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Biomedical subjects

A Seymour

Publications and source records attributed to A Seymour.

At least 19 recordsLinked to original sources
PubMed1996

Glomerular-specific imprinting of the mouse gsalpha gene: how does this relate to hormone resistance in albright hereditary osteodystrophy?

The gene for alpha-stimulating guanine-nucleotide binding polypeptide, Gnas, has been considered as a candidate for the imprinting effects ascribed to distal mouse Chromosome (Chr) 2. Its human homologue (GNAS1) appears, from clinical and biochemical studies of patients with Albright hereditary osteodystrophy, to be paternally imprinted. GNAS1 maps to 20q13, a region that shows linkage conservation with distal mouse Chr 2. We have mapped Gnas within the imprinting region on distal Chr 2 by linkage analysis. To establish if Gnas is imprinted, we have looked for expression differences in tissues taken from mice carrying maternal duplication/paternal deficiency for distal Chr 2 (MatDp2) and its reciprocal (PatDp2). RNA in situ hybridization revealed high levels of Gnas mRNA in glomeruli of PatDp2 embryos at late gestation and lower levels in glomeruli of MatDp2 embryos. These results strongly suggest that Gnas is maternally imprinted and suggest that the mouse gene may be imprinted in a manner opposite that predicted in human.

Alleles↗
PubMed1995

Comparative efficacy of oral doses of clindamycin and erythromycin in the prevention of bacteraemia.

Two antibiotics, clindamycin and erythromycin, were compared in a double-blind trial to test their efficacy in the prevention of post-dental extraction bacteraemia with streptococci in a group of 40 healthy patients. Tolerance to the oral doses was tested by questionnaire. Levels of drug in the serum were estimated using a microbiological assay. An in-vitro blood culture system was used as an analogy of the persistence of a bacteraemia in the presence of high levels of antibiotic. Isolates of streptococci were identified to species level. Minimum inhibitory concentrations of clindamycin and of erythromycin for each isolate were estimated. Results showed satisfactory levels of antibiotics in the blood for activity against oral streptococci. Clindamycin was slightly more effective than erythromycin in the prevention of post-extraction streptococcal bacteraemia but that efficacy was only 45%. Clindamycin as a single oral dose of 600 mg was well tolerated by patients compared with erythromycin 1.5 g.

Abdominal Pain↗
PubMed1994

Evidence for a differential location of vasoconstrictor endothelin receptors in the vasculature.

1. There are at least two subtypes of vascular endothelin (ET) receptors. Stimulation of the ETA receptors on vascular smooth muscle cells leads to vasoconstriction, whereas activation of the ETB receptors on endothelial cells elicits vasodilatation. Several reports in the literature have suggested the presence of a vasoconstrictor non-ETA receptor on vascular smooth muscle which has pharmacological similarities to the ETB receptor. The present study was undertaken to determine the location of this ETB-like receptor within the vascular system. 2. Fourteen vascular smooth muscle preparations from six species were used to determine the effect of the ETA receptor antagonist, BQ-123, on concentration-response curves elicited by ET-1 and the ability of the ETB receptor agonist, sarafotoxin S6c, to cause contraction. The vessels fell into two categories. One group was sensitive to BQ-123 and insensitive to sarafotoxin S6c and, thus, probably contained ETA receptors. The other group, with vasoconstrictor ETB-like receptors, was insensitive to BQ-123 and sensitive to sarafotoxin S6c. 3. Vessels from cynomolgus monkeys, when studied in vitro, appeared to contain primarily ETA receptors, although the potency of BQ-123 was quite variable, suggesting the possibility of ETA receptor subtypes. In contrast, both ET-1 and sarafotoxin S6c, given as intravenous injections in conscious monkeys, produced transient, equipotent, and dose-related increases in blood pressure. The highest dose of sarafotoxin S6c (1 nmol kg-1, i.v.) also caused a marked secondary depressor response (-80 +/- 6 mmHg) that lasted approximately 10 min. The pressor responses suggest that the vasoconstrictor ETB-like receptors are present in cynomolgus monkeys. 4. The data suggest the presence of two distinct vasoconstrictor ET receptor subtypes on smooth muscle cells. The ETA receptors are primarily located on the high pressure side of the circulation. The vasoconstrictor ETB-like receptors appear to be concentrated on the low pressure side.

Animals↗
PubMed1993

Clinical improvement and amyloid regression after liver transplantation in hereditary transthyretin amyloidosis.

Familial amyloid polyneuropathy (FAP) is a fatal autosomal dominant disorder. Progressive peripheral and autonomic neuropathy are associated with neural and visceral deposition of amyloid, derived most commonly from the Met-30 variant of the plasma protein transthyretin. We have reported previously that orthotopic liver transplantation causes prompt replacement of variant transthyretin by the donor wild-type in the plasma. We now report clinical outcome 1-2 years after transplantation. Three of the first four patients have improved general wellbeing, walking ability, and bowel function, and one of them has regained normal bladder and bowel function. There has been little objective improvement in peripheral neuropathy. The fourth patient, who had the most severe neurological deficits and a complicated postoperative course, has not improved but there has been no further deterioration in contrast to the inexorable progression before transplantation. Quantitative scintigraphy with radiolabelled serum amyloid P component showed visceral amyloid deposits in all three patients studied; in two who were followed serially the deposits regressed after transplantation in association with the clinical improvement. Another FAP patient who was also monitored prospectively for 2 years but who did not undergo transplantation, showed, as expected, progression of neuropathy and increased visceral amyloid deposition. Liver transplantation does therefore have important benefits in FAP during the first 2 years after surgery. Neurological decline is halted and amyloid deposits can be mobilised. The best timing and long-term results of the procedure must now be established.

Adult↗
PubMed1993

Necrotizing pancreatitis and multisystem organ failure associated with toxoplasmosis in a patient with AIDS.

Extraneural manifestations of toxoplasmosis often are not recognized antemortem in patients with AIDS. We describe a patient who was seropositive for human immunodeficiency virus and presented with lethargy, abdominal tenderness, rapidly progressive ventilatory failure, rhabdomyolysis, myoglobinuria, and disseminated intravascular coagulation. Although the diagnosis of pancreatitis was not considered while the patient was alive, an autopsy demonstrated pancreatic necrosis associated with toxoplasmal cysts. No other infection was evident. This case suggests that Toxoplasma gondii can cause severe pancreatitis in patients with AIDS.

AIDS-Related Opportunistic Infections↗
PubMed1992

Oncogenic forms of p53 inhibit p53-regulated gene expression.

Mutant forms of the gene encoding the tumor suppressor p53 are found in numerous human malignancies, but the physiologic function of p53 and the effects of mutations on this function are unknown. The p53 protein binds DNA in a sequence-specific manner and thus may regulate gene transcription. Cotransfection experiments showed that wild-type p53 activated the expression of genes adjacent to a p53 DNA binding site. The level of activation correlated with DNA binding in vitro. Oncogenic forms of p53 lost this activity. Moreover, all mutants inhibited the activity of coexpressed wild-type p53, providing a basis for the selection of such mutants during tumorigenesis.

Base Sequence↗
PubMed1992

In vitro susceptibility of Haemophilus influenzae to cefaclor, cefixime, cefetamet and loracarbef.

The susceptibility of 2,212 Haemophilus influenzae isolates cultured in UK clinical laboratories in 1991 was determined for four orally-administered beta-lactam drugs. These isolates included 1,893 ampicillin-susceptible, 191 beta-lactamase-positive and 128 ampicillin-resistant, beta-lactamase-negative Haemophilus influenzae. While 150 (6.8%) isolates were resistant to cefaclor (MIC > or = 16 mg/l) and 85 (3.8%) to loracarbef, all were inhibited by < or = 2 mg/l cefetamet and < or = 1 mg/l cefixime and were therefore susceptible to these agents. Ranges and modes of inhibition zone diameters and MICs indicated that the susceptibility of a variable proportion of the 191 beta-lactamase-positive isolates to cefaclor, loracarbef and cefetamet was reduced compared with the fully susceptible population. In contrast, a major reduction in susceptibility to all four antimicrobial agents was seen among the 128 ampicillin-resistant (MIC 1-64 mg/l) beta-lactamase-negative isolates such that these accounted for 53% and 67% of the total number of organisms resistant to cefaclor and loracarbef respectively. In addition, 23 of 25 isolates inhibited only by > or = 1 mg/l cefetamet and all eight inhibited only by > or = 0.5 mg/l cefixime showed this type of resistance to ampicillin. Results indicate the importance of detecting non-beta-lactamase-mediated resistance to ampicillin and any concomitant diminished susceptibility to other beta-lactam drugs.

Ampicillin Resistance↗
PubMed1992

Antimicrobial resistance in Haemophilus influenzae from England and Scotland in 1991.

Twenty-two laboratories in England and Scotland sent 2212 clinical isolates of Haemophilus influenzae to The London Hospital Medical College (LHMC) between 1 January and 31 March 1991. After confirmation of identity, the prevalence of resistance was determined and compared with results from previous similar surveys. beta-Lactamase was produced by 8.3% of non-capsulate isolates and 21% of 52 type b isolates; both figures were higher than the 6% and 18% figures recorded, respectively, in 1986. There was an increase in the prevalence of non-beta-lactamase-mediated diminished susceptibility to ampicillin (5.8%) and co-amoxiclav (6.1%) compared with 1986 (4%). Whereas fewer H. influenzae isolates were resistant to tetracycline (1.4%) or chloramphenicol (0.8%), there was an increase in resistance to trimethoprim (6.8%) and to sulphamethoxazole (16.9%) compared with 1986 (4.2% and 3.5% respectively). In addition, 95 isolates (4.3%) were resistant to both of these anti-folate antimicrobials. Six isolates (one type b from CSF) were resistant to all drugs tested, except for co-amoxiclav. Overall, the results demonstrated that changes have occurred in the last decade in England and Scotland, such that H. influenzae isolates are increasingly likely to be resistant to ampicillin, co-amoxiclav and co-trimoxazole.

Chloramphenicol Resistance↗
PubMed1992

The antimicrobial susceptibility of Moraxella catarrhalis isolated in England and Scotland in 1991.

Between 1 January and 31 March 1991, 20 laboratories in England and Scotland sent a total of 413 consecutive clinical isolates of Moraxella catarrhalis to The London Hospital Medical College (LHMC). After confirmation of identity, the susceptibility of all isolates to 11 antimicrobial agents was determined. Of the 375 (90.8%) isolates which were found at LHMC to be beta-lactamase-positive, 174 produced zones of inhibition around 2 micrograms ampicillin disc which were greater than or equal to 20 mm in diameter and 252 were inhibited by less than or equal to 0.5 mg/L of ampicillin. However, 71 of these 375 had been reported to be ampicillin-susceptible by peripheral centres. While beta-lactamase had not been detected in 35 of these 71 isolates, the other 36 had been reported to be ampicillin-susceptible and beta-lactamase-positive. All 38 beta-lactamase-negative isolates produced zones greater than or equal to 30 mm in diameter and were inhibited by less than or equal to 0.06 mg/L of ampicillin. No M. catarrhalis isolate was found to be resistant to co-amoxiclav, tetracycline, chloramphenicol or cefaclor. Two strains showed intermediate susceptibility to erythromycin (MIC 1 mg/L) and 27 required greater than or equal to 32 mg/L of sulphamethoxazole for inhibition. Resistance to trimethoprim was uniform (MICs 2-128 mg/L). Two isolates showed intermediate susceptibility to cefixime (MIC 2 mg/L) but none was resistant to the new oral cephalosporin cefetamet or to the oral carbacephem loracarbef.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Bacterial Agents↗
PubMed1992

Women whose mental illnesses recur after childbirth and partners' levels of expressed emotion during late pregnancy.

Expressed emotion (EE) in the partners of 25 pregnant women with a history of psychosis or severe depression and in 13 pregnant control subjects without any previous psychiatric disorder was assessed in the ninth month of pregnancy. At this time, no patient presented as a case according to RDC. Eleven subjects with a history of psychiatric disorder experienced a further episode of illness in the six months following delivery. Partners of women who became ill had made fewer critical and positive comments about their wives during the pregnancy than the partners of women who remained well. Poor self-rated social adjustment in the partners was also predictive of recurrence of illness after delivery.

Adult↗
PubMed1991

Failure of two macrolide antibiotics to prevent post-extraction bacteraemia.

Two macrolide antibiotics, erythromycin and josamycin, were compared in a double-blind trial to examine their efficacy in the prevention of post-dental extraction bacteraemia in a group of healthy patients. An in vitro blood culture system was used. Isolates of streptococci were identified to species level. Minimum inhibitory concentrations (MICs) of erythromycin and of josamycin for each isolate were estimated by an agar dilution technique, with controls. Levels of drug in the serum of volunteers and of patients were assayed after oral doses of the macrolide antibiotics. Levels found achieved early peaks and satisfactory concentrations for activity against streptococci. Within the specified parameters, the results demonstrated that the antibiotics failed to prevent survival in blood culture of various strains of streptococci for up to 24 hours following collection of the blood. It is recommended that an alternative antibiotic to either erythromycin or to josamycin be used to achieve prophylaxis against streptococci in infective endocarditis risk patients who are allergic to penicillin.

Adolescent↗
PubMed1990

Comparative efficacy and tolerance of erythromycin and josamycin in the prevention of bacteraemia following dental extraction.

The tolerance and pharmacokinetics of erythromycin stearate and josamycin base were compared in healthy dental students. The efficacy and tolerance of the two antibiotics were compared in the prevention of bacteraemia following dental extraction. Erythromycin achieved higher serum levels at the time of extraction in dental patients than did josamycin. Erythromycin was rapidly and better absorbed than josamycin in the student volunteers, but josamycin caused less gastrointestinal side effects than erythromycin. Both antibiotics were only marginally more effective than placebo in preventing bacteraemia following dental extraction.

Adult↗
PubMed1990

Predominance of resistant oral streptococci in saliva and the effect of a single course of josamycin or erythromycin.

We have investigated the influence of the macrolides erythromycin and josamycin on the selection of resistant oral streptococci by sampling saliva of volunteers before and after oral administration of 1.5 g of either agent followed by a further 0.5 g of the same drug after 6 h, as in routine prophylaxis for oral or dental procedures. The small proportion of resistant organisms present before antibiotic administration increased substantially 48 h after the macrolides were given. After antibiotic administration mean counts of oral streptococci resistant to 1, 4 and 64 mg/l erythromycin were 23%, 17% and 6%, respectively, of the total numbers of streptococci isolated; after josamycin, the values were 13%, 6% and 4% respectively. The proportion of resistant streptococci then declined gradually but remained above pre-antibiotic levels three months later. Streptococci isolated on media containing 64 mg/l of macrolides were mainly Streptococcus sanguis and S. mitis with one isolate of S. salivarius; the majority were resistant to 256 mg/l erythromycin, josamycin, all other macrolides tested and clindamycin. Amoxycillin and pristinamycin were the only compounds tested that were inhibitory to these organisms at therapeutically attainable concentrations.

Adolescent↗
PubMed1987

Resistance of clinical isolates of Haemophilus influenzae in United Kingdom 1986.

Between 1 January and 31 March 1986, 2434 strains of Haemophilus influenzae collected from 23 laboratories in the United Kingdom were examined. With the same criteria as previous studies in 1977 and 1981 the prevalence of resistance was: ampicillin 7.8% (6.2% beta-lactamase producers and 1.6% non-producers), tetracycline 2.7%, chloramphenicol 1.7%, trimethoprim 4.2%, and sulphamethoxazole 3.5%. of the 87 capsulated strains, 15 produced beta-lactamase, nine were resistant to ampicillin but did not produce beta-lactamase, and two strains, one of which produced beta-lactamase, were resistant to chloramphenicol and tetracycline. Since 1977 the prevalence of resistance to ampicillin, chloramphenicol, and trimethoprim has increased significantly. During 1981-6 strains resistant to ampicillin but not producing beta-lactamase and strains resistant to trimethoprim have significantly increased.

Ampicillin↗
PubMed1983

Accuracy of methods used for susceptibility testing of Haemophilus influenzae in United Kingdom laboratories.

Antibiotic susceptibility test reports on 1841 strains of Haemophilus influenzae from 25 microbiology laboratories were compared with results obtained with the same strains at The London Hospital Medical College. Of strains found to be sensitive to the antibiotics tested, 0.5% were reported as tetracycline-resistant, 1.6% as ampicillin-resistant, and 6.2% as trimethoprim-resistant. Of strains found to be resistant to these antibiotics, 37% were reported as tetracycline-sensitive, 27% as ampicillin-sensitive, and 66.7% as trimethoprim-sensitive. Factors found to be of significance in improving accuracy of sensitivity reporting included use of chromogenic cephalosporin and low-content antibiotic discs for detection of ampicillin resistance, and use of lysed blood agar rather than chocolated blood agar to detect trimethoprim sensitivity.

Ampicillin↗