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Biomedical subjects

J Higgins

Publications and source records attributed to J Higgins.

At least 37 records · Page 2Linked to original sources
PubMed1991

The acetylator phenotypes of Saudi Arabians with coronary arterial atheroma.

The acetylator phenotypes were determined by means of a sulfamethazine test in 101 Saudi Arabian patients with authenticated coronary atheroma; 65 were found to be slow acetylators. This distribution of phenotypes is not significantly different from that in 220 controls, 148 of whom were slow acetylators. This finding makes it unlikely that compounds containing a primary aromatic amino or a hydrazino group are involved in the aetiology or pathogenesis of coronary atheroma.

Acetylation↗
PubMed1990

Expanded clinical evaluation of lovastatin (EXCEL) study: design and patient characteristics of a double-blind, placebo-controlled study in patients with moderate hypercholesterolemia.

The randomized, double-blind, placebo-controlled trial described in this report was undertaken to clarify the dose-response relation of lovastatin therapy to lipid-modifying efficacy (lipid/lipoprotein modification) and drug-related adverse events in a population with moderately elevated fasting plasma total cholesterol (240 to 300 mg/dl) and low-density lipoprotein cholesterol (greater than or equal to 160 mg/dl). Men or women (postmenopausal or surgically sterile), aged 18 to 70 years, were entered into the trial with minimal exclusion criteria. After 4 to 6 weeks of an American Heart Association phase I diet or a more stringent diet, 8,245 patients from 362 sites were randomized to 1 of 5 parallel diet and drug treatment groups: placebo (n = 1,663) or lovastatin, 20 mg (n = 1,642) and 40 mg (n = 1,645) with the evening meal, and 20 mg (n = 1,646) or 40 mg twice daily (n = 1,649). The regimen of diet and lovastatin (or placebo) was followed for 48 weeks. The 5 treatment groups were similar at baseline. The total cohort had the following characteristics: 59% were men (mean age 56 years); 92% were white; 59% had completed at least 1 year of education beyond high school; 57% had a history of cardiovascular and associated disease; 40% had a history of hypertension; and 29% had coronary artery disease. Health habits were similar among groups, with 18% of patients reporting cigarette smoking, 14% reporting that they consume greater than 1 alcoholic beverage daily and 67% reporting no strenous exercise. Mean lipid/lipoprotein levels were also similar among groups, with the following average levels: total cholesterol (258 mg/dl), low-density lipoprotein cholesterol (180 mg/dl), high-density lipoprotein cholesterol (45 mg/dl) and triglycerides (median = 155 mg/dl). The large size of this trial, its placebo-controlled, double-blind design and the similarity of treatment groups at baseline should allow clear documentation of the long-term effects of lovastatin treatment and generalization of the results to a substantial portion of patients who may be candidates for lipid-modifying therapy.

Adult↗
PubMed1990

A computerized respiratory sinus arrhythmia program for the non-invasive assessment of parasympathetic activity.

The availability of sophisticated signal analysis methods based on the use of micro-computers allows an accurate non-invasive assessment of parasympathetic activity, through the measurement of the respiratory sinus arrhythmia. The program described herein is in Quickbasic and consists of 5 programs. At termination of the computer analysis the results are printed which include the average heart rate for inspiration and expiration, the averaged standard deviation of the R-R intervals for inspiration and expiration, and the R-R interval in milliseconds averaged for all inspiratory and expiratory cycles. Significant correlations were obtained when comparing the analyses of the computerized program with a manual method.

Analog-Digital Conversion↗
PubMed1990

Inactivated simian immunodeficiency virus vaccine failed to protect rhesus macaques from intravenous or genital mucosal infection but delayed disease in intravenously exposed animals.

Eight rhesus macaques were immunized four times over a period of 8 months with a psoralen-UV-light-inactivated whole simian immunodeficiency virus vaccine adjuvanted with threonyl muramyl dipeptide. Eight unvaccinated control animals received adjuvant alone. Only the vaccinated animals made antibodies before challenge exposure to the viral core and envelope as determined by Western blotting (immunoblotting) and virus-neutralizing antibodies. Ten days after the final immunization, one-half of the vaccinated and nonvaccinated monkeys were challenged exposed intravenously (i.v.) and one-half were challenge exposed via the genital mucosa with virulent simian immunodeficiency virus. All of the nonvaccinated control monkeys became persistently infected. In spite of preexisting neutralizing antibodies and an anamnestic antibody response, all of the immunized monkeys also became persistently infected. However, there was evidence that the clinical course in immunized i.v. infected animals was delayed. All four mock-vaccinated i.v. challenge-exposed animals died with disease from 3 to 9 months postchallenge. In contrast, only one of four vaccinated i.v. challenge-exposed monkeys had died by 11 months postchallenge.

Adjuvants, Immunologic↗
PubMed1990

Immunization with a live, attenuated simian immunodeficiency virus (SIV) prevents early disease but not infection in rhesus macaques challenged with pathogenic SIV.

An infectious, virulence-attenuated molecular clone of simian immunodeficiency virus (SIV), SIVMAC-1A11, was derived from an SIV isolate that causes fatal immunodeficiency in rhesus macaques. When inoculated intravenously in rhesus macaques, SIVMAC-1A11 induced transient viremia (1 to 6 weeks) without clinical disease and a persistent humoral antibody response. The antibodies were directed mainly against the viral envelope glycoproteins, as determined by immunoblots and virus neutralization. The potential of this virulence-attenuated virus to protect against intravenous challenge with a pathogenic SIVMAC strain was assessed. Five rhesus macaques were each given two intravenous inoculations with SIVMAC-1A11 7 months apart. Three of the five immunized monkeys and four naive control animals were then challenged with 100 to 1,000 100% animal infectious doses of pathogenic SIVMAC. All seven animals became persistently viremic following the challenge. Four of four unimmunized animals developed severe clinical signs of simian acquired immunodeficiency syndrome by 38 to 227 days after challenge and were euthanatized 91 to 260 days postchallenge. However, no signs of illness were seen in immunized monkeys until 267 to 304 days postchallenge, when two of three immunized animals developed mild thrombocytopenia and lymphopenia; one of these animals died with clinical signs of simian immunodeficiency disease at 445 days after challenge. The two SIVMAC-1A11-immunized monkeys that were not challenged were healthy and antibody positive 22 months after the initial immunization. Thus, although live SIVMAC-1A11 was immunogenic and did not induce any disease, it failed to protect rhesus macaques against infection with a moderately high dose of pathogenic virus. However, immunization prevented severe, early disease and prolonged the lives of monkeys subsequently infected with pathogenic SIV.

Animals↗
PubMed1990

Emergency eye injuries.

This study analyses all patients presenting with eye complaints to the casualty section of a Brisbane Hospital during a one month period. Eye complaints constituted 3.6 per cent of all patients. A foreign body was involved in 57 per cent of all eye injuries. The patients were subject to a trial assessing the effectiveness of antibiotic treatment following removal of the foreign body. There was no significant difference between antibiotic and placebo (sterile saline).

Corneal Injuries↗
PubMed1988

Laboratory and clinical variables to predict outcome in hemolytic-uremic syndrome.

To develop a guide to the prognosis of children with hemolytic-uremic syndrome, we reviewed the medical records of 78 patients with this diagnosis seen at The Children's Hospital, Boston, from 1976 through 1986. Two outcome groups were defined as follows: a "good outcome" group, which contained 6 patients with no serious sequelae at hospital discharge, and a "bad outcome" group, which contained 12 patients who died, had chronic renal failure, or had central nervous system sequelae at hospital discharge. Differences between the two groups in routine laboratory tests available within 48 hours of admission were identified by bivariate analysis. Using serum calcium (less than or equal to 2 mmol/L) plus urine output (less than 0.4 mL/kg/h) over a 24-hour period as a test to predict outcome, we identified patients who died, had chronic renal failure, or had serious central nervous system sequelae, with 75% sensitivity, 98% specificity, and 90% positive predictive value.

Adolescent↗
PubMed1987

A comparative investigation of glycinebetaine and dimethylsulphoxide as liposome cryoprotectants.

The release of streptomycin from lecithin liposomes following a freeze-thaw cycle was used to measure the cryoprotective activities of glycinebetaine and dimethylsulphoxide (DMSO). At concentrations between 4 and 8% w/v in the external solution, glycinebetaine was superior to DMSO at freezing rates faster than 50 degrees C min-1. At lower rates their activities were similar, and drug loss ranged between 10 and 20% depending upon freezing rate and cryoprotectant concentration. The pattern of streptomycin loss when the concentrations of cryoprotectants inside and outside the liposome were varied indicated that glycinebetaine, in contrast to DMSO, does not diffuse across the liposome membrane. The activity of glycinebetaine was not impaired by the presence in the membrane of cholesterol or charged lipids.

Betaine↗
PubMed1987

Unique p24 epitope marker to identify multiple human immunodeficiency virus variants in blood from the same individuals.

The human immunodeficiency virus (HIV) was isolated from the blood of 192 of 410 seropositive individuals. Original isolations were made in peripheral blood mononuclear cell (PBMC) cultures, and only one-fifth of the HIV isolates could be adapted to replicate in continuous T-cell lines. Of the 192 HIV isolates, 42 had the characteristic p24 antigen marker of the acquired immunodeficiency syndrome-associated retrovirus type 2 strain of HIV (HIV ARV-2) and 150 resembled the human T-cell lymphotropic virus type III strain of HIV (HIV HTLV-III). Significantly, primary PBMC cultures from two patients yielded multiple variants. When these variants were exposed to continuous T-cell lines, only one of them continued to replicate. The remaining variants were lost and could not be reisolated following passage back into PBMC cultures. We conclude the following from these studies: PBMC cultures are more efficient at isolating HIV than continuous T-cell lines are; some patients harbor more than one genetic variant of HIV in the blood at the same time; and continuous T-cell lines are likely to yield only a portion of the HIV variants originally present in the blood.

Antigens, Viral↗
PubMed1986

Seroepidemiologic survey of captive Old-World primates for antibodies to human and simian retroviruses, and isolation of a lentivirus from sooty mangabeys (Cercocebus atys).

Sera from 526 Old-World monkeys and apes, representing 50 species and 20 genera and living in US zoos and vivaria, were screened for antibodies to HTLV-I, HTLV-III/LAV, and simian-AIDS retrovirus, type I (SRV-I). Sera were screened initially by ELISA, and ELISA-positive sera, as well as ELISA-negative sera from cage contacts, were further tested by Western blotting. A large number of false-positive and a small number of false-negative ELISA sera were identified. Although most true positive reactions were directed to a single retrovirus, a number of individuals from 4 species were positive for more than one retrovirus. Specific seroreactivity to HTLV-I was found in 39/526 (7%) animals of 15 species. True positive reactions to SRV-I were found in 21/516 (4%) animals, including talapoins and 2 species of macaques. Specific serologic reactions to HTLV-III/LAV were detected in 23/526 (4%) monkeys. Many of the HTLV-III/LAV seropositive animals were from one mixed-species zoo exhibit, containing sooty mangabeys, mandrills, Kolb's guenons, and talapoins. A type D virus was isolated from the blood of 3/10 SRV-I antibody-positive Tonkeana macaques, but from none of 11 seropositive talapoins. A lentivirus was isolated from the blood of 4/7 HTLV-III/LAV seropositive sooty mangabeys, but not from seropositive talapoins in the same exhibit or from 2 seropositive colobus from another zoo. The sooty mangabey lentivirus produced generalized lymphadenopathy, leukopenia, and decreased levels of T4 lymphocytes in 2 experimentally infected rhesus macaques.

Animals↗
PubMed1986

Treatment of metastatic colorectal cancer with hepatic artery combination chemotherapy.

Treatment of patients with hepatic metastases from colorectal cancer using hepatic artery floxuridine (FUDR) has been reported to induce high partial remission rates and perhaps prolonged survival. However, several investigators, including our own group, have obtained response rates of only 30%. Alkylating agents can increase the efficacy of antimetabolites. Based on clinical data and pharmacokinetic considerations the authors have combined FUDR with mitomycin C and carmustine (BCNU) by the arterial route. Thirty-six patients with hepatic metastases from colorectal cancer received FUDR 0.3 mg/kg/day 2 weeks of 4, mitomycin C 15 mg/M2 over 1 hour every 8 weeks, and BCNU 150 mg/M2 over 1 hour every 8 weeks--all via the hepatic artery using Infusaid pumps (Infusaid, Sharon, MA). The mitomycin C and BCNU were alternated monthly at the start of each FUDR cycle. The patient characteristics were as follows: 78% hepatomegaly, 44% also extrahepatic tumor, 42% prior systemic 5-fluorouracil. Combined partial and complete response rates were independent of prior chemotherapy: 71% if untreated, 67% with prior 5-fluorouracil. Median survival for the combined response/stable disease group was 13.7 months from the start of hepatic artery chemotherapy, and 4.5 months for the six nonresponders. Based on these data the authors have begun a randomized trial comparing single-agent FUDR to the FUDR, mitomycin C, BCNU combination.

Antineoplastic Combined Chemotherapy Protocols↗