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Biomedical subjects

C Ahn

Publications and source records attributed to C Ahn.

At least 19 recordsLinked to original sources

Risk factors for new atherothrombotic brain infarction in 664 older men and 1,488 older women.

The relation between obesity and new ABI is also unclear. The Framingham Study found that relative weight was not a risk factor for new ABI in older men but was a weak risk factor for new ABI in older women. Barrett-Connor and Khaw found no association between body mass index and new ABI in older men or women. The present study showed that obesity was not a risk factor for new ABI in older men. Obesity was a risk factor for new ABI in older women by univariate analysis but not by multivariate analysis. However, because obesity is associated with other risk factors for ABI and new coronary events, we would try to lower weight in obese older men and women.

Age Factors

Polygenic inheritance of Tourette syndrome, stuttering, attention deficit hyperactivity, conduct, and oppositional defiant disorder: the additive and subtractive effect of the three dopaminergic genes--DRD2, D beta H, and DAT1.

Polymorphisms of three different dopaminergic genes, dopamine D2 receptor (DRD2), dopamine beta-hydroxylase (D beta H), and dopamine transporter (DAT1), were examined in Tourette syndrome (TS) probands, their relatives, and controls. Each gene individually showed a significant correlation with various behavioral variables in these subjects. The additive and substractive effects of the three genes were examined by genotyping all three genes in the same set of subjects. For 9 of 20 TS associated comorbid behaviors there was a significant linear association between the degree of loading for markers of three genes and the mean behavior scores. The behavior variables showing the significant associations were, in order attention deficit hyperactivity disorder (ADHD), stuttering oppositional defiant, tics, conduct, obsessive-compulsive, mania, alcohol abuse and general anxiety-behaviors that constitute the most overt clinical aspects of TS. For 16 of the 20 behavior scores there was a linear progressive decrease in the mean score with progressively lesser loading for the three gene markers. These results suggest that TS, ADHD, stuttering oppositional defiant and conduct disorder, and other behaviors associated with TS, are polygenic, due in part to these three dopaminergic genes, and that the genetics of other polygenic psychiatric disorders may be deciphered using this technique.

Adolescent

Endothelial area as a prognostic indicator for invasive breast carcinoma.

BACKGROUND: Vascular enumeration using antibodies to Factor VIII has been reported to be an independent prognostic indicator of invasive breast carcinoma. METHODS: To eliminate potential subjectivity in distinguishing between individual vessels, especially in areas of tangled capillaries, total endothelial area (EA) was assessed using a Samba 4000 image analyzer. One hundred seventy-eight invasive breast carcinomas (Stage 1 and 2, mean follow-up: 71 months) were immumostained for the presence of CD34, the human hematopoietic progenitor cell antigen also present in endothelium, and EA was quantitated within 5 adjacent 20X fields (0.74 mm2). Additionally, these same vessels were manually counted from the image analyzer. Manual counts were also made from a photomicrograph representative of a single 10X field (1.06 mm2). RESULTS: High grade carcinomas contained greater endothelial area than low grade carcinomas (P = 0.0001). Endothelial area was prognostically significant (P = 0.004) in univariate analysis of disease-free survival (DFS) and overall survival (OS), as were stage of disease, tumor size, and combined histologic grade (P < or = 0.024). Manual vessel counts from the monitor were significant for OS only. Manual vessel counts from photomicrographs showed no statistically significant association with DFS or OS. In multivariate analysis, EA, but not vessel enumeration, remained as an independent predictor for OS (lymph node negative patients only, n = 87) and for DFS (lymph node positive patients only, n = 91). For the entire group of patients (lymph node negative and lymph node positive) independent predictors of DFS and OS were tumor grade and size (P < or = 0.006). CONCLUSIONS: Of the three methods used to evaluate tumor angiogenesis, total endothelial area, as objectively evaluated by image analysis, was the only independent prognostic indicator for OS for patients with lymph node negative invasive breast carcinoma.

Adult

Risk factors for new coronary events in a large cohort of very elderly patients with and without coronary artery disease.

Independent risk factors for new coronary events in older men include age, prior coronary artery disease, cigarette smoking, systemic hypertension, diabetes mellitus, serum total cholesterol, and serum high-density lipoprotein cholesterol (inverse association). Independent risk factors for new coronary events in older women include age, prior coronary artery disease, cigarette smoking, systemic hypertension, diabetes mellitus, serum total cholesterol, serum high-density lipoprotein cholesterol (inverse association), and serum triglycerides (weak association).

Aged

Correlation of paroxysmal supraventricular tachycardia, atrial fibrillation, and sinus rhythm with incidences of new thromboembolic stroke in 1476 old-old patients.

The relationship between supraventricular tachycardia and the incidence of thromboembolic stroke has not been previously reported. We investigated in a prospective study the incidence of new thromboembolic stroke in 1476 patients, mean age 81 years, with atrial fibrillation, paroxysmal supraventricular tachycardia, or sinus rhythm detected by 24-hour ambulatory electrocardiograms. New thromboembolic stroke developed at 31-month follow-up in 87 of 201 patients (43%) with atrial fibrillation, at 43-month follow-up in 84 of 493 patients (17%) with paroxysmal supraventricular tachycardia, and at 45-month follow-up in 143 of 782 patients (18%) with sinus rhythm (p < 0.0001 comparing atrial fibrillation with paroxysmal supraventricular tachycardia or sinus rhythm). Kaplan-Meier survival curves showed a higher significance of thromboembolic stroke in patients with atrial fibrillation, compared to patients with paroxysmal supraventricular tachycardia or sinus rhythm (log-rank: p < 0.0001). Multivariate Cox regression model showed that independent significant predictors of thromboembolic stroke were: a) atrial fibrillation (relative risk = 3.31); b) prior thromboembolic stroke (relative risk = 2.85); c) sex (relative risk for women = 0.75); and d) age (relative risk = 1.02). These data show that atrial fibrillation is an independent predictor of thromboembolic stroke in elderly patients, and that paroxysmal supraventricular tachycardia is not associated with thromboembolic stroke.

Aged

Delayed primary repair of intrathoracic esophageal perforation: is it safe?

The management of intrathoracic esophageal perforation with delayed diagnosis is a subject of controversy. Because of the obvious advantages of primary repair as a simple single-stage operation, this technique was preferentially used to treat 18 of 22 consecutive patients with esophageal perforation. These patients were stratified into three groups according to the time interval between perforation and repair: group A, less than 6 hours, five patients (28%); group B, 6 to 24 hours, six patients (33%); and group C, more than 24 hours, seven patients (39%). Group A patients were older (p < 0.05) and group B had fewer iatrogenic perforations (B, 17%; A, 80%; C, 57%, p < 0.1). Additional tissue was used to buttress the repair site in all three groups (A, 3/5 patients, 60%; B, 4/6 patients, 67%; C, 6/7 patients, 86%; p = not significant). In seven patients (39%), a fundic wrap was used to reinforce the site of primary repair. The outcomes of the three groups were analyzed. Group A had the lowest proportion of postoperative leaks (A, 0/4 patients, 0%; B, 4/6 patients, 67%; C, 5/6 patients, 83%; p < 0.05) and postoperative morbidity (A, 2/5 patients, 40%; B, 6/6 patients, 100%; C, 6/7 patients, 86%; p < 0.1). However the increased incidence of leak and morbidity did not lead to an increase in mortality. One death occurred in each group, with an overall mortality of 17% (A, 1/5 patients, 20%; B, 1/6 patients, 17%; C, 1/7 patients, 14%; p = not significant). We conclude that in the era of advanced intensive care capabilities, primary repair of intrathoracic esophageal perforation can be safely accomplished in most patients regardless of the time interval between perforation and operation. Leakage at the suture site is common unless primary repair is carried out without delay. Postoperative leakage, however, is usually inconsequential and does not necessarily result in an adverse outcome.

Aged

Cost and outcome of osteocutaneous free-tissue transfer versus pedicled soft-tissue reconstruction for composite mandibular defects.

Thirty-nine patients underwent reconstruction of composite mandibular defects following resection for squamous cell carcinoma. Thirty-four underwent immediate reconstruction, while 5 were reconstructed secondarily. Twenty-one received soft-tissue reconstruction only with a pectoralis major myocutaneous flap, 14 underwent osteocutaneous free-tissue transfer, and 4 received a reconstruction plate with free-tissue transfer for soft-tissue coverage. The mandibular defects in the pectoralis major myocutaneous flap group tended to be posterolateral, while free-tissue transfer defects were more severe, usually involving the anterior mandible. Length of surgery and duration of intensive care unit care were significantly longer for free-tissue transfer patients, while flap complications were more common in the pectoralis major myocutaneous flap patients. Facial appearance scores were higher for the free-tissue transfer group by both patient and physician assessment. Social function, speech, and oral function did not differ significantly. Patients reconstructed secondarily with free-tissue transfer reported significant improvement in appearance, oral continence, and social function, with little change in speech intelligibility, deglutition, or diet tolerance. The cost of the main hospitalization was significantly higher in the free-tissue transfer group than in the pectoralis major myocutaneous flap group, although when the costs of subsequent hospitalizations are included, the difference in total cost narrows. Despite more adverse defects, free-tissue transfer provided more predictable aesthetic results and expeditious return to normal social function than did pectoralis major myocutaneous flap reconstruction. The fiscal impact of these complex reconstructions is, however, significant. Cost-containment issues are presented and recommendations are made.

Aged

Prevalence of atrial fibrillation and association of atrial fibrillation with prior and new thromboembolic stroke in older patients.

OBJECTIVE: To correlate atrial fibrillation with the incidence of new thromboembolic (TE) stroke in older patients with and without prior TE stroke. DESIGN: In a prospective study of 2101 older patients, electrocardiograms showed that atrial fibrillation was present in 283 patients (13%). At 42-month mean follow-up, atrial fibrillation was associated with the incidence of new TE stroke in patients with and without prior TE stroke. SETTING: A large long-term health care facility where 2101 older patients were studied. PATIENTS: The 2101 patients included 1451 women and 650 men, mean age 81 +/- 8 years (range 60 to 103). MEASUREMENTS AND MAIN RESULTS: Atrial fibrillation was present in 283 of 2101 patients (13%). The mean age was 84 +/- 7 years in patients with atrial fibrillation and 81 +/- 8 years in patients with sinus rhythm (P = .0001). The prevalence of atrial fibrillation was 5% in patients aged 60 to 70 years, 14% in patients aged 71 to 80 years, 13% in patients aged 81 to 90 years, and 22% in patients aged 91 to 103 years (P < .0001). Mean follow-up was 31 +/- 18 months in patients with atrial fibrillation and 44 +/- 27 months in patients with sinus rhythm (P = .0001). Previous TE stroke occurred in 123 of 283 patients (43%) with atrial fibrillation and in 431 of 1818 patients (24%) with sinus rhythm (P < .0001). New TE stroke occurred in 131 of 283 patients (46%) with atrial fibrillation and in 303 of 1818 patients (17%) with sinus rhythm (P < .0001). The log-rank test showed that patients with atrial fibrillation had a significantly higher probability of developing new TE stroke than those with sinus rhythm (P < .0001). The multivariate Cox regression model showed that independent risk factors for new TE stroke were male sex (relative risk = 1.3), prior TE stroke (relative risk = 3.1), and atrial fibrillation (relative risk = 3.3). CONCLUSIONS: Atrial fibrillation, prior TE stroke, and male sex are independent risk factors for the development of new TE stroke in older patients.

Age Factors

Utilization of the leucocin A export system in Leuconostoc gelidum for production of a Lactobacillus bacteriocin.

The lactacin F complex, composed of LafA and LafX peptides, is produced by Lactobacillus johnsonii VPI 11088 (ATCC 11506) and is active against various lactobacilli and Enterococcus faecalis. The genetic determinants encoding the lactacin F peptides, LafA and LafX, are organized in a chromosomal operon comprised of genes lafA, lafX, and ORFZ. The lactacin F operon was introduced into Leuconostoc (Lc.) gelidum UAL187-22 which produces leucocin A. Leucocin A, a plasmid-encoded bacteriocin, inhibits E. faecalis, Listeria monocytogenes, and other lactic acid bacteria. The culture supernatant of the Leuconostoc transformant containing the lactacin F operon inhibited both lactacin F-and leucocin A-sensitive indicators. Concurrent expression of both bacteriocins did not alter the production of native leucocin A. Additive inhibitory effects due to the presence of both bacteriocins were not observed. An isogenic derivative of UAL187-22, which has lost the leucocin-encoding plasmid, was unable to produce active lactacin F when transformed with the appropriate recombinant plasmid. The ability of Lc. gelidum UAL187-22 to produce lactacin F demonstrates that the export system for leucocin A is capable of producing both bacteriocins simultaneously.

Amino Acid Sequence

Estimation of a common odds ratio under binary cluster sampling.

We present results from a simulation study for the estimation of a common odds ratio in multiple 2 x 2 tables when the data are correlated within clusters. We model the correlation of the data by the beta-binomial distribution. Through a simulation study, we compare the Mantel-Haenszel estimator with Rao and Scott's estimator in terms of their biases, observed variances, relative efficiencies of their variances and 95 per cent coverage proportions. We limit the simulation study to the case where there are the same number of subjects in each cluster and the same number of observations in each row of each stratum. When rho = 0, we recommend use of the Mantel-Haenszel estimator gamma MH with an unadjusted variance and Rao and Scott's estimator gamma RSP with a pooled design effect. In general, when rho > 0, we recommend the Mantel-Haenszel estimator gamma MH with an adjusted variance and Rao and Scott's estimator gamma RSP with a pooled design effect.

Bias

Phase I study of mitomycin C and menadione in advanced solid tumors.

A phase I study of mitomycin C with menadione (2-methyl-1,4-naphthoquinone, a vitamin K analogue which lowers intracellular pools of reduced glutathione) was designed as an approach to overcoming tumor cell resistance to alkylating agent chemotherapy. Patients with refractory solid tumors (n = 51) were treated with a 48-h continuous intravenous infusion of menadione followed by a bolus intravenous dose of mitomycin C at the completion of the menadione infusion. Initial menadione doses of 8.0 and 4.0 g/m2 over 48 h were associated with hemolysis, so subsequent dose levels of menadione ranged from 1.0 to 3.0 g/m2 with mitomycin C from 5 to 20 mg/m2. All three patients treated with menadione at 8.0 g/m2 and the single patient treated at 4.0 g/m2 with mitomycin C at 5 mg/m2 developed clinically significant hemolysis despite the presence of red blood cell glucose-6-phosphate dehydrogenase. Subsequently, a revised escalation scheme for menadione was used, and all patients tolerated menadione doses of 1-2.5 g/m2 over 48 h with mitomycin C doses up to 20 mg/m2. Since the 3.0 g/m2 dose of menadione was associated with mild hemolysis in three of four patients, the maximum tolerated dose of menadione was established at 2.5 g/m2. All of the mitomycin dose levels were tolerated without unexpected toxicities attributable to the combination. Prolonged infusions of menadione at doses which have been associated with lowering of intracellular glutathione pools in short-term exposure are limited by dose-dependent hemolysis, probably due to depletion of erythrocyte glutathione by menadione-related redox cycling. There was no detectable deleterious effect of pre-exposure to menadione on mitomycin C tolerance. We recommend a combination of menadione at 2.5 g/m2 as a continuous intravenous infusion and mitomycin C at 15 mg/m2 for further study in solid tumors, for which treatment with single-agent mitomycin C is appropriate.

Adult

Mitomycin C and menadione for the treatment of lung cancer: a phase II trial.

A phase II trial of menadione [2.5 gm/m2 as a continuous intravenous (i.v.) infusion over 48 hours] followed by mitomycin C (10-20 mg/m2 i.v. bolus) administered every 4 to 6 weeks was performed in 23 patients with advanced lung cancer. Menadione, a vitamin K analog which lowers intracellular pools of reduced glutathione (GSH), was combined with mitomycin C in an attempt to overcome thiol-mediated resistance to alkylating agent chemotherapy. The median age of patients entered on this trial was 62 years; performance status ranged from 60-90%. Two of the 23 patients (9%; 95% confidence interval, 1% to 28%) had objective responses lasting 3.5 months and 13 months respectively, while 4 additional patients developed short unconfirmed responses (lacking follow-up response data to estimate response duration). Median survival for all patients was 5.5 months. Treatment with mitomycin C and menadione was well tolerated except for hematologic toxicity and cardiac events of unclear relationship to the study drugs. Thirty-one percent of treatment courses were complicated by grade 3 or 4 hematologic toxicity including one episode of hemolytic anemia. One patient developed interstitial pneumonitis. Two patients developed a decrease in left ventricular ejection fraction: one patient remained asymptomatic, but the other patient developed congestive heart failure. Although only 9% of patients had confirmed objective responses, 28% (5 of 18) of the patients with non-small cell lung cancer demonstrated biological activity (tumor regression fulfilling the criteria for objective response on a single occasion but 3 patients lacking a follow-up measurement to document response duration) to this combination of mitomycin C and menadione. We conclude that further studies of chemomodulation in non-small cell lung cancer are appropriate.

Adult

Mitomycin C and menadione for the treatment of advanced gastrointestinal cancers: a phase II trial.

A phase II trial of menadione (2.5 g/m2 as a continuous intravenous infusion over 48 h) followed by mitomycin C (10-20 mg/m2 i.v. bolus) administered every 4-6 weeks was performed in 43 patients with advanced gastrointestinal cancer. Menadione, a vitamin K analog that lowers intracellular pools of reduced glutathione, was combined with mitomycin C in an attempt to overcome thiol-mediated resistance to alkylating-agent chemotherapy. The median age of patients entered on this trial was 58 years; performance status ranged from 60%-100%. None of the 43 evaluable patients obtained an objective response to this combination regimen. Median survival was 6.6 months. Treatment with menadione and mitomycin C was reasonably well tolerated except for hematological toxicity. A total of 27% of treatment courses were complicated by grade 3 or 4 hematological toxicity including one episode of hemolytic anemia and one episode of hemolytic uremic syndrome. One patient developed irreversible interstitial pneumonitis, and 1 patient had an asymptomatic decrease in the left-ventricular ejection fraction. Despite preclinical evidence indicating that menadione pretreatment enhances the cytotoxicity of mitomycin C, our study documents the resistance of advanced gastrointestinal cancers, particularly colorectal cancer, to mitomycin C modulated by menadione.

Adult