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Biomedical subjects

H Austin

Publications and source records attributed to H Austin.

At least 37 records · Page 2Linked to original sources
PubMed1999

Prospective study of barrier contraception for the prevention of sexually transmitted diseases: study design and general characteristics of the study group.

BACKGROUND AND OBJECTIVES: The AIDS epidemic has brought barrier contraceptives to the forefront of public health research. A comprehensive evaluation of the efficacy of barrier contraceptive use in preventing sexually transmitted diseases (STDs), including AIDS, is necessary to inform both potential users and public health policy makers. This study was undertaken to evaluate the efficacy of condoms and vaginal spermicide products, used alone or in combination, in preventing gonorrhea and chlamydia among women attending an STD clinic. GOAL OF THIS STUDY: To describe the general characteristics of the study group and its follow-up experience. STUDY DESIGN: Women who met the eligibility criteria were invited to participate. The initial visit included an interview, a behavioral intervention promoting barrier methods, a physical examination, and instructions to complete a sexual diary. Participants received free barrier contraceptives and returned for six monthly follow-up visits. DESIGN RESULTS: Participants (n = 1,122) were low income, single (74%) black (89%) women with a median age of 24. The behavioral intervention led to the use of barrier protection in more than 70% of reported acts of vaginal intercourse. Barriers were used consistently (100% of sexual acts) during 51% of the months of follow-up. A total of 148 cases of gonorrhea (28 per 1,000 months) and 122 cases of chlamydia infection (23 cases per 1,000 months) were diagnosed during follow-up. CONCLUSION: This study represents a practical solution to a complex set of design considerations. The study protocol was successful in promoting consistent and proper use of barrier methods.

Adult↗
PubMed1999

Correlates of herpes simplex virus seroprevalence among women attending a sexually transmitted disease clinic.

BACKGROUND: Infections by herpes simplex viruses type 1 (HSV-1) and type 2 (HSV-2) are common in the United States. Herpes simplex virus type 2 is transmitted sexually, and the prevalence of antibodies to HSV-2 has increased in recent years. GOALS OF THIS STUDY: The objective of the present study was to estimate the seroprevalence of HSV-1 and HSV-2 antibodies among women attending a sexually transmitted disease (STD) clinic and to evaluate factors associated with HSV-1 and HSV-2 seropositivity. STUDY DESIGN: The report describes a cross-sectional study conducted at an STD clinic. This study included 1,103 women between the ages of 18 and 35. Eighty-nine percent of the subjects were African Americans. The remaining subjects were white. RESULTS: The overall prevalence of HSV-1 and HSV-2 antibodies among study subjects was 72% and 64%, respectively. Both HSV-1 and HSV-2 seropositivity were related directly to age and were higher among African Americans than whites. The prevalence of HSV-2 antibodies also increased with the number of lifetime sexual partners, an early age at first coitus, a history of syphilis, and the absence of HSV-1 antibodies. Drug use and recent use of barrier contraception were unrelated to either HSV-1 or HSV-2. COMMENT: Despite efforts by the public health community to prevent AIDS by promoting safe sexual practices, the prevalence of HSV-2 seropositivity has increased in recent years. Increased numbers of partners and an early age at first coitus are important correlates of HSV-2 infection. Public health interventions to prevent HSV-2 infection should target teenagers. Women of reproductive age attending STD clinics may also comprise an important target for interventions to prevent perinatal herpes.

Adolescent↗
PubMed1999

Mechanical failure of the latex condom in a cohort of women at high STD risk.

BACKGROUND AND OBJECTIVES: Mechanical failure may reduce the efficacy of condoms. Little is known about frequency and determinants of condom failure in groups at high risk of sexually transmitted diseases (STD). GOAL: To measure condom breakage and slippage rates and evaluate potential determinants of failure among women attending a public STD clinic. STUDY DESIGN: Women attending an STD clinic participated in a 6-month prospective study of barrier contraception for the prevention of STD. They completed sexual diaries that were reviewed at monthly follow-up visits. No data were collected from the male partners. Baseline characteristics of the participants and time-dependent behaviors were evaluated as potential determinants of condom failure. RESULTS: Of 21,852 condoms used by 892 women, 500 broke during intercourse (2.3%) and 290 slipped (1.3%). Breakage was more common among young, black, single nulliparae who engaged in high-risk behavior. Slippage was more common among married women with children. Failure rates decreased with condom use, with coital frequency, and with use of spermicides. CONCLUSION: User characteristics and experience are determinants of breakage and slippage, which are often regarded only as the effect of product design flaws. Attention to modifiable determinants of failure may improve user counseling and product labeling.

Adolescent↗
PubMed1999

Recombinant human Dnase I (rhDNase) in patients with lupus nephritis.

Systemic lupus erythematosus (SLE) is characterized by the production of pathogenic autoantibodies to nucleoprotein antigens, including double-stranded DNA (dsDNA). The deposition of IgG dsDNA immune complexes in glomeruli is thought to be crucial for disease pathogenesis and complement activation. rhDNase catalyzes the hydrolysis of extracellular DNA and has been shown to delay the development of dsDNA antibodies, reduce proteinuria, and delay mortality in a lupus-prone murine model. We conducted a 40d, phase Ib, randomized, double-masked, placebo-controlled trial to determine the safety and pharmacokinetics of rhDNase, and to measure any changes in markers of disease activity in 17 patients with lupus nephritis. Patients were assigned to receive either: (1) 25 microg/kg rhDNase (n = 8); (2) 125 microg/kg rhDNase (n=6); or (3) placebo (n = 3) initial single intravenous (IV) dose followed by 10 subcutaneous (SC) doses. Skin biopsies performed on nine patients pre- and post-treatment were studied for immune complex deposition by immunofluorescence. Serum cytokine levels (sIL2-R, IL-6, IL-10, and TNF-alpha) were analyzed by ELISA. Cytokine secretion and antibody production were measured by ELISPOT analysis and ELISA. Serum hydrolytic activity of rhDNase was achieved after IV administration at 25 and 125 microg/kg, but not after SC administration at either dose. A t 1/2 of 3-4h was estimated from serum concentration profiles following IV administration. Serum dsDNA antibodies were unchanged (mean values: 33 IU/mL vs 39 IU/mL [pre- and post-treatment] for the 25 microg/kg group, and 74 IU/mL vs 74 IU/mL for the 125 microg/kg group, and 14 IU/mL vs 20 IU/mL for the placebo group). Complement levels (C3 and C4) and circulating immune complexes did not change appreciably during the treatment period for any of the groups. Serum cytokine profiles by ELISA revealed no changes in sIL-2 receptor, IL-6, IL-10, or TNF-alpha. There was no change in the number of cells secreting either Th1 or Th2 specific cytokines, nor in the number of cells secreting dsDNA antibodies. Neutralizing antibodies to rhDNase were not detected in serum at any time during the study. Immune complex deposition was unchanged in pre- and post-treatment in skin biopsies in both dose groups. rhDnase was well tolerated without significant adverse events following administration, and treatment was not associated with the development of neutralizing antibodies to rhDNase. Serum rhDNase concentrations capable of hydrolytic activity of rhDNase were achieved for a few hours following IV, but not SC administration. Serum markers of disease activity were unchanged during the study period.

Adult↗
PubMed1999

The relationship between polymorphisms in the endothelial cell nitric oxide synthase gene and the platelet GPIIIa gene with myocardial infarction and venous thromboembolism in African Americans.

STUDY OBJECTIVES: To determine whether the polymorphic dinucleotide repeats found in intron 4 of the endothelial cell nitric oxide synthase (ecNOS) gene and the platelet GPIIIa PLA(1)/A(2) polymorphism are associated with myocardial infarction (MI) and venous thromboembolism (VTE) in African Americans. Because these two genes may interact physiologically, the third objective was to determine if there was a relationship between the polymorphisms with respect to MI and VTE. DESIGN: A hospital-based case-control study. After informed consent was obtained, blood used for DNA extraction was drawn from the subjects. SETTING: The study was conducted in the Anticoagulant Clinic and the Cardiology Clinic at Grady Memorial Hospital in Atlanta Georgia. PATIENTS: Subjects were recruited from African-American patients with a reported history of MI (n = 110) or VTE (n = 91). Control subjects (n = 185) without a history of cardiovascular or venous disease were recruited from an outpatient clinic. MEASUREMENTS AND RESULTS: The 393 ecNOS allele was more common among MI cases (36%; p = 0.01) and VTE cases (35%; p = 0.04) than among control subjects (26%). There was no association between the GPIIIa genotypes and either MI or VTE. However, among the MI subjects, there was a strong association between the ecNOS 393/393 genotype and the Pl(A2) allele. It was also found that the frequency of the 393 allele was higher in African-American persons (0.26) compared with what has been reported for Australian Caucasians (0. 14) and Japanese (0.10). CONCLUSIONS: The 393 allele but not the Pl(A2) allele was significantly associated with both MI and VTE in African Americans. Homozygosity for the 393 allele was significantly associated to the diagnosis of MI prior to the age of 45. The combination of the 393 allele and a Pl(A2) allele was also highly associated with MI. The frequency of the 393 allele was significantly higher in African Americans than what has been reported for other populations. This study furthers not only extends the association of the 393 allele to VTE but has demonstrated an interaction with the Pl(A2) allele with respect to MI.

Adult↗
PubMed1998

Relation of three genetic traits to venous thrombosis in an African-American population.

A mutation in the Factor V gene (Factor V Leiden), a variant in the 5,10-methylenetetrahydrofolate reductase gene (MTHFR), and an insertion/deletion polymorphism of the angiotensin I-converting enzyme gene (ACE) may be related to abnormal blood clotting. The authors examined the associations between these genetic traits and venous thrombosis among African Americans. This study comprised 93 patients with venous thrombosis and 185 control subjects attending clinics at an urban, public hospital in Atlanta, Georgia, in 1995-1996. Subjects' DNA was extracted from blood and assayed for these genetic traits. Odds ratios were obtained from logistic regression and used as a measure of association between each genetic trait and venous thrombosis. Factor V Leiden was unrelated to venous thrombosis, but the mutation ws too rare among our African-American subjects to evaluate adequately its relation to venous thrombosis. The homozygous and heterozygous genotypes for the V allele of the MTHFR gene were unrelated to venous thrombosis (odds ratio = 0.9, 95% confidence interval 0.5-1.8). Subjects with the deletion/deletion ACE polymorphism experienced a moderate increase in venous thrombosis risk compared with persons with the other genotypes (odds ratio = 1.5, 95% confidence interval 0.9-2.6). However, women with this ACE genotype experienced no increased risk (odds ratio = 0.9, 95% confidence interval 0.5-1.9), whereas men with this genotype had nearly three times the risk (odds ratio = 2.8, 95% confidence interval 1.2-6.2; p value for interaction = 0.06). These data indicate that the prevalence of Factor V Leiden and the V allele of the MTHFR gene is low among African Americans. The D allele of the ACE gene is equally prevalent among African Americans and whites and may be related to venous thrombosis among African-American men.

Adolescent↗
PubMed1998

A pilot study of 2-chloro-2'-deoxyadenosine in the treatment of systemic lupus erythematosus-associated glomerulonephritis.

OBJECTIVE: To determine the safety and tolerability, as well as the clinical and immunologic effects, of 2-chloro-2'-deoxyadenosine (2-CdA) in patients with systemic lupus erythematosus-associated glomerulonephritis. METHODS: In a phase I study, 12 patients with proliferative lupus nephritis received 2-CdA either in weekly escalating intravenous treatments (0.15 mg/kg/week x 4, 0.1875 mg/kg/week x 4, 0.225 mg/kg/week x 4; n = 5) or in a continuous 7-day infusion (0.05 mg/kg/day; n = 7). Safety, renal improvement, and immunologic effects were evaluated for 12 months. RESULTS: Patients treated with 2-CdA showed peripheral lymphocyte depletion without a significant reduction in neutrophil, monocyte, or platelet numbers or hematocrit levels. Naive and memory T cells were decreased, as were lymphocytes with markers of early and late activation. Peripheral B cell depletion was not associated with significant decreases in serum immunoglobulin levels. Continuous infusion induced better clinical responses than weekly infusions, as evidenced by 1) the percentage of patients showing complete response (43% versus 0%), 2) the percentage with at least 50% reduction in proteinuria (43% versus 20%), 3) the percentage with at least a 50% reduction in urinary dysmorphic red cells (57% versus 0%), and 4) the percentage in whom cellular casts disappeared (43% versus 0%). Several infections occurred; these responded to standard antibiotic therapy. CONCLUSION: In this pilot study, 2-CdA was safely administered to 12 patients with lupus nephritis. It induced prolonged reductions in lymphocyte populations and may be efficacious in selected patients with lupus nephritis when administered as a continuous infusion.

Adult↗
PubMed1998

Prevalence of the prothrombin 20210 G-to-A variant in blacks: infants, patients with venous thrombosis, patients with myocardial infarction, and control subjects.

A genetic variation in the prothrombin gene is located in the 3-untranslated region at position 20210 where a G-->A transition occurs. The prevalence of the mutation is 1% to 2% in white populations, and the mutation is associated with an increased risk of venous thrombosis and myocardial infarction. We report the prevalence of the A allele in blacks at birth; in black control subjects with no history of heart attack, stroke, or blood clots; in black patients with venous thrombosis; and in black patients with myocardial infarction. Among 318 infants, the prevalence of the A allele was 0.2% (1 heterozygote), with an exact, one-sided upper 95% confidence limit of 0.7%. Among 185 control subjects the variant was absent, yielding an exact, one-sided upper 95% confidence limit of 0.8% for the A allele. The heterozygous genotype was found in 2 of 91 subjects with deep vein thrombosis and in none of 123 subjects with myocardial infarction. The very low prevalence of the A allele indicates that the prothrombin variant is not a major cause of venous thrombosis or myocardial infarction in blacks.

3' Untranslated Regions↗
PubMed1998

Surveillance for Creutzfeldt-Jakob disease among persons with hemophilia.

BACKGROUND: Although Creutzfeldt-Jakob disease (CJD) has been shown to be transmissible through blood components in rodent models, no human blood-to-blood transmission has been documented. If blood transmission were possible in humans, persons with hemophilia in the United States would be at higher risk of contracting CJD, because they receive large numbers of blood components. Nearly one-half of the hemophilia population contracted HIV in the 1980s, and many of these people have since died with neurologic complications. This study investigated whether some hemophilia patients with neurologic disorders may have died with CJD. STUDY DESIGN AND METHODS: Hemophilia treatment Centers across the United States were invited to participate in this retrospective surveillance study. The centers were asked to send any available formalin-fixed paraffin block brain samples from hemophilia decedents. Slides were prepared at the Centers for Disease Control and Prevention and reviewed by three expert neuropathologists. Two slides were stained for the prion protein at the request of one of the neuropathologists. RESULTS: Specimens from 24 decedents with genetic bleeding disorders were collected and reviewed.The panel found no evidence of CJD in any of the specimens. CONCLUSIONS: Although the study sample is small, these results support the growing evidence that CJD is not being transmitted in the nation's blood supply.

Adult↗
PubMed1998

Phase 1 trial of transforming growth factor beta 2 in chronic progressive MS.

Transforming growth factor (TGF)-beta2 is a pleiotropic cytokine associated with remissions in multiple sclerosis (MS) and amelioration of allergic encephalomyelitis. We assessed the safety of TGF-beta2 in an open-label trial of 11 patients with secondary progressive (SP) MS. Five patients had a reversible decline in the glomerular filtration rate. There was no change in expanded disability status scale or MRI lesions during treatment. Systemic TGF-beta2 may be associated with reversible nephrotoxicity, and further investigation of its therapeutic potential in MS should be performed with caution.

Adult↗
PubMed1998

Determination of serum creatinine prior to iodinated contrast media: is it necessary in all patients?

The risk of contrast-associated nephrotoxicity (CAN) is increased in the presence of preexisting renal disease. Although routine determination of serum creatinine (Cr) prior to imaging studies is the traditional method of assessing renal function, it is a costly and time-consuming practice. The purpose of this study was to investigate whether a patient survey could identify patients with a high likelihood of having normal Cr values and who, therefore, did not require serum testing. A survey was administered to 673 consecutive adult patients who were scheduled for contrast-enhanced computed tomography. Survey questions were designed to elicit a history of renal disorders as well as additional risk factors for CAN. Each patient had a Cr level determined within 48 hours prior to the injection of iodinated contrast media. Cr levels were assessed in the patients who gave negative responses to all survey questions. The degree to which positive responses to each survey question predicted elevated Cr levels was determined using the odds ratio (OR). Among the 673 respondents, 577 (85%) had normal Cr values (< or =1.3 mg/dL for women and < or =1.4 mg/dL for men). Completely negative responses to the questionnaire occurred in 191 (28%) of 673 of respondents, and 176 (92%) of these 191 had normal Cr values. A Cr cutoff value of 1.7 mg/dL is used in our department, i.e., patients with Cr values >1.7 mg/dL usually do not receive iodinated contrast media. Using this Cr cutoff value, 189 (99%) of 191 patients with negative responses had Cr values less than or equal to the cutoff value. The survey questions most strongly associated with elevated Cr values pertained to preexisting renal disease (OR 13.6), proteinuria (OR 8.7), prior kidney surgery (OR 8.1), hypertension (OR 5.4), gout (OR 4.6), and diabetes (OR 3.2). If the survey had been limited to these six questions, completely negative responses would have occurred in 450 (67%) of 673, 424 (94%) of these 450 would have normal Cr values, and 446 (99%) of 450 would have had Cr values at or below the 1.7 mg/dL cutoff for iodinated contrast. A completely negative response to a simple (six question) patient survey prior to iodinated contrast administration can identify a significant fraction of patients with normal Cr levels. Use of this survey could reduce by 67% the number of patients undergoing routine Cr determinations prior to imaging studies. This could reduce costs, decrease delays, and increase patient satisfaction associated with imaging studies.

Adult↗
PubMed1998

Psychiatric symptoms and an anterior cranial fossa meningioma.

We present a case of a patient admitted to a psychiatric hospital with psychotic symptoms and cognitive impairment but who was subsequently found to have an anterior interhemispheric falx meningioma. There must be a high index of suspicion for organic brain disease in patients over age 45 years presenting with psychotic symptoms and seizures for the first time.

Dementia↗
PubMed1998

Deletion polymorphism in the angiotensin-converting enzyme gene as a thrombophilic risk factor after hip arthroplasty.

Despite thromboprophylaxis, deep vein thrombosis is a common complication of major orthopedic surgery. Predisposing genetic risk factors are unknown. In this case-control study, we investigated the association of the insertion (I)/deletion (D) angiotensin converting enzyme (ACE) gene polymorphism, Factor V Leiden (R506Q) mutation, and 5,10 methylenetetrahydrofolate reductase (MTHFR) gene polymorphism with post-operative venous thrombosis in 85 patients who underwent elective total hip arthroplasty. The odds of a thrombotic event following hip surgery among subjects with the DD genotype of the ACE gene was increased more than 10-fold compared to subjects with the II genotype (odds ratio 11.7 [95% confidence interval 2.3-84.5]); it was increased 5-fold in subjects with the ID genotype compared to the II genotype (odds ratio 5.0 [95% confidence interval 1.1-34.9]). Mean plasma ACE level in control subjects not on ACE inhibitors at the time of study (n=43) was lowest in persons homozygous for the I allele (18.9+/-7.95 U/l), intermediate in patients with the ID genotype (31.6+/-10.8 U/l) and highest in subjects homozygous for the D allele (44.0+/-7.14 U/l). Mean plasma ACE level among cases was higher (33.0 U/l, n=25) than among controls (29.4 U/l, n=43) but this difference was not statistically significant. Neither the Factor V Leiden mutation nor MTHFR gene polymorphism increased the risk of thrombosis following hip replacement. These results demonstrate that the I/D ACE gene polymorphism is a potent risk factor for thrombosis in subjects undergoing total hip arthroplasty.

Activated Protein C Resistance↗
PubMed1997

Estimating a relative risk across sparse case-control and follow-up studies: a method for meta-analysis.

Meta-analysis is the quantitative technique of combining results from different studies. There is a variety of procedures available for combining effect measures across epidemiologic studies. None of these methods provides an overall effect estimate when the data are sparse within studies and come from different study designs. In this paper we discuss the statistical relations between case-control studies and two types of follow-up studies. We use these relations to develop an exact methodology for combining results across study designs. We also use these relations to derive Mantel-Haenszel type formulae for summarizing results across studies. We illustrate these techniques with data pertaining to breast implants and connective tissue disease.

Breast Implants↗
PubMed1997

A case-control study of lung cancer at a foundry and two engine plants.

A nested case-control study of lung cancer was conducted among workers at an iron foundry and two engine manufacturing plants whose lung cancer mortality rates were slightly higher than expected. The study included 231 lung cancer cases and 408 controls for whom complete work histories were obtained. There was no association between usual plant of employment and lung cancer mortality. The odds ratio for persons employed for 20 or more years in the foundry compared with persons employed in the engine plants was 0.90 (95% confidence interval: 0.55, 1.5). Long-term employment as an engine plant worker was associated with odds ratios slightly, but not statistically significantly, below unity. In the foundry, only usual employment in the material handling departmental group and any employment in the quality control departmental group were statistically significantly directly related to lung cancer risk. However, the number of subjects so employed was small and there was no dose-response relation between length of employment in these departmental groups and lung cancer risk. Cases were less frequently employed than were controls in engine plant machining and assembly jobs and departments. It is concluded that employment in this facility was either unrelated, or only weakly related, to lung cancer risk.

Carcinogens↗
PubMed1997

Environmental tobacco smoke and lung cancer mortality in the American Cancer Society's Cancer Prevention Study. II.

Environmental tobacco smoke (ETS) has been classified as a human lung carcinogen by the United States Environmental Protection Agency (EPA), based both on the chemical similarity of sidestream and mainstream smoke and on slightly higher lung cancer risk in never-smokers whose spouses smoke compared with those married to nonsmokers. We evaluated the relation between ETS and lung cancer prospectively in the US, among 114,286 female and 19,549 male never-smokers, married to smokers, compared with about 77,000 female and 77,000 male never-smokers whose spouses did not smoke. Multivariate analyses, based on 247 lung cancer deaths, controlled for age, race, diet, and occupation. Dose-response analyses were restricted to 92,222 women whose husbands provided complete information on cigarette smoking and date of marriage. Lung cancer death rates, adjusted for other factors, were 20 percent higher among women whose husbands ever smoked during the current marriage than among those married to never-smokers (relative risk [RR] = 1.2, 95 percent confidence interval [CI] = 0.8-1.6). For never-smoking men whose wives smoked, the RR was 1.1 (CI = 0.6-1.8). Risk among women was similar or higher when the husband continued to smoke (RR = 1.2, CI = 0.8-1.8), or smoked 40 or more cigarettes per day (RR = 1.9, CI = 1.0-3.6), but did not increase with years of marriage to a smoker. Most CIs included the null. Although generally not statistically significant, these results agree with the EPA summary estimate that spousal smoking increases lung cancer risk by about 20 percent in never-smoking women. Even large prospective studies have limited statistical power to measure precisely the risk from ETS.

Adult↗