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Biomedical subjects

D Grant

Publications and source records attributed to D Grant.

At least 145 records · Page 8Linked to original sources

Gene deletion causing adrenal hypoplasia congenita and hypogonadotrophic hypogonadism.

We report a patient with X-linked adrenal hypoplasia congenita and hypogonadotrophic hypogonadism in whom there were no clinical or biochemical features of either glycerol kinase deficiency or Duchenne muscular dystrophy. (The adrenal hypoplasia congenita and glycerol kinase loci map in Xp21 distal to Duchenne muscular dystrophy, and proximal to DXS727). DNA isolated from our patient was analysed by PCR amplification with primers for appropriate loci in the Xp21 region. This analysis revealed the absence of DXS319, which lies near the adrenal hypoplasia congenita deletion critical region, and the presence of DXS727, which is distal to the gene. The absence of glycerol kinase deficiency biochemically and clinically was consistent with the presence of one glycerol kinase exon product from PCR primers P17/P18 which lies within the glycerol kinase gene. The hypogonadotrophic hypogonadism is universally found in X-linked adrenal hypoplasia congenita and is thought to be pituitary in origin. These findings suggest that a gene locus resulting in hypogonadotrophic hypogonadism is present in the Xp21 region and is an integral part of the adrenal hypoplasia congenita gene or in close relationship to it.

Adolescent↗

Use of splenic ultrasound: a new wave for immune thrombocytopenic purpura.

AIMS: To examine whether a therapeutic dose of ultrasound waves, when directed through the thoracic wall to the spleen, would significantly affect the platelet count in patients with stable immune thrombocytopenic purpura (ITP). METHODS: Continuous ultrasound at 1 W/cm2 spatial average-time average (SATA) intensity for up to one minute/5 cm2 treatment field was well tolerated in 13 patients with ITP and one with non-Hodgkin's lymphoma. Five healthy controls were also similarly treated. Peak platelet increments occurred four to eight hours after ultrasound treatment in the ITP group (n = 16 treatments). RESULTS: The mean peak platelet increment was 6.25 x 10(9)/l with a 5% confidence interval of the mean (95% CI) of 3.32 to 8.93 x 10(9)/l (p = 0.0004). The mean peak platelet increment of normal controls was 6.6 (n = 5; 95% CI = -2.3 to 15.5; p = 0.21) and for sham treated patients it was 0.66 (n = 11; 95% CI = -1.5 to 2.8; p = 0.60). There was a significant inverse correlation between patient age in the ITP group and peak platelet increment (r = -0.60; p = 0.015). CONCLUSIONS: Splenic ultrasound is a novel approach to the treatment of ITP, and may find a place in its diagnosis or management.

Adult↗

Food poverty: Rowntree revisited.

A pilot exercise preceding a major study of the effects of poverty on adequacy of diet is reported on. The inability of many low income households to afford a healthy diet is serious in nature and widespread in extent.

Adult↗

Homeless & hungry: the evidence from Liverpool.

Much research has established the link between low incomes and poor nutritional standards. A research team from the Centre for Consumer Education & Research at Liverpool John Moores' University recently found that 30% of all families with children in Britain today are spending less on food than what is required to achieve a dietary which adheres, at minimum cost, to the Department of Health's Dietary Recommended Values (DRVs). But very little, if any, research has investigated the nutritional implications of a particularly extreme form of material deprivation--homelessness. This pilot study therefore sets out to study the dietaries of a number of homeless families in Liverpool--homeless as defined by living in Bed & Breakfast accommodation. Not only do such families have to contend with dependency upon welfare benefits when purchasing their foodstuffs; they also have to labour under inadequate cooking facilities. The study has involved these families keeping a dietary diary of all food and drink consumed. This information has then been analysed for its nutrient composition, using the Microdiet computer programme at Liverpool JMU. The results will show that, in every single case, the dietaries of these homeless families fall substantially short of the government's own nutritional guidelines and are, without doubt, unhealthy in the extreme. This paper is thus an examination of the nature and extent of the problem, using the science of nutrition and dietetics: not a policy prescription (although this is obvious) not a policy analysis. A study of the dietary implications of homelessness for 100 individuals (the largest ever undertaken) on Merseyside will be undertaken between September 1993 and June 1994.

Adolescent↗

Diagnosis and treatment of thyrotoxicosis in childhood. A European questionnaire study.

A covering letter and a questionnaire covering the diagnosis and treatment of thyrotoxicosis in childhood was circulated between October 1992 and February 1993 amongst 672 European members of the European Thyroid Association (ETA) and members of the European Society for Pediatric Endocrinology (ESPE). Almost 50% replied to the letter and 99 individuals or groups from 22 countries completed the questionnaire. A consensus was reached on the use of total thyroxine (T4) and/or free T4 and thyrotropin as routine diagnostic tools. Two-thirds included total triiodothyronine (T3) and/or free T3 and 32% used a thyrotropin-releasing hormone test. Surprisingly, thyroglobulin autoantibodies were used as a routine test by 78%; 63% included thyrotropin receptor antibodies and 60% microsomal antibodies, whereas only 50% measured thyroperoxidase antibodies. For thyroid imaging, 40% performed a thyroid scintigram and 56% measured the size of the thyroid gland by ultrasound. Antithyroid drugs (ATD) were the basic initial treatment of choice given by 99% of the respondents for children with uncomplicated Graves' disease. Carbimazole, methimazole and thiamazole were the most frequently used drugs, with a median initial dose of 0.8 mg.kg-1.day-1. Two-thirds added beta-blockers and a few used sedatives. The ATD dose was adjusted for each patient by 39%, whereas 56% combined ATD with T4 for long-term treatment; 84% gave treatment for a fixed period (44% for 1-2 years). Surgery was considered the treatment of choice in children with an adenoma (83%), with a nodular (53%) or large goiter (16%) and recurrence after ATD (14%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Small bowel transplantation.

After struggling for three decades, SBT is finally emerging as a clinical reality. To become the standard therapy for the treatment of end-stage intestinal failure, SBT must offer a better quality of life, fewer risks, and lower costs than home TPN. To achieve this standard, protocols must be refined to obtain lower rates of rejection and infection as well as more consistent graft function.

Clinical Protocols↗

Mangafodipir (MnDPDP)-and MnCl2-induced endothelium-dependent relaxation in bovine mesenteric arteries.

Mn++ complexed to DPDP (N,N'-dipyridoxylethylenediamine-N,N'-diacetate-5,5'-bis(phosphate) generic name: mangafodipir), abbreviated MnDPDP, acts as an effective contrast enhancing agent for liver MRI. In clinical trials, a commonly reported side effect after i.v. administration of MnDPDP was facial flushing, most probably due to peripheral vasodilation. The present study was conducted to address possible mechanisms to explain the flushing effect. Nitric oxide is known to be stabilized in the presence of both uncomplexed and complexed Mn++ and this stabilization is probably due to the superoxide-scavenging properties of Mn++. The present study has demonstrated that both MnDPDP and MnCl2 relax phenylephrine precontracted bovine mesenteric artery strips in concentration-dependent manner. It was also found that a concentration of 10 microM MnDPDP, MnEDTA or MnCl2 gave approximately the same relaxation response as 0.1 microM acetylcholine. DPDP and EDTA had no appreciable intrinsic relaxation potential Mn(++)-induced relaxation was abolished when the endothelial layer was removed from the arteries. In addition, the Mn(++)-induced relaxation was attenuated by the nitric oxide synthase inhibitor N-nitro-arginine and the putative superoxide anion generator 6-anilino-5,8-quinolinedione, but not by the cyclooxygenase inhibitor indomethacin. Both N-nitro-arginine and 6-anilino-5,8-quinolinedione were found to induce an endothelium-dependent constriction of the bovine mesenteric artery strips. An approximately 2-fold increase in the intracellular concentration of cyclic GMP was detected after the addition of 10 microM MnDPDP or 0.1 microM acetylcholine. The increase in cyclic GMP coincided with the onset of relaxation and was effectively abolished by pretreatment with N-nitro-arginine.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

Synergistic effects of tumour necrosis factor and morphine on gut barrier function.

OBJECTIVE: To study the effects of tumour necrosis factor (TNF) and morphine on intestinal permeability, intestinal transit and bacterial translocation in the rat. DESIGN: A randomized interventional controlled experiment. SETTING: University surgery and microbiology research laboratory. PARTICIPANTS: Forty-four rats in five groups as follows: control (n = 9); treated with morphine every 2 hours for 8 hours (n = 9); treated with TNF for 5 minutes (n = 10); treated with TNF plus morphine every 2 hours for 8 hours (n = 6); and treated with TNF plus morphine every 3 hours for 24 hours (n = 10). MAIN OUTCOME MEASURES: Intestinal permeability as measured by the uptake of chromium-51 ethylenediaminetetraacetate (51Cr-EDTA) over 8 hours, intestinal transit as measured by the amount of 51Cr-EDTA remaining in the gastrointestinal tract at the time of animal sacrifice, intestinal bacteria counts and translocation of bacteria as measured from bacterial counts of mesenteric lymph nodes, spleen and liver at the time of sacrifice. RESULTS: Morphine increased intestinal transit time and ileal bacteria counts (p < 0.05). TNF alone did not increase intestinal permeability or bacterial translocation. TNF plus morphine increased intestinal transit time, intestinal permeability, bacterial counts and bacterial translocation (p < 0.05). CONCLUSIONS: Morphine or increased intestinal transit time, or both, increases the concentration of intestinal bacteria. Morphine plus TNF increases intestinal bacteria counts, intestinal permeability and bacterial translocation. Morphine alone does not increase intestinal permeability or bacterial translocation.

Analysis of Variance↗