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Biomedical subjects

M Fox

Publications and source records attributed to M Fox.

At least 55 records · Page 3Linked to original sources
PubMed1992

Stage I seminoma of the testis: is post-orchidectomy surveillance a safe alternative to routine postoperative radiotherapy?

Experience with the management of 128 patients with Stage I testicular seminoma over a 10-year period, 1980-1989, is presented. Fifty-six patients were treated with post-orchidectomy radiation therapy and 72 patients were put on surveillance. Patients thought to be at higher risk of relapse were generally treated with radiotherapy. There have been no tumour related deaths in this series; 5.4% of the irradiated group and 18% of patients on surveillance have relapsed to date. All relapses have been salvaged with further therapy and are currently in complete remission. In this interim analysis, surveillance appears to be a safe alternative to adjuvant radiation therapy provided regular, prolonged follow-up can be ensured. Surveillance is, however, time consuming and resource demanding, and should be undertaken only as part of a formal clinical study. Adjuvant post-orchidectomy radiotherapy should be considered the treatment of choice until further long-term data are available.

Adult↗
PubMed1992

Epidemiology of nematode infections of Soay sheep (Ovis aries L.) on St Kilda.

The epidemiology of nematode infections of Soay sheep on the island of St Kilda over a period of 2 years (August 1988-August 1990) spanning a host population crash is described. Infective larvae (L3) levels on pasture were high (2422 +/- 365 L3/kg D.M. grass in midsummer 1988) when host population density was high, decreasing after the sheep population declined by 70% in early 1989 (601 +/- 14 L3/kg D.M. in midsummer 1989). The availability of infective larvae to sheep increased during the winter of 1988-1989, probably as a result of concentration of existing larvae on grass as vegetation was destroyed by bad weather and overgrazing. Increased availability of pre-parasitic stages was accompanied by a marked increased in faecal egg counts from sheep of all ages and both sexes. Prevalence and intensity of infection (faecal egg counts) were higher in males than females throughout the 2-year study (chi 2 = 208.3, P < 0.005 and F1, 2000 = 304, P < 0.001 respectively), except during the lambing periods, and decreased with age in both sexes. Changes in prevalence and intensity of strongyle infections were associated with changes in host population density. Prevalence and intensity of Dictyocaulus filaria larvae in faeces increased during the host population crash. Infection intensity decreased with age (F1, 203 = 44.02, P < 0.001) and was higher in males than females (F1, 203 = 13.45, P < 0.001).

Analysis of Variance↗
PubMed1992

Sleep-disordered breathing in elderly people and subjective sleep-wake disturbance.

Sleep-disordered breathing and subjective reports of sleep-wake disturbances are both common in elderly people but previous studies investigating the relationship between the two have produced uncertain results. We hypothesized that there is no relationship between sleep-disordered breathing and subjective reports of sleep-wake disturbance. Ninety-three random-sampled retirement-village residents, mean age 77.6 years, were monitored overnight with a portable microprocessor-based system. The respiratory disturbance index (RDI) was used as a measure of sleep-disordered breathing. Subjects were interviewed regarding sleep-wake patterns and snoring history and the Mini Mental State Examination, Geriatric Depression Scale and Nelson Adult Reading Test were administered. The sleep-wake responses were entered into a principal components analysis. Two components, reflecting night-time and daytime disturbance, accounted for 34% of the variance. Multiple regression analyses were performed using RDI as a continuous dependent variable, and three predictor variables, night-time, and daytime disturbance and history of snoring. Together, these variables accounted for only 2% of the variance. We conclude there is no relationship between mild and moderate sleep-disordered breathing and subjective sleep-wake disturbance in this population.

Aged↗
PubMed1992

Color Doppler mapping of aortic regurgitation in aortic stenosis: comparison with angiography.

Color flow Doppler mapping has become the principal noninvasive method used for the qualitative grading of aortic regurgitation (AR). However, the performance of the color Doppler method in patients with AR accompanying aortic stenosis (AS) has not been studied. We therefore compared results of color Doppler and semiquantitative angiographic grading of AR in 32 patients with AS (mean valve area = 0.7 cm2) undergoing supravalvular aortography in the course of cardiac catheterization. Color Doppler demonstrated AR in all 27 patients who had AR by aortography. As expected, neither the maximal jet area nor the jet length discriminated patients by angiographic grade. The best correlation between color Doppler and aortography occurred when the ratio of maximal jet height (JH) to left ventricular outflow tract (LVOT) height was used to grade AR on a scale of 0-4. Four of 5 patients without AR by aortography had either absent or grade 1 AR by color Doppler. Although there was considerable overlap of color Doppler grades in patients with 1+ AR by aortography, grade 3 or 4 AR by color Doppler was always associated with III+ or IV+ AR by aortography. Thus, color Doppler sensitively depicts AR in patients with AS, and the ratio of JH to LVOT height by color Doppler correctly identifies patients with III+ or IV+ AR by aortography. Methods for distinguishing among milder grades require further evaluation.

Aortic Valve↗
PubMed1992

Prenatal diagnosis of glucose-6-phosphate-dehydrogenase deficiency.

Prior to the development of the DNA-based technology reliable prenatal diagnosis of G6PD deficiency was not possible. We show that, using PCR amplification and restriction endonuclease digestion, prenatal diagnosis is possible. We have now been able to determine that the male fetus of a mother heterozygous for G6PD Mediterranean had inherited the maternal X chromosome with the normal G6PD gene.

Adult↗
PubMed1992

Molecular cloning of the human Goodpasture antigen demonstrates it to be the alpha 3 chain of type IV collagen.

To characterize the autoantigen of Goodpasture's (anti-glomerular basement membrane) disease, a molecule of 26-kD reactive with autoantibodies from patients' sera was purified from collagenase digests of sheep glomerular basement membrane. Short internal amino acid sequences were obtained after tryptic or cyanogen bromide cleavage, and used to deduce redundant oligonucleotides for use in the polymerase chain reaction on cDNA derived from sheep renal cortex. Molecules of 175 bp were amplified and found to come from two cDNA sequences. One was identical to that of a type IV collagen chain (alpha 5) cloned from human placenta and shown to be expressed in human kidney. The other was from a type IV collagen chain with close similarities to alpha 1 and alpha 5 chains, and was used to obtain human cDNA sequences by cDNA library screening and by further polymerase chain reaction amplifications. The correspondence of the derived amino acid sequence of the new chain with published protein and cDNA sequences shows it to be the alpha 3 chain of type IV collagen. Its gene, COL4A3, maps to 2q36-2q37. The primary sequence and other characteristics of this chain confirm that it carries the Goodpasture antigen.

Amino Acid Sequence↗
PubMed1992

Role of endothelin-1 and big endothelin-1 in modulating coronary vascular tone, contractile function and severity of ischemia in rat hearts.

The effect of endothelin-1 (ET-1) and big ET-1 on coronary flow and contractile function was determined in isolated nonischemic and ischemic rat hearts. Both ET-1 (IC50 = 12 pMol) and big ET-1 (IC50 = 2 nMol) reduced coronary flow in a concentration-dependent manner, although ET-1 was > 100-fold more potent. Both compounds decreased contractility, an effect which was lost when coronary flow was held constant, indicating that ET-1 and big ET-1 decrease contractility secondary to reducing coronary flow. Mechanical reduction in coronary flow to levels equivalent to those seen for ET-1 or big ET-1 caused similar reductions in contractility. Both 30 pMol ET-1 and 10 nMol big ET-1 pretreatment significantly reduced the time to contracture in globally ischemic rat hearts, suggesting a proischemic effect. Phosphoramidon (100 microM, endothelin-converting enzyme inhibitor) and BQ-123 (0.3 microM, ETA receptor antagonist) abolished the preischemic increase in coronary perfusion pressure induced by big ET-1 as well as its proischemic effect, whereas only BQ-123 abolished the cardiac effect of ET-1. Neither phosphoramidon nor BQ-123 had an effect on severity of ischemia when given alone. Phosphoramidon was also given i.v. to rats subjected to coronary occlusion and reperfusion and was found to significantly reduce infarct size 24 hr postischemia. Thus, in isolated rat hearts, big ET-1 appears to be converted to ET-1 and is a potent coronary constrictor.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Morphology of rejection in experimental pancreas transplantation and its modification by cyclosporin A administration.

Histology of pancreas transplant rejection is complicated by non-specific appearances related to undrained exocrine secretions. Using a rat model of pancreas transplantation with exocrine drainage into the urinary tract, morphology of acute rejection has been studied with minimal interference from non-specific change. Unmodified acute rejection was complete after 7-9 days. Intralobular lymphocytic infiltration, which differentiated allografts from isografts, was present 5 days after transplantation and lymphocytic infiltration of islets and blood vessel walls developed between 5th and 7th days. Cyclosporin A immunosuppression of allografts resulted in marked attenuation of the cellular infiltrate. The nature of the infiltrate and its suppression with cyclosporin A indicated an allograft reaction.

Acute Disease↗
PubMed1991

Calculation and display of electrostatic potentials.

A general methodology is developed for incorporating accurate electrostatic information from ab initio molecular orbital calculations into molecular mechanics calculations. Examples are given of the method applied to simple aromatic organic molecules. A program has been developed for displaying the results of the ab initio calculations on a Silicon Graphics workstation. The technique developed here provides an alternative method for including electrostatic interactions in molecular mechanics calculations and is compared with other methods for determining atomic charges.

Computer Graphics↗
PubMed1991

The Chinese hamster HPRT gene: restriction map, sequence analysis, and multiplex PCR deletion screen.

The fine structure of the Chinese hamster hypoxanthine guanine phosphoribosyltransferase (HPRT) gene has been determined; the gene has nine exons and is dispersed over 36 kb DNA. Exons 2-9 are contained within overlapping lambda bacteriophage clones and exon 1 was obtained by an inverse polymerase chain reaction (PCR). All the exons have been sequenced, together with their immediate flanking regions, and these sequences compared to those of the mouse and human HPRT genes. Sequences immediately flanking all exons but the first show considerable homology between the different species but the region around exon 1 is less conserved, apart from the preserved location of putative functional elements. Oligonucleotide primers derived from sequences flanking the HPRT gene exons were used to amplify simultaneously seven exon-containing fragments in a multiplex PCR. This simple procedure was used to identify total and partial gene deletions among Chinese hamster HPRT-deficient mutants. The multiplex PCR is quicker to perform than Southern analysis, traditionally used to study such mutants, and also provides specific exon-containing fragments for further analysis. The Chinese hamster HPRT gene is often used as a target for mutation studies in vitro because of the ease of selection of forward and reverse mutants; the information presented here will enhance the means of investigating molecular defects within this gene.

Animals↗
PubMed1991

Characterization and chromosomal mapping of a genomic clone encoding human alanine:glyoxylate aminotransferase.

We have previously reported the isolation of a genomic clone encoding human liver-specific peroxisomal alanine:glyoxylate aminotransferase (AGT, EC 2.6.1.44), the deficient enzyme in primary hyperoxaluria type 1 (PH1) (P. E. Purdue, Y. Takada, and C. J. Danpure, J. Cell Biol. 111: 2341-2351, 1990). This clone has now been characterized, revealing that the coding sequence is distributed among 11 exons covering 10 kb. The nucleotide sequences of each exon have been determined, confirming that this clone corresponds to previously characterized AGT cDNA (Y. Takada, N. Kaneko, H. Esumi, P. E. Purdue, and C. J. Danpure, Biochem. J. 268: 517-520, 1990). In addition, to provide sequence data for the design of exon-specific PCR primers, the intron sequences immediately flanking each exon have been determined. Furthermore, in an attempt to identify putative transcriptional control sequences we have determined the sequence of 1.25 kb directly upstream of the cDNA 5' end. The results of genomic Southern blotting indicate that human AGT is probably encoded by a single copy gene, and a combination of in situ hybridization and PCR analysis of rodent/human somatic cell hybrids suggests that this gene is located on chromosome 2q36-q37. The gene symbol AGXT has been assigned for this locus.

Alanine Transaminase↗
PubMed1991

Cerebral blood flow, cross-brain oxygen extraction, and fontanelle pressure after hypoxic-ischemic injury in newborn infants.

The relationship between mean arterial pressure, intracranial pressure, cerebral blood flow, cross-brain oxygen extraction, cerebral metabolic rate, and outcome was studied during therapy in nine neonates on 3 consecutive days after severe hypoxic-ischemic cerebral injury. Cross-brain oxygen extraction was significantly higher (5.06 +/- 0.5 vs 2.05 +/- 0.8 ml/dl; p = 0.012) in the five neonates who survived with normal neurologic outcome than in the four who died or sustained severe brain damage. In contrast, global cerebral blood flow in the five neonates with normal neurologic outcome was significantly lower (25.6 +/- 8.2 vs 83.2 +/- 44.9 ml/100 gm brain/min; p less than 0.05) during the study period. The differences in cross-brain oxygen extraction and global cerebral blood flow between infants who had neurologic recovery and those who died or sustained brain damage occurred in the presence of acceptable values for intracranial pressure, mean arterial pressure, and cerebral perfusion pressure. Our preliminary data suggest that cross-brain oxygen extraction and possibly global cerebral blood flow may be important variables associated with severe neuronal injury and death after hypoxic-ischemic cerebral injury.

Asphyxia Neonatorum↗
PubMed1991

Mortality and morbidity of prostatectomy. How far does preselection and pre-operative care influence the result?

Mortality and morbidity rates of prostatectomy have been progressively reduced over the past years, but with increasing ageing of the population, a limit is reached when medical complicating factors ensue, beyond which operative intervention carries an unacceptable risk. Results of surgery have little meaning if patients who are not fit or too old are excluded and not shown. It is with the above objectives in view that a prospective study is reported where all patients who presented or were admitted with prostatic symptoms over 1 year were recorded. There were 246 patients. Age, presentation and ASA (American Society of Anesthesiologists) status, post-operative problems and stay were noted. Joint assessment with a senior anaesthetist was performed in all higher-risk patients. 132 patients were operated on, 91% by transurethral resection of the prostate. 66% were ASA 2 and 3. Age itself bore no relation to length of post-operative stay but ASA status did. There was no mortality. However, 12 (9%) ASA 4 cases were excluded from surgery. It is concluded that with careful assessment, patients who are old and medically compromised can undergo prostatectomy safely, but one has to identify accurately those unsuitable for surgery and offer alternative treatment.

Age Factors↗
PubMed1991

Effects of glycemic control on red cell deformability determined by using the cell transit time analyzer.

There is considerable evidence that blood viscosity is greater than normal in diabetes, and decreased red blood cell deformability has been suggested as the cause. However, viscosity can be influenced by changes in the properties of blood proteins in addition to red cells. Direct interpretation of red cell filtrometry data in terms of deformability has been complicated by the interfering effect of white cells and platelets and clogging of micropores. We have thus used the cell transit time analyzer, a new filtrometric procedure that eliminates these complications and produces an individual red cell micropore transit time profile, to reassess diabetic red cell deformability. Samples from 26 patients with diabetes and an equal number of subjects without diabetes who served as controls were assayed by the cell transit time analyzer at 2 and at 4 cm hydrostatic pressure. Samples from patients with diabetes and controls were sex and age matched for daily runs. At 2 cm H2O, red blood cell transit time for the patients with diabetes was 2.73 +/- 0.05 milliseconds as compared with 2.67 +/- 0.05 milliseconds for controls (p not significant). The ratio of transit time for patients with diabetes to that of controls (Td/Tnd) was 1.03 +/- 0.01 (p less than 0.05, Wilcoxon) at 2 cm H2O and 1.02 +/- 0.01 (p not significant) at 4 cm H2O.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗