Extraocular muscle regeneration in primates. Local anesthetic-induced lesions.

Retrobulbar administration of several local anesthetics (0.75% bupivacaine, 2.0% mepivacaine or 2.0% lidocaine plus 1:100,000 epinephrine) in monkeys resulted in a low incidence of muscle fiber lesions in the extraocular muscles closest to the site of injection. Most lesions resulted in the degeneration and regeneration of muscle fibers on the surface of the muscles, but occasionally a massive internal lesion was seen. In contrast, large lesions were common in rectus muscles that received direct injections of local anesthetics in both monkeys and humans. The morphology and temporal sequence of muscle fiber degeneration and regeneration was similar to that seen in primate thumb muscles injured by anesthetic agents.

Thyrotropin-releasing hormone: medullary site of action to induce gastric ulcers and stimulate acid secretion.

This study evaluated the hypothesis that the dorsal motor nucleus (DMN) of the brainstem may mediate the ulcerogenic and acid-stimulatory effects of thyrotropin-releasing hormone (TRH) in rats. To accomplish this, intra-DMN microinjections of TRH (50 and 500 ng) were performed and their effects on acid secretion and gastric ulcer formation evaluated in the pylorus-ligation model. The high (500 ng), but not the low dose of TRH (50 ng) produced gastric glandular lesions in 64% of the rats with a mean severity index (no. of ulcers/rat) of 6.4 +/- 0.98 and significantly increased gastric acid output. The ulcerogenic and gastric secretory response to intra-DMN TRH was site-specific. We conclude that presynaptic TRH fibers may modulate vagal activity at the level of the DMN and propose that descending TRH pathways may play a role in experimental ulcerogenesis through acid hypersecretion.

Brain vasoactive intestinal peptide: a potent stimulant of gastric acid secretion.

Vasoactive intestinal peptide (VIP) belongs to a rapidly expanding family of cerebrogastrointestinal oligopeptides. This report describes a potent dose-, time- and vagus-dependent stimulation of gastric acid secretion by brain VIP. Physiologic evidence favoring a role of VIP on acid secretion was provided by the finding that immunoneutralization of endogenous brain VIP produced a significant decrease of acid secretion. These and other data contained herein suggest that the mechanism by which central VIP stimulates acid secretion appears to involve peripheral cholinergic pathways.

A temporary distal arteriovenous fistula improves venous hemodynamics in a model of venous occlusion.

The formation of a temporary distal arteriovenous fistula (dAVF) has been used clinically to palliate patients with symptomatic venous hypertension. This study tested the efficacy of a temporary dAVF for the treatment of venous hypertension in an experimental model. Twenty-four New Zealand white rabbits were divided into two experimental groups. Group I rabbits (n = 12) underwent standardized ligation of the iliac and femoral venous systems. Group II rabbits (n = 12) underwent standardized ligation of the iliac and femoral venous systems with the formation of a temporary dAVF. Venous obstruction was documented with venography, and venous hypertension was documented with femoral venous pressure measurements. Venous pressure, resistance, blood flow, vein circumference, vein cross-sectional area, vein wall thickness, and venography were compared between four rabbits from each group at 2, 4, and 8 weeks. The effect of differences in baseline venous pressures was eliminated by subtracting the venous pressure in the unobstructed rabbit limb from the pressure in the obstructed rabbit leg. Group II rabbits had a lower standardized venous pressure (4.4 +/- 2.2 versus 9.5 +/- 4.2 mm Hg, p less than 0.01) and venous outflow resistance (0.16 +/- 0.08 versus 0.36 +/- 0.18, p less than 0.05) than did group I rabbits. Group II rabbits also had a larger superficial femoral vein circumference (3.46 +/- 0.67 versus 2.57 +/- 0.08 mm, p less than 0.05) and cross-sectional area (0.66 +/- 0.31 versus 0.31 +/- 0.09 mm2, p less than 0.01) than did group I rabbits. The improvement persisted throughout the 6-week study, which suggested an improved venous outflow.

Leukocyte depletion enhances cultured endothelial retention on vascular prostheses.

Approximately 90% of endothelial cells that are seeded or cultured onto vascular prostheses are lost from the flow surface within 24 hours of implantation. To determine the contribution of leukocytes to endothelial cell loss, 111In-labeled, cultured canine jugular venous endothelial cells were grown to confluence on fibronectin-coated polyester elastomer tubes measuring 4 mm inner diameter and 30 mm in length. Autogenous cell-lined tubes were implanted as bilateral carotid replacement grafts in six dogs made leukopenic by cyclophosphamide. Similar unilateral grafts were placed in 12 control dogs. Grafts were removed and perfusion-fixed from six control animals after 2 hours of in vivo arterial perfusion and from the other six animals after 6 hours of perfusion. One graft was removed and perfusion-fixed from each leukopenic animal after 2 hours of implantation and the other after 6 hours. Attachment of endothelial cells to the grafts was measured by indium-labeling technique. Retention of endothelium on grafts removed after 2 hours was measured by planimetric counting with scanning electron microscopy and on those removed after 6 hours by radioisotope quantification. Endothelial cell retention after 2 hours was 37.6% +/- 27.0% in control dogs and 97.0% +/- 3.4% in leukopenic animals (p less than 0.0007). After 6 hours retention was 35.9% +/- 23.2% in control animals and 86.5% +/- 6.0% in leukopenic animals (p less than 0.0009). Leukocyte surface activity was present in less than 1% of the leukopenic dogs compared with 8.5% of the other in vivo midgrafts after 2 hours. These results suggest that leukocytes play a significant role in the loss of seeded endothelium from vascular prostheses.

Inhibition of gastric acid secretion by immunoneutralization of endogenous brain thyrotropin-releasing hormone.

Previous studies have shown that intracisternal (i.c.), but not intravenous administration of thyrotropin-releasing hormone (TRH), an endogenous tripeptide (pGlu-His-Pro-NH2), produces a time-, dose-dependent and vagus-mediated stimulation of acid secretion in rats. This study was designed to test the hypothesis that endogenous brain TRH plays a role in regulation of acid secretion in the pylorus-ligation model. In confirmation of previous reports, i.c. TRH (1 microgram) significantly (P less than 0.01) stimulated gastric acid output, gastric secretory volume and decreased gastric intraluminal pH. Intracerebroventricular (i.c.v.) infusion of TRH antiserum (anti-TRH) 30 min prior to pyloric occlusion significantly reduced acid output, secretory volume and raised gastric pH. This inhibitory gastric acid secretory response to i.c.v. anti-TRH appears to be specific since i.c.v. infusion of normal rabbit serum or antisera raised against neurotensin (NT), Leu-enkephalin (L-enk), gonadotropin-releasing hormone (GnRH), somatostatin (SRIF) and alpha-melanocyte stimulating hormone (alpha-MSH) were without measurable effect. The findings of this study indicate that endogenous brain TRH, but not NT, L-enk, GnRH, SRIF or alpha-MSH plays a physiological role in regulation of acid secretion.

Risk factors for traumatic infant death in Oregon, 1973 to 1982.

A retrospective study of risk factors for traumatic infant deaths in Oregon occurring from 1973 through 1982 was performed using vital records and medical examiner records. A total of 146 such deaths occurred during this period. Relative risks were calculated for various risk factors in the study group compared with all Oregon births. Factors found to be significantly associated with all traumatic deaths were low maternal age, out-of-hospital birth, unwed mother, late or no prenatal care, low birth weight, and low maternal education. Race, sex, and birth order were not associated with traumatic infant death. The traumatic deaths were grouped into homicides and accidents. The same risk factor associations, with the exception of out-of-hospital birth, were found for each group.

Behavioral differences between neonatal and adult 6-hydroxydopamine-treated rats to dopamine agonists: relevance to neurological symptoms in clinical syndromes with reduced brain dopamine.

Administration of L-dopa or apomorphine to neonatal and adult 6-hydroxydopamine (6-OHDA)-treated rats resulted in different behavioral responses depending on the age at which dopaminergic fibers were destroyed. When neonatal 6-OHDA-treated rats were tested as adults, they exhibited marked stereotypies, self-biting and self-mutilation behavior (SMB) when given these dopamine agonists. Self-biting as well as the incidence of SMB in neonatal 6-OHDA-treated rats showed dose-related changes between 10 and 100 mg/kg of L-dopa. This SMB and self-biting after L-dopa was observed as early as 22 to 24 days of age. Adult 6-OHDA-treated rats did not exhibit SMB or self-biting to L-dopa (100 mg/kg) or apomorphine (10 mg/kg), but did display paw treading and head nodding--behaviors not observed in neonatal 6-OHDA-treated rats. In addition, the locomotor response to apomorphine (1 mg/kg) was significantly greater in adult 6-OHDA-treated rats than in neonatal 6-OHDA-treated rats. Brain dopamine was reduced markedly in striatum, nucleus accumbens and olfactory tubercles in both 6-OHDA treatment groups with the reduction being slightly greater in rats treated with 6-OHDA neonatally. Serotonin content was elevated in striatum of rats treated neonatally with 6-OHDA, but not in adult 6-OHDA-treated rats. SMB and behaviors observed after L-dopa in rats treated neonatally with 6-OHDA were not apparent after L-dopa in rats with brain serotonin or norepinephrine reduced. Rats with brain dopaminergic fibers destroyed neonatally exhibited self-biting and SMB after L-dopa, suggesting that neonatal reduction of this amine is responsible for the SMB and self-biting in neonatal 6-OHDA-treated rats. 5-Hydroxytryptophan administration to neonatal 6-OHDA-treated rats did not induce SMB, indicating that release of serotonin by L-dopa is not responsible for this behavior. Because inhibition of dopamine-beta-hydroxylase did not alter the SMB response to L-dopa observed in neonatal 6-OHDA-treated rats, norepinephrine synthesized from L-dopa does not appear to contribute to the response. High doses of a decarboxylase inhibitor sufficient to inhibit conversion of dopa to dopamine in brain did not reduce the incidence of SMB. Administration of haloperidol (1 mg/kg) reduced the incidence of SMB, but did not antagonize the self-biting or the taffy pulling exhibited by L-dopa. In contrast, cisflupentixol completely blocked the SMB and self-biting induced by L-dopa.(ABSTRACT TRUNCATED AT 400 WORDS)

Neonatal-6-hydroxydopamine treatment: model of susceptibility for self-mutilation in the Lesch-Nyhan syndrome.

Neonatal-6-OHDA treated rats given L-DOPA after a decarboxylase inhibitor showed a high incidence of self-mutilation behavior (SMB) and self-biting. These behaviors were not observed in adult-6-OHDA-treated rats or in controls. Since inhibition of dopamine-beta-hydroxylase did not prevent or inhibit the SMB exhibited in neonatal-6-OHDA-treated rats after L-DOPA, norepinephrine is not likely to be contributing to this response. The age dependent effects observed are consistent with the hypothesis that neonatal reduction of dopamine-containing fibers is responsible for the SMB susceptibility observed in Lesch-Nyhan disease, making the neonatal-6-OHDA-treated rat a model of this neurological syndrome.