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Biomedical subjects

K Kennedy

Publications and source records attributed to K Kennedy.

At least 19 recordsLinked to original sources
PubMed2000

Mode of delivery and childhood blood pressure.

A number of studies have shown that children born by cesarean section have lower blood pressure during the neonatal period. The aim of this study was to investigate whether mode of delivery influenced childhood blood pressure: at age 7.5 to 8 y in a cohort of 756 children born preterm, at 7 to 9 y in a pilot study of 166 children born at term in the United Kingdom, and in a cohort of 650 Tasmanian children born at term. In the preterm cohort, systolic blood pressure was significantly lower in children born by cesarean section rather than delivered vaginally (99.3+/-10.0 versus 101.4+/-9.4 mm Hg; 95% confidence interval, -0.69 to -3.46; p = 0.003), with a significant trend to having a higher pressure in those born by breech versus forceps versus spontaneous vaginal delivery versus cesarean section. These findings were not replicated in the term cohorts. This raises the hypothesis that there is a sensitive period for programming later blood pressure by factors associated with mode of delivery and that this period does not extend to full-term.

Blood Pressure↗
PubMed1999

The effect of site-directed mutagenesis of two transmembrane serine residues on agonist-specific coupling of a cloned human alpha2A-adrenoceptor to adenylyl cyclase.

1. The effects of substitution of the Ser200 and Ser204 residues with alanine on the signalling properties of the cloned human alpha2A-adrenoceptor, stably expressed in Chinese hamster ovary (CHO) cell lines, have been investigated using noradrenaline and the structural isomers of octopamine. 2. The Ser-->Ala200 or the Ser-->Ala204 mutant forms of the alpha2A-adrenoceptor, when expressed in cells in the absence of pertussis toxin pretreatment, are two orders of magnitude more sensitive to inhibition of cyclic AMP production by (+/-)-para-octopamine and (+/-)-meta-octopamine, respectively, than cells expressing the wild-type receptor. Binding studies indicate that the effects are not due to an increased agonist affinity for the mutant receptors and that they are likely to be due to agonist-mediated conformational changes in receptor structure. 3. After incubation with pertussis toxin, (+/-)-meta-octopamine (100 microM and above) produced a stimulation of cyclic AMP levels in cells expressing the Ser-->Ala204 mutant form of the alpha2A-adrenoceptor but showed no stimulation in cells expressing the Ser-->Ala200 mutant receptor. Under these conditions (+/-)-para-octopamine did not produce any increases in cyclic AMP production in cells expressing either of the mutant receptor forms or the wild-type receptor. 4. The results emphasise the importance of the Ser200 and Ser204 residues of the alpha2A-adrenoceptor in exerting an inhibitory influence on the ability of (+/-)-para-octopamine and (+/-)-meta-octopamine respectively, to induce a receptor-agonist conformation capable of inhibiting forskolin-stimulation of cyclic AMP levels. 5. It is clear that Ser204 also prevents meta-octopamine from generating a receptor-agonist conformation that can increase cyclic AMP levels, emphasising the importance of this residue in the agonist-specific coupling of this receptor to different second messenger systems.

Adenylate Cyclase Toxin↗
PubMed1999

Double-blind, randomized trial of a synthetic triacylglycerol in formula-fed term infants: effects on stool biochemistry, stool characteristics, and bone mineralization.

BACKGROUND: The low sn-2 palmitate content of infant formulas results in formation of fatty acid calcium soaps in the stools and reduced calcium absorption. OBJECTIVE: Our objective was to test the hypotheses that increasing the proportion of sn-2 palmitate in formula for term infants would result in greater skeletal mineral deposition and reduced stool hardness. DESIGN: Healthy term neonates were randomly assigned to receive standard formula (n = 103) or formula containing 50% sn-2 palmitate (high-sn-2 formula; n = 100) for 12 wk. One hundred twenty breast-fed infants were also studied. The main outcome measures were 1) radial (single-photon absorptiometry) and whole-body (dual-energy X-ray absorptiometry) bone mineral content (WBBMC) at 12 wk and 2) stool frequency, volume, and consistency at 6 and 12 wk. Secondary outcome measures included stool fatty acid content. RESULTS: Infants receiving high-sn-2 formula had higher WBBMC (128.1 +/- 9.7 compared with 122.7 +/- 10.1 g, adjusted for size and sex), softer stools at 6 and 12 wk, and a lower proportion of stool soap fatty acids than did infants receiving the control formula. Breast-fed infants had adjusted WBBMC values (128.3 +/- 9.1 g) similar to those of infants fed high-sn-2 formula and significantly higher than those of infants fed the control formula. CONCLUSIONS: Changing the stereoisomeric structure of palmitate in infant formula resulted in higher WBBMC, reduced stool soap fatty acids, and softer stools more like those of breast-fed infants. The greater bone mass measured could be important if it persists beyond the trial period; this merits further investigation.

Absorptiometry, Photon↗
PubMed1999

A proinflammatory role for IL-18 in rheumatoid arthritis.

IL-18 is a novel cytokine with pleiotropic activities critical to the development of T-helper 1 (Th1) responses. We detected IL-18 mRNA and protein within rheumatoid arthritis (RA) synovial tissues in significantly higher levels than in osteoarthritis controls. Similarly, IL-18 receptor expression was detected on synovial lymphocytes and macrophages. Together with IL-12 or IL-15, IL-18 induced significant IFN-gamma production by synovial tissues in vitro. IL-18 independently promoted GM-CSF and nitric oxide production, and it induced significant TNF-alpha synthesis by CD14(+) macrophages in synovial cultures; the latter effect was potentiated by IL-12 or IL-15. TNF-alpha and IFN-gamma synthesis was suppressed by IL-10 and TGF-beta. IL-18 production in primary synovial cultures and purified synovial fibroblasts was, in turn, upregulated by TNF-alpha and IL-1beta, suggesting that monokine expression can feed back to promote Th1 cell development in synovial membrane. Finally, IL-18 administration to collagen/incomplete Freund's adjuvant-immunized DBA/1 mice facilitated the development of an erosive, inflammatory arthritis, suggesting that IL-18 can be proinflammatory in vivo. Together, these data indicate that synergistic combinations of IL-18, IL-12, and IL-15 may be of importance in sustaining both Th1 responses and monokine production in RA.

Animals↗
PubMed1999

Rational inhibitor design, synthesis and NMR spectroscopic study by transferred nuclear overhauser spectroscopy of novel inhibitors of cinnamyl alcohol dehydrogenase, a critical enzyme in lignification.

Cinnamyl alcohol dehydrogenase is one of the enzymes controlling the first two committed steps of lignification. Using a 3-dimensional similarity model of this enzyme, a series of novel phosphonates (1-5) was designed as potential inhibitors. Phosphonates 1-5 were synthesized in good yield by reaction of the corresponding cinnamaldehydes with tetraethylmethylene diphosphonate. Monophosphonic acids 6 and 7 were obtained by basic hydrolysis of the corresponding phosphonates while phosphonamidate 8 was synthesized by reacting benzylamine with the iminium salt intermediate of the monophosphonic acid. Using recombinant cinnamyl alcohol dehydrogenase (CAD, EC 1.1.1.195) the inhibitory activity of these compounds was evaluated and compared with that of the carbonyl analogues. Inhibition kinetic studies showed compounds 2 and 3 to be mixed type linear inhibitors while compound 4 was uncompetitive. 1H NMR studies of inhibitor 2, for which Ki and Ki' were 20 and 86 microM, respectively, in the presence of CAD based on selective line-broadening showed an increased interaction of the 3-OMe group of the aromatic ring of the inhibitor with the active site of the CAD. A transferred nuclear overhauser effect spectroscopy (TRNOESY) experiment for inhibitor 2 with CAD was used to determine the conformation of this compound bound to CAD. These results were found to be consistent with the 3-dimensional structural model of the enzyme.

Alcohol Oxidoreductases↗
PubMed1999

Popliteal vessels in knee surgery. A magnetic resonance imaging study.

Popliteal artery injury during surgery of the knee is rare but can have devastating consequences. The position of knee flexion has been thought to be protective for the popliteal artery, allowing it to fall back from the knee joint. No prior study has provided in vivo cross sectional evidence of the behavior of the popliteal vessels during knee flexion with the effect of gravity. Magnetic resonance imaging was used in nine volunteers to measure the distance of the popliteal artery and veins from the posterior proximal tibia at two levels corresponding to the levels of osteotomy in total knee arthroplasty and in high tibial osteotomy. Scans were taken with the knee in full extension and at 90 degrees flexion with the patient in the supine position, allowing for the effect of gravity. Considerable variation in behavior of the vein and the artery was observed at the high tibial osteotomy cross sectional level and the total knee arthroplasty cross sectional level. In two knees at the high tibial osteotomy cross sectional level and in two knees at the total knee arthroplasty cross sectional, level the artery moved closer to the posterior tibia with knee flexion. Even with the effect of gravity included, knee flexion does not guarantee removal of the popliteal vessels from potential harm during surgery of the knee.

Arthroplasty, Replacement, Knee↗
PubMed1997

Differential expression of the CCK-A and CCK-B/gastrin receptor genes in human cancers of the esophagus, stomach and colon.

The expression of cholecystokinin (CCK) and gastrin (G) receptors in human gastrointestinal cancers remains poorly documented and is still of a controversial nature. We have measured the levels of mRNA for CCK-A and CCK-B/gastrin receptors using quantitative reverse transcription-polymerase chain reaction (RT-PCR) in primary digestive cancers and hepatic metastases. CCK-A-receptor mRNA was detected in 5 out of 8 esophageal cancers (0.1-1 fg/microg), in 5 out of 8 gastric cancers (0.05-4.2 fg/microg) and in 5 out of 12 colon cancers (0.1-1 fg/microg RNA). CCK-B/gastrin mRNA was not detected in esophageal cancers but was detected in 7 out of 8 gastric cancers (0.05-5.2 fg/microg), and in only 2 out of 12 colon adenocarcinomas (0.05-1 fg/microg RNA). The expression of the CCK-A receptor in esophageal, gastric and colon cancers and of the CCK-B/gastrin receptor in the majority of gastric adenocarcinomas screened may be an important indicator of the influence of CCK and gastrin of local or systemic origin on the growth of these cancers.

Adenocarcinoma↗
PubMed1997

Identification of two amino acids of the human cholecystokinin-A receptor that interact with the N-terminal moiety of cholecystokinin.

A region between residues 38 and 42 of the human cholecystokinin-A (CCK-A) receptor was shown to be involved in the binding of CCK but not in that of JMV 179 and JMV 180, two peptides closely related to CCK (Kennedy, K., Escrieut, C., Dufresne, M., Clerc, P., Vaysse, N., and Fourmy, D. (1995) Biochem. Biophys. Res. Commun. 213, 845-852). In the present study, we have identified the residues of both the receptor and the ligand responsible for this differential binding. Residues Trp-39 and Gln-40 of the receptor were crucial for binding of the C-terminal nonapeptide of CCK as W39F and Q40N mutants demonstrated parallel decreases in both affinity and potency to induce accumulation of inositol phosphates (12.9- and 20.9-fold). The W39F and Q40N mutant receptors bound CCK analogues modified at their C-terminal end, including JMV 179 and JMV 180, as well as the C-terminal amidated heptapeptide of CCK, with identical affinities to the wild-type receptor. In contrast, W39F and Q40N mutants bound CCK octapeptide with the same decreased affinity as the CCK nonapeptide. The modeling of the CCK-A receptor and the docking of the peptide agonists [Thr,Nle]CCK9 and CCK-8 indicated that their N terminus was connected to the receptor through a strong bond network involving Trp-39 and Gln-40 thus confirming experimental data. These first molecular data identifying the agonist binding site of the human CCK-A receptor represent an important step toward the complete delineation of the agonist binding site and the understanding of the molecular mechanisms that govern differential activation of this receptor by CCK-related peptides.

Amino Acid Sequence↗
PubMed1997

Increasing immunization: a Medicaid managed care model.

OBJECTIVE: To evaluate the impact of an immunization outreach program on immunization rates. SETTING: A Pennsylvania independent practice association model managed care organization (100% Medicaid). DESIGN: Retrospective cohort study (N = 2511) of children 30 to 35 months of age from two age cohorts that compared immunization rates for Advisory Committee on Immunization Practices schedules for diphtheria-tetanus-pertussis, oral polio vaccine, measles-mumps-rubella, and Haemophilus influenza type b. An evaluation of the outreach component of the program compared treatment and nontreatment subgroups of one age cohort (N = 1002). INTERVENTION: The immunization program targeted approximately 19 000 members from birth to 6 years of age. The program components included computerized tracking and reminders, member and provider education, provider incentives, member incentives, and home visiting outreach. RESULTS: Data indicate that the treatment group has higher completed immunization rates at 35 months of age than does the control group. Furthermore, data show that members with home visits have significantly higher completed immunization rates than do other members. The corresponding comparisons for age-appropriate immunizations by 24 months indicate a nonsignificant trend of increased rates. CONCLUSION: The data provide evidence supporting a correlation between comprehensive strategies (computerized tracking, member and provider education and incentives, and home visiting) and increased immunization rates. Those individuals who received home visits were more likely to complete an immunization series by 35 months of age than those who did not. However, within the Mercy Health Plan program, age-appropriate immunizations are not significantly affected by home-visiting outreach.

Child, Preschool↗
PubMed1997

Suprascapular neuropathy. Results of non-operative treatment.

We retrospectively reviewed the results of non-operative treatment of suprascapular neuropathy in fifteen patients seen between November 1983 and February 1991. The clinical diagnosis was confirmed with electrodiagnostic studies. The treatment consisted of a program of physical therapy to improve the range of motion of the shoulder and to strengthen the surrounding muscles. The average duration of follow-up was three years and eleven months (range, one year to eight years and ten months). The latest evaluation included electrodiagnostic studies of the affected extremity and dynamic isokinetic testing of both upper extremities. The result was excellent for five patients and good for seven. The three remaining patients had operative treatment because of persistent symptoms; one of these patients had an excellent result, one had a good result, and one had a poor result. The results suggest that, in the absence of a well defined lesion producing mechanical compression of the suprascapular nerve, suprascapular neuropathy should be treated non-operatively.

Adolescent↗
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↗