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Biomedical subjects

A Slama

Publications and source records attributed to A Slama.

At least 37 records · Page 2Linked to original sources
PubMed2000

[Bladder leiomyosarcoma: report of a case].

Leiomyosarcoma of the urinary bladder is an extremely rare disease. In this study, which also includes a review of the literature, a new case of urinary bladder leiomyosarcoma has been reported in a 65-year old male, which was detected during an investigation of total hematuria accompanied by burning upon micturition. The clinical examination was normal, but ultrasonography followed by bladder endoscopy showed the presence of a large bladder tumor. The definitive diagnosis of this type of tumor can only be made after histological and immunohistochemical investigation, and to avoid unnecessary surgery it is essential to first differentiate it from an inflammatory pseudosarcoma. Although in the present study the outcome following total cystoprostatectomy was favorable at 3 months follow-up, in general the prognosis is uncertain due to the potentially invasive character of this type of tumor. Given the limited number of studies on the subject treatment still remains controversial, but is essentially based on surgical excision, possibly with adjuvant chemotherapy.

Aged↗
PubMed2000

[Paratesticular rhabdomyosarcoma].

The authors report a case of embryonal paratesticular rhabdomyosarcoma in a 9-year-old child and discuss the treatment modalities in the light of data from the literature.

Child↗
PubMed1999

Persistent mitochondrial dysfunction and perinatal exposure to antiretroviral nucleoside analogues.

BACKGROUND: Zidovudine is commonly administered during pregnancy to prevent mother-to-child HIV-1 transmission. We investigated mitochondrial toxic effects in children exposed to zidovudine in utero and after birth. METHODS: We analysed observations of a trial of tolerance of combined zidovudine and lamivudine and preliminary results of a continuing retrospective analysis of clinical and biological symptoms of mitochondrial dysfunction in children born to HIV-1-infected women in France. Mitochondrial dysfunction was studied by spectrophotometry and polarography of respiratory-chain complexes in various tissues. FINDINGS: Eight children had mitochondrial dysfunction. Five, of whom two died, presented with delayed neurological symptoms and three were symptom-free but had severe biological or neurological abnormalities. Four of these children had been exposed to combined zidovudine and lamivudine, and four to zidovudine alone. No child was infected with HIV-1. All children had abnormally low absolute or relative activities of respiratory-chain complexes I, IV, or both months or years after the end of antiretroviral treatment. No mutation currently associated with constitutional disease was detected in any patient. INTERPRETATION: Our findings support the hypothesis of a link between mitochondrial dysfunction and the perinatal administration of prophylactic nucleoside analogues. Current recommendations for zidovudine monotherapy should however be maintained. Further assessment of the toxic effects of these drugs is required.

Acidosis, Lactic↗
PubMed1999

[Peripartum cardiomyopathy. Clinical case series].

We report a retrospective analysis of four cases of peripartum cardiomyopathy admitted, within a 10-year period, to the maternity hospital of Sousse. The age of the patients was over 30 years, two had gemellary pregnancies and two suffered toxaemia. Congestive cardiac failure, mainly of the left ventricle, with acute pulmonary oedema, was the main symptom. Chest X-ray showed a cardiothoracic index above 0.58 and echocardiography a left ventricular telediastolic diameter above 5.7 cm and a shortening ratio of 25% or less. Endomyocardial biopsy for ascertaining the diagnosis was not available. Treatment included bed rest, water and salt restriction, digitalis, a diuretic and an anticoagulant in case antepartum cardiomyopathy, a converting enzyme inhibitor and a diuretic in case of postpartum cardiomyopathy. Three patients recovered totally and in one echocardiography showed a persisting impaired left ventricular function. Five neonates had a favourable outcome and one foetus died in utero. Main problems raised by peripartum cardiomyopathy are discussed.

Adult↗
PubMed1999

Defects in activation and transport of fatty acids.

The oxidation of long-chain fatty acids in mitochondria plays an important role in energy production, especially in skeletal muscle, heart and liver. Long-chain fatty acids, activated to their CoA esters in the cytosol, are shuttled across the barrier of the inner mitochondrial membrane by the carnitine cycle. This pathway includes four steps, mediated by a plasma membrane carnitine transporter, two carnitine palmitoyltransferases (CPT I and CPT II) and a carnitine-acylcarnitine translocase. Defects in activation and uptake of fatty acids affect these four steps: CPT II deficiency leads to either exercise-induced rhabdomyolysis in adults or hepatocardiomuscular symptoms in neonates and children. The three other disorders of the carnitine cycle have an early onset. Hepatic CPT I deficiency is characterized by recurrent episodes of Reye-like syndrome, whereas severe muscular and cardiac signs are associated with episodes of fasting hypoglycaemia in defects of carnitine transport and translocase. Convenient metabolic investigations for reaching the diagnosis of carnitine cycle disorders are determination of plasma free and total carnitine concentrations, determination of plasma acylcarnitine profile by tandem mass spectrometry and in vitro fatty acid oxidation studies, particularly in fresh lymphocytes. Application of the tools of molecular biology has greatly aided the understanding of the carnitine palmitoyltransferase enzyme system and confirmed the existence of different related genetic diseases. Mutation analysis of CPT II defects has given some clues for correlation of genotype and phenotype. The first molecular analyses of hepatic CPT I and translocase deficiencies were recently reported.

Adult↗
PubMed1999

Recognition and management of fatty acid oxidation defects: a series of 107 patients.

In a personal series of 107 patients, we describe clinical presentations, methods of recognition and therapeutic management of inherited fatty acid oxidation (FAO) defects. As a whole, FAO disorders appear very severe: among the 107 patients, only 57 are still living. Including 47 siblings who died early in infancy, in total 97 patients died, of whom 30% died within the first week of life and 69% before 1 year. Twenty-eight patients presented in the neonatal period with sudden death, heart beat disorders, or neurological distress with various metabolic disturbances. Hepatic presentations were observed in 73% of patients (steatosis, hypoketotic hypoglycaemia, hepatomegaly, Reye syndrome). True hepatic failure was rare (10%); cholestasis was observed in one patient with LCHAD deficiency. Cardiac presentations were observed in 51% of patients: 67% patients presented with cardiomyopathy, mostly hypertrophic, and 47% of patients had heart beat disorders with various conduction abnormalities and arrhythmias responsible for collapse, near-miss and sudden unexpected death. All enzymatic blocks affecting FAO except CPT I and MCAD were found associated with cardiac signs. Muscular signs were observed in 51% of patients (of whom 64% had myalgias or paroxysmal myoglobinuria, and 29% had progressive proximal myopathy). Chronic neurologic presentation was rare, except in LCHAD deficiency (retinitis pigmentosa and peripheral neuropathy). Renal presentation (tubulopathy) and transient renal failure were observed in 27% of patients. The diagnosis of FAO disorders is generally based on the plasma acylcarnitine profile determined by FAB-MS/MS from simple blood spots collected on a Guthrie card. Urinary organic acid profile and total and free plasma carnitine can also be very helpful, mostly in acute attacks. If there is no significant disturbance between attacks, the diagnosis is based upon a long-chain fatty acid loading test, fasting test, and in vitro studies of fatty acid oxidation on fresh lymphocytes or cultured fibroblasts. Treatment includes avoiding fasting or catabolism, suppressing lipolysis, and carnitine supplementation. The long-term dietary therapy aims to prevent periods of fasting and restrict long-chain fatty acid intake with supplementation of medium-chain triglycerides. Despite these therapeutic measures, the long-term prognosis remains uncertain.

Disease Management↗
PubMed1999

[Epidemiology of gastro-esophageal-reflux in general practice. . Predictive factors for health care utilization in the course of a year].

AIM: To assess the epidemiology and course of GORD, treatment demand, and factors predictive of GORD course in a 1-year study in patients with heartburn consulting general practitioners. METHODS: A total of 984 patients with pyrosis were included by general practitioners. After the initial visit, they had follow up at 3, 6 and 12 months by phone contact. RESULTS: Most patients (87%) had been suffering from heartburn for 4+/-1.5 years; upper GI endoscopy had been performed in 63% of patients. Patients evaluated the symptoms of the current episode as mild (6%), moderate (60%), or severe/incapacitating (34%). During the year of follow up, 12% of the patients were free of heartburn; the mean number of consultations with general practitioners and gastroenterologists was 5.1 and 0.5 respectively. At day 90, discomfort due to heartburn was absent in 4% of patients, slight in 51%, moderate in 32%, and severe in 6%. At day 360, predictive factors for discomfort were: discomfort related to heartburn on D90, the length of time the patients had been suffering from GORD, and the main reason for consultation on D1; patients for whom heartburn was not the main reason for consultation on D1 experienced a higher level of discomfort. The predictive factors for the extent of treatment demand over 12 months were: age, discomfort related to heartburn on D90, severity on D1, the frequency of episodes prior to the episode on D1 and the levels of stress and anxiety measured on D1. CONCLUSIONS: Epidemiologic characteristics of patients with heartburn consulting a general practitioner were different from these of the general population. Treatment demand depends both on severity of heartburn and level of stress and anxiety.

Adult↗
PubMed1998

On-demand treatment of gastro-oesophageal reflux symptoms: a comparison of ranitidine 75 mg with cimetidine 200 mg or placebo.

AIM: To compare the effects of ranitidine 75 mg with those of either cimetidine 200 mg or placebo given on demand for relief of typical symptoms of gastro-oesophageal reflux disease during a 15-day period. METHODS: A total of 1336 patients (aged > or = 18 years) with heartburn episodes were recruited and randomly assigned to a ranitidine 75 mg, cimetidine 200 mg or placebo group. Depending on the occurrence or persistence of heartburn, treatment was administered as required up to three times daily, with at least 2 h between drug doses. Antacids were allowed as rescue medication if symptoms persisted for at least 2 h after the third medication on any given day. The primary end-point was defined as the proportion of patients with relief of at least 75% of heartburn episodes during the study period (i.e. relief occurring within 2 h after drug ingestion and lasting for at least 5 h). RESULTS: Analysis was performed in an intention-to-treat population comprising 504 subjects in the ranitidine group, 515 in the cimetidine group and 270 in the placebo group. Primary end-point success rates were 41, 38 and 28%, respectively, for the three groups (P < 0.001 for ranitidine vs. placebo, P = 0.274 for ranitidine vs. cimetidine). Ranitidine 75 mg was significantly more effective than placebo in providing overall heartburn relief (P < 0.001). The differences between the ranitidine and cimetidine groups were not significant, except for a greater reduction in heartburn frequency in the ranitidine group at the end of the study period (P < 0.05). Drug dose was lower and less rescue medication was used in the ranitidine group than the placebo group. The three treatment groups did not differ in terms of tolerability. CONCLUSION: On-demand ranitidine 75 mg or cimetidine 200 mg are safe and effective treatment for reflux-related symptoms.

Adolescent↗
PubMed1998

Effects of tablet and effervescent formulations of ranitidine 75 mg and cimetidine 200 mg on gastric acidity and oesophageal acid exposure in healthy humans.

BACKGROUND: Because of their tolerance and safety, low doses of H2-receptor antagonists are now increasingly used in some countries for self-care medication of gastro-oesophageal reflux symptoms. AIM: The purpose of this randomized, double-blind, placebo-controlled, five-way crossover study was to determine and to compare the effects of low doses of ranitidine and cimetidine both on gastric pH and on oesophageal acid exposure. METHODS: Gastric and oesophageal pH were simultaneously monitored in 20 healthy subjects using two glass pH electrodes, after placebo and single doses of ranitidine 75 mg and cimetidine 200 mg (effervescent and tablet forms), for 4 h before and after a meal. RESULTS: During the fasting period, median gastric pH rose significantly with both drugs, but more rapidly with the effervescent forms; the oesophageal acid exposure was significantly decreased by all drug regimens. After the meal, although there was no significant difference in gastric pH values, oesophageal acid exposure was significantly decreased in comparison with placebo with both forms of ranitidine (P < 0.05), and also for ranitidine tablets in comparison with cimetidine tablets (P < 0.05). CONCLUSIONS: Low doses of ranitidine and cimetidine increase gastric pH, with a more pronounced effect for ranitidine. Effervescent formulations of both drugs induce a slightly more rapid initial increase in pH than tablets. Ranitidine demonstrates a more prolonged effect than cimetidine and decreases oesophageal acid exposure monitored after a meal ingested 4 h after the drug intake.

Adult↗
PubMed1997

Distribution and pharmacological characterization of somatostatin receptor binding sites in the sheep brain.

Somatostatin binding sites have been localized and quantified in the sheep brain using 125I-Tyr0-DTrp8-somatostatin, by quantitative high resolution light microscopic autoradiography. Sections were analyzed by densitometry on radioautographic film, and subsequently on slides coated with photoemulsion. Specific somatostatin binding sites were concentrated in the medial habenula, superior colliculus, dorsal motor nucleus of the vagus nerve, inferior olive, spinal trigeminal nucleus, and cerebellum. In competition experiments, octreotide, a sst2/sst3/sst5 selective agonist only partially displaced 125I-Tyr0-DTrp8-somatostatin in the three cerebellar layers while it was fully active as compared to somatostatin 14 and 28 in the deeper layers of the parietal cortex. Moderate to low somatostatin receptor densities were present in the mesencephalic periaqueductal gray, dorsal raphe, thalamic paraventricular nucleus, interpeduncular nucleus, pineal gland, dorsal tegmental, dorsolateral tegmental and parabrachial nuclei, nucleus of the solitary tract. The distribution of somatostatin binding sites generally correlates with the data obtained on slides dipped in photoemulsion which provided better resolution and more precise localization. In most of the labeled areas, 125I-Tyr0-DTrp8-somatostatin receptor binding was distributed between both neuropil and perikarya. Perikarya bearing 125I-Tyr0-DTrp8-somatostatin receptors were observed in areas which did not display detectable binding sites on film such as the preoptic-anterior hypothalamic complex and arcuate nucleus and in the locus coeruleus. In conclusion, the distribution of 125I-Tyr0-DTrp8-somatostatin binding sites in sheep brain is very reminiscent of other mammals being closer to the human than to rodents.

Animals↗
PubMed1997

Species differences between male rat and ram pituitary somatostatin receptors involved in the inhibition of growth hormone secretion.

The sheep is a valuable model in which to study GH neuroregulation as its pattern of GH secretion is very close to that in humans. Furthermore, important differences in somatostatin (SRIH) action between rats and sheep have been found previously. Our goal was to compare in male rat and ram pituitaries the binding characteristics of somatostatin receptors and the effect of SRIH and 17 analogues on GH release. Using radioautography, SRIH binding was seen to be evenly distributed over the anterior pituitary of both species. In the binding assay, binding sites were three times more concentrated in rats than in sheep. Important interspecies differences in the action of SRIH and its analogues were found: they inhibited GH at lower concentrations in rats than in sheep. Seven peptides displayed greater inhibitory ability in sheep than in rats while three were more potent in rats. Agonistic potencies to inhibit GH release in rats were correlated with somatostatin receptors subtype 2 (sst2) affinities. Our data confirm and extend the quantitative differences between rat and sheep in SRIH inhibitory action on GH secretion and confirm that ligand-binding properties of a given receptor subtype cannot be extrapolated across species.

Animals↗
PubMed1996

Correlations between water maze performance and cortical somatostatin mRNA and high-affinity binding sites during ageing in rats.

Somatostatin levels and high-affinity (somatostatin-1) binding sites are decreased in post-mortem cortical samples of Alzheimer's disease patients but the relationships between such modifications and the cognitive deficits remain to be established. We investigated these relationships in the ageing rat. Three age groups (3-4, 14-15 and 26-27 months) were tested in a modified version of the Morris water maze. Somatostatin mRNA levels were quantified by in situ hybridization and somatostatin binding sites by radioautography using the selective agonist octreotide (SMS 201995) as a competing drug to evaluate high-affinity (somatostatin-1) and low-affinity (somatostatin-2) binding sites. The number of somatostatin mRNA-containing cells was not modified with age or memory performance in cortical, hippocampal and hypothalamic regions, but somatostatin mRNA densities were significantly decreased with age and with memory performance in the frontal and parietal cortex. In the frontal cortex somatostatin mRNA densities were already decreased in 14- to 15-month-old rats, whereas the decrease was observed only in 26- to 27-month-old rats in the parietal cortex. A decrease in somatostatin-1 binding was observed with memory performance, independently of age, in the basolateral amygdala only, while somatostatin-2 binding sites were not affected. In the frontal and parietal cortex, a significant correlation occurred between the latency to find the invisible platform in the water maze and somatostatin mRNA (r = -0.54 and 0.59 respectively, P < 0.02). These results indicate that ageing rats with memory impairments display some of the features of the somatostatinergic deficits observed in Alzheimer's disease.

Aging↗
PubMed1996

The increase in growth hormone secretion in experimentally induced arthritic rats is an adaptive process involved in the regulation of inflammation.

In Sprague-Dawley rats, Freund-adjuvant-induced arthritis (AIA) results in an increase in the amplitude of ultradian growth-hormone (GH)-secretory episodes without modification of their frequency. This is most apparent at the time of maximal inflammation, i.e. 14-21 days after inoculation of the adjuvant. GH responsiveness to a maximal dose of clonidine (10 micrograms/100 g body weight, BW), a secretagogue known to act at the hypothalamic level, is comparable in AIA and control rats. In contrast, GH response to a maximal dose of GH-releasing hormone (GHRH, 1 microgram/100 g BW), a peptide acting directly on pituitary somatotropes, is greater in AIA than in control rats. Furthermore AIA affects significantly neither hypothalamic somatostatin and GHRH mRNA levels nor pituitary GH content. In adult rats treated neonatally with monosodium glutamate (MSG), a neurotoxin which destroys the majority of GHRH neurons of the arcuate nucleus and reduces considerably plasma GH levels, clinical symptoms observed 14 days after inoculation of the Freund adjuvant are more marked than in AIA. The MSG-treated rats exhibit in particular a significantly higher increase in hindpaw diameter. Pulsatile administration of GH (40 micrograms/day/rat, with successive periods of 2 h of GH and 4 h of mineral oil) restoring the endogenous GH-secretory pattern throughout the 15-day period of arthritis development prevents hindpaw diameter increase. These results indicate that the impact of AIA on GH regulation occurs at the pituitary but not the hypothalamic level and suggest that increased GH secretion observed in AIA rats is an adaptive mechanism involved in the regulation of the inflammatory process.

Animals↗