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S Pugh

Publications and source records attributed to S Pugh.

At least 37 records · Page 2Linked to original sources
PubMed1995

A new method for active surveillance of adverse events from diphtheria/tetanus/pertussis and measles/mumps/rubella vaccines.

We describe a new method for active post-marketing surveillance of vaccine safety based on patient records. We studied the association between diphtheria/tetanus/pertussis (DTP) vaccination and febrile convulsion, and between measles/mumps/rubella (MMR) vaccination and febrile convulsion and idiopathic thrombocytopenic purpura (ITP) in five district health authorities in England by linking vaccination records with computerised hospital admission records. We found an increased relative incidence for convulsions 0-3 days after DTP vaccination. The effect was limited to the third dose of vaccine for which the attributable risk (all ages) was 1 in 12,500 doses. Completion of vaccination by 4 months instead of 10 months after the change in the UK to an accelerated immunisation schedule may have resulted in a 4-fold decrease in febrile convulsions attributable to DTP vaccine. 67% of admissions for a convulsion 6-11 days after MMR vaccination were attributable to the measles component of the vaccine (risk 1 in 3000 doses). An excess of admissions for a convulsion 15-35 days after MMR vaccination was found only for vaccines containing the Urabe mumps strain (1 in 2600 Urabe doses). There was a causal association between MMR vaccination and ITP resulting in admission 15-35 days subsequently; there was no evidence of a mumps strain-specific effect. The estimated absolute risk of 1 in 24,000 doses was 5 times that calculated from cases passively reported by clinicians. This finding emphasises the need for active surveillance of adverse events. The record linkage method that we used is an effective way to identify vaccine-attributable adverse events.

Diphtheria-Tetanus-Pertussis Vaccine↗
PubMed1994

New murine polymorphisms detected by random amplified polymorphic DNA (RAPD) PCR and mapped by use of recombinant inbred strains.

Oligonucleotide primers of random sequence that were 12 bases in length, 58% in GC content, and lacking internal palindromes were designed. By random amplified polymorphic DNA (RAPD) PCR, these primers were used to survey for DNA variations between the progenitors of the mouse AXB and BXA recombinant inbred sets (A/J and C57BL/6J). We identified 17 DNA variants detected by 10 primers. Map positions for these variants were determined by comparing their strain distribution patterns in the AXB, BXA recombinant inbred sets with strain distribution patterns of previously published loci. When necessary, BXD and NXSM recombinant inbred sets were also used. These 17 new loci mapped to 12 chromosomes. The 10 primers were also used to survey 20 inbred mouse strains including the progenitors of other recombinant inbred sets and four mouse strains recently inbred from the wild (CAST/Ei, MOLF/Ei, PERA/Ei, and SPRET/Ei).

Animals↗
PubMed1994

Patients with adenomatous polyps and carcinomas have increased colonic mucosal prostaglandin E2.

Colorectal carcinoma in humans and animal models is associated with increased synthesis of prostaglandin E2 (PGE2). PGE2 synthesis was measured in normal and neoplastic human colorectal mucosa to investigate its role in the adenoma-carcinoma sequence. Paired mucosal biopsy specimens for PGE2 synthesis and histological examination were obtained during 39 diagnostic colonoscopies. Twelve control patients in whom colonoscopies and histology were normal synthesised similar amounts of PGE2 at all sites. Their results were (mean (SD) pg PGE2/mg tissue) caecum 102.8 (15.9) (n = 6), ascending colon 110.8 (24.3) (n = 10), transverse colon 103.9 (19.5) (n = 11), descending colon 102.9 (23.2) (n = 12), sigmoid colon 96.4 (18.0) (n = 12), and rectum 107.1 (17.6) (n = 12). Nineteen patients had a total of 27 adenomatous polyps (rectum (1), sigmoid (22), descending (1), transverse (1), and ascending colon (1): histology-tubular (16), tubulo-villous (8), and villous adenomous (3)). The polyps (178.0 (55.0), n = 27) synthesised more PGE2 than controls (p < 0.001), but the values in polyp-associated mucosa (mean (SD) 115.4 (21.9), n = 15) were not different to control results. Eight patients had carcinomas (rectal (2), sigmoid (4), and caecal (2)) all of which were adenocarcinomas. The cancers (193.6 (40.2), n = 8) synthesised more PGE2 than control specimens (p < 0.001), but were not different to polyps. Cancer-associated mucosa (140.3 (27.7) n = 8) synthesised more PGE2 than control and polyp-associated mucosa. Colorectal neoplasia is associated with a progressive increase in PGE2 synthesis which may have a role in tumourigenesis and be a pathophysiological explanation for the beneficial effects of NSAIDs in animal models and human disease.

Adenocarcinoma↗
PubMed1993

Risk of aseptic meningitis after measles, mumps, and rubella vaccine in UK children.

Cases of aseptic meningitis associated with measles/mumps/rubella vaccine were sought in thirteen UK health districts following a reported cluster in Nottingham which suggested a risk of 1 in 4000 doses, substantially higher than previous estimates based on cases reported by paediatricians (4 per million). Cases were ascertained by obtaining vaccination records of children with aseptic meningitis diagnosed from cerebrospinal fluid samples submitted to Public Health Laboratories or discharged from hospital with a diagnosis of viral meningitis. Both methods identified vaccination 15-35 days before onset as a significant risk factor and therefore indicative of a causal association. With both, half the aseptic meningitis cases identified in children aged 12-24 months were vaccine-associated with onset 15-35 days after vaccine. The study confirmed that the true risk was substantially higher than suggested by case reports from paediatricians, probably about 1 in 11,000 doses. However, the possibility that the aseptic meningitis induced by vaccination was largely asymptomatic and a chance laboratory finding in children investigated for other clinical conditions, particularly febrile convulsions, could not be excluded. Comparison of national reports of virus-positive mumps meningitis cases before and after the introduction of this vaccine indicated that the risk from wild mumps was about 4-fold higher than from vaccine. Altogether, 28 vaccine-associated cases were identified, all in recipients of vaccines containing the Urabe mumps strain. The absence of cases in recipients of vaccine containing the Jeryl Lynn strain, despite its 14% market share, suggested a higher risk from Urabe vaccine. A prospective adverse event surveillance system using the study methods is currently being established to assess the risk, if any, from the Jeryl Lynn strain which is now the only mumps vaccine used in the UK.

Child, Preschool↗
PubMed1993

Bleeding oesophageal varices in alcoholic cirrhosis: long-term follow-up of endoscopic sclerotherapy.

Between 1977 and 1984, 53 consecutive unselected patients with bleeding oesophageal varices and alcoholic cirrhosis were treated by endoscopic sclerotherapy. Ten died during their index bleed, and 10 died within the following year due to hepatic failure (five), non-liver related causes (three), bleeding varices (one) and hepatocellular carcinoma (one). After the first year, a further three patients died of bleeding varices, eight died of hepatic failure (including one hepatocellular carcinoma) and six died of unrelated problems. Patients with hepatic disease of Childs-Pugh grade C died earlier than those of grade A and B grade (p < 0.01). There were 24 variceal recurrences within 1 year of completing sclerotherapy and seven recurrences later. Abstemious alcoholics rarely rebled and none developed recurrent varices after 18 months without recurrence. The size of the original varices, the number of sessions required to obliterate them, and the total volume of sclerosant used did not correlate with duration of remission. Continuing drinkers were more likely to present with bleeding varices (six of nine) than asymptomatic recurrences (one of 23) (p < 0.0001). In this study endoscopic sclerotherapy prevented deaths from variceal bleeds but there was a continued risk of death from hepatic failure and other unrelated causes.

Adult↗
PubMed1992

Organization and chromosomal locations of Rap1a/Krev sequences in the mouse.

The human RAP1A gene encodes a protein that apparently can antagonize the function of oncogenic ras genes in gene transfer experiments, but its normal function is unknown. To understand the function of this gene, we have undertaken a study of the mouse homolog, Rap1a. The complete coding sequence of a mouse Rap1a cDNA has been determined, and genomic clones representing three distinct Rap1a species were recovered. We find that Rap1a is located on distal mouse Chromosome (Chr) 3 near Nras, Ampd-1, Tshb, Ngfb, and Atp1a1. Two related sequences (Rap1a-rs1 and Rap1a-rs2) were also characterized. Rap1a-rs1, which was not localized, has a sequence very similar to the Rap1a cDNA, suggesting that it has been recently acquired by the mouse genome. Rap1a-rs2 is more distantly related to the gene sequence and is located on Chr 2 near Actc-1.

Amino Acid Sequence↗
PubMed1992

Multilocus markers for mouse genome analysis: PCR amplification based on single primers of arbitrary nucleotide sequence.

Polymerase chain reaction (PCR) based on single primers of arbitrary nucleotide sequence provides a powerful marker system for genome analysis because each primer amplifies multiple products, and cloning, sequencing, and hybridization are not required. We have evaluated this typing system for the mouse by identifying optimal PCR conditions; characterizing effects of GC content, primer length, and multiplexed primers; demonstrating considerable variation among a panel of inbred strains; and establishing linkage for several products. Mg2+, primer, template, and annealing conditions were identified that optimized the number and resolution of amplified products. Primers with 40% GC content failed to amplify products readily, primers with 50% GC content resulted in reasonable amplification, and primers with 60% GC content gave the largest number of well-resolved products. Longer primers did not necessarily amplify more products than shorter primers of the same proportional GC content. Multiplexed primers yielded more products than either primer alone and usually revealed novel variants. A strain survey showed that most strains could be readily distinguished with a modest number of primers. Finally, linkage for seven products was established on five chromosomes. These characteristics establish single primer PCR as a powerful method for mouse genome analysis.

Animals↗
PubMed1992

Successful therapy with ribavirin of late onset respiratory syncytial virus pneumonitis complicating allogeneic bone transplantation.

A 21-year-old patient developed interstitial pneumonitis nine months post bone marrow transplant for acute myeloblastic leukaemia. Immunofluorescence of broncheoalveolar lavage fluid revealed the presence of respiratory syncytial virus (RSV). Aerosolized ribavarin therapy resulted in rapid resolution of the pneumonitis with full recovery without any side effects. Ribavarin therapy should be considered early in the management of BMT patients who develop RSV pneumonitis.

Adult↗
PubMed1991

Medical audit and formulary management: a policy for rational use of thrombolytic drugs.

In this article we report on the development, introduction, and maintenance of a policy to promote rational use of thrombolytic drugs by hospital doctors. The work was undertaken within the framework of the voluntarily operated Riverside East drugs guide (formulary) management system (FMS). The policy was introduced in October 1988 and revised in November 1989 to coincide with the launch of the new, expensive thrombolytic drugs, alteplase (rt-PA, Actilyse) in 1988 and antistreplase (APSAC, Eminase) in 1989. Streptokinase was recommended as the first-line drug for patients who had not received it within the last 6 months. The policy was communicated to all staff in meetings and a drugs guide bulletin and reinforced by ward pharmacists. Results over a 15 month period show voluntary compliance by prescribers with the recommended policy. One hundred and seventy-four patients (22% cardiac admissions) presented with acute myocardial infarction. Of these 43 (25%) received streptokinase, the first-line recommended drug, 7 received alteplase and none received anistreplase. The savings in drug expenditure from using streptokinase rather than alteplase or anistreplase for the 15-month period of investigation were over pounds 27,000. This work represents an example of the effectiveness of the Riverside East FMS model in influencing prescribing behaviour.

Anistreplase↗
PubMed1991

Antibiotic therapy, clinical features and outcome of 36 adults presenting to hospital with proven influenza: do we follow guidelines?

The impact of the 1989/1990 influenza epidemic on the Nottingham hospitals was assessed in a retrospective survey. Thirty-six cases of proven influenza were identified, 14 of whom died. Non-survivors were more likely to be confused, uraemic and to lack focal chest signs and symptoms. Antibiotic therapy both prior to admission and following hospitalization was not optimal and, in many cases, failed to follow previously published guidelines. Such guidelines need emphasis during influenza epidemics.

Adult↗
PubMed1991

Poisoning with oxybutynin.

A case of poisoning with 100 mg of oxybutynin in a 34-year-old female is reported. The main features were anticholinergic effects, including stupor, followed by disorientation and agitation on awakening, dilated pupils, dry skin and retention of urine. She had a sinus tachycardia which resolved 3 h after admission, and in addition ventricular ectopics and bigeminy which continued for a further 30 h. She recovered fully on symptomatic treatment alone.

Adult↗
PubMed1991

A fall in duodenal PGE2 synthesis precedes histological changes and ulceration in the cysteamine model of duodenal ulceration.

The temporal association of histological damage and mucosal prostaglandin E2 (PGE2) synthesis was examined in the cysteamine model of duodenal ulceration in the rat. Four groups of 10 animals were used; a control group (which had a light ether anaesthetic, an i.m. injection of vehicle and were killed 18 h later) and three treatment groups (which were similarly treated but injected with cysteamine (0.3 mg/g body weight) and killed at 6, 18 or 24 h). Estimates of duodenal PGE2 synthesis and histological assessment of mucosal damage were performed. There were four early deaths in the 24-h group due to intra-thoracic haemorrhage. The 6-h group appeared normal macroscopically. There were seven established and three early ulcers in the 18-h group and two established and four early ulcers in the survivors of the 24-h group. Microscopically, the 6-h group did not differ from controls, but the 18 and 24-h groups showed evidence of mucosal damage compared to the control group (P less than 0.001). All three treatment groups synthesized less PGE2 than did the control group (P less than 0.001). Thus at 6-h post-injection, a decrease in PGE2 synthesis was evident but mucosal damage occurred later. Histological features correlated negatively with PGE2 synthesis (P less than 0.001).

Animals↗