Biotin deficiency in protein-energy malnutrition

Several of the clinical and biochemical manifestations of biotin deficiency also occur in severe protein-energy malnutrition (PEM). Average plasma biotin concentrations were lower in 16 malnourished children (10 with marasmus, 3 with kwashiorkor and 3 with marasmic kwashiorkor) than in 31 controls. Lymphocyte mitochondrial carboxylase activities were studied in 11 controls and in 10 patients with PEM; on the average, they were lower in the patients. Their activation indices (the ratio of enzyme activity in cells incubated with biotin to activity in cells incubated without the vitamin) were higher in PEM. All these differences were statistically significant. None of these parameters were age-dependent in a range between 3 and 72 months. Carboxylase activities and plasma biotin levels increased to normal during nutritional recovery in two malnourished patients who were further studied. These results suggest that there is biotin deficiency in severe PEM. Urinary biotin concentrations, expressed per g of creatinine, were higher in the patients than in the controls; this may have been caused by increased renal clearance or by the reduced creatinine excretion which occurs in malnourished individuals. It will be important in future studies to determine the relative contribution of biotin deficiency to the malnourished phenotype.     

Rare testicular tumors. Apropos of 15 cases

In a series of 141 patients treated over the last ten years for testicular tumour, 15 presented lesions considered to be rare: 9 Leydig cell tumours, 3 epidermoid cysts, 1 leiomyoma, 1 primary testicular lymphoma and one testicular localisation of a known leukaemia. The clinical, endocrine and histological features of these different tumours are reviewed on the basis of the present series and a wider discussion of other rare testicular tumours. Leydig cell tumours, epidermoid cysts, mature benign teratomas and testicular lymphomas are the most frequent. Leiomyomas, metastatic tumours and connective tissue tumours are exceptional. Sertoli cell tumours are rare and are similar to Leydig cell tumours in that they raise problems concerning their possible endocrine activity and the evaluation of their malignant potential. The general therapeutic rule of radical orchidectomy for any testicular tumour is still valid.     

Closing patellar tendon defects after anterior cruciate ligament reconstruction: absence of any benefit

The most common graft in anterior cruciate ligament (ACL) surgery involves using the central one-third of the patellar tendon. Knowledge concerning the postoperative disability after harvesting the patellar tendon is, however, limited. The aim of this study was to evaluate the impact patellar tendon suture and bone grafting of the patellar bone defect might have in terms of functional outcome and patellofemoral pain after harvesting the bone-tendon-bone graft, compared with leaving the harvested site non-sutured and non-grafted. Sixty patients, scheduled for arthroscopically assisted ACL reconstruction, were randomly allocated to two groups. In group I, suture of the patellar tendon and bone grafting of the patellar defect were performed. In group II, the tendon gap and the patellar defect were left open. Preoperatively, there was no significant difference between the groups when comparing objective knee stability, as measured with a KT-1000 laxity meter, Lysholm score, Tegner activity level, IKDC score, or patellofemoral pain score. Both groups had a significantly improved Lysholm score at the 2-year follow-up, without any difference between them. Tegner's activity level was significantly lower at follow-up, compared with the pre-injury level in both groups. The patellofemoral pain score improved significantly after the reconstruction, without any difference between the groups. Ultrasonography did not reveal any difference between the groups in terms of healing of the tendon gap. This study revealed no differences in donor site morbidity, functional outcome, patellofemoral pain score or knee joint stability between the two treatment groups. The conclusion is that suture of the patellar tendon and bone grafting of the patellar defect do not improve the functional results or reduce donor site morbidity after arthroscopically assisted ACL. Received: 17 December 1996 Accepted: 30 July 1997     

Robust optimal design for the estimation of hyperparameters in population pharmacokinetics.

The expectation of the determinant of the inverse of the population Fisher information matrix is proposed as a criterion to evaluate and optimize designs for the estimation of population pharmacokinetic (PK) parameters. Given a PK model, a measurement error model, a parametric distribution of the parameters and a prior distribution representing the belief about the hyperparameters to be estimated, the EID criterion is minimized in order to find the optimal population design. In this approach, a group is defined as a number of subjects to whom the same sampling schedule (i.e., the number of samples and their timing) is applied. The constraints, which are defined a priori, are the number of groups, the size of each group and the number of samples per subject in each group. The goal of the optimization is to determine the optimal sampling times in each group. This criterion is applied to a one-compartment open model with first-order absorption. The error model is either homoscedastic or heteroscedastic with constant coefficient of variation. Individual parameters are assumed to arise from a lognormal distribution with mean vector M and covariance matrix C. Uncertainties about the M and C are accounted for by a prior distribution which is normal for M and Wishart for C. Sampling times are optimized by using a stochastic gradient algorithm. Influence of the number of different sampling schemes, the number of subjects per sampling schedule, the number of samples per subject in each sampling scheme, the uncertainties on M and C and the assumption about the error model and the dose have been investigated.     

Abuse liability of flunitrazepam among methadone-maintained patients

Abuse liability and acute subjective and psychomotor effects of flunitrazepam were assessed in ten methadone-maintained males with history of benzodiazepine and alcohol use, who voluntarily participated in a double-blind, controlled, cross-over, randomized clinical trial. There were six experimental sessions in which a single oral dose of flunitrazepam 1, 2, and 4 mg; triazolam 0.5 and 0.75 mg; and placebo was given. Evaluations included physiological measures; psychomotor performance tasks (simple reaction time, Digit Symbol Substitution Test, balance task, Maddox-wing device); and self-administered subjective effects questionnaires [Addiction Research Center Inventory (ARCI), Profile of Mood States (POMS), a series of visual analog scales (VAS)]. All drugs but flunitrazepam 1 mg caused an impairment of psychomotor tasks. Effects were more evident with the highest doses of both drugs. Only flunitrazepam 4 mg produced a significant decrease in balance time. Triazolam 0.75 mg induced increases in sedation measured by ARCI-PCAG, depression in POMS, and VAS-drowsiness scores. Flunitrazepam 4 mg caused euphoria-related effects as measured by increases in ARCI-MBG and “high” scores in the VAS. Our findings of flunitrazepam-induced euphoria in methadone-maintained subjects together with epidemiological evidence of flunitrazepam abuse by opioid dependents, suggest that it may be included in the group of benzodiazepines with a relatively high abuse potential. Received: 13 February 1998/Final version: 1 May 1998     

Short-term outcome analysis of a randomized study comparing laparoscopic vs open colectomy for colon cancer

The authors examined the impact of the laparoscopic approach on the early outcome of resected colon carcinomas. The role of laparoscopic techniques in the treatment of colon carcinomas is questionable. Previous studies have suggested technical feasibility of surgical resections of these cancers by laparoscopic means and have implied a benefit to laparoscopic technique for patients undergoing colorectal resections. A prospective, randomized study was conducted comparing laparoscopic assisted colectomy (LAC) open colectomy (OC) for colon cancer. We present the preliminary results in relation to the short-term outcome and judge the feasibility of the laparoscopic procedure to as a way of performing accurate oncologic resection and staging. Benefit has been demonstrated with LAC in this setting. Passing flatus, oral intake, and discharge from hospital occurred earlier in LAC- than OC-treated patients The mean operative time was significantly longer in the LAC group than in the OC group. The overall morbidity was significantly lower in the LAC group. No significant differences were observed between both groups in the number of lymph nodes removed or the pathological stage following the Astler-Coller modification of the Dukes classification. The laparoscopic approach improves the short-term outcome of segmental colectomies for colon cancer. However, the further follow-up of these patients will allow us to answer in the near future whether or not the LAC may influence the long-term outcome.Presented at the annual meeting of the Society of American Gastrointestinal Surgeons (SAGES), Orlando, FL, USA, 11–14 March 1995