Cyclosporin-A nephrotoxicity and acute cellular rejection in renal transplant recipients: correlation between radionuclide and histologic findings

Serial radionuclide studies using both Tc-99m DTPA (perfusion) and I-131 hippuran (tubular function) were correlated with histologic findings in 25 patients with renal transplants. These cases included 15 cases of cyclosporin-A nephrotoxicity (CsA-NT) and ten cases of acute cellular rejection that were retrospectively selected on the basis of biopsy findings and favorable clinical response to therapy specific for each of these conditions. The serial radionuclide studies enabled the correct diagnosis in 12 of 15 cases of CsA-NT and eight of ten cases of acute rejection. Posttherapy radionuclide studies, furthermore, demonstrated improvement consistent with clinical response. In all cases, the radionuclide results were available at least 24 hours before biopsy findings. These results indicate that serial radionuclide studies evaluating interval changes in both perfusion and tubular function are of significant value in the diagnosis and follow-up of CsA-NT and acute cellular rejection in transplant recipients. This initial experience suggests a sensitivity of 80%.     

Opiate control of spontaneous locomotor activity in a urodele amphibian

An intraperitoneal injection of the preferential opiate receptor agonist (+/-) bremazocine HCl given to male rough-skinned newts acutely and dose-dependently reduced their spontaneous locomotor activity. Inversely, and contrary to the situation generally observed in other vertebrates, administration of the opiate receptor antagonist naloxone HCl dose-dependently and acutely stimulated locomotion. Given at a behaviorally active dosage, naloxone counteracted the inhibitory effect of bremazocine on locomotion. The behavioral influence of the two substances was observed using two different sampling techniques (continuous recording for 3 minutes: repeated instantaneous sampling for 60 minutes). These data are discussed in view of our current knowledge on the opiate regulation of locomotor activity in vertebrates.     

Cleft lip and palate, sensorineural deafness, and sacral lipoma in two brothers: a possible example of the disorganisation mutant.

We report two brothers of Chinese origin who have an apparently unique syndrome of cleft lip/palate, profound sensorineural deafness, and a sacral lipoma. Additional findings which were not common to both were aberrant digital appendages on the heel and thigh of one boy and an anterior sacral meningocele and dislocated hip in the other. Intelligence is normal in both. Both boys suffer from functional constipation but biopsy studies showed no evidence of Hirschsprung's disease. The parents, who are normal, are not related. Inheritance is probably autosomal or X linked recessive. A possible link with the disorganisation mouse mutant is discussed.     

Homozygosity of the short arm of chromosome 17 in cervical carcinoma.

We have determined the frequency of heterozygosity of the short arm of chromosome 17 in 20 cervical tumours using the highly polymorphic probe pYNZ22. Only 25% of the tumours were heterozygous at this locus. This is significantly lower than the level of 86% heterozygosity for this locus in the general population indicating that loss of one allele occurs in cervical cancer. Heterozygosity for a locus on the long arm of the same chromosome showed no significant difference between the tumours and the general population indicating that genetic loss was confined to the short arm of the chromosome. The analysis of premalignant lesions showed 70% of patients were heterozygous suggesting that loss of material from the short arm of chromosome 17 took place at a late stage in tumour development. This report confirms predictions made from previous karyotypic analysis and is the first indication of allele loss on the short arm of chromosome 17 in cervical cancer.     

Create culture of integrity to defeat research fraud, funding agencies say.

Widely reported cases of research fraud have eroded public confidence in scientific research. When funding agencies met last fall they underscored the importance of integrity in the research process and discussed steps that could be taken to promote it.     

Anti-endotoxin therapy in primate bacteremia with HA-1A and BPI.

OBJECTIVE: The in vivo neutralizing activities of an anti-lipopolysaccharide (LPS) antibody HA-1A (Centoxin [Centocor, Malvern, PA]), a human immunoglobulin M monoclonal antibody, and of bactericidal/permeability-increasing protein (BPI), an endogenously produced human LPS-neutralizing protein, were studied in a primate model of lethal Escherichia coli bacteremia. SUMMARY BACKGROUND DATA: HA-1A has been used with variable success against LPS activity in some animal models and in a recently reported clinical trial. However, no data assessing the efficacy of this agent in subhuman primates is available. Bactericidal/permeability-increasing protein is a product of polymorphomononuclear cells (PMNs) that is stored in azurophilic granules and exhibits LPS-neutralizing activity in vitro and in some in vivo models. METHODS: Immediately after E. coli infusion and in a blinded fashion, three baboons were treated with BPI (5 mg/kg bolus infusion and 95 micrograms/kg/min infusion over 4 hr). Three animals received 3 mg/kg BW of HA-1A, whereas another three baboons received a placebo treatment. RESULTS: The BPI-treated animals demonstrated significantly (p < 0.03) lower circulating LPS-limulus amoebocyte lysate (LAL) activity compared with the control animals, but this reduction in LPS-LAL activity was not associated with improved survival. HA-1A treatment did not reduce LPS-LAL activity. However, both BPI and HA-1A treatment did attenuate the pro-inflammatory cytokine response. CONCLUSION: The current data suggests that incomplete neutralization of endotoxin activity does not alter mortality from severe bacteremia. Given the diversity of mediator production under such circumstances, a strategy of combination therapy in the form of anti-lipopolysaccharide and anticytokine treatment may be necessary to achieve optimal survival.     

Is incidental appendectomy a safe practice?

In an attempt to determine the safety of appendectomy performed as an incidental procedure, the authors reviewed 853 operations (458 hysterectomies and 395 cholecystectomies) performed by five surgeons at one hospital between 1981 and 1984 and compared the results in 35% of the patients who underwent incidental appendectomy with those in the remainder. Factors studied were operative time, postoperative stay, postoperative fever and leukocytosis, the need for intravenous fluids, parenteral analgesia and antibiotics, and infectious complications. Most of these variables differed between individual surgeons, but the addition of incidental appendectomy did not significantly alter any variable for an individual surgeon or for the group as a whole. Incidental appendectomy seems to be a safe practice and one that does not alter the outcome of hysterectomy or cholecystectomy but does protect against subsequent appendicitis.     

Learning and retention of movement sequences in Parkinson's disease.

The purpose of this study was to examine motor learning and retention given extensive practice in two fundamentally different movement sequences. One sequence was a memory-driven task (performing a series of whole body positions from memory) and the other a context-driven task (buttoning). Practice took place over 3 weeks, with performance measured weekly; retention was measured weekly for 3 weeks after practice. There were 7 people with Parkinson's disease (PD) and 7 age-matched neurologically healthy people who participated in this study. Both groups improved performance on both tasks with practice, with the majority of the change for the PD group occurring between 1 and 2 weeks of practice. Although those with PD did not necessarily perform as well as age-matched controls, they learned both sequences in a manner similar to age-matched controls, and exhibited retention across the 3-week retention interval. If people with PD are given sufficient practice they can learn and retain both memory-based and context-driven movement sequences as well as age-matched controls. The results provide support for maintaining physical activity and for intervention through movement therapy.