METABOLIC AND CNS CORRELATES OF COGNITIVE DYSFUNCTION WITH RENAL FAILURE

Experimental uremia in primates has been demonstrated to produce severe decrements in psychological functions which are related to the accumulation of toxic metabolites in blood. More recent neurophysiological research has referred uremic encephalopathy to disrupted sodium-potassium exchange in uremic brain. The present clinical investigations have found decrements in cognitive functioning with repeated testing in patients maintained on intermittent hemodialysis, which were correlated with plasma concentrations of potassium and creatinine. Power Spectral Density analyses of EEG indicated a shift to lower frequencies in these patients as compared to control subjects. No significant departure from normal functioning has been determined in patients receiving renal transplant tested within 60 days post-surgically.     

Phase I clinical study of LL-D49194α1 with retrospective pharmacokinetic investigations in mice and humans

Summary LL-D491941 is a new cytotoxic antibiotic selected for clinical phase I study because of its impressive pre-clinical anti-tumour activity and its low toxicity profile in experimental animals. A total of 15 patients were treated in centres in Glasgow and Amsterdam at doses ranging from 0.25 to 4 mg/m². One minor response was noted in a patient with colonic carcinoma. The study was suspended following the discovery of unexpected cardiotoxicity. As this toxicity was not consistent with the standard (EORTC) European Organisation for Research and Treatment of Cancer toxicology profile, we chose to investigate the pharmacokinetics of LL-D491941 in mice and humans in more detail to try to explain this phenomenon. A major difference in plasma protein binding was discovered between mice and patients, with a suggestion of non-linear kinetics being noted at higher doses in humans. It is likely that these differences in drug handling account for the unexpected and serious toxicity encountered in this trial.     

Toward a safer label

Pharmacy literature has reminded hospital pharmacists that our computer generated intravenous and medication labels often fall short in the area of legibility and usability. A new computer system and Zebra Stripe S-500 printers (Zebra Technologies Corporation, Vernon Hills, IL) allowed Methodist Medical Center to reexamine our labels and to join with nursing to develop a safer, more user friendly set of labels. These new labels have been well received by our nursing staff.     

Prospective memory: a neuropsychological study

To examine the neuropsychology of prospective remembering, older adults were divided preexperimentally into 4 groups on the basis of their scores on 2 composite measures: one assessing frontal lobe function and the other assessing medial temporal lobe function. The groups reflected the factorial combination of high and low functioning for each neuropsychological system, and they were tested on an event-based laboratory prospective memory task. High-functioning frontal participants showed better prospective remembering than low-functioning frontal participants. There was no significant difference in prospective memory performance attributable to medial temporal functioning. The results support the theoretical notion that frontal lobe processes play a key role in prospective remembering. Discussion focuses on the particular components of prospective memory performance that frontal lobes might mediate.     

Prospective study of microchimerism in transplant recipients

BACKGROUND: We evaluated peripheral blood microchimerism in 48 consecutive organ transplant recipients (35 kidneys, ten livers, one kidney-liver, one kidney-pancreatic islet, one kidney pancreas) up to 12 months post-transplantation. Patients were categorized according to the presence or absence of rejection episodes, and the patterns of microchimerism in the two groups were then compared. METHODS: DNA was extracted from donor, pre-transplant, and post-transplant peripheral blood samples. Several polymerase chain reaction (PCR)-based assays were developed for the detection of microchimerism. Assay sensitivities ranged from 0.0001 to 3%. RESULTS: Microchimerism was detected only in sex-mismatched cases (male donors and female recipients) using nested PCR for a Y-chromosome marker. There were ten such cases (six kidneys, two livers, and two combined organ transplants). In patients without rejection (n = 7), there was a peak of donor-DNA at 1-3 wk post-transplantation followed by a second peak between 3 wk and 4 months. In patients with biopsy-proven rejection (n = 3), the peaks were absent and the levels of microchimerism were extremely low (< 0.001%). Microchimerism levels declined in all 10 patients and were barely detectable 1 yr post-transplantation. Microchimerism was not detected in the remaining 38 patients despite using a battery of sensitive PCR-based assays. CONCLUSIONS: In our study, microchimerism was detected using the Y-chromosome PCR assay only and the level of donor-DNA in a given patient varied over time. This study highlights the difficulties in establishing a correlation between microchimerism and transplant tolerance.     

Double-blind comparison of fluoxetine and desipramine in the treatment of depressed women with advanced HIV disease: a pilot study

A double-blind, placebo-controlled study was conducted to assess the relative efficacy and tolerability of fluoxetine and desipramine in depressed, human immunodeficiency virus (HIV)-positive women. Although difficulty in the recruitment and retention of participants led to insufficient power to detect differences between treatment groups, results indicated that participants experienced improvement in their depression. However, for most women, significant depressive symptoms remained after 6 weeks of treatment. In addition, although most participants reported at least one adverse event after treatment began, most of the side effects, regardless of treatment condition, were mild to moderate in severity. Important barriers to study participation and completion are discussed, as well as suggestions for increasing the involvement of depressed, HIV-positive women in future treatment studies.     

Endoscopic evaluation of 125 cases of upper gastrointestinal bleeding.

The fiberoptic panendoscope has been shown to be superior to the UGI series in diagnosing the site(s) of upper gastrointestinal bleeding (UGIB). Recent data has shown that gastritis has replaced peptic ulcer disease (PUD) as the leading cause of UGIB since the diagnosis can now be made with the endoscope. Our clinical experience differs from this. One hundred twenty five cases of UGIB from December 1975 to December 1978 were reviewed. The patients ranged in age from 11 to 91 years. There were 83 males and 42 females included in the study. Twenty-four per cent of the patients were actively bleeding at the time of endoscopic examination, and 62% received two or more units of blood. Endoscopic examination was technically successful in all patients, and there were no deaths or complications. One hundred twenty three lesions were found in 117 patients for a diagnostic accuracy of 93.9%. In eight patients, no bleeding site was found, resulting in a failure rate of 6.1%. PUD accounted for 74.9% of the bleeding sites, while gastritis accounted for only 0.8%. Mallory-Weiss tears of the esophagus accounted for 9.8% and esophageal varices for 4.9%. Thirty-five per cent of the patients had associated lesions, with gastritis and esophagitis being the most common. Eighteen patients (14.4%) required surgical intervention. Seventeen patients had PUD. There was one death, for a mortality rate of 5.5%. The medical mortality rate was 0.9%. The benefits of endoscopy in UGIB are still controversial. An important subgroup of patients with the "visible vessel" in the ulcer bed has been identified recently by others. If not bleeding at the time of endoscopy, 70% will rebleed. It is our opinion that it is important to identify this patient, as well as to know if one is treating gastritis, PUD, or varices. Finally, electrocoagulation of bleeding points, as well as the development of the laser and application of adhesives or clotting agents through the endoscope, will change the management of UGIB.     

Effects of hydration and dehydration on body composition analysis: a comparative study of bioelectric impedance analysis and hydrodensitometry.

Since 1983, bioelectric impedance has been researched with respect to its validity and reliability in the determination of body composition. It continues to be compared to hydrostatic weighing, the anthropometric "gold standard". This study was designed to investigate the relationship between bioelectric impedance analysis (BIA) and hydrodensitometry (HW) under three conditions: control, hydration and dehydration. Caucasian males (aged 18-44 years) served as subjects (n = 10). Body composition was determined by BIA and HW before intervention, 30 minutes post-hydration, and following a combination of exercise and sitting in a steam room to decrease body weight by two to four percent (mean = 2.81%). Statistical treatment by two-way analysis of variance for repeated measures revealed that although there were no significant differences between the two techniques of body composition determination under any of the three conditions, there was a statistically significant decrease in percent body fat determined in the dehydrated state as compared to the control and hydrated conditions. Recommendations include the determination of hydration state prior to engaging in body composition analysis by either method.