Acetylcholine stimulates release of endothelium-derived relaxing factor in coronary arteries of human organ donors.

OBJECTIVE: To determine whether cholinergic stimulation of human coronary endothelial cells induces the release of endothelium-derived relaxing factor (EDRF), denuded human coronary artery rings or denuded rabbit aorta rings were either directly perfused or superfused by the effluent of intact or denuded human coronary artery segments in a perfusion bioassay system. DESIGN: Coronary vessels were dissected from hearts of organ donors and prepared for use as donor segments and detector rings in the perfusion bioassay system. Segments were continuously perfused by an oxygenated Krebs-Ringer solution. Rings were suspended between two stirrups, one of which was connected to an isometric force transducer. They were either directly perfused (no tissue had been previously perfused by the same Krebs-Ringer) or superfused by the effluent of an endothelium-intact or -denuded coronary segment. Human rings were contracted with prostaglandin F2 alpha (2 x 10(-6) M) and rabbit rings were contracted with phenylephrine (10(-6) M). RESULTS: Tension in detector tissue did not change during superfusion with effluent from endothelium-denuded or -intact human coronary artery segments, showing that there was no basal release of EDRF/nitric oxide (NO) in this preparation. Acetylcholine (ACh) (10(-6) or 10(-5) M) added to the perfusate increased the tension of the precontracted endothelium-denuded human rings directly perfused (50 +/- 32%) but not of the precontracted rabbit rings, showing that ACh is a potent agonist of human coronary vascular smooth muscle. ACh added to the coronary segment in the endothelium-intact superfusion mode had no effect in 33% or induced a small relaxation (8.8 +/- 1.6%) in 66% of the preparations. Hemoglobin (10(-5) M), a scavenger of EDRF/NO, caused a further increase in tension (32 +/- 15%). Adding calcium ionophore (A 23187;10(-5) M), which stimulates EDRF/NO release through a nonreceptor-mediated mechanism, to the coronary artery segment induced a relaxation in the endothelium-perfused detector rings which did not relax to ACh (30 +/- 2%); this relaxation was reversed by methylene blue (10(-5) M), a blocker of soluble guanylate cyclase. NO endothelin, a potent vasoconstrictor released by the endothelial cells, was detected in the effluent of intact coronary vessels. CONCLUSION: The results suggest that in two-thirds of the six preparations studied, cholinergic stimulation can release EDRF from human donor coronary artery endothelial cells.

Halothane 1.5 MAC, isoflurane 1.5 MAC, and the contractile responses of coronary arteries obtained from human hearts.

Active vasoconstriction of epicardial coronary arteries can cause myocardial ischemia in patients with coronary artery disease. Relief of vasoconstriction can improve blood flow to the heart. The purpose of this study was to determine if 1.5 MAC halothane and 1.5 MAC isoflurane would each attenuate contractions evoked by three putative mediators of coronary constriction in coronary arteries removed from the hearts of human beings. Hearts were obtained in the operating room from five patients undergoing cardiac transplantation and from six brain-dead patients undergoing organ donation procedures. Coronary arteries were dissected free, cut into rings, and studied in organ chambers. Endothelium-dependent relaxations to 10(-6) M bradykinin were examined; they indicated a variable degree of endothelial dysfunction in vessels used in the experiments. Contractile responses to 40 mM KCl were tested and were used as control contractions. Contractions evoked by serotonin, histamine, and prostaglandin F2 alpha were measured and were expressed as a percent of contractile responses evoked by 40 mM KCl. Halothane depressed the agonist-induced contractions. Maximal contractile responses to serotonin were 130% +/- 28% in untreated rings and 63% +/- 10% in rings exposed to halothane (P less than 0.03). Responses to histamine were 183% +/- 46% untreated and 121% +/- 26% during halothane administration (P less than 0.05), and responses to prostaglandin F2 alpha were 227% +/- 42% untreated and 148% +/- 18% with halothane (P less than 0.05). Isoflurane had no effect on contractions. The results demonstrate that 1.5 MAC halothane, but not 1.5 MAC isoflurane, attenuates contractile responses evoked by putative mediators of coronary vasoconstriction in coronary arteries removed from the hearts of human beings.

Direct delivery of medication into a brain tumor through multiple chronically implanted catheters.

A recurrent malignant glioma was treated with cisplatin delivered directly into the tumor. The drug was delivered via 68 small catheters distributed evenly throughout the tumor area. Each catheter was connected to an osmotic minipump that delivered 0.5 microliter of drug solution each hour for 10 days. There were no side effects from the catheter implantation, chemotherapy, or catheter removal. Although the chemotherapy halted progression of the tumor, it recurred, and the patient died 6 months after treatment.

Stereotactic administration of intratumoral chronic chemotherapy of recurrent malignant gliomas.

There is a continuous search for more efficient treatment of malignant cerebral gliomas. The work of Penn and Croin demonstrates clearly that survival of rats having experimental gliomas is significantly increased by intratumoral chemotherapy. It has been shown that chronic depth electrodes for the investigation of epileptic patients is a reliable and safe method. Using this proven technology originally developed by Talairach, Szikla and co-workers we have developed catheters for intratumoral chemotherapy. Three patients have been treated. It is premature to pretend that this is a treatment which will lengthen the patient's life. Nevertheless, the feasibility of the technique, its precision and safety are assured. Following this course of treatment, we have seen no deteriorations, no side effects, no bone marrow depressions, and no sign of toxicity. Chemical analysis has shown that cisplatin was delivered to the tumor.

Extracranial and intracranial meningiomas.

Meningiomas constitute about 18% of primary intracranial tumors, and they are rarely observed in patients under 30 years of age. In this study, we present the case of a 17-year-old patient who was first seen for a right cervical mass. Further investigation revealed that a meningioma of the posterior cranial fossa had invaded the temporal bone, the infratemporal fossa and the right parapharyngeal region and was at the origin of that cervical mass. This intra- and extracranial meningioma was completely resected in two stages with very satisfactory results. We have reviewed the literature pertaining to the extracranial extensions of meningiomas originating in the posterior fossa.

Lobulated fibers in neuromuscular diseases.

Lobulated fibers have been observed in biopsies of 13 patients with various neuromuscular disorders including limb-girdle muscular dystrophy (3), distal myopathy (2), scapuloperoneal muscular dystrophy (2), congenital myopathy, Kugelberg-Welander syndrome, hypothyroidism, steroid myopathy, osteomalacia and systemic lupus erythematosus (on steroids). In all cases there were fibers characterised by small subsarcolemmal triangular aggregates or more diffuse collections extending into the interior of the muscle fiber. These were strongly reactive with oxidative enzymes, acid phosphatase, periodic acid-Schiff (PAS), Verhoeff-van Gieson (VVG) and also stained red with the Gomori trichrome technique. In 5 cases core-like fibers were also seen. Morphometric analysis of the NADH-tetrazolium reductase (NADH-TR) preparations in 11 cases showed atrophy of the lobulated fibers. Ultrastructural studies of lobulated fibers disclosed large peripheral mitochondrial aggregates and focal areas with Z-line streaming and disrupted myofibrils. We consider this structural change of the muscle fiber as a reflection of muscle cell disruption and suggest that they may progress from lobulated fibers to more atrophic core-like fibers.

Rhabdomyosarcoma of the ovary: ultrastructural study of a case and review of literature.

Pure rhabdomyosarcomas are extremely rare and lethal primary neoplasms of the ovary. The available literature revealed 14 such cases. This report describes the light and electron microscopic findings of another case. At the electron microscopic level, rhabdomyogenesis recapitulates skeletal muscle differentiation during early fetal life. Rhabdomyoblasts in the ovary may arise from either the uncommitted stromal fibroblasts or from fibroblasts of endometriotic stroma. The age of patients at diagnosis ranged between 13 months and 86 years with 60% of women aged 40 years and older. About 50% of the cases were diagnosed with disease beyond the ovary, and survival ranged between 18 days and 15 months after diagnosis. Aggressive combination therapy including surgery, radiation, and chemotherapy appears to be the only hope for improved survival.

Ovarian Sertoli-Leydig cell tumor with rhabdomyosarcoma: an ultrastructural study.

The clinical and light and electron microscopic findings of a moderately differentiated, virilizing, Sertoli-Leydig cell tumor (SLT) with pleomorphic rhabdomyosarcoma of the ovary are presented. The tumor recapitulates the primitive embryonal testis and rhabdomyogenesis, respectively. The natural history, including pathogenesis, of this peculiar and rare tumor is discussed in the light of the pertinent literature on SLT and ovarian rhabdomyosarcoma. It seems that when rhabdomyosarcoma is a significant or predominant component of SLT, as occurred in this case, the prognosis is poor and is that of rhabdomyosarcoma in general.