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Biomedical subjects

K Reynolds

Publications and source records attributed to K Reynolds.

At least 19 recordsLinked to original sources
PubMed2001

Solution-Phase parallel synthesis of 5-carboxamido 1-benzyl-3-(3-dimethylaminopropyloxy)-1H-pyrazoles as activators of soluble guanylate cyclase with improved oral bioavailability.

A lipophilicity constrained library of 5-carboxamido 1-benzyl-3-(3-dimethylaminopropyloxy)-1H-pyrazoles was prepared by solution-phase parallel synthesis with removal of acidic by-products using the strongly basic MP-carbonate resin. Compounds show both activation of soluble guanylate cyclase and inhibition of platelet aggregation. Compound 12 also shows 22% oral bioavailability in rats.

Administration, Oral↗
PubMed2001

Synthesis and biological evaluation of novel pyrazoles and indazoles as activators of the nitric oxide receptor, soluble guanylate cyclase.

Database searching and compound screening identified 1-benzyl-3-(3-dimethylaminopropyloxy)indazole (benzydamine, 3) as a potent activator of the nitric oxide receptor, soluble guanylate cyclase. A comprehensive structure-activity relationship study surrounding 3 clearly showed that the indazole C-3 dimethylaminopropyloxy substituent was critical for enzyme activity. However replacement of the indazole ring of 3 by appropriately substituted pyrazoles maintained enzyme activity. Compounds were evaluated for inhibition of platelet aggregation and showed a general lipophilicity requirement. Aryl-substituted pyrazoles 32, 34, and 43 demonstrated potent activation of soluble guanylate cyclase and potent inhibition of platelet aggregation. Pharmacokinetic studies in rats showed that compound 32 exhibits modest oral bioavailability (12%). Furthermore 32 has an excellent selectivity profile notably showing no significant inhibition of phosphodiesterases or nitric oxide synthases.

Animals↗
PubMed2001

MAPS: a microarray project system for gene expression experiment information and data validation.

SUMMARY: MAPS is a MicroArray Project System for management and interpretation of microarray gene expression experiment information and data. Microarray project information is organized to track experiments and results that are: (1) validated by performing analysis on stored replicate gene expression data; and (2) queried according to the biological classifications of genes deposited on microarray chips.

Computer Communication Networks↗
PubMed2000

p53 and related proteins in epithelial ovarian cancer.

We conducted a retrospective immunohistochemical evaluation of the prognostic significance of the expression of p53 and the related proteins Bax, Bcl-2, growth arrest and DNA damage (Gadd45), murine double minute 2 (Mdm2) and p21(WAF1/CIP1) in chemonaive tumours taken from 66 patients with ovarian cancer. Ki-67 expression (a marker of cell proliferation) was also evaluated immunohistochemically, while apoptosis within malignant cells was determined with the terminal deoxynucleotidyltransferase-mediated dUTP nick-end labelling (TUNEL) assay. The expression of each of the following proteins was significantly associated in the tumours (P < 0.05 unless otherwise stated): Bax with Bcl-2 (P < 0.01); Bax with Mdm2; p21(WAF1/CIP1) with Gadd45 (P < 0.01); p21(WAF1/CIP1) with p53; p53 with Mdm2. Univariate analysis showed that expression of p53, Bax, bulk residual disease and International Federation of Gynecology and Obstetricians (FIGO) stage were all strongly correlated with response to chemotherapy (P < 0.01). Similarly, the FIGO stage and Ki-67 expression (P < 0.01), as well as pathological subtype and bulk residual disease (P < 0.05), were prognostic factors for disease progression. The FIGO stage and Ki-67 expression were significant prognostic factors for overall survival (P < 0.01), with Gadd45 expression and pathological subtype also significant (P < 0.05) in a univariate analysis. Multivariate analysis for response to chemotherapy showed that expression of p53, Bax and FIGO stage were all independent prognostic factors (P < 0.01). The FIGO stage was the most important independent prognostic factor for progression and survival on multivariate analysis (P < 0.01). However, Ki-67 expression was also an independent prognostic factor for disease progression (P < 0.05) and approached significance for survival (P = 0.055). Taken together, these data suggest that determination of Ki-67 expression could supplement established prognostic factors.

Adult↗
PubMed2000

Requirement for expert histopathological assessment of ovarian cancer and borderline tumors.

The distinction between borderline ovarian tumours (BOT) and ovarian carcinoma is made by histopathological assessment. Of 64 patients managed according to institutional BOT protocols, 27 (42%) had been referred with a diagnosis of ovarian carcinoma that was subsequently changed to BOT following histopathological review. The 70% 6-year event-free survival of the patients with a revised diagnosis was not significantly different from those who were referred with a diagnosis of BOT. This change in diagnosis is important as it avoids the need for chemotherapy for most patients and results in patients receiving appropriate information concerning prognosis. Interestingly, 24 patients (38.1%) reported a family history of epithelial cancer, a finding that has not been reported previously. Campaign

Adult↗
PubMed2000

Utility of intravenously administered contrast material at CT colonography.

PURPOSE: To determine if intravenously administered contrast material improves overall reader confidence in the assessment of the colon, large-bowel wall conspicuity, and diagnostic accuracy in the detection of colorectal polyps and cancers at computed tomographic (CT) colonography. MATERIALS AND METHODS: Two hundred patients underwent CT colonography in both supine and prone positions. A five-point scale was used to assess the effect of contrast enhancement on overall reader confidence and bowel wall conspicuity. Eighty-one patients underwent CT colonography with complete colonoscopic or surgical correlation; diagnostic accuracy was compared in 48 patients who received contrast material and 33 who did not. RESULTS: Bowel preparation was ideal in 38 (19%) of 200 patients. Enhanced prone CT images had significantly better scores for reader confidence (4.9 +/- 0.1 vs 4.6 +/- 0.1, P: <.005) and bowel wall conspicuity (4.6 +/- 0.2 vs 4.2 +/- 0.2, P: <.005) compared with those of nonenhanced prone images despite no significant difference in bowel distention (3.8 +/- 0.2 vs 3.9 +/- 0. 1, P: =.8). Enhancement significantly improved the ability to depict medium (6-9-mm) polyps (75% vs 58%, P: <.05). Three large (10-19-mm) polyps were detected only with contrast enhancement; two remained submerged despite dual positioning. CONCLUSION: The use of intravenously administered contrast material significantly improved reader confidence in the assessment of bowel wall conspicuity and the ability of CT colonography to depict medium polyps in suboptimally prepared colons.

Adult↗
PubMed2000

The role of availability as a moderator of family fruit and vegetable consumption.

The public health objective to improve the diet of Americans includes increasing the consumption of fruits and vegetables (F&V). The availability of F&V in the home has been suggested but not confirmed as one environmental factor that influences the types and quantities of F&V eaten by family members. Using a model of parental and child influences on a child's intake of F&V, the authors investigated F&V availability as a moderating variable for the relationships between the model constructs and how the relationships might change with varying levels of F&V availability. Path analysis and multigroup structural equation modeling were the analytic tools. Results indicated that homes with more F&V available had a richer and generally stronger set of motivating factors for parent and child F&V consumption than homes with low F&V availability. Findings have implications for parental involvement in interventions to enhance the diet of fourth-grade children.

Adult↗
PubMed2000

Alterations in hepatic perfusion resulting from splanchnic venous luminal compromise caused by pancreatic carcinoma.

OBJECTIVE: We determined whether alterations in hepatic enhancement exist on dual phase helical CT of the liver in patients with splanchnic venous luminal compromise resulting from pancreatic adenocarcinoma. SUBJECTS AND METHODS: We examined the extent of hepatic enhancement on dual phase helical CT in 22 patients with pancreatic adenocarcinoma. Eleven patients had splanchnic venous luminal narrowing (flattening along at least 120 degrees of the circumference) of the superior mesenteric vein with (n = 3) or without (n = 8) portal vein involvement caused by tumor. In the remaining patients, splanchnic vasculature appeared normal. An additional 16 patients without pancreatic or hepatic abnormality who underwent dual phase helical CT served as control subjects. We compared the extent of arterial phase and portal venous phase enhancement among the three groups. RESULTS: The group of patients with splanchnic venous luminal compromise had significantly higher hepatic enhancement during the arterial phase (p < 0.01) and lower enhancement during the portal venous phase (p < 0.05) compared with the other two groups of patients. No significant difference in hepatic enhancement during either phase was noted between the control subjects and the patients with normal vasculature. CONCLUSION: Because hepatic enhancement correlates with perfusion, splanchnic venous luminal compromise resulting from pancreatic adenocarcinoma likely causes decreased portal venous flow and compensatory increased hepatic arterial flow. This finding supports other evidence of a homeostatic mechanism that maintains hepatic perfusion.

Adenocarcinoma↗
PubMed2000

Measuring self-efficacy in substance abuse intervention in obstetric practices.

BACKGROUND: This study presents findings on the effect of an office-based obstetrics training program (given the acronym OBIWOM) on substance use assessment, management, and referral self-efficacy among obstetricians and staff of private, community-based obstetric practices. METHODS: Participants were obstetricians and staff from 10 of 27 available community-based, private obstetric practices in the target areas, for a practice participation rate of 37%. This study used a delayed treatment design to compare self-efficacy between practice staff randomly assigned to an immediate or delayed intervention group. RESULTS: Self-efficacy increased significantly after intervention from baseline to first follow-up for the immediate group, while no change was shown for the delayed (control) group. The impact of the intervention on self-efficacy was replicated in the assessment construct only after the intervention for the delayed group. CONCLUSION: This research shows that education and training can effectively improve self-efficacy in obstetricians and their staff in the management of substance use and pregnancy.

Adult↗
PubMed2000

Unraveling the realities of vascular access: the Network 11 experience.

Arteriovenous (AV) fistulae are well recognized as the preferred vascular access for hemodialysis, yet national data show that only 23% of patients used an AV fistula in 1997. To identify barriers to the placement of native AV fistulae, the Renal Network of the Upper Midwest, Inc. (End-Stage Renal Disease [ESRD] Network 11) initiated a vascular access project to look at the process of referral for patients beginning hemodialysis in the first 6 months of 1999. Of these patients, 63% began hemodialysis with a catheter as the only access, 22% had an AV fistula placed (but only 14% used an AV fistula for their first dialysis treatment), and 15% began with a graft. About 40% of patients were referred to a nephrologist less than 1 month before dialysis, allowing little chance for permanent access placement. Yet 27% of patients used a catheter on the first hemodialysis treatment and were seen by a nephrologist more than 1 month before starting dialysis, indicating the presence of an opportunity to improve. At 6 months after initiation of dialysis, 25% of patients who began dialysis using a catheter were using an AV fistula and 35% were using a graft. Network 11 plans to use this information to promote early referral of patients to a nephrologist and subsequent prompt referral of such patients to a vascular surgeon. Other activities to improve vascular access management are also indicated.

Adolescent↗
PubMed2000

Injuries and risk factors in an 18-day Marine winter mountain training exercise.

OBJECTIVES: This study determined the incidence of and risk factors for injuries among 356 Marines during a winter mountain training exercise. METHODS: Marines received a podiatry screening and completed a questionnaire on race, education, tobacco use, height, weight, and fitness (4.8-km run, sit-ups, pull-ups). RESULTS: Forty-five Marines (12.6%) reported at least one injury each, 68.9% of which were traumatic injuries. Total injuries resulted in 114 days of limited duty time. A final foot examination (N = 141) revealed 118 injuries (82.2% blisters and abrasions, 11.9% frostnip). White ethnicity was a risk factor for overall injuries, and forefoot varus alignment was a risk factor for traumatic injuries. Lower education and rank and smokeless tobacco use were associated with foot injuries. The Marine ski-march leather boot and smoking were related to foot cold injuries. CONCLUSIONS: Military winter training is associated with injuries and lost training time. Risk factors were identified, suggesting that these injuries may be preventable.

Adult↗
PubMed1999

Adequacy of prenatal care and prescription of zidovudine to prevent perinatal HIV transmission.

In 1994, data were published on the effectiveness of zidovudine in preventing perinatal transmission of HIV infection. Using data from surveillance projects in San Antonio, Dallas, and Houston, Texas, U.S.A., we linked records of children born from 1987 through 1996 with records of their HIV-infected mothers. Prenatal care was measured by Kotelchuck's Adequacy of Prenatal Care Utilization (APNCU) Index. We examined the association between adequacy of prenatal care and four measures of zidovudine prescription: prenatal, intrapartum, neonatal, and the complete regimen. Inclusion criteria was that the mother's HIV infection was diagnosed before a live birth; 221 mother-infant pairs were included in the analysis. Overall, 68% received inadequate or no prenatal care. Over time, the proportion of mother-infant pairs with adequate prenatal care doubled (24%-48%; relative risk [RR], 2.0; 95% confidence interval [CI], 1.3-3.0), and the proportion prescribed prenatal zidovudine tripled (20%-67%; RR, 3.4; 95% CI, 2.4-4.9). In logistic regression, APNCU (adjusted odds ratio [aOR], 2.6; 95% CI, 1.1-6.2) and time period (aOR, 19.9; 95% CI, 8.1-48.7) were associated with prenatal prescription of zidovudine. The benefits of prenatal care, including HIV testing and zidovudine treatment, underscore the urgent need to improve access to and use of prenatal care services.

Adult↗
PubMed1999

Auditory preference for conspecific song in isolation-reared zebra finches.

Seven female and six male zebra finches, Taeniopygia guttata, were reared in acoustic isolation from song and tested for their preference for conspecific song when 28-53 days old by allowing them to select exposure to zebra finch or European starling, Sturnus vulgaris, song. The birds hopped more frequently on a perch that generated zebra finch song than one that produced starling song, and they spent more time listening to zebra finch song. There were no sex differences. The results indicate that during their sensitive period for song learning, and prior to experience with song, zebra finches prefer conspecific song to heterospecific song. Copyright 1999 The Association for the Study of Animal Behaviour.

Journal Article↗
PubMed1999

Production of influenza-stimulated tumor necrosis factor-alpha by monocytes following acute influenza infection in humans.

Tumor necrosis factor-alpha (TNF-alpha) is often measured in the serum or plasma of patients with severe infections, and marked elevation correlates with poor outcome. The relationship of TNF-alpha to protection from disease is frequently not observed because prospective studies of infectious agents are difficult to perform. We took advantage of a human antiviral influenza challenge study to correlate TNF-alpha production with seroconversion and symptom development. TNF-alpha production was measured by ELISA in the plasma compartment or was measured by intracellular production at the single cell level in the monocyte gated population. Monocyte TNF-alpha was associated with asymptomatic seroconversion, whereas there was no change in the plasma at the times measured. Measurement of TNF-alpha at the single cell level by flow cytometry may allow for better differentiation of the protective role of this cytokine in future studies.

Adolescent↗
PubMed1999

FDA evaluations using in vitro metabolism to predict and interpret in vivo metabolic drug-drug interactions: impact on labeling.

Recent advances in in vitro metabolism methods have led to an improved ability to predict clinically relevant metabolic drug-drug interactions. To address the relationships of in vitro metabolism data and in vivo metabolism outcomes, the Office of Clinical Pharmacology and Biopharmaceutics in the Center for Drug Evaluation and Research, Food and Drug Administration, evaluated a number of recently approved new drug applications. The goal of these evaluations was to determine the contribution of in vitro metabolism data in (1) predicting in vivo drug-drug interactions, (2) determining the need to conduct an in vivo drug-drug interaction study, and (3) incorporating findings into drug product labeling. Ten cases are presented in this article. They fall into two major groups: (1) in vitro data were predictive of in vivo results, and (2) in vitro data were not predictive of in vivo results. Discussion of these cases highlights factors limiting predictability of in vivo metabolic interactions from in vitro metabolism data. The integration of these findings into drug product labeling is also discussed.

Data Collection↗
PubMed1999

Magnetic resonance imaging of actinomycosis presenting as pelvic malignancy.

Pelvic actinomycosis is associated with long-standing use of an intrauterine contraceptive device and may present with clinical signs and symptoms of pelvic malignancy. Diagnostic imaging can confirm the presence of a pelvic mass and tissue infiltration but findings are often non-specific. We present a case of pelvic actinomycosis with tubo-ovarian abscess in which magnetic resonance imaging demonstrated lower signal intensity tissue on T2 weighted sequences than would be typical for pelvic malignancy or infection and was useful in confirming regression of pelvic disease in response to antibiotic therapy.

Actinomycosis↗