Biomedical subjects
D Price
Publications and source records attributed to D Price.
Living kidney donation in Europe: legal and ethical perspectives--the EUROTOLD Project.
The demand for organ replacement by transplantation continues to outstrip supply, leading to unnecessary morbidity and health care costs. "Space capacity" (i. e. cadaver organs not currently harvested for transplant) has been tackled within Western Europe in particular by many strategies--medical, social, educational and legal--but with varying degrees of success. Despite this, the use of living donors has not been fully exploided in many European countries to fill this gap. The total picture is, however, one of marked differences between countries and between centres within countries. In Turkey and Greece, living donors generally account for 60-90% of all renal donors. Countries within Scandinavia also have a high rate of living donor use, especially Norway. By contrast the percentage is far more modest, for example in Spain, Ireland, France and Germany. In the United Kingdom the rate is only 6% with a range of between 0 and 20%. Sources of living donors also show substantial variations between countries, notably the extent to which non-genetically related donors are used. A European Commission sponsored study has been established to acquire a broad understanding of the interaction of ethical values, cultural traditions and social customs on willingness to donate. It will also aim to assess the effect of national laws on professional attitudes to living donor transplantation. This is a collaborative project between the University Department of Surgery, Leicester General Hospital, the Department of Law, De Montfort University and the Department of Mathematics, Newcastle University. Transplant units throughout Europe, including France, Germany, Switzerland, Norway, The Netherlands, Eire and Turkey are collaborating to exchange information and views on living donor transplantation.
Short AV interval VDD pacing does not prevent tilt induced vasovagal syncope in patients with cardioinhibitory vasovagal syndrome.
Eleven subjects (mean age 50 years, range 33-71 years), who had previously received permanent dual chamber pacemakers for cardioinhibitory vasovagal syncope, underwent paired Westminster protocol tilt tests, one with short AV delay VDD pacing and one without pacing, to test the hypothesis that continuous ventricular pacing would prevent the cardiac initiation of vasovagal syncope. Nine (82%) of the paced tilts produced positive vasovagal outcomes compared with seven (64%) of the unpaced tilts. No important differences in the heart rate or blood pressure behavior during tilt or the time to positive vasovagal outcomes were observed between the paired tilts. There was more accelerated syncope/presyncope once symptoms had developed during the paced tilts of subjects in whom both study tilts were positive, although this did not reach statistical significance (P = 0.054). This study shows that atrial synchronous ventricular pacing does not prevent the initiation, or progression, of tilt induced vasovagal syncope in predisposed subjects.
Notes on Nambiquara demography.
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Pivotal role of colony stimulating factor-1 in lupus nephritis.
Spontaneous autoimmune renal injury in MRL-lpr mice shares many features of human lupus nephritis. We noted a prominent increase of macrophages (M phi) in the glomerulus of MRL-lpr mice. Since colony stimulating factor-1 (CSF-1) regulates M phi growth and is a potent chemoattractant, we explored the possibility that there was an increase in CSF-1 in MRL-lpr mice. We detected a biphasic increase in circulating CSF-1 in MRL-lpr mice as compared to congenic MRL- ++ mice other strains with the lpr gene, and normal mice. There was an increase in CSF-1 steady state mRNA transcripts in the kidney but not in the liver, lung or bone marrow. By in situ hybridization our studies identified the glomeruli as the predominant source of renal CSF-1. Enhanced CSF-1 is expressed by the mesangial cells at the same time (4 weeks of age) that M phi begin to accumulate in the glomeruli, well in advance of the loss of renal function. We have isolated pure populations of glomerular M phi in culture from MRL-lpr mice. These glomerular M phi require CSF-1 to survive and proliferate. Therefore, these data suggest that CSF-1 is increased in the glomerulus prior to the influx and accumulation of M phi. We propose that CSF-1 expression in the kidney is pivotal in the attraction and accumulation of M phi and in turn responsible for initiating tissue destruction.
Abnormal acidic amino acids and N-acetylaspartylglutamate in hereditary canine motoneuron disease.
Hereditary canine spinal muscular atrophy (HCSMA) is a lower motor neuron disease found in Brittany Spaniels that shares clinical and pathological features with human amyotrophic lateral sclerosis (ALS). Since acidic excitatory amino acids and the neuropeptide N-acetyl-aspartyl-glutamate (NAAG) are reduced in spinal cord and cerebral cortex in ALS, the levels of these substances were measured in nervous tissue in Brittany Spaniels heterozygous and homozygous for HCSMA. Significant reductions in the levels of endogenous aspartate, glutamate, N-acetylaspartate (NAA), and NAAG were found in the spinal cord in homozygous but not heterozygous HCSMA. In contrast, the activity of N-acetylated-alpha-linked-amino dipeptidase (NAALADase), an enzyme that cleaves NAAG into NAA and Glu, was significantly increased. None of these parameters was affected in the motor cortex or occipital cortex. Since NAA and NAAG are highly concentrated in motoneurons, they may play a role in the pathogenesis of motor neuron disease.
Quantification of tissue plasma volume in the rat by contrast-enhanced magnetic resonance imaging.
Magnetic resonance imaging enhanced with a macromolecular contrast medium (MMCM), albumin-Gd-DTPA, was used to estimate the plasma volume in vivo in the myocardium, lung, liver, and skeletal muscle of 10 normal rats. The plasma volumes of the same tissues in a parallel group of six rats were estimated in vitro by a conventional radioisotopic technique (111In-transferrin). Plasma volumes of myocardium, lung, liver, and skeletal muscle estimated by the MR technique (microliter plasma cc-1 of tissue) were 101, 109, 163, and 11.0, respectively, while plasma volumes measured by the 111In-transferrin radioisotope technique (mg plasma g-1 of tissue) were 78.6, 215, 143, and 11.2, respectively. Assuming a ratio of densities of aerated lung to blood of 0.45 and of other tissues to blood of 1.0, correlation between the methods was excellent (R2 = 0.99) indicating that MR imaging enhanced with MMCM permits reliable in vivo estimation of tissue plasma volume in the rat.
The impact of spina bifida on the medical services of Newfoundland and Labrador.
This institution receives all live spina bifida patients from Newfoundland and Labrador. The aim of this study is to determine the outcome of these patients and the impact on the medical system. On a retrospective chart review, 274 patients born between 1967 and 1990 were studied. An analysis of the statistical variables showed that the incidence per 1,000 live births has remained stationary in Newfoundland and Labrador; there is a slight female predominance; 64% were born to young mothers and the peak incidence occurred in March, April, and May. A total of 179 patients of 254 who underwent surgery were alive and underwent rehabilitation programmes. Only 35% are wheelchair bound; the rest are ambulatory. One hundred sixty-one are of school age or older, 78 are in regular high school (3 dropouts), 36 are in special education, 6 graduated from high school, 4 are in university, 15 had no neurological deficit, 7 were lost in follow-up, 5 died, 9 had gross mental retardation, and 1 is the mother of three normal children. To attain these results these patients had multiple admissions and surgical procedures and the patients are seen twice a year in a rehabilitation and multidisciplinary clinic. From this study, the utilization of the medical services and impact on the community is great. However, the majority of these patients appear to attain a surprisingly high quality of life.
Education for the management of obstetric conditions in rural general practice. A curriculum statement for a major in obstetric studies in the Rural Training Programme of the Faculty of Rural Medicine, Royal Australian College of General Practitioners.
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Education for general practitioners proposing to administer anaesthesia in rural general practice.
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Positive and negative regulatory elements of the rabbit embryonic epsilon-globin gene revealed by an improved multiple alignment program and functional analysis.
The epsilon-globin genes of mammals are expressed in early embryos, but are silenced during fetal and adult erythropoiesis. As a guide to defining the regulatory elements involved in this developmental switch, we have searched the sequences of epsilon-globin genes from different mammals for highly conserved segments. The search was facilitated by the development of a new program, called yama, to generate a multiple alignment of very long sequences using an improved scoring scheme. This allowed us to generate a multiple alignment of sequences from a more divergent group than previously analyzed, as demonstrated here for representatives of four mammalian orders. In parallel experiments, we constructed a series of deletion mutations in the 5' flank of the rabbit epsilon-globin gene and tested their effect on an epsilon-globin-luciferase hybrid reporter gene. These results show that 121 bp of 5' flank, containing CACC, CCAAT and ATA motifs, is sufficient for expression in erythroid K562 cells. Both positive and negative cis-acting control sequences are located between 218 and 394 bp 5' to the cap site, in a region previously proposed to be a silencer. The positive regulatory sequence contains conserved binding sites for the nuclear protein YY1 adjacent to another highly conserved sequence. The negative element contains a conserved sequence followed by a purine-rich segment. This analysis maps the upstream control sequences more precisely and points to a very complex regulatory scheme for this gene.
Gaucher's disease with mitral valve calcification.
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Undiagnosed maternal Fallot tetralogy presenting in pregnancy.
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Interferon modulation of 5-fluorouracil: use in neoadjuvant therapy inhibits experimental liver metastases in nude mice.
Experimental liver metastasis was studied in 4-5 week old athymic nude mice that were injected intrasplenically with a human colorectal tumor cell line (LoVo). A treatment schedule combining 5-fluorouracil and interferon (IFN) was previously shown to inhibit liver metastases. When this treatment was delayed until after splenectomy at 1, 2 and 3 weeks after tumor cell injections, liver metastases were not inhibited. However, when IFN was given during the interval between tumor cell injections and splenectomy (as neoadjuvant therapy), liver metastases were inhibited in the 2 and 3 week groups, but not in the 1 week group.
Tonic and phasic orientation in full-term and preterm infants.
Thirty-three full-term infants and thirty-eight preterm infants (on average born at 30 weeks gestation) were tested for their latency to turn toward checkered stimulus patterns (phasic orienting or "attention-getting") and for the duration of their initial fixation (tonic orienting or "attention-holding"). Plotted against the logarithm of the subjects' postconceptional age, turning latency fell linearly between 36 and 120 weeks, while fixation time fell abruptly at 53 weeks. Preterm and full-term infants showed the same developmental trends, implying that both of these attentional behaviors are biologically timetabled and that neither is greatly affected by premature extrauterine experience. Unexpectedly, phasic orientation in the first 30 postnatal days was significantly faster in preterm than in full-term infants, and fixation times failed to differ. Despite the necessary functional integration of phasic and tonic orienting in mature visual scanning and attention, the present results suggest an independence in their early postnatal development and that neither is mature at birth.
Tumour localisation with a radioactively labelled reshaped human monoclonal antibody.
A genetically reshaped human IgG1 monoclonal antibody (Hu2PLAP) with anti-tumour specificity, was radiolabelled with Indium-111 by chelation with a new macrocyclic compound (DOTA) which allows the production of stable radioimmunoconjugates for in vivo application. This was used to image seven patients with malignant disease, of whom two had been previously exposed to mouse monoclonal antibodies and had developed human anti-mouse antibodies (HAMA). Successful tumour localisation was seen in the four patients with active disease and antigen positive tumours. No patient showed any antibody responses against Hu2PLAP, but three out of six patients tested showed an immune response against the macrocycle DOTA. Reshaped human monoclonal antibodies with anti-tumour specificity may facilitate repeated administrations of radioactive antibodies, thus allowing new possibilities, both in the diagnosis and treatment of cancer.