Pharmacokinetics of cyclosporine as a function of energy--protein deficiency in children with chronic renal failure.

The present study was conducted to determine whether malnutrition in patients with chronic renal failure requiring cyclosporine therapy for renal transplantation has some effect on the clinical pharmacokinetics of cyclosporine. Eleven pediatric patients were enrolled in this study before renal transplantation and divided into two groups (group I: six well-nourished patients with a deficit in weight/height ratio < or = 7%; group II: five malnourished patients with a deficit in weight/height > 8%). The patients received a single oral dose of cyclosporine (3.0 mg/kg). Blood samples were collected for a 26-hour period, and serum concentrations of cyclosporine were measured using fluorescence-polarization immunoassay technology. The results suggest that, when malnutrition is present, the median Cmax of cyclosporine decreases by almost threefold (from 387.5 ng/mL in group I to 136.1 ng/mL in group II). An observed 52% reduction in AUC0-infinity (from 2,856.0 ng/mL/hr in group I to 1,481.4 ng/mL/hr in group II) was caused by the increased volume of distribution (from 4.6 L/kg in group I to 11.1 L/kg in group II). The elimination half-life (t1/2) was longer in group II compared with that of group I (12.4 hr for group II; range, 7.8-13.5 hr versus 8.9 hr for group I; range, 5.2-16.0 hr). Differences in t1/2 were not statistically significant at 5% confidence intervals. The effects of energy malnutrition on the pharmacokinetics of cyclosporine could explain in part some of the interindividual variability. This study provides pharmacokinetic guidelines for the use of cyclosporine.

[Chemico-clinical permanent program of the NIH. I. The first phase of the program]. / Programa permanente químico-clínico de los INS. I. La primera fase del progrma.

BACKGROUND INFORMATION: This is the report of the first phase of an internal/external permanent program of the MNIH (Mexican National Institutes of Health). The permanent program evolved from a previous one operating from 1984 to 1988 in the MNIH (Refs 1-5). OBJECTIVE: To evaluate the precision of the assay systems used currently by the clinical chemistry laboratories of the MNIH. MATERIAL AND METHODS: A single batch of a lyophylized control serum prepared for the program by an agency of the Ministry of Health was used throughout the study. During a period of four months, the participants were provided with flasks of the control serum every two weeks to assay the analytes included in the routine daily work of each laboratory. They also received every two weeks an update of the mean of means and interlab CV of the information available. RESULTS: The 11 participants reported 6278 results of 24 analytes (6 enzymes, 8 electrolytes and 10 organic metabolites) assayed in 179 systems. The majority of the systems (162/179 = 91%) were autoanalyzers. There were 168 systems which could be evaluated in precision and 115 in accuracy. The rate of imprecision was 15% (25/168) and of inaccuracy 17% (19/115). CONCLUSIONS: 1. The participants were able to act as a reference group to assign the value of 12 analytes in a control serum with low concentration of most analytes. 2. Imprecision was concentrated in two participants (Labs B and J with 15 of the 25 imprecisions: see table 2). The second phase of the program will be to identify and if possible eliminate the sources of variation in the systems of participants B and J.

Idiopathic gastroparesis in patients with unexplained nausea and vomiting.

Nausea and vomiting are symptoms sometimes associated with motor dysfunction. We compared a group of young patients suffering from chronic nausea and/or vomiting and normal upper gastrointestinal x-ray series with a control group. The members of both groups underwent isotopic examinations of their stomachs. The aim of the study was to find a simple method of checking the stomach and proving a motor dysfunction in a group of patients with chronic, inexplicable nausea and vomiting. Patients and controls fasted for at least 6 hr were given 0.5 mCI of [99mTc] diethylene triaminopentaacetic acid orally in 150 cc milk with 50 g cornflakes. A time-activity curve was obtained and radioactivity over the stomach was recorded exponentially. The parameter of the T1/2 emptying time was used. In normal controls T1/2 emptying time ranged from 18 to 26 min. Twenty-five symptomatic patients were examined, three of whom achieved normal values, but 22 patients showed pathologic results ranging from 36 to 184 min. In patients with chronic nausea and/or vomiting an isotopic examination of the stomach may provide a simple and rapid diagnostic method of evaluation.

Stress fractures of the femoral neck following strenuous activity.

Stress fractures of the femoral neck following sustained strenuous physical activity are uncommon. In 194 military recruits in elite basic training who had sustained 257 stress fractures, most of them in long bone diaphyses, nine such fractures were located in the femoral neck. Seven of these fractures were transverse and undisplaced, and were treated successfully by bed rest and non-weight bearing for 6-8 weeks. The other two fractures displaced into a varus position. One of them was treated successfully by manipulation and plaster of paris spica immobilization. Solid union of the fracture followed within 3 months. The second displaced fracture was treated by two successive procedures of internal fixation because it did not unite after the first intervention and slipped again into varus position. It is therefore suggested that unstable stress fractures of the femoral neck should be initially operated on and stabilized by rigid internal fixation, in order to avoid displacement and severe disability.

High ligation or embolization of varicocele.

The presence of a varicocele was confirmed in 121 of 123 patients complaining of scrotal pain or infertility, in whom radionuclide scanning was performed. In the first 29 patients (retrospective study), a high ligation of the internal spermatic vein was performed. In 94 patients, a percutaneous venography was done via the jugular vein followed by embolization by Gianturco coils (occluding spring embolus, Cook Group Company, USA) in 84 of them. In eight patients, due to technical difficulties during the embolization trial, a high ligation was performed at a later date. Eleven patients underwent embolization after failed high ligation. A posttreatment follow-up radionuclide study revealed recurrences in two of the 95 patients who underwent embolization. Embolization can be performed on an outpatient basis with minimal risks. Reembolization is feasible, and it in no way prevents a further high ligation should this be necessary.

Differential diagnosis between Kaposi's sarcoma and pseudo-Kaposi's arteriovenous malformation by scintigraphy.

Kaposi's sarcoma and pseudo-Kaposi's arteriovenous malformation differ greatly in cause, evolution, prognosis, and treatment; yet their clinical macroscopic manifestations are similar. A simple and safe method of distinguishing between them is described.

Dynamic, diagnostic, and pharmacological radionuclide studies of the esophagus in achalasia.

The esophagus was evaluated in 15 patients with achalasia by continuous gamma camera imaging following ingestion of a semi-solid meal labeled with 99mTc. The images were displayed and recorded on a simple computerized data processing/display system. Subsequent ciné mode images of esophageal emptying demonstrated abnormalities of the body of the esophagus not reflected by the manometric examination. Computer-generated time-activity curves representing specific regions of interest were better than manometry in evaluating the results of myotomy, dilatation, and drug therapy. Isosorbide dinitrate significantly improved esophageal emptying.

Exposure to radioiodine in the preconception and conception periods. A case report.

A case of radiation exposure shortly before conception is presented. The patient refused abortion and was delivered of a healthy infant. On reconsideration of the case, it was decided that the recommendation to terminate the pregnancy on the grounds of excessive exposure to radiation was unjustified. We feel that physicians should be aware that abortion in such cases is not always necessary.

Sequential use of technetium 99m MDP and gallium 67 citrate imaging in the evaluation of painful total hip replacement.

Fourteen patients with 20 total hip joint replacements were studied for 14 painful prosthetic hips. Clinical examination, plain film radiographs and 99Tcm-MDP bone scans failed to differentiate between infection and mechanical loosening of a prosthesis. Sequential use of 99Tcm-MDP and 67Ga-citrate bone scans were performed in an attempt to discover underlying infectious process. Increased focal uptake of both radiopharmaceuticals over the same hip indicated an infectious process responsible for prosthetic loosening. There were no false positive gallium examinations. Sequential use of 99Tcm-phosphate compounds and 67Ga-citrate is recommended for differentiation between mechanical loosening of a prosthesis and loosening of a prosthesis secondary to an infectious process.