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Biomedical subjects

R Goldstein

Publications and source records attributed to R Goldstein.

At least 55 records · Page 3Linked to original sources
PubMed1999

An epidemic of burkholderia cepacia transmitted between patients with and without cystic fibrosis.

Burkholderia cepacia is an important pathogen in cystic fibrosis (CF) and an infrequent cause of nosocomial infection in non-CF patients. This report describes a large hospital outbreak that appeared to involve both patient groups, a previously unrecognized phenomenon. Ribotype restriction fragment length polymorphism (RFLP) profiles and pulsed-field gel electrophoresis-resolved macrochromosomal RFLPs were analyzed, a ribotype-based phylogenic tree was constructed, and case-control and cohort studies were performed. A single dominant clone was found in both CF and non-CF groups. Phylogenic analysis suggests that it has evolved independently and that such highly transmissible strains can emerge rapidly and randomly. Acquisition risk in the CF patients was linked to hospitalization (odds ratio=5.47, P=.0158, confidence interval=1. 28-26.86) and was associated with significantly increased mortality rates. Infection control policies must now consider this threat of transmission between non-CF and CF patients.

Adolescent↗
PubMed1999

Persistence of human immunodeficiency virus in semen after adding indinavir to combination antiretroviral therapy.

Changes in human immunodeficiency virus (HIV) type 1 concentration and protease genotype were evaluated in semen specimens from 22 HIV-positive men before and 6 months after the addition of indinavir to dual nucleoside therapy. Seminal HIV was detected by polymerase chain reaction analysis for DNA or RNA for 59% of men before combination treatment and persisted at 6 months for 31% of the men who initially had seminal HIV detected (P = .026). The maximum levels of cell-free RNA, cell-associated RNA, and proviral DNA in semen before treatment and at 6 months were 400,000 and 10,000 copies/mL, 70,000 and 27,000 copies/mL, and 80,000 and 3,000 copies/mL, respectively. Three of the four men with persistent seminal DNA had plasma viral loads of > 10,000 copies/mL before treatment. One patient who became intolerant to indinavir had seminal HIV RNA detected by PCR analysis after 6 months. Although none of the cultures of semen specimens from the four men with PCR analysis-detectable seminal DNA after 6 months yielded HIV, indinavir resistance mutations were identified in a seminal leukocyte DNA specimen from one patient, and a second patient whose therapy was switched to saquinavir had different protease inhibitor resistance mutations in seminal and blood leukocyte DNA specimens. HIV-1 protease inhibitor resistance mutants may emerge in the semen of patients receiving combination therapy.

Anti-HIV Agents↗
PubMed1999

Natural history of fetuses with cleft lip.

The prospect of fetal surgery for cleft lip is predicated on our ability to accurately identify fetuses with clefts and exclude those that have associated anomalies. Prenatal ultrasound is currently the most appropriate means with which to do this. We reviewed the ultrasonographic data from two large perinatal referral institutions to determine the natural history of fetuses with cleft lip who may be candidates for fetal surgery. Forty fetuses had a cleft lip diagnosed prenatally by ultrasound. In this group, severe associated anomalies were common (30 of the 40) and multiple (23 of the 40) in a majority of fetuses. Life-threatening anomalies, such as central nervous system and cardiac anomalies, were the most common defects. As a result, many fetuses were aborted therapeutically or died in the perinatal period. Out of 12 surviving fetuses, only six had isolated clefts, and two surviving fetuses, diagnosed with isolated cleft lip, had no defect identified postnatally. This information has important implications for the perinatal management of fetuses with cleft lip and the potential role of fetal intervention.

Abnormalities, Multiple↗
PubMed1999

Minimal incidence of serum antibodies reactive with intact primary isolate virions in human immunodeficiency virus type 1-infected individuals.

Immunoglobulin G reactive with primary isolate virions was detected in 36% of serum samples from individuals infected with human immunodeficiency virus type 1. Of these individuals, serum samples from only 7% captured significant quantities of virus. Virion-specific antibody correlated with CD4 counts and, of more significance, primary isolate neutralization. Further dissection of this response should lead to the identification of antibodies and antigenic epitopes for vaccine purposes.

CD4 Lymphocyte Count↗
PubMed1999

A measure of limited joint motion and deformity correlates with HLA-DRB1 and DQB1 alleles in patients with rheumatoid arthritis.

OBJECTIVE: To assess factors associated with a poor outcome in rheumatoid arthritis (RA), a measure was developed of limited joint motion and deformity, a deformity index (DI), and correlated biochemical and genetic variables with the magnitude of the DI. METHODS: Forty patients were evaluated in a cross sectional study. Clinical measures included the DI and Health Assessment Questionnaire, and disease variables included the erythrocyte sedimentation rate, C reactive protein, rheumatoid factor, and HLA-DRB1 and DQB1 alleles. RESULTS: Significant correlations were noted between increasing DI and duration of RA and concentration of C reactive protein. Patients with a DQB1*301 allele or DR4 allele had a higher DI than those without, and a positive trend was noted between increasing DI and dose of DRB1 RA susceptibility alleles. The trend was lost when a non-linear regression technique was used to remove the effect attributable to C reactive protein, suggesting an interrelation between persistent inflammation and genetics in determining total joint damage. CONCLUSIONS: The DI may be useful to study interactions between genetic and inflammatory processes in rheumatoid disease progression.

Adult↗
PubMed1999

PARP alleles within the linked chromosomal region are associated with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by various autoantibodies that recognize autoantigens displayed on the surface of cells undergoing apoptosis. The genetic contribution to SLE susceptibility has been widely recognized. We previously reported evidence for linkage to SLE of the human chromosome 1q41-q42 region and have now narrowed it from 15 to 5 cM in an extended sample using multipoint linkage analysis. Candidate genes within this region include (a) PARP, poly(ADP-ribose) polymerase, encoding a zinc-finger DNA-binding protein that is involved in DNA repair and apoptosis; (b) TGFB2, encoding a transforming growth factor that regulates cellular interactions and responses; and (c) HLX1, encoding a homeobox protein that may regulate T-cell development. Using a multiallelic, transmission-disequilibrium test (TDT), we found overall skewing of transmission of PARP alleles to affected offspring in 124 families (P = 0.00008), preferential transmission of a PARP allele to affected offspring (P = 0.0003), and lack of transmission to unaffected offspring (P = 0.004). Similar TDT analyses of TGFB2 and HLX1 polymorphisms yielded no evidence for association with SLE. These results suggest that PARP may be (or is close to) the susceptibility gene within the chromosome 1q41-q42 region linked to SLE.

Alleles↗
PubMed1998

Liver and kidney transplantation for polycystic disease.

BACKGROUND: With the poor results of resective and fenestration procedures for polycystic liver disease (PCLD), we present the first series of patients receiving orthotopic liver transplantation for this condition. METHODS: Five of our six patients with PCLD had polycystic kidney disease also. Three of these five received combined organ transplants, while the other two required subsequent kidney transplants. RESULTS: Forty-eight and 52 months after orthotopic liver transplantation, all surviving patients had relief of their pain, distention, and anorexia. Two patients had succumbed to infectious complications and died at 15 and 24 months after transplant. CONCLUSIONS: We conclude that patients with PCLD can be transplanted safely for the relief of their distention and anorexia, with good results. Those patients with both PCLD and polycystic kidney disease who are not dialysis dependent can be managed for several years with isolated liver transplantation and then receive kidney transplantation if needed. Those who are dialysis dependent should receive combined liver-kidney transplantation. Unfortunately, patients with polycystic disease seem to be very susceptible to infectious complications after organ transplantation.

Adult↗
PubMed1998

Unsafe sex in men who have sex with both men and women.

The sexual behaviors of bisexually active men, defined as men having sex with a man and a woman in previous 6 months, were compared with men who had sex with men only. Differential sexual practices associated with HIV risk between the two groups of men, as well as in the bisexual men with their male and female partners, were evaluated. Cross-sectional analyses were performed on baseline data from a prospective cohort of 508 young gay men recruited from bars, college campuses, and a health center in Boston from 1993 to 1994. Odds ratios (OR) and 95% confidence intervals (CI) were calculated on categorical variables, and McNemar's chi2 was used to compare the behaviors of bisexual men with their male versus female sex partners. Six months before the interview, 47 (10%) men had male and female sex partners, and 383 men had only male sex partners during the past year or ever. Fifty-eight percent of the men in the study had a female sexual partner in their lifetime, and 18% during the past year. Bisexual men were more likely to have drinking problems as identified by the Michigan Alcoholism Screening Test (MAST; OR = 3.96, 95% CI = 1.54-10.20), and fewer male partners over their lifetime (mean +/- standard deviation [SD], 24+/-42; median, 7; versus mean +/- SD, 69+/-516; median, 12), although this difference was not statistically significant. The two groups had similar levels of unprotected anal intercourse (25.5% versus 29.5%); however, bisexual men were half as likely to have anal sex as homosexual men (OR = 0.50; 95% CI = 0.27-0.93). Bisexual men were three times as likely to have unprotected sex with their female partner as their male partner (OR = 3.0; 95% CI = 1.02-8.8). Stratified analysis revealed similar discordant behavior while sober (OR = 4.0), drinking (OR = 7.0), and while drinking with concurrent drug use (OR = 8.0). Among this cohort of men who have sex with men (MSM), a sizable proportion also had vaginal sex with female partners in the previous 6 months. Bisexually active men were more likely to have unprotected sex with their female partners compared with their male partners, potentially increasing the risk for HIV and other sexually transmitted diseases. Behavioral interventions directed toward MSM need to address bisexual behaviors.

Alcohol Drinking↗
PubMed1998

The social context of drinking, drug use, and unsafe sex in the Boston Young Men Study.

The objective of this study was to evaluate the relation between drinking, drug use, and unprotected anal intercourse in young men who have sex with men. A cross-sectional analysis of first-visit data from a prospective cohort of 508 young gay men recruited from 1993 through 1994 from bars, college campuses, and the Fenway Community Health Center in Boston was performed. The major outcome measures were any unprotected anal intercourse, after drinking and when sober, stratified by type of sexual partner (steady or nonsteady) during the previous 6 months and during the most recent sexual encounter. The average age of the cohort was 23.3 years; 77.6% were white, and 76.4% were in college. These young men had a median of 10.5 male sexual partners in their lifetimes, and 3 sexual partners in the previous 6 months before enrollment. One hundred and thirty-four (26%) reported unprotected anal intercourse during the previous 6 months. Individuals who had unprotected anal intercourse were more likely to have a drinking problem (odds ratio [OR] = 1.95; 95% confidence interval [CI] = 1.26-3.01) and drank more (20.4 ml/day versus 13.9 ml/day; p < or = 0.01), compared with individuals who did not engage in unprotected anal intercourse. Overall, men were significantly less likely to have unprotected anal intercourse after alcohol or drug use, based on a series of paired analysis (OR = 0.27; 95% CI = 0.15-0.48). However, when we stratified by type of sexual partner, men were significantly more likely to have unprotected anal intercourse with their nonsteady sexual partners after drinking than when sober (OR = 4.33; 95% CI = 1.37-13.7), but were significantly less likely to have unprotected anal intercourse with steady partners (OR = 0.27; 95% CI = 0.15-0.48). The patterns observed as already mentioned for drinking were also found for substance use in general. Men who were more likely to have unprotected anal intercourse after substance use were significantly more likely to have a drinking problem (OR = 7.65; 95% CI = 2.34-24.59). These results suggest that the role of alcohol and unsafe sex in young gay men is complex, with the role of situational factors of paramount importance. Alcohol and substance use interventions designed to reduce HIV risk need to specify the role of substance use in the sexual context to be successful.

Adult↗
PubMed1998

HPRT- mutant T cells in the peripheral blood and synovial tissue of patients with rheumatoid arthritis.

OBJECTIVE: To investigate the frequency and characteristics of hprt- mutant T lymphocytes in the peripheral blood and synovium of rheumatoid arthritis (RA) patients compared with controls, and to correlate these findings with disease parameters. METHODS: An hprt- T cell assay was performed on blood and synovial samples from 93 RA patients, 8 osteoarthritis (OA) patients, and 19 control subjects. T cell clones were studied by flow cytometry and evaluated for fibronectin adhesion. RESULTS: RA patients showed a 5-fold increase in the frequency of mutant T cells in the peripheral blood compared with that in control peripheral blood, and a further 10-fold increase in the mutant T cell frequency in synovial tissue. In OA patients, the synovium also had a significantly higher frequency of hprt- mutant T cells compared with the peripheral blood, but at a lower level than in the rheumatoid synovium. RA peripheral blood mutant T cell clones displayed elevated fibronectin adhesion and beta1 integrin expression, similar to that observed in the RA synovial T cell lines. CONCLUSION: The origin of the mutated T cells in the peripheral blood of these patients appears to be the inflamed synovium of RA, and to a lesser extent, of OA, where the cells are exposed to a mitogenic and genotoxic environment.

Adult↗
PubMed1998

Clinical correlates, serum autoantibodies and the role of the major histocompatibility complex in French Canadian and non-French Canadian Caucasians with SLE.

OBJECTIVE: To investigate the predisposing role of major histocompatibility complex (MHC) genes to autoantibody production and clinical manifestations comparing French Canadian and Non-French Canadian Caucasians with systemic lupus erythematosus (SLE) METHODS: Ninety-one Caucasian patients with SLE were studied. Clinical manifestations, autoantibody expression and HLA-A, B, (serology), DR, DQ and C4A gene deletion (restriction fragment length polymorphism [RFLP] typing) were determined. RESULTS: Photosensitivity was present in all SLE subjects with anti-Ro antibodies (P=0.001, RR=13.1, CI=1.8, 564). Photosensitivity was further associated with the HLA-A1, C4A gene deletion haplotype. More strikingly, C4A gene deletion was associated with anti-Ro (P=0.008, RR=4.6, CI=1.4, 16.2) and anti-La (P=0.02, RR=11.7, CI=1.4, 549) autoantibodies. This relationship was also significant for anti-Ro antibody in the French Canadian patients (P=0.01, RR=21.3, CI=1.7, 105.3). In contrast, anti-dsDNA autoantibodies were negatively associated with photosensitivity (P=0.02, RR=0.3, CI=0.07, 0.8) and correlated with HLA-DR15 (P=0.006, RR=4.2, CI=1.5, 12.8) and Dw2 (P=0.009, RR=3.9, CI=1.4, 11.9). CONCLUSION: C4A gene deletion has a previously unrecognized powerful association with anti-Ro and anti-La autoantibodies. These results support the concept of divergent MHC gene associations with autoantibody expression and emphasize the influence of ethnicity on the immunogenetic study of SLE.

Adult↗
PubMed1998

Evaluation of enalapril combined with diltiazem ER in patients with stage 3-4 essential hypertension.

Enalapril combined with an extended-release formulation of diltiazem was evaluated in a 12-week multicenter trial of 112 patients with Stages 3-4 essential hypertension. Patients were randomized to once daily therapy with enalapril 5 mg plus diltiazem ER 120 mg or 180 mg. Dosages could be titrated and other antihypertensive agents added for blood pressure control. Efficacy was assessed with sitting blood pressures at trough (24 hours postdose). Overall, there was a decrease of -21.7/-18.4 mmHg. Patients responding to enalapril/diltiazem ER alone had a reduction of -15.0/-16.3 mmHg. Of all patients, 70% achieved a trough sitting diastolic blood pressure of < 95 mmHg. Common drug-related adverse experiences were headache, dizziness, rash, and asthenia/fatigue. This once daily fixed-combination of enalapril/diltiazem ER was generally well tolerated and effective when given alone or with other antihypertensives in Stage 3-4 hypertension.

Adult↗