New antiepileptic drugs.
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Anticonvulsants↗
Biomedical subjects
P Twomey
Publications and source records attributed to P Twomey.
A case of auto-erotic asphyxia in a long-term psychiatric setting.
The syndrome of auto-erotic asphyxia (AEA) involves the deliberate induction of cerebral hypoxia to produce or enhance sexual excitement. This sexual practice is normally only discovered when death results from the act because these individuals rarely seek professional advice. The practice of AEA in the living case presented here was initially misinterpreted as parasuicidal behaviour. This type of sexual behaviour should always be considered a differential for parasuicidal activity involving asphyxia. Aetiology, treatment and the need for health professionals to be aware of this syndrome are discussed.
Adult↗
Direct evidence for in vivo nitroxide free radical production from a new antiarrhythmic drug by EPR spectroscopy.
The new Class I anti-arrhythmic agent 2,2,5,5-tetramethyl-3-pyrroline-1-carboxamide derivative, is currently being evaluated in clinical trials in patients with a high risk for cardiac arrhythmias. In this study we show that this antiarrhythmic drug can be chemically converted to the nitroxide free radical analog. Further, using an in vivo Electron Paramagnetic Resonance (EPR) spectroscopy model by detecting free radicals in the distal portion of the tail of an anesthetized mouse, we demonstrate that the drug is oxidized to the corresponding nitroxide. In vitro studies using Chinese hamster V79 cells suggest that the oxidation products of the drug, namely, the hydroxylamine and the nitroxide protect against oxidative damage induced by hydrogen peroxide (H2O2). Taken together, our results suggest that, in addition to the antiarrhythmic effects of the parent drug, sufficient levels of nitroxides may accumulate from the parent drug in vivo to provide antioxidant defense to cardiac tissue that may be subject to ischemia and oxidation-driven injury.
Animals↗
Nutrition support in clinical practice: review of published data and recommendations for future research directions. Summary of a conference sponsored by the National Institutes of Health, American Society for Parenteral and Enteral Nutrition, and American Society for Clinical Nutrition.
In the last 30 years, marked advances in enteral feeding techniques, venous access, and enteral and parenteral nutrient formulations have made it possible to provide nutrition support to almost all patients. Despite the abundant medical literature and widespread use of nutritional therapy, many areas of nutrition support remain controversial. Therefore, the leadership at the National Institutes of Health, The American Society for Parenteral and Enteral Nutrition, and The American Society for Clinical Nutrition convened an advisory committee to perform a critical review of the current medical literature evaluating the clinical use of nutrition support; the goal was to assess our current body of knowledge and to identify the issues that deserve further investigation. The panel was divided into five groups to evaluate the following areas: nutrition assessment, nutrition support in patients with gastrointestinal diseases, nutrition support in wasting diseases, nutrition support in critically ill patients, and perioperative nutrition support. The findings from each group are summarized in this report. This document is not meant to establish practice guidelines for nutrition support. The use of nutritional therapy requires a careful integration of data from pertinent clinical trials, clinical expertise in the illness or injury being treated, clinical expertise in nutritional therapy, and input from the patient and his/her family. (Journal of Parenteral and Enteral Nutrition 21:133-156, 1997).
Cachexia↗
The effect of amphotericin B, aztreonam, imipenem and cephalosporins on the bone marrow progenitor cell activity.
The effects of certain antibiotics on the colony forming activity of human bone marrow cells in semisolid methylcellulose medium in vitro and on murine BM cells in spleen colony forming units (cfu-s) in vivo were evaluated. Amikacin, gentamicin, piperacillin, co-trimoxazole and pentamidine had little or no effect on human bone marrow progenitor cell function; amphotericin B, aztreonam, ceftazidime and imipenem caused significant suppression of human colony forming unit-erythroid (cfu-e), burst forming unit-erythroid (bfu-e) and colony forming unit-granulocyte macrophage (cfu-gm) at both peak and trough serum concentrations. At molar equivalent concentrations ceftazidime, cefotaxime and cefoperazone caused significant decreases in human cfu-e, bfu-e and cfu-gm in vitro (P less than 0.01) and murine cfu-s in vivo (P less than 0.05); cefoxitin, cefuroxime, ceftizoxime and ceftriaxone did not suppress human bone marrow progenitor cell activity. Gentamicin, piperacillin and ceftriaxone had no effect on murine cfu-s formation. Further studies to evaluate the effect of these antibiotics on human bone marrow in vivo are suggested.
Amphotericin B↗
Potent graft antitumor effect in natural killer-resistant disseminated tumors by transplantation of interleukin 2-activated syngeneic bone marrow in mice.
The current study is a continuation of our previous work showing that bone marrow activated in interleukin 2 has antitumor and antiviral activity in vitro. The antitumor efficacy of IL-2-activated bone marrow cells in vivo was assessed here. Our results indicated that bone marrow cells activated in IL-2 for 3 days (ABM) have antitumor activity in vivo and cause significant tumor regression in mice being treated with ABM and concurrent i.p. administration of IL-2. In mice also bearing larger tumor burdens, those receiving ABM and i.p. IL-2 showed the most significant tumor regression. The ABM seem to be more potent than conventional IL-2-activated spleen lymphokine-activated killer cells. In studies done using lower dosages of IL-2 or log lower number of cells, the ABM caused more significant tumor regression than lymphokine-activated killer cells. We also assessed the antitumor efficacy of short term (1 day) IL-2-activated bone marrow, the short term-activated bone marrow being preferred in bone marrow, transplantation because of the minimum amount of cells lost due to its shorter incubation period. We also showed that short term-activated bone marrow caused tumor regression similar to ABM and could reconstitute lethally irradiated mice similar to fresh bone marrow. Therefore, the biomodulation of bone marrow cells could be used as an active therapeutic tool in autologous bone marrow transplantation, producing graft versus tumor effects without any graft versus host effect.
Animals↗
Local control in rectal cancer. A clinical review and meta-analysis.
We reviewed the factors influencing local control of potentially curable rectal cancer in 106 patients. There was improvement in stage-adjusted local control associated with increasing use of adjuvant radiation therapy. A meta-analysis of the English-language literature through 1988 also supported the effectiveness of adjuvant radiation therapy in all but the lowest-risk patients. No effect on survival was identified in either analysis, but a reduction of up to 40% in local recurrence rates may be achieved with doses of 3000 cGy or more.
Humans↗
Successful treatment of adrenal metastases from large-cell carcinoma of the lung.
Although on a weight basis the adrenal gland is the most common site of extranodal spread from lung cancer, antemortem diagnosis and successful therapy of adrenal metastasis are rare. We have treated two patients with apparently solitary metastases in the adrenal gland from large-cell carcinomas of the lung using a combination of adrenalectomy and vigorous therapy to the primary site. Both patients experienced symptomatic relief, and, in contrast to the expected short survival in lung cancer with distant metastasis, they remain well six years and 14 years after treatment.
Adrenal Gland Neoplasms↗
Clinical problems in radiotherapy of carcinoma of the pancreas.
Since 1975, 94 patients with localized unresectable carcinoma of the pancreas have been irradiated using helium and heavier particles at the University of California Lawrence Berkeley Laboratory. Despite surgical exploration and an extensive diagnostic workup including radiological, nuclear medicine, and computer-assisted tomographic studies, many patients proved to have occult liver metastases manifested within 9 months post treatment. In addition, local and regional control of the primary neoplasm (approximately 20%) has been difficult to obtain even with doses of 6000 equivalent rad in 7 1/2 weeks. Gastric and biliary obstruction have required surgical bypass procedures since irradiation has not been successful in relieving obstructive symptoms. Evidence of gastrointestinal injury has been present in postradiation therapy in approximately 10% of patients, a figure which might be higher if more patients had a longer survival (average 10 months). Some patients require pancreatic enzyme supplementation because of pancreatic deficiency either secondary to tumor or treatment. Further improvement in local control and survival requires better diagnostic methods for evaluation of local and metastatic spread, improved therapy for local and regional disease, as well as therapy directed at occult liver metastases that are frequently present.
Adenocarcinoma↗
Immunopathology of B-cell lymphomas induced in C57BL/6 mice by dualtropic murine leukemia virus (MuLV).
Combined clinicopathologic and immunomorphologic evidence is presented that would indicate that a murine leukemia virus (MuLV) with the dualtropic host range is capable of producing a clinically malignant lesion composed of immunoblasts and associated plasma cells in C57BL/6 mice. This process, morphologically diagnosed as an immunoblastic lymphoma of B cells using standard histopathologic criteria, was found to be distinctly polyclonal with regard to immunoglobulin (Ig) isotype when analyzed for both surface and cytoplasmic Ig. Further studies demonstrated that this clinicopathologically malignant, dualtropic MuLV-induced, polyclonal immunoblastic lymphoma of B cells in C57BL/6 mice was normal diploid and unable to be successfully transplanted to nonimmunosuppressed syngeneic recipients. Although all serum heavy and light chain components were found to be progressively elevated as the tumor load increased, the polyclonal increase in serum immunoglobulins was most pronounced for mu heavy and kappa light chains (ie, mu greater than gamma 2A greater than alpha greater than gamma 2B greater than gamma 1; kappa greater than lamba). The dissociation of clinicopathologic and biologic criteria for malignancy in the presently described dualtropic (RadLV) MuLV-induced B-cell lesion is sharply contrasted with the thymotropic (RadLV), MuLV-induced T-cell lymphoblastic lymphoma in C57BL/6 mice. This process is also a clinicopathologically malignant lesion but, when one uses biologic criteria, is found to be distinctly monoclonal, aneuploid, and easily transplanted to nonimmunosuppressed syngeneic recipients. The close clinicopathologic and biologic similarities of the dualtropic MuLV-induced animal model to corresponding human B-cell lymphoproliferative diseases are stressed.
Animals↗
Randomized study of 5-FU and CCNU in pancreatic cancer: report of the Veterans Administration Surgical Adjuvant Cancer Chemotherapy Study Group.
Between the years 1973-1977, 152 male patients from 28 participating Veterans Hospitals with histologically proven nonresectable cancer of the pancreas were randomized in a two-arm study. The treated group was to receive combination chemotherapy with 5-FU and CCNU, and the controls were to receive no chemotherapy. Both groups were comparable with respect to age, amount of weight loss, extent of histologically proved metastases, and operation performed. In the treatment group, drug therapy was begun between 10 and 60 days postoperatively. Intravenous 5-FU, 9 mg/kg, was administered on five consecutive days, and CCNU, 70 mg/m2, was given orally on the first day of each course. In the absence of toxicity, the course was repeated every six weeks for life; 146 drug courses were given. The incidence of toxicity was not great. One or more toxic reactions were reported for one-third of the drug courses administered, but for the most part, these were mild. The most frequent toxic reaction was vomiting in 17% of the courses, and hematologic toxicity-primarily leukopenia-in 15% of the drug courses. There was no evidence of a beneficial effect on survival from drug treatment in the group as a whole or in any subgroup analyzed. The median survival of the control group was 3.9 months, and of the drug-treated group, 3.0 months.
Adenocarcinoma↗
Malnutrition in veterans administration surgical patients. Updated standards.
A prospective nutritional assessment of 106 hospitalized Veterans Administration surgical patients was performed; 60 healthy, age-matched outpatient veterans were studied for controls. Standard biochemical and anthropometric indices were measured. Malnutrition was defined for each index as a value more than 2 SD below the mean established from the VA control population, the values from which were also compared with conventionally accepted published standards of malnutrition. Striking discrepancies in the incidence of abnormal nutritional indices in our patients were observed, depending on which standard was used. The frequencies of abnormal in our surgical patients using VA control values or published norms, respectively, were: albumin level, 43% vs 19%; hematocrit value, 38% vs 27%; total iron-binding capacity, 30% vs 37%; arm muscle circumference, 11% vs 0%; and triceps skin fold, 19% vs 35%. Future studies of nutritional assessment in hospitalized patients should use control subjects closely related to the target population in age and other demographic variables.
Anthropometry↗
Respiratory gas tensions and pH in healing wounds.
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Animals↗
Utility of skin testing in nutritional assessment: a critical review.
To evaluate the claim that delayed cutaneous hypersensitivity skin testing is useful in nutritional assessment of hospitalized patients, we reviewed the English language literature of the last 12 years. Although several hundred publications discussed delayed cutaneous hypersensitivity testing and nutritional status, only 15 provided new, objective data correlating these variables in hospitalized adults. Of these, only three provided age-matched control groups to control for antigen variability, lack of prior exposure, and other technical problems. The majority of reports took no account of diseases (cancer, immune disease, infection) or therapies (radiation, drugs, surgery) known to affect skin test response. In the reports specifying different degrees of malnutrition, the most important group, those with less than obvious malnutrition, were not abnormal by skin testing. Ten reports described serial skin testing during nutritional intervention. Non reported serially tested controls without nutritional intervention, important since serial testing alone can augment skin test response. Nonnutritional intercurrent therapy which might affect skin tests was seldom mentioned. In the few reports specifying that nutritional repletion was even achieved, repleted patients were not separated from unrepleted in subsequent analyses. No report examined skin testing for its predictive accuracy, cost/benefit ratio, or influence on outcome. Because of these problems in experimental design, the frequent lack of appropriate controls, and the low specificity of abnormal delayed cutaneous hypersensitivity responses, we conclude that the utility of skin testing in nutritional assessment remains unproved.
Humans↗
Assessing nutritional assessment.
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Humans↗
Nutrition support in clinical practice: review of published data and recommendations for future research directions. National Institutes of Health, American Society for Parenteral and Enteral Nutrition, and American Society for Clinical Nutrition.
In the last 30 years, marked advances in enteral feeding techniques, venous access, and enteral and parenteral nutrient formulations have made it possible to provide nutrition support to almost all patients. Despite the abundant medical literature and widespread use of nutritional therapy, many areas of nutrition support remain controversial. Therefore, the leadership at the National Institutes of Health, The American Society for Parenteral and Enteral Nutrition, and The American Society for Clinical Nutrition convened an advisory committee to perform a critical review of the current medical literature evaluating the clinical use of nutrition support; the goal was to assess our current body of knowledge and to identify the issues that deserve further investigation. The panel was divided into five groups to evaluate the following areas: nutrition assessment, nutrition support in patients with gastrointestinal diseases, nutrition support in wasting diseases, nutrition support in critically ill patients, and perioperative nutrition support. The findings from each group are summarized in this report. This document is not meant to establish practice guidelines for nutrition support. The use of nutritional therapy requires a careful integration of data from pertinent clinical trials, clinical expertise in the illness or injury being treated, clinical expertise in nutritional therapy, and input from the patient and his/her family.
Humans↗
Effect of exposure to 94 per cent oxygen on the metabolism of wounds.
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Animals↗