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Biomedical subjects

F Robert

Publications and source records attributed to F Robert.

At least 91 records · Page 5Linked to original sources

Prolonged isolated fever due to attenuated extracerebral toxoplasmosis in patients infected with human immunodeficiency virus who are receiving trimethoprim-sulfamethoxazole as prophylaxis.

We report two cases of prolonged fever in deeply immunocompromised patients with AIDS who had been receiving trimethoprim-sulfamethoxazole (TMP-SMZ) as primary prophylaxis for several months. Investigations of the cause of fever yielded normal or negative findings except that the polymerase chain reaction (PCR) for Toxoplasma gondii in the blood was positive in both cases, and PCR of the bronchoalveolar lavage fluid was positive in one case. After a few days of treatment with pyrimethamine plus clindamycin, the two patients became afebrile and the T. gondii PCR became negative. The patients probably had disseminated toxoplasmosis attenuated by TMP-SMZ. PCR examination of blood for evidence of T. gondii genome may be useful in screening for causes of unexplained fever in patients with AIDS, even those who receive prophylaxis with TMP-SMZ.

AIDS-Related Opportunistic Infections↗

Assessment of non-invasive new imaging techniques in the diagnosis of heart liposarcoma.

Two patients, with recurrent acute pericarditis as the first presentation of liposarcoma, were admitted to our department between August and December 1992. The pericarditis was pericardial in one case and retroperitoneal with pericardial inflammation in the other. In contrast to most reported cases, where diagnosis was made post-mortem, diagnosis and surgical decision were based on non-invasive imaging techniques, without cardiac angiography. In cases of recurrent acute pericarditis resistant to usual drugs, new imaging techniques, such as computed tomodensitometry and magnetic resonance imaging, can detect rare causes such as liposarcomas in which prognosis is critically dependent on early diagnosis.

Acute Disease↗

Use of random amplified polymorphic DNA as a typing method for Candida albicans in epidemiological surveillance of a burn unit.

Burn patients are particularly exposed to deep-seated nosocomial infections caused by Candida species. Superficial carriage of C. albicans is a potential source of infection and dissemination, and typing methods could be useful to trace the different isolates. We report the use of random amplified polymorphic DNA to type isolates of C. albicans in the Hôpital Cochin burn unit. This molecular typing method, which is based on PCR with arbitrary short primers, was evaluated on a panel of 32 C. albicans strains isolated from various anatomical sites of unrelated patients, and the strains showed 22 different patterns. Random amplified polymorphic DNA was then used in the epidemiological surveillance of the patients in the burn unit over a 9-month period. Seven patterns were identified among 84 isolates from 18 patients. One pattern (pattern A) corresponding to isolates from 7 of the 18 patients (68% of isolates) predominated throughout the 9-month study, while some strains with other profiles were isolated only once. Some profiles appeared to show a particular geographic pattern within the unit, suggesting transmission from room to room. These results underline the importance of fungal surveillance in such patients and the need to inform nursing staff of measures to prevent the spread of Candida spp. from patient to patient.

Burn Units↗

Intramedullary schwannoma.

OBJECTIVE: To present the imaging findings for two cases of intramedullary schwannoma involving the thoracic cord and the conus medullaris. PATIENTS AND METHODS: a 34-year-old man and a 53-year-old woman presented with symptoms of weakness and pain in the lower limbs. Myelography and magnetic resonance imaging as well as other examinations, were performed. RESULTS: The imaging failed to indicate the correct diagnosis in either patient. However, intramedullary schwannoma was confirmed pathologically in both patients. Subtotal excision resulted in local tumour recurrence at 5 and 3 years, respectively. CONCLUSIONS: Intramedullary schwannoma should be considered in the differential diagnosis of spinal cord tumours. The importance of accurate diagnosis from frozen sections at surgical biopsy is emphasized .

Adult↗

[Conservative treatment of sub-clinical noninfiltrating cancers of the breast (102 EOA in situ, TONO)].

102 patients with sub-clinical intra ductal non invasive breast cancer (T0N0) treated by limited surgery and curative radiation therapy. Follow-up ranged from 2 to 10 years with a median follow-up of 59 months. The long term survival rate of this therapeutic approach, consisting of simple excision without any adjuvant treatment and radical mastectomy was close to 100%. The actuarial local recurrence rate was only 8.6% at 10 years (confidence interval: 4.6 to 12.6%), which strongly suggests that radiation therapy is active on multicentric foci. Salvage surgery could be performed in every case of local recurrence. The survival rate of in situ breast cancer (T0N0) treated by conservative radio-surgery is comparable to that of radical mastectomy, while cosmetic results and psychological impact appear to be better for the conservative technique (breast preservation rate = 91 to 96%).

Breast Neoplasms↗

Tyrosine hydroxylase activity in the locus coeruleus of conscious rats: differences with the anesthetized rats.

Microdialysis was used to estimate in vivo tyrosine hydroxylase (TH) activity in locus coeruleus (LC) of conscious rats. An aromatic amino acid decarboxylase inhibitor, difluoromethyl-DOPA (DFMD), was perfused through the dialysis probe and the DOPA accumulating in dialysates was measured. A 3 h perfusion of a 6 x 10(-4) mol/l DFMD solution was needed to obtain measurable levels of DOPA in LC dialysates: a linear increase in DOPA concentrations was first observed and, then, a steady state. DOPA disappeared completely after inhibition of TH by alpha-methyl-p-tyrosine, showing that it reflects TH activity. The DFMD perfusion needed in this study was six times higher in concentration and three times longer in duration than the one required in a previous study we performed in LC of anesthetized rats. Furthermore, TH activity was found lower than the one we previously reported. We conclude that these differences could be explained by the effects of halothane anesthesia on DFMD and DOPA degradation and/or on LC neurons TH activity itself.

Anesthetics↗

Phase 2 study of prolonged administration of oral etoposide in combination with weekly cisplatin in advanced non-small cell lung cancer.

We administered chemotherapy consisting of a 21-day course of oral etoposide (50 mg/m2/day) and a 3-weekly dose of cisplatin (30-33 mg/m2/week) to 23 chemotherapy-naive patients with advanced non-small cell lung cancer (NSCLC). Six patients achieved a partial response (28.6%; 95% confidence interval, 11.3-52.2%), with a median response duration of 4 months and a median overall survival of 5 months. Besides alopecia, myelosuppression was the most significant drug-related toxicity. Observed side effects in 59 cycles of chemotherapy were granulocytopenia (< 1,000/microliters) in 23% of the treatment cycles, thrombocytopenia (< 75,000/microliters) in 25%, anemia (< 10 g/dl) in 64%, and nausea-vomiting (grades > or = 2) in 8%. Mild renal insufficiency (serum creatinine, 1.5-2.1 mg/dl) occurred in six patients. Three toxic deaths were observed during or immediately after cycle 1, and were related to granulocytopenia. We conclude that this regimen has modest activity in advanced NSCLC; but this therapeutic approach does not appear to produce a major improvement in the treatment of this disease. Thus, in advanced NSCLC, continued evaluation of new chemotherapeutic agents should remain the major emphasis of investigational therapy.

Administration, Oral↗

Autosomal dominant arteriopathic leuko-encephalopathy and Alzheimer's disease.

A 49-year-old man suffered from progressive dementia and seizures leading to death after 2 years. CT scans showed severe cortical-subcortical atrophy and hypodensity of the white matter. His father had died at about the same age with similar clinical signs. Two sisters and one brother were also affected. Neuropathological study revealed predominant involvement of the cerebral white matter with myelin loss, gliosis and type I lacunes. The small arteries and arterioles of the white matter and basal ganglia, and, to a lesser extent those of the subarachnoidal space, displayed fibrosis and replacement of the media by an eosinophilic, PAS positive, Congo Red negative, granular substance. Electron microscopy showed swollen myocytes surrounded by collagen, elastin and a compact electron-dense material. Immunofluorescence using antibodies against IgA, IgG, IgM, C1q and C3 stained the abnormal media weakly. In the cortex, there were diffuse senile plaques and neurofibrillary tangles. Immunohistochemistry demonstrated beta/A4 positive material in cortical senile plaques but not in arterial walls. Adventitial macrophages were, however, immunoreactive for gamma-trace. Systemic arterioles were normal. The vascular changes and leukoencephalopathy are comparable to those described in 'Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy' (CADASIL). Similar vascular changes were also observed in nonfamilial cases. An association with Alzheimer changes in the cortex has not been described previously. The relationship between both diseases and the role of each in the causation of the dementia is unclear.

Alzheimer Disease↗

Multicenter phase II study of brequinar sodium in patients with advanced gastrointestinal cancer.

Eighty-six patients with advanced colorectal, gastric or pancreatic carcinoma and no prior exposure to chemotherapy were treated with brequinar sodium. Brequinar was administered at a median weekly dose of 1200 mg/m2 intravenously. The toxicity was moderate, with thirty patients (35%) experiencing grade 3 or 4 toxicity. Objective responses were observed in 1/32 evaluable colorectal and 2/29 evaluable gastric carcinoma patients. There were no objective responses in 17 evaluable pancreatic cancer patients. We conclude that, at this dose and schedule, brequinar does not have sufficient activity in these gastrointestinal malignancies to warrant further evaluation.

Adult↗

Long-term effect of RU24722 on tyrosine hydroxylase in the rat locus coeruleus: differential effects of two enantiomeric forms.

RU24722, as a racemic mixture, has been found to act on neuronal activity and the long-term regulation of tyrosine hydroxylase in the locus coeruleus of the rat. In this study, the effects of two enantiomeric derivatives of RU24722 (3 alpha and 16 alpha forms), as compared to the racemic form itself, are studied. The short-term effect was estimated 20 min after treatment by measuring variations in 3,4-dihydroxyphenylacetic acid content in the locus coeruleus. The long-term effect was determined by evaluating tyrosine hydroxylase protein concentration in the locus coeruleus 3 days after a single injection. Comparison of actions of both enantiomers showed that the 16 alpha form was 3-fold more potent in eliciting tyrosine hydroxylase protein elevations at three days, whereas the 3 alpha isomer increased 3,4-dihydroxyphenylacetic acid content 2-fold more in the short-term. These results seem to show that the 16 alpha configuration is crucial for the long term regulation of tyrosine hydroxylase protein elicited by RU24722 within the locus coeruleus.

3,4-Dihydroxyphenylacetic Acid↗

Hemostatic abnormalities associated with monoclonal gammopathies.

To confirm and expand previous observations about the association of monoclonal gammopathies with hemostatic defects, a prospective evaluation was made in 42 patients with lymphoplasmacytic disorders. The incidence of bleeding complications was low, despite the diversity of abnormal hemostatic tests observed in these patients. Patients with myeloma frequently had abnormal coagulation tests, including thrombin time (64%), fibrin degradation products (32%), platelet aggregation tests with different agonist (30% to 55%), and bleeding time (22%). The lack of platelet response to ristocetin and normal ristocetin cofactor activity in four patients with myeloma may suggest a Bernard-Soulier-type defect. Serum viscosity was negatively correlated with platelet aggregation with collagen, ristocetin, and adenosine diphosphate. In patients with immunoglobulin myeloma, there was a positive correlation between an increased viscosity and a prolonged thrombin time. This study demonstrates the wide variety of coagulation abnormalities in lymphoplasmacytic disorders, usually without significant clinical implications.

Adult↗