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Biomedical subjects

G Lamb

Publications and source records attributed to G Lamb.

At least 19 recordsLinked to original sources
PubMed2001

Genetic association studies of schizophrenia using the 8p21-22 genes: prepronociceptin (PNOC), neuronal nicotinic cholinergic receptor alpha polypeptide 2 (CHRNA2) and arylamine N-acetyltransferase 1 (NAT1).

Schizophrenia is a common, genetically heterogeneous disorder with a lifetime prevalence of approximately 1% in the general population. Linkage studies of affected families have now strongly implicated a susceptibility locus on chromosome 8p21-22. Tests of allelic association with markers on 8p21-22 should be able to localise any quantitative trait nucleotides (QTN's) or susceptibility mutations to within a few hundred kilobases. Three brain expressed candidate susceptibility genes, prepronociceptin (PNOC), neuronal cholinergic receptor, nicotinic, alpha polypeptide 2 (CHRNA2) and arylamine N-acetyltransferase 1 (NAT1) have been mapped to chromosome 8p21-22. A case-control, allelic association study was performed using a novel highly polymorphic dinucleotide repeat, D8S2611 near the PNOC gene, two previously characterised dinucleotide repeats, D8S131 and D8S131P at the CHRNA2 locus and an RFLP at the 3'UTR of the arylamine N-acetyltransferase 1 (NAT1) gene. No differences were found in allele frequencies between the patient and control groups. DNA variations or mutations at or near the three genes under study are unlikely to increase susceptibility to schizophrenia in our population sample.

3' Untranslated Regions↗
PubMed2001

When cultures clash: physician, patient, and family wishes in truth disclosure for dying patients.

We describe two cases involving male foreign nationals (a Chinese and a Georgian) treated in a U.S. hospital. Both patients had terminal illnesses, and both cases involved clashes between families and the treating physicians, which occurred because of differing cultural beliefs about truth disclosure. Based on the specific backgrounds of these two patients, we discuss ethical and cultural considerations and make suggestions for physicians who care for ethnically diverse patients.

Aged↗
PubMed2000

Characterization of the UDP-glucuronosyltransferase 1A locus in lagomorphs: evidence for duplication of the UGT1A6 gene.

The UGT1 locus is felt to be highly conserved between species, as is evident from the characterization of the locus in rodents and humans. In rabbits, cDNAs encoding proteins homologous to human UGT1A4, UGT1A6, and UGT1A7 have previously been identified. Here we demonstrate by Southern blot analysis, using exon 1 divergent 5' segments from rabbit UGT1A4 and UGT1A6 cDNAs, the existence of a cluster of highly related genes that are homologous to each of these exon 1 sequences. In comparing rabbit and human, it is evident that the UGT1A4 and UGT1A6 gene clusters in rabbit have undergone gene duplication. This is particularly evident with rabbit UGT1A6. The human UGT1A6 cDNA anneals to only a single gene fragment, as displayed by Southern blot analysis, indicating that the UGT1A6 exon 1 sequence is highly conserved. However, up to six rabbit UGT1A6 genes could be predicted from Southern blot analysis. To examine the potential linkage of the rabbit UGT1A6 genes, multiple UGT1A6 exons were identified from genomic DNA by extended polymerase chain reaction techniques and cloning of the UGT1A6 exon 1 sequences. Five unique UGT1A6 exon 1 gene sequences were characterized that could be predicted to encode proteins that are 98% similar in amino acid structure. Using a conserved region of the rabbit UGT1A6 cDNA as a probe to screen cDNA libraries, we identified a second UGT1A6 cDNA, termed UGT1A6alpha. In addition, a cDNA that encodes a protein similar to human UGT1A3 was also cloned. Characterization of UGT1A6alpha demonstrated the protein to be 98.9% identical to UGT1A6. The expression of rabbit UGT1A3, UGT1A4, and UGT1A6 displayed catalytic activities similar to their human orthologs. However, UGT1A6alpha was catalytically divergent from UGT1A6, indicating that UGT1A6 and UGT1A6alpha do not arise from allelic polymorphism. These results demonstrate that lagomorphs have evolved at least five additional UGT1A6 genes, an event that is not duplicated in rodents or humans.

Amino Acid Sequence↗
PubMed1999

The use of dynamic interventional MRI in developmental dysplasia of the hip.

Conventional methods of imaging in the investigation of developmental dysplasia of the hip all have disadvantages, either in definition or in exposure to radiation. We describe a new open-configuration MR scanner which is unique in that it allows anaesthesia and access to the patient within the imaging volume for surgical procedures and application of casts. We performed 13 scans in eight anaesthetised infants. Dynamic imaging revealed two dislocated hips which were then visualised during reduction. Hip spicas were applied without removing the patient from the scanner. In one hip, an adductor tenotomy was carried out. In all patients, stressing the hips during dynamic imaging allowed an assessment of stability. This was particularly useful in two hips in which an analysis of stability in different positions facilitated the planning of femoral osteotomies. This method of imaging provides new and important information. It has great potential in the investigation of developmental dysplasia of the hip and, with ultrasound, may allow management without the need for radiography.

Anesthesia, General↗
PubMed1995

A comparison of the efficacy of dopexamine and dobutamine for increasing oxygen delivery in high-risk surgical patients.

Peri-operative increase of oxygen delivery has been shown to reduce mortality in high-risk surgical patients. This study compares the effectiveness of dopexamine and dobutamine when used to increase cardiac output as part of a regimen to increase oxygen delivery. Sixteen surgical patients were randomly allocated to receive either dopexamine or dobutamine, which was increased to a stable dose defined as either oxygen delivery index > 600 ml/min/m2, or tachycardia > 20% above baseline, other dysrhythmias or angina. At this "stable" dose there were significant increases in cardiac index (2.4 +/- 0.2 vs 3.7 +/- 0.3 l/min/m2) and oxygen delivery (380 +/- 73 vs 579 +/- 40 ml/min/m2) in the dopexamine group (P < 0.05); but not the dobutamine group. Five out of eight patients receiving dopexamine and three out of eight receiving dobutamine reached target oxygen delivery. Three dobutamine patients, but no dopexamine patients, had angina or dysrhythmias. In preoperative high-risk surgical patients, dopexamine can allow greater increases in oxygen delivery than dobutamine, due to cardiac effects that limit the dobutamine infusion rate.

Adrenergic beta-Agonists↗
PubMed1994

Effects of a nitric oxide synthase inhibitor in humans with septic shock.

OBJECTIVE: Studies in animals have indicated that increased production of nitric oxide from an inducible isoform of nitric oxide synthase contributes to the pathophysiology of endotoxic and cytokine induced shock. The aim of this study was to determine the role of nitric oxide in septic shock in humans. METHODS: The study was a randomised, double blind, placebo controlled investigation of the effects of the nitric oxide synthase inhibitor NG monomethyl-L-arginine (L-NMMA) in 12 patients with severe sepsis associated with hypotension. Measurements of haemodynamic, haematological, and biochemical variables were made. RESULTS: L-NMMA (0.3 and 1 mg.kg-1) produced a dose dependent increase in mean arterial pressure, systemic vascular resistance, pulmonary vascular resistance, central venous pressure, and pulmonary artery occlusion pressure, and a decrease in cardiac output and heart rate. In response to the highest dose of L-NMMA systemic vascular resistance increased from 547(SEM 92) to 889(143) dyne.s.cm-5, mean arterial blood pressure increased from 80.9(2.9) to 100.5(6.1) mm Hg, and cardiac output decreased from 11.2(2.1) to 8.9(1.9) litres.min-1. Continuous infusion of L-NMMA (1 mg.kg-1 x h-1) produced sustained haemodynamic changes. Platelet numbers decreased during the course of the study in both the L-NMMA and the placebo group and did not differ significantly between the groups. CONCLUSIONS: Low doses of L-NMMA cause a widespread increase in vascular tone and raise blood pressure in patients with septic shock. Overproduction of nitric oxide appears to be an important mechanism in septic shock in patients, and inhibition of nitric oxide synthesis might provide a novel therapeutic approach to this condition. However, L-NMMA produced a fall in cardiac output and it is possible that this would worsen tissue perfusion. Larger studies examining the effects of L-NMMA on mortality and morbidity are now required.

Adult↗
PubMed1994

Unusual complication of coumadin toxicity.

Coumadin is a coumarin anticoagulant that induces a state similar to vitamin K deficiency and is routinely used for chronic oral anticoagulation. Intramural hematoma of the bowel is a rare complication of anticoagulant therapy. In this paper, we describe such a case of an anticoagulated patient who had complaints of abdominal pain and who had inadvertently been taking higher dose of coumadin. Although the diagnosis can usually be made by history and plain abdominal x-ray, we report here some radiographic signs that can be seen on a CT-scan of the abdomen and are relatively specific for this diagnosis. We stress the importance of recognizing the disorder because the management is conservative and surgery is reserved for cases in which no improvement is seen.

Drug Overdose↗
PubMed1993

Comparison of clinical information gained from routine blood-gas analysis and from gastric tonometry for intramural pH.

The measurement of gastric intramucosal pH (pHi) has been advocated to assist in decision-making for critically ill patients. To assess whether the information obtained from the measurement of pHi can be obtained from other measurements of metabolic acidosis, we studied 20 consecutive patients admitted to the intensive care unit. A mean of eight (range two to fourteen) data sets per patient were obtained, comprising measurement of arterial pH, pO2, pCO2, and oxygen saturation, tonometer balloon fluid pCO2, arterial pressures, and cardiac output. Bicarbonate concentration, base deficit or excess in blood and extracellular fluid, and pHi were calculated from these measurements. Relations between the variables and pHi were assessed by within-subject correlation comparisons. There were significant correlations (r > 0.6, p < 0.001) between markers of metabolic acidosis (base deficit in blood and extracellular fluid and bicarbonate concentration) and pHi. A blood base deficit of -4.65 or less and an extracellular-fluid base deficit of -6.13 or less could estimate pHi below 7.32 (lower limit of normal range) with sensitivity of at least 77% and specificity of at least 96%. There was no patient in whom either pHi or blood base deficit consistently reflected acidosis when the other variable did not. We conclude that the information that is obtained by gastric tonometry for pHi can be obtained more simply from measurements of metabolic acidosis; these variables can be calculated from routinely available blood-gas measurements.

Acidosis↗
PubMed1992

Psychometric examination of instruments using aggregated data.

The techniques used to examine the psychometric properties of instruments that measure concepts where individual responses are aggregated to form an index describing a group level phenomenon are reviewed. This examination includes assessing the content validity of items to determine how well they measure group level concepts as well as analyzing reliability and validity at the aggregated rather than individual level. Additional techniques to test for within and between group variability are presented. The latter approaches are useful in determining the consistency and adequacy of individual responses at the group level.

Group Processes↗
PubMed1987

Dose and stage dependency for the development of local skin reactions caused by Trypanosoma congolense in goats.

Intradermal inoculation of metacyclic forms of Trypanosoma congolense propagated in vitro caused skin reactions in goats similar to the local skin reaction (chancre) induced by the bite of an infected tsetse fly. The onset, size and duration of these local skin reactions were dose-dependent. Whereas one cultured metacyclic T. congolense was sufficient to cause a local skin reaction in a goat, over 10(7) bloodstream forms of T. congolense were necessary to elicit a detectable skin reaction and while T. congolense parasites present in lymph did not cause local skin reactions, trypanosomes collected from oedematous fluid of the chancre did. - Using non-dividing irradiated bloodstream forms it was estimated that 10(8) T. congolense were required to induce a detectable local skin reaction. - Intradermal needle inoculation of procyclic forms (uncoated trypomastigotes) of T. congolense propagated in vitro induced an intense inflammatory response which was similar to that found in the early phases of the reaction elicited by metacyclic trypanosomes. This suggests that the uncoated trypomastigotes which are known to be present in the saliva of infected tsetse may play a role in the initial development of the chancre. - The data obtained for the local skin reaction suggest the presence of an intracutaneous dividing stage of T. congolense which is intermediate between the metacyclic and bloodstream forms.

Animals↗
PubMed1982

An assessment of ultrasound scanning in the recognition of colorectal liver metastases.

The preoperative detection of visible liver metastases in patients with colorectal cancer is important in determining a rational treatment policy. The accuracy of haptic ultrasound scanning was assessed in 100 patients with primary colorectal cancer. Each patient had a 99mTc-sulphur colloid scan, ultrasound scan, and liver function test. All patients came to laparotomy and the liver was carefully palpated. With very few exceptions the combination of isotope and ultrasound scanning gave accurate information on the state of the liver in all patients in this series. Alkaline phosphatase was the only enzyme whose serum activity was consistently elevated in the presence of liver metastases. Ultrasound scanning of the liver is a simple, safe, accurate, and non-invasive method for preoperative assessment of the state of the liver in patients with primary colorectal cancer.

Colonic Neoplasms↗
PubMed1982

School absence: a problem for the pediatrician.

Children who are frequently or persistently absent from school tend to perform poorly in school and are likely to drop out before graduation from high school. Excessive school absence was significant implications in terms of maladaptive behavior, wasted opportunities, and future unemployment and welfare costs. Epidemiologic information about this problem suggests that physical and mental health problems of students or their families are the sole or contributing cause of this behavior in more than 50% of cases. Excessive school absence may signal such health problems as poor coping with or management of chronic illness, masked depression, teenage pregnancy, substance abuse, inappropriate responses to minor illnesses, or severe family dysfunction. School absence patterns appear to be a readily available, easy-to-use marker of childhood dysfunction which lends itself to screening large numbers of children for unmet health needs. Attention to this area of child behavior as part of routine health care will frequently uncover previously unrecognized health problems in children and their families.

Absenteeism↗