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Biomedical subjects

C Thomas

Publications and source records attributed to C Thomas.

At least 19 recordsLinked to original sources
PubMed1992

Inhibition of glutathione reductase by flavonoids. A structure-activity study.

A structure-activity study of fourteen chemically related flavonoids was conducted to evaluate their abilities to inhibit glutathione reductase (GR). By comparing the I50 values of flavonoids from different classes possessing an identical hydroxyl configuration, we determined the following order of potency for inhibition of GR: anthocyanidin > dihydroflavonol = chalcone > flavonol > catechin. Enzyme inhibition by delphinidin chloride and myricetin was partially prevented in a N2 atmosphere which implicates a role for oxygen in the mechanism of inhibition. To determine the role of oxygen species in enzyme inhibition, GR was preincubated with either mannitol, diethylenetriaminepenta-acetic acid (DETAPAC), superoxide dismutase (SOD), catalase (CAT), or SOD and CAT prior to assays for enzyme inhibition by flavonoids. Enzyme inhibition by delphinidin chloride and myricetin was suppressed by the addition of SOD, suggesting that superoxide (O2-.) is involved. However, inhibition by quercetin and morin was not sensitive to antioxidants. To further investigate the role of O2-. in GR inhibition, a superoxide generating system was utilized in the presence and absence of flavonoid. The O2-. generating system failed to inhibit GR in the absence of flavonoid but enhanced the inhibition by myricetin, indicating that the O2-. did not directly inhibit GR but reacted directly with certain flavonoids to form a reactive intermediate which, in turn, inhibited GR. These findings suggest that the mechanism of inhibition of GR by flavonoids is complex and may have oxygen-dependent and oxygen-independent components.

Antioxidants↗
PubMed1992

Use of fluorine-19 nuclear magnetic resonance spectroscopy and hydralazine for measuring dynamic changes in blood perfusion volume in tumors in mice.

BACKGROUND: One method of evaluating the mechanism of action of agents which alter tumor oxygenation is to determine their effects on tumor blood flow. PURPOSE: This study tests applicability of a new approach using an emulsion of the inert fluorocarbon perfluorooctylbromide (PFOB) at nontoxic doses as a tracer in fluorine-19 (19F) nuclear magnetic resonance (NMR) spectroscopy to evaluate dynamic changes in vascular perfusion volume in transplanted tumors. METHODS: The PFOB emulsion (100% wt/vol) was injected into the tail vein in tumor-bearing C3H/He or nu/nu mice immobilized in a magnet interfaced to a spectrometer, either as a single bolus injection of 8 mL/kg body weight or in multiple injections to a total dose of 24 mL/kg. A 7-mm external surface coil was placed over the tumor. Signal from the PFOB in the tumor volume seen by the coil rapidly reached equilibrium and was maintained for at least 2 hours, and multiple doses of PFOB emulsion resulted in a linear increase in 19F signal strength. Since the 19F signal strength was directly proportional to the perfusion volume of the tumor vasculature, reduction of signal intensity should correspond directly to any reduction in volume caused by a change in the tumor blood flow. To investigate this hypothesis, the vasoactive agent hydralazine (5 mg/kg) was injected intravenously after administering the PFOB emulsion to induce changes in tumor blood supply. KHT and RIF-1 murine sarcomas, the HT29 human colon carcinoma, and the HX118 human melanoma tumors were studied. In a comparative analysis of changes in blood flow induced by hydralazine, we studied Xe-133 clearance in KHT murine sarcoma and SCCVII/Ha (SCCVII) murine squamous cell carcinoma. RESULTS: Hydralazine significantly reduced the 19F signal intensity in the murine tumors RIF-1 and KHT and in the HT29 human tumor, with little reduction in the SCCVII/Ha murine and HX118 human tumors. Hydralazine induced a statistically significant 64% decrease in mean clearance rate in the KHT tumor, while SCCVII/Ha tumors showed no significant change, indicating that hydralazine restricted blood flow to a greater extent in the tumor type that showed reduced 19F signal from the PFOB emulsion. CONCLUSION: These data demonstrate the potential of PFOB emulsion as a tracer in NMR spectroscopy for studying tumor vasculature.

Animals↗
PubMed1992

Psychosis and idiopathic precocious puberty in two 7-year-old boys.

The authors present case reports of psychosis and idiopathic precocious puberty (IPP) with tall stature in two 7-year-old boys. Other similarities in the two cases are discussed. Review of the literature revealed only one report regarding the role of accelerated sexual maturation in the clinical picture of psychoses in children and one case report of Pervasive Developmental Disorder and IPP in a 5-year-old girl. Possible mechanisms by which psychosis and IPP with tall stature may be related are discussed.

Attention Deficit Disorder with Hyperactivity↗
PubMed1992

Neurophysiological evaluation of sensorimotor functions of the leg: comparison of evoked cortical potentials following electrical and mechanical stimulation, long-latency muscle responses, and transcranial magnetic stimulation.

Twenty-two patients with localized lesions of the central nervous system (unilateral cerebral ischaemia, cervical myelopathy, spinal tumour, familial spastic paraplegia) underwent neurophysiological evaluation of sensorimotor deficits of the leg. Functional methods using muscle stretch as stimulus, i.e. long-latency muscle responses and cortical potentials evoked by dorsiflection of the foot, were compared with transcranial magnetic stimulation and somatosensory evoked cortical potentials following electrical stimulation of the posterior tibial nerve. The functional neurophysiological methods yielded no diagnostic superiority with respect to the procedures using artificial (i.e. magnetic and electrical) stimulation. However, in most cases of missing compound motor action potentials following transcranial magnetic stimulation or missing electrically evoked cortical potentials, the long-latency muscle responses still allowed quantitative assessment of sensorimotor function.

Adult↗
PubMed1992

Magnetic resonance spectroscopy studies on experimental murine and human tumors: comparison of changes in phosphorus metabolism with induced changes in vascular volume.

The responses of two experimental murine tumors and two human tumor xenografts to the vasodilator hydralazine were compared using two magnetic resonance spectroscopy endpoints. Changes in tumor metabolism were determined using 31P MRS where inorganic phosphate levels relative to total phosphate (Pi/total) were measured, and alteration in tumor blood volume was examined using 19F MRS with perfluorooctylbromide (PFOB) as tracer. The integrated 19F signal from PFOB is dose dependent and stable for at least 2 hr after injection. The murine tumors SCCVII/Ha and KHT both showed changes in tumor metabolism after hydralazine, as an increase in Pi/total. However, hydralazine reduced vascular volume in the KHT tumor, demonstrated by reduced 19F signal from PFOB, but no such reduction was seen in the SCCVII/Ha tumor. In contrast, hydralazine had no effect on phosphorus metabolism in the HT29 and HX118 human tumor xenografts, but reduced vascular volume in both tumors. These results demonstrate that the effects of vasoactive agents such as hydralazine on tumor phosphorus metabolism are only partially consistent with changes in vascular volume, measured by the 19F MRS technique.

Animals↗
PubMed1992

Silver-stained nucleolar organizer proteins in urothelial bladder lesions. A morphometric study.

The diagnostic value of image analysis of silver-stained nucleolar organizer regions (AgNORs) has been investigated in 170 urothelial bladder lesions obtained by transurethral biopsies in the same number of patients. According to the WHO classification 25 specimens showed a flat non-invasive growth pattern with simple hyperplasia or mild dysplasia (H/D1 = 10), as well as moderate (D2 = 10) to severe atypia (Cis = 5). 135 samples were of papillary and/or infiltrating type including polypoid cystitis (pC = 5), true papillomas (G0 = 7), and carcinomas of different malignancy grade (G1 = 30, G2 = 55, G3 = 38). 10 biopsies served as normal controls. Benign non-neoplastic urothelium (controls, H/D1, pC) exhibited few but large AgNORs (mean number [MNN] = 3.3 +/- 0.5, mean area [MNA] = 0.29 +/- 0.08 micron 2), whereas carcinomatous lesions (Cis, G1-G3) showed numerous small silver-stained dots within their nuclei (MNN = 6.9 +/- 1.1; MNA = 0.12 +/- 0.04 micron 2). Both parameters, MNN and MNA, were inversely correlated (r = -0.69, p less than 0.001); their quotient (NQ = MNN/MNA) revealed a clear cut difference in the AgNOR content of benign (control, H/D1:NQ = 12.8 +/- 2.5) and moderate to severe atypical flat urothelial lesions (D2, Cis: NQ = 44.2 +/- 12.8, p less than 0.001). This parameter also discriminated between G1 (NQ = 40.7 +/- 17.3), G2 (NQ = 57.5 +/- 18.8), and G3 carcinomas (NQ = 79.0 +/- 21.8, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Histocytochemistry↗
PubMed1992

[Pulmonary pasteurellosis in a young patient with multiple trauma].

A case is reported of an 18-year-old male patient who had a road traffic accident, with head and chest injuries. The patient was admitted to the surgical intensive care unit 24 h later because of an alteration of his level of consciousness. He required artificial ventilation. Five days later, he developed right-sided lower lobe pneumonia, treated with positive end-expiratory pressure. A Gram negative organism was found on bronchial brushing, but not in haemocultures. It was identified as Pasteurella multocida, sensitive to beta-lactamines, but not to amikacin. Cefotaxime, which had been started immediately after the arrival of the Gram stain result, was continued. Artificial ventilation was discontinued on day 12, and the patient left the unit on day 15. The patient was probably a P. multocida carrier, being in close contact with animals before his accident. This bacteria is often found in infected animal bite wounds. Pneumonia due to this bacteria usually occurs in immunodepressed patients, which was not the case here.

Adolescent↗
PubMed1992

Immunotherapy with stimulated autologous lymphocytes in a case of a juvenile anaplastic glioma.

The effect of immunotherapy with stimulated autologous lymphocytes (SAL) in malignant gliomas is documented and discussed in a bioptical and autoptical case study. A five-year-old child with a recurrently operated and radiated right hemispheric anaplastic astrocytoma died six weeks after immunotherapy with mitogen-activated killer cells and recombinant Interleukin-2. The autopsy revealed a large butterfly glioma with partially necrotic gelatinous tissue at the site of the SAL reservoir. The tumor cell density on the right was less than on the left hemisphere, and T-lymphocyte content was higher on the right hemisphere. These results demonstrate a local effect of SAL therapy in vivo, although the tumor progression as a whole could not be stopped. They also demonstrate the need of a detailed neuropathological examination in all cases of immunotherapy of malignant gliomas.

Brain Neoplasms↗
PubMed1992

Depressive symptoms and mortality in elderly persons.

Studies on the relationship between depression and mortality in elderly community populations have yielded contradictory findings, although an association frequently is found in studies of elderly psychiatric patients. These different results may be due to differences in the measures of depression, the populations under study, the covariates in the analysis, or to sample attrition. In this study of elderly residents of an urban neighborhood, depressive symptoms are measured at two time points. People are classified as consistently nonsymptomatic (N-N), with emergent symptoms (N-D), in remission (D-N), or persistently symptomatic (D-D). Symptoms of depression, sociodemographic characteristics, and measures of changes in health, functional status, number of chronic medical conditions, and social support are examined in relation to mortality in multivariate Cox regression models. Although symptoms of depression are not found to be related to time-to-death, older people, those with declines in health and functional status, and men have greater relative risks of mortality over a three-year follow-up.

Aged↗
PubMed1992

The effects of propofol on brain electrical activity, neurologic outcome, and neuronal damage following incomplete ischemia in rats.

This study compares the effects of propofol and fentanyl/N2O on spontaneous brain electrical activity, neurologic outcome, and neuronal damage due to incomplete cerebral ischemia in rats. Thirty Sprague-Dawley rats were assigned to one of three groups: group 1 (n = 10) received 70% N2O in O2 plus fentanyl (bolus 10 micrograms.kg-1, infusion 25 micrograms.kg-1.h-1); group 2 (n = 10) received 70% N2 in O2 and propofol (infusion 0.8-1.2 mg.kg-1.min-1) adjusted to maintain EEG burst suppression during ischemia; group 3 (n = 10) was anesthetized with propofol and received 6 ml.kg-1 10% glucose intraperitoneally 15 min before the start of ischemia. Incomplete cerebral ischemia was produced by right common carotid artery occlusion combined with hemorrhagic hypotension (35 mmHg) for 30 min. Arterial blood gases, pH, and rectal temperature were kept constant in all groups. Plasma glucose was lower during ischemia in propofol-anesthetized rats compared to that in fentanyl/N2O- (P = 0.009) and glucose-loaded propofol-treated rats (P = 0.008). Neurologic outcome and brain tissue injury were significantly better in propofol-anesthetized compared to fentanyl/N2O-anesthetized rats (P less than 0.05). Elevated plasma glucose in propofol-treated rats resulted in similar neurologic outcome and histopathologic injury as seen in propofol-anesthetized rats given no glucose. Recovery of EEG theta-alpha activity after ischemia was inversely correlated to neurologic deficit (fentanyl/N2O: r = -0.71; propofol: r = -0.83; P less than 0.01). These results show that propofol improves neurologic outcome and decreases neuronal damage from incomplete cerebral ischemia when compared to fentanyl/N2O. This effect is not dependent on plasma glucose.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Photoactivation of hypericin generates singlet oxygen in mitochondria and inhibits succinoxidase.

Photosensitized inhibition of mitochondrial succinoxidase by hypericin was measured in vitro and found to be drug-dose, light-dose, and wavelength dependent. Singlet oxygen generation, monitored using the singlet oxygen trap tetramethylethylene, and oxygen consumption in isolated mitochondria sensitized by hypericin were also light-dose and wavelength dependent. Unequivocal evidence for the generation of singlet oxygen was obtained using kinetic isotope ratios of products from the reaction between singlet oxygen and geminally deuterated tetramethylethylene. An action spectrum for the inhibition of succinoxidase was measured at wavelengths between 400 and 700 nm and found to parallel the recorded visible absorption spectrum of hypericin in isolated mitochondria. The greatest singlet oxygen generation, oxygen consumption, and succinoxidase inhibition occurred with white light or 600 nm irradiation. These data are consistent with a type II singlet-oxygen-mediated mechanism for hypericin induced photosensitized inhibition of mitochondrial succinoxidase.

Animals↗
PubMed1992

Oxygen dependence of hypericin-induced phototoxicity to EMT6 mouse mammary carcinoma cells.

The photodynamic effect of hypericin on EMT6 mouse mammary carcinoma cells was investigated in vitro under aerobic and hypoxic conditions. Under aerobic conditions, hypericin-induced photocytotoxicity was dose dependent within a 1-50 microM range. Under hypoxic conditions, cells were resistant to hypericin-induced phototoxicity. In the dark, no cytotoxicity was observed at any hypericin concentration tested either aerobically or hypoxically. Cellular accumulation of hypericin, examined by chemical extraction and spectroscopy, occurred under both hypoxic and aerobic conditions. Fluorescence photomicrographs of cells exposed to hypericin corroborate drug uptake in the plasma membrane and subcellular regions. Our results demonstrate that hypericin cytotoxicity to EMT6 mouse mammary carcinoma cells in vitro is both light and oxygen-dependent. These results suggest that EMT6 cell kill caused by photoactivated hypericin is mediated by an oxygen-dependent mechanism, rather than by a type I oxygen-independent mechanism.

Aerobiosis↗
PubMed1992

Paraurethral actinomycosis.

Actinomycosis of the genitourinary tract is rare. Herein we report a case of actinomycosis of the urethra following staged hypospadia repair. Pathophysiology and treatment options of this rare lesion are discussed.

Actinomycosis↗
PubMed1992

Pediatric cardiology: auscultation from 280 miles away.

New long-distance audio/video and data communications links among health-care facilities promise to reduce rural patients' travel time and waiting time for subspecialty consultations. To offer a satisfactory alternative to face-to-face examination, the long-distance system must meet the subspecialty's minimum criteria. For pediatric cardiology in particular, the system has to permit satisfactory cardiac auscultation. A preliminary test of remote auscultation that uses an electronic stethoscope involved two pediatric cardiologists, one listening hands-on with an acoustic stethoscope, the other listening independently at long distance with the electronic instrument. Taking the acoustic findings as the reference standard, the electronic stethoscope did not miss the one case of heart disease, correctly recommended echocardiogram follow-up in the two cases requiring it, and agreed on 80% of the murmurs' qualitative specifics. The patients' parents also indicated that the system was highly acceptable. We are following up these results with a full-scale study of the effectiveness and parental acceptance of remote auscultation.

Cardiology↗
PubMed1992

[Renal toxicity of intraperitoneal cisplatin: a case report].

The new technique of treating ovarian tumours by giving cisplatin intra-peritoneally does have its risks. This case history reports the case of a patient who was treated in this way and following the treatment had renal failure severe enough to require dialyses. The methods of administering cisplatin through this route have not yet been worked out completely. It is absolutely to over hydrate the patient beforehand.

Acute Kidney Injury↗
PubMed1991

Twenty five years of case finding and audit in a socially deprived community.

OBJECTIVE: To evaluate audit and case finding (whole population care) in a community over 25 years. DESIGN: Contemporary screening for and audits of care of chronic disease and risk factors; retrospective review of computerised practice records; and comparisons of mortality and social indices with neighbouring communities. SETTING: One general practice in Glyncorrwg, West Glamorgan. SUBJECTS: 1800 people registered with the practice in 1987 and 558 people who died from 1964 to 1987, whose records had been retained. MAIN OUTCOME MEASURES: Detection of high blood pressure, smoking, airways obstruction, obesity, diabetes, and alcohol problems in adults aged 20-79; prevalence of smoking in this population and in hypertensive and diabetic groups; age standardised mortality ratios in relation to indices of social deprivation. RESULTS: In the population aged 20-79 (1207 patients) 249 (21%) had peak expiratory flow rate less than 50% of expected value or which improved by 15% or more with an inhaled beta agonist, 207 (17%) had body mass index at or over 30 kg/m2, 118 (10%) had untreated mean arterial pressures greater than 159/104 mm Hg (three readings), 80 (7%) (65 (16%) men, 15 (4%) women) had recognised alcohol problems, and 35 (3%) had diabetes. The proportion of men aged 20-64 who said they smoked fell from 61% (290/476) in 1968-70 to 36% (162/456) in 1985 whereas that of women who smoked was unchanged (43%, 187/436 v 42%, 190/448 respectively). In 116 screened hypertensive patients group mean blood pressure fell from 186/110 mm Hg before treatment to 146/84 mm Hg at 1987 audit, as did the proportion of smokers (56% v 20%), but body mass index and total cholesterol concentration showed no significant change. In 34 diabetic patients mean blood pressure and the proportion of smokers fell (171/93 mm Hg v 155/81 mm Hg; 44% v 12%). The age standardised mortality ratio in 1981-6 was lower than in a neighbouring village without a developed case finding programme (actual to expected deaths less than 65 = 21 to 22 in Glyncorrwg, 48 to 30 in control village). CONCLUSIONS: Whole population care through organised case finding and audit is feasible but only with a labour intensive approach combining accessibility, flexibility, and continuity, as well as a planned and structured approach, which requires substantial expansion of staff numbers and assiduous recording. It may reduce risks for at least some high risk groups. Despite their shortcomings the available data are consistent with the hypothesis that whole population care helps reduce mortality. Incentives in the new contract, which encourage the uncritical development of structured process, may diminish health outputs.

Adult↗