Biomedical subjects
Publications and source records attributed to J Overton.
A method is described for the determination of retinol binding protein (RBP) by immunonephelometry. The assay is sensitive to 5 microg/l and has acceptable imprecision. The method correlates with an established ELISA assay. A provisional normal range is proposed for daytime random urine samples. The increased excretion of RBP in adult subject with type 1 diabetes mellitus is demonstrated.
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STUDY OBJECTIVE: Erroneous time documentation of emergency treatment caused by the variation in the accuracy of timepieces has profound medical, medicolegal, and research consequences. The purpose of this study was to confirm the variation of critical timepiece settings in an urban emergency care system noted in previous studies and to implement and monitor the results of a prospective program to improve time synchronization. METHODS: Timepieces (n = 393) used by firefighters, paramedics, and emergency physicians and nurses were randomly sampled immediately before and at two time intervals (1 and 4 months) after attempted synchronization to the US atomic clock standard. The setting on each timepiece was compared with the atomic clock. From the data, a mathematical simulation estimated the number of time-related documentation errors that would occur in 2,500 simulated cardiac arrest cases using timepieces with accuracy similar to those found in the EMS system before and after attempted synchronization. RESULTS: Before attempted synchronization, the timepieces had a mean error of 2.0 (95% confidence interval 1.8 to 2.3) minutes. One month after attempted synchronization, the mean error decreased significantly to .9(.8 to 1.1) minute. However, it increased to 1.7 (1.5 to 1.9) minutes within 4 months. Mathematical simulation before attempted synchronization predicted that 93% of cardiac arrest cases would contain a documentation error of 2 minutes or more and that 41% of cases would contain a documentation error of 5 minutes or more. Attempted synchronization cut the 2-minute documentation error rate in half and reduced the 5-minute documentation error rate by three fourths. However, the error rates were predicted to return to baseline 4 months after attempted synchronization. CONCLUSION: Emergency medical timepieces are often inaccurate, making it difficult to reconstruct events for medical, medicolegal, or research purposes. Community synchronization of timepieces to the atomic clock can reduce the problem significantly, but the effects of a one-time attempted synchronization event are short-lived.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Exacerbation of pre-existing liver disease after halothane anaesthesia has been reported in adult patients. A prospective study was performed in 38 children with biopsy-proven liver disease to assess the effect of surgery and halothane anaesthesia on liver function. Plasma liver enzyme levels were measured immediately preoperatively and again four to eight days after surgery and halothane anaesthesia. Minor elevations of both AST and ALT occurred in four patients but this was not associated with a clinical deterioration in the patients' postoperative recovery. In the children studied pre-existing liver disease did not predispose to a deterioration of liver function following surgery and halothane anaesthesia.
In humans the biliary excretion of trifluoroacetic acid, the major halothane metabolite, has not been studied. We investigated the biliary excretion of trifluoroacetic acid in two infants aged five months and two months following halothane anaesthesia for the operation of choledocholithotomy. Bile, urine and faeces were collected continuously for five days after operation and trifluoroacetic acid excretion measured. Estimates of halothane uptake, daily bile flow and the proportion of daily bile flow collected via the T-tube drainage catheter were subject to percentage errors possibly as large as 50%. Of the total trifluoroacetic acid produced from halothane metabolism, it was estimated that 17% in the five-month-old infant and 20% in the two-month infant was excreted in bile. In the five-month-old infant where approximately 80% of the bile produced entered the duodenum in the normal way, no faecal trifluoroacetic acid was detected suggesting an enterohepatic circulation for this metabolite.
It has been postulated that trifluoroacetyl chloride, a halothane metabolite, can bind covalently with the phosphatidylethanolamine component of the hepatic cell membrane and cause cell necrosis. Breakdown of the necrotic hepatocyte would release N-trifluoroacetyl-ethanolamine (TFAE) into the serum with subsequent urinary excretion. An original High Performance Liquid Chromatography (HPLC) method for the measurement of TFAE is described. In six children 1% halothane was administered for one hour and the halothane uptake measured. Urinary excretion of TFAE was measured for up to eight days and found to be 0.09 +/- 0.07% or less of the absorbed halothane. In children TFAE is not a major urinary metabolite of halothane.
An attempt was made in children to identify a urinary halothane-cysteine conjugate which had been described previously in adult patients following administration of halothane. If this conjugate was found it would indicate that a reductive metabolite of halothane binds covalently with the sulphydryl-containing amino acid, cysteine, a reaction which could lead to hepatic injury. The potential halothane-cysteine conjugate, N-acetyl-S-(2-bromo-2-chloro-1,1-difluoroethyl)-L-cysteine (acetyl BCFEC), was prepared and the identity of the compound established using hydrogen-1 and carbon-13 NMR spectroscopy and methane chemical ionization mass spectrometry. A measurement technique for acetyl BCFEC was developed using HPLC with u.v. detection at 200 nm. In six children after halothane anaesthesia, one child being studied twice, urine was collected for up to 1 week and analysed for acetyl BCFEC. Little or no acetyl BCFEC was detected in any of the 43 urine samples tested, indicating that in children it is not a significant urinary metabolite of halothane.
Halothane (1% v/v inspired) was administered for 60 min to six children of mean age 74 months (range 14-119 months). Uptake of halothane was measured from the difference in the concentration in inspired and expired gas and varied from 176 to 310 mg kg-1, depending on minute ventilation. After administration of halothane ceased, its elimination in expired gas was measured in four patients until the conclusion of anaesthesia; 32-37% of the absorbed halothane was expired 90 min after halothane administration ceased. Urinary excretion of trifluoroacetic acid, fluoride and bromide was measured for up to 1 week. Of the absorbed halothane, 11.4% (range 6.3-18.2%) was excreted in urine as trifluoroacetic acid and 0.37% (range 0.10-0.64%) as inorganic fluoride. The urinary half-life of trifluoracetic acid was 41.8 h (range 10.4-59.1 h). The quantitative and qualitative metabolism of halothane via the reductive and oxidative pathways in children are comparable to values found in adults. No differences in the metabolism of halothane by children were found which would explain the different incidence of halothane-associated hepatitis compared with adults.
Fusion of the amniotic folds over the chick embryo provides an example of epithelial fusion in which one group of ectodermal cells appears to contribute to traction and a second group appears to respond by moving to the midline, becoming internalized and degenerating. Neutral red staining of living embryos and transmission electron microscopy indicate that a patch of dying cells is present in the fusion region. Scanning electron microscopy shows that ectoderm cells at the rim of the amniotic folds are cylindrical in shape with long axes oriented parallel to the rim. These cells have a smooth surface, but show increasing amounts of blebbing toward the midline. Characteristically, a globular region of rounded cells showing extreme blebbing is present at the midline. Just anterior to the globular region, flattened cells are present on the surface with many taut cellular processes. Orientation of ectodermal cells around the region of fusion suggests that traction is exerted from these flattened cells. When treated with cytochalasin D, posterior progression of the zone of fusion is blocked. Also, the flattened cells anterior to the globular region round up, revealing many elongated, anteriorly-directed cytoplasmic processes presumably leading to sites of original attachment.
Cultured human epithelial cells stained with antibody to desmosomal proteins by indirect immunofluorescence showed linear arrays of desmosomes en face between stratified cells. To confirm that an extensive linear pattern existed on the cell surface, subconfluent cultures were viewed using scanning electron microscopy. Aligned arrays of blunt protrusions lying parallel to each other and extending in the direction of the long axis of the cell were observed on the surface of groups of superficial cells in intact cultures. That this pattern was indeed related to desmosomal distribution was verified by transmission microscopy of thin sections cut in a plane between the upper and lower surfaces of flattened stratified cells to view desmosomes directly. A similar arrangement of desmosomes was seen in intact tissue, using epidermal sheets separated from newborn foreskin. The same pattern found in flattened cells was sometimes apparent in more rounded basal cells where the cytoplasm was beginning to extend. Since desmosomal plaques are associated with keratin filaments, the alignment of desmosomes must occur in association with cytoskeletal changes as cells become flattened toward the distal epithelial surface. The primary initiation of desmosomal alignment remains to be investigated. However, the present findings demonstrate an increasingly regular membrane-cytoskeletal spatial interaction as stratified epithelial cells of skin mature.
Chick corneal epithelium takes on its mature conformation between 11 and 16 days of incubation. Earlier work has shown that desmosome frequency increases during this period, reaching its highest rate at 15 1/2 days. In the present report aggregation rates of cells from embryos of 11 days and those of 15 1/2 days are compared. Younger cells, which form fewer desmosomes, aggregate at a more moderate rate than older cells. In addition, younger cells bind less concanavalin A (ConA) than older cells. To determine if increase in ConA binding could be related to these cellular responses, aggregating cells were exposed to endoglycosidase H (EndoH) and to deoxymannojirimycin. This treatment should permit comparison of the response of cells that have a normal complement of N-linked oligosaccharides with those that have reduced high-mannose or complex type sugars. The effectiveness of EndoH under the conditions used was confirmed by failure of treated glycoprotein after separation by SDS-PAGE and electroblotting to bind ConA. Aggregation rates of both older and younger cells were unaffected, as measured by disapperance of single cells, though older cells formed somewhat smaller aggregates at the highest dosage used. Desmosome formation was markedly reduced in the presence of the enzyme, even in the absence of other changes in the fine structure. At the highest dose of the enzyme the fine structure of older but not younger cells showed indications of blockage of transport. Deoxymannojirimycin appears to cause a build-up of high-mannose groups, since treated cells showed increased incorporation of [3H]mannose.(ABSTRACT TRUNCATED AT 250 WORDS)
In the 4 years January 1981 to December 1984, 186 children received 1362 halothane anaesthetics. Twenty-five patients were anaesthetized with halothane at least 10 times in a year. No patient developed postoperative jaundice. Sixty-nine children were exposed to two halothane anaesthetics within 28 days on 149 occasions and serial estimations of serum liver enzyme concentrations were obtained. Minor increases in the concentrations of serum AST and ALT were recorded in 10.6% and 4.7% of patient entries, respectively. Postoperative GGT and SAP concentrations were increased in 2.7% of patient entries. Patients in whom enzyme values were increased before the first anaesthetic were no more likely than other subjects to develop further changes.