Biomedical subjects
Publications and source records attributed to R J Ward.
The swabbing of the arm with ethanol before venepuncture significantly raised the apparent blood ethanol concentration, when compared to the unswabbed arm. In contrast, when isopropanol was substituted for ethanol in these studies, no change in the blood ethanol concentration was determined.
The penicillin acylase gene (pac) from Escherichia coli ATCC 11105 was cloned into pUC 9 and the resulting vector (pUPA-9), when transformed into E. coli strain 5K, allowed the constitutive overproduction of mature penicillin acylase when grown at 28 degrees C. The enzyme was purified from the periplasmic fraction of E. coli pUPA-9 by hydrophobic interaction chromatography and anion exchange. Crystals of penicillin acylase were grown in batch using polyethylene glycol 8000 as a precipitant. The crystals (space group P1) diffracted to beyond 2.3 A.
Adverse outcomes associated with respiratory events constitute the single largest class of injury in the American Society of Anesthesiology Closed Claims Study (522 of 1541 cases; 34%). Death or brain damage occurred in 85% of cases. The median cost of settlement or jury award was +200,000. Most outcomes (72%) were considered preventable with better monitoring. Three mechanisms of injury accounted for three-fourths of the adverse respiratory events: inadequate ventilation (196; 38%), esophageal intubation (94; 18%), and difficult tracheal intubation (87; 17%). Inadequate ventilation was used to describe claims in which it was evident that insufficient gas exchange had produced the adverse outcome, but it was not possible to identify the exact cause. This group was characterized by the highest proportion of cases in which care was considered substandard (90%). The esophageal intubation group was notable for a recurring diagnostic failure: in 48% of cases where auscultation of breath sounds was performed and documented, this test led to the erroneous conclusion that the endotracheal tube was correctly located in the trachea. Claims for difficult tracheal intubation were distinguished by a comparatively small proportion of cases (36%) in which the outcome was considered preventable with better monitoring. A better understanding of respiratory risks may require investigative protocols that initiate data collection immediately upon the recognition of a critical incident or adverse outcome.
The authors examined the American Society of Anesthesiologists Closed Claims Study database to define the role of nerve damage in the overall spectrum of anesthesia-related injury that leads to litigation. Of 1,541 claims reviewed, 227 (15%) were for anesthesia-related nerve injury. Ulnar neuropathy represented one-third of all nerve injuries and was the most frequent nerve injury. Less-frequent sites of nerve injury were the brachial plexus (23%) and the lumbosacral nerve roots (16%). In a large proportion of cases, the exact mechanism of injury was unclear despite evidence of intensive investigation in the claim files. Median payment for nerve damage claims involving disabling injury was $56,000, which was significantly lower than the $225,000 median payment for claims for disabling injury not involving nerve damage (P less than 0.01). The closed claims reviewers judged that the standard of care had been met significantly more often in claims involving nerve damage than in claims not involving nerve damage. The authors conclude that nerve damage is a significant source of anesthesia-related claims but that the exact mechanism of nerve injury is often unclear. In particular, ulnar nerve injuries seemed to occur without identifiable mechanism.
Diabetes mellitus is found with increased frequency in patients with both primary and secondary hemochromatosis. In these conditions, the pancreas shows fibrosis and iron overload of acini, interstitium, and islet B cells. Previous morphological studies have only described changes found in advanced stages of disease, while abnormalities of the initial stage of iron overload have, as yet, not been reported. Rats fed a carbonyl iron-supplemented diet for 4-15 months showed storage iron deposition (ferritin and hemosiderin) in many organs, in a pattern similar to primary human hemochromatosis. Electron microscopic examination of the pancreas showed ferritin particles segregated in lysosomes of acinar cells, as well as diffuse cytosiderosis of macrophages in the interstitial septa. In the islets, iron deposits were discrete and only in B cells. In the absence of electron-microscopic studies of incipient pancreatic cytosiderosis in human subjects, the present experimental animal study may contribute to a better understanding of the pathway leading to the extensive lesions found in the advanced stages of the human iron overloading diseases.
Haemosiderin isolated from different iron-loading syndromes, primary haemochromatosis (PHC) and secondary haemochromatosis (SHC) biochemically exhibited differences in both their iron core and peptide composition. The rate of release of iron from PHC haemosiderin to oxalate was 3-fold greater than that from SHC haemosiderin. The major peptides separated by SDS-PAGE showed a major band at Mr 20,000 for PHC haemosiderin and at Mr 15,000 for SHC haemosiderin.
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Iron release from both human and horse spleen haemosiderin to desferrioxamine was substantially less than that released from ferritin samples. This finding contradicts a previous report [Kontoghiorges, Chambers & Hoffbrand (1987) Biochem. J. 241, 87-92]. Differences in phosphate content of cores and in core size between haemosiderin and ferritin did not account for the different iron-release rates. Iron released to acetate was found to stimulate lipid peroxidation in liposomes, whereas that released to stronger chelators such as citrate and desferal did not. Absorption spectra and gel-filtration studies suggest that the acetate-solubilized iron was in the form of low-molecular-mass (less than 5 kDa) ferrihydrite fragments.
For the past 3 years, the Committee on Professional Liability of the American Society of Anesthesiologists has been studying records of closed malpractice claims files for anesthesia-related patient injuries. The database of 1004 lawsuits was examined to define the impact of the "standard of care," as judged by a practicing group of anesthesiologists, on the likelihood and amount of financial recovery. We found that payment was made in more than 80% of claims made by patients who were judged to have received substandard anesthetic care. Payment also was made in more than 40% of claims when the anesthesia care was judged to be appropriate. We conclude that in the tort-based system of compensation for anesthesia-related injury, the patient has a high probability of financial recovery for injury caused by substandard care. However, if the anesthesiologist provides appropriate care there is still a greater than 40% chance that payment will be made for the claim of malpractice.
The purpose of this study was to examine the dose versus EEG response relationship, the speed of onset, and the thiopental requirement for induction of anesthesia with small doses of sufentanil and fentanyl. The power spectrum of the electroencephalogram (EEG) was used to quantify the effect of the opioids. Eight male surgical patients, 52-80 yr old, were randomly divided into eight groups of ten to receive fentanyl, 5, 7, 10, or 13 micrograms/kg, or sufentanil, 0.5, 0.7, 1.0, or 1.3 micrograms/kg. The opioid was given iv over 1 min at a constant rate of infusion. Three to four minutes after the start of the opioid dose, thiopental was given iv in 25 mg increments every 30 s until the patient was unconscious. Power in the 1-3 Hz band reached maximum levels in less than 4 min after the start of opioid administration. At fentanyl doses of 7.0 micrograms/kg or less, or sufentanil doses of 1.0 micrograms/kg or less, the EEG effects did not increase in proportion to the dose of opioid. There was not a significant difference in the maximum power achieved in the 1-3 Hz band for sufentanil, 0.5, 0.7 and 1.0, and fentanyl, 5 and 7 micrograms/kg. Doses of fentanyl, 10 or 13 micrograms/kg, or sufentanil, 1.3 micrograms/kg were substantially more effective; the maximum power increased significantly between 7 and 10 micrograms/kg of fentanyl and 1.0 and 1.3 micrograms/kg of sufentanil (P less than 0.0001). The potency of sufentanil and fentanyl were compared by super-imposing, the dose versus response (power) curves. The potency ratio was 1:8 (sufentanil:fentanyl).(ABSTRACT TRUNCATED AT 250 WORDS)
A double-blind study of patients selected at random compared the analgesic and adverse effects of intrathecal methadone (1 mg) with those of intrathecal morphine (0.5 and 1 mg). The study was conducted on 30 patients who underwent major orthopedic or urologic surgery. The intrathecal opioid was administered at the end of surgery, and assessments began 1 h thereafter and continued for 20 h. Pain measurements, supplementary analgesia requirements, and adverse effects were recorded. Intrathecal morphine (0.5 and 1 mg) provided effective and prolonged analgesia. Methadone, however, was unable to ensure the same degree of analgesia; consequently, the median pain scores were consistently higher following methadone than morphine (0.5 and 1 mg) (P less than 0.05). The time to the onset of discomfort severe enough to require supplemental morphine was longer after intrathecal morphine than that following methadone (24 and 29 h with morphine 0.5 and 1 mg; 6.5 h with methadone; P less than 0.05). Respiratory depression (increases PaCO2) was not associated with methadone and morphine 0.5 mg but was common following morphine 1 mg (P less than 0.05). Facial pruritus was unique to intrathecal morphine. Urinary retention requiring bladder catheterization was more frequent following morphine than methadone, although this was not statistically significant. Nausea and vomiting were common to all groups. Intrathecal morphine (0.5 and 1 mg) provides superior postoperative analgesia to 1 mg methadone. Various explanations for the observed differences between the drugs are discussed, including the possibility that the dose of methadone used in the subarachnoid space was inadequate and that a larger dose might have produced an effect equal to that of morphine.
Anesthesiologist-reviewers examined 1,175 anesthetic-related closed malpractice claims from 17 professional liability insurance companies. The claims were filed between 1974 and 1988. The reviewers were asked to determine if the negative outcome was preventable by proper use of additional monitoring devices available at the time of the review even if not available at the time the incident occurred, and if so, which devices could have been preventative. In 1,097 cases sufficient information was available to make a judgment regarding preventability of the morbidity or mortality by application of additional monitoring devices. It was determined that 31.5% of the negative outcomes could have been prevented by application of additional monitors. Using the insurance industry's scale of 0 (no injury) to 9 (death), the median severity of injury for incidents deemed preventable was 9 compared with 5 for those deemed not preventable (P less than 0.01, scale detailed in text). The severity of injury scores were the same for preventable mishaps occurring during regional or general anesthesia, suggesting that additional monitoring devices may be equally efficacious in preventing serious negative outcomes during either regional or general anesthesia. The judgements or settlements of the incidents judged preventable by additional monitoring were 11 times more costly (P less than 0.01) than those mishaps not judged preventable. The monitors determined by the reviewers to be most useful in mishap prevention were pulse oximetry plus capnometry. Applied together, these two technologies were considered potentially preventative in 93% of the preventable mishaps.(ABSTRACT TRUNCATED AT 250 WORDS)
Although mitochondrial aldehyde dehydrogenase (ALDH2) has been thought to play a major role in acetaldehyde detoxification, and the high incidence of 'alcohol flushing' among Orientals is attributed to the inherited deficiency of ALDH2, the role of cytosolic aldehyde dehydrogenase (ALDH1) cannot be ignored. On the premise that alcohol flushing in Caucasians could be related to ALDH1 abnormalities, we examined the enzyme properties and electrophoretic mobilities of ALDH1 partially purified from red blood cells of nine unrelated alcohol flushers. One exhibited very low activity (10-20% of control level), and another exhibited moderately low activity (60%) and altered kinetic properties. The electrophoretic mobilities of these two samples were also distinguishable from the control samples. Immunological quantitation indicated that the amounts of ALDH1 protein in these two samples were not reduced in parallel with their enzyme deficiency. In the first case, the two characteristics, i.e. very low enzyme activity and alcohol flushing, were inherited by her daughter.
Ratings by self, supervisors and peers of surgical residents were compared and contrasted, and the correlation between these ratings and the scores on the American Board of Surgery In-Training Examination (ABSITE) were studied. In addition, comparisons were made between ratings by residents of their peers (n = 32) and of attending surgeons (n = 61) with whom they had worked. The ratings consisted of scores from 1 to 5 in each of ten areas of clinical competence. Results indicated that over-all ratings by peers and supervisors were highly intercorrelated (r = 0.92; p less than 0.001) and that the average of over-all ratings by peers and supervisors correlated moderately with the total raw score on ABSITE (r = 0.58; p less than 0.01). Factor analyses suggested that the dimensions underlying the three sets of ratings differed considerably. It appeared that ratings by supervisors were influenced primarily by the interpersonal skills of the residents and secondarily by ability. In contrast, self-ratings by the residents were apparently mainly influenced by their perceptions of their own ability, followed by interpersonal skills and effort. Ratings by peers, on the other hand, seemed to reflect the over-all impression of the peers of the resident being rated. Comparisons between ratings of peers and attending surgeons by residents revealed that residents view attending surgeons as having a more balanced level of competence, across areas of both ability and interpersonal skills. Ratings of peers were lower than were the ratings of attending physicians by the residents in the areas of technical ability, knowledge of basic science and clinical knowledge.(ABSTRACT TRUNCATED AT 250 WORDS)
Mössbauer spectroscopy has indicated significant differences in the iron-containing cores of various haemosiderins. In the present study, haemosiderin was isolated from a number of animal species including man. In addition, haemosiderin was isolated from patients with primary idiopathic haemochromatosis or with secondary (transfusional) iron-overload. The iron cores of the animal and normal human haemosiderin appear to be very similar by Mössbauer spectroscopy, and the electron diffraction data indicate a ferrihydrite structure similar to that of ferritin cores. The haemosiderin isolated from secondary iron-overload shows anomalous behaviour in its temperature-dependent Mössbauer spectra. This can be understood in terms of the microcrystalline goethite structure of the cores as indicated by electron diffraction. The haemosiderin cores obtained in the case of primary haemochromatosis have an amorphous Fe(III) oxide structure and show Mössbauer spectra characteristic of a magnetically disordered material, which only orders at very low temperatures.
Haemosiderin iron cores isolated from patients with secondary haemochromatosis have a goethite-like (alpha-FeOOH) crystal structure whereas those from patients with primary haemochromatosis are amorphous Fe (III) oxide. Haemosiderin cores isolated from normal human spleen are crystalline ferrihydrite (5Fe2O3.9H2O). The disease-specific structures are significantly different from the ferrihydrite structure of associated ferritin cores. The results are important in understanding the biological processing of iron in pathological states and in the clinical treatment of iron-overload diseases.
Using Triton WR-1339 to inhibit plasma metabolism of VLDL, hepatic secretion of VLDL was measured in vivo in control and alcohol-fed rats. The composition of VLDL secreted from livers of chronically alcohol-fed rats was compared with pair-fed controls. The results show that the cholesterol, esterified and nonesterified, as well as the triacylglycerol content of VLDL secreted by the alcohol-fed rats was significantly reduced; protein and phospholipid constituents of the VLDL were unaltered. The apoprotein components of the VLDL showed no apparent difference between the two groups. However, fatty-acid composition of VLDL triacylglycerol and phospholipids show a significant reduction in 20:4 and an increase in 18:2 fatty acids in the alcohol-fed rats. VLDL secretion rates by chronic alcohol-fed rats was reduced significantly compared to the control animals, and this observation has been implicated in the pathogenesis of alcoholic fatty liver.