contained less than 0.6% lead; however, seven samples had lead levels in excess of 50%. The remainder ranged from 3.31 to 37.3%. Third-world-manufactured kohls were purchased in the United States and Britain, suggesting that this hazard is no longer confined to the third world. Those kohls that contained lead were sold in violation of laws on lead in cosmetics in both of these nations. Third-world physicians and health care workers appear to be unaware of possible lead uptake from unsuspected traditionally used items. Physicians in developed nations with patients from Asia, the Middle East, and North Africa need to factor in the possibility of past or present lead intake from unorthodox sources such as kohl.

Antimony↗

Exposure of endothelial cells to free heme potentiates damage mediated by granulocytes and toxic oxygen species.

Endothelial damage may follow exposure to toxic oxygen species generated by closely apposed ("marginated") granulocytes. Because iron markedly catalyzes oxidant damage in diverse systems, we wondered whether intercalculated heme, and/or its constituent iron, might potentiate oxidant damage of endothelium. Cultured monolayers of porcine aortic endothelial cells were exposed for brief periods to purified hemin. Uptake of heme was rapid, dose dependent, and not reversible by buffer or serum washes. Despite high levels of cell-associated heme, no direct heme-mediated cytotoxicity occurred, but heme-loaded endothelium became highly sensitive to oxidant challenge by (a) reagent H2O2, (b) enzymatically generated oxidants (xanthine/xanthine oxidase), or (c) phorbol-activated polymorphonuclear leukocytes. An increase in endothelial cell lipid peroxidation accompanied heme-augmented oxidant cytolysis, and both parameters were reduced in parallel by micromolar amounts of the hydrophobic oxygen radical scavenger/iron chelator U74500A. Endothelial uptake of heme was inhibited by a specific heme-binding protein, hemopexin. Concomitantly, hemopexin completely blocked augmented H2O2- and polymorphonuclear leukocyte-mediated cytotoxicity but only if added simultaneously and stoichiometrically with hemin. Significant loss of protection occurred if hemopexin addition was delayed 15 minutes, and protection was completely lost after a 60-minute interval. The iron moiety of heme was critical to oxidant sensitization because neither iron-free protoporphyrin IX nor tin-protoporphyrin was able to sensitize endothelial cells to H2O2 or activated polymorphonuclear leukocytes. These results may provide mechanistic insights into atherogenesis, reperfusion injury, and the organ injury accompanying hemoglobinemia or myoglobinemia.

Animals↗

Ketogenic diets in the treatment of epilepsy: short-term clinical effects.

The classical 4:1 ketogenic diet, the medium-chain triglyceride (MCT) diet and a modified MCT diet were used in the treatment of 55 children and four adults with intractable epilepsy. During a three-month treatment period 51 of 63 studies (81 per cent) showed greater than 50 per cent reduction in seizure frequency. This improvement was independent of diet used and type of seizure experienced by patients. The diets were found to be acceptable and of therapeutic benefit to the children, but treatment of the four adult patients with the MCT diet was unsuccessful. There was no correlation between EEG changes and clinical response. The three ketogenic diets were shown to be effective in the short-term management of children whose epilepsy is poorly controlled with anticonvulsant drugs.

Adolescent↗

Vitamin C intoxication and hyperoxalemia in chronic hemodialysis patients.

We studied vitamin C levels in 25 stable patients on chronic hemodialysis who were taking 0.5-1 g vitamin C orally daily and/or dialyzed against dialysate containing 33.3 micrograms/ml of vitamin C. We also studied the relationship between serum vitamin C and oxalate levels in 7 patients on chronic hemodialysis. All patients had markedly elevated pre- and postdialysis levels of vitamin C. The predialysis levels of vitamin C showed extremely good correlation to the serum oxalate levels. Overingestion of vitamin C in food or as supplementation may lead to excessive serum levels of vitamin C, resulting in hyperoxalemia that may contribute to vascular disease in patients on chronic hemodialysis.

Adolescent↗

Target specificity and cell surface structures involved in the human cytolytic T lymphocyte response to endothelial cells.

Two long-term cytolytic T lymphocyte (CTL) lines derived from the peripheral blood lymphocytes (PBL) of a single donor were analyzed for target specificity and involvement of cell surface molecules in CTL-target interactions. One line, AH2, was generated after stimulation with B lymphoblastoid cells. Cytolysis by these cells was restricted to targets expressing the appropriate HLA-A2 specificity and was blocked by mAb recognizing CD2, CD3, CD8, LFA-1, and LFA-3. The second line, AE1, was generated after stimulation with cultured endothelial cells derived from human newborn preputial microvessels. These CTL lysed all human target cells tested, except autologous cells and the Class I negative cell line Daudi. In addition, mAb specific for CD2, CD3, and CD8 did not affect cytolysis. Anti-LFA-1 and -LFA-3 mAb blocked cytolysis of B lymphoblastoid targets but not endothelial targets. These results indicate that some CTL utilize as yet uncharacterized cell surface structures for CTL-target interactions.

Antigens, Surface↗

Circadian temperature rhythm and circadian-circaseptan (about 7-day) aspects of murine death from malaria.

About-7-day (circaseptan) and circadian rhythms were sought and found in host-parasite relations of mice infected with Plasmodium berghei. Five inbred male DBA mice, about 18 weeks of age, were implanted with transsensors for temperature telemetry. Core temperature, monitored every 10 min for 3 days before the intravenous or intraperitoneal inoculation of 10(5) infected erythrocytes and thereafter until death, was analyzed by cosinor. A statistically highly significant circadian rhythm exhibited similarly synchronized acrophases. Core temperatures on the days immediately after malarial infection were mostly within the range of temperatures observed before injection. A mesor-hypothermic stage preceded death by several days. In a second study, 24 male BALB/c and 42 male DBA mice, 12 weeks of age, housed in three rooms on different regimens of light and darkness (alternating at 12-hr intervals), staggered by 8 hr, were inoculated ip with 10(4) infected erythrocytes, one-half at noon, the other half at midnight, within 0.5 hr of blood withdrawal. Thus, one endeavored to cover six circadian host stages (02, 06, 10, 14, 18, and 22 hr after light-on). At 54 and 51% overall mortality (irrespective of inoculation time), a circadian rhythm in susceptibility to malaria was demonstrated in these mice by the single cosinor fit of a 24-hr period (P less than 0.003 and less than 0.020, respectively). The single cosinor fit of a 7-day period further demonstrated a circaseptan rhythm (P = 0.014) in the mortality of both strains following the inoculation of P. berghei. The acrophase (360 degrees = 168 hr) was at -325 degrees from the inoculation time with 95% confidence limits extending from -276 to -378 degrees. Such predictable time relations of P. berghei to its murine host await the exploration of mechanisms underlying the circadian and infradian (7-day) rhythmicities here demonstrated and quantified with their uncertainties. Irrespective of mechanisms, information on such periodicities may also guide attempts to optimize treatment by timing according to the interactions of plasmodial virulence and host resistance that remain to be quantified separately.

Animals↗

Pacemaker malfunction following transthoracic countershock.

Electrical cardioversion or defibrillation may be necessary in patients with implanted artificial cardiac pacemakers. Sudden discharge of high electrical energy employed in DC transthoracic countershock procedures may damage the sensitive pacemaker circuitry and result in malfunction. We report a case in which, following synchronized DC countershock, a non-programmable demand pacemaker functioned in the R-wave triggered mode rather than the R-wave inhibited mode as designed. Further, the pacemaker output voltage was reduced to about half its specified output. Such a malfunction may not be readily apparent, and requires careful analysis following electric shock.

Aged↗