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Biomedical subjects

Gary Koch

Publications and source records attributed to Gary Koch.

12 recordsLinked to original sources
PubMed2005

Porphyromonas gingivalis bacteremia induces coronary and aortic atherosclerosis in normocholesterolemic and hypercholesterolemic pigs.

OBJECTIVES: The aim of this study was to determine whether recurrent intravenous injections with Porphyromonas gingivalis (P gingivalis), mimicking periodontitis-associated bacteremia, promotes coronary artery and aortic atherosclerosis in pigs. METHODS AND RESULTS: Pigs (n=36) fed low- or high-fat chow were divided into P gingivalis-sensitized and P gingivalis-challenged groups or P gingivalis-sensitized controls and saline-treated controls. Pigs were sensitized with 10(9) killed P gingivalis subcutaneously. Four weeks later all sensitized pigs in the group to be challenged started intravenous injections thrice weekly for 5 months with 10(6) to 10(7) colony forming units of P gingivalis while controls received saline. Anti-P gingivalis antibody, serum cholesterol, and complete blood counts were assayed monthly. Pigs were euthanized 2 weeks after the last injection, and coronary arteries and aortas were analyzed by histomorphometry and immunohistochemistry. Anti-P gingivalis antibody was increased by P gingivalis exposure. P gingivalis-challenged pigs developed a significantly greater amount of coronary and aortic atherosclerosis than controls in the normocholesterolemic group and nearly significant in the hypercholesterolemic group. P gingivalis was detected by polymerase chain reaction in arteries from most (94%, 16 of 17) P gingivalis-challenged pigs but not controls. CONCLUSIONS: Recurrent P gingivalis bacteremia induces aortic and coronary lesions consistent with atherosclerosis in normocholesterolemic pigs and increases aortic and coronary atherosclerosis in hypercholesterolemic pigs.

Animals↗
PubMed2005

Impact of maternal-fetal surgery for myelomeningocele on the progression of ventriculomegaly in utero.

OBJECTIVE: Intrauterine myelomeningocele (MMC) repair decreases hindbrain herniation and the need for postnatal ventriculoperitoneal shunting. We examined the impact of intrauterine repair on the progression of ventriculomegaly in utero. STUDY DESIGN: Fetuses with MMC were identified through computerized databases from June 1988 to April 2003. A retrospective cohort design was used to evaluate the impact of intrauterine repair on ventricular progression with a multivariate linear regression model that included baseline ventricle measurement, gestational age, level of lesion, and gender. RESULTS: Fourteen fetuses with intrauterine repair and 39 fetuses with postnatal repair were identified. The natural history of progression of ventricular diameter increased in a linear fashion throughout gestation (0.57 mm/week). After adjusting for confounding variables, no transient or sustained difference was observed in the rate progression of ventriculomegaly between intrauterine and postnatal repair (0.27 +/- 0.35 mm/week; P=.45). CONCLUSION: Intrauterine MMC repair does not impact the progression of ventriculomegaly.

Cerebral Ventricles↗
PubMed2004

The short-term effect of interdisciplinary medication review on function and cost in ambulatory elderly people.

OBJECTIVES: To determine whether a medication review by a specialized team would promote regimen changes in elders taking multiple medications and to measure the effect of regimen changes on monthly cost and functioning. DESIGN: A randomized-controlled trial. SETTING: Health center ambulatory clinic. PARTICIPANTS: Community-dwelling older adults taking five or more medications were assessed at baseline and 6 weeks. A medication-change intervention group of 57 elders was compared with a control group of 76 elder adults. INTERVENTION: The primary intervention was a comprehensive review and recommended modification of a patient's medication regimen. Changes were endorsed by each patient's primary physician and discussed with each patient. MEASUREMENTS: Measures were the Timed Manual Performance Test, Physical Performance Test, Functional Reach Assessment, subtests from the Wechsler Adult Intelligence Scale, a modified Randt Memory Test, the Center for Epidemiological Studies-Depression Scale, the Self-Rating Anxiety Scale, and the Rand 36-item Health Survey 1.0. Comorbidity was determined using the International Classification of Diseases, Ninth Revision, Clinical Modification. Medication usage was determined using brown bag review. RESULTS: Intervention subjects decreased their medications by an average of 1.5 drugs. No differences in functioning were observed between groups. Intervention subjects saved an average $26.92 per month in wholesale medication costs; control subjects saved $6.75 per month (P<.006). CONCLUSION: Although the intervention significantly reduced the medications taken and monthly cost, most patients were resistant to reducing medications to the recommended level. Further study is needed to understand patient resistance to reducing adverse polypharmacy and to devise better strategies for addressing this important problem in geriatric health. Greater focus on prescriber behavior is recommended.

Aged↗
PubMed2004

Retention of primary care physicians in rural health professional shortage areas.

OBJECTIVES: We tested the assumption that average job retention duration is shorter for physicians in rural health professional shortage areas (HPSAs) than for physicians in rural non-HPSAs. METHODS: In 1991, we surveyed nationally representative samples of primary care physicians who recently had moved to rural HPSAs and non-HPSAs who were without service obligations. We resurveyed these physicians in 1996 and 1997 to learn of any job changes. RESULTS: Physicians in rural HPSAs (n=308) demonstrated retention similar to that of the non-HPSA cohort (n=197) (hazard ratio for leaving=1.28; 95% confidence interval=0.97, 1.69; P=.08), even with adjustments for group demographic differences (P=.24). CONCLUSIONS: Average retention duration for generalist physicians in rural HPSAs is identical to or slightly shorter than for those in rural non-HPSAs. Poor recruitment is likely to be the principal dynamic underlying local rural shortages.

Chi-Square Distribution↗
PubMed2003

Atypical and conventional antipsychotic drugs in treatment-naive first-episode schizophrenia: a 52-week randomized trial of clozapine vs chlorpromazine.

The purported advantages of second-generation or "atypical" antipsychotics relative to first-generation antipsychotics have not been examined in patients with a first episode of schizophrenia. This flexible-dose study examined efficacy and safety in a randomized, double-blind, 52-week trial, comparing chlorpromazine (CPZ) and clozapine (CLZ) in treatment naive patients experiencing their first episode of schizophrenia. In all, 160 inpatients with first-episode schizophrenia or schizophreniform disorder were randomized to CPZ or CLZ and followed them for 52 weeks or until dropout. The primary efficacy measure was time to first remission and proportion of time remaining in remission. The analysis was supplemented by comparisons on a profile of clinical symptoms and side effects. Of these first-episode patients, 80% achieved remission within 1 year (79% CPZ, 81% CLZ). The Kaplan-Meier estimated median time to first remission was 8 weeks for CLZ vs 12 weeks for CPZ (chi(2)(1)=5.56, p=0.02). Both the rate of first achieving remission and the odds for being in remission during the trial were almost doubled for the CLZ group in comparison with the CPZ group. At 12 weeks, CLZ was superior on many rating scale measures of symptom severity while CPZ was not superior on any. These symptom differences remained significant when controlling for EPS differences. By 52 weeks many of the symptom differences between groups were no longer significantly different. Generally, CLZ produced fewer side effects than CPZ, particularly extrapyramidal side effects. There was no significant difference between treatments in weight change or glucose metabolism. For each prior year of untreated psychosis, there was a 15% decrease in the odds of achieving remission (OR=0.85; CI 0.75-0.95). A high proportion of first-episode patients remitted within 1 year. We detected no difference in the proportion of first-episode patients receiving CLZ or CPZ that achieved remission. However, first-episode patients receiving CLZ remitted significantly faster and remained in remission longer than subjects receiving CPZ. While the CLZ group showed significantly less symptomatology on some measures and fewer side effects at 12 weeks, the two treatment groups seemed to converge by 1 year. Longer duration of untreated psychosis was associated with lower odds of achieving remission.

Adolescent↗
PubMed2003

Effects of hyperfibrinogenemia on vasculature of C57BL/6 mice with and without atherogenic diet.

OBJECTIVE: Elevated fibrinogen is correlated with severe atherosclerosis, as defined by the occurrence of ischemic events, but the mechanistic basis for this correlation remains unknown. To study this relationship, we examined spontaneous and diet-induced atherosclerosis in transgenic mice with hyperfibrinogenemia (elevated fibrinogen). METHODS AND RESULTS: Normal and transgenic mice were fed either an atherogenic diet or simple breeder chow. We measured plasma fibrinogen levels and identified an age-dependent and diet-dependent increase in fibrinogen. After 8 to 12 months, aortic sections were prepared and stained, and lipid-containing lesions were counted, measured, and assessed for maturity. Lipid-filled deposits appeared spontaneously in a small number of mice on breeder chow; typical fatty streak-type lesions appeared in almost all of the diet-fed animals. Morphometric analysis showed that neither the number nor the size of lesions was influenced by either fibrinogen level or genotype. CONCLUSIONS: Our data showed that neither fibrinogen concentration nor genotype had a statistically significant effect on the initiation, initial growth, or early progression of atherosclerotic lesions.

Animals↗
PubMed2003

Subject's Global Assessment of Relief: an appropriate method to assess the impact of treatment on irritable bowel syndrome-related symptoms in clinical trials.

The lack of validated outcome measures is a key limitation for the evaluation of drug efficacy in the treatment of irritable bowel syndrome (IBS). In clinical trials with tegaserod, the Subject's Global Assessment (SGA) of Relief (a global measure that includes overall wellbeing, abdominal pain/discomfort, and bowel function) was used to identify responders. A total of 1680 patients with IBS with constipation were included in two clinical studies comparing tegaserod with placebo. The SGA of Relief was obtained weekly by a single, self-administered question with five possible answers. Responders for the SGA of Relief reported statistically significant (P<.001) and clinically relevant improvements in multiple IBS-related symptoms compared with nonresponders. Response was also associated with a significant improvement in quality of life. The SGA of Relief is reliable as a new outcome measure for assessing response to therapy in IBS patients and has demonstrated responsiveness and reproducibility.

Adolescent↗
PubMed2002

Echocardiographic predictors of adverse outcomes in primary pulmonary hypertension.

OBJECTIVES: The aim of this study was to evaluate the relationships between echocardiographic findings and clinical outcomes in patients with severe primary pulmonary hypertension (PPH). BACKGROUND: Primary pulmonary hypertension is associated with abnormalities of right heart structure and function that contribute to the poor prognosis of the disease. Echocardiographic abnormalities associated with PPH have been described, but the prognostic significance of these findings remains poorly characterized. METHODS: Echocardiographic studies, invasive hemodynamic measurements and 6-min walk tests were performed and outcomes prospectively followed in 81 patients with severe PPH. Subjects were participants in a 12-week randomized trial examining the effects of prostacyclin plus conventional therapy compared with conventional therapy alone. RESULTS: During the mean follow-up period of 36.9 +/- 15.4 months, 20 patients died and 21 patients underwent transplantation. Pericardial effusion (p = 0.003) and indexed right atrial area (p = 0.005) were predictors of mortality. Pericardial effusion (p = 0.017), indexed right atrial area (p = 0.012) and the degree of septal shift in diastole (p = 0.004) were predictors of a composite end point of death or transplantation. In multivariable analyses incorporating clinical, hemodynamic and echocardiographic variables, pericardial effusion and an enlarged right atrium remained predictors of adverse outcomes. Six-minute walk results, mixed venous oxygen saturation and initial treatment randomization were also independently associated with a poor prognosis. CONCLUSIONS: Pericardial effusion, right atrial enlargement and septal displacement are echocardiographic abnormalities that reflect the severity of right heart failure and predict adverse outcomes in patients with severe PPH. These characteristics may help identify patients appropriate for more intensive medical therapy or earlier transplantation.

Adult↗
PubMed2002

Computerised assessment of maximum urinary flow: an efficient, consistent and valid approach.

OBJECTIVES: To evaluate the relative accuracy of a computerised method to quantitatively assess maximum urinary flow. METHODS: A total of 1147 uroflows were evaluated by the computerised method and by three experts from different European countries. The sample consisted of uroflows from the respective visits by a 20% sample of randomly chosen patients (n = 223) with lower urinary tract symptoms with participation in two clinical trials in which the efficacy and safety of Permixon was evaluated. The proportions of automated maximum flow values included in the 10% extended range of experts (and their 95% confidence intervals) were assessed, as well as the concordance coefficients between experts and the computerised method and the paired Student's t-test for the average differences between experts and computer. RESULTS: The rate of agreement between experts and computer varied between about 95 and 100% over factor levels for visit, type of machine and country. Concordance coefficients indicated good agreement between experts and the automated method. When looking at average differences between experts and the computer, the smallest differences were observed between experts 2, 3 and the computer (differences not statistically significant). Statistically significant average differences were observed between expert 1 and the other experts as well as between expert 1 and the computer. CONCLUSIONS: The computerised assessment decreases the fraction of variability of maximum urinary flow caused by artifacts as well as intra- and inter-expert variation. The computerised assessment of maximum urinary flow is an efficient, consistent and valid approach to quantitatively assess maximum urinary flow in clinical trials.

Decision Making, Computer-Assisted↗
PubMed2002

Comparison of a phytotherapeutic agent (Permixon) with an alpha-blocker (Tamsulosin) in the treatment of benign prostatic hyperplasia: a 1-year randomized international study.

OBJECTIVE: While the lipido-sterolic extract of Serenoa repens (LSESr)-Permixon((R))-has been shown to have an equivalent efficacy to finasteride in patients with benign prostatic hyperplasia (BPH), to date, there has been no valid comparison of phytotherapy with alpha-blockers. The aim of this study was to assess the equivalent efficacy of Permixon and tamsulosin. METHODS: Eight hundred and eleven men with symptomatic BPH (I-PSS> or =10) were recruited in 11 European countries for a 12-month, double-blind randomized trial. After a 4-week run-in period, 704 patients were randomly assigned to either tamsulosin 0.4mg/day (N=354) or Permixon 320mg/day (N=350). I-PSS, QoL and Q(max) were evaluated at baseline and periodically for 1 year. Prostate volume and serum prostate-specific antigen (PSA) were measured at selection and at endpoint. The endpoint analysis was performed on the per-protocol population of 542 patients (tamsulosin: N=273; Permixon: N=269). RESULTS: At 12 months, I-PSS decreased by 4.4in each group and no differences were observed in either irritative or obstructive symptom improvements. The increase in Q(max) was similar in both treatment groups (1.8ml/s Permixon, 1.9ml/s tamsulosin). PSA remained stable while prostate volume decreased slightly in the Permixon-treated patients. The two compounds were well tolerated, however, ejaculation disorders occurred more frequently in the tamsulosin group. CONCLUSION: This study demonstrates that Permixon and tamsulosin are equivalent in the medical treatment of lower urinary tract symptoms in men with BPH, during and up to 12 months of therapy.

Adrenergic alpha-Antagonists↗
PubMed2002

[Comparison of a phytotherapeutic agent (Permixon) with an alpha-blocker (Tamsulosin) in the treatment of benign prostatic hyperplasia: a 1-year randomized international study].

OBJECTIVE: While the lipidosterolic extract (LSESr) of Serenoa repens--Permixon--has been shown to have an equivalent efficacy to finasteride in patients with benign prostatic hyperplasia (BPH), to date, there has been no valid comparison of phytotherapy with alpha-blockers. The aim of this study was to assess the equivalent efficacy of Permixon and tamsulosin. METHODS: Eight hundred and eleven men with symptomatic BPH (international prostdate symptom score, I-PSS > or = 10) were recruited in 11 European countries for a 12-month, double-blind randomized trial. After a 4-week run-in period, 704 patients were randomly assigned to either tamsulosin 0.4 mg per day (N = 354) or Permixon 320 mg per day (N = 350). I-PSS, QoL and maximum urinary flow rate (Qmax) were evaluated at baseline and periodically for 1 year. Prostate volume and serum prostate-specific antigen (PSA) were measured at selection and at endpoint. The endpoint analysis was performed on the per-protocol (PP) population of 542 patients (tamsulosin: N = 273; Permixon: N = 269). RESULTS: At 12 months, I-PSS decreased by 4.4 in each group and no differences were observed in either irritative or obstructive symptom improvements. The increase in Qmax was similar in both treatment groups (1.8 ml/s Permixon, 1.9 ml/s tamsulosin). PSA remained stable while prostate volume decreased slightly in the Permixon-treated patients. The two compounds were well tolerated, however, ejaculation disorders occurred more frequently in the tamsulosin group. CONCLUSION: This study demonstrated that Permiwon and tamsulosin are equivalent in the medical treatment of lower urinary tract symptoms in men with BPH, during and up to 12 months of therapy.

Adrenergic alpha-Antagonists↗