Biomedical subjects

C Cook

Publications and source records attributed to C Cook.

At least 55 records · Page 3Linked to original sources

PubMed1998

Decreased mortality from necrotizing pancreatitis.

BACKGROUND: Necrotizing pancreatitis has been associated with mortality rates of 25% to 80%. We reviewed our experience to determine whether aggressive debridement and comprehensive critical care improves survival. METHODS: The records of 989 patients with the diagnosis of pancreatitis admitted between January 1990 and September 1997 were retrospectively reviewed. Twenty-six patients required surgery for necrotizing pancreatitis and are the subjects of this review. RESULTS: Five of twenty-six patients (19%) died. For all patients, mean Ranson's score was 4.3 of 11, mean admission APACHE II score was 17.2, and mean Multiple Organ Dysfunction (MOD) score was 9.1. Poor outcome was associated with infected pancreatic necrosis (P = 0.03), elevated APACHE II score on admission (P = 0.04), and progression of MOD during the week after admission (P = 0.02). CONCLUSIONS: This review demonstrates improved survival in seriously ill patients with necrotizing pancreatitis as a result of comprehensive surgical and critical care.

Adult↗

PubMed1998

The nuclear/mitotic apparatus protein NuMA is a component of the somatodendritic microtubule arrays of the neuron.

Neurons are terminally post-mitotic cells that utilize their microtubule arrays for the growth and maintenance of axons and dendrites rather than for the formation of mitotic spindles. Recent studies from our laboratory suggest that the mechanisms that organize the axonal and dendritic microtubule arrays may be variations on the same mechanisms that organize the mitotic spindle in dividing cells. In particular, we have identified molecular motor proteins that serve analogous functions in the establishment of these seemingly very different microtubule arrays. In the present study, we have sought to determine whether a non-motor protein termed NuMA is also a component of both systems. NuMA is a approximately 230 kDa structural protein that is present exclusively in the nucleus during interphase. During mitosis, NuMA forms aggregates that interact with microtubules and certain motor proteins. As a result of these interactions, NuMA is thought to draw together the minus-ends of microtubules, thereby helping to organize them into a bipolar spindle. In contrast to mitotic cells, post-mitotic neurons display NuMA both in the nucleus and in the cytoplasm. NuMA appears as multiple small particles within the somatodendritic compartment of the neuron, where its levels increase during early dendritic differentiation. A partial but not complete colocalization with minus-ends of microtubules is suggested by the distribution of the particles during development and during drug treatments that alter the microtubule array. These observations provide an initial set of clues regarding a potentially important function of NuMA in the organization of microtubules within the somatodendritic compartment of the neuron.

Animals↗

PubMed1998

Reduced systemic availability of an antiarrhythmic drug, bidisomide, with meal co-administration: relationship with region-dependent intestinal absorption.

PURPOSE: The aim of this research was to determine the mechanism by which a co-administered meal decreases the oral absorption of bidisomide and does not influence the oral absorption of the chemically-related antiarrhythmic agent, disopyramide. METHODS: Bidisomide plasma levels, following oral administration and intravenous infusion in the fasted state and with various meal treatments, were determined in human subjects. A dialysis technique was employed to examine the potential for drug binding to meal homogenates. Plasma levels, following drug administration through duodenal and jejunal intestinal access ports and following various meal treatments with oral drug co-administration, were compared for bidisomide and disopyramide in a canine model. RESULTS: Bidisomide plasma AUC was significantly reduced following oral drug co-administration with breakfast compared to fasted-state controls in human subjects and in dogs independent of the composition of the solid cooked breakfast. While intravenous bidisomide infusion in human subjects showed a statistically significant reduction in AUC 15 minutes after oral administration of a high fat breakfast as compared to drug infusion in the fasted state, the reduction (-13%) was substantially smaller than the reduction (from -43% to -63%) observed with oral bidisomide meal co-administration. The percentages of bidisomide and disopyramide lost by binding to homogenates of cooked breakfast were 25.0 +/- 5.7% and 23.7 +/- 7.7%, respectively, as determined by dialysis at 4 hours. In dogs, the extent of absorption of disopyramide was comparable from oral, duodenal and mid-jejunal administration while the extent of bidisomide absorption from mid-jejunal administration was significantly lower than for oral or duodenal administration. Non-viscous liquid meals decreased Cmax but not AUC, while viscous homogenized solid meals decreased both Cmax and AUC for bidisomide with oral drug-meal co-administration. Oral non-caloric hydroxypropyl methylcellulose meals decreased bidisomide to the same extent as homogenized solid meals but did not lower disopyramide AUC. CONCLUSIONS: The significant reduction in bidisomide plasma levels observed with meal co-administration in human subjects was predominantly mediated through a reduction in drug absorption and was independent of solid meal composition. The difference in meal effect on the absorption of the two drugs in humans did not appear to be a function of drug binding to cooked meal components over typical human upper gastrointestinal residence times. In dogs, the high-viscosity medium generated by oral co-administration of a solid meal reduced the upper intestinal absorption of bidisomide and disopyramide. Bidisomide AUC was decreased since it was well absorbed in the upper but not lower small intestine. Disopyramide AUC was not significantly affected since it was well absorbed from both regions. A similar mechanism may play a role in drug plasma level reductions following oral co-administration with solid meals for drugs showing similar regionally-dependent absorption profiles.

Animals↗

PubMed1997

Müllerian-inhibiting substance in follicular fluid and serum: a comparison of patients with tubal factor infertility, polycystic ovary syndrome, and endometriosis.

OBJECTIVE: To determine Müllerian inhibiting substance (MIS) levels in follicular fluid (FF) and sera of IVF patients. DESIGN: Prospective study. SETTING: Fertility center. PATIENT(S): Sixty-six patients: 20 with tubal factor infertility, 17 with polycystic ovary syndrome (PCOS), and 29 with endometriosis. INTERVENTION(S): All patients underwent ovarian stimulation with hMG and/or FSH, as well as oocyte retrieval for IVF. MAIN OUTCOME MEASURE(S): Follicular fluid and serum MIS levels and oocyte fertilization rates. RESULT(S): Levels of MIS in FF and sera of PCOS patients were significantly higher than those in tubal factor patients: 7.01 +/- 1.52 versus 1.65 +/- 0.23 ng/mL (mean +/- SE) and 2.97 +/- 0.52 versus 0.92 +/- 0.19 ng/mL, respectively. In endometriosis patients, follicular fluid and serum MIS levels were not significantly different from those in tubal factor patients. In PCOS patients, the percentage of immature oocytes retrieved (17.9% +/- 5.0%) was significantly higher compared with tubal factor (1.5% +/- 1.0%) and endometriosis (9.2% +/- 2.3%) patients. The percentage of oocytes fertilize was significantly lower in PCOS patients (30.2% +/- 5.3%) compared with tubal factor (62.2% +/- 5.5%) and endometriosis (37.5% +/- 5.7%) patients. CONCLUSION(S): Women with PCOS had higher serum and follicular fluid MIS levels, a higher percentage of immature oocytes, and lower fertilization rates than women with endometriosis or pelvic adhesions.

Adult↗

PubMed1997

The role of the social worker in perinatal substance-abuse.

Perinatal substance use affects approximately 10-15% of the population at any given time. Although it is not completely clear whether perinatal substance use is the cause of poor outcomes or a result of related factors such as poverty, environmental deprivation, violence in the home, or depression, the impact on maternal well-being and neonatal outcomes is enormous and the cost to society high. As this issue continues to receive state and national attention, the role for social workers as essential members of the treatment team is increasingly important.

Adolescent↗

PubMed1997

Faith-based health needs assessment: implications for empowerment of the Faith community.

Churches are often caught in the middle of the struggle between health care institutions and managed care organizations. A faith-based center of excellence model is proposed that would establish a middle ground between the secular and "sacred" aspects of health care. Such a model would focus on using the faith community to influence the behavior and lifestyle of persons within the organized public health model, thus providing a new model of ministry. This process can increase an understanding of the tools needed for the clergy to be better caregivers, more influential co-change agents, and more informed about data-driven outcome ministry. This integrated process is critical for real change in health outcomes, for the improvement of primary prevention, and for reducing disease mortality.

Community Health Services↗

PubMed1996

Characterization of 4-aminobiphenyl-hemoglobin adducts in maternal and fetal blood-samples.

The maternal-fetal exchange of the potent tobacco-related human carcinogen 4-aminobiphenyl was studied in women smokers during pregnancy. The number of cigarettes smoked per day by each of the women in the study was assessed via questionnaire and by measurement by immunoassay of serum and urine cotinine in maternal and fetal blood samples. Maternal and fetal blood samples were classified as coming from nonsmokers (n = 74), individuals smoking less than 1 pack of cigarettes per day (n = 16), individuals smoking 1 pack of cigarettes per day (n = 19), individuals smoking 1-2 packs of cigarettes per day (n = 19), and individuals smoking greater than 2 packs of cigarettes per day (n = 20). Both maternal and fetal blood samples were obtained at the time of delivery. 4-Aminobiphenyl was extracted from both maternal and fetal blood samples using organic extractions and the released amine was qualitatively and quantitatively characterized by analysis of the samples by gas chromatographic and mass spectrometric analysis. Background levels of 4-aminobiphenyl-hemoglobin adducts were detected in maternal nonsmokers (18.3 +/- 12.7 pg 4-aminobiphenyl/g hemoglobin, mean +/- SD) and in fetal samples (8.88 +/- 5.8 pg/g hemoglobin). Increasing levels of 4-aminobiphenyl-hemoglobin adducts were found as the smoking status of the women increased, ranging from 144 +/- 22.2 ( < 1 pack/d) to 633 +/- 87.9 ( > 2 packs/d). A corresponding increase in the presence of fetal 4-aminobiphenyl-hemoglobin adducts was also detected (74 +/- 17.8, < 1 pack/d, to 319 +/- 50.5, > 2 packs/d). This study confirms that the potent tobacco-related carcinogen 4-aminobiphenyl crosses the human placenta and binds to fetal hemoglobin in significantly higher concentrations in smokers when compared to nonsmokers.

Aminobiphenyl Compounds↗

PubMed1996

Porous ceramics as bone graft substitutes in long bone defects: a biomechanical, histological, and radiographic analysis.

Three porous ceramic bone graft materials were compared with regard to their ability to heal a 2.5 cm defect created surgically in a bilateral canine radius model. The ceramic materials were analyzed at 12 and 24 weeks after surgery and included tricalcium phosphate, hydroxyapatite, and collagen hydroxyapatite, which contained a mixture of 35% tricalcium phosphate and 65% hydroxyapatite with added collagen. Each material was evaluated alone and with added bone marrow aspirate. All the implants were compared with a graft of autogenous cancellous bone in the contralateral radius. Biomechanical testing and radiographic evaluation revealed that the addition of bone marrow aspirate was essential for tricalcium phosphate and hydroxyapatite to achieve results comparable with those of cancellous bone. Collagen hydroxyapatite performed well without the addition of bone marrow, although the addition of marrow did have a positive effect. Further qualitative radiographic and histological analysis demonstrated that tricalcium phosphate was the only ceramic that showed any sign of degradation at 24 weeks. This observed degradation proved to be an important factor in evaluating radiographs because the radiodensity of collagen hydroxyapatite and hydroxyapatite interfered with the determination of radiographic union. At 24 weeks, tricalcium phosphate with bone marrow was the material that performed most like cancellous bone. In this study, the biomechanical and radiographic parameters of tricalcium phosphate with bone marrow were roughly comparable with those of cancellous bone at 12 and 24 weeks. Tricalcium phosphate was the only implant that showed significant evidence of degradation at 24 weeks by both histological and radiographic evaluations, and this degradation took place only after a degree of mechanical competence necessary for weight-bearing was achieved.

Animals↗

PubMed1996

Phosphocreatine and creatine kinase in piglet cerebral gray and white matter in situ.

Rates of adenosine triphosphate (ATP) metabolism are higher in cerebral gray matter than in white matter. Like other excitable tissues, brain contains a phosphocreatine (PCr)/creatine kinase (CK)/ATP system including cytosolic (B-CK) and mitochondrial (Mi-CK) isozymes. High B-CK activity is present in white and gray matter while Mi-CK is mostly in gray matter. An in situ localizing 31P-NMR technique, one-dimensional chemical shift imaging (1D-CSI), has been used to study the PCr/CK/ATP system in these regions. In the metabolically mature 4-week-old piglet, the PCr/nucleoside triphosphate (NTP) ratio measured by the 1D-CSI technique is at least 50% higher in white than gray matter. Total creatine (Cr), ATP, and total NTP concentrations are the same in rapidly frozen rat white and gray matter, suggesting that PCr/Cr ratio is much higher in white matter. The PCr increases more in gray than white matter between 4 days and 4 weeks of age in piglet brain. The CK catalyzed reaction rate constant, measured by combining the saturation transfer experiment with the 1D-CSI, is also much higher in white than gray matter at both ages. The postnatal maturational increase in the CK rate constant is greater in gray matter. In summary, these differences in PCr concentration and CK reaction rates and isozymes characterize two physiologically different PCr/CK/ATP systems in gray and white matter.

Animals↗

PubMed1994

Individual differences in the macronutrient preference profile of outbred rats: implications for nutritional, metabolic, and pharmacologic studies.

While screening outbred male Holtzman Sprague-Dawley rats for their macronutrient (protein, carbohydrate, and fat) preferences, we noticed substantial group-to-group variation in the preference profile. This led us to analyze preference data on two hundred and seventy rats collected over a three-year period to determine whether preferences could be predicted. The results led us to conclude that observed variations in macronutrient preference profiles may be secondary to genetic heterogeneity in the outbred population. We have also shown that the outcome of the pharmacologic effects of two agents (insulin and enterostatin) on appetitive behavior will vary from animal to animal within a single group. Accordingly, researchers must be aware that the breeding history of the laboratory animal is a major factor in the outcome of the experiment and interpretation of the findings.

Animal Nutritional Physiological Phenomena↗

PubMed1994

The gut-brain peptide cyclo(His-Pro) is secreted in a pulsatile fashion in fasting humans.

Histidyl-proline diketopiperazine (CHP) is a cyclic dipeptide that is found in many animal tissues, most notably brain and gut. It has been found to have a variety of biologic actions and has been postulated to play a role in appetitive behavior and energy metabolism. This study was conducted in order to characterize the secretory pattern of CHP during a 24 h fast. Four subjects (2 obese and 2 lean) were studied during the latter 24 h of a 36 h fast. Blood was sampled every 10-15 min and assayed for CHP concentration using a specific radioimmunoassay. Analysis revealed that circulating CHP oscillates in humans and that diurnal variation occurred but only in the obese subjects.

Adult↗

PubMed1994

Conservative treatment of plantar heel pain: long-term follow-up.

In order to evaluate the long-term results of patients treated conservatively for plantar heel pain, a telephone follow-up survey was conducted. After eliminating those patients with worker's compensation-related complaints and those with documented inflammatory arthritides, data on 100 patients (58 females and 42 males) were available for review. The average patients was 48 years old (range 20-85 years). The average follow-up was 47 months (24-132 months). Clinical results were classified as good (resolution of symptoms) for 82 patients, fair (continued symptoms but no limitation of activity or work) for 15 patients, and poor (continued symptoms limiting activity or changing work status) in 3 patients. The average duration of symptoms before medical attention was sought was 6.1, 18.9, and 10 months for the three groups, respectively. The three patients with poor results all had bilateral complaints, but had no other obvious risk factors predictive of their poor result. Thirty-one patients stated that, even with the understanding that surgical treatment carries significant risk, they would have seriously considered it at the time medical attention was sought; twenty-two of these patients eventually had resolution of symptoms. Although the treatment of heel pain can be frustrating due to its indolent course, a given patient with plantar fasciitis has a very good chance of complete resolution of symptoms. There is a higher risk for continued symptoms in over-weight patients, patients with bilateral symptoms, and those who have symptoms for a prolonged period before seeking medical attention.

Adult↗

PubMed1993

Placental microvascular changes in twin pregnancies with abnormal umbilical artery waveforms.

OBJECTIVE: To determine whether there is a relationship between umbilical artery Doppler waveforms and placental histology in twin pregnancies. METHODS: The placental vasculature was examined histologically in 41 cases of twin pregnancy in women who had undergone antenatal Doppler umbilical artery waveform analysis. RESULTS: Those fetuses with abnormal systolic-diastolic ratios (S/Ds) showed a reduction in the placental tertiary stem villi arterial vessels compared with fetuses with normal S/Ds. The mean count of small arterial vessels (diameter less than 90 mu) in the placentas from cases with normal S/Ds (below the 95th percentile) was 5.6, whereas the mean arterial count for those with high S/Ds (above the 99th percentile) was 3.9 (P = .039). CONCLUSIONS: In twin pregnancies complicated by placental insufficiency, there is microvascular disease restricted to the placenta of the affected fetus. This suggests that the placental vascular lesion originates in the fetal circulation rather than in the uteroplacental vasculature.

Birth Weight↗

PubMed1992

Enzyme packed bed system for the on-line measurement of glucose, glutamate, and lactate in brain microdialysate.

Rapid measurement of glucose, glutamate, and lactate is important in understanding the dynamics of the energy balance of the brain. Glutamate is also the main excitatory neurotransmitter. A general immobilized enzyme-based flow injection assay system is described which uses oxidase and peroxidase enzymes to convert the analyte into an oxidized ferrocene species which is detected electrochemically by reduction. The enzymes glucose oxidase, glutamate oxidase, lactate oxidase, and horseradish peroxidase are immobilized with near 100% efficiency onto 10-microns tresyl-activated silica beads (1000- and 500-A pore size). The beads are slurry-packed into 2- x 20-mm columns to give beds for glucose, glutamate, or lactate which are stable for greater than 40 days. The flow injection assays described have detection limits from 1.8 to less than 20 pmol and have been configured to have linear calibration responses over the range of basal and stimulated levels of the three compounds found in 5-microL microdialysate samples from the rat striatum. The assays are used for automated on-line measurement of glucose, glutamate, and lactate in striatal microdialysate at 2.5-min intervals.

Animals↗

PubMed1992

Ten-year experience with mitral valve replacement in the elderly.

Limited data are available on mitral valve replacement in the elderly patient. Therefore we report our 10-year experience including predictors of perioperative mortality and subsequent long-term cardiac mortality in elderly patients with mitral valve replacement compared to younger patients. Of the 126 consecutive patients with mitral valve replacement, 26 were older (77 +/- 4, group 1) and 100 were younger (62 +/- 9, group 2) than 70 years. Bioprostheses were used more frequently in patients in group 1 (65% vs 7%, p less than 0.0001). Of the 21 clinical, ECG, hemodynamic, and angiographic variables studied, patients in group 1 had higher pulmonary artery systolic pressure (57 +/- 15 vs 48 +/- 19, p less than 0.05), fascicular block on ECGs (70% vs 33%, p less than 0.005), and greater pump time on cardiopulmonary bypass (160 +/- 75 vs 120 +/- 50 minutes, p less than 0.025). A trend toward a higher perioperative mortality rate was also seen in group 1 (27% vs 12%, p = 0.058). Predictors of perioperative mortality by multivariate analysis were the presence of aortic calcification and prolonged pump time on cardiopulmonary bypass in group 1 and coronary artery disease, female sex, elevated mean pulmonary artery pressure, and postoperative complete atrioventricular block in group 2. During a mean 4-year follow-up period, cardiac mortality and total mortality rates were 42% and 54%, respectively, for group 1 compared to 24% and 35%, respectively, for group 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1992

Transforming growth factor-alpha and epidermal growth factor messenger ribonucleic acid and protein levels in human placentas from early, mid, and late gestation.

OBJECTIVE: Human placenta expresses receptors for transforming growth factor-alpha and epidermal growth factor throughout pregnancy. Experiments were performed to determine whether epidermal growth factor or transforming growth factor-alpha might be synthesized by placental cells and act through an autocrine mechanism to influence functioning of placental cells in vivo. STUDY DESIGN: Human placentas from early, mid, and late gestations were analyzed for transforming growth factor-alpha and epidermal growth factor messenger ribonucleic acid and proteins. Polyadenylic acid-positive ribonucleic acid was isolated from placentas from 10, 11, 13, 21, 32, 38, 39, and 40 weeks of gestation and analyzed by Northern analysis for hybridization with complementary deoxyribonucleic acid probes specific for epidermal growth factor or transforming growth factor-alpha. Levels of immunoreactive epidermal growth factor and transforming growth factor-alpha were measured by specific radioimmunoassays in pools of placentas from early, mid, and late gestations, and levels of epidermal growth factor and transforming growth factor-alpha receptor-active protein were measured by radioreceptor assay. RESULTS: All placentas had a strong transforming growth factor-alpha hybridization band at 4.5 kb and a weak epidermal growth factor hybridization band at 5.2 kb. High levels of transforming growth factor-alpha immunoreactive protein (90 to 180 ng/mg protein) and low levels of immunoreactive epidermal growth factor (3 to 9 pg/mg protein) were detected in pools of placentas from early, mid, and late gestations. High levels of epidermal growth factor and transforming growth factor-alpha receptor-active protein (250 ng/mg protein) were also detected. CONCLUSION: Human placentas contain relatively high levels of immunoreactive and receptor-active transforming growth factor-alpha, as well as transforming growth factor-alpha messenger ribonucleic acid, throughout gestation. This finding suggests that transforming growth factor-alpha may act by an autocrine system to influence human placental cell function in vivo.

Blotting, Northern↗

PubMed1992

Effect of plasma from premenstrual syndrome and control patients on human platelet and rat brain synaptosome monoamine oxidase B activity.

The present study determined the kinetic properties of platelet monoamine oxidase (MAO) in patients with premenstrual syndrome (PMS) and control subjects during the pre- and postmenstrual intervals. In addition, we investigated the effects of plasma obtained during the pre- and postmenstrual intervals from both subject groups on MAO activity in washed human platelets and rat brain synaptosomes. The Vmax of platelet MAO in postmenstrual PMS patients was significantly less than that during the premenstrual phase. Plasma from both subject groups (10-100 microliters) inhibited platelet and synaptosomal MAO in a dose-dependent manner to approximately the same degree at each time interval. The results indicate that although human plasma contains endogenous substances which inhibit MAO activity, alterations in their concentration are probably not responsible for the previously reported transient changes in platelet MAO activity in PMS.

Animals↗

PubMed1991

Purification and properties of NADP-linked glucose-6-phosphate dehydrogenase from Acetobacter hansenii (Acetobacter xylinum).

The NADP-linked glucose-6-phosphate dehydrogenase from Acetobacter hansenii (formerly known as Acetobacter xylinum) has been purified to apparent homogeneity. The sequence of the 10 N-terminal amino acids was determined. The subunit molecular weight of the enzyme is 53,000 as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis; gel filtration studies under nondenaturing conditions revealed that the molecular weight of the enzyme is 200,000 to 220,000 at pH 6.5 and 9.5, suggesting that the native enzyme is a tetramer. Specificity studies at both pH 6.5 and 9.5 demonstrated that the enzyme is a typical NADP-preferring glucose-6-phosphate dehydrogenase. The enzyme's catalytic activity increases with increasing pH, kcat being approximately 4 times greater at pH 9.5 than at pH 6.7 and the Km for NADP+ being 3 times lower at the higher pH; but the Km for glucose 6-phosphate is nearly 20 times higher at pH 9.5 than at pH 6.7, suggesting that the enzyme is catalytically more efficient at the lower pH. At pH 6.7, initial velocity measurements, product inhibition by NADPH, and inhibition by glucosamine 6-phosphate yielded results that were consistent with a steady-state random mechanism. At pH 9.5, steady-state kinetic analyses suggested that the mechanism is ordered, with coenzyme binding first, but nonlinear double-reciprocal plots were observed in the presence of NADPH when glucose 6-phosphate was varied and a complete kinetic analysis was not undertaken. Among several nucleotides and potential inhibitory ligands examined, only 2',5'-ADP inhibited the enzyme significantly.

Amino Acid Sequence↗