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Biomedical subjects

J Rey

Publications and source records attributed to J Rey.

At least 55 records · Page 3Linked to original sources
PubMed1999

The mutant genotype is the main determinant of the metabolic phenotype in phenylalanine hydroxylase deficiency.

Phenylketonuria and mild hyperphenylalaninemias are allelic disorders caused by mutations in the phenylalanine hydroxylase (PAH) gene. Following identification of the disease-causing mutation in 11 PAH-deficient patients, we tested the activity of the mutant gene products in an eukaryotic expression system. Two mutations markedly reduced PAH activity (A259V and L333F), one mutation mildly altered the enzyme activity (E390G), while the majority of mutant genotypes reduced the in vitro expression of PAH activity to 15-30% of controls. Comparing the predicted residual activity derived from expression studies to the clinical phenotypes of our PAH-deficient patients, we found that homozygosity for the L333F and E390G mutations resulted in severe and mild PAH deficiencies, respectively, both in vivo and in vitro, while compound heterozygosity (L333F/E390G) resulted in an intermediate dietary tolerance. Similarly, in vitro expression studies largely predicted dietary tolerance in compound heterozygotes for the A259V/IVS12nt1 (typical PKU), A259V/A403V, G218V/I65T, and G218V/R158Q mutations (mild variants). Taken together, these results support the view that expression studies are useful in predicting residual enzyme activity and that the mutant genotype at the PAH locus is the major determinant of metabolic phenotype in hyperphenylalaninemias.

Alleles↗
PubMed1999

[Thymoma and hypogammaglobulinemia. Good's syndrome: apropos of a case and review of the literature].

INTRODUCTION: Good's syndrome is defined as the association of thymoma, hypogammaglobulinemia, and repetitive bronchopulmonary infections. We report one case and review the clinical and immunological features of this syndrome. EXEGESIS: We describe the case of a 67-year-old man who presented with both severe bronchopulmonary infection resistant to antibiotherapy and thymoma. Definite diagnosis was based on the existence of hypogammaglobulinemia. Treatment with intravenous immunoglobulins led to positive outcome. CONCLUSION: Good's syndrome occurs in only 5% of parathymic diseases. To prevent further bronchial tube destruction and pulmonary surgery, it must be diagnosed and treated early.

Agammaglobulinemia↗
PubMed1999

Mastitis caused by Mycoplasma mycoides subspecies mycoides (large colony type) in goat flocks in Spain.

We describe three different outbreaks of mastitis caused by M. mycoides subspecies mycoides LC type (Mmm LC) in three goat flocks from the Extremadura Region of south-west Spain. Thirty-two fast-growing isolates were obtained on Hayflick's and Friis's media with inhibitors from different specimens. All were identified as Mmm LC in spite of their cultural, biochemical and serological features.

Animals↗
PubMed1999

Excessive concern with physical appearance leading to a diagnosis of adrenal adenoma.

We report an unusual case of Cushing's syndrome manifested by anxiety over body image in a 26-year-old nurse. Initial presentation was a 'dermatological non-disease'. Clinical signs became increasingly evident during the course of the disease, justifying an adrenal gland evaluation which showed a secreting adrenocortical adenoma. Surgical treatment led to recovery with return to normal appearance and cessation of her aesthetic complaints. Our observation shows that persistent aesthetic complaints may sometimes reveal early hypercorticism.

Adrenocortical Adenoma↗
PubMed1999

Catastrophic arterial reactivity during primary antiphospholipid syndrome--a case report.

Arterial reactivity leading to acute thrombosis at the site of a needle stick injury has never been described during antiphospholipid syndrome. The authors report a case characterized by a succession of thrombotic events occurring during or immediately after arterial angiographies or arterial surgery, in which catastrophic arterial reactivity can be strongly suspected. In this particular patient, it can be postulated that damage to the endothelial cells of the vessels injured during manipulation may have precipitated or aggravated the preexisting susceptibility to thrombosis.

Adult↗
PubMed1999

[Distribution of the genotypes of hepatitis C virus in intravenous drug addicts in Argentina].

Intravenous drug addiction (IVD) is an unfrequent risk factor in Argentina, representing less than 10% of patients (pts) with chronic HCV infection seen in our Unit. In order to study the genotypes (Gt) in IVD and compare them with a non drug addicted control population, 68 pts with a history of IVD were enrolled in this study and compared with 68 non drug addict (NDA) pts with chronic HCV, with similar age and gender distribution. In all pts a liver biopsy was performed. Genotyping was done by INNO LiPA (Innogenetics, Belgium). Mean age in both groups was 35 +/- 7.8 years and 50 were males. No difference was observed between both groups in the prevalence of Gt1a, Gt2a/c and in those with mixed infections. The prevalence of Gt1b in IVD was 19.1% and in NDA 38.2% (p = 0.0228). A highly significant difference was also observed in the prevalence of Gt3a, of 42.6% in IVD and only 11.8% in NDA (p = 0.0001). Gt1a was the second most frequent genotype in IVD pts (26.5%). Simultaneous HIV infection was present in 8 IVD pts (11.8%) and in none of NDA group. Liver biopsies showed a higher prevalence of mild chronic hepatitis in NDA (57.3%) than in IVD (32.4%) (p = 0.0058). Severe chronic hepatitis with advanced fibrosis or cirrhosis was more frequent in the Gt3 of the group with IVD when compared with Gt3 of the NDA group. It can be concluded that in accordance with other geographical areas, Gt3a is far more prevalent in intravenous drugs addicts than in the general population in Argentina where Gt1b is more frequent. Mild forms of chronic hepatitis are less frequent in IVD. In spite of the relatively small group with HCV co-infection with HIV, it seems important to note that 2/8 (25%) showed severe hepatitis C or cirrhosis.

Adult↗
PubMed1998

[Pseudo-Glanzmann thrombasthenia in the course of autoimmune thrombocytopenic purpura].

INTRODUCTION: Auto-immune thrombocytopenic purpura is associated with platelet anti-glycoprotein antibodies, particularly with anti-GPIIb/IIIa complex. Persistence of these antibodies sometimes leads to acquired auto-immune thrombopathy. EXEGESIS: We report the case of a woman treated by splenectomy for auto-immune thrombocytopenic purpura, who developed 5 years later an ecchymotic syndrome despite normal platelet count. High bleeding time and platelet aggregation defect in vitro were evidenced. Following the initial thrombocytopenia, anti-glycoproteins GPIIb/IIIa with lupus anticoagulant and benign monoclonal gammapathy were noticed. Platelet controls showed that hypoaggregant activity was secondary to the persistence of anti-GPIIb/IIa antibodies. CONCLUSION: This acquired auto-immune thrombopathy simulating Glanzmann's thrombasthenia was secondary to the persistence of platelet anti-glycoproteins GPIIb/IIIa.

Aged↗
PubMed1998

[Protein and energy needs of the infant with severe malnutrition. Application in a hospital environment for the treatment of malnutrition caused by deficient intake].

Severe malnutrition is defined by a weight for height below 70% of international standards or by presence of oedema in a clinically undernourished child. Severe malnutrition associated with oedema is called kwashiorkor. The origin of oedemas of kwashiorkor is still debated, but its relation with protein deficiency is strongly questioned. The same dietary management is now recommended for malnutrition with or without oedema. Present recommendations are based, as for well nourished children, on the separate estimation of nutritional requirements for maintenance and growth. Total requirements vary between 0.7 g/kg/day in the first few days of treatment to 5 g/kg/day or more when weight gain is maximum. As a result of high energy requirement during catch-up growth, protein requirements never exceed 10 to 12% of total energy needs.

Child Nutrition Disorders↗
PubMed1998

Child and adolescent psychotherapy research: developmental issues.

Describes developmental issues that pose current challenges to the design of treatment outcome investigation with children and adolescents. Normal childhood development and the development of childhood disorders are discussed using the transactional model of development. Challenges in diagnostic decision making, the selection of the most appropriate treatment regimen, and the measurement methods are highlighted. Recognition of the need to study child treatments through long-term follow-up periods underscores the need for resolution of these developmental issues.

Adolescent↗
PubMed1998

A European multicenter study of phenylalanine hydroxylase deficiency: classification of 105 mutations and a general system for genotype-based prediction of metabolic phenotype.

Phenylketonuria (PKU) and mild hyperphenylalaninemia (MHP) are allelic disorders caused by mutations in the gene encoding phenylalanine hydroxylase (PAH). Previous studies have suggested that the highly variable metabolic phenotypes of PAH deficiency correlate with PAH genotypes. We identified both causative mutations in 686 patients from seven European centers. On the basis of the phenotypic characteristics of 297 functionally hemizygous patients, 105 of the mutations were assigned to one of four arbitrary phenotype categories. We proposed and tested a simple model for correlation between genotype and phenotypic outcome. The observed phenotype matched the predicted phenotype in 79% of the cases, and in only 5 of 184 patients was the observed phenotype more than one category away from that expected. Among the seven contributing centers, the proportion of patients for whom the observed phenotype did not match the predicted phenotype was 4%-23% (P<.0001), suggesting that differences in methods used for mutation detection or phenotype classification may account for a considerable proportion of genotype-phenotype inconsistencies. Our data indicate that the PAH-mutation genotype is the main determinant of metabolic phenotype in most patients with PAH deficiency. In the present study, the classification of 105 PAH mutations may allow the prediction of the biochemical phenotype in >10,000 genotypes, which may be useful for the management of hyperphenylalaninemia in newborns.

Alleles↗
PubMed1998

Physiopathogenic investigations in a case of familial stiff-skin syndrome.

BACKGROUND: Stiff-skin syndrome (SSS) is a rare cutaneous syndrome characterized by stony-hard skin and limitation of joint mobility. Its cause is still unknown. OBJECTIVE: Biological investigations were performed in a new case of SSS. METHODS: Collagen production and DNA biosynthesis were studied from fibroblast culture. Proinflammatory cytokines (TNF-alpha, IL-6 and TGF-beta2) were measured in the patient's serum. Results were compared with pathological findings. RESULTS: Collagen production and DNA biosynthesis were normal whereas the level of circulating cytokines was high. Histological examination of the skin showed mild fibrosis in the dermis whereas the fascia was not thickened. CONCLUSION: Our clinical and biological findings suggest that in this case, cutaneous changes may be related to an inflammatory process rather than to a primary fibroblast defect or a fascial abnormality as previously hypothesized.

Collagen↗
PubMed1997

Critical limits to define a lab adverse event during phase I studies: a study in 1134 subjects.

OBJECTIVE: The first goal of phase I drug development is the determination of maximal tolerated dose, which must be established by case-by-case analysis, sometimes using a laboratory adverse event. Since no accurate rule defining lab adverse events, has been validated yet, we propose a new "combined method" based on combination of two thresholds: inclusion values and magnitude of variation. Using this combined method, the label "lab adverse event" is applied if any lab value exceeds the inclusion threshold and is associated with a variation from baseline exceeding the variation threshold defined from reference change limit. Thus, this study aimed to test this combined method on a large healthy volunteer population, studied in 19 phase I centres worldwide, and on five lab parameters: alanine amino transferase, aspartate amino transferase, alkaline phosphatases, creatinine and polymorphonuclear leukocytes. METHODS: The inclusion threshold from each center was used. Reference change limits were defined from volunteers previously included in comparable studies and were expressed as absolute values: increases of 10 IU.l-1 for alanine amino transferase or aspartate amino transferase, 15 IU.l-1 for alkaline phosphatases, 15 mumol.l-1 for creatinine and a 0.34 10(9).l-1 decrease for polymorphonuclear leukocytes. Comparison between the "combined method" and a normal range method was made using positive predictive value and a ratio between relevant and irrelevant results. This application was implemented in all young healthy volunteers (1134) included in 38 phase I studies sponsored by Rhone Poulenc Rorer from 1991 to 1993. RESULTS: Seventy seven subjects (6.7%) were indicated in final study reports as having a lab adverse event (reference group). Of 179 subjects with lab abnormalities defined by the normal range method, 77 belonged to the reference group, inducing a poor 0.43 positive predictive value. Of ninety subjects with lab adverse events defined by the "combined method", seventy-five belonged to the reference group, inducing a two-fold higher 0.83 positive predictive value. The combined method produced a high ratio of relevant/irrelevant results (5 = 75/15) compared with the low ratio (0.76 = 77/102) achieved using the normal range method. CONCLUSION: This new "combined method", leading to a better definition of lab adverse event, seems an accurate and useful tool for routine case-by-case analysis within phase I drug development studies.

Adolescent↗