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Biomedical subjects

K Kennedy

Publications and source records attributed to K Kennedy.

At least 37 records · Page 2Linked to original sources
PubMed1996

Triage: techniques and applications in decision making.

Correct decision making may have far-reaching consequences. Triage is an area in which decision-makers must know what they are doing, why they are doing it, and which actions to take to achieve a satisfactory outcome. Triage has its origins in military history and today is used in a variety of medical settings. In this article we focus on the role of triage in disaster situations, its application in military settings, and its use in disaster medicine. Useful concepts enabling correct decision making by the triage officer include the application of computer technology and a review of methods of patient categorization. The dynamic nature of triage and the role of the triage officer as part of a team approach to disaster patient management are highlighted. We explore techniques for the successful training and education of triage officers and investigate a model of the emergency physician as the triage officer.

Decision Making↗
PubMed1996

Continuous quality improvement in health maintenance organizations: an application of the HEDIS model.

One aspect of the Clinton Healthcare Reform programme is to assist health maintenance organizations (HMOs) in collecting and analysing data for the purpose of continuous quality improvement. The HEDIS 2.0 quality performance measurement model is currently in use and endorsed by the National Committee for Quality Assurance (NCQA). Outlines a process using HEDIS 2.0 by which an HMO can identify crucial problem areas and track the success of the solution process. Discusses the use of other relevant statistical tools.

Data Interpretation, Statistical↗
PubMed1996

Direct quantitation of the number of individual penicillin-binding proteins per cell in Escherichia coli.

The penicillin-binding proteins (PBPs) are a set of enzymes that participate in the terminal stages of bacterial peptidoglycan assembly. As their name implies, these proteins also covalently bind and are inhibited by beta-lactam antibiotics. Although many studies have examined the relative binding affinities of a number of beta-lactam antibiotics, a surprisingly small number of studies have addressed the absolute numbers of each of the PBPs present in the bacterial cell. In the present study, the PBP values initially reported in Escherichia coli almost 20 years ago by B. G. Spratt (Eur. J. Biochem. 72:341-352, 1977) were refined. The individual PBPs from a known number of bacteria radiolabeled with [3H]benzylpenicillin were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The radioactive bands were located, excised, and quantitatively extracted from the gel slices. The radioactivity was measured by scintillation counting, and the absolute disintegrations per minute were calculated. From the specific activity of the labeled penicillin, the absolute disintegrations per minute, and the CFU per milliliter, a determination of the number of each of the PBPs per cell was made. The measurements were performed on multiple samples to place statistical limits on the numbers obtained. The values for the individual PBPs found in E. coli deviated in several ways from the previously reported observations. Of particular significance is the higher number of molecules of PBP 2 and 3 observed, since these PBPs are known to participate in cell morphogenesis. The PBP content in both rich Luria broth medium and M9 minimal medium was determined, with the slower-growing cells in minimal medium possessing fewer of the individual PBPs per cell.

Bacterial Proteins↗
PubMed1995

Site-directed mutagenesis of a serine residue in cinnamyl alcohol dehydrogenase, a plant NADPH-dependent dehydrogenase, affects the specificity for the coenzyme.

Using recombinant cinnamyl alcohol dehydrogenase isoform 2 (CAD2, EC 1.1.1.195), an NADPH-dependent aromatic alcohol dehydrogenase involved in lignification in vascular plants, we have investigated the detailed steady-state kinetic mechanism of CAD2 and the role of a serine residue in determining the cofactor specificity of CAD2. Site-directed mutagenesis (S212D) and overexpression of the WT and mutant S212D forms of CAD2 in Escherichia coli, followed by kinetic studies on the purified WT and mutant proteins, confirmed the involvement of S212D in recognizing the phosphate group of NADPH and provided information on the structural requirements for NADPH specificity. From substrate kinetic patterns and product inhibition studies both WT and S212D mutant forms of CAD2 have been shown to follow rapid equilibrium random bireactant kinetics with the value of the interaction factor (alpha) for WT (0.25) being significantly less than that for S212D CAD2 (0.45). The changes in binding energy arising from the mutation on the binding of the 2'-phosphate site of the coenzyme were assessed. A marked degree of physical interaction was detected between the enzymatic binding sites of the coniferyl alcohol substrate and the 2'-phosphate binding region, which are quite distant in the three-dimensional structure. The inhibition by 2',5'-ADP and 5'-AMP was found to be weak for both WT and S212D CAD2. Strong substrate inhibition was detected for CAD2, and its implications for plant physiological studies were assessed.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Oxidoreductases↗
PubMed1995

Identification of a region of the N-terminal of the human CCKA receptor essential for the high affinity interaction with agonist CCK.

The discovery of an N-terminally truncated isoform of the cholecystokinin A subtype (CCKA) receptor exhibiting an atypical pharmacology led us to study the effects of N-terminal truncation on the pharmacology of the human CCKA receptor. We cloned the cDNA encoding the full CCKA receptor and constructed two truncated forms, one which lacked the first 37 amino acids (CCKAT38) and another which lacked the first 42 amino acids (CCKAT43). Expression of the receptors in COS-7 cells showed that the CCKAT38 receptor displayed a pharmacological profile identical to that of the full receptor. In contrast, the CCKAT43 receptor did not directly bind agonist CCK9; however, the agonist could compete for binding at low affinity sites. Binding of the partial agonist JMV180 and the antagonist JMV179 were unaffected. These results identify for the first time a part of the N-terminal, close to the membrane, of the human CCKA receptor that is essential for the high affinity interaction with CCK.

Amino Acid Sequence↗
PubMed1995

Baseline cyst formation after luteal phase gonadotropin-releasing hormone agonist administration is linked to poor in vitro fertilization outcome.

OBJECTIVE: To investigate the prognostic significance of baseline ovarian cysts after luteal phase GnRH agonist (GnRH-a) administration for IVF-ET. DESIGN: All nondonor IVF-ET cycles in one program in which luteal phase GnRH-a was administered between July 1993 and January 1994 were assessed for the formation of baseline ovarian cysts defined as a mean diameter > or = 15 mm. Outcome data from the IVF cycles were compared between patients with and without baseline ovarian cysts. RESULTS: Of 78 IVF cycles, baseline cysts > or = 15 mm were noted in 26 cycles. Cycles in which cysts were formed were associated with significantly older patients with significantly higher baseline FSH values. Cycles in which cysts were present demonstrated fewer follicles, retrieved oocytes, and embryos. Cyst cycles also demonstrated a lower peak E2 level, implantation rate, and clinical pregnancy rate (PR) per initiated cycle (7.7% versus 32.7%). Cyst cycles also demonstrated a higher cancellation rate. Logistic regression modeling, accounting for age, confirmed significantly lower clinical PRs in cycles with a baseline cyst. CONCLUSIONS: Baseline cyst formation after luteal phase GnRH-a administration is both a marker for poor responders and a reliable predictor of poor stimulation and low PRs in a given IVF-ET cycle.

Chorionic Gonadotropin↗
PubMed1995

The small for gestational age infant: accelerated or delayed pulmonary maturation? Increased or decreased survival?

OBJECTIVE: Small for gestational age (SGA) neonates have been considered to have accelerated pulmonary maturation and thus a lower risk for respiratory distress syndrome (RDS) than appropriate for gestational age (AGA) neonates. This, however, has not been thoroughly examined. Therefore, we compared SGA infants with AGA infants of the same gestational age (GA) with respect to risk of RDS, respiratory failure, or death. POPULATION: An indigent population born in a large county hospital. METHODS: Multivariate analyses were performed controlling for GA alone or for GA, race, sex, and congenital anomalies. Because the proper method to identify SGA infants is unclear, we performed separate analyses using different GA estimates (obstetric or pediatric) and intrauterine growth grids (hospital-specific grids or grids for a healthy, geographically-defined population). RESULTS: SGA infants did not fare better than AGA infants in any analysis. SGA infants had significantly increased risk in some analyses of RDS and in almost all analyses of respiratory failure or death. The risk associated with being SGA was generally comparable to that associated with male sex or White race. CONCLUSION: The concept that intrauterine growth retardation accelerates lung maturation and improves outcome is not supported in comparisons of SGA and AGA infants of the same GA, sex, and race. This widely accepted concept deserves critical re-evaluation.

Fetal Growth Retardation↗
PubMed1995

Are cancer patients subject to employment discrimination?

We sought to determine whether patients undergoing treatment for cancer had experienced discrimination in employment and, if so, how that discrimination was manifested. We also sought to determine what variables affected the rate of discrimination, including age, gender, occupation, and employer size. We surveyed 422 patients diagnosed with cancer who were being treated at an acute-care, comprehensive cancer center in Houston, Texas, or were being followed after therapy. Whereas 76% of respondents indicated that they were working at the time of diagnosis and 82% said that they wanted to work full- or part-time, only 56% were working at the time of the study. Type of occupation was the main determinant of whether individuals were employed after diagnosis. The study documents self-reported discrimination in employment on the basis of cancer. Additional research is needed to determined the measures, including legal recourse, necessary to enable cancer patients to obtain and continue work.

Adolescent↗
PubMed1994

Association of human corticotropin-releasing hormone to its binding protein in blood may trigger clearance of the complex.

Late in the last trimester of human pregnancy, as plasma CRH levels rise, the concentration of circulating CRH-binding protein (CRH-BP) falls. We have investigated, using nonpregnant subjects, the hypothesis that CRH has a negative effect on plasma levels of CRH-BP. A specific RIA developed with the aid of recombinant binding protein has been used to measure CRH-BP. Subjects given iv infusions of human CRH for 10 h showed a sustained fall in plasma CRH-BP for the duration of the infusion. Intravenous bolus injection of human CRH produced a rapid reduction in CRH-BP levels to 54% of the basal value, whereas ovine CRH was without effect, even though both peptides are cleared from the plasma at similar rates and have similar effects on the pituitary-adrenal axis. The rapid clearance was concluded to be related to ligand affinity, as ovine CRH has a 200-fold lower affinity than human CRH for CRH-BP. We suggest that the rising levels of CRH are responsible for the reduction in CRH-BP concentrations observed in late pregnancy, and that this reduction is triggered by the binding of CRH-BP to its ligand.

Animals↗
PubMed1993

Outpatient treatment of febrile episodes in low-risk neutropenic patients with cancer.

BACKGROUND: Hospitalization and intravenous (IV) broad-spectrum antibiotics are the standard of care for all febrile neutropenic patients with cancer. Recent work suggests that a low-risk population exists who might benefit from an alternate approach. METHODS: A prospective randomized clinical trial was performed comparing oral ciprofloxacin 750 mg plus clindamycin 600 mg every 8 hours with IV aztreonam 2 g plus clindamycin 600 mg every 8 hours for the empiric outpatient treatment of febrile episodes in low-risk neutropenic patients with cancer. RESULTS: The oral regimen cured 35 of 40 episodes (88% response rate), whereas the IV regimen cured 41 of 43 episodes (95% response rate, P = 0.19). Although the cost of the oral regimen was significantly less than that of the IV regimen (P < 0.0001), it was associated with significant renal toxicity (P < 0.05), which led to early termination of the study. Overall, combining its safety and efficacy, the IV regimen was superior (P = 0.03). CONCLUSIONS: This prospective study suggested that outpatient antibiotic therapy for febrile episodes in low-risk neutropenic patients with cancer is safe and effective. Better oral regimens are needed.

Administration, Oral↗
PubMed1993

Improvements in the microbiological quality of food samples from a hospital cook-chill system since the introduction of HACCP.

A cook-chill system of catering was introduced in Waterford Regional Hospital in December 1989. An intensive system of microbiological monitoring was put in place from day one and after 16 months a Hazard Analysis Critical Control Point (HACCP) system was introduced. Continuous monitoring showed an improvement in the microbiological quality of the food when using HACCP, with more than 90% of samples having total viable counts of less than 1 x 10(3) g-1 and the virtual elimination of pathogens. The introduction of HACCP allowed a reduction in the level of sampling and provided a useful set of records for quality assurance.

Cooking↗
PubMed1993

The need to reevaluate trisomy screening for advanced maternal age in prenatal diagnosis.

OBJECTIVES: Fluorescence in situ hybridization aneuploidy screening promises immediate results. To evaluate aneuploidy screening in prenatal diagnosis, the prenatal records at Oregon were reviewed. STUDY DESIGN: Karyotype reports of 7240 amniocentesis samples referred for advanced maternal age were retrospectively reviewed for numeric and structural chromosome abnormalities. RESULTS: The frequency of abnormal karyotypes was 2.5%; 1.4% were age-related trisomies and sex-chromosome aneuploids, and 1.1% were non-age-related abnormalities. The incidence of structural rearrangements was 0.9%, of which 70% were familial but not suspected on the basis of family history. CONCLUSIONS: Structural chromosome abnormalities were twice as common as previously reported, representing a significant unrecognized risk for subsequent pregnancies and other family members. Fluorescence in situ hybridization aneuploidy screening would not routinely detect structural chromosome abnormalities, which were twice as frequent as numeric aneuploidy at age 35 years. Routine use of fluorescence in situ hybridization for prenatal diagnosis should not be adopted without a prospective study of its accuracy, reliability, and impact on prenatal diagnosis.

Amniocentesis↗
PubMed1993

Factors to consider in determining the adequacy of dialysis.

Advances in recent technology and the trend toward reducing dialysis times has had a detrimental effect on morbidity and mortality rates. Urea Kinetic Modeling provides the dialysis staff with essential information to help ensure optimum care and increase the probability of success. Urea Kinetic Modeling has not been utilized by many centres because it was thought to be too time consuming and too complicated. Simplification of the variables without jeopardizing the outcome makes Urea Kinetic Modeling a much more feasible option to determine dialysis adequacy. All parameters in Urea Kinetic Modeling are dependent, interrelated and all are required to describe dialysis adequacy. Urea Kinetic Modeling allows the physician, dietician and nurse to individualize dialysis prescriptions, determine excessive or inadequate protein intake and to review delivered versus desired treatment times.

Blood Flow Velocity↗
PubMed1992

Extending lactational amenorrhoea in Manila: a successful breast-feeding education programme.

An experimental breast-feeding education programme conducted at the Philippine General Hospital in Manila demonstrated that women could be motivated to improve their breast-feeding practices and lengthen their period of lactational amenorrhoea in comparison to a control group. Mothers who participated in the programme breast-fed their babies more frequently, delayed the introduction of regular supplements, used fewer bottles and pacifiers and maintained night feeding longer than mothers who were not exposed to the positive breast-feeding messages. The programme was successful in lengthening the period of amenorrhoea among women with elementary, high school, or technical school education, but not among college-educated women. Different educational approaches may be necessary for women of different education levels.

Adult↗
PubMed1991

Assay of plasma cannabidiol by capillary gas chromatography/ion trap mass spectroscopy following high-dose repeated daily oral administration in humans.

Plasma levels of cannabidiol (CBD) were ascertained weekly in 14 Huntington's disease patients undergoing a double-blind, placebo-controlled, crossover trial of oral CBD (10 mg/kg/day = about 700 mg/day) for 6 weeks. The assay procedure involved trimethylsilyl (TMS) derivatization of CBD and the internal standard delta-6-tetrahydrocannabinol (THC), capillary column gas chromatography, ion trap mass spectroscopy in positive ion chemical ionization mode using isobutane, and calculations of CBD levels based on peak ion intensity of the 387 M + H peak of delta-6-THC-TMS and the 459 M + H peak of CBD-2TMS. The sensitivity of the assay was about 500 pg/ml, and the precision was about 10-15%. Mean plasma levels of CBD ranged from 5.9-11.2 ng/ml over the 6 weeks of CBD administration. CBD levels averaged 1.5 ng/ml one week after CBD was discontinued, and were virtually undetectable thereafter. The elimination half-life of CBD was estimated to be about 2-5 days, and there were no differences between genders for half-life or CBD levels. Additionally, no plasma delta-1-THC, the major psychoactive cannabinoid of marijuana, was detected in any subject.

Administration, Oral↗
PubMed1991

Controlled clinical trial of cannabidiol in Huntington's disease.

Based on encouraging preliminary findings, cannabidiol (CBD), a major nonpsychotropic constituent of Cannabis, was evaluated for symptomatic efficacy and safety in 15 neuroleptic-free patients with Huntington's Disease (HD). The effects of oral CBD (10 mg/kg/day for 6 weeks) and placebo (sesame oil for 6 weeks) were ascertained weekly under a double-blind, randomized cross-over design. A comparison of the effects of CBD and placebo on chorea severity and other therapeutic outcome variables, and on a Cannabis side effect inventory, clinical lab tests and other safety outcome variables, indicated no significant (p greater than 0.05) or clinically important differences. Correspondingly, plasma levels of CBD were assayed by GC/MS, and the weekly levels (mean range of 5.9 to 11.2 ng/ml) did not differ significantly over the 6 weeks of CBD administration. In summary, CBD, at an average daily dose of about 700 mg/day for 6 weeks, was neither symptomatically effective nor toxic, relative to placebo, in neuroleptic-free patients with HD.

Adolescent↗