Biomedical subjects
Publications and source records attributed to J Gilbert.
The critical care management of acute injury to the cervical spinal cord is discussed from the perspective of the pathophysiology of the injury process and its ramifications. Emphasis is placed upon resolution of cardiovascular derangements, spinal cord resuscitation, and respiratory support utilizing practical therapeutic interventions.
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The Fusarium mycotoxin moniliformin (hydroxycyclobutenedione) has been determined in maize using a novel method with a recovery of 70-80% at 400-1600 micrograms/kg and 60% at the detection limit of 100 micrograms/kg. The method requires extraction of the toxin into aqueous tetra-n-butylammonium hydroxide and removal of cations from this solution by ion-exchange chromatography. Following clean-up by partitioning against dichloromethane, further quaternary ammonium reagent was added to the aqueous phase which was absorbed onto a hydrophilic matrix and the tetra-n-butylammonium moniliformate ion pair extracted into dichloromethane. After evaporation of the organic eluent, the residue was dissolved in aqueous sodium chloride and moniliformin quantitated by ion-pair high-performance liquid chromatography with UV detection. A batch of five samples may be analysed in 5-6 h including the chromatographic determination.
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A practical evaluation has been carried out of six previously published extraction and clean-up methods for aflatoxin M1 in liquid milk. The procedures evaluated incorporated the most widely used stages of clean-up including solvent extraction and silica gel chromatographic clean-up, selective solvent extraction of the extracted residue, the use of deproteination prior to hydrophilic column liquid-liquid partition or solvent extraction and the use of pre-packed reversed-phase cartridges for the direct extraction of aflatoxin M1 from the milk. Analysis times for each method, recoveries and relative costs are reported together with fluorescence high-performance liquid chromatography chromatograms, obtained under identical conditions to compare the relative cleanliness of the final extracts produced by each method. A pre-packed reversed phase cartridge method was shown to be the most satisfactory in terms of speed, cost and cleanliness of the final residue.
We measured the concentration of gamma-aminobutyric acid (GABA), glutamic acid, and o-phosphoethanolamine in autopsied brain of 9 patients who died with idiopathic Parkinson's disease and 10 control subjects. In the control striatum GABA showed an uneven rostrocaudal distribution pattern with rostral subdivisions containing about 40 to 50% higher levels. When compared with controls, GABA concentrations in Parkinson's disease striatum were generally elevated. The GABA elevation was most pronounced in the caudal subdivision of the putamen; this striatal subdivision also showed the most severe dopamine loss. We observed in the caudal putamen a significant negative correlation between the (elevated) GABA and (reduced) dopamine levels (the latter expressed as the sum of dopamine plus 3-methoxytyramine). Milder nonsignificant elevations of GABA levels were observed in intermediate and rostral putamen followed by the caudate head subdivisions. GABA levels were normal in all extrastriatal brain areas examined. Striatal glutamic acid levels were markedly elevated in 3 of the 9 patients with Parkinson's disease. We suggest that the altered GABA metabolism in the striatum, especially the putamen, is consequent to the nigrostriatal deficiency in this disorder. This secondary change in striatal GABA function is likely to contribute to the basal ganglia dysfunction produced by the striatal dopamine loss and thus may be related to certain aspects of parkinsonian symptomatology.
Collisionally activated dissociation mass spectra, observed with a hybrid tandem instrument, of the chemical ionization protonated molecular ions of sulphonamide drugs have been used as the basis of a rapid screening procedure for these drugs in crude extracts of pig's kidney by scanning to detect the parents of a characteristic daughter fragment. Extracts were introduced without chromatography by a moving belt interface. Detection limits of 0.1 mg/kg were achieved. Confirmation was made by obtaining daughter ion spectra of the protonated molecular ions. Multiple reaction monitoring with a stable isotope analogue as internal standard permitted the quantification of targeted compounds with high sensitivity and precision.
The relative binding affinities of 48 steroids for four classes of hormone receptor (progestin, PR; androgen, AR; glucocorticoid, GR; mineralocorticoid, MR) have been analyzed by correspondence analysis. The steroids were, for the most part, derivatives of nortestosterone, differing by their degree of unsaturation, by the presence or absence of a 17 alpha-ethynyl group, and by the length of the C-13 alkyl substituent. Derivatives of norprogesterone were included as reference compounds. Distribution maps visualizing the results of the mathematical analysis revealed that the majority of the test steroids were within the zone of influence of AR and PR and had limited affinity for GR and MR. Overall lack of specificity and enhanced affinity for GR and MR were induced by increasing unsaturation and by the presence of a C-13 ethyl group. The general and specific conclusions of the analysis confirm and extend previous intuitive and partial interpretations of the data. Correspondence analysis, however, has the advantage of taking into account the sum total of the available information, without any preconceived notion of the relative importance of a specific structural feature or biological parameter and, furthermore, enables simultaneous representation on a single graph of the receptor and steroid fields. The present example demonstrates the use of this type of methodology in processing routine screening data involving multiple parameters.
The syndrome of sudden cardiac death in southeast Asians has only recently been given attention in the American medical literature. This case report describes a patient who presented with this rare syndrome. The physical examination, Holter monitor, 2-D echocardiogram, exercise treadmill test, radionuclide ventriculogram, coronary angiography, and endomyocardial biopsy were all normal. Programmed ventricular stimulation reproducibly induced sustained polymorphic ventricular tachycardia. Oral procainamide, oral quinidine and oral quinidine plus propranolol were not successful in suppressing inducible polymorphic ventricular tachycardia. The arrhythmia remained inducible after six weeks of oral amiodarone therapy. However, he has no clinical recurrences while on amiodarone after one year of follow-up.
Twenty-five (37%) patients with cystic fibrosis attending our clinic have experienced acute meconium ileus equivalent. In one year 37 of 40 episodes were treated with single dose oral Gastrografin with an 81% success rate, 75% being treated as outpatients. Patients found this treatment preferable to other recommended treatment.
The monoclonal antibodies HMFG-1 and HMFG-2 are directed against different epitopes on a large molecule in the human milk fat globule and are also expressed on breast tumors. Here we examine the relative intensity of staining of the two antibodies in formalin fixed paraffin embedded tissue sections from malignant and benign mammary lesions. Most ductal carcinomas and their lymph node metastases stained more strongly with HMFG-2 whereas primary lobular carcinomas are more variable but the majority of their lymph node metastases stained more strongly with HMFG-1. Western blots of gel separated extracts of formalin fixed, paraffin embedded tumor tissue, stained with the antibodies in an ELISA assay, show that the molecular weight of components expressing the antigenic determinants varies. Smaller molecular weight components recognised by HMFG-2 and present in metastatic tumors may be lost during tissue processing. To assess the importance of the molecular weight parameter in tumor classification and prognosis it will be necessary to use frozen tissue.
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Rats and dogs chronically treated with high doses of sulbactam are known to sequester protein-bound glycogen in their hepatocytes. As a result, previous UK studies of sulbactam/ampicillin excluded patients suffering from diabetes mellitus. This study examined the effects of sulbactam/ampicillin compared to flucloxacillin/ampicillin on diabetic control, the ability to mobilize glycogen and the pancreatic beta cell response to glucagon, in diabetic patients suffering from soft tissue infection. There was no significant effect between treatment groups on any of these parameters. Sulbactam/ampicillin is unlikely to have an adverse effect on diabetic control in clinical practice when used short term in the doses employed in this study.
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An instrument providing cyclic stress to cells cultured in vitro has been developed. The unit uses a vacuum to deform a plastic Petri dish yielding 0.13% compression to cells on the inner surface, measured by strain gauge recordings. A regimen of 25 s stress and 5 min relaxation induced no significant change in synthesis of a 45 X 10(3) Mr protein that comigrates with actin, whereas a 52 X 10(3) Mr protein that comigrated with tubulin decreased from 12.7 +/- 0.451% of the total protein synthesized in control, static cells to 8.53 +/- 0.182% in stressed cells. The unit may have a broad application in monitoring biochemical changes in response to stress in cells such as muscle, lung, tendon, ligament and bone that are normally subjected to tension or compression.
Several cryosurgical techniques for freezing hepatic parenchyma have been developed. To assess the efficacy of sonographic monitoring of hepatic cryosurgery, an experimental animal model was devised. Real-time sonography was used to monitor the in vivo evolution of hypothermically induced hepatic cryolesions in four mongrel dogs. The results suggest that sonography is an effective and accurate means of monitoring the entire freezing and thawing cycle in hepatic cryosurgery.
A monoclonal antibody (D5) raised against affinity-purified cytosol estradiol receptor (REC) from human myometrium has been used to stain human tissues by means of an indirect immunoperoxidase method. Good staining was obtained with ethanol-, glutaraldehyde-, or Carnoy's-fixed material but not with formalin or Bouin's fixation. Cytoplasmic staining of human breast tumors exhibited a highly significant correlation (P less than 0.001) with REC assayed by conventional estradiol-binding assay provided that allowance was made for both staining intensity and cellularity of the tumor; no correlation existed with soluble progesterone receptor content. Both patient age and tumor differentiation influenced staining patterns in the same way as did REC content. Cultured REC-positive human breast tumor cell lines (MCF-7, ZR-75-1, and CA-2) showed positive staining as did cultured epithelium from human milk. Epithelia in normal breast and fibroadenoma exhibited variable staining that rarely reached the intensity seen in REC-positive tumor cells. The staining patterns of human normal endometrium, myometrium, fallopian tube, ectocervix, endocervix, and ovary and neoplastic endometrium and ovary are described. In every situation thus far examined only cytoplasmic staining has been observed.