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Biomedical subjects

S Little

Publications and source records attributed to S Little.

At least 73 records · Page 4Linked to original sources
PubMed1994

Physical mapping of the split hand/split foot locus on chromosome 7 and implication in syndromic ectrodactyly.

Split hand/split foot (ectrodactyly; SHSF) is a human developmental malformation characterized by missing digits and claw-like extremities. An autosomal dominant form of this disorder has been mapped to 7q21.3-q22.1; the locus has been designated SHFD1. We have constructed a physical map consisting of overlapping yeast artificial chromosome clones for the entire region. Somatic cell hybrid and fluorescent in situ hybridization analyses were used to define SHSF-associated chromosomal rearrangements in twelve patients. An SHFD1 critical interval of 1.5 Mb was established by analysis of five patients with deletions. Translocation or inversion breakpoints found in six patients were mapped within 700 kb of each other in the critical region. Of note is that eight of the patients analyzed (67%) are in fact classified as having syndromic ectrodactyly. Thus, these mapping data establish a relationship between simple split hand/split foot and this more complex group of human birth defects. Finally, we have mapped DLX5, a member of the Distal-less homeobox gene family, to the SHFD1 critical interval.

Abnormalities, Multiple↗
PubMed1994

Comparison of the effects of cilazapril in an elderly and nonelderly hypertensive general practice population.

The ACE inhibitor cilazapril was studied in mild to moderate hypertensive patients in general practice to evaluate the effect of age on hypotensive response to low (0.5 and 1 mg) doses. Six hundred and seventy-one patients entered a two week single-blind placebo run-in period and 524 patients were eligible to receive active treatment titrated up to a maximum dose of 5 mg. All patients received 0.5 mg of cilazapril once daily for four weeks. The dose was titrated at monthly intervals to 1, 2.5 and 5 mg once daily if DBP remained > 90 mmHg. If DBP < or = 90 mmHg patients remained at their current dose level until the end of the study. Three hundred and twenty-nine patients < 65 years old and 195 patients > or = 65 years old took active treatment. Binary logistic regression detected no statistically significant difference in response between the two groups (P > 0.2) at low doses of cilazapril. Cumulative response rates (DBP < or = 90 mmHg) for all patients were 24.5%, 40.4%, 54.5% and 62.7% for the escalating dose groups. Cumulative augmented response rate (DBP < or = 90 mmHg and/or reduction in DBP of > or = 10 mmHg) at the 5 mg dose level was 76.7% for all patients. Cilazapril was well tolerated with the pattern of adverse events reflecting those currently documented. A higher proportion of patients than expected responded to the low doses of cilazapril. This effect was not age dependent. These doses are lower than the recommended maintenance doses of 2.5-5 mg in the UK data sheet.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Enhancing rehabilitation through mutual aid: outreach to people with recent amputations.

Social workers in a rehabilitation hospital established an outreach service through which volunteers with previous amputations visited patients with recent amputations, acting as role models and offering emotional support and information. Volunteers received in-depth training and continued with their own system of support. Patients who were visited had strong positive responses to the program. Critical components of the program were developing a collaborative partnership between volunteers and social workers; demonstrating credibility to health care professionals; linking emotional support, information, and affirmation; providing benefits to both patient and volunteer; and strengthening linkages among patient, community, and institution.

Adaptation, Psychological↗
PubMed1993

A randomized, double-blind, multi-centre, parallel-group study comparing the tolerability and efficacy of moclobemide and dothiepin hydrochloride in depressed patients in general practice.

A randomized, double-blind, multi-centre, parallel-group study compared the tolerability and efficacy of 450 mg of moclobemide and 75-150 mg of dothiepin in the management of depressed patients in general practice. Patients who fulfilled the DSM-III-R criteria for major depressive disorder and who scored 13 or more on the Hamilton Depression Rating Scale were admitted. The trial lasted six weeks. The dose of moclobemide was 150 mg three times daily and that of dothiepin was 75 mg daily for the first two weeks and 150 mg thereafter. Assessments were made at baseline and after one, three and six weeks using the HDRS, the Zung SRS and the CGI. Adverse events and vital signs were monitored at each visit, and laboratory screening tests performed at the beginning and end of the study. Sixty-four general practitioners from four centres recruited 345 patients: 175 received dothiepin and 170 moclobemide; 265 completed six weeks of treatment. Thirty-eight dothiepin-treated patients (22%) and 42 who received moclobemide (25%) dropped out, most commonly because they experienced adverse events. More patients on dothiepin (24) than on moclobemide (16) dropped out for this reason; the incidence of adverse events was 10% higher in the dothiepin-treated group and of "side effects" more than 10% higher, the latter difference being statistically significant. Both treatments resulted in significant improvement; this was greater in the dothiepin-treated group and the difference was statistically significant, although clinically small.

Adolescent↗
PubMed1992

Prevalence of anthelmintic-resistant nematodes in fibre-producing goats in Scotland.

Six cashmere goat herds in Scotland were surveyed to assess the prevalence of anthelmintic resistance and the species of nematode involved. Resistance was determined in vivo by a faecal egg count reduction test and in vitro using an egg hatch assay and specific faecal egg identification techniques. Benzimidazole resistance was present in five of the herds, insufficient eggs were obtained from the other herd to draw firm conclusions. Teladorsagia (Ostertagia) species predominated in four of the five herds in which resistance was detected and Haemonchus contorus was the dominant species in the other.

Animals↗
PubMed1992

Prenatal diagnosis for the cystic fibrosis mutation 1717-1, G-->A using arms.

A family carrying two cystic fibrosis mutations, delta F508 and 1717-1, G-->A, requested prenatal diagnosis. In order to eliminate the need for labelling of allele-specific oligonucleotides and to simplify the analysis, 1717-1, G-->A was detected using an ARMS (amplification refractory mutation system) method (Newton et al., 1989). Fetal DNA was obtained by chorionic villus sampling (CVS) and the ARMS technique was used to exclude the 1717-1, G-->A mutation. The fetus was found to be heterozygous for the delta F508 mutation. ARMS is a simple, quick, non-radioactive method suitable for detecting DNA mutations in various clinical situations.

Adenine↗
PubMed1992

Development, multiplexing, and application of ARMS tests for common mutations in the CFTR gene.

The amplification refractory mutation system (ARMS) is a simple, rapid and reliable method for the detection of any mutation involving single base changes or small deletions. We have applied ARMS methodology to the detection of mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Single ARMS tests have been developed for 11 CFTR mutations found in the northwest of England. ARMS reactions for the most common mutations have been multiplexed to give a test which will detect the presence of the delta F508, G551D, G542X, and 621 + 1G----T mutations in a DNA sample. The multiplex test has been validated by the analysis of over 500 previously genotyped samples and has been found to be completely accurate. The rapid detection of the most common mutations has enabled early molecular confirmation of suspected cystic fibrosis in neonates, rapid typing of cystic fibrosis patients and their relatives, and testing of sperm and egg donors.

Base Sequence↗
PubMed1991

Isotretinoin and lung function in systemic sclerosis.

During an open prospective study of the synthetic retinoid isotretinoin in ten patients with systemic sclerosis, one patient developed an eosinophilic pleural effusion and two patients were noticed to have asymptomatic deterioration in pulmonary function tests. The pulmonary function of all treated patients was then compared retrospectively with a similar control group of patients not treated with isotretinoin. There was a significantly greater decrease in the 1-s forced expiratory volume and transfer coefficient in the patients with systemic sclerosis being treated with isotretinoin in comparison to the untreated control patients. Studies of lung function in patients treated with isotretinoin for other indications are required.

Adult↗
PubMed1991

The effect of smoking on the development of allergic disease and specific immunological responses in a factory workforce exposed to humidifier contaminants.

The effects of smoking on the development of work related asthma and on the production of specific IgE and IgG antibodies to antigen from a contaminated humidifier are described for a sample of 258 workers from a printing factory. Current smoking was associated with low production of IgG antibody but with higher production of IgE antibody. No dose response for either antibody was found when numbers of cigarettes or pack-years smoked were considered. Work related asthma was detected in 12 workers by peak flow recordings. Six were current smokers and one was an ex-smoker. One subject with work related asthma had a high (and one a marginal) concentration of specific IgE to humidifier antigen.

Air Conditioning↗
PubMed1989

A short N-proximal region of prochymosin inhibits the secretion of hybrid proteins from Escherichia coli.

A gene encoding bovine prochymosin (PC) was fused to the coding sequence (phoA) for the Escherichia coli alkaline phosphatase (AP) signal peptide and expressed in E. coli under the control of the phoA promoter. Upon induction, an AP-PC fusion protein was produced which was neither processed nor exported into the periplasm. We investigated this lack of secretion by constructing a series of gene fusions in which different regions of the PC gene were inserted between the coding regions of the AP leader and mature protein. Analysis of the cellular location of the proteins encoded by these fusions revealed that a region of PC (between amino acids 6 and 29) prevented processing and secretion of an AP-PC fusion when inserted near to the AP signal peptide. In contrast, when this 'blocking sequence' was inserted elsewhere in AP the hybrid proteins were efficiently processed and translocation was initiated.

Alkaline Phosphatase↗
PubMed1989

Genetic structure, function and regulation of the transposable element IS21.

The IncP plasmid R68.45 and other plasmids carrying tandem repeats of the insertion sequence IS21 [= (IS21)2] produce replicon fusions via transposition at high frequencies in Escherichia coli and other gram-negative bacteria, whereas plasmids with a single IS21 copy, e.g. R68, give replicon fusions rarely. The 2131 bp nucleotide sequence of IS21 was determined; at the ends there were 11 bp inverted repeats with one mismatch. Two adjacent open reading frames, istA and istB, were located on one DNA strand of IS21. In E. coli maxicells, polypeptides of 46 kDa (the istA gene product) and 30 kDa (the istB gene product) were expressed by (IS21)2 plasmids, but not by IS21 plasmids. Genetic analysis of (IS21)2 plasmids indicates that the IS21-IS21 junctions form a promoter, which initiates transcription of the istAB operon in one of the two IS21 elements. A single IS21 element fused to an inducible external tac promoter expressed both proteins after induction, but did not promote effective replicon fusion, unless an IS21-IS21 junction (the preferred site for IS21 transposase action) was also present on the plasmid carrying the tac-IS21 construct. The sequences located between the IS21 elements in (IS21)2, 3 bp in R68.45 or 2 bp in pME28, were not recovered in the replicon fusion products. Homologous recombination between the directly oriented IS21 elements in the fusion products led to plasmids with a single IS21 insertion. Analysis of the latter showed that IS21 had a low, but not totally random specificity of insertion and created target duplications of 4 bp (occasionally 5 bp).(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1989

An assessment of tenoxicam, a nonsteroidal anti-inflammatory drug of long half-life, in patients with impaired renal function suffering from osteoarthritis or rheumatoid arthritis.

Fifty-eight patients, aged 48-87 years, with impaired renal function and mean initial creatinine clearance of 52.1 mls/min were recruited to a 12-week open study of tenoxicam 20 mg/day for osteoarthrosis or rheumatoid arthritis. Renal function was measured before and after a brief run-in period when patients discontinued all nonsteroidal anti-inflammatory drugs, taking paracetamol alone, prior to monthly monitoring thereafter. Fifty-four % of patients completed the study, the others being withdrawn from lack of efficacy (17%), adverse events (24%) or both (5%). During the run-in period the mean creatinine clearance of 28 patients completing the trial improved to 64.7 mls/min and then dropped to 57.9 mls/min during the course of 12 weeks treatment with tenoxicam. Serial analysis of haematological and biochemical safety parameters showed no drug-induced change of significance. Twenty-three% of patients felt worse and 45% better at the end of treatment. Seventeen patients withdrew because of adverse events. These were normally gastrointestinal and always unrelated to further deterioration in renal function. Tenoxicam, 20 mg/day, can be given safely for a period of at least three months in patients with mild or moderate renal impairment.

Aged↗