Search PubMed⌕ Search

Biomedical subjects

M Armstrong

Publications and source records attributed to M Armstrong.

At least 73 records · Page 4Linked to original sources
PubMed1996

CYP2D6 allelic frequencies in young-onset Parkinson's disease.

Parkinson's disease (PD) is thought to develop as a result of interactions between genetic susceptibility factors and environmental exposures. One candidate gene is CYP2D6, which codes for the debrisoquine 4-hydroxylase cytochrome P450. Impairment of debrisoquine 4-hydroxylase activity has been associated with an increased risk of PD in patients with younger age at disease onset. Genotyping studies in patients with an older age at onset have reported modest increases in risk associated with the CYP2D6 B and A alleles; however, the risk for young-onset PD has not been adequately evaluated. We designed a case-control study to investigate the role of nonfunctional CYP2D6 allelic risk factors for young-onset PD in a sizable patient population and compared the distributions of CYP2D6 genotypes between young-onset ( < or = 51 years) PD patients (n = 108) and controls (n = 236). In contrast with the results from genotyping studies conducted among patients with an older age at onset, there were no significant differences in CYP2D6 allelic frequencies between young-onset PD cases and controls. The frequency of the B allele was slightly lower in the young-onset PD cases than in the controls (0.14 versus 0.20) (X2 = 2.66, p = 0.10). The presence of one or more B alleles was not associated with an increased risk of young-onset PD (odds ratio 0.58; 95% CI 0.33 to 1.00), nor was the presence of one or more nonfunctional alleles (i.e., A, B, D, and D2) (odds ratio 0.68; 95% CI 0.41 to 1.13). This study suggests that the young-onset PD population may differ from the older-onset population with respect to risk factors.

Age of Onset↗
PubMed1996

Role of the enteric nervous system in piglet cryptosporidiosis.

Piglet cryptosporidiosis is characterized by intestinal villous damage and malabsorption and by reduced NaCl absorption in response to prostaglandin (PG) release from inflamed tissue. We hypothesized that the PG effect is mediated by the enteric nervous system. Piglets were infected with cryptosporidium and ileal mucosa was studied in Ussing chambers. Studies with tetrodotoxin and indomethacin showed that 75% of the PG-induced alteration in NaCl transport was mediated by the enteric nervous system. Prostacyclin was elevated in infected tissue, and its analog, carbacyclin, mimicked the altered transport response in indomethacin-treated tissue. This carbacyclin response was abolished by tetrodotoxin. The vasoactive intestinal peptide (VIP) receptor antagonist, VIP-10-28, and the muscarinic antagonist, atropine, individually reduced and together abolished the response to carbacyclin, whereas the nicotinic blocker, hexamethonium, reduced the carbacyclin response by 75%. The somatostatin analog, octreotide, and the a-2 adrenergic agonist, clonidine, each abolished the carbacyclin response and partially or completely rectified the altered NaCl transport of the infection. These results indicate that PGs alter NaCl transport in this infection primarily by stimulating cholinergic interneurons that innervate VIPergic and cholinergic motor nerves. The enteric nervous system may be a potential target for pharmacological control of the acute diarrhea in this infection.

Animals↗
PubMed1995

Effect of insulin-like growth factor type 1 on critical-size defects in diabetic rats.

A number of investigators have reported on the clinically significant relationship between diabetes mellitus and impaired wound healing. Diabetic patients have an increased frequency of infection, delayed scar formation, and poor bony union. Investigations completed in our laboratory have demonstrated that insulin-like growth factor type 1 (IGF-1), a somatomedin C, has shown promise for accelerating bony repair. The purpose of this study was to examine the effects of recombinant IGF-1 on standardized, critical-size calvarial defects in 25 adult, male streptozocin-induced diabetic rats. From our study, it appears that IGF-1 exerts a potentiating effect on the repair of bony defects in diabetes-induced rats.

Animals↗
PubMed1995

Clinically achievable plasma deferoxamine concentrations are therapeutic in a rat model of Pneumocystis carinii pneumonia.

The iron-chelating drug deferoxamine (DFO) has been shown to be active in animal models of Pneumocystis carinii pneumonia (PCP), with effective daily intraperitoneal bolus dosages being 400 and 1,000 mg of DFO mesylate kg of body weight-1 in mouse and rat models, respectively. Continuous infusion produced a moderately improved response in a rat model. The data reported here demonstrate that the response achieved by continuous infusion of 195 and 335 mg of DFO mesylate kg-1 day-1 in the rat model is associated with mean concentrations in plasma of 1.3 and 2.5 micrograms of DFO ml-1 and mean concentrations in lung tissue of 4.9 and 6.0 micrograms of DFO g of lung tissue-1, respectively. Since current clinical use of DFO mesylate for the treatment of iron overload produces higher concentrations in the plasma of patients, DFO may prove to be a useful anti-PCP treatment. The 2.4- to 3.8-fold higher DFO concentration observed in lung tissue compared with that observed in plasma may be important in the response of PCP to DFO.

Animals↗
PubMed1995

Identification of possible artifacts in the association of official analytical chemists sporicidal test.

Two laboratories tested four different brands of alkaline 2% glutaraldehyde sterilants by the Association of Official Analytical Chemists sporicidal test. Each laboratory found survival of Clostridium sporogenes spores on spore-labeled unglazed porcelain penicylinders (cylinders) to vary from test to test, and survival did not always correlate with increasing sterilant exposure time. These results were consistent with a theory that there may be random conditions within the test that prevent the sterilant from contacting all spores. Further studies indicated that the prior history of the unglazed porcelain cylinders and whether the C. sporogenes culture grown in egg-meat media had been processed (homogenized) to eliminate visible pieces of egg-meat media were important factors affecting the results and repeatability of this test.

Journal Article↗
PubMed1994

The first step?

Explore the source record for details and available documents.

Humans↗
PubMed1994

Dentists and community care.

April 1993 saw the introduction of the 'Community Care' element of the 1990 NHS and Community Care Act. The term 'Community Care' describes the relocation of long-stay hospital residents to community accommodation. Much public attention has recently been focused on the welfare of psychiatric patients in the community, in particular whether they currently receive adequate care and supervision.

Deinstitutionalization↗
PubMed1994

Glutamine stimulates prostaglandin-sensitive Na(+)-H+ exchange in experimental porcine cryptosporidiosis.

BACKGROUND/AIMS: Recent studies of piglet cryptosporidiosis showed an injury-induced impairment of sodium-glucose cotransport and a prostaglandin-mediated inhibition of neutral NaCl absorption. Because glutamine has been shown to stimulate both neutral and electrogenic Na+ absorption, this study examined the mechanism of prostaglandin-mediated inhibition of NaCl absorption and the effect of glutamine on these processes. METHODS: Ileal mucosa from control and infected pigs was mounted in Ussing chambers for flux studies or incubated with [14C]glutamine or [14C]-glucose for metabolism studies. RESULTS: Glucose and glutamine induced equivalent increases, 2-2.5 microEq.cm-2.h-1, in Na+ absorption and short-circuit current in control ileum. Despite a reduction in villous surface area to one third of the control, glutamine enhanced both neutral and electrogenic Na+ absorption in the infected ileum by 3.5 +/- 0.5 microEq.cm-2.h-1, whereas glucose was only half as effective (P < 0.05). In addition, glutamine was oxidized to CO2 at rates three times those of glucose. Indomethacin enhanced, whereas amiloride, prostaglandin E2, and Cl-free solutions inhibited the glutamine-induced neutral Na+ transport. CONCLUSIONS: Glutamine-stimulated neutral Na+ absorption is mediated by a prostaglandin-sensitive apical Na(+)-H+ exchange mechanism. The heightened Na(+)-H+ exchange and tissue oxidation of glutamine suggest that glutamine is superior to glucose for use in oral rehydration solutions.

Animals↗
PubMed1994

The cytochrome P450 CYP2D6 allelic variant CYP2D6J and related polymorphisms in a European population.

DNA from two subjects showing anomalous CYP2D6 phenotype-genotype relationships was analysed for the presence of new CYP2D6 mutations by single strand conformational polymorphism (SSCP) analysis. One of these subjects was homozygous for polymorphisms in exon 1 and exon 9 previously detected in Oriental populations and termed the CYP2D6J allele. The frequency of these polymorphisms and their effect on phenotype was investigated in a European population with a small Chinese population as a control group. Subjects homozygous for both polymorphisms showed impaired metabolism of debrisoquine whereas subjects with the exon 9 mutation only appeared to show similar metabolism to the wild-type. The CYP2D6J allele frequency was 0.05 in the European group compared with 0.47 for the Chinese group. The relationship between the CYP2D6J allele and the exon 9 polymorphism and the presence of insertions upstream of CYP2D6 detectable by RFLP analysis with Xba I was investigated. In the Chinese group the insertion appeared to be associated with the CYP2D6J allele but in the European group no association was detected. Subjects homozygous for the CYP2D6J allele appear to show a similar debrisoquine phenotype to those heterozygous for CYP2D6-inactivating mutations but the exon 9 polymorphism or the presence of an upstream insertion without an associated CYP2D6B or CYP2D6J allele does not appear to affect enzyme activity.

Alleles↗
PubMed1994

The prognostic value of facial electroneurography in Bell's palsy.

Twenty six patients with Bell's palsy were studied at presentation using electroneurography. Ninety-four per cent of those who recovered completely could have been predicted by ENoG within 10 days of onset. Of the 18 patients who recovered completely, 13 had a total palsy at presentation.

Action Potentials↗
PubMed1994

Suppurative keratitis caused by Streptococcus pneumoniae after cataract surgery.

Six elderly patients are described (age range 76-86 years) in whom a characteristic peripheral suppurative keratitis developed 1-36 months after uncomplicated cataract surgery. A corneal section had been used in all patients and four or five interrupted nylon sutures were present at the time of onset. Streptococcus pneumoniae was cultured from a corneal scrape in all cases. Treatment with appropriate antibiotics resulted in slow resolution though supplementary topical steroids were necessary in five of the six patients, and corneal opacification persists in all cases.

Aged↗
PubMed1994

Genotyping for polymorphisms in xenobiotic metabolism as a predictor of disease susceptibility.

Polymorphisms in many xenobiotic metabolizing enzymes occur leading to variation in the level of enzyme expression in vivo. Enzymes showing such polymorphisms include the cytochrome P450 enzymes CYP1A1, CYP1A2, CYP2A6, CYP2D6, and CYP2E1 and the phase two metabolism enzymes glutathione S-transferase MI (GSTMI) and arylamine N-acetyltransferase 2 (NAT2). In the past, these polymorphisms have been studied by phenotyping using in vivo administration of probe drugs. However, the mutations which give rise to several of these polymorphisms have now been identified and genotyping assays for polymorphisms in CYP1A1, CYP2A6, CYP2D6, CYP2E1, GSTMI, and NAT2 have been developed. Specific phenotypes for several of the polymorphic enzymes have been associated with increased susceptibility to malignancy, particularly lung and bladder cancer, and Parkinson's disease. These associations are likely to be due to altered activation or detoxication of chemicals initiating these diseases, including components of tobacco smoke and neurotoxins. The substrate specificity and tissue distribution of polymorphic enzymes implicated in disease causation discussed with particular reference to previously described disease-phenotype associations.

Animals↗