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Biomedical subjects

W W Monafo

Publications and source records attributed to W W Monafo.

At least 19 recordsLinked to original sources

The effects of lumbar sympathectomy on regional spinal cord blood flow in rats during acute hemorrhagic hypotension.

It has not previously been determined whether the sympathetic nervous system has a role in the regulation of regional blood flow in the spinal cord. The authors used 14C-butanol distribution to measure regional spinal cord blood flow at seven cord levels, in the sciatic nerve, and in the biceps femoris muscle in 36 rats, 18 of which had undergone excision of both lumbar sympathetic chains at least 6 days previously. Blood flows were measured during pentobarbital anesthesia. Mean arterial blood pressure (MABP) was monitored and arterial pO2, pCO2, and pH were determined prior to flow measurement. Anesthetic dose and duration were controlled. Measurements were made in normotensive rats and in rats with MABP maintained at either 69 +/- 3 mm Hg or 48 +/- 3 mm Hg for 1 hour by the withdrawal of arterial blood. One-half of the rats in each group had undergone sympathectomy. The resting cord blood flow was lower than control values following sympathectomy only at the S1-4 cord level (p less than 0.01) and cauda equina (p less than 0.01), and was marginally lower at the L1-2 and L3-6 levels (p less than 0.1). Cord blood flow was unaffected by sympathectomy during moderate hypotension. During severe hypotension, cord blood flow was less than control at the C3-5 level (p less than 0.05), but did not differ from control at the other six levels. Flows in nerve and muscle were consistent with known effects of sympathectomy on peripheral tissues. It is concluded that, at most, sympathectomy may moderately decrease resting blood flow in the cord levels caudal to L-1. Sympathectomy has no major effect on regional spinal cord blood flow in rats stressed by either moderate or severe arterial hemorrhage.

Animals

Topical silicone gel for the prevention and treatment of hypertrophic scar.

We studied the effects of a silicone gel bandage that was worn for at least 12 hours daily on the resolution of hypertrophic burn scar. In a second cohort, the prevention of hypertrophic scar formation in fresh surgical incisions by this bandage was also evaluated. In 19 patients with hypertrophic burn scars, elasticity of the scars was quantitated serially with the use of an elastometer. An adjacent or mirror-image hypertrophic burn scar served as a control. Scar elasticity was increased after both 1 and 2 months compared with that in controls. There was corresponding improvement clinically that persisted for at least 6 months. In the other cohort, scar volume changes in 21 surgical incisions were measured before and after 1 and 2 months. Gel-treated incisions gained less volume than control incisions after both intervals. Clinical assessment corroborated this quantitative demonstration of a decrement in scar volume. We concluded that topical silicone gel is efficacious, both in the prevention and in the treatment of hypertrophic scar.

Administration, Topical

Squamous cell carcinoma of the anal canal.

Between 1979 and 1988, 33 patients with squamous cell carcinoma of the anal canal were treated with chemoradiation. There were 24 women and 9 men, from 37 to 90 years of age (median: 63 years). Complete tumor regression occurred in 29 of the 33 patients (88%), only one of whom later developed recurrence. In the other four patients, there was persistent tumor after 3 months; three of these patients died within 2 years; and one is alive with distant metastases 2 years later. During the first 5 years of the study, seven patients with complete tumor regression underwent planned abdominoperineal resection following chemoradiation. Four of the abdominoperineal resection specimens were free of tumor, but three were not. These three patients, who had abdominoperineal resection within 3 months of chemoradiation, are disease-free. Ten of the 29 patients who had complete tumor regression had biopsies of the primary site 3 months after treatment. All biopsies were negative for residual carcinoma. At present, 26 patients (79%) are alive and disease-free from 2 to 10 years post-treatment (median: 4 years). Two patients died of unrelated causes, four of cancer, and one is alive with cancer. Complications of the chemoradiation required surgical intervention in two patients, and two others developed severe hematologic toxicity, for a complication rate of 12% (4 of 33 patients). There was no treatment-related mortality. These results support the efficacy of chemoradiation treatment for carcinoma of the anal canal. They suggest that abdominoperineal resection no longer need be part of the planned initial management, and that posttreatment biopsy of the primary site is unnecessary, unless palpable or visible abnormalities are present 3 months after treatment.

Adult

Effects of 4-aminopyridine on protein phosphorylation in heat-blocked peripheral nerve.

The topical application of 4-aminopyridine (4-AP) reverses within 1-3 min the partial conduction block that results from heating 5-mm segments of rat posterior tibial, peroneal and sural nerves to 45 degrees C for several minutes. Nerves previously blocked in vitro or in vivo were incubated in vitro in the presence of [gamma-32P]ATP. The rate of phosphorylation of soluble nerve proteins that had entered the media was determined. Labeled proteins were separated electrophoretically and autoradiograms prepared. We found that 5 mM 4-AP increases the phosphorylation rate in heat-blocked nerve by approximately 50-fold. The process is calcium-dependent and is heat-labile. Soluble proteins with a molecular weight in the 53-55 kDa range are preferentially but not exclusively phosphorylated in the presence of 4-AP at levels effective in restoring conduction. The results suggest that the potassium channel blocker 4-AP may restore conduction by inducing changes in channel proteins.

4-Aminopyridine

Effect of adrenalectomy or sympathectomy on spinal cord blood flow in hypothermic rats.

We used [14C]butanol distribution to measure regional spinal cord blood flow (RSCBF) in three groups of pentobarbital-anesthetized rats: 1) normals (n = 16); 2) after bilateral adrenalectomy (n = 18); and 3) after excision of the abdominal sympathetic chains (n = 12). Half of the rats in each group were maintained near normothermia; the remainder were colled to a rectal temperature of 25-27 degrees C. In intact rats, there was a 24-37% increase in RSCBF during hypothermia in the cord region C3-L6 inclusive. Neither operative procedure altered RSCBF during normothermia. In hypothermic adrenalectomized rats, RSCBF was elevated only in the C3-C5 cord segment. After sympathectomy, RSCBF was unchanged during hypothermia. In the cauda equina, flow fell in all hypothermic rats. The hypothermia-associated increases in RSCBF were not related to changes in mean arterial blood pressure. We conclude that adrenalectomy near-totally ablates the hypothermia-associated increase in RSCBF measured in intact rats and that abdominal sympathectomy totally ablates it. This evidence complements morphological evidence for adrenergic innervation of the spinal cord vasculature.

Adrenalectomy

'Lethal' burns. A progress report.

Sixteen consecutive patients, nine of whom also had inhalation injury, had burns over 72% body surface area or more. The expected death rate was 94%. In fact, all of the eight patients still alive after 48 hours survived. The early deaths were primarily due to inhalation injury, the treatment of which remains an unsolved problem. A mixture of cerium nitrate and silver sulfadiazine was used for topical wound antisepsis. The wound flora was sparse: 447 of 814 wound-surface cultures were sterile; Gram-negative bacteria were recovered in 13%. This efficacious wound bacteriostasis appeared primarily responsible for the absence of late death.

Adolescent

Cimetidine inhibits burn edema formation.

Large doses of cimetidine significantly inhibit edema formation in thermally injured rat skeletal muscle. Tissue sodium influx and potassium efflux is also sharply restricted. These effects were obtained even if the administration of cimetidine was delayed for up to 4 hours after injury, but no beneficial effect occurred if drug administration was delayed for 14 hours, when most of the edema had already accumulated. The minimal effective dose is between 0.1 to 0.2 mg/gm.

Animals

Topical therapy.

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Administration, Topical

The treatment of burned children.

Burn shock in infants and children is satisfactorily treated by the initial intravenous administration of balanced hypertonic sodium solutions; monitoring of plasma sodium and/or osmolarity permits necessary adjustment of the sodium concentration of administered fluids. This approach has been safe. Its principal advantage is in minimizing acute gains in body weight, which may be alarming otherwise, especially in children. Clinical and bacteriological data are presented indicating that cerium nitrate-silver sulfadiazine cream is a highly efficient topical antiseptic agent for both major and minor burn wounds and that it has low toxicity. Cerium nitrate-silver sulfadiazine cream can be readily employed in any clinical setting.

Adolescent

Topical chemotherapy for burns using cerium salts and silver sulfadiazine.

These experimental data indicate that cerium compounds exert a measurable antimicrobial action in vitro. In vivo the simultaneous use of cerium sulfadiazine and silver sulfadiazine was more effective than silver sulfadiazine alone or the combination of cerous nitrate and silver sulfadiazine. When cerous nitrate was used clically, gram-positive bacteria predominated. In contrast, wounds exposed to silver salts alone harbor a predominately gram-negative flora. The combination of cerous nitrate and silver sulfadiazine appears to provide a broad spectrum inhibitory to both types of organisms. It is apparent that a sampling problem exists in any attempt to monitor wounds that may exceed a square meter in extent. These bacteriologic data pertain only to the surface flora. The need to culture tissue samples of burn wounds has been emphasized. Our experience, however, is that invasion of deep tissue without dense surface colonization, greater than 10(5), is infrequent. Furthermore, fragments of eschar were submitted regularly for culture; those results confirmed the surface culture findins. The characteristic yellow-green color of cerium nitrate treated eschars may results from oxidation of trivalent cerium to yellow ceric ions. Free silver and sulfadiazine ions are available also in small amounts because of limited ionization of the highly insoluble silver sulfadiazine. This might promote the in vivo formation of cerous sulfadiazine and would provide a continuous source of ionic cerium for microbial inhibition. The modification of silver sulfadiazine cream by incorporating cerous nitrate into it strikingly enhances its topical antiseptic effect in burn wounds without increasing toxicity.

Administration, Topical

Bacterial contamination of skin used as a biological dressing. A potential hazard.

Bacterially contaminated skin used as a biological dressing on burn wounds can cause serious or even lethal infections, three examples of which are cited. Cadaver-skin allografts were frequently found to contain pathogenic bacteria. The frequency of infections due to the use of contaminated skin grafts on open wounds is unknown.

Autopsy

Renal function after thermal trauma: the effects of treatment on renal blood flow and sodium and water excretion.

Effective renal plasma flow, urine sodium excretion, and glomerular filtration rates were reduced markedly to 44%, 46%, and 60% of normal, respectively, in rats subjected to thermal trauma. A sodium load of about 2 mEq. per 100 Gm. of body weight restores these functions toward normal. Doubling the concomitant water load had no discernible beneficial effect, but rats resuscitated with the larger water load were in greater positive water balance. These experimental data suggest that the water loads commonly administered clinically for the treatment of burn shock may be unnecessarily large.

Animals