Temporary axonal conduction block and axonal loss in inflammatory neurological disease. A potential role for nitric oxide?
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Action Potentials↗
Biomedical subjects
M Davies
Publications and source records attributed to M Davies.
The predictive value of transabdominal ultrasonography in the diagnosis of biliary tract complications after orthotopic liver transplantation.
BACKGROUND: In transplant recipients with choledococholedocostomy (CDCD), endoscopic retrograde cholangiopancreatography (ERCP) remains the gold standard for the diagnosis of biliary leak or strictures. Transabdominal ultrasonography (TAUS) has been used to screen patients with suspected biliary tract complications, prior to ERCP, although the clinical effectiveness remains unclear. AIMS: To assess the predictive value of TAUS in the diagnosis of biliary tract complications after liver transplantation. METHODS: 144 consecutive ERCP and corresponding ultrasonogram reports performed over a 67 month period in 79 patients after liver transplantation were analysed retrospectively. RESULTS: 77 ERCP patients had both a TAUS and a successful ERCP. Biliary tract abnormalities were found at TAUS in 49 (64%) of the 77 patients. TAUS had an overall sensitivity of 77%, and specificity of 67%, with positive and negative predictive values of 26% and 95% respectively, when adjusted for the prevalence rate of biliary complications after liver transplantation of 12.8% in our population. The use of bile duct calibre as sole criterion for an abnormal scan improved the specificity (76%) and with a corresponding reduction in sensitivity (66%). The risk of false negative TAUS was similar in both the early and late post-transplant periods. CONCLUSIONS: A normal TAUS after liver transplantation with CDCD makes the presence of biliary complications unlikely.
Adult↗
Bone loss in celiac disease is related to secondary hyperparathyroidism.
Celiac disease is a major cause of intestinal malabsorption. Previous studies have demonstrated that celiac disease is associated with significant osteoporotic bone loss. These studies have suggested that successful treatment of the malabsorption is associated with amelioration of the bone loss. Such studies have failed to examine bone mass at peripheral skeletal sites which is more likely to be responsive to changes in parathyroid hormone (PTH) in response to calcium malabsorption. We have examined bone density in the lumbar spine, femoral neck, and distal forearm in 35 patients with celiac disease who had been established on gluten-free diet. In addition, the concentrations of PTH and 1,25-dihydroxyvitamin D (1,25(OH)2D) were measured. Bone density was below that expected for the subject's age and gender at all sites. This was most marked in the distal forearm where the bone density was 1.40 SD below expected (p < 0.0001). In the forearm, there was a negative relationship between bone density and PTH concentration (r = -0.49, p = 0.009). In the forearm and lumbar spine, there was a negative relationship between 1,25(OH)2D concentration and bone density. Bone mass was not related to the concentration of 25-hydroxyvitamin D at any of the skeletal sites measured. Bone density is reduced in the peripheral skeleton in celiac disease and this deficit persists despite treatment with apparent normalization at axial skeletal sites. This reduction in bone mass is related to the presence of secondary hyperparathyroidism which should be sought in all patients with treated celiac disease.
Adult↗
Novel mutations in the 1alpha-hydroxylase (P450c1) gene in three families with pseudovitamin D-deficiency rickets resulting in loss of functional enzyme activity in blood-derived macrophages.
Pseudovitamin D-defiency rickets (PDDR) is an autosomal recessive disorder characterized by hypocalcemia, rickets (which are resistant to treatment with vitamin D), and low or undetectable serum levels of 1,25-dihydroxyvitamin D (1,25(OH)2D). The symptoms are corrected with 1,25(OH)2D treatment, and the disease is now believed to result from a defect in the cytochrome P450 component (P450c1; CYP27B1) of the renal 25-hydroxyvitamin D-1alpha-hydroxylase (1-OHase). We have studied genomic DNA from three families with PDDR and have identified the same homozygous mutation in the P450c1 gene in two of the index cases, causing a frameshift in exon 8, resulting in a premature stop codon in the heme-binding domain. The two cases in the third kindred were compound heterozygotes with missense mutations in exons 6 and 9. We have also identified a C/T polymorphism in intron 6 of the P450c1 genomic DNA. Interferon gamma-inducible 1-OHase activity in blood-derived macrophages was shown by 1,25(OH)2D synthesis in all control cells tested (37-184 fmol/h/106 cells) and those from the PDDR family parents (34-116 fmol/h/106 cells) but was totally absent from the patients' cells, indicating a defect in their macrophage 1-OHase, similar to the presumed renal defect. The assumption of similarity between the renal and macrophage P450c1 was supported by our ability to clone a 514 bp sequence, including the heme-binding region of the macrophage P450c1 cDNA from controls, which was identical to that published for both the renal and keratinocyte P450c1 cDNAs.
24,25-Dihydroxyvitamin D 3↗
Transverse cerebellar diameter on cranial ultrasound scan in preterm neonates in an Australian population.
OBJECTIVE: Fetal measurement of transverse cerebellar diameter (TCD) has been shown to correlate well with gestational age (GA), even in the presence of growth retardation. The aim of this study was to define the normal range of TCD in preterm neonates in an Australian population between 23 and 32 weeks GA. METHODOLOGY: Infants admitted to the Royal Women's Hospital, Melbourne, having routine cranial ultrasound scans (< 1500 g and/or of gestational age </= 32 weeks at birth) had their TCD measured on a cranial scan performed during the first 3 days of life. The posterior fossa was examined through the asterion using a General Electric LOGIQ 500 scanner (GE Medical Systems, Waukesha, USA) and TCD measurement was taken in the coronal plane. RESULTS: 106 infants < 1500 g and/or of GA </= 32 weeks at birth had their TCD measured between 1 January 1997 and 30 November 1997. Transverse cerebellar diameter and associated 95% confidence intervals are described for infants between 23 and 32 weeks GA. The linear regression equation relating TCD and GA was: TCD (mm) = -12.9 + 1.61 x GA (weeks). R2 = 0.80, P < 0.001. CONCLUSION: This is the only study of TCD measurement using cranial ultrasound in a group of preterm newborns, and forms the basis for nomograms of TCD which can be used as a tool to assist in the assessment of GA, even in growth-retarded preterm newborns, and in the diagnosis of cerebellar hypoplasia.
Cephalometry↗
Mutagenesis of the rat alpha1 subunit of the gamma-aminobutyric acid(A) receptor reveals the importance of residue 101 in determining the allosteric effects of benzodiazepine site ligands.
The gamma-aminobutyric acid(A) (GABA(A)) receptor contains a binding site (or sites) for benzodiazepines and related ligands. Previous studies have shown that the residue occupying position 101 (rat numbering) of the alpha subunit is particularly important in determining how some of these compounds interact with the receptor. We have made multiple substitutions (F, Y, K, Q, and E) of the histidine at this position of the rat alpha1 subunit and coexpressed the mutant subunits with beta2 and gamma2 subunits in Xenopus oocytes. The effects of flunitrazepam, Ro15-1788, and Ro15-4513 on GABA-gated currents were then examined using electrophysiological techniques. Three substitutions (F, Y, and Q) had little effect on the ability of flunitrazepam to potentiate GABA-induced currents and had relatively modest effects on the EC(50) value of the flunitrazepam response. Other mutations (K and E) resulted in drastic reduction of flunitrazepam recognition. All substitutions also affected the EC(50) values for Ro15-1788 and Ro15-4513, and some led to dramatic changes in their efficacy. For example, H101Y, H101K, and H101Q produced receptors at which Ro15-1788 acted as a partial agonist (maximum potentiation of 164, 159, and 130%, respectively), whereas Ro15-4513 acted as a partial agonist at H101F, H101K, and H101E (potentiation of 122, 138, and 110%, respectively) and an antagonist at H101Y and H101Q. These results indicate that the characteristics of the residue at position 101 of the alpha1 subunit play a crucial role in determining the efficacy of benzodiazepine-site ligands.
Allosteric Regulation↗
An appreciation of Jane Bunster 17 April 1930-16 June 1999
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Journal Article↗
An appreciation of Jane Bunster. 17 April 1930-16 June 1999.
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Adult↗
Cost-effectiveness of systemic and regional chemotherapy for the treatment of patients with unresectable colorectal liver metastases.
BACKGROUND: Management of unresectable colorectal liver metastases (CLM) can be by regional (hepatic arterial infusion [HAI]) or systemic chemotherapy, or by symptom control alone. In this study the costs of each type of management were related to clinical outcome in 134 patients with CLM. METHODS: The costs (both in terms of health care and to society) and benefits (treatment-added survival and normal quality of life survival) of chemotherapy treatment of 85 patients (HAI with implanted pump: 51 patients; and systemic chemotherapy: 34 patients) were compared with those in 49 patients managed by symptom control only. RESULTS: HAI chemotherapy cost the most (Pound Sterling 18,263 per patient) and symptom control the least (Pound sterling 2136 per patient). When survival was included, HAI was the most cost-effective treatment (health care cost per life year gained with HAI vs. systemic chemotherapy: Pound Sterling 24,604; systemic chemotherapy vs. symptom control: Pound Sterling 32,788), but there was no difference with regard to health care cost per normal quality of life gained. Societal costs incurred by lost work time and welfare payments during illness were higher for HAI (Pound Sterling 12,897) than systemic chemotherapy (Pound Sterling 9143) or symptom control (Pound Sterling 8090) because HAI-treated patients lived longer and, although working longer and contributing more productivity to society, lost more work days than other patients. CONCLUSIONS: The least expensive management for CLM was symptom control, whereas systemic and HAI chemotherapies were equally cost-effective in producing added normal quality survival for health care resources expended. Although overall societal costs were higher for HAI than for either systemic chemotherapy or symptom control, the cost benefit was difficult to interpret because of uncertain attitudes regarding continued work during terminal illness.
Antineoplastic Agents↗
The dental management of patients with natural rubber latex allergy.
Reports of allergic reactions to natural rubber latex have increased during the past two decades with both dental personnel and patients being affected. A dental management protocol is outlined for patients who have latex allergy. This includes: the identification of patients at high risk for developing latex allergy; the creation of a controlled, 'latex free' environment in the dental surgery; and the provision of emergency drugs and equipment that are free from natural rubber latex and may be required for the management of an allergic reaction.
Clinical Protocols↗
Identification of a unique domain in bovine brain GABAA receptors that is photoaffinity labelled by [3H]Ro15-4513.
We have used photoaffinity labelling and protein cleavage techniques to identify the site of photoincorporation of [3H]Ro15-4513 into the alpha subunit of the bovine gamma-aminobutyric acid type A (GABAA) receptor. Bovine brain membranes were photoaffinity labelled with [3H]Ro15-4513 and after solubilization and denaturation, proteins were specifically cleaved at either cysteine or tryptophan residues. Peptides were resolved by sodium dodecyl sulphate polyacrylamide gel electrophoresis. Cleavage at cysteine residues generated a labelled peptide of Mr 6.5K, while cleavage at tryptophan residues generated a labelled peptide with an Mr of 5K. Cleavage products of this size indicate that the site of [3H]Ro15-4513 incorporation occurs between the end of the first transmembrane domain and the first four amino acids of the third transmembrane domain (residues 247-289). This region of the GABAA receptor has not previously been implicated in the formation of the benzodiazepine binding site and may be part of a unique recognition domain for inverse agonists.
Affinity Labels↗
Risk language and dialects. Lottery can be used to show risks.
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Probability↗
Adolescent depression: controlled desipramine treatment and atypical features.
The study was designed to test the efficacy of desipramine in adolescents with major depression (MDD). In addition, we assessed the presence of atypical features of MDD, consisting of mood reactivity and two of four associated features (rejection sensitivity, hyperphagia, hypersomnia, and leaden paralysis). Patients were randomized to desipramine (DMI) or placebo for 6 weeks, provided they failed to improve (e.g., meeting MDD criteria and a Hamilton Depression Scale score > or = 18) after 2 weeks on single blind placebo. Of 94 adolescents (ages 13-18) who were diagnosed as having MDD, 64 entered the study and 62 received placebo for 2 weeks. Of these, 45 were randomized to DMI or placebo. Completed analyses did not reveal significant improvement for the active treatment compared to the placebo. A large proportion of adolescents responded to placebo (50%), suggesting the need for very large samples to detect differential treatment efficacy, should it exist. A relatively high rate of atypical depression was observed (47% in the 64 patients entered). In view of the demonstrated specificity of monoamine oxidase inhibitor efficacy in adults with atypical features of MDD, this clinical subtype may have relevance to future investigation of therapeutic interventions in adolescent MDD.
Adolescent↗
Bikunin present in human peritoneal fluid is in part derived from the interaction of serum with peritoneal mesothelial cells.
We recently reported that peritoneal fluid mainly contains two proteoglycans; one is the interstitial proteoglycan referred to as decorin, and the other an uncharacterized small chondroitin sulfate proteoglycan. In the present study, we have used a two-step process to isolate the small chondroitin sulfate proteoglycan free of decorin. The purified molecule ran as a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis with apparent molecular mass 50 kd made up of a chondroitin-4-sulfate glycosaminoglycan chain and a 30-kd core protein. NH2-terminal analysis of the core protein showed significant sequence homology with bikunin, a component of the human inter-alpha-trypsin inhibitor (IalphaI) family. A Western blot analysis using anti-human inter-alpha-trypsin inhibitor confirmed the identity of the small chondroitin sulfate proteoglycan as bikunin, and a trypsin inhibitor counterstain assay confirmed its anti-trypsin activity. Examination of serum from patients receiving continuous peritoneal dialysis suggests that free bikunin in peritoneal fluid may be the result of leakage of serum proteins into the peritoneum. Our findings further show that the interaction of serum with peritoneal mesothelial cells offers a new and novel explanation for the presence of bikunin in peritoneal fluid.
Alpha-Globulins↗
Peter B. Samuels Award. Restenosis after percutaneous transluminal angioplasty.
BACKGROUND: Determine the feasibility of studying the natural history of the atherosclerotic plaque following percutaneous transluminal angioplasty (PTA), using duplex scanning. METHODS: Twenty-three patients with 40 stenoses (>70% and <5 cm in length) in the iliac and femoro-popliteal segments were studied by duplex scanning before PTA, on day 1, weekly for 8 weeks, and at 3 months, 6 months, and 1 year. The following measurements were made: thickness of the plaque, minimal lumen diameter (MLD), and peak systolic velocity ratio (PSVR). A PSVR >2.0 was used to indicate >50% lumen diameter reduction. RESULTS: Thirty stenoses were available for measurement and analysis. Mean reduction in plaque thickness after angioplasty was greater in echolucent plaques (2.33 +/- 0.9 mm) than echogenic plaques (0.83 +/- 0.6 mm; P < 0.0001). Successful angioplasty (PSVR <2.0) and increase in MLD in echolucent plaques was the result of plaque compression; in echogenic plaques, of wall dilatation. The incidence of restenosis (PSVR >2.0) at 6 months was 12 of 30 (40%) remaining unchanged at 1 year; of the lesions that restenosed, 33% recurred before week 8 and the remainder between weeks 8 and 24, suggesting different mechanisms. During follow-up, all plaques showed "growth"; <2 mm in 17 (57%; group A) and >2 mm in the remaining 13 (43%; group B). The incidence of restenosis (PSVR >2.0) was 4 of 17 (23%) in group A and 8 of 13 (61%) in group B (P <0.05). CONCLUSION: Duplex scanning provides valuable information on both luminal diameter and plaque thickness; it may be used to study the natural history of plaques following angioplasty and also the effects of therapeutic agents aimed at reducing restenosis.
Angioplasty, Balloon↗
Simultaneous evaluation of basal follicle-stimulating hormone and 17 beta-estradiol response to gonadotropin-releasing hormone analogue stimulation: an improved predictor of ovarian reserve.
OBJECTIVE: To compare different predictors of ovarian reserve. DESIGN: Prospective study. SETTING: The Assisted Conception Unit, University College London Hospitals. PATIENT(S): One hundred seventy-seven patients undergoing IVF treatment. INTERVENTION(S): Blood samples were collected on cycle day 2 to determine basal levels of FSH and 17beta-E2 and the FSH/LH ratio, and on cycle days 3 and 4 to assess the increase in FSH (deltaFSH) and 17beta-E2 (deltaE2) after the commencement of GnRH analogue (GnRH-a) stimulation. Ultrasound scans were performed during ovarian stimulation to assess the number of follicles. MAIN OUTCOME MEASURE(S): Day 2 FSH and 17beta-E2 levels, the FSH/LH ratio, and the deltaFSH and deltaE2 after the commencement of GnRH-a stimulation were correlated with the number of follicles obtained after ovarian stimulation. RESULT(S): All the possible predictors considered, except for the day 2 E2 level and the deltaFSH, correlated significantly with the ovarian response. The best single correlation was between the number of follicles and the deltaE2 (GnRH-a test). When the FSH level was evaluated simultaneously, the correlation was strengthened, resulting in a better negative predictive value. CONCLUSION(S): Simultaneous evaluation of basal levels of FSH and of the response of E2 to GnRH-a stimulation seems to be the best marker of ovarian reserve and a sensitive predictor of response to ovarian stimulation in patients undergoing IVF treatment.
Adult↗
Linguistic dissociations in Williams syndrome: evaluating receptive syntax in on-line and off-line tasks.
Williams syndrome (WS) is a neurodevelopmental disorder of genetic origin which results in relatively spared language in the face of serious non-verbal deficits. There is controversy, however, about how intact WS language abilities are. The discussion has focused on impairments of lexico-semantics and of morphological feature analysis, with the presumption that WS syntax is intact. We challenged this view and assessed WS receptive syntax by using two tasks testing various syntactic structures: an on-line word monitoring task and an off-line picture-pointing task. WS performance on the off-line task was generally poor. By contrast, their performance on the on-line task was far better and allowed us to ascertain precisely which aspects of WS receptive syntax are preserved and which are impaired. WS participants were sensitive to the violation of auxiliary markers and phrase structure rules but, unlike both the normal young and elderly controls, they did not show sensitivity to violations of subcategory constraints. The present study suggests that there exist dissociations within WS language which are not restricted to lexico-semantics or to morphological feature analysis, but which also invade their processing of certain syntactic structures. We conclude by arguing that WS syntax is not intact and that their language might turn out to be more like second language learning than normal acquisition.
Adolescent↗