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Biomedical subjects

K R Gough

Publications and source records attributed to K R Gough.

At least 19 recordsLinked to original sources

Molecular epidemiology of tetM genes in Neisseria gonorrhoeae.

OBJECTIVE: To examine the epidemiology of the tetM gene in Neisseria gonorrhoeae strains with high level resistance to tetracycline (TRNG) using a polymerase chain reaction (PCR) assay. METHODS: A single tube PCR was developed which distinguishes between the American and Dutch variants of the tetM gene. Between 1988 and 1995, 518 strains of TRNG (tetracycline MIC > 8.mg/l) were referred to the Gonococcus Reference Unit by other laboratories or isolated from routine swabs taken at local clinics. The strains were analysed for plasmid content, auxotype, serovar, and the tetM gene type. Travel details of the patients were determined by a questionnaire. RESULTS: A PCR product was obtained from all TRNG examined. 387 TRNG strains produced a 778 bp PCR product (American type tetM) and 131 produced a 443 by PCR product (Dutch type tetM). Infections acquired in the United Kingdom contributed 57% of the TRNG strains included in this study; 82% of these carried the American type of tetM. The number of UK acquired TRNG received by the GRU increased each year except 1993--from four strains received in 1990 to 92 in 1995. After the United Kingdom, Caribbean and African countries contributed most strains, with 56 and 60 TRNG acquired in each area respectively. All strains originating in Africa, except one from South Africa, contained the American type tetM. Infections caught in Nigeria and Kenya contributed most strains (15 and 14 respectively). The TRNG originating from Caribbean countries comprised 36% Dutch tetM type. Infections caught in Jamaica accounted for 82% of the Caribbean strains. All 35 TRNG strains originating in the Far East contained the Dutch type tetM. 25 of the Far East strains were also penicillinase producing (PPNG). Infections originating in Indonesia accounted for 49% of the Far East strains but these belonged to 12 different auxotype/serovar combinations. A geographical variation in the type of penicillinase coding plasmids found in PPNG/TRNG was also detected. CONCLUSIONS: These data suggest that the Dutch type tetM may have originated in the Far East and the American type in the African continent. Subsequent spread has resulted in a heterogeneous distribution of TRNG types in other parts of the world. At completion of the survey the numbers of TRNG imported each year from the major overseas sources had reached a plateau while UK contracted TRNG continued to rise providing evidence for the establishment of endemic TRNG strains in the United Kingdom.

Bacterial Proteins↗

Comparison of three methods for culture confirmation of Neisseria gonorrhoeae strains currently circulating in the UK.

AIMS: To establish the current sensitivity of two commercial kits for culture confirmation of Neisseria gonorrhoeae strains circulating in the UK. METHODS: A total of 544 strains were studied (199 gonococci from male patients attending hospitals in the county of Avon, 204 unselected N gonorrhoeae isolates from male patients in Leeds, 20 strains referred to the Gonococcus Reference Unit because of difficulties with the Syva fluorescent antibody test (FAT), and 121 strains collected over a four year period which had not reacted with serotyping antibodies). Strains were tested by sugar utilisation in cysteine trypticase base agar (CTA test), the Phadebact Monoclonal GC Test and Syva MicroTrak Neisseria gonorrhoeae Culture Confirmation Test. The auxotype and serovar of each strain were also determined. RESULTS: The sugar utilisation test confirmed the identity of 99% (197/199) of gonococci from Avon and 97% (198/204) of those from Leeds. The Syva FAT confirmed 76% (151/199) of isolates from Avon and 84% (171/204) of those from Leeds. The Phadebact test confirmed all but one isolate from the 403 strains from both cities. Half of the 20 referred FAT negative isolates also give a negative result in the Syva FAT; however, only 10% of the remainder gave a strong reaction in our laboratory. All serotyping antibody negative strains were negative in the FAT, although all these and all of the 20 strains that give a negative result in the FAT gave positive reactions in the other culture confirmation tests. Typing tests revealed a greater diversity amongst the FAT negative strains from Leeds than those from Avon. CONCLUSIONS: Considerable differences in the sensitivity of the MicroTrak but not with the Phadebact or CTA tests were found for the identification of isolates from two geographically distinct areas of the UK. Our results suggest that the Syva FAT would not be suitable, if used alone, for culture confirmation in Avon or Leeds.

Agglutination Tests↗

Double-blind randomized multicenter study comparing Maalox TC tablets and ranitidine in healing of duodenal ulcers.

The efficacy of ranitidine 150 mg twice daily and Maalox TC three tablets four times daily were compared in patients with endoscopically confirmed duodenal ulcer. Seventy-nine patients were randomly allocated to double-blind, double-dummy treatment, stratified for smokers. Endoscopy was repeated after four weeks. Those unhealed continued treatment for a further two weeks before final endoscopy. Per protocol analysis in 53 patients showed ulcer healing rates at week 4 and at weeks 4 and 6 combined of 78 and 89% on Maalox TC, and of 81 and 91% on ranitidine, respectively. The same analysis gave overall healing rates of 81% in smokers and 100% in nonsmokers, irrespective of treatment. Both treatments provided early ulcer pain relief. Diarrhea was a commoner side effect in patients on Maalox TC. The study showed Maalox TC and ranitidine were equally effective in healing duodenal ulceration.

Adult↗

Laboratory detection of ciprofloxacin resistant Neisseria gonorrhoeae.

During 1989 and 1990 strains of Neisseria gonorrhoeae with reduced susceptibility to ciprofloxacin were isolated in laboratories across the United Kingdom. Treatment failures were associated with some of these infections. These strains were detected by quantitative susceptibility testing because the zone of inhibition around 5 micrograms ciprofloxacin discs shows little decrease in size even with those that are the most resistant. This study determined that strains with reduced susceptibility to ciprofloxacin (MIC of greater than or equal to 0.05 mg/l) produced no zone of inhibition around a commercially available disc containing 30 micrograms of nalidixic acid. Ciprofloxacin sensitive (MIC of less than 0.05 mg/l) strains, however, grew with a large zone (greater than 21 mm) around this disc. These observations suggest that laboratories could adopt this disc test to detect those strains for which ciprofloxacin is not appropriate treatment.

Ciprofloxacin↗

Identification of Neisseria gonorrhoeae using the Neisstrip rapid enzyme detection test.

A rapid enzyme activity strip test (Neisstrip, Lab M Ltd, Bury) was compared retrospectively with Phadebact Monoclonal GC coagglutination (Pharmacia Diagnostics, Uppsala, Sweden), cystine trypticase agar sugar utilisation (CTA), and Gonochek II (J W Turner, Liverpool) enzyme methods for identification of 95 Neisseria spp and related species. These had been previously identified using standard methods and included 29 that had given aberrant results. Neisstrip identified correctly all but two, including nine incorrectly identified by Phadebact and 18 erroneously identified using CTA sugars. Results were similar to those obtained with Gonochek II. After this a prospective study was performed testing 400 oxidase positive isolates derived from clinical samples cultured on gonococcal selective medium. Two organisms, both Moraxella spp, were incorrectly identified as N gonorrhoeae by the Neisstrip. The superoxol test, when used with either the Phadebact or Neisstrip tests, maintained 100% sensitivity and specificity. The Neisstrip is a rapid, economic test that is accurate and easy to interpret. It may be used alone or in conjunction with a superoxol test or a coagglutination test, which is relatively accurate but more expensive, and found by some technical staff to be more difficult to interpret.

Aminopeptidases↗

Value of a centralised approach in the management of haematemesis and melaena: experience in a district general hospital.

All patients presenting with acute upper gastrointestinal bleeding between November 1986 and April 1988 were admitted to a centralised joint medical/surgical unit, with a policy of early clinical and endoscopic assessment and rapid surgical intervention in those at high risk. Of the 430 patients admitted 69.5% were over the age of 60 and 30% had significant additional medical conditions. 50.4% were bleeding from peptic ulcers and one third had been taking non-steroidal anti-inflammatory agents. Fifty five patients underwent surgery, which in two thirds was carried out within 24 hours of admission, usually for continued bleeding. In patients with peptic ulcer the operation rate was 21.6%. Overall mortality was 3.7%, and in those with bleeding gastric or duodenal ulcers 5.5%; surgical mortality in the later group was 15.2%. All patients who died had serious concomitant pathology and 87% were over 70 years of age. Adoption of a centralised approach to management of haematemasis and melaena is feasible in a District General Hospital and associated with an improved survival.

Adult↗

Penicillin-binding protein 2 genes of non-beta-lactamase-producing, penicillin-resistant strains of Neisseria gonorrhoeae.

Oligonucleotides that correspond to regions of the penicillin-binding protein 2 gene (penA) that differ between penicillin-sensitive and penicillin-resistant strains have been used as probes to classify the penA genes in a collection of penicillin-resistant gonococci isolated in Britain. 44/47 of those gonococcal strains that had minimal inhibitory concentrations of greater than or equal to 0.25 microgram benzylpenicillin per ml contained extensively altered penA genes which appeared to be very similar (or identical) to one or other of the two classes of altered penA genes that have been described previously. Since these two classes of altered penA genes are related, it appears that the great majority of the altered penA genes on non-beta-lactamase-producing penicillin-resistant gonococci have a clonal origin. The other three penicillin-resistant strains had altered penA genes that were different to those described previously. A crucial step in the development of the altered forms of PBP2 with decreased affinity for penicillin appears to have been the insertion of an extra codon within the transpeptidase domain of the penA gene. This insertion was found in the penA gene of all gonococci with minimal inhibitory concentrations of greater than 0.016 microgram benzylpenicillin per ml but was not found in any strains with minimal inhibitory concentrations of less than or equal to 0.016 microgram per ml.

Acyltransferases↗

Steroid sensitive systemic disease with anaemia in the elderly: a manifestation of giant cell arteritis?

Nine elderly patients presented with features of a multisystem disorder thought to be either a connective tissue disease of undefined type or disseminated malignancy. Associated features were a normochromic anaemia, raised erythrocyte sedimentation rate (ESR) (or plasma viscosity) and raised serum alkaline phosphatase levels. None had symptoms to suggest either giant cell arteritis or polymyalgia rheumatica. Temporal artery biopsy was performed before trial of corticosteroid therapy in four, and two showed giant cell arteritis. All nine responded dramatically to corticosteroids and the anaemias resolved. One died after 6 y, and the rest are well after 1 to 7 y.

Age Factors↗

Interim analysis of a comparative trial of ranitidine and cimetidine in the prevention of duodenal ulcer.

A multicenter, double-blind, double-dummy maintenance trial was performed using ranitidine 150 mg or cimetidine 400 mg taken orally at night for 12 months. A total of 454 patients with healed duodenal ulcer entered the trial. This interim analysis of the results shows that based on the findings of endoscopic assessments performed four, eight, and 12 months after starting treatment, the relapse rate for duodenal ulcer was significantly lower in those taking ranitidine than in those treated with cimetidine. There were no serious unwanted effects attributable to either drug.

Adult↗

Ranitidine and cimetidine in prevention of duodenal ulcer relapse. A double-blind, randomised, multicentre, comparative trial.

In a comparative trial of preventive medication for duodenal ulceration with 51 participating centres, 484 patients were recruited for a year's maintenance treatment with the recommended bedtime dose of ranitidine (150 mg; n = 243) or cimetidine (400 mg; n = 241). These outpatients had recently healed duodenal ulcers, confirmed by endoscopy before and after healing, and ulcer relapse was monitored by endoscopy every 4 months. The distribution of factors likely to influence ulcer recurrence was similar in the two treatment groups. A life-table method of analysis showed that the ulcer relapse rate was consistently and significantly lower on ranitidine that on cimetidine (8% v 21%, p = 0.0018 at 4 months; 14% v 34%, p less than 0.0001 at 8 months; and 23% v 37%, p = 0.004 at 12 months). Crude relapse rate calculations, which underestimate the probability of ulcer recurrence, also confirmed the significant superiority of ranitidine 150 mg over cimetidine 400 mg nightly in preventing ulcer recurrence throughout the year.

Adult↗

The organisation and evaluation of an open-access dysphagia clinic.

We describe our experience in organising an open access dysphagia clinic. Any patient with dysphagia for solids of at least one week's duration can be seen within one week of referral. One hundred and nine 'new' patients were referred in the first year. Fifty-five (50.4%) had peptic or malignant strictures. The majority of these received definitive treatment within ten days of the date of referral. This system of referral and treatment improves the speed of detection and treatment of patients with oesophageal stenosis.

Adult↗