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Biomedical subjects

M Christopher

Publications and source records attributed to M Christopher.

At least 19 recordsLinked to original sources
PubMed2005

Effects of different aspirin formulations on platelet aggregation times and on plasma salicylate concentrations.

BACKGROUND: Early aspirin treatment is widely used to inhibit platelet activity and to reduce morbidity and mortality in patients presenting with an acute myocardial infarction or a stroke. A number of different aspirin formulations have been used for this purpose; however, a comparison of their effectiveness in inhibiting early platelet aggregation has not been determined. METHODS: In this study, we determined plasma salicylate concentrations and platelet inhibitory activities at various times after ingestion of three commonly used aspirin formulations: soluble aspirin (Alka-Seltzer), 325 mg, chewed baby aspirin, 324 mg, and whole compressed non-enteric coated aspirin, 324 mg. Twenty-four healthy volunteers, 18-39 years of age, participated in the prospective single-blinded triple-crossover study. Plasma salicylate concentrations and inhibition of arachidonic acid-induced platelet aggregation were determined on post-dose blood samples collected at 2.5, 5.0, 7.5, 10, 15, 20, 25, 30, and 40 min. All subjects crossed over to the other two formulations with at least 2 weeks between ingestions. RESULTS: The median platelet inhibition times for the chewed, soluble, and whole aspirin formulations were 7.5, 7.5, and 10.0 min, respectively. Soluble and chewed aspirin were found to inhibit platelet aggregation faster than whole aspirin (p<0.001); however, there were no significant differences in platelet aggregation times between the soluble and chewed formulations (p<0.163). Inhibition of platelet aggregation was found to occur at an average plasma salicylate concentration of 2.46 microg/mL, regardless of method of ingestion. CONCLUSION: The results indicate that soluble and chewed aspirin inhibit platelet aggregation in a shorter period of time than does whole aspirin. The results suggest that chewing baby aspirin or taking soluble buffered aspirin may be the preferred route of administration for early platelet inhibition.

Administration, Oral↗
PubMed2005

An evolutionary approach to the architecture of effective healthcare delivery systems.

PURPOSE: Aims to show that material flow concepts developed and successfully applied to commercial products and services can form equally well the architectural infrastructure of effective healthcare delivery systems. DESIGN/METHODOLOGY/APPROACH: The methodology is based on the "power of analogy" which demonstrates that healthcare pipelines may be classified via the Time-Space Matrix. FINDINGS: A small number (circa 4) of substantially different healthcare delivery pipelines will cover the vast majority of patient needs and simultaneously create adequate added value from their perspective. RESEARCH LIMITATIONS/IMPLICATIONS: The emphasis is firmly placed on total process mapping and analysis via established identification techniques. Healthcare delivery pipelines must be properly engineered and matched to life cycle phase if the service is to be effective. PRACTICAL IMPLICATIONS: This small family of healthcare delivery pipelines needs to be designed via adherence to very specific-to-purpose principles. These vary from "lean production" through to "agile delivery". ORIGINALITY/VALUE: The proposition for a strategic approach to healthcare delivery pipeline design is novel and positions much currently isolated research into a comprehensive organisational framework. It therefore provides a synthesis of the needs of global healthcare.

Delivery of Health Care, Integrated↗
PubMed2005

Leptospirosis--an overview.

One of the important causes of acute febrile illness in a country where malaria, typhoid and dengue are also not uncommon, leptospirosis, a zoonotic disease spread by rodents, is endemic in Tamil Nadu, Kerala and Andamans; and is now being increasingly reported from other parts of India, perhaps with better facility to diagnose the disease. Disease of profound importance in view of its grave outcome, in its icteric form (Weil's disease), may have a mortality of as high as 40%. Worst prognosticator is the presence of multi-organ failure (MOF), as in any other septicemia. Andaman hemorrhagic fever (AHF), a type peculiar to Andamans, is now being described elsewhere in the country also. IgM ELISA, Dot-ELISA, dip-stick method and slide agglutination test (SAT) are newer screening methods for diagnosis of leptospirosis, but are only genus-specific. Identifying specific serovar is possible by Micro-agglutination test (MAT) and culture method only. Anicteric type of disease, however, is easily treatable with penicillin and has a good prognosis. Oral doxycycline can be used for prophylaxis during the risk of exposure.

Humans↗
PubMed2001

Methylation and mutational analysis of p27(kip1) in prostate carcinoma.

BACKGROUND: We have previously identified 12p12-13 as a region of frequent genetic loss in prostate carcinoma. A candidate tumor suppressor gene at this locus is the cyclin dependent kinase inhibitor p27(kip1), which has been implicated as a marker of aggressive prostate carcinoma. Herein, we examine metastatic prostate tumors, xenografts, and cell lines for gene inactivation via mutational inactivation or promoter hypermethylation. METHODS: Mutation analysis was performed on metastatic prostate tumors of 18 patients, eight prostate carcinoma cell lines, and 18 xenografts by PCR amplification of the entire open reading frame of p27(kip1). PCR products were sequenced directly using internal primers. Methylation analysis was performed on four cell lines and nine xenografts using direct sequencing of cloned PCR products of bisulfite treated DNA. Presence of a CpG was consistent with methylation of that cytosine in the original sample. RESULTS: With the exception of the previously reported homozygous deletion, no additional mutations were identified. Methylated CpG residues were identified in three xenografts (LuCAP23, LuCAP35, and PC82) and the methylated residues clustered at six sites; the cytosines 69, 149, 191, 286, 349, and 487 base pairs 5' of the ATG start codon. However, no sample demonstrated promotor methylation in all sequenced clones and the number of methylated base pairs ranged from seven to three, not the level usually associated with gene silencing. CONCLUSIONS: Mutational inactivation of p27(kip1) is a rare event in metastatic prostate carcinoma. While CpG methylation does occur, it is an infrequent event and does not appear to be the mechanism of p27(kip1) down regulation in prostate carcinoma.

Cell Cycle Proteins↗
PubMed2001

Role of ethics committees, ethics networks, and ethics centers in improving end-of-life care.

This article chronicles the work of Midwest Bioethics Center, several community-state partnerships, and other local and national initiatives to determine their proper role and appropriate contribution. Professional education and development, institutional reform, and community engagement are areas of concern because ethics committees, networks, and centers sponsor workshops and conferences on palliative care for healthcare professionals, hold public forums, develop advance care planning projects, and provide expertise to legislators and other policymakers. The leading edge of the work being done by ethics committees, networks, and centers appears to be using continuous quality improvement methods, specifically the development of quality indicators, to promote accountability in end-of-life care reform efforts. This work is something that ethics committees can and should take on.

Journal Article↗
PubMed2001

Learning from different cultures--a cultural diversity project in end-of-life care.

In January 1997, Midwest Bioethics Center (MBC) launched PATHWAYS to Improve End-of-Life Care, a three-year multifaceted community initiative to improve care of the dying in the Kansas City metropolitan area. Pathways focused on professional education and development, institutional reform, and public engagement, using thirteen different strategies to accomplish dozens of projects. Ultimately, more than 2,000 professionals and other community leaders were involved and more than 600 organizations participated. This article describes a cultural diversity project on end-of-life care that developed from this program.

Attitude to Death↗
PubMed1999

Insulin secretion in growth hormone-deficient adults: effects of 24 months' therapy and five days' acute withdrawal of recombinant human growth hormone.

Beta-cell function in growth hormone (GH)-deficient (GHD) adults is poorly documented. Beta-cell function was therefore studied in 10 GHD adults (age, 40+/-3 years; weight, 79.3+/-4.8 kg; body mass index [BMI], 27.5+/-1.3 kg x m(-2)) before and after 6- and 24-month recombinant human GH (rhGH) therapy (0.24 IU x kg(-1) x wk(-1)) compared with 10 age-, sex-, weight-, and BMI-matched control subjects. With rhGH therapy, fat-free mass (FFM) increased (48.2+/-4.9, 52.5+/-4.8, and 59+/-6.8 kg, respectively) and fat mass (FM) decreased (33.8%+/-2.8%, 28.0%+/-3.0%, and 29.4%+/-2.5%, respectively), as did serum cholesterol. Oral glucose tolerance initially deteriorated at 6 months, but improved toward the control value by 24 months. Fasting insulin (FI) increased significantly, as did the acute insulin response to oral glucose (deltaAIR(OGTT)/deltaG) at 30 minutes (FI: pretreatment 9.8+/-0.8, 6 months, 14.0+/-1.8, 24 months 12.5+/-1.6 v control 11.4+/-1.9 mU x L(-1); deltaAIR(OGTT)/deltaG: pretreatment 201+/-24, 6 months 356+/-41, 24 months 382+/-86 v control 280+/-47 mU x mmol(-1)). However, the acute insulin response to intravenous (IV) glucose (AIR(G)) and IV glucagon at euglycemia and hyperglycemia did not change with rhGH therapy and were similar to the control group values. Importantly, the expected reciprocal relationships (as observed for the control group) between the various insulin secretory parameters and insulin sensitivity (SI) either were not present or were statistically weak in GHD subjects, despite the 35% decrease in SI by 24 months of rhGH therapy. In particular, over time, there was an attenuation of insulin secretion with respect to the ongoing insulin resistance with rhGH therapy, particularly for AIR(G) at 24 months. After 5 days of rhGH withdrawal, insulin secretion decreased and SI improved in GHD subjects. It is concluded that the current long-term rhGH treatment regimens appear to impact on insulin secretion such that the normal relationships between insulin secretion and SI are altered despite the favorable impact on body composition and serum lipid profiles.

Adult↗
PubMed1999

My mother's gift--the link between honesty and hope.

Doctors and other care providers often refuse to be direct and straightforward with patients needing end-of-life care because they do not want to take away hope. But the resiliency of hope is not linked with continuing life. Using introspection, a review of the literature, and a sampling of opinions gleaned from members and friends of the Midwest Bioethics Center, the author of this article concludes that all patients should be given full and forthright knowledge about the prognoses--not in spite of the patient's need for hope, but in hope's service.

Chronic Disease↗
PubMed1999

PATHWAYS to improve end-of-life care--a community approach.

Midwest Bioethics Center responded to the SUPPORT study with a strategic initiative called PATHWAYS to Improve End-of-Life Care: A Community Approach. This article introduces that initiative and reviews its substantial contributions in the broad sense. The effects of this program, although its evaluation has yet to be completed, are far-reaching because PATHWAYS tackled the problem of dying, not as a medical problem, but as a problem for the community as a whole.

Community Health Services↗
PubMed1998

Defects of insulin action and skeletal muscle glucose metabolism in growth hormone-deficient adults persist after 24 months of recombinant human growth hormone therapy.

We have previously reported that GH-deficient (GHD) adults are severely insulin resistant. In the present study, we determined the effects of 6 months (n = 7) and 24 months (long-term; n = 11) of recombinant human GH (rhGH) therapy (approximately 0.22 IU/kg.week) on body composition and fasting biochemical (including lipid) parameters, and baseline and insulin-stimulated: 1) rates of hepatic glucose production, total glucose disposal (Rd), total glycolysis (GF) and glucose storage (GS); and 2) skeletal muscle glucose processing [using the euglycemic-hyperinsulinemic (approximately 60 mU/L) clamp technique with tritiated glucose infusion coupled with skeletal muscle biopsies]. To allow baseline comparison, these measurements were also obtained from 10 control subjects matched to the pretreated GHD adults for age, sex, and body mass index. Long-term rhGH therapy in GHD adults induced significant improvements in fat mass, abdominal fat mass and fat free mass, and reductions in fasting cholesterol and low-density lipoprotein-cholesterol levels (P < 0.05-0.01 vs. pretreatment values). However, there was a significant increase in fasting insulin (13.1 +/- 0.9 vs. 8.6 +/- 1.1 mU/L; P < 0.01) and connecting peptide (0.56 +/- 0.05 vs. 0.41 +/- 0.06 nmol/L; P < 0.05). Although rates of baseline hepatic glucose production, GF, and GS were unchanged, the insulin-stimulated increment (delta) in Rd, GF, and GS remained markedly attenuated in the long-term rhGH-treated GHD adults [pretreatment: delta Rd 16.6 +/- 3.4, delta GF 3.0 +/- 1.2, delta GS 13.6 +/- 3.0 vs. 24 months of rhGH: delta Rd 17.2 +/- 3.3, delta GF 3.1 +/- 0.9, delta GS 14.1 +/- 2.5 vs. controls: delta Rd 42.6 +/- 4.3, delta GF 9.2 +/- 1.9, delta GS 35.9 +/- 4.5 mumol/kg fat free mass.min; P < 0.05-0.01 vs. controls]. Additionally, there was a sustained reduction in the insulin-stimulated skeletal muscle glycogen synthase fractional velocity (pretreatment: 0.29 +/- 0.03 vs. 24 months of rhGH: 0.24 +/- 0.03 vs. controls: 0.48 +/- 0.04; both P < 0.05 vs. controls), which was accompanied by a sustained 44% decrease in baseline glycogen content and a 70% increase in baseline im glucose concentrations in the presence of low-to-normal glucose 6-phosphate levels and persisting euglycemia. Stepwise regression analysis revealed that body weight and fasting free fatty acid and high-density lipoprotein (HDL)-cholesterol accounted for 82% of the variance in the insulin sensitivity index in long-term rhGH-treated adults, and that the 24-month fasting insulin-like growth factor 1 was a negative predictor of the change in insulin sensitivity (r = -0.82; P < 0.01). In conclusion, despite improvements in body composition and lipid profiles, the severe defects of in vivo insulin sensitivity and skeletal muscle intracellular glucose phosphorylation and glycogen synthase activity, which are associated with modestly elevated insulin-like growth factor 1 levels, normal free fatty acid levels, and the development of hyperinsulinemia, persist with long-term rhGH therapy.

Adult↗
PubMed1996

Peritoneal fluid analysis in peripartum mares.

OBJECTIVE: To characterize, in mares, changes in peritoneal fluid that occurred within the first 7 days after routine foaling. DESIGN: Prospective observational trial. ANIMALS: 15 mares. PROCEDURE: Abdominocentesis was performed within 10 days before foaling and again 12 hours, 3 days, and 7 days after each horse foaled. Data recorded for each sample included total nucleated cell count, differential cell count, specific gravity, fibrinogen concentration, and total protein concentration. Smears of each sample were examined by a single clinical pathologist. RESULTS: There were not any significant differences over time in specific gravity, total protein concentration, fibrinogen concentration, total nucleated cell count, or number of small mononuclear cells. Mean numbers of neutrophils and large mononuclear cells in samples collected after foaling were significantly higher than mean numbers in samples collected before foaling. For 11 of 14 horses, all samples were characterized cytologically as transudates without cytologic abnormalities. CLINICAL IMPLICATIONS: Results of analysis of peritoneal fluid from peripartum mares suggest that nucleated cell count, protein concentration, and specific gravity of peritoneal fluid from mares that have recently foaled should be normal. Thus, peritoneal fluid abnormalities detected in mares within a week after foaling should usually be attributed to a systemic or gastrointestinal problem and not to the foaling process itself.

Animals↗
PubMed1996

Insulin resistance in growth hormone-deficient adults: defects in glucose utilization and glycogen synthase activity.

Fourteen GH-deficient (GHD) adults were compared with 12 age-, sex-, and body mass index-matched control subjects using a baseline tritiated glucose equilibration period and euglycemic-hyperinsulinemic (approximately 55 mU/L) clamp in conjunction with paired muscle biopsies for measurement of glycogen synthase fractional velocity (FV0.1). Despite similar basal rates of total glucose disposal (Rd), there was a 64% reduction in the insulin-stimulated rise (delta) in Rd in the GHD adults compared to that in controls [16.6 +/- 2.8 vs. 44.7 +/- 6.0 mumol/kg fat free mass (FFM)/min; P < 0.001], which was mainly due to a decreased glucose storage (GS) rate (delta GS, 12.6 +/- 2.9 vs. 39.5 +/- 7.5 mumol/kg FFM/min; P < 0.01). Furthermore, the insulin sensitivity indexes of Rd (0.39 +/- 0.07 vs. 0.85 +/- 0.11; P < 0.05) and GS (0.25 +/- 0.07 vs. 0.72 +/- 0.13 mumol/kg FFM/min per mU/L; P < 0.02) were reduced in GHD adults compared to the control values. The insulin sensitivity of the glycolytic pathway was also reduced by approximately 50% in GHD adults (P = 0.07 vs. controls). Insulin-stimulated FV0.1 was decreased in GHD adults (0.31 +/- 0.02 vs. 0.47 +/- 0.03; P < 0.005) despite similar basal FV0.1. Using multiple and stepwise regression analysis, duration of GH deficiency, fasting triglycerides and fasting insulin accounted for 67% of the variance in the insulin sensitivity index of Rd. In conclusion, the severe insulin resistance in GHD adults is mainly due to the inhibition of the GS pathway and glycogen synthase activity in peripheral tissues, which is related to the duration of GH deficiency, fasting triglycerides, and fasting insulin.

Adult↗
PubMed1995

Multiple defects of both hepatic and peripheral intracellular glucose processing contribute to the hyperglycaemia of NIDDM.

Non-insulin-dependent diabetic (NIDDM) patients were studied during a modified euglycaemic state when fasting hyperglycaemia was normalized by a prior (-210 to -150 min)--and later withdrawn (-150-0 min)--intravenous insulin infusion. Glucose metabolism was assessed in NIDDM patients (n = 10) and matched control subjects (n = 10) using tritiated glucose turnover rates, indirect calorimetry and skeletal muscle glycogen synthase activity determinations. Total and non-oxidative exogenous glycolytic flux rates were measured using appearance rates of tritiated water. A + 180 min euglycaemic hyperinsulinaemic (40 mU.m-2.min-1) clamp was performed to determine the insulin responsiveness of the various metabolic pathways. Plasma glucose concentration increased spontaneously during baseline measurements in the NIDDM patients (-120 to 0 min: 4.8 +/- 0.3 to 7.0 +/- 0.3 mmol/l; p < 0.01), and was primarily due to an elevated rate of hepatic glucose production (3.16 +/- 0.13 vs 2.51 +/- 0.16 mg.kg FFM-1.min-1; p < 0.01). In the NIDDM subjects baseline glucose oxidation was decreased (0.92 +/- 0.17 vs 1.33 +/- 0.14 mg.kg FFM-1.min-1; p < 0.01) in the presence of a normal rate of total exogenous glycolytic flux and skeletal muscle glycogen synthase activity. The simultaneous finding of an increased lipid oxidation rate (1.95 +/- 0.13 vs 1.61 +/- 0.07 mg.kg FFM-1.min-1; p = 0.05) and increased plasma lactate concentrations (0.86 +/- 0.05 vs 0.66 +/- 0.03 mmol/l; p = 0.01) are consistent with a role for both the glucose-fatty acid cycle and the Cori cycle in the maintenance and development of fasting hyperglycaemia in NIDDM during decompensation. Insulin resistance was demonstrated during the hyperinsulinaemic clamp in the NIDDM patients with a decrease in the major peripheral pathways of intracellular glucose metabolism (oxidation, storage and muscle glycogen synthase activity), but not in the pathway of non-oxidative glycolytic flux which was not completely suppressed during insulin infusion in the NIDDM patients (0.55 +/- 0.15 mg.kg FFM-1.min-1; p < 0.05 vs 0; control subjects: 0.17 +/- 0.29; NS vs 0). Thus, these data also indicate that the defect(s) of peripheral (skeletal muscle) glucose processing in NIDDM goes beyond the site of glucose transport across the cell membrane.

Biopsy↗
PubMed1987

Natural course of the human bite wound: incidence of infection and complications in 434 bites and 803 lacerations in the same group of patients.

Human bites and common lacerations are frequent in certain residential groups in institutions for the care of developmentally disabled individuals. We screened the records of such an institution and studied the course and outcome of 434 human bite wounds and 803 lacerations in the same group of clients. Infection developed in 13.4% of the lacerations, and 17.7% of the bite wounds (chi 2 = 3.474; p greater than 0.06). Prophylactic antibiotics were administered after 14.0% of the bite wounds, and 3.2% of the lacerations. Infection supervened after prophylactic antibiotics in 29.5% of the bites and 34.6% of the lacerations. No patient with a bite wound required debridement, initial or subsequent surgical intervention other than wound closure, admission to hospital, or intravenous antibiotics. There is no recorded instance of a bite wound complication other than immediate loss of tissue. These data substantiate a higher incidence of infection in human bite wounds, but they are scant support for admonition that such wounds are indication for routine antimicrobial prophylaxis or aggressive surgical intervention.

Anti-Bacterial Agents↗
PubMed1980

Quantitative study of motor endplates in muscle fibres dissociated by a simple procedure.

Large numbers of single muscle fibres can be obtained reproducibly from glutaraldehyde-fixed skeletal muscle by the method described here. With suitable modifications, one can estimate acetylcholine receptor number (alpha-bungarotoxin binding sites) and endplate area in parallel portions produced from the same muscle sample, so that small differences (e.g. with growth or between muscle types) become detectable. Microdissection further increases the precision of evaluation of junctional, perijunctional and extrajunctional binding sites. Other applications are illustrated.

Acetylcholinesterase↗