Search PubMed⌕ Search

Biomedical subjects

R H Davis

Publications and source records attributed to R H Davis.

At least 109 records · Page 6Linked to original sources

Comparative trial of azapropazone and indomethacin plus allopurinol in acute gout and hyperuricaemia.

This study compared the effects of azapropazone and indomethacin plus allopurinol in the management of acute gout and hyperuricaemia. A group of 93 patients predominantly based in general practice were randomly allocated to the two treatment regimens (azapropazone (days 1-225) or indomethacin (1-28) followed by allopurinol (29-225)) on a double-blind double dummy basis. Azapropazone produced a substantial reduction in serum uric acid levels by day 4 compared with day 1 (P<0.002) and was superior to indomethacin with regard to recorded levels of serum uric acid at day 4 (P<0.01) and day 28 (P<0.05). From day 28 onwards allopurinol produced and azapropazone maintained similar reductions in serum uric acid. Both treatments rapidly controlled the initial acute attacks of gout and both produced side effects similar in frequency and nature. Fewer breakthrough attacks of gout occurred in the azapropazone group (12) than the indomethacin/allopurinol group (21).Although the results achieved in both treatment groups were similar it has been shown that azapropazone is effective monotherapy for controlling both acute attacks of gout and hyperuricaemia.

Adult↗

N-acetyl-L-glutamate synthase of Neurospora crassa. Characteristics, localization, regulation, and genetic control.

N-Acetylglutamate synthase, an early enzyme of the arginine pathway, provides acetylglutamate for ornithine synthesis in the so-called "acetylglutamate cycle." Because acetylglutamate is regenerated as ornithine is formed, the enzyme has only a catalytic or anaplerotic role in the pathway, maintaining "bound" acetyl groups during growth. We have detected this enzyme in crude extracts of Neurospora crassa and have localized it to the mitochondria along with other ornithine biosynthetic enzymes. The enzyme is bound to the mitochondrial membrane. The enzyme has a pH optimum of 9.0 and Km values for glutamate and CoASAc of 6.3 and 1.6 mM, respectively. It is feedback-inhibited by L-arginine (I0.5 = 0.16 mM), and its specific activity is augmented 2-3-fold by arginine starvation of the mycelium. Mutants of the newly recognized arg-14 locus lack activity for the enzyme. Because these mutants are complete auxotrophs, we conclude that N-acetylglutamate synthase is an indispensible enzyme of arginine biosynthesis in N. crassa. This work completes the assignment of enzymes of the arginine pathway of N. crassa to corresponding genetic loci. The membrane localization of the enzyme suggests a novel mechanism by which feedback inhibition might occur across a semipermeable membrane.

Acetyltransferases↗

Irritable urethral syndrome: follow up study in general practice.

Two years after a microbiological study of the urethral syndrome 25 of 31 women had had further symptoms, but only two had sought medical help for their symptoms in the year after the study. Analysis of patients' records showed that women with the urethral syndrome had higher consultation and sterilisation rates and more psychosomatic symptoms and relationship problems than matched control patients. Using the Nottingham health profile women with the urethral syndrome were more likely to mention that health problems affected their sex lives and were more likely to see themselves as having health problems than control patients. Women who have the urethral syndrome are considerable drain on the doctor's time, and management needs to be directed towards the anxious patient who makes such demands. Seeing the condition as the "irritable urethral syndrome" may help both doctor and patient to recognize the psychosomatic aspect of the problem.

Family Practice↗

Effect of lidamidine hydrochloride and loperamide on gastric emptying and transit of the small intestine. A double-blind study.

We performed a double-blind randomized study in 24 healthy volunteers, to evaluate the effects of two doses of lidamidine hydrochloride, loperamide, and placebo on transit of the small intestine and gastric emptying. Transit time of the small intestine was determined by measuring the rise in breath hydrogen excretion after ingestion of lactulose. Although there was a trend for prolonged intestinal transit time in both lidamidine groups, this difference was not significant compared with that in the placebo group. Loperamide significantly slowed transit when compared with placebo or lidamidine (p less than 0.001). Gastric emptying was assessed by using a solid-phase radiolabeled meal. Three parameters of gastric emptying were analyzed: half-emptying time, area under the gastric emptying curve, and beta. Although there was a trend for a longer half-emptying time in the group that received 12 mg of lidamidine, this difference approached, but did not reach, statistical significance (p = 0.06) compared with placebo. The area under the gastric emptying curve, a potentially more sensitive parameter for measuring gastric emptying, was significantly increased in the group receiving 12 and 18 mg of lidamidine (p less than 0.05) compared with the group receiving loperamide or placebo. In summary, lidamidine significantly delayed gastric emptying but had no significant effect on small bowel transit. These data suggest that the antidiarrheal properties of lidamidine are the result of enhanced absorption or inhibition of secretion of fluid and electrolytes.

Adolescent↗

Bactericidal action of nafcillin, vancomycin, and three cephalosporins against nafcillin-susceptible and nafcillin-resistant coagulase-negative staphylococci.

Coagulase-negative staphylococci (S. epidermidis, 43 strains; S. warneri, 16 strains; S. haemolyticus, five strains; and others, four strains) were tested by the agar dilution method for nafcillin susceptibility: 53 were susceptible with a minimal inhibitory concentration (MIC) of less than or equal to 2 micrograms/ml; four were of indeterminate susceptibility, MIC = 4-16 micrograms/ml; and 11 were resistant, MIC greater than or equal to 32 micrograms/ml. The bactericidal activities from 0 to 24 hr for nafcillin, vancomycin, cephalothin, cefazolin, and cefamandole, each at 16 micrograms/ml in broth, were determined for all the isolates. The data indicate that a nafcillin agar dilution susceptibility test result of resistance does not consistently predict lack of killing activity by the cephalosporins. It is likely that each cephalosporin would have to be tested against individual coagulase-negative staphylococci in order to determine a suitable therapeutic or prophylactic cephalosporin, if a cephalosporin were to be used. Vancomycin was bactericidal for all the nafcillin-resistant coagulase-negative organisms tested.

Cefamandole↗

Transfer of thiocyanate into chicken eggs.

Laying hens were fed thiocyanate (SCN) as a solution of potassium thiocyanate (KSCN) in their drinking water to determine whether dietary SCN was transferred into eggs. The thiocyanate content of their eggs was measured before and during thiocyanate administration. Egg thiocyanate content increased from 6 micrograms SCN/g albumen to 31 micrograms SCN/g (a 400% increase) in the period immediately following thiocyanate administration and then fell progressively, seeming to stabilize much closer to but still well above control levels.

Administration, Oral↗

Acetylglutamate kinase-acetylglutamyl-phosphate reductase complex of Neurospora crassa. Evidence for two polypeptides.

Mutations at the arg-6 locus in Neurospora crassa are divided into two complementation groups (A and B) and a third noncomplementing group. There are many suppressible nonsense mutations among mutants in complementation group B and one in the noncomplementing group; no nonsense mutations exist among mutants in complementation group A (Davis, R. H., and Weiss, R. L. (1983) Mol. Gen. Genet. 192, 46-50). We show here that the mutants are defective in either or both of two enzymes of arginine biosynthesis, acetylglutamate kinase and/or acetylglutamyl-phosphate reductase. Mutants in complementation group A lack acetylglutamate kinase, those in complementation group B lack acetylglutamyl-phosphate reductase, and those in the noncomplementing group lack both activities. Mutants in group B also have reduced levels of acetylglutamate kinase. The enzymes from purified mitochondria are readily separable by gel filtration and by Blue A dye affinity chromatography. Acetylglutamate kinase appears to be an octamer with a molecular weight of 400,000, whereas acetylglutamyl-phosphate reductase appears to be a dimer with a molecular weight of 93,000. This suggests that the two activities reside on distinct polypeptides. These results are best accommodated by the following model: the arg-6 locus encodes a single mRNA which is translated into a single polypeptide; the latter is then cleaved post-translationally to yield two physically separable enzymes.

Aldehyde Oxidoreductases↗

Universal claim form for items of service payments in general practice.

A universal claim form was designed to replace 12 different forms currently in use by general practitioners in the National Health Service to claim payment for items of service. This form was evaluated over a period of three months in a group practice. It was acceptable to doctors, staff, and the staff of the family practitioner committee. Considerably more claims were made during the trial period than during the same period the previous year.

Evaluation Studies as Topic↗

Development of an improved multi-pressure-sensor probe for recording muscle contraction in human intestine.

We have developed an improved semiconductor recording probe for monitoring motility of the upper small intestine in humans. The probe consists of six ultraminiature silicon pressure sensors spaced 10 cm apart and encased in a flexible polyurethane sheath. The probe is small [2.67 mm (8F) diameter], is easily passed transnasally, and is tolerated by patients for prolonged recording periods (24-36 hr) with a minimum of discomfort. The initial semiconductor and catheter material were those designed for use in the cardiovascular system, but they proved to be easily damaged by gastric acid and enzymes. After improvement of this probe, we now have recordings from more than 100 patients for an approximate total of 6000 hr of recording time. The improved probe is a durable recording device that facilitates the investigation of motility of the small intestine in humans in health and disease.

Humans↗

Nausea, vomiting, and abdominal pain after Roux-en-Y anastomosis: motility of the jejunal limb.

The Roux-en-Y anastomosis is a surgical procedure performed to divert the pancreaticobiliary juices from the gastric pouch in patients who have alkaline reflux gastritis or esophagitis, or both, that develop after vagotomy and Billroth I or II operations. After the Roux-en-Y procedure the inflammation subsides but is often replaced by a characteristic group of symptoms--chronic abdominal pain, nausea, and vomiting worsened by eating. Using a semiconductor recording probe, we investigated the Roux limb in 7 subjects who were fasted and then fed (liquid and solid meals). In the fasted state the migrating motor complex was either completely absent or grossly disrupted. Only 1 subject converted to a fed-state motility pattern in the Roux limb after a liquid meal (Osmolite), and all 7 subjects failed to convert to a fed state after a solid meal. These studies suggest that the Roux-en-Y syndrome of pain, nausea, and vomiting is secondary to a defect in motor function and that the Roux limb is acting as an area of functional obstruction.

Adult↗

Distinct roles of putrescine and spermidine in the regulation of ornithine decarboxylase in Neurospora crassa.

We wished to identify metabolic signals governing changes in ornithine decarboxylase (L-ornithine carboxy-lyase, EC 4.1.1.17) activity in Neurospora crassa. By manipulations of the ornithine supply and by the use of inhibitors of the polyamine pathway, we found that spermidine negatively governs formation of active ornithine decarboxylase and that putrescine promotes inactivation of the enzyme. Direct addition of putrescine or spermidine to cycloheximide-treated cells confirmed the role of putrescine in enzyme inactivation and showed that spermidine had no effect on this process. Increases in ornithine decarboxylase activity caused by blocking spermidine synthesis occurred prior to a significant decrease in the spermidine pool. This is consistent with our previous finding that only 10-20% of the spermidine pool is freely diffusible within N. crassa cells. We presume that only this small fraction of the pool is active in regulation.

Cyclohexylamines↗

Structural gene for ornithine decarboxylase in Neurospora crassa.

To define the structural gene for ornithine decarboxylase (ODC) in Neurospora crassa, we sought mutants with kinetically altered enzyme. Four mutants, PE4, PE7, PE69, and PE85, were isolated. They were able to grow slowly at 25 degrees C on minimal medium but required putrescine or spermidine supplementation for growth at 35 degrees C. The mutants did not complement with one another or with ODC-less spe-1 mutants isolated in earlier studies. In all of the mutants isolated to date, the mutations map at the spe-1 locus on linkage group V. Strains carrying mutations PE4, PE7, and PE85 displayed a small amount of residual ODC activity in extracts. None of them had a temperature-sensitive enzyme. The enzyme of the PE85 mutant had a 25-fold higher Km for ornithine (5mM) than did the enzyme of wild-type or the PE4 mutant (ca. 0.2 mM). The enzyme of this mutant was more stable to heat than was the wild-type enzyme. These characteristics were normal in the mutant carrying allele PE4. The mutant carrying PE85 was able to grow well at 25 degrees C and weakly at 35 degrees C with ornithine supplementation. This mutant and three ODC-less mutants isolated previously displayed a polypeptide corresponding to ODC in Western immunoblots with antibody raised to purified wild-type ODC. We conclude that spe-1 is the structural gene for the ODC.

Alleles↗

Migrating action potential complex: unmasked by 6-hydroxydopamine.

We have previously described the myoelectric characteristics of a single moving ring contraction, the migrating action potential complex (MAPC), in rabbit ileal loops exposed to certain bacteria or their enterotoxins. The MAPC is thought to act as a defense mechanism of the host, clearing unwanted substances from the lumen. In the present study, 6-hydroxydopamine, a substance that selectively destroys adrenergic varicosities containing the neurotransmitter norepinephrine, unmasked the MAPC from the activity front of the migrating motor complex in an unanesthetized rat model. The animals developed diarrhea and lost weight. The study suggests that the MAPC may also be a physiological complex and under the modulation of the enteric nervous system. The MAPC may not be seen under normal control conditions because the complex migrates with the activity front and is under inhibitory control. Destroying the inhibitory mechanisms unmasked the MAPC from the activity front of the migrating motor complex and allowed neural transmission of the ring contraction.

Action Potentials↗