The effect of palytoxin on neuromuscular junctions in the anococcygeus muscle of the rat

Palytoxin, a highly toxic natural product isolated from zoanthids of the genus Palythoa, is accumulated by a wide range of fishes and marine invertebrates used as food in the Indo-Pacific. It is responsible for many incidents of human morbidity and mortality. The toxin is a potent smooth muscle spasmogen. The cause of the contraction of smooth muscle is unclear, but recent work strongly suggests that it is primarily initiated by the release of neurotransmitters from the motor innervation of the smooth muscle. We show here that palytoxin caused the swelling of the muscle cells and some internal organelles of the anococcygeus muscle of the rat, but no substantial structural damage to the tissue. Axons and Schwann cells were also swollen but the most dramatic feature was the depletion of synaptic vesicles from putative release sites in the axons. Some axons were physically damaged following exposure to the toxin, but this was relatively uncommon (<10% of all axons studied). In the majority of axons there was no damage to nerve terminal membranes, but there was damage to mitochondria. The depletion of vesicles involved all types – clear, dense-cored, large and small. Our observations and pharmacological data gathered elsewhere, provide a neuropathological basis for the spasmogenic activity of palytoxin.     

The 1989 report of the North American Pediatric Renal Transplant Cooperative Study

This report of the North American Pediatric Transplant Cooperative Study summarizes data contributed by 57 participating centers on 754 children with 761 transplants from 1 January 1989 to 16 February 1989. Data collection was initiated in October 1987 and follow-up of all patients is ongoing. Transplant frequency increased with age; 24% of the patients were less than 5 years, with 7% being under 2 years. Common frequent diagnoses were: aplastic/dysplastic kidneys (18%), obstructive uropathy (16%), and focal segmental glomerulosclerosis (12%). Preemptive transplant, i.e., transplantation without prior maintenance dialysis, was performed in 21% of the patients. Dialytic modalities pretransplant were peritoneal dialysis in 42% and hemodialysis in 25%. Bilateral nephrectomy was reported in 29%. Live-donor sources accounted for 42% of the transplants. Among cadaveric donors, 41% of the donors were under 11 years old. During the first post-transplant month, maintenance therapy was used similarly for live-donor and cadaver source transplants, with prednisone, cyclosporine, and azathioprine used in 93%, 83%, and 81%, respectively. Triple therapy with prednisone, cyclosporine, and azathioprine was used in 78%, 75%, and 75% of functioning cadaver source transplants at 6 months, 12 months, and 18 months as opposed to 60%, 63%, and 54% for live-donor procedures, with single-drug therapy being uncommon. Rehospitalization during months 1–5 occurred in 62% of the patients, with treatment of rejection and infection being the main causes. Additionally, 9% were hospitalized for hypertension. During months 6–12 and 12–17, 30% and 28% of the patients with functioning grafts were rehospitalized. Times to first rejection differed significantly for cadaver and live-donor transplants. The median time to the first rejection was 36 days for cadaver transplants and 156 days for live-donor transplants. Overall, 57% of treated rejections were completely reversible although the complete reversal rate decreased to 37% for four or more rejections. One hundred and fifty-two graft failures had occurred at the time of writing, with a 1-year graft survival estimate of 0.88 for live-donor and 0.71 for cadaver source transplants. In addition to donor source, recipient age is a significant prognostic factor for graft survival. Among cadaver donors, decreasing donor age is associated with a decreasing probability of graft survival. Thirty-five deaths have occurred; 16 attributed to infection and 19 to other causes. The current 1-year survival estimate is 0.94. There have been 9 malignancies.A list of all participating centers and the names of the investigators is printed on pages 552–553     

Administration of Half-Dose Theophylline Together with Ketotifen to Asthmatic Children—A Double-Blind, Placebo-Controlled Study

Administration of theophylline to asthmatic children is frequently associated with an adverse influence on their behavior. The efficacy and behavioral effects of the administration of high-dose theophylline (T) and ketotifen (K) in various combinations were evaluated prospectively in a double-blind, placebo controlled study in 55 children with moderately severe perennial asthma. During a baseline period of 2 weeks, theophylline (serum level of 10-20 μg/ml) was administered to all the children. After this period the patients were randomly allocated into four comparable groups. The children were treated during a 12-week period with: T + K-Placebo (T group); T + K (T + K group); half-dose T + K (T/ 2 + K group); or placebo of both T and K (P group). During the 12-week treatment period, as compared to the baseline period, only the three groups of children who received active therapy (T + P, T + K, T/2 + K) showed a similar reduction in the number of days with asthmatic symptomatology, improvement of the total asthmatic symptoms score, and increased PEFR. The behavioral activity of the children (assessed by the Conner's rating scale) improved significantly only in the groups receiving placebo or T/2 + K. The results of this study suggest that a combination therapy of half the recommended therapeutic dose of theophylline with ketotifen can be clinically as effective as therapy with a full dose of theophylline, but with significantly less adverse behavioral effects.     

Immunological blockade of endogenous thyrotropin-releasing hormone impairs recovery from hyperglycemia in mice

Administration of antiserum to thyrotropin-releasing hormone (TRH) into the lateral cerebral ventricle of mice significantly attenuated recovery from hyperglycemia induced by treatment with 2-deoxyglucose but had no effect on the plasma glucose of saline-treated mice. TRH, injected centrally together with the anti-TRH antibody, reversed the effect of the antiserum and blocked the development of hyperglycemia. These findings suggest that activation of TRH neurons in the central nervous system may be a physiological event influencing recovery from hyperglycemia.     

Unsupervised fuzzy clustering analysis supports behavioral cutoff criteria in an animal model of posttraumatic stress disorder.

BACKGROUND: Unsupervised fuzzy clustering (UFC) analysis is a mathematical technique that groups together objects in the multidimensional feature space according to a specified similarity measurement, thereby yielding clusters of similar data points that can be represented by a set of prototypes or centroids. METHODS: Since clinical studies of mental disorders distinguish between affected and unaffected individuals, we designed an inclusion/exclusion criteria (cutoff behavioral criteria [CBC]) approach for animal behavioral studies. The effect of classifying the study population into clearly affected versus clearly unaffected individuals according to behaviors on two behavioral paradigms was statistically significant. RESULTS: Here the raw data from previous studies were subjected to UFC algorithms as a means of objectively testing the validity of the concept of the CBC for our experimental model. The first UFC algorithm yielded two clearly discrete clusters, found to consist almost exclusively of the exposed animals in the one and unexposed animals in the other. The second algorithm yielded three clusters corresponding to animals designated as clearly affected, partially affected, and clearly unaffected. The algorithm for physiological data in addition to behavioral data failed to elicit discrete clusters. CONCLUSIONS: The UFC analysis yielded data that support the conceptual contention of the CBC and lends additional validity to our previous behavioral studies.     

Inflammatory pseudotumor of the lung — fibrous histiocytoma type

A 7 1/2-year-old girl with an inflammatory pseudotumor of the lung is presented. The nature of the lesion was not recognized pre-or intraoperatively. The lesion was rubbery, yellowish, and well-defined but not encapsulated. Histologically, a spindle-cell lesion with a storiform pattern and chronic inflammatory-cell infiltrate was seen. The immunological and ultrastructural studies supported an inflammatory origin. The lesion corresponds to the fibrous histiocytoma variant of inflammatory pseudotumor of the lung, as defined recently by Matsubara et al. [17]. This must be distinguished from rare benign neoplasms of the lung such as benign fibrous histiocytoma, leiomyoma, Schwannoma, and histiocytosis.     

Histomorphometric analysis of innervation of the anterior cruciate ligament in osteoarthritis

The aim of this study was to determine whether there are quantitative changes in the innervation of the anterior cruciate ligament in osteoarthritis. Eleven whole anterior cruciate ligaments were obtained at autopsy from cadavera of individuals with advanced osteoarthritis; five healthy ligaments were used as controls. The ligaments were transected and stained with hematoxylin and eosin, oil red O for fat, and a modification of Gairn's gold chloride method. The latter stain permits visualization of axons, mechanoreceptors, and free nerve endings that are not apparent on routine stains. The ratio of nerve tissue to periligamentous synovial tissue was determined histomorphometrically by the point-counting method. The nerve tissue was located almost exclusively in the periligamentous synovial tissue. There was a statistically significantly greater area of nerve tissue (as a percentage of the total area) around the anterior cruciate ligaments in the osteoarthritic group than around the ligaments in the control group (p < 0.02). The nerve tissue was distributed evenly throughout the periligamentous synovial tissue in the specimens in both groups. A neurological role has been proposed for the anterior cruciate ligament in osteoarthritis. This study provides morphological evidence for neural pathology of the anterior cruciate ligament in subjects with osteoarthritis.