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Biomedical subjects

K Holmes

Publications and source records attributed to K Holmes.

54 records · Page 3Linked to original sources
PubMed1980

Metal sensitivity causing loosened joint prostheses.

Metal sensitivity, as measured by an in-vitro assay on peripheral blood lymphocytes, was evaluated in patients with failed joint prostheses. Lymphocyte transformation to chromium, cobalt, and nickel was measured in 24 patients having revision surgery for a painful or loose prosthesis and compared with that in 11 patients who had a successful hip prothesis in situ for at least 2 years previously. A positive response (lymphocyte stimulation index greater than 3) to at least one of the metals was found in 71% of the revision group compared to 9% of controls (P < 0.01). The positive correlation between prosthesis failure and in-vitro metal sensitivity suggests that cell-mediated immunity to metals to metals may play a role in prosthesis failure. Furthermore, this simple in-vitro test may provide the basis of a useful diagnostic test for an often difficult clinical problem.

Aged↗
PubMed1979

Internal motions in myosin.

High-resolution proton nuclear magnetic resonance (1H NMR) measurements were made on myosin, heavy meromyosin (HMM), myosin subfragment 1 (S1), light meromyosin (LMM), and actin. A strong signal from amino acid side chains undergoing motions too fast to be accounted for by simple rotations of groups on a rigid backbone was obtained from myosin. Comparison of myosin, HMM, S1, and LMM showed that the mobile region is located almost entirely in S1 and accounts for approximately 22% of its structure. Adenosine triphosphate (ATP) and ATP analogues had no measurable effect on the S1 spectrum. Actin, on the other hand, quenched the internal motions of S1. When S1 was titrated with actin, an association was obtained which was in agreement with other measured values. The actin effect was reversed by adding magnesium pyrophosphate (MgPPi) or adenyl-5'-yl imidophosphate (MgAMPPNP). Quantitative treatment of the broad signals from myosin and its subfragments substantiated the existence of two flexible regions in myosin. The highly mobile portion of myosin may be located in the "swivel" between S1 and the rest of myosin or in the actin binding site or in both. These possibilites are discussed, and a new possible mechanism for muscle cross bridge elasticity is proposed.

Actins↗
PubMed1976

Changes in lymphocyte function during pregnancy.

A gradual increase in spontaneous lymphocyte DNA synthesis was demonstrated in each trimester of pregnancy. Autoradiographic studies indicated that lymphocytes were primarily responsible for this activity. PHA-induced lymphocyte transformation in both fetal calf serum and autologous serum was significantly reduced in the second and third trimesters of pregnancy. Spontaneous lymphocyte DNA synthesis was significantly reduced in patients with mild pre-eclampsia. However, no significant differences were seen in patients with severe pre-eclampsia in the third trimester of pregnancy compared with the normal control subjects. No evidence was adduced to implicate inhibitory humoral factors affecting the peripheral blood lymphocytes in pregnany patients in experiments in which washed lymphocytes were cultured in medium containing heterologous serum. In vitro experiments demonstrated that cortisol, progesterone and HPL caused a significant reduction in lymphocyte DNA synthesis, and HGH and HCG had a variable effect. However, only cortisol was regularly inhibitory at physiological concentrations. The progesterone effect was dose-related, producing 90 per cent inhibition of activity at a concentration of 10 mug/ml. No synergism could be shown between HPL and progesterone on lymphocyte transformation. The increase in activity of circulating immunoreactive cells during pregnancy and its depression with the onset of pre-eclampsia is discussed.

Chorionic Gonadotropin↗
PubMed1975

Disparity between inhibitory and killing effects of BL-P1654.

The activity of BL-P1654, a semisynthetic penicillin, was studied in vitro against Enterobacteriaceae and compared with carbenicillin against Pseudomonas. There was a marked diminution in bactericidal activity of BL-P1654 when tested in broth medium.

Bacteria↗
PubMed1975

In vitro evaluation of a new quinolone antibacterial.

The activity of R-802, a quinolone antibacterial agent, was studied in vitro and found to be active against Enterobacteriaceae; less than 4 mug of drug per ml was required to inhibit most isolates. The majority of Pseudomonas aeruginosa grew in a concentration of 256 mug of R-802 per ml when studied in broth against an inoculum of 10(8) organisms per ml.

Anti-Bacterial Agents↗
PubMed1972

Evaluation of a new cephalosporin antibiotic, cephapirin.

Cephapirin sodium, a parenterally administered derivative of cephalosporanic acid, was tested in vitro against 150 stock cultures of Enterobacteriaceae and 30 stock cultures each of Pseudomonas aeruginosa and Staphylococcus aureus. Both broth- and agar-dilution techniques were employed with two sizes of inocula of organisms. At a concentration of 7.5 mug or less/ml, cephapirin inhibited and killed 100% of strains of Escherichia coli and Proteus mirabilis and more than 80% of Klebsiella species when tested against an inoculum of 10(5) bacterial cells/ml. However, even at 100 mug/ml, only a few isolates of other Enterobacteriaceae and Pseudomonas were inhibited. A 100-fold increase in the inoculum resulted in decreased susceptibility of organisms. All penicillin-susceptible as well as penicillin-resistant S. aureus isolates were inhibited and killed by 5 mug or less of cephapirin/ml when tested with an inoculum of either 10(4) or 10(6) organisms/ml. The drug also was studied in various doses in the treatment of 77 patients with diverse infections. Cephapirin was effective in the treatment of 27 of 32 patients with pulmonary infection, as well as in 6 of 7 patients with staphylococcal or streptococcal soft tissue infection. Of 25 patients with urinary-tract infections, 19 developed a negative culture during therapy. A single 4-g intramuscular dose of cephapirin was effective in only 2 of 11 patients with gonococcal urethritis or endocervicitis. Two patients with gonococcal urethritis treated with multiple injections were cured. The drug was well tolerated except for pain at the site of injection in 14 patients and phlebitis in 4 patients. No abnormalities in renal or hepatic function could be attributed to cephapirin. In addition, no abnormalities were found in the renal tubules of rabbits challenged with 500 mg of cephapirin/kg. If further studies document that cephapirin is well tolerated by the parenteral route, it may have advantages over cephalothin or cephaloridine.

Acetamides↗
PubMedDate not supplied

Acute and persistent viral infections of differentiated nerve cells.

Within the nervous system the highly specialized structure and function of nerve cells renders the pathogenesis of viral infections amazingly complex. In vivo and in vitro studies reveal that viruses may display tropism for distinct types of cells such as neurons, myelin-forming cells, or astrocytes. In neurons, RNA viruses mature in the cell body and in dendrites close to synapses, from which they can spread to synaptic endings. Undefined host factors and stage of differentiation may favor defective viral assembly, which, in turn, results in persistent infections of neurons. In myelin-forming cells, lytic infection results is persistent infections of neurons. In myelin-forming cells, lytic infection results in degeneration of myelin and, consequently, in altered conduction in those axons that are ensheathed by a myelin-forming cell. In addition, breakdown of myelin may induce an autoimmune response, which then leads to further demyelination. Autoimmune demyelination may also occur when glial cells other than myelin-forming cells are infected. Astrocytes are prone to persistent infection or viral transformation.

Animals↗
PubMedDate not supplied

Efficacy of nonoxynol 9 contraceptive sponge use in preventing heterosexual acquisition of HIV in Nairobi prostitutes.

OBJECTIVE: To determine the efficacy of the nonoxynol 9 contraceptive sponge in preventing sexual acquisition of the human immunodeficiency virus (HIV). DESIGN: Prospective, randomized placebo-controlled trial. SETTING: Research clinic for prostitutes in Nairobi, Kenya. PATIENTS AND INTERVENTIONS: One hundred thirty-eight HIV-seronegative women were enrolled, of whom 74 were assigned to nonoxynol 9 sponge use and 64 to placebo use. These two groups did not significantly differ with respect to demographic characteristics, sexual practices, or prevalence of genital infections at enrollment, except for a lower number of sex partners per week and a higher initial prevalence of genital ulcers among women assigned to nonoxynol 9 sponge use. Among the 116 women who returned for follow-up, the mean durations of follow-up were 14 and 17 months for the two groups, respectively. MAIN OUTCOME MEASURE: HIV seroconversion. RESULTS: Nonoxynol 9 sponge use was associated with an increased frequency of genital ulcers (relative risk [RR], 3.3; P less than .0001) and vulvitis (RR, 3.3; P less than .0001) and a reduced risk of gonococcal cervicitis (RR, 0.4; P less than .0001). Twenty-seven (45%) of 60 women in the nonoxynol 9 sponge group and 20 (36%) of 56 women in the placebo group developed HIV antibodies. The hazard ratio for the association between nonoxynol 9 sponge use and HIV seroconversion was 1.7 (95% confidence interval [CI], 0.9 to 3.0). Using multivariate analysis to control for the presence of genital ulcers at enrollment, the adjusted hazard ratio for the association between nonoxynol 9 sponge use and seroconversion was 1.6 (95% CI, 0.8 to 2.8). CONCLUSIONS: Genital ulcers and vulvitis occurred with increased frequency in nonoxynol 9 sponge users. We were unable to demonstrate that nonoxynol 9 sponge use was effective in reducing the risk of HIV infection among highly exposed women.

Adult↗
PubMedDate not supplied

Current management of congenital diaphragmatic hernia.

Infants born with congenital diaphragmatic hernia have a high mortality which is essentially due to the associated lung hypoplasia. However, there have been several recent innovations, both in the surgical approach and in techniques of neonatal intensive care, which have improved the outlook for some of these critically ill infants.

Extracorporeal Membrane Oxygenation↗