A drug interaction study between ticlopidine and cyclosporin in heart transplant recipients

Objectives: Previous uncontrolled studies have suggested an interaction between ticlopidine, a major antiplatelet agent, and cyclosporin in heart- and kidney-transplant recipients. The aims of this study were to examine in a randomised, double-blind fashion, the possible interaction between cyclosporin A and ticlopidine (250 mg per day) and the tolerability of this combination in heart-transplant recipients. Methods: Twenty heart-transplant recipients were randomised into either a treated or a placebo group. Blood samples were drawn for time-course evaluation of cyclosporin blood levels over a period of 12 h, following the morning intake of cyclosporin and, for platelet aggregation studies, before and after 14 days of ticlopidine administration. Twenty four-hour urine samples were collected for 6-β-hydroxycortisol measurements, before and after 14 days of ticlopidine. Results: Although given at half the recommended daily dosage, ticlopidine significantly reduced platelet aggregation. Pharmacokinetic parameters indicate that the bioavailability of cyclosporin A was not significantly modified by ticlopidine. However, one patient in the ticlopidine group was withdrawn because of a major fall in cyclosporin blood level within 3 days of treatment. Urinary excretion of 6-β-hydroxycortisol was augmented after treatment in the ticlopidine group compared with the placebo group, suggesting that induction of drug metabolism might have occurred. Data also show quite a large intra-individual variability in cyclosporin bioavailability in the placebo group, suggesting that poor absorption of the drug formulation and/or poor compliance might have contributed to the decreased cyclosporin blood levels in the patient withdrawn from this study and in previous uncontrolled studies. Conclusion: Cyclosporin bioavailability was not clearly modified by a half dosage of ticlopidine in this study. We, however, recommend closely monitoring cyclosporin blood levels when prescribing ticlopidine. Further studies will be needed with new formulations of cyclosporin or when using the full dosage of ticlopidine. Received: 20 July 1996 / Accepted in revised form: 12 February 1997     

Diagnostic value of 4 biological markers: lactate dehydrogenase, phosphoglucoisomerase, carcinoembryonic antigen and gammaglutamyl transpeptidase, systematically determined in patients in a hematology-oncology department

This article is concerned with a prospective study about the systematical, simultaneous and comparative assay of four biological markers (carcino-embryonic antigen, lactate dehydrogenase, gammaglutamyl transferase and phosphohexose isomerase). This study was conducted in a department of Hematology and oncology on 258 patients. The dosage of each marker separately does not appear to be of diagnostical interest because of a lack of sensibility and specificity. But when there is a positive statistical correlation between several makers, their simultaneous dosage may allow the diagnostic of cancer and sometimes the determination of its origin.     

Tail stump spermatozoa: morphogenesis of the defect. An ultrastructural study of sperm and testicular biopsy

We have studied the ultrastructure of testes biopsies and immotile spermatozoa from a supposed secondary infertile male. A wide range of tail defects has been described in testes and semen. Among these, tail stump spermatozoa occurs rarely. Although the origin of this defect is unknown, testes sections revealed that damage occurs during spermiogenesis at the latest stages during flagellum elongation in spermatids.     

Renal and hemodialysis clearances of endogenous natriuretic peptide. A clinical and experimental study

The purpose of the present study was to assess the plasma levels of atrial natriuretic peptide (ANP) in chronically uremic patients not submitted to dialysis and to determine the predialysis plasma concentration of ANP, the effect of ultrafiltration on plasma levels of ANP (hemodialysis, (HD), and the HD clearance of ANP in a population of adult patients treated with maintenance HD. The mean plasma ANP concentration (pg/ml) in HD was 370.2 +/- 35.5 pg/ml (mean +/- SEM) before HD and decreased to 165.3 +/- 15.2 after HD (p less than 0.01). Both values were significantly higher than in controls (28 +/- 2; n = 39). The changes in plasma ANP levels correlated inversely with those in plasma protein concentration (r = -0.53; p less than 0.03; y = 48.6 +/- 0.8 x). ANP clearance across the cuprophan membrane averaged 13 +/- 6.4 ml/mn. Resting plasma ANP values in the 16 uremic patients ranged between 16 and 277 pg/ml (124 +/- 11 pg/ml). These levels were significantly higher than those observed in controls (p less than 0.01). In these patients there was a highly significant correlation between serum creatinine and plasma ANP concentrations (p less than 0.01; r = 0.75; y = 0.2x + 3). Furthermore we report the results of the determination of the renal clearance of ANP in normal dogs. In all dogs a fall in plasma ANP concentration was recorded between the aorta (28.6 +/- 4.5 pg/ml) and the renal vein (14.2 +/- 2.7 pg/ml). The renal extraction ratio averaged 51.3 +/- 3.7%. Mean ANP renal clearance was 38.2 +/- 5.2 ml/mn.(ABSTRACT TRUNCATED AT 250 WORDS)     

Expression and functional activity of CXCR-4 and CCR-5 chemokine receptors in human thymocytes

In this paper we addressed the expression of the HIV co-receptors CXCR-4 and CCR-5 in human thymocytes by phenotypic, molecular and functional approaches. Cytofluorimetric analysis disclosed that CXCR-4 was constitutively expressed by freshly isolated thymocytes (~10 000 molecules/cell in about 30% of thymocytes); the receptor was endowed with functional activity, as it mediated polarization, migration and intracellular Ca2+ increase in response to its ligand, SDF-1. On the contrary, CCR-5 expression in freshly isolated thymocytes was significantly lower (<4000 molecules/cell in less than 5% of the cells), and no functional response to CCR-5 agonists could be documented. Northern blot analysis of freshly isolated thymocytes showed high CXCR-4 mRNA levels, whereas the message for CCR-5 was barely detectable. On the other hand, a modest increase in the expression of CCR-5 was associated with in vitro thymocyte stimulation, and CCR-5 density at the cell surface attained CXCR-4 figures in most cases. None the less, no functional response to CCR-5 agonists could be documented in in vitro stimulated thymocytes. In vitro infection of thymocytes by CAT-expressing recombinant HIV bearing the envelope glycoproteins from different isolates showed that T-tropic strains, which use CXCR-4 as a co-receptor, were more efficient in infecting thymocytes than M-tropic strains, which preferentially use CCR-5. Altogether, these data indicate that expression of the major co-receptors involved in infection by M-tropic HIV strains is very poor in human thymocytes, and would suggest that thymocyte infection by M-tropic HIV strains may be a rare event in vivo.     

Molecular detection of Histoplasma capsulatum var. capsulatum in human clinical samples

We developed a seminested PCR for the diagnosis of histoplasmosis that amplifies a portion of the Histoplasma capsulatum H antigen gene. This assay is highly sensitive and specific, being able to detect genomic material corresponding to less than 10 yeast cells without cross-reaction against other bacterial or fungal pathogens.     

Regulation of cognitive activity and early communication development in young autistic, mentally retarded, and young normal children

Based on the Piagetian framework, this study examined regulation of cognitive activity and developmental communication profiles and their interrelationship in groups of autistic, mentally retarded, and normal children of comparable overall, verbal, and oculo-manual developmental ages (from 6 to 24 months). Regulation of activity was assessed with both an object permanence test and an original behavior grid, and development of communication skills with the Guidetti-Tourrette scales (French adaptation of the Seibert-Hogan scales). The results showed evidence of certain types of dysregulation of cognitive activity and a general delay in communication ability in autistic children compared to the other two groups. Moreover, although the intensity of some of these disorders decreased in relation to the developmental levels of social interaction and joint attention in normal children, they were related to both high and low levels of development of social interaction only in autistic children. These findings raise the hypothesis of a relationship between a disorder of disengaging from an activity and developmental levels of social interaction noted at two transitory periods of early development (12 and 24 months) only in children with autism. Developmental and neuropsychological interpretations of this particular pattern are proposed.     

Oxidative stress response involving induction of protective enzymes in Candida dubliniensis.

Candida dubliniensis is a yeast species closely related to Candida albicans, but in contrast to C. albicans, limited information is available on the virulence factors of this important fungal pathogen. The objective of the present study was to determine if this species was able to evoke an adaptive response to oxidants. C. dubliniensis, treated with a low concentration of either H(2)O(2) or methyl viologen (a superoxide generating agent), mounts an adaptive response that results in increased survival against lethal doses of both oxidants. This response was characterized by the induction of enzymes with known antioxidant function. C. dubliniensis strains were less resistant to oxidants than C. albicans, displaying higher susceptibility to their toxic effects. The adaptive response described here might be responsible, among other factors, for the ability of this pathogen to cause infections in individuals with impaired immunity.     

The behavioral summarized evaluation: Validity and reliability of a scale for the assessment of autistic behaviors

The Behavioral Summarized Evaluation (BSE), is a 20-item paper- and-pencil rating scale specifically designed for the measurement of behavioral parameters which could be related to biological data in autistic children involved in educational programs, neurophysiological studies, and therapeutic trials. The development of the scale, the validity, and reliability studies are presented in this paper. The results suggest that the BSE is an acceptable tool for the assessment of autistic behaviors, easy to handle, and accessible to both professionals and paraprofessionals of the medico-educative staff. It is a useful addition to the bioclinical researcher's evaluation battery for bioclinical and therapeutic studies. However, more work is suggested to further investigate the psychometric properties of this behavior assessment instrument.This study was supported by CNRS, by INSERM U 316 Nervous System from the Foetus to the Child, Development, Circulation, Metabolism, L. Pourcelot, CNAMTS No. 2748/88, FRM 1986, Conseil Régional Région Centre, Contrat No.7.040.000, INSERM, and Fondation Langlois. The authors thank S. Lancrenon, Department of Biophysics and Biomathematics (J. Fermanian), C.H.U. Pitie-Salpetriere, Paris, for her helpful suggestions and assistance. They also thank Mrs. Barre and Miss Lioret for their technical work.     

Retroperitoneoscopy: A laparoscopic approach for adrenal and renal surgery

Objectives

Retroperitoneoscopy has gained acceptance for urologic surgery. We assessed the safety and efficacy of this procedure for renal and adrenal surgery.

Methods

Since December 1994, 20 patients (18 to 75 years old) have undergone laparoscopic adrenalectomy and nephrectomy, including simple nephrectomy in 8, partial nephrectomy in 1, radical nephrectomy in 2, tumorectomy with cyst excision in 1, and adrenalectomy in 8. The retroperitoneal space was created by blunt dissection with the index finger, completed by insufflation, without balloon dissection.

Results

Average kidney size was 65 mm (range 50 to 108), and average adrenal tumor size was 31 mm (range 20 to 40). The average operating time was 127 minutes (range 60 to 180) for nephrectomy and 84 minutes (range 45 to 140) for adrenalectomy. The average hospital stay was 3 days (range 1 to 7) for nephrectomy and 2.4 days (range 1 to 4) for adrenalectomy. Average blood loss was 65 mL for both nephrectomy and adrenalectomy. Conversion from the laparoscopic procedure to open surgery was never required. Peritoneal effraction and ureteral injury occurred in only 4 patients and 1 patient, respectively.

Conclusions

The laparoscopic retroperitoneal approach is safe and effective for simple renal nephrectomy and for excision of small adrenal tumors. Perioperative morbidity and hospital stay are reduced.