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Biomedical subjects

G Stuart

Publications and source records attributed to G Stuart.

15 recordsLinked to original sources

Endocarditis with acute mitral regurgitation caused by Fusobacterium necrophorum.

Infective endocarditis is uncommon in young children, especially in the absence of structural heart disease. We report the case of a 2-year-old boy who presented with acute rupture of the mitral valve chordae 6 weeks after an episode of Fusobacterium necrophorum septicemia. His heart had been structurally normal before. Mitral valve replacement was successfully performed. This is the first recorded case of endocarditis in a child caused by necrobacillosis.

Bacteremia

The effect of estrous cycle and buthionine sulfoximine on glutathione release from the in vitro perfused rat ovary.

There is little known regarding the intracellular mechanisms of modification of damage in the ovary. Ovarian perfusion of en block dissections of the rat right ovary with aorta and vena cava were done to determine (a) if glutathione (GSH) is released by the ovary, (b) if the release is cycle dependent, and (c) if GSH released is the product of de novo ovarian synthesis. All perfused ovaries released GSH and the release was maximal at estrus and least at metestrus. Perfusion with buthionine sulfoximine, a specific inhibitor of gamma-glutamylcysteine synthetase, resulted in a dose-dependent reduction in GSH released, indicating inhibition of de novo synthesis during perfusion.

Animals

Regulation of total ovarian glutathione content in the rat.

Glutathione (GSH) is an important intracellular thiol capable of altering metabolism following exposure to certain important biologic toxicants including radiation and cyclophosphamide. In order to evaluate the inhibition of glutathione synthesis in the ovary, 30-day-old Sprague Dawley rats were treated with either saline or 0.6 mumol/kg (0.133 mg/kg), 6.0 mumol/kg (1.33 mg/kg), or 4.5 mmol/kg (1000 mg/kg) buthionine sulphoximine (BSO) IP and sacrificed at 0, 1, 2, 4, 6, 8, and 24 h. There was an inhibition of glutathione synthesis with 4.5 mmol/kg (1000 mg/kg) BSO with a nadir at 8 h (P less than 0.001) and complete recovery at 24 h. In the subsequent experiments rats were divided into four groups. All animals received either saline or BSO 4.5 mmol/kg/day (1000 mg/kg/day) from day 27 to 30 of life and either saline or PMSG 5 IU IP on day 29 of life. BSO reduced ovarian content of GSH (saline-saline compared with BSO-saline, P less than 0.0001), which was countered by the prior administration of PMSG (BSO-saline compared with BSO-PMSG, P less than 0.005). Glutathione levels were as follows: saline-saline 4.3 +/- 0.04; saline-PMSG 5.0 +/- 0.4; BSO-saline 2.13 +/- 0.2; BSO-PMSG 3.24 +/- 0.2 nmol/mg ovary. These findings suggest the ovary is susceptible to GSH depletion by in vivo administration of BSO. Gonadotropin (PMSG) is capable of effecting a partial return of total ovarian GSH content.

Animals

Research resources.

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Community Mental Health Services

Active immunization of human ovarian cancer patients against a common carcinoma (Thomsen-Friedenreich) determinant using a synthetic carbohydrate antigen.

In a phase I study, ten ovarian cancer patients with extensive metastatic disease despite chemotherapy were immunized three to eight times subcutaneously with the synthetic form of the immunodominant disaccharide (beta Gal1----3 alpha GalNAc) of the Thomsen-Friedenreich antigen conjugated to KLH (TF alpha-KLH) plus DETOX adjuvant. Six patients were given a "low" dose of TF alpha-KLH (100 micrograms/injection) and four patients were given a "high" dose (500 micrograms/injection). All patients received a single low-dose cyclophosphamide treatment (200 mg/m2 i.v.) 3 days prior to commencement of the series of immunizations. Immunizations were 2 weeks apart. Little or no toxicity was noted. As expected, all patients (prior to immunization) had naturally occurring IgM antibodies against the synthetic TF alpha hapten. None of the patients had detectable pre-existing IgG or IgA antibodies against synthetic TF alpha hapten. Nine of the ten ovarian cancer patients showed a significant increase in IgM titer above pre-existing levels following immunizations with TF alpha-KLH plus DETOX adjuvant. These same patients also produced IgG anti-TF alpha and eight of these also produced IgA anti-TF alpha, although the IgA responses were weaker. Most of the IgG responses followed the IgM responses by 2-4 weeks. Two patients produced a vigorous IgG response after their first TF alpha-KLH injection, suggesting a recall response. Both direct ELISAs on various solid-phase synthetic carbohydrate antigens and hapten inhibition experiments confirmed the TF alpha hapten specificity of the antibodies. IgM and IgG anti-TF alpha-specific antibodies reacted with natural TF antigen, by ELISA and FACS analysis, although the titers were generally lower than the titers against the immunizing TF alpha hapten. Increased levels of cytotoxic antibodies against TF-expressing tumor cell targets were detected in eight of the ten patients following immunization. One patient who had no detectable cytotoxic antibodies prior to immunization developed increasingly strong cytotoxic antibodies as a function of the number of immunizations. The low antigen dose patients showed as good or better humoral immune responses than the high antigen dose patients. All four high-dose and four of six low-dose patients developed moderate to strong DTH reactions at the vaccination sites. Our results demonstrate that KLH is an acceptable carrier for carbohydrate haptens in humans and that DETOX is an appropriate nontoxic adjuvant for the generation of high-titer specific anti-carbohydrate responses in human cancer patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenocarcinoma

Cisplatin-cyclophosphamide versus carboplatin-cyclophosphamide in advanced ovarian cancer: a randomized phase III study of the National Cancer Institute of Canada Clinical Trials Group.

PURPOSE: Given the potential for improved tolerance, a trial was initiated to compare the toxicity and efficacy of a standard regimen of cisplatin-cyclophosphamide (75 mg/m2 and 600 mg/m2, respectively) with an experimental regimen of carboplatin-cyclophosphamide (300 mg/m2 and 600 mg/m2, respectively) in women with postoperative macroscopic residual ovarian cancer. PATIENTS AND METHODS: Between 1985 and 1989, 447 (417 eligible) patients were randomized. Treatment arms were well balanced; most patients had stage III (82%), grade 3 (54%) tumors with bulky residual (greater than 2 cm in 59%), and good performance status (Eastern Cooperative Oncology Group [ECOG] 0 or 1, 77%). Response was assessed after six 4-week cycles. RESULTS: The treatments were equally deliverable, with 76% of patients completing their allocated regimen. The reported reasons for failure to complete treatment differed; toxicity/refusal predominated on the cisplatin arm, and progressive disease predominated on the carboplatin arm (P = .0092). Cisplatin-treated patients were more likely to develop neuropathy and nephropathy, and carboplatin patients experienced myelosuppression, particularly thrombocytopenia. Efficacy was similar, with no significant differences for the cisplatin and carboplatin arms in clinical response rate (57% v 59% in those with measurable disease), pathologic response rate (52% v 54% in those suitable for relaparotomy), time to progression (median, 56 v 58 weeks), or overall survival (median, 100 weeks v 110 weeks). Time to progression and survival were predicted by residual disease size, performance status, and treatment center (with those treated at centers that accrued more patients doing better). CONCLUSION: Neither regimen is optimal in that relapse remains the norm. It may be inappropriate to expect that any single regimen can be an effective therapy for all patients with advanced ovarian cancer. Both cisplatin and carboplatin are likely to have a role in future treatment strategies.

Adult

The optimal dose of oral norethindrone acetate for addition to transdermal estradiol: a multicenter study.

The effects of adding one of three doses (0.5, 0.75, or 1.0 mg/d) of norethindrone acetate for 12 days each month to continuous, transdermal estradiol (0.05 mg/d) have been determined in a prospective, randomized, multicenter study. Significant symptomatic and psychological improvements were observed and, with one exception, were not opposed by the added progestogen. Distinct redness at the site of last patch application was reported by 10% of patients and faint erythema by 30%. However, less than 5% of patients discontinued treatment because of skin problems. Breakthrough bleeding occurred infrequently and all three doses of norethindrone acetate induced a regular pattern of bleeding with secretory transformation in the endometrium. There was no hyperplasia or carcinoma.

Administration, Cutaneous

Relationship of psychotic symptoms to haloperidol-stimulated prolactin release.

Prolactin (PRL) response to a single dose of intravenous haloperidol (0.5 mg) was measured as a marker of tuberoinfundibular dopamine (TIDA) activity in 24 neuroleptic-free, male, psychotic patients. The PRL responses were then correlated with psychotic symptoms measured with Andreasen's Scales for the Assessment of Positive and Negative Symptoms (SAPS, SANS). Correlation analyses revealed a significant inverse relationship between PRL response and the severity of delusional symptoms. There was no significant correlation between the symptoms of hallucinations, formal thought disorder, or global negative symptoms and PRL response to haloperidol, nor were there any significant correlations between basal PRL and symptom severity. These results suggest that among the positive and negative symptoms associated with psychoses, only delusions may be associated with TIDA overactivity.

Adult

Idiopathic infantile arterial calcification in two siblings: failure of treatment with diphosphonate.

Two siblings with idiopathic infantile arterial calcification are reported. The fetal and postnatal echocardiographic features were a large pericardial effusion, thickened pulmonary and aortic valves, poor pulsation of the descending aorta, and calcification of the great vessels. In one patient calcification was first detected at 33 weeks' gestation. Despite treatment with disodium etidronate both children died.

Calcinosis

Pleomorphic xanthoastrocytoma: report of two cases.

Two cases of pleomorphic xanthoastrocytoma are presented to draw attention to this relatively benign variant of glioma. The circumscribed tumors, each with a cystic component, were located superficially, one in the mesial right temporal lobe and one in the right temporoparietal region. The patients were aged 12 and 14 years, and it is now almost 7 years since the onset of symptoms in the 12-year-old boy. The optimal plan of management is discussed.

Adolescent

Cerebral metastatic melanoma presenting as spastic paraparesis.

A case of bilateral deposits from melanoma in the posterior frontal parasagittal region of the brain is recorded. A mechanism to explain the mode of spread is suggested. C.T. head scanning in patients with disseminated malignancy should be considered prior to invasive investigations or major surgical procedures.

Adult

Peritoneal dialysis.

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Acute Kidney Injury