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Biomedical subjects

R Anderson

Publications and source records attributed to R Anderson.

At least 271 records · Page 15Linked to original sources

The pro-oxidative riminophenazine B669 neutralizes the inhibitory effects of Mycobacterium tuberculosis on phagocyte antimicrobial activity.

The effects of clofazimine, a riminophenazine antimicrobial agent, and its analogue B669 on phagocyte functions have been investigated. Clofazimine, at concentrations attainable in vivo, and B669, in particular, increased the intracellular killing ability of phagocytes following appropriate cell stimulation. Similarly, nitro blue tetrazolium reduction, hydrogen peroxide production, lysosyme release and hexose monophosphate shunt activity were all increased by treating phagocytes with the riminophenazines. It has previously been shown that a 25 kDa glycolipoprotein derived from Mycobacterium tuberculosis inhibits phagocyte functions associated with phagocyte antimicrobial activity. The present study confirms these observations. A further aspect of the study examined the ability of riminophenazines to reverse the inhibition of phagocyte functions by the 25 kDa mycobacterial fraction. Whilst both riminophenazines were capable of partially but significantly reversing the inhibition due to the mycobacterial fraction, the restorative capacity of B669 was greater than that of clofazimine.

Anti-Bacterial Agents↗

Development of a guinea pig model to assess immunogenicity of Haemophilus influenzae type b capsular polysaccharide conjugate vaccines.

There is currently no animal model which reliably predicts the immunogenicity of Haemophilus influenzae type b (Hib) polysaccharide-protein conjugate vaccines in human infants. We evaluated various Hib vaccines in guinea pigs using techniques similar to the United States potency test for adsorbed diphtheria and tetanus toxoids with a view to developing a method for evaluating the potency of a combined adsorbed tetanus, diphtheria, pertussis and Hib conjugate vaccine. Groups of 6-8 guinea pigs received 1.5 single human doses of vaccine at 0 and at 6 or 8 weeks and were bled at 6 weeks and 2 weeks after the booster injection. Total antibodies to polyribosylribitolphosphate (PRP), the Hib capsular polysaccharide, were measured in individual animals and in serum pools by radioimmunoassay. The relative antibody responses of guinea pigs to Hib conjugate vaccines qualitatively resembled those of human infants. Unconjugated polysaccharide was not immunogenic; PRP-D produced a low antibody response, HbOC, PRP-T (Merieux) and Hib-T (MPMBL) produced a low response to the first dose and a strong anamnestic response to the booster (geometric mean anti PRP > 1 micrograms ml-1). PRP-OMP uniquely produced a strong response after the first dose which was further boosted by the second dose. Experimental Hib-T vaccine lots with low levels of conjugation were poorly immunogenic in guinea pigs. Combinations of DTP and Hib-T vaccines showed equivalent or greater immunogenicity than Hib-T alone. We propose that the guinea pig model may be useful to verify the immunogenicity of PRP conjugate vaccines and for pre-clinical evaluations of DTP-Hib combination vaccines containing PRP conjugates.

Animals↗

Vitamin E, pulmonary functions, and phagocyte-mediated oxidative stress in smokers and nonsmokers.

Relationships among the plasma levels of vitamin E (VE), the numbers and prooxidative activities of circulating phagocytes, serum alpha-1-protease inhibitor (API), and pulmonary functions were investigated in 83 asymptomatic male cigarette smokers and 65 nonsmoking controls. Plasma levels of VE, of cholesterol, and of API were measured using high performance liquid chromatography, spectrophotometry, and nephelometry, respectively, whereas reactive oxidant (ROS) generation by activated blood phagocytes was measured using a whole blood luciginen-enhanced chemiluminescence method. Smoking was associated with significantly increased circulating neutrophil counts (p 0.0001), serum API (p 0.0001) and phagocyte-derived ROS-generation (p 0.0001), and decreased spirometric values (FEV1: p 0.0138 and FEF25-75: p 0.0654). Plasma VE and cholesterol levels were not significantly different between smokers and nonsmokers. However, in smokers both plasma VE and cholesterol correlated significantly and positively with serum API (r 0.24, p 0.03 and r 0.30, p 0.005, respectively), neutrophil counts (r 0.24, p 0.03 and r 0.25, p 0.03, respectively), and phagocyte-derived ROS-generation (r 0.32, p 0.003 and r 0.32, p 0.003, respectively), and significantly and inversely with FEV1 (r -0.23, p 0.03 and r -0.22, p 0.04, respectively) and FEF25-75 (r -0.32, p 0.003 and r -0.26, p 0.02, respectively). In nonsmokers plasma VE, but not cholesterol, was positively correlated with FEV1 (r 0.34, p 0.007) and FEF25-75 (r 0.40, p 0.001). The results suggest that VE protects the lungs of both smokers and nonsmokers and may act as a mobilizable antioxidant in response to smoking-induced oxidative stress.

Adult↗

An epidemiologic analysis of Mycobacterium avium complex disease in homosexual men infected with human immunodeficiency virus type 1.

Cofactors associated with the Mycobacterium avium complex (MAC) disease and its prognosis in incident cases of AIDS in homosexuals were studied. We compared 51 men in whom MAC disease developed as the initial AIDS-defining illness (termed AIDS illness hereafter); 157 men who had MAC disease subsequent to another AIDS illness; and 884 men who had only non-MAC AIDS illnesses. MAC disease was the initially diagnosed AIDS illness more often in Baltimore (6.9%) and Los Angeles (5.6%) than in Chicago (2.6%) and Pittsburgh (0) (P < .01). MAC disease also was a more common subsequent AIDS illness in Baltimore (14.3%) and Los Angeles (22.4%) than in Chicago (8.5%) and Pittsburgh (6.5%) (P < .0001). Prophylaxis for Pneumocystis carinii infection increased the occurrence of MAC disease as the initial AIDS illness (from 2.3% to 12.5%; P < .0001). A low white blood cell (WBC) count was slightly more predictive of MAC disease than was a low CD4+ cell count. At 0-6, 7-12, and 13-18 months before diagnosis, the WBC cell counts of 75.0%, 61.1%, and 50.0%, respectively, of those with MAC disease as the initial AIDS illness were < or = 3,400/microL. Men in whom cytomegalovirus disease developed were at higher risk for subsequent MAC disease (relative hazard = 2.65; P < .0001). MAC disease also increased the risk for subsequent cytomegalovirus disease (relative hazard = 3.96; P < .0001).

AIDS-Related Opportunistic Infections↗

Optic nerve decompression in cranial base fibrous dysplasia.

Fibrous dysplasia of the anterior cranial base involves the bony orbit and optic canal. Although fibrous dysplasia is benign, it may produce a mass effect along the course of the optic nerve, inducing visual disturbances. Optic canal decompression in patients without clinical signs of optic neuropathy is controversial. We describe five patients with extensive fibrous dysplasia of the anterior cranial base involving the orbit and optic canal. These patients underwent transcranial optic canal decompression before signs of severe visual loss during correction of dystopias and craniofacial deformity induced by fibrous dysplasia. Cranial orbital reconstruction was performed by means of split rib and cranial bone grafts. Postoperative follow-up did not reveal disturbances in visual function, extraocular motility, or evidence of cerebrospinal fluid fistulas. This suggests that early, radical resection of orbital fibrous dysplasia with optic canal decompression may be effective in preventing visual loss with minimal risk of other neurological sequelae. Subsequent orbital reconstruction involving split-thickness rib and cranial bone grafting yields satisfactory cosmetic results.

Adolescent↗

Population pharmacokinetics of stavudine (d4T) in patients with AIDS or advanced AIDS-related complex.

The population pharmacokinetics and bioavailability of oral stavudine (d4T; 2',3'-dideoxy-3'-deoxythymidine) was determined in 81 patients with AIDS or AIDS-related complex (ARC) enrolled in phase I and phase I/II dose-ranging trials. Each patient underwent inpatient pharmacokinetic studies following administration of the first oral stavudine dose; 59 patients were restudied after chronic therapy for an average of 19 days. Thirty-three of these patients also received a single intravenous stavudine dose prior to starting an oral regimen. A two-compartment model with first-order absorption and elimination was used as the structural pharmacokinetic model. A basic model provided the following population parameter estimates (interpatient variability expressed in parentheses as percent coefficient of variation): clearance/bioavailability = 30.9 (24.5%) liters/h; volume of distribution/bioavailability = 8.42 (not modeled) liters; volume of distribution at steady state/bioavailability = 68.9 (105%) liters; intercompartmental clearance/bioavailability = 12.4 (26%) liters/h; and first-order absorption rate constant = 1.32 (78.9%) liters/h. In the subset of 33 patients receiving both intravenous and oral doses, the bioavailability of stavudine was estimated to be 99.1% (18.5%). Total body weight, stage of disease (AIDS versus ARC), and an oral stavudine dose of > or = 200 mg were found to have a statistically significant but a clinically marginal effect on the estimate of the oral clearance of stavudine. This analysis shows the high degree of bioavailability of stavudine in patients with AIDS and ARC and the relatively low degree of interpatient variability in oral drug clearance compared with those of other nucleosides. Population pharmacokinetic analysis is a useful tool for assessing the combined effects of several patient variables on the pharmacokinetic properties of drugs in human immunodeficiency virus-infected patients.

AIDS-Related Complex↗

Glucosyl diglyceride lipid structures in Deinococcus radiodurans.

The structures of two lipids from the radiation-resistant bacterium Deinococcus radiodurans are reported here: 1,2-diacyl-3-alpha-glucopyranosyl-glycerol and 3-O-[6'-O-(1",2"-diacyl- 3"-phosphoglycerol)-alpha-glucopyranosyl]-1,2-diacylglycerol. These lipids are strikingly different from previously characterized polar lipids from this organism, in that they are not unique to the genus Deinococcus and indeed have counterparts in both gram-negative and gram-positive bacteria. Moreover, as examples of glucose-containing lipids, they further illustrate the diversity of carbohydrate-containing lipids in D. radiodurans, from which lipids containing galactose and N-acetylglucosamine have already been structurally characterized.

Carbon Isotopes↗

Neutralization of respiratory syncytial virus after cell attachment.

Little is known about the mechanisms of antibody-mediated neutralization of respiratory syncytial virus (RSV) which causes recurrent infections in human despite the virtually universal presence of neutralizing serum antibodies. Human serum neutralization titers showed strong correlation with post-cell-attachment neutralizing titers for both RSV-convalescent sera and control sera but showed less strong correlation with cell-attachment blocking titers. Neutralization was effective for the first 60 min of infection, indicating that immune serum-mediated neutralization of RSV infection largely involves inhibition of early events following cell attachment.

Adhesiveness↗

Role of social class in excess black stroke mortality.

BACKGROUND AND PURPOSE: It has been suggested that a substantial proportion of the excess stroke mortality among black Americans may be attributable to relatively lower socioeconomic status (SES) in this group. In this report we provide the first quantitative estimates of the proportion of excess black stroke mortality attributable to SES for a large population-based cohort. METHODS: We used data from the National Longitudinal Mortality Study for persons 45 years and older (73,400 white men, 87,528 white women, 6522 black men, and 8816 black women). Sex-specific proportional hazards model were used to estimate excess black stroke mortality with and without adjustment for education and income (measures of SES). The contribution of SES to the excess black stroke risk was estimated from the difference in regression coefficients for race in these models. RESULTS: In men, low SES was associated with increased stroke mortality (P < or = .0001) and accounted for 14% to 46% of the excess black stroke risk (P < .05). However, we could find no association between SES and stroke mortality in women, and SES did not account for a significant proportion of the excess stroke mortality in black women. CONCLUSIONS: Although SES proved to account for a statistically significant proportion of excess male black stroke mortality, overall SES explained less than one quarter of the observed excess between ages 45 and 65. In women, SES did not significantly reduce the estimated excess black stroke mortality. Although SES may be playing a role in excess black stroke mortality, a substantial proportion of the excess appears attributable to other sources, including cerebrovascular risk factors that are unrelated to SES, unmeasured lifestyle influences, social resources, and genetic factors.

Black or African American↗

Anterior tibial tendon rupture.

Twelve patients with rupture of the anterior tibial tendon are presented. Nine patients were aware of an acute event prior to their symptom onset and three were not aware of any acute event. Complete rupture of the tendon was noted in 10 patients and incomplete rupture was seen in two patients. Treatment was individualized based on age, etiology, preinjury function, patient health, and personal considerations. Five patients were treated without surgery. Three preferred no orthotic devices, and two believed their function was improved with an ankle-foot orthosis. Seven patients were treated operatively using a variety of individualized reconstructive techniques. All operatively treated patients demonstrated increased function and strength. Based on our findings, operative reconstruction is recommended in appropriate patients.

Adolescent↗

Measurement of anti-acetylcholine receptor auto-antibodies in myasthenia gravis.

Two different acetylcholine receptor (AChR) preparations derived from amputated human muscle (AChRAMP) and from the human rhabdomyosarcoma cell line TE671 (AChRTE671) were compared in radio-immunoprecipitation assays for the detection of AChR auto-antibodies in serum specimens from 20 patients with proven myasthenia gravis. Tests performed with the AChRTE671 and AChRAMP antigen preparations were positive in all the patients and in 19/20 respectively. A high degree of correlation (r = 0.94) was evident between the two auto-antigen preparations. Assays based on the use of TE671-derived antigen represent a useful alternative to the conventional assay using AChRAMP for the detection of AChR auto-antibodies.

Autoantibodies↗

Physical activity and the initiation of high-risk health behaviors in adolescents.

The association of physical activity to the initiation of health risk behaviors was examined in a 3-yr prospective study of a population-based cohort of 1245 adolescents aged 12-16 yr. Four hundred thirty-seven students (35% of the cohort) were identified at baseline via self-report survey as never having smoked cigarettes, consumed alcohol, used marijuana, or carried a weapon. Three measures of physical activity were obtained at baseline: leisure-time physical activity (LTPA), level of aerobic fitness (AF), and participation in competitive athletics. Significant associations, with notable gender differences, were observed between physical activity and the initiation of cigarette smoking and alcohol use. The cumulative proportion of male students initiating alcohol use was 48%, 42%, and 24% for high, moderate, and low LTPA, respectively (P < 0.01). Males who participated in competitive athletics were significantly more likely than nonathletes to initiate alcohol use (44% vs 17%, P < 0.01). The cumulative proportion of female students initiating cigarette use was 10%, 23%, and 22% for high, moderate, and low LTPA, respectively (P < 0.05) and 7%, 28%, and 16% for high, moderate, and low AF, respectively (P < 0.05). No association was found between physical activity and weapon carrying. These results indicate that in this cohort of adolescents, the most active or most fit females were less likely to initiate cigarette smoking. In contrast, the most active males or males who participated in competitive athletics appeared more at-risk for initiating alcohol consumption than their less active counterparts.

Adolescent↗

The politics of delegation.

The American Nurses Association has stated that every patient needs a nurse, and they are right. But what do patients need a nurse to do? Politics has arisen around this issue in two ways: the development of new patient care delivery system models that use unlicensed assistive personnel to help professional staff, and a decrease in inpatient census has been seen throughout the country, resulting in changes in jobs and job locations. We argue that the best way to deal with these two factors is for nurses to redefine their functions, to focus on the professional aspects of care that only they can deliver and to keep open minds about where the delivery of services may take place. In the long run, this approach will take the profession much farther than blind adherence to outdated tradition.

American Nurses' Association↗