Histologic, morphometric, and biochemical evolution of vein bypass grafts in a nonhuman primate model. II. Modification of early changes by platelet inhibition with aspirin and dipyridamole

The objective of this study was to determine the early influence of platelet inhibition on the histologic, morphometric, and biochemical evolution of vein bypass grafts in a nonhuman primate model. Cephalic vein grafts were interposed bilaterally in the femoral arteries of 15 stump-tailed macaque monkeys fed a diet that sustains plasma cholesterol levels of approximately 225 mg/dl. All animals received in combination aspirin, 80 mg/day, and dipyridamole, 50 mg/day. Grafts were excised from five animals for analysis on each of postoperative days 3, 7, 14, 30, 60, and 90. In animals subjected to platelet inhibition, cholesterol content in the graft was 170 +/- 52 micrograms/100 mg at 90 days, 205% of the level in ungrafted vein (p less than 0.01). This change was small in comparison with the increase to 686% of ungrafted vein observed in our study of control animals. In stepwise regression analysis, cholesterol content of grafts was best predicted by prevalence of foam cells (r2 = 0.82), and the proportion of intima as a fraction of total wall area was best predicted by the presence of macrophages (r2 = 0.69). Platelet inhibition did not decrease the extent of intimal hyperplasia. The prevalence of adherent platelets (r = -0.72) and the amount of fibrin (r = -0.78) correlated inversely with the amount of endothelium present during the first 14 days. The strength of these correlations declined with time, despite persistent lack of endothelium in some areas. Medial fibrosis occurred to the same extent as in control grafts, as did the early appearance of platelet factor VIII and fibronectin and the lack of vasa vasorum at 3 days followed by reappearance at 7 days. These data demonstrate that platelet inhibition dramatically reduces lipid uptake by grafts in the first 90 days but has less influence over histologic or morphometric changes.     

Mammaplasty on breast implants (or cutaneous expansion in treating distended skin)]

The authors present their experience of the use of skin expansion in secondary surgery to previously implanted breasts. This technique constituted a relatively simple solution with minimal scarring for certain cases in which the residual breast volume was insufficient or non-existent and in which it was impossible to reconstruct a breast with acceptable shape and volume after removal of the implant.     

Reflex myoclonus in olivopontocerebellar atrophy.

The presence of reflex myoclonus in response to touching and pin-pricking the wrist or stretching the fingers and to photic stimulation was assessed in 24 patients with a presumed diagnosis of olivopontocerebellar atrophy (OPCA) and in 30 age matched control subjects. Reflex myoclonus to soma-esthetic stimulation was found in 23 patients and in none of the controls. Photic myoclonus was present in 12 patients and in none of the controls. Electrophysiological study of the reflex myoclonus showed enhanced (> 10 microV) somatosensory evoked potentials and an associated reflex electromyographic discharge (C-wave) in 15 patients. These findings indicate that reflex myoclonus is common in OPCA and probably of cortical origin.     

A phase I clinical and pharmacokinetic study of the topoisomerase I inhibitor topotecan (SK&F 104864) given as an intravenous bolus every 21 days.

Topotecan (SK&F 104864) is a novel antitumor agent whose mechanism of action is inhibition of the DNA unwinding protein topoisomerase I. An analog of camptothecin, topotecan was designed to be more water soluble in an effort to decrease the severe and sporadic toxicities experienced during phase I/II trials of the parent compound. In this phase I clinical and pharmacological trial, topotecan was given as a bolus intravenous (i.v.) infusion over 30 min every 21 days. A total of 42 patients entered the study, receiving doses ranging from 2.5 to 22.5 mg/m2. The maximum tolerated dose (MTD) of topotecan given in this schedule was 22.5 mg/m2. Myelosuppression, primarily neutropenia, was dose-limiting. The extent of prior therapy did not predict for more severe neutropenia. Non-hematologic toxicities were mild and included low-grade to moderate fever, nausea, vomiting, alopecia, diarrhea and skin rashes. There were no objective partial or complete responses, although there was a suggestion of antitumor activity in three patients. Topotecan undergoes pH-dependent hydrolysis of the lactone ring; only the closed, lactone form is active. The lactone form predominated during infusion, with hydrolysis occurring rapidly following the end of infusion. There were linear relationships between dose administered and peak plasma lactone concentrations as well as AUC lactone to AUC total. The lactone was rapidly cleared from plasma with a total body clearance of 25.7 (+/- 6.7) l/h/m2. The plasma lactone concentration declined rapidly with a harmonic mean terminal half-life of 3.4 (+/- 1.1)h. Lactone hydrolysis and renal excretion were the major routes of elimination.(ABSTRACT TRUNCATED AT 250 WORDS)     

Refractory potassium repletion due to cisplatin-induced magnesium depletion

Cisplatin is a common cause of hypomagnesemia and hypokalemia due to renal magnesium (Mg) and potassium (K) losses. Magnesium plays an important role in the maintenance of intracellular K. An unrecognized and untreated Mg depletion can lead to a refractory K repletion. We describe two patients with hypomagnesemia-associated refractory hypokalemia following cisplatin following cisplatin therapy. Potassium supplementation failed to replace the K deficit. Profound hypokalemia persisted until hypomagnesemia was recognized and corrected. In neither patient was the concurrent hypomagnesemia recognized until the 11th and 9th hospital days. These two cases demonstrated the association of a refractory K repletion and an Mg deficiency. Thus, both serum K ion and Mg levels should routinely be assessed in patients who require cisplatin therapy.     

Pilomatrix carcinoma. A new case

We present a new case of Pilomatrix Carcinoma after having review the 22 cases previously published. The tumor arisen in a 74 years old male, in the left preauricular region. The lesion was excised with wide margins. A year after there is not any evidence of recurrence or metastases.     

Involvement of pp60c-src with two major signaling pathways in human breast cancer.

The phosphotyrosine residues of receptor tyrosine kinases serve as unique binding sites for proteins involved in intracellular signaling, which contain SRC homology 2 (SH2) domains. Since overexpression or activation of the pp60c-src kinase has been reported in a number of human tumors, including primary human breast carcinomas, we examined the interactions of the SH2 and SH3 domains of human SRC with target proteins in human carcinoma cell lines. Glutathione S-transferase fusion proteins containing either the SH2, SH3, or the entire SH3/SH2 region of human SRC were used to affinity purify tyrosine-phosphorylated proteins from human breast carcinoma cell lines. We show here that in human breast carcinoma cell lines, the SRC SH2 domain binds to activated epidermal growth factor receptor (EGFR) and p185HER2/neu. SRC SH2 binding to EGFR was also observed in a nontumorigenic cell line after hormone stimulation. Endogenous pp60c-src was found to tightly associate with tyrosine-phosphorylated EGFR. Association of the SRC SH2 with the EGFR was blocked by tyrosyl phosphopeptides containing the sequences surrounding tyrosine-530, the regulatory site in the SRC C terminus, or sequences surrounding the major sites of autophosphorylation in the EGFR. These results raise the possibility that association of pp60c-src with these receptor tyrosine kinases is an integral part of the signaling events mediated by these receptors and may contribute to malignant transformation.     

Cluster of iniencephaly in Miami

This report details a cluster of 5 cases of iniencephaly with anencephaly and rachischisis occurring over a 4-month period at Jackson Memorial Hospital/University of Miami Medical Center in Miami, Florida. All 5 cases of this rare, lethal, congenital malformation seen in the cluster included diaphragmatic defects with accompanying hernia, omphalocele, small adrenals, renal dysmaturity, gastrointestinal malformations, cleft lip and palate, and hypoplastic lungs. No single causative agent for this cluster was identified. A brief review of the literature regarding categorization of these malformations and as a discussion of the embryological basis for these lesions and possible etiologic factors are included.