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Biomedical subjects

C A Brooks

Publications and source records attributed to C A Brooks.

12 recordsLinked to original sources
PubMed1992

Assessment of the in vivo immunosuppressive activity of the major cyclosporine metabolite by leukemia allograft rejection.

AM1 (M17) is the major metabolite of cyclosporine found in the blood of human transplant recipients, and trough levels of this derivative exceed those of the parent compound approximately two-fold. Studies performed in vitro indicate that AM1 retains only 10-20% of the biological activity of the parent compound, but very little is known about its in vivo immunosuppressive effects. We therefore developed a rapid and sensitive method, based on the rejection of allogeneic L1210 (H-2d) leukemia cells by C57BL/6 (H-2b) mice, to assess the immunosuppressive activity of AM1 in vivo. Rejection of the leukemia allograft was determined by analyzing the spleens from mice injected intravenously with 10(5) L1210 cells for the presence of H-2Kd-positive cells by flow cytometry using an FITC-conjugated monoclonal anti-H-2Kd antibody. Nonimmunosuppressed mice rejected the allogeneic cells and survived indefinitely. Spleens from these mice were virtually free of H-2Kd-positive cells (0.51 +/- 0.21%) by day 7. In contrast, C57BL/6 mice treated with 10 mg/kg/day s.c. of CsA all died from the L1210 challenge (mean survival time of 9 +/- 1 days). Spleens from mice treated in this manner contained 11.02 +/- 3.31% H-2Kd-positive cells on day 7. There was a direct correlation between the dose of CsA administered (7.5-50 mg/kg/day) and the percentage of H-2Kd-positive cells in the spleen. We then compared the immunosuppressive activity of AM1 and CsA in this model. AM1 was purified from the urine of CsA-treated renal allograft recipients by a combination of preparative adsorption-desorption chromatography and preparative elution high-performance liquid chromatography. AM1 at a dose of 10 mg/kg/day exhibited no demonstrable immunosuppressive effect, and trough levels of AM1 on day 7 were only 36 +/- 4 ng/ml. Increasing the dose of AM1 to 50 mg/kg/day resulted in only 1.05 +/- 0.16% H-2Kd-positive cells in the spleens (P = NS) and a mean trough level of 221 +/- 27 ng/ml. In contrast, mice treated with 50 mg/kg/day of CsA exhibited 17.7 +/- 2.9% H-2Kd-positive cells in their spleens and a mean trough CsA level of 3036 +/- 277 ng/ml. The half-life of a single subcutaneous dose of 10 mg/kg of AM1 (4.6 hr) was significantly shorter than that of CsA (9.7 hr) in mice. Compared with CsA, the lack of immunosuppressive effect of AM1 in vivo therefore appears to be due to a combination of decreased immunosuppressive activity and increased rate of clearance in mice.

Animals↗
PubMed1991

Impairment, disability, handicap and medical expenses of persons aging with spinal cord injury.

Data from 205 Craig Hospital patients with spinal cord injuries (SCI) were analysed with regard to level of injury, age, length of time since SCI, disability (as measured by the Functional Independence Measure), handicap (as measured by the Craig Handicap Assessment and Reporting Technique), and average annual costs for services relating to the SCI. Differences in disability, handicap, and costs of care were analysed by chronological age and length of time since injury. Older individuals showed significant increases in disability and handicap. When chronological age was added to the number of years post-injury, significant increases in disability, handicap, and costs of care were noted at all neurological levels.

Adolescent↗
PubMed1989

A seroepidemiologic survey of the prevalence of herpes simplex virus type 2 infection in the United States.

The prevalence of infection with the genital herpes simplex virus type 2 (HSV-2) has been difficult to ascertain, primarily because of the large percentage of subclinical cases and the limitations in specificity of serologic assays for antibody to HSV-2. To obtain an improved estimate of the distribution of HSV-2 infection in the United States, we used an HSV type-specific antibody assay to test serum samples from 4201 participants in the second National Health and Nutrition Examination Survey. The results in our sample indicate that in the period from 1976 to 1980, 16.4 percent of the U.S. population 15 to 74 years of age (approximately 25 million persons) was infected with HSV-2 (95 percent confidence interval, 14.2 to 18.6 percent). Age and race were the demographic factors associated most strongly with the presence of HSV-2 antibody. The prevalence of the antibody increased from less than 1 percent in the group under 15 years old to 20.2 percent in the group 30 to 44 years old; it increased only slightly thereafter. In the oldest group, 60 to 74 years of age, the prevalence was 19.7 percent in whites and 64.7 percent in blacks. Among blacks of all age groups, but not whites, higher rates were observed in women than in men. The associations were weaker with respect to marital status, income, education, urban residence, and region of the country. After control for age, sex, and race, only the association with marital status remained significant; the rate was increased in persons previously married--i.e., divorced, separated, or widowed. We conclude that the prevalence of HSV-2 infection in the United States is higher than has previously been recognized and that many infections with this sexually transmitted virus may be subclinical.

Adolescent↗
PubMed1986

Predicting acute pelvic inflammatory disease: a multivariate analysis.

A multivariate logistic regression analysis of patient symptoms and signs and laboratory findings associated with the diagnosis of acute pelvic inflammatory disease was performed with use of data from 628 women who were clinically diagnosed as having the disease for the first time at the University of Lund, Sweden. In 414 women (65.9%) acute pelvic inflammatory disease was laparoscopically confirmed. We developed a mathematical model that correctly predicted 87.0% of the cases of acute pelvic inflammatory disease and had an overall correct classification rate of 75.6%. Variables that were good predictors of acute pelvic inflammatory disease were purulent vaginal discharge, erythrocyte sedimentation rate greater than or equal to 15 mm/hr, positive gonorrhea result, adnexal swelling on bimanual examination, and rectal temperature greater than or equal to 38 degrees C. Furthermore, we developed "mixed model I" and "mixed model II," which combine simple clinical parameters and laparoscopy in varying degrees. In mixed model I the sensitivity, specificity, and overall classification values were 93%, 67.2%, and 84.5%; in mixed model II these values were 100%, 67.2%, and 89.2%. Use of relatively simple and reproducible clinical parameters can identify those women who would most benefit from laparoscopy to diagnose acute pelvic inflammatory disease.

Acute Disease↗
PubMed1984

The distribution of six enzymes of oxidative metabolism along the rat nephron.

Using quantitative methods, citrate synthase (CS), fumarase, beta-hydroxyacyl-coenzyme A (CoA) dehydrogenase (beta OAC), 3-keto-acid CoA transferase (KCT), malic dehydrogenase (MDH), and malic enzyme were measured in seven defined parts of the nephron and in thin limb and papilla areas dissected from freeze-dried microtome sections of rat kidney. The results not only show a wide range of activity along the nephron for each of the enzymes, but that the proportions between the enzymes vary markedly among the different parts of the nephron. This suggests the existence of major regional differences in the capacity to oxidize specific metabolites. The ratio between two citrate cycle enzymes, fumarase and CS, was 4- or 5-fold higher in proximal segments than in the glomerulus or thin limb areas. The ratio between beta OAC (an enzyme of fatty acid oxidation) and CS was 3- to 5-fold higher in the middle proximal segments than in glomeruli or thin limb and papilla areas. The key enzyme for ketone body metabolism, KCT, was essentially confined to the thick tubule segments. Malic enzyme, in contrast to the other five enzymes, was highest in the proximal straight segments. New methods, sufficiently sensitive for this histochemical study, are described for malic enzyme and 3-keto-acid CoA transferase.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMedDate not supplied

National surveillance for neonatal herpes simplex virus infections.

To explore the magnitude and descriptive epidemiology of neonatal herpes simplex virus (HSV) infection, the Centers for Disease Control (CDC) conducted an 18-month hospital-based surveillance study in which 184 cases were reported. Only 22% of mothers had a history of genital HSV infection and only 9% had genital lesions at the time of delivery. Cesarean delivery initiated prior to membrane rupture failed to prevent infection in 15 cases. These data confirm previous observations that most mothers of infected neonates have no history of genital HSV and are asymptomatic at delivery. Furthermore this study suggests that intrauterine infection may be an important route of transmission and underscores the limitations of current prevention strategy.

Adolescent↗