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Biomedical subjects

R F Brown

Publications and source records attributed to R F Brown.

At least 55 records · Page 3Linked to original sources

Synthesis and biological evaluation of a series of parenteral 3'-quaternary ammonium cephalosporins.

The preparation and biological evaluation of a series of 7 beta-[2-(2-aminothiazol-4-yl)-2(Z)-methoximinoacetamido]cep halosporins, substituted at the 3'-position with monocyclic or bicyclic nitrogen-containing heterocycles are described. The resulting family of parenteral compounds displays a broad spectrum of antibacterial activity. Some compounds exhibit a similar level of Gram-negative activity to that of the "third-generation" cephalosporins with increased staphylococcal activity. The in vitro and in vivo antimicrobial activity, structure-activity relationships, beta-lactamase stability, and in vitro and in vivo pharmacological evaluations are presented.

Animals↗

The histopathology of rat lung following exposure to zinc oxide/hexachloroethane smoke or installation with zinc chloride followed by treatment with 70% oxygen.

The effects of inhaled zinc oxide/hexachloroethane smoke (11,580 mg x min/m3) and intratracheally instilled zinc chloride (2.5 mg/kg body weight) have been studied in rat lung. The effects of subsequent treatment with 70% oxygen have been studied after both procedures. Both the inhalation of the smoke and instillation of zinc chloride produced similar effects that included pulmonary edema, alveolitis and, at a later stage, some fibrosis. After zinc chloride instillation, the pathological changes largely spared the periphery of the lung, while following smoke inhalation they were more diffuse. Subsequent oxygen administration had little effect on the development or progression of the pathological changes.

Administration, Inhalation↗

Screening, diagnosis, and management of dyslipoproteinemia in children.

The authors provide an extensive and comprehensive review of dyslipoproteinemia in children. An effective program for CVD reduction in this population will include an accessible screening program to identify high-risk children, high-quality measurements of TC and LP-C, careful follow-up of screening results with multiple measurement to classify risk status and diagnose primary dyslipidemia, a key role for family and education, and consistent and long-term follow-up for diet and drug adherence, efficacy, and safety.

Adolescent↗

The biochemical and pathological changes produced by the intratracheal instillation of certain components of zinc-hexachloroethane smoke.

Zinc chloride which is formed by igniting a mixture of zinc oxide and hexachloroethane in the production of white smokes has been shown to produce oedema when given to rats as a single instillation. The oedematous reaction, as assessed by histopathology and measurements of alveolar surface protein in lavage fluid, is variable, dose-dependent, and maximal at 3 days but at sub-lethal doses it regresses after 7 days. The parent compound, zinc oxide, does not produce these effects. In some animals there is evidence of a fibrogenic response at 7 days post-exposure although it is currently unknown whether or not this effect is progressive.

Animals↗

The repeated dose toxicity of a zinc oxide/hexachloroethane smoke.

Mice, rats and guinea pigs were exposed to the smoke produced by ignition of a zinc oxide/hexachloroethane pyrotechnic composition, 1 h/day, 5 days/week, at three different dose levels, together with controls. The animals received 100 exposures except for the high dose guinea pigs, which underwent 15 exposures, because of high death rate during the first few days of exposure. The test material had very little effect on weight gain, but there was a high rate of early deaths in the top dose of mice. A variety of incidental findings was seen in both decedents and survivors, but organ specific toxicity was, with one exception, confined to the respiratory tract. The most important of these findings was a statistically significant increase in the frequency of alveologenic carcinoma in the high dose group mice (p less than 0.01) and a statistically significant trend in the prevalence of the same tumour over all dose groups and the controls. A variety of inflammatory changes was seen in the lungs of all species and some appeared to be treatment-related. Fatty change in the mouse liver was more common in the middle and high dose groups than the controls. The aetiology of the tumour incidence is discussed and it is pointed out that hexachloroethane and zinc, as well as carbon tetrachloride, which may be present in the smoke, may be animal carcinogens in appropriate circumstances. Carbon tetrachloride is a known human carcinogen.

Animals↗

Use of enzyme immunoassay for the rapid diagnosis of Chlamydia trachomatis endocervical infection in female adolescents.

Enzyme immunoassay (EIA) has been proposed as an alternative to tissue culture for the detection of Chlamydia trachomatis in cervical specimens. The diagnostic efficacy of EIA was compared to tissue culture in 113 teenaged females attending an adolescent reproductive health program. Infection was diagnosed by tissue culture in 16% of subjects. Compared with tissue culture, EIA demonstrated a sensitivity of 100%, specificity of 88%, positive predictive value of 62%, and a negative predictive value of 100%. These data indicate that EIA is an acceptable alternative to tissue culture when screening for C. trachomatis endocervical infection in adolescent females.

Adolescent↗

An investigation of possible models for the production of progressive pulmonary fibrosis in the rat. The effects of repeated intratracheal instillation of bleomycin.

Pulmonary fibrosis is a common later sequel to damage to the lung caused by a wide variety of agents. Bleomycin is an antineoplastic drug used in the treatment of squamous cell carcinomas and lymphomas. It is known to cause pulmonary fibrosis is both man and experimental animals. Bleomycin, dissolved in saline, was given by intratracheal instillation (dose = 0.5 U/animal; dose vol. = 0.5 ml/animal) to groups of at least 5 rats. Groups received either a single dose or 2, 3 or 4 doses each given a week apart. They were then sacrificed at periods of up to 90 days after the last dose. Subsequent histology revealed varying degrees of alveolitis, type II pneumocyte hyperplasia, alterations to alveolar structure including obliteration, degeneration, collapse and enlargement with significant interstitial fibrosis. The lesion appeared to be diffusely distributed throughout the lung. After a single dose or 2 doses regression of the lesion was observed with time following dosing whereas with 3 or 4 doses of bleomycin the changes increased progressively in extent and severity. Three or more doses of intratracheal instilled bleomycin appear to be a good model of progressive pulmonary fibrosis in the rat.

Animals↗

Skull x-ray examinations after head trauma. Recommendations by a multidisciplinary panel and validation study.

The value of skull radiography in identifying intracranial injury has not yet been satisfactorily defined. A multidisciplinary panel of medical experts was assembled to review the issue of skull radiography for head trauma. The panel identified two main groups of patients--those at high risk of intracranial injury and those at low risk of such injury--and developed a management strategy for imaging in the two groups. The high-risk group consists primarily of patients with severe open or closed-head injuries who have a constellation of findings that are usually clinically obvious. These patients are candidates for emergency CT scanning, neurosurgical consultation, or both. The low-risk group includes patients who are asymptomatic or who have one or more of the following: headache, dizziness, scalp hematoma, laceration, contusion, or abrasion. Radiographic imaging is not recommended for the low-risk group and should be omitted. An intermediate moderate-risk group is less well defined, and skull radiography in this group may sometimes be appropriate. A prospective study of 7035 patients with head trauma at 31 hospital emergency rooms was conducted to validate the management strategy. No intracranial injuries were discovered in any of the low-risk patients. Therefore, no intracranial injury would have been missed by excluding skull radiography for low-risk patients, according to the protocol. We conclude that use of the management strategy is safe and that it would result in a large decrease in the use of skull radiography, with concomitant reductions in unnecessary exposure to radiation and savings of millions of dollars annually.

Brain Injuries↗

Salmonella typhi 205aTy, a strain with two attenuating auxotrophic characters, for use in laboratory teaching.

The need for p-aminobenzoic acid of a previously reported pab mutant in a Salmonella typhi strain causes loss of virulence (mouse median lethal dose by the intraperitoneal route with mucin, ca. 10(7) CFU, versus less than 200 CFU for related pab+ strains). This strain, however, gave p-aminobenzoic acid-independent revertants at a low frequency (ca. 4 X 10(-10) per bacterium per generation). It was therefore given, by transduction and mutation, a transposon-generated, nonreverting (rate, less than 3 X 10(-11) per bacterium per generation) mutation at purA, causing a requirement for adenine; such a mutation in a wild-type strain caused about the same loss of virulence as the pab mutation. The pab purA strain, 205aTy, has mouse median lethal dose of ca. 5 X 10(7) and is expected to be unable to cause typhoid fever. Since strain 205aTy behaves like a typical Vi-positive S. typhi strain in nearly all common tests, we propose that it is a safe strain for use in laboratory teaching, proficiency testing, and the like.

4-Aminobenzoic Acid↗

Antibodies to marine caliciviruses in the Steller sea lion (Eumetopias jubatus Schreber).

Sera from 145 Steller sea lions (76 adults, three subadults, 37 pups, and 29 fetuses) were tested for neutralizing antibodies to nine marine calicivirus serotypes. Antibodies were found to San Miguel sea lion virus (SMSV) types 1, 5, 6, 7, 8, 10 and 13, and to Tillamook (bovine) calicivirus, but no antibodies were found to the walrus calicivirus. Titers (microtiter neutralization assay) ranged from 1:20 to 1:320, with many positive reactions at the higher dilutions (greater than or equal to 1:80). Antibodies to SMSV's 5 and 10 were most common among animals sampled in Alaskan waters, while antibodies to SMSV-6 were most common among pups from the southern Oregon coast. These data provide evidence that Steller sea lions, like their California sea lion (Zalophus c. californianus Lesson) counterparts, have experienced widespread exposure to multiple serotypes of marine caliciviruses.

Animals↗

First isolation of a calicivirus from the Steller sea lion (Eumetopias jubatus).

A calicivirus was isolated from the rectum of a Steller sea lion (Eumetopias jubatus) pup on Rogue Reef, off the southern Oregon coast. Based on the results of neutralization tests with specific typing antisera, the isolate was identified as San Miguel sea lion virus serotype 6 (SMSV-6). Blood obtained from nine of 37 pups (24%) during virus sample collection procedures had specific neutralizing antibodies to SMSV-6. The isolation of SMSV-6 from a Steller sea lion represents, to our knowledge, the first isolation of any virus from this widely distributed marine mammal species, and serves to reconfirm the host-nonspecificity of yet another calicivirus of marine origin.

Animals↗

The in vitro penetration and distribution of T-2 toxin through human skin.

The penetration and distribution of T-2 toxin in excised human abdominal skin has been determined for a dose range of 1.0-2.6 micrograms/cm2 skin using an ethanol vehicle and a saline receptor solution. In all cases the overall percentage penetration of T-2 after 48 h was low, the greatest amounts of toxin being present in the stratum corneum with less in the epidermis and relatively little in the dermis. Vehicle: skin partition coefficients support this finding. Neither penetration nor distribution were changed by a rabbit serum receptor solution. Electron micrographs showed that at 1.8 micrograms/cm2 and above the contents of the intercellular space are leached out to leave the integument as a porous membrane. The distribution of T-2 within the skin after 48 h would suggest that for doses up to 2.6 micrograms/cm2 the irritative and inflammatory effects on the skin would be of more immediate concern than would systemic toxicity.

Diffusion↗

Differentiation of murine erythroleukemic cells during exposure to microwave radiation.

Cultures of murine erythroleukemic cells undergoing erythroid differentiation in response to induction by hexamethylene bisacetamide (HMBA) were exposed to 1180-MHz microwave (MW) radiation for 48 h while maintained at 37.4 degrees C by variable-temperature air flow. Exposures at 1180 MHz were at 5.5, 11, and 22 mW/cm2 with a normalized specific absorption rate of 3.32 W/kg per mW/cm2. HMBA-induced control cells were incubated in a 37.4 degrees C water bath. Mean cell doubling time was 16.5 h in both the irradiated cultures and the control cultures. About 65% of the cells of irradiated cultures and control cultures were benzidine-positive differentiated cells. Both the irradiated cultures and the control cultures contained approximately 58 micrograms of hemoglobin/mg total cytoplasmic protein. The absence of any change in these parameters suggests that MW radiation at 1180 MHz and similar frequencies exerts no effect on proliferation and differentiation of mammalian cells in the absence of hyperthermia.

Acetamides↗

Inhalation toxicity of a smoke containing Solvent Yellow 33, Disperse Red 9 and Solvent Green 3 in laboratory animals.

The repeated-dose inhalation toxicity of a smoke containing a mixture of three dyes was tested in female mice, rats and guinea pigs. The green component dye (Solvent Green 3) was retained in the lungs. Particularly in the rats marked collections of alveolar macrophages were found. In the same species several other adverse findings were noted: these included adenocarcinomas of the breast in the high-dose group and a dose-related incidence of biliary hyperplasia. Fatty change was noted in the livers of the test-group mice. A large proportion of the high-dose guinea pigs died during the exposure period, for which reason exposure was stopped early in that group, otherwise the guinea pigs were little affected. However, all test groups of all species showed reductions in growth during the exposure period.

Animals↗

Experimental determination of whole body average specific absorption rate (SAR) of mice exposed to 200-400 MHz CW.

A maximum of six live mice, mouse cadavers, prolate spheroids molded from muscle-equivalent tissue, or saline-filled culture flasks, were exposed to continuous wave radiation in a TEM cell at frequencies between 200 and 400 MHz. Whole-body average specific absorption rate (SAR) was determined from power meter measurements of incident, reflected, and transmitted powers. The SARs for both live mice and cadavers were approximately twice that for the prolate spheroid models, and when housed in Plexiglas restraining cages, about 2 1/2 times greater. An error multiplying factor is identified, that quantitatively expresses how SAR data obtained by the three-power-meter method becomes progressively more noisy as the irradiation frequency is lowered or as the TEM cell cross section is increased.

Animals↗