Effect of liver hypothermic preservation: exploration and protection.

BACKGROUND/AIMS: The principal aim of conservation is to maintain the viability of grafts. This requires the addition of a cellular protector allowing better conservation of the graft. The aim of this work is to evaluate the effect of trimetazidine (TMZ) addition to Wistar rat livers conserved in Krebs-Henseleit solution, compared to the livers preserved only in Krebs-Henseleit solution (24 h at 4 degrees C). METHODS: 40 Wistar female rats divided into 5 groups were used: the first group consists of nonpreserved livers, the second consists of livers preserved only in the Krebs-Henseleit solution, and the other 3 groups consist of livers preserved in Krebs solution with different concentrations of TMZ added (16.5, 49.5 and 165 microg/ml). RESULTS: The obtained results show an improvement in the state of the liver in the presence of a high concentration of TMZ, which approaches normal physiological conditions. We note a clear diminution of transaminase activities, as well as an amelioration in metabolic capacities of the liver if the mitochondrial esterase pathway is supported in Wistar rats by a reduction of histological injuries. CONCLUSION: A TMZ concentration of 165 microg/ml clearly restored the metabolic capacities of the liver. Indeed, TMZ limited the appearance of necrotic areas and almost suppressed apoptotic cells.

Comparison of three methods for cyclosporine therapeutic monitoring.

Cyclosporine (CsA) is an immunosuppressive drug used extensively in human transplants of solid organs or bone marrow as well as in the treatment of autoimmune diseases. To optimize immunosuppressive efficacy and minimize adverse reactions, blood CsA concentrations are monitored to allow appropriate dosage adjustments. To establish objective criteria to compare various techniques of CsA monitoring, we performed a detailed study over 5 months to compare and evaluate three immunoassays methods in comparison to the reference method of high-performance liquid chromatography (HPLC). Our study included 976 samples that were evaluated by: the COBAS INTEGRA 800 (Roche Laboratories); the V-Twin (Dade Behring Laboratories); and the AxSYM FPIA (Abbott Laboratories). Our results showed that all of the immunoassays yielded slightly higher concentrations than HPLC. However CsA concentrations obtained by AxSYM were most close to those of HPLC, so that this method seemed to be more specific than the other two.

[Fixed drug eruption induced by sulfaguanidine]. / Erythème pigmenté fixe à la sulfaguanidine.

INTRODUCTION: Fixed drug eruption is a lesion induced by drugs. The family of drugs usually incriminated are sulfonamides, tetracyclines and pyrazols. We describe nine cases of fixed drug eruption induced by sulfaguanidine, a sulfonamide with local action. CASE REPORTS: All the patients presented one or more fixed drug eruption reactivation lesions induced by sulfaguanidine as self-medication for diarrhea. The number of lesions increased in 7 cases after reactivation. The delay in occurrence of the fixed drug eruption decreased during the different episodes. The lesions predominated on the hands in 8 cases of 9. DISCUSSION: The sulfaguanidine must be added to the list of drug-induced fixed drug eruptions with limited absorption from the gastrointestinal tract.

[Pharmacologic study of monohydrated caffeine in the treatment of apnoea of premature infant]. / Etude pharmacologique de la caféine monohydratée dans le traitement des apnées du prématuré

UNLABELLED: Monohydrated caffeine was the only respiratory xanthine available in our country to treat apnea of premature infant. The aim of this study was to evaluate plasma levels of this molecule at dosages of 20 mg/kg (equal to 18 mg/kg of caffeine base) as a loading dose and 5 mg(-1) kg(-1) (equal to 4.5 mg(-1) kg(-1) of caffeine base) as a maintenance dose. PATIENTS AND METHODS: The study was prospective including premature infants less than 34 weeks of gestational age born between the 1st of july 2001 and 15th december 2001 and receiving monohydrated caffeine to prevent apnea. Each premature infant has received orally a loading dose of 20 mg/kg in the first hours of life followed, 24 h after, by a maintenance dose orally once a day of 5 mg/kg until 35 weeks of post-conceptional age. Caffeinemia plasma levels were measured by high performance liquid chromatography immediately before the second dose to determine the loading residual rate and immediately before the sixth dose to determine the maintenance residual rate. RESULTS: Twenty-one premature infants were included. Their medium term was 31.4 weeks (27.4-33.3 weeks), birth weight was 1684 g (1000-2800 g) and sex-ratio M/F was 1.3. Fifteen infants (71.4%) have presented apnea with an average of 4.1 episodes per infant and per day. Tolerance of the medicament was good in all cases. The medium loading residual rate was 3.26 microg/ml (1.75-7.80) and the medium maintenance residual rate was 4.26 microg/ml (2.13-7.64). CONCLUSION: Prescribed at a dosage close to twice the recommendations of the literature, monohydrated caffeine does not provide efficient plasma rates. This is probably due to a difference in its oral bio-availability compared with caffeine citrate and further study with greater dosages is needed to appreciate its efficacy.

[Epidemiologic data in renal lithiasis in adults]. / Données épidémiologiques de la lithiase rénale chez l'adulte.

The morpho-costitutional analysis of 574 urinary lithiasis emitted by tunisean adults permitted to define an épidemiology's profile. This resemble to the épidemiology's profile of under-developed conry: Amore raised frequency of the renal lithiasis at the man than at the woman with a sec ratio of 2.4. An average age of +14 years with a peak to 4th decade in 2 sexes. The upper localitation of the calculi is founded in 94% cases. The fréquency of the relapses, the mode of expulsion and the size of calculi are différent of those published in the litérature. Probably because the time of study which last 4 years is too short, so it don't enable us to find a result like the literature. The surgery is the mode of most fréquent élimination (51%). This s dû to the présence great size calculi in our popûlation and to the récent introduction of the lithotritie in our country.

Similarities and/or dissimilarities of CYP2D6 polymorphism in three Tunisian ethnic groups: Arabs, Berbers, Numides.

Using the validated probe drug debrisoquine and the 8 h urinary metabolic ratio debrisoquine/4 hydroxy-debrisoquine, we have determined the phenotype of the debrisoquine CYP2D6 dependent polymorphic metabolism in 464 Arabs, 227 Berbers and 215 Numides to elicit similarities or dissimilarities of poor metabolizer (PM) prevalence. We found 2.36 per cent of PM in Arabs, 3.08 per cent in Berbers and 2.33 per cent in Numides. These figures are similar to those observed in Middle East populations, and cannot be considered as different from those observed in Caucasians.

Analysis of N-acetyltransferase (NAT2) in three ethnic groups in Tunisia.

Acetylation status was compared, using caffeine as a probe drug, in the three main racial/ethnic groups living in Tunisia: Arabs, Berbers and Numides. The frequency of slow acetylators appears identical in these three groups and is different from that observed in Caucasians. However, the NAT-2 activity as a whole is lower in Tunisians than in Caucasians. These differences might be attributable to the various population mixings which occurred in the past, given the geographical position of Tunisia. It may be asked whether these differences are relevant in term of efficiency and/or frequency of adverse drug reactions when medicines whose metabolism is NAT-2 dependent are used. This hypothesis deserves to be tested.

Urolithiasis in Tunisian children: a study of 120 cases based on stone composition.

The composition of urinary stones in children depends on socioeconomic conditions and hygiene, geographical area, and dietary habits. We analyzed urinary stones from 120 consecutive Tunisian children (81 males, 39 females) aged 5 months to 15 years. The stone was located in the upper urinary tract in 91 cases (76%). Stone analysis included both a morphological examination and an infrared analysis of the nucleus and the inner and peripheral layers. The main components of bladder calculi were whewellite (69%) and struvite (22%), whereas the main component of upper urinary tract calculi was whewellite (67%). The nucleus of bladder stones was composed of ammonium urate (45%), struvite (28%), cystine (10%), and carbapatite (7%). The nucleus of kidney and ureteral calculi was mainly composed of ammonium urate (38%), whewellite (24%), carbapatite (13%), or struvite (11%). Based on stone composition, urinary tract infection was involved in the nucleation or growth of a third of calculi. Endemic urolithiasis involving simultaneous nutritional, metabolic, and infectious factors, and defined by its nucleus composed of ammonium urate without struvite, represented 40% of cases. Exclusive metabolic factors - including genetic diseases such as primary hyperoxaluria, cystinuria, and hypercalciuria - were responsible for less than 25% of cases.

[Urinary calculi in children: contribution of anamnesis, biological exploration and physical analysis of calculi to the etiological diagnosis]. / La lithiase urinaire de l'enfant: contributions de l'anamnèse, de l'exploration biologique et de l'analyse physique des calculs au diagnostic étiologique.

BACKGROUND: It is always of importance to define the cause of urinary calculi disease in children to prevent recurrence and possible impairing of renal function. Nevertheless, etiology is not always easy to prove and must be deduced from both clinical and biological arguments. PATIENTS AND METHODS: The aim of this prospective study including 39 Tunisian children with urinary stones was to identify etiology and stone risk factors and detail the part of clinical and biological data and results of physical analysis of stones in determining the cause of the stone. RESULTS: In 31 cases among 39, clinical and biological data were not sufficient to identify clearly the stone etiology. When considering the structure and stone composition, the cause of the stone could be determined in 97.4% of the cases. An inherited disease was found responsible for the stone in 11 children, urinary tract infection in 13 cases, idiopathic hypercalciuria in nine cases and a nutritional deficiency disease in seven cases. In one case, polycystic kidney disease with metabolic risk factors could explain the stone process. No precise etiology was found in one case. Among infection stones, struvite stones could be related to urea-splitting bacteria while other calculi, containing whitlockite and protein matrix could be related to other micro-organisms. Earlier severe chronic diarrhoea episodes were noted in six among seven children presenting stones with a nucleus mainly composed of ammonium urate. CONCLUSION: Clinical data, biological data from both urine and blood of the patients and also the structure and composition of the stones are needed to identify the cause of urinary calculi. Such a procedure could provide the stone etiology in most cases.

[Primary hyperoxaluria: Tunisian experience apropos of 24 pediatric cases]. / Hyperoxalurie primitive: l'expérience tunisienne à propos de 24 cas pédiatriques.

We report on 24 children (10 girls) presenting with primary hyperoxaluria. The mean age at diagnosis was 6.3 years (range: 3 months-14.8 years). The mean interval between initial symptom and diagnosis was 1.3 year. The average follow-up period was 22 months (range: 1-60 months). At the time of diagnosis the renal function was normal in 6 children, moderately altered in 1 and severely in 17. During the follow-up the renal function remained stable in 6 patients, improved in 2, deteriorated in 4. The 12 patients with end-stage renal disease at diagnosis remained unchanged. Urolithiasis were present in all patients older than 2 years, and in 1 among the 5 infants. Medullary nephrocalcinosis was observed in 3 patients in whom the renal function was preserved. Diffuse nephrocalcinosis was present in all patients with end-stage renal failure. Improvement of renal function was secondary to stone removal in 2 patients. Extracorporeal shock wave lithotripsy performed in 7 patients was efficient only in 3. In 10 patients oxalate bone disease was correlated with both renal function and dialysis duration, whereas retinal involvement noted in 6 patients was not.

[Etiologic factors of urinary lithiasis in Tunisian children]. / Facteurs étiologiques de la lithiase urinaire de l'enfant en Tunisie.

Fifty-five Tunisian children with urinary stones, between the ages of 8 months and 15 years, underwent morphological and infrared spectrophotometric analysis of their stones. This study provides an approach to the aetiological profile of urinary stones in Tunisian children. The nucleus of the stones was composed of acidic ammonium urate in 48% of cases with a morphology suggestive of phosphorus deficiency associated with a history of diarrhoea. In 24% of cases, the nucleus contained struvite indicating the presence of urinary tract infection by urease-positive bacteria. The main growth factors of urinary stones were hyperoxaluria and urinary tract infection. In 5 cases, the stones were due to a hereditary lithogenic metabolic disease : cystinuria in 1 case and primary hyperoxaluria in 4 cases.