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Biomedical subjects

M Armstrong

Publications and source records attributed to M Armstrong.

At least 55 records · Page 3Linked to original sources

On which day is pain worst following adult tonsillectomy?

Anecdotal evidence from several ENT departments suggests that pain following tonsillectomy is worst on the second and/or third days after surgery. This study tests this hypothesis. A pilot study with 19 subjects suggested this theory might well be true. A fuller study was then carried out on 91 subjects with standardised surgical and anaesthetic techniques, and standardised analgesia for five days postoperatively. Pain on the second and third postoperative days was compared with that eight hours after the operation and on the first, fourth and fifth postoperative days. No statistically significant difference was found. There is increasing pressure for early discharge from hospital after surgery. If pain following tonsillectomy is not going to become worse at home, this will tend to make early discharge more acceptable to patients.

Adolescent↗

Gliotoxicity, reverse transcriptase activity and retroviral RNA in monocyte/macrophage culture supernatants from patients with multiple sclerosis.

In investigating a possible link between a novel retroviral agent (provisionally called MSRV), recently characterised in multiple sclerosis (MS), and the neuropathology of MS, it was found that there was a significant correlation between gliotoxicity and reverse transcriptase activity in monocyte/macrophage culture supernatants (MMCS) unique to MS patients. MMCS from healthy controls and patients with other neurological diseases did not display either gliotoxicity or reverse transcriptase activity. The observed gliotoxic effect was an initial, intermediate filament network disorganization and subsequent cell death which was specific to astrocytes and oligodendrocytes. The reverse transcriptase activity and MSRV-specific RNA were observed during the first 2 weeks of culture in MMCS from patients with active MS. The further elucidation of the molecular form(s) of this gliotoxic factor and its original source may be crucial in elucidating important etiopathogenic mechanisms in MS.

Animals↗

Safety of direct laryngoscopy as an outpatient procedure.

The safety of outpatient direct laryngoscopy has recently been challenged in the literature. We reviewed the first 589 direct laryngoscopies performed at a new outpatient surgery center. There were nine unplanned admissions to the hospital, including five airway emergencies that developed within the first 30 min after extubation. Three patients required reintubation before leaving the operating room. On postoperative telephone follow-up, 9% complained of mild to moderate sore throat. There were no major complications after discharge. We conclude that the risk of airway emergencies after direct laryngoscopy is less than 1% in carefully selected patients. The procedure can be safely performed as an outpatient procedure as long as transportation to a hospital is readily available for the few patients in whom complications arise.

Adult↗

Modified quantitative association of official analytical chemists sporicidal test for liquid chemical germicides.

The Association of Official Analytical Chemists (AOAC) test for sporicidal activity of disinfectants (966.04) is used in the United States as the legal criteria for classifying a liquid as a chemical sterilant and also as the indicator of the highest level of disinfectant. This qualitative test contains procedures that may cause inaccurate results. A modified, quantitative version of the AOAC sporicidal test has been developed that uses a specified minimum number of spores (2.0 x 10(sup5)) of Bacillus subtilis or Clostridium sporogenes dried onto porcelain penicylinders. This modified test was validated with three commercial sterilant chemicals tested on three separate groups of spore-labeled cylinders.

Journal Article↗

Prohibitin, a putative negative control element present in Pneumocystis carinii.

Little is known about the molecules involved in the regulation of Pneumocystis carinii replication and development in vitro and in vivo. We describe in this report the identification of a P. carinii gene encoding the P. carinii prohibitin protein. In mammals, the prohibitin gene product has been shown to negatively regulate cell proliferation. A cDNA clone encoding the P. carinii prohibitin gene was isolated from a P. carinii cDNA library and identified on the basis of amino acid sequence homology with prohibitin from mammalian sources. Southern blot analysis confirmed that the prohibitin cDNA clone was of P. carinii origin. Western blot analysis of total P. carinii protein indicated that the prohibitin gene is transcribed and translated in vivo. The P. carinii prohibitin gene was expressed in vivo in human fibroblasts and shown to arrest the cell cycle in the G1 phase. The results obtained suggest a potential role for P. carinii prohibitin in the regulation of P. carinii proliferation and development.

Amino Acid Sequence↗

Antipsychotic drug-induced movement disorders in schizophrenics in relation to CYP2D6 genotype.

BACKGROUND: Approximately 5-10% of Caucasians (poor metabolisers) show impaired metabolism of at least 20 therapeutically important drugs, including a number of commonly used antipsychotic agents, because they lack the cytochrome p450 enzyme CYP2D6. The molecular basis of this defect is now well understood and simple genotyping tests using the polymerase chain reaction (PCR) have been developed. METHOD: To determine whether poor metabolisers are more susceptible to acute dystonic reactions and chronic movement disorders associated with the administration of antipsychotic drugs, we determined CYP2D6 genotypes in a group of 76 schizophrenics using previously described methods involving PCR and restriction fragment length polymorphism analysis. RESULTS: There was no difference in genotype frequencies between the schizophrenics and a normal control population, suggesting that CYP2D6 genotype was not a factor in determining susceptibility to the disease. However, four of the five poor metabolisers compared with 44% of the remaining subjects were suffering from a movement disorder at the time of the study, although because of the small number of poor metabolisers in the group the difference was not statistically significant. Poor metabolisers were not more likely to suffer an acute dystonic reaction. CONCLUSIONS: CYP2D6 genotype is not a determinant of susceptibility to acute dystonic reactions but may be a contributory factor in antipsychotic drug-induced movement disorders including tardive dyskinesia.

Antipsychotic Agents↗

Peptide YY inhibits intestinal Cl- secretion in experimental porcine cryptosporidiosis through a prostaglandin-activated neural pathway.

Peptide YY (PYY) is a powerful inhibitor of intestinal secretion mediated by cAMP agonists such as vasoactive intestinal peptide and prostaglandin E2. We hypothesized that PYY would attenuate the secretory diarrhea in piglet cryptosporidiosis, which is mediated by prostaglandins E2 and I2. Control and infected ileal tissues from piglets were studied in Ussing chambers. The addition of PYY to the serosal bathing solution abolished net Cl- secretion in infected tissue. The inhibitory effect of PYY was eliminated with the prostaglandin synthesis inhibitor indomethacin and with the nerve conduction blocker tetrodotoxin. PYY completely blocked the antiabsorptive and secretory effects of the prostaglandin I2 analog carbacyclin, which has previously been shown to operate through enteric nerve pathways in this tissue. In contrast, PYY had no inhibitory effect on the secretory responses induced by prostaglandin E2 or vasoactive intestinal peptide. Results suggest that the antisecretory effects of PYY are mediated by inhibition of prostaglandin I2 induction of enteric nerves. Thus, PYY may play an important role in moderating the secretory diarrhea in cryptosporidiosis.

Animals↗

Speech perception in noise with implant and hearing aid.

OBJECTIVE: To compare the perception of speech in quiet and in noise by adults using a cochlear implant on its own or a cochlear implant and hearing aid together. STUDY DESIGN: Repeated measures. SETTING: Laboratory study using subjects' own speech processors. PATIENTS: Two groups of cochlear implant users (Australian and American) with some residual hearing in the non-implanted ear (pure tone average thresholds at 500 Hz, 1 kHz, and 2 kHz of 75-112 dB HL). INTERVENTION(S): Conventional hearing aid and cochlear implant in opposite ears. MAIN OUTCOME MEASURES: Speech perception was evaluated using recorded lists of CUNY sentences and lists of CNC words in quiet and in background noise. RESULTS: Speech scores were significantly higher with implant and hearing aid together compared to implant alone. The binaural advantage was greater in background noise than it was in quiet for CUNY sentences in the American listeners. CONCLUSION: Severely-to-profoundly hearing impaired adults may benefit from combined fitting of implants and conventional hearing aids in opposite ears.

Adult↗

Human insulin receptor substrate-1: variant sequences in familial non-insulin-dependent diabetes mellitus.

The aetiology of NIDDM is uncertain, although family and twin studies indicate an important role for genetic factors in disease onset. The function and position of IRS-1 within the insulin signalling pathway make it a prime candidate gene for the development of insulin resistance and NIDDM. Insulin resistant families were identified by studying unaffected first degree relatives from families with 2 or more living NIDDM subjects. Insulin sensitivity was determined in the relatives using the insulin tolerance test, and 15 families were identified as insulin resistant. One NIDDM subject from the 10 most resistant families was selected and the entire coding region of IRS-1 analysed by SSCP analysis. Four normoglycaemic subjects with no family history of diabetes served as controls. Five variant sequences of IRS-1 were identified with the NIDDM subjects; 2 silent polymorphisms at codons 235 (GGG to GGA) and 893 (CCG to CCC): 2 non-conservative mutations (Ala513Pro; Gly972Arg) and a codon deletion (Ser681-7 to Ser681-6). The influence of the non-conservative mutations alone, and in combination with other abnormalities of the insulin signalling pathway on peripheral insulin action, remains to be determined.

Base Sequence↗

Relationship between insulin sensitivity and insulin receptor substrate-1 mutations in non-diabetic relatives of NIDDM families.

Insulin receptor substrate-1 (IRS-1) occupies a key position in the insulin-signalling pathway. Two mutations of the IRS-1 gene (Gly(972)Arg and Ala(513)Pro) have been described, although their roles in the development of insulin resistance and non-insulin-dependent diabetes mellitus (NIDDM) remain controversial. Insulin resistance has been described in non-diabetic relatives of NIDDM families, suggesting that it may be due to an inherited defect of insulin action. We therefore examined the relationships between the two mutations and insulin sensitivity in 93 non-diabetic first degree relatives from North European families with 2 or more living NIDDM subjects. Anthropometric measurements, an oral glucose tolerance test, and an insulin tolerance test to assess insulin sensitivity (K(ITT)) were performed. Basal insulin sensitivity was assessed by homeostasis model assessment (HOMA). Comparisons were made between the following relative subgroups: with (n = 9) and without (n = 84) the 972 mutation; with (n = 5) and without (n = 88) the 513 mutation; and with either one or both mutations (n = 13) or without either (n = 80). General linear model analysis was used to compare K(ITT) and HOMA between the subgroups with the anthropometric variables known to influence insulin sensitivity as covariates. There were no significant differences between the subgroups for K(ITT) and HOMA. In conclusion, the 513 and 972 mutations, alone and in combination, are not associated with decreased insulin sensitivity in non-diabetic relatives of NIDDM families.

Adult↗

Variant sequences of the Hexokinase II gene in familial NIDDM.

UNLABELLED: Hexokinase II (HKII) plays a central role in the intracellular metabolism of glucose in skeletal muscle, catalysing the phosphorylation of glucose to glucose 6-phosphate. It is therefore considered to be a potentially important candidate gene in the development of insulin resistance and non-insulin-dependent diabetes mellitus (NIDDM). The aim of this study was to screen the HKII gene for mutations in NIDDM subjects from insulin-resistant families. Insulin sensitivity was assessed in unaffected first degree relatives from families with two or more living NIDDM subjects, and 15 families were identified as being insulin resistant. In 15 NIDDM subjects (one from each family) and 4 normoglycaemic control subjects, all 18 exons of the HKII gene were amplified by the polymerase chain reaction, and the products screened for mutations using a combination of single-stranded conformational polymorphism analysis and direct sequencing. Six sequence variations were detected in the NIDDM subjects; four silent polymorphisms [GAT vs GAC at codon 251 in exon 7, AAT vs AAC at codon 692 in exon 15, CCG vs CCC at codon 736 in exon 15, and CTG vs CTA at codon 766 in exon 16]; a single base change [T-->C], 22 base pairs distal to the exon-intron junction of exon 17 in the 5'-splice donor; and a single amino acid substitution [Gln142-->His] in exon 4, which was identified in 6 of the 15 NIDDM subjects. The frequency of the mutated codon 142 allele however, was comparable between NIDDM subjects with familial NIDDM (n = 56) and normoglycaemic control subjects (n = 48) (18.8% and 14.6% for NIDDM subjects and control subjects respectively; chi 2 = 0.6, p > 0.25). In addition, measures of insulin sensitivity were comparable in normal glucose tolerant subjects with (n = 20) and without (n = 40) the codon 142 polymorphism. IN CONCLUSION: (1) mutations in the coding regions of the HKII gene are unlikely to be major determinants in the development of insulin resistance and familial NIDDM; although (2) the influence of the codon 142 mutation in combination with other abnormalities of the insulin-signalling pathway on insulin action remain to be addressed.

Amino Acid Sequence↗

Successful medical therapy of Acanthamoeba keratitis with topical chlorhexidine and propamidine.

INTRODUCTION: Following laboratory studies on new potential chemotherapy for Acanthamoeba keratitis, when chlorhexidine and propamidine provided an additive in vitro effect, a series of 12 patients with culture-proven Acanthamoeba keratitis from three UK centres was monitored during and after therapy. METHODS: In all cases the clinical diagnosis was confirmed by amoebal culture. In some instances identification of the protozoa by direct microscopy of corneal tissue was possible. The medication was provided topically in drop form until the keratitis had resolved. In vitro sensitivity to chlorhexidine and propamidine was performed on all isolates and compared with sensitivity to a range of other drugs used for treatment of the infection. RESULTS: In vitro drug testing confirmed that trophozoites and cysts of all 12 Acanthamoeba isolates were fully sensitive to chlorhexidine and propamidine. Therapy was satisfactory for controlling and eradicating the acanthamoebal infection in all patients. Three patients developed discrete stromal infiltration at the site of infection that resolved 1 week after commencing therapy, with or without use of steroids. Two patients developed a late inflammatory effect in the stromal scar at 6 months, which resolved with steroids. No clinical evidence of chlorhexidine toxicity was found in any patients. CONCLUSIONS: The combination of topical chlorhexidine and propamidine was very effective for treating Acanthamoeba keratitis provided the drugs were continued for a sufficient period. No drug toxicity or resistance of Acanthamoeba isolates was observed in the 12 treated patients.

Acanthamoeba↗

Continuous extradural infusion of ropivacaine for prevention of postoperative pain after major orthopaedic surgery.

We studied 151 patients undergoing total hip or knee arthroplasty, or cruciate ligament reconstruction in a multicentre study in Australia and New Zealand. Patients were openly allocated randomly to one of five treatment groups or to a control group. General anaesthesia was induced after introduction of extradural block with 0.5% ropivacaine. After surgery, patients received an extradural infusion of 0.2% ropivacaine at 6, 8, 10, 12 or 14 ml h-1 or received no postoperative extradural infusion (control group). All patients had access to i.v. PCA morphine for supplementary analgesia. Morphine consumption was lower in all treatment groups compared with the control group, decreasing with increasing ropivacaine infusion rate. Median VAS scores were lower in all ropivacaine infusion groups compared with the control group for the first 10 h of the study; however by the end of the study, VAS scores were similar in all groups. The higher ropivacaine infusion rates caused a slower convergence of spread of the initial sensory block and a higher degree of motor block. The overall incidence of side effects was similar, with the exception of a higher incidence of urinary retention and hypotension in the groups receiving the higher rates of ropivacaine. The quality of treatment scores were similar for all treatment groups (Br. J. Anaesth. 1996; 76: 606-610).

Adult↗

Growth rate characteristics of acoustic neuromas associated with neurofibromatosis type 2.

Neurofibromatosis type 2 (NF2) is a dominantly inherited disorder characterized by the occurrence of bilateral acoustic neuromas (ANs and other central nervous system tumors. Magnetic resonance images and audiologic data on 22 patients with NF2 who underwent multiple studies at the National Institutes of Health between 1983 and 1993 were reviewed to determine the growth characteristics of ANs in these patients. The average growth rate of ANs in NF2 patients was 0.30 cm3 per year and was significantly higher in older patients (0.75 cm3 per year) than in younger ones (0.12 cm3 per year). Larger ANs were more commonly found in patients with concomitant spinal tumors or meningiomas. NF2 patients with spinal tumors but not meningiomas demonstrated faster growth rates than patients without additional tumor burden. The data from this study suggest that older patients or patients with associated spinal tumors have faster growing ANs and therefore should be followed closely and treated aggressively.

Adolescent↗

Investigation of microbial keratitis: an audit from 1988-1992.

An audit was performed of the investigation of 263 cases of microbial keratitis severe enough to be admitted to the Manchester Royal Eye Hospital over the 5-year period, 1988-1992. A pathogen isolation rate of 37% was noted during the first year which increased to 79% (p < 0.05) by the final year of audit. In late 1991 a new method of inoculating enrichment broths was introduced, which also contributed by increasing the yield from corneal scrapes. The audit process resulted in the development of and adherence to our investigation protocol, improved communication between Manchester Royal Eye Hospital and the microbiology laboratory, the implementation of a new investigatory method, and a significantly improved microbial isolation rate.

Adolescent↗

Relationship between genotype for the cytochrome P450 CYP2D6 and susceptibility to ankylosing spondylitis and rheumatoid arthritis.

OBJECTIVES: To determine whether particular genotypes for the cytochrome P450 enzyme CYP2D6, a polymorphic enzyme, are associated with susceptibility to ankylosing spondylitis (AS) and rheumatoid arthritis (RA), or linked with any specific clinical or familial features of the two conditions. METHODS: CYP2D6 genotypes were determined in 54 patients with AS, 53 patients with RA, and 662 healthy controls. Leucocyte DNA was analysed for the presence of mutations by restriction fragment length polymorphism analysis with the restriction enzyme Xbal and by two separate polymerase chain reaction assays. RESULTS: On the basis of odds ratio (OR), individuals with two inactive CYP2D6 alleles were more susceptible to AS than controls (OR 2.71, 95% confidence interval (CI) 1.04 to 7.08), with a stronger effect for the CYP2D6B allele (OR 4.11, 95% CI 1.54 to 11.0). No significant differences in the distribution of overall genotypes and allele frequencies were observed between RA and controls. No significant relationships were found between the skeletal, extraskeletal or familial features of AS or RA (iritis, psoriasis, inflammatory enteropathy and rheumatoid nodules, kerato-conjunctivitis sicca, pleuritis, rheumatoid and antinuclear factors) and the overall genotype. CONCLUSIONS: Our findings suggest a modest association between homozygosity for inactive CYP2D6 alleles, particularly CYP2D6B alleles, and susceptibility to AS. However, our results fail to demonstrate a genetic link between CYP2D6 genotype and RA.

Aged↗