A pharmacokinetic comparison of the corn oil versus microemulsion gelcap formulation of cyclosporin used de novo after renal transplantation

The initial poor absorption of the corn oil-based, gel capsule oral formulation of cyclosporin (CyA) greatly limits its use for inception of immunosuppressive therapy. Insufficient drug concentrations during the early post-transplant period predispose to renal allograft rejection. The present study served to compare the time required to achieve therapeutic CyA concentrations after de novo administration of the corn oil-based gel capsule (CyA-GC; n = 11) versus the microemulsion (CyA-ME; n = 11) formulation of CyA. During the 1st month after renal transplantation, patients underwent serial pharmacokinetic profiling from which we obtained observed and dose-corrected values of several parameters. Although patients in neither the CyA-GC nor the CyA-ME group adequately absorbed the drug during days 0–2, from day 3 to 4 patients in the CyA-ME group showed significantly greater absorption than those in the CyA-GC group (P = 0.041). Patients in the CyA-ME group reached the 1st month target average concentration (C_av) values ( ≥ 550 ng/ml) earlier than those in the CyA-GC group and required significantly lower daily CyA doses (P = 0.018). We conclude that therapeutic CyA levels can be achieved more rapidly and with lower doses of the drug after de novo administration of CyA-ME than with CyA-GC. Received: 13 September 1996 Accepted: 7 January 1997     

Does a single device prevent further slipping of the epiphysis in children with slipped capital femoral epiphysis?

All 170 patients (212 hips) treated between 1946 and 1992 for slipped capital femoral epiphysis (SCFE) with fixation in situ with a single device were reviewed to evaluate the incidence of further slipping of the epiphysis after primary treatment. In 154 hips, a smooth device without anchorage in the epiphysis was used and in 58, a device anchored in the epiphysis. In 3 hips, further slipping of the epiphysis occurred after primary treatment with no obvious cause. In 10 hips, an obvious cause for further slipping of the epiphysis was found. These 10 hips were re-operated due to the loss of epiphyseal grip in 6 hips, unsatisfactory placement of the device in 1, while in the remaining 3 hips, the device was removed before physeal closure. Twenty-six hips (12.3%) were re-operated because the device had lost its epiphyseal grip before physeal closure, and in 25 of these hips the device was smooth and had no anchorage in the epiphysis. The conclusion of this study is that a single device with anchorage in the epiphysis is stable enough to prevent further slipping of the epiphysis in hips with SCFE.     

Assumptions and Validations of Statistical Tests for Functional Neuroimaging

We contrast two statistical methods: three-dimensional cluster analysis and statistical parametric mapping. We show that three-dimensional cluster analysis is based on a neurobiological theory of the regulation of blood flow and, unlike statistical parametric mapping, carries a minimum of assumptions that are tested. Statistical parametric mapping is a formal approach, which is based on a multitude of assumptions of which the majority have not been validated. We also demonstrate that in practice three-dimensional cluster analysis has a reasonable balance between sensitivity and the probability of false positives, giving high reproducibility with data on e.g. colour discrimination.     

Articulation of Asthma and Its Care Among Low-Income Emergency Care Recipients

Low-income minority patients from East St. Louis, Illinois, a depressed midwestern urban city, who had visited acute care settings with asthma symptoms, participated in a focus group. Questions were constructed around the Health Belief Model to characterize participants' experiences in receiving asthma care, their confidence in long-term asthma self-management, barriers they perceived to managing their asthma, and recommendations they would make for improving asthma care in their community. Analysis of comments suggests an appreciable understanding of asthma triggers, limited coping behaviors for asthma symptoms, very limited practice of active asthma management, perception of the health care system as frequently insensitive to their needs or their knowledge of their own care, exchange of well-articulated information regarding how to deal with the system, and an apparent lack of awareness of any potential contribution of patient education or support system.     

Genetics: Genetic analysis prior to selective fetal reduction in multiple pregnancy: technical aspects and clinical outcome

Multiple pregnancies resulting from ovarian stimulation areat a higher risk of carrying at least one fetus affected byMendelian or chromosomal anomalies, the incidence of which isdirectly related to the order of multiples. Genetic analysisbefore fetal reduction was offered to both high-and low-riskpregnant women carrying two or more fetuses after ovulationinduction. Chorionic villus sampling (CVS) and fetal reductionwere achieved by transabdominal needling. The use of short-termculture, the polymerase chain reaction and fresh tissue enzymaticanalyses have made it possible for genetic diagnosis to be availablein a few days. A total of 100 patients had multifetal pregnancyreduction performed by a single operator; all of them completedpregnancy and none was lost at follow-up. The total fetal lossbefore 24 weeks was 7% and no statistically significant relationshipwas found with the final number of fetuses and CVS. Perinatallosses (3.9%) were only present in the series with a final numberof two fetuses. Pregnancy duration and birthweight were significantlyhigher in singletons than in twins, but were not related toCVS. The rate of chromosomal disorders was higher (7.2%) inthe study series than in singleton pregnancies not undergoingfetal reduction. Diagnostic error due to incorrect samplingwas reported in 1.5% of cases. These data support fetal reductionas a valuable strategy to improve the outcome of multiple pregnancy.The outcome of pregnancies reduced to singletons was significantlybetter than of those reduced to twins, and was not related toCVS. Therefore, prenatal genetic diagnosis should become anintegral part of counselling on multiple pregnancy, and is stronglyrecommended when reduction to singleton pregnancy is requested.     

Nitrobid therapy in sudden sensorineural hearing loss

The efficacy of local application of Nitrobid oinment in the treatment of idiopathic sudden sensorineural hearing loss has been presented Overall good to fair recovery occured in 40% of the patients, important prognostic indicators were found to be severity of initial hearing loss, time from onset to initial visit, age of the patient and hearing status of the opposite ear.     

Use of omeprazole in Zollinger-Ellison syndrome: a prospective nine-year study of efficacy and safety

H⁺, K⁺-ATPase inhibitors such as omeprazole are the antisecretory agents of choice for the management of gastric acid hypersecretory states, including the Zollinger-Ellison syndrome. However, long-term follow-up data on the overall efficacy and safety of these agents in large numbers of patients are lacking. In the current study we examined the long-term efficacy and safety of omeprazole in 116 patients with Zollinger-Ellison syndrome treated with oral omeprazole at a single centre for up to 114 months (mean ± S.E.M. = 38 ± 3 months). The initial omeprazole maintenance dose was established according to the acute upward dose titration method in 89/116 patients (77%). Gastric acid output was effectively controlled using 60 mg of omeprazole once daily in 41/89 patients (46%) and 22/89 patients (25 %) required twice daily omeprazole therapy. The mean ranitidine equivalent dose for patients who required 60 mg omeprazole once daily (2.5 ± 0.2 g/day) was significantly lower than the mean ranitidine equivalent dose for patients who required more than 60 mg omeprazole once daily (4.3 ± 0.3 g/day). Long-term omeprazole maintenance therapy was discontinued in 36/116 patients (31%) but in no cases was discontinuation due either to drug-induced side-effects or uncontrolled gastric acid output. Fasting serum gastrin levels were significantly elevated above pre-treatment levels at only one time point during follow-up and were likely due to tumour growth rather than a drug effect. The final long-term omeprazole maintenance doses were lower than the initial doses but correlated closely with the preomeprazole basal acid output (r= 0.41, P < 0.001) and ranitidine equivalent dose requirements (r= 0.49, P < 0.001). We conclude that omeprazole effectively and safely controls gastric acid hypersecretion in all patients with Zollinger-Ellison syndrome for up to nine years without evidence by tachyphylaxis.     

OVERHEATING IN BED AS AN IMPORTANT FACTOR IN MANY COMMON DERMATOSES

Background. Extensive questioning of patients with a wide variety of skin disorders led to the impression that nocturnal overheating was probably an important factor in the initiation and the perpetuation of many skin disorders. Methods. In order to test the hypothesis, 12 “clean-skinned” subjects (6M/6F) aged 18 to 45 years were monitored electronically every 30 seconds during an 8 hour sleep period (2300 to 0700 hours), sleeping under a standard 10 tog duvet. Results. All the subjects were too hot by 3 to 4°C. All showed changes in their EEG patterns with reduced REM sleep, increased awakenings, and all showed changes in their sleep stage patterns. In addition, they all showed evidence of increased sweating in the “heat-sink” area. Conclusions. The mechanisms where by such changes could be implicated in the precipitation and perpetuation of skin disease are discussed. “Lifestyle” modification as a very effective, noninvasive, therapeutic regime is recommended. Further research along these lines would probably be very valuable and instructive.     

Penile blood flow changes in the flaccid and erect state in potent young men measured by duplex scanning

We studied penile blood flow changes with duplex ultrasound scanning in 8 potent young men during the flaccid state and during the erect state induced by visual sexual stimulation. Measured parameters obtained from the cavernous arteries were arterial diameter, peak blood flow velocity and blood flow acceleration. The mean arterial diameter change was 72% associated with average blood flow velocity and acceleration changes of approximately 200%. Actual values for blood flow velocity and acceleration were considerably higher when compared to papaverine-induced values measured in psychogenically impotent men. Visual sexually stimulated penile arterial changes are not analogous to papaverine-induced arterial changes and these differences raise questions about the appropriateness of using psychogenically impotent men as controls for measurement of penile arterial function with duplex scanning.