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Biomedical subjects

M J Jones

Publications and source records attributed to M J Jones.

At least 37 records · Page 2Linked to original sources

Phenobarbital does not increase early labeling of bilirubin from 4-[14C]-delta-aminolevulinic acid in man and rat.

delta-Aminolevulinic acid-4-[14C] and [3H]-bilirubin were administered intravenously to five patients with Gilbert's syndrome and four healthy control subjects on two occasions: before and on days 10 through 14 of a course of phenobarbital (2.5 mg/kg/day). The resulting curves of [3H]-bilirubin and [14C]-bilirubin in plasma were analyzed by computer to determine a number of parameters of physiological interest. As expected, phenobarbital produced a highly significant fall in the plasma concentration of unconjugated bilirubin as a result of a significant increase in hepatic bilirubin clearance in all subjects; plasma bilirubin turnover was unaltered. Surprisingly, the drug produced no change in the incorporation of [14C]-delta-aminolevulinic acid into [14C]-early labeled bilirubin. To explain this unexpected finding, the effects of phenobarbital (75 mg/kg/day for 6 days) on incorporation of [14C]-delta-aminolevulinic acid and 2-[14C]-glycine into [14C]-early labeled bilirubin and on the activity of the enzyme delta-aminolevulinic acid synthase were studied in nonfasted, adult, male Sprague-Dawley rats. At the dose and duration of treatment used, phenobarbital administration increased total hepatic delta-aminolevulinic acid synthase activity and produced a significant increase of 70% in the incorporation of [14C]-glycine into early labeled bilirubin. By contrast, no increase in the incorporation of [14C]-delta-aminolevulinic acid into early labeled bilirubin was observed. These data suggest that delta-aminolevulinic acid is an inappropriate precursor for studies of the rate of heme biosynthesis, presumably because it bypasses delta-aminolevulinic acid synthase, the physiological rate-limiting enzyme in the heme biosynthetic pathway.

Aminolevulinic Acid↗

Cognitive and functional competence after anaesthesia in patients aged over 60: controlled trial of general and regional anaesthesia for elective hip or knee replacement.

OBJECTIVE: To determine the influence of general or regional anaesthesia on long term mental function in elderly patients. DESIGN: Prospective study of patients randomly allocated to receive general or regional anaesthesia. SETTING: The patients' homes and a large teaching hospital in Cardiff. SUBJECTS: 146 Patients aged 60 and over scheduled for elective hip or knee replacement. MAIN OUTCOME MEASURES: Scores achieved in tests of cognitive function and functional competence. RESULTS: 72 Patients were allocated to receive general anaesthesia and 74 regional anaesthesia. Anaesthetic technique did not influence the duration of the operation, time to mobilisation postoperatively, requirements for analgesia after the operation, or duration of stay in hospital. Three months after the operation there was an improvement in the score for the recognition component (76 ms, 95% confidence interval 9 to 144) and the response component (82 ms, 5 to 158) of the choice reaction time in the group receiving general anaesthesia compared with the group receiving regional anaesthesia. This was the only significant difference between the two groups in the assessments of cognitive and functional competence. Eleven patients receiving regional anaesthesia and 12 receiving general anaesthesia reported that their memory and concentration were worse than before the operation, but this was not confirmed by testing. CONCLUSION: Cognitive and functional competence in elderly patients was not detectably impaired after either general or regional anaesthesia when attention was paid to the known perioperative influences on mental function.

Activities of Daily Living↗

Relationship between resonance and gas exchange during high frequency jet ventilation.

We have studied the relationship between gas exchange and mechanical frequency response during high frequency jet ventilation (HFJV) at 0.5-5.0 Hz in anaesthetized pigs. The mechanical gain curve showed a minimal "anti-resonant" response at 0.8 Hz (f1) and a maximal "resonant" response at 5.0 Hz (f2). This finding may be explained by modelling the thorax and abdomen as a system of coupled masses and compliances which undergo two different modes of forced oscillation in the frequency range studied. Gas exchange was optimal in the frequency range between the minimal and maximal responses. The tidal volumes produced were greater than anatomical deadspace, suggesting that gas transport was mainly convective in this range.

Animals↗

Measurement of entrainment ratio during high frequency jet ventilation.

We have measured tidal (VT), entrained (Ve) and "blowback" (Vbb) volumes during high frequency jet ventilation (HFJV) through a Mallinckrodt Hi-Lo Jet tracheal tube in anaesthetized patients. The above volumes were calculated by digital integration of the appropriate regions of flow curves derived from a pneumotachograph placed between the bias flow tubing and the tracheal tube. At a driving pressure of 1 bar, lung minute ventilation increased with increasing ventilatory frequency, whilst tidal volumes decreased. The contribution of entrainment to tidal volume (Ve/VT) remained constant, although the volumes entrained were relatively small and varied widely from subject to subject. Blowback volumes were considerable, especially at ventilatory frequencies used clinically (1-2 Hz). We conclude that it is not possible to entrain predictable concentrations of volatile agents from the low pressure bias flow during HFJV.

Adult↗

Wrist slashing in a detention center. Case report and review of the literature.

Suicides that occur in custody are rare and thus require extensive forensic analysis. Asphyxia by hanging is the most common means of suicide: at least 87.5% of successful suicides are committed in this way. A unique case of suicide in custody is presented in which a prisoner slashed his wrist with an eyeglass lens. The evidence and proceedings that led to this suicide are reviewed and the data are compared with known behavioral patterns. The world literature concerning suicide while incarcerated is reviewed.

Adult↗

Hearing aids for high-frequency hearing loss.

This cross-over study compares the relative benefits of a standard NHS contracted hearing aid with a high-frequency emphasis commercial aid in subjects with high-frequency hearing loss. Disability questionnaires and free-field speech-in-noise (FAAF II) tests were used to assess subjects unaided and after 6 weeks of wearing each aid. Total FAAF II test scores showed no significant difference with either aid, but analysis of frequency-specific subscores demonstrated less use of low-frequency information when using the high-frequency emphasis aid. Overall questionnaire responses relating to conversation showed more benefit with the high-frequency emphasis aid. Subjects generally preferred this aid, possibly due to less low-tone gain than the standard NHS aid.

Aged↗

Adhesion of Macroconidia to the Plant Surface and Virulence of Nectria haematococca.

To study spore attachment of the cucurbit pathogen Nectria haematococca (anamorph, Fusarium solani f. sp. cucurbitae), mutants with adhesion-deficient macroconidia were isolated. The adhesion-deficient mutants were selected after treatment with N-methyl-N' -nitro-N-nitrosoguanidine followed by repeated enrichment for macroconidia which did not attach to polystyrene. Two independently derived mutants produced macroconidia with an approximately 50% reduction in attachment to polystyrene and to zucchini fruits. When macroconidia were inoculated into wounded zucchini fruits, the adhesion-deficient mutants were as virulent as the wild-type strain. However, in disease assays in which macroconidia were deposited onto the surface of unwounded zucchini, the mutants were less virulent than the wild type. Thus, adhesion of N. haematococca macroconidia to its host surface appears to be a virulence factor.

Journal Article↗

Randomized trial of recombinant alpha 2b-interferon with or without indomethacin in patients with metastatic malignant melanoma.

alpha-Interferon has antitumor activity in a variety of malignancies but is frequently associated with unacceptable toxic side-effects. The routine use of agents potentially capable of reducing these side-effects has not been recommended out of concern for possible reductions in the therapeutic activity of interferon. We conducted a prospective randomized trial of alpha-interferon given with or without indomethacin to patients with malignant melanoma to determine what effect, if any, indomethacin might have on the toxic, immunomodulatory, and therapeutic properties of interferon in this disease. 53 patients were stratified according to performance status and randomized to receive alpha 2b-interferon, 20 million units per m2 i.v., 5 days per week for 4 weeks followed by 10 million units per m2 s.c. three times per week, either with or without indomethacin, 25 mg orally three times a day. The overall major response rate was 13% (three complete responders and three partial responders among 47 evaluable patients) and was the same on both arms. The mean maximal temperature elevation induced by interferon was significantly reduced (from 102.1 to 100.7, P = 0.0002) by indomethacin, but the incidence and severity of interferon-related fatigue, reduction in performance status, headache, depression, confusion, elevations in liver function tests, and myelosuppression were no different in either arm of the study. Indomethacin did not reduce the frequency of dose reductions for toxic side-effects and did not permit the administration of higher interferon doses. Peripheral blood natural killer activity was significantly enhanced in patients during maintenance therapy whether or not they received indomethacin. Indomethacin appeared to inhibit augmentation of natural killer activity during high dose induction therapy. Immunological changes did not correlate with response status. We conclude that indomethacin can reduce the fever associated with interferon therapy in patients with malignant melanoma without interfering with its therapeutic or chronic immunomodulatory activities. Since fever is rarely the dose-limiting toxicity of interferon, indomethacin is of marginal benefit to patients with malignant melanoma receiving interferon at the doses outlined in this study.

Adult↗

Effects on the lower oesophageal sphincter of cisapride given before the combined administration of atropine and neostigmine.

Twenty healthy female patients undergoing laparoscopy were allocated randomly to receive either cisapride 10 mg i.v. in 5% dextrose 20 ml or placebo 15 min before antagonism of residual neuromuscular blockade with atropine 1.2 mg and neostigmine 2.5 mg. Barrier pressure (BrP = lower oesophageal sphincter (LOS) pressure minus gastric pressure) increased significantly (by 25%) following cisapride, but not placebo, within 10 min of injection; following the combined administration of atropine and neostigmine, there was an abrupt decrease in mean BrP in the cisapride group from 37.0 (SEM 4.5) cm H2O to 24.1 (3.2) cm H2O (P less than 0.01) and in the control group from 26.6 (4.8) cm H2O to 19.9 (3.1) cm H2O (P less than 0.05) 2 min after injection. Subsequently, there was a small increase in BrP to values not significantly lower than control measurements. Thus the administration of cisapride before antagonism of neuromuscular blockade with atropine and neostigmine failed to block the adverse effect of atropine on the LOS.

Adult↗

Effect of a eutectic mixture of local anaesthetic agents (EMLA) on tourniquet pain in volunteers.

We studied the effects of EMLA on tourniquet pain in 10 healthy male volunteers. The tourniquet inflation time which was tolerated was significantly longer with EMLA (46.4 (SEM 3.5) min) compared with placebo (37.5 (2.7) min) (P less than 0.05). Linear analogue pain scores increased in both groups over the study period, but were significantly less in the EMLA group at 40 min (P less than 0.05). We conclude that tourniquet pain has a significant cutaneous component.

Adult↗

The M1 air crash. The demands placed on anaesthetic and intensive care services of two hospitals.

The M1 air crash provided an enormous challenge to the anaesthetic and intensive care services of the hospitals which admitted the survivors, many of whom had serious injuries. This account describes some of the problems which were encountered in two of the hospitals, details the workload imposed on the anaesthetists and the staff of the Intensive Therapy Units and identifies factors which, if improved, might advance the management of multiple casualties admitted from the scene of a major disaster.

Accidents, Aviation↗

The influence of anesthetic methods on mental function.

The effect of anesthetic methods on mental function has been the subject of much discussion and debate over many years. Although it is commonly recognized that sedative, narcotic, and anesthetic agents have observable effects on cerebral function at the time of administration, more subtle and less easily detectable effects may persist into the postoperative period. Identifying and describing the effects of these drugs requires reliable and reproducible methods of measurement. The tests used for evaluating the effect of anesthetic methods on mental function are reviewed. The roles played by intraoperative and postoperative factors and their possible involvement in detectable decrement in mental function are described. Early postoperative effects of anesthetic methods on cognitive function are discussed, and the evidence for prolonged changes in mental function following anesthesia (particularly in the elderly) is reviewed.

Anesthesia↗

The lower oesophageal sphincter in the first trimester of pregnancy: comparison of supine with lithotomy positions.

Measurement were made of gastric pressure (GP), lower oesophageal sphincter pressure (LOSP) and barrier pressure (BrP) in the supine and lithotomy positions in 17 healthy women undergoing termination of pregnancy in the first trimester. Values in the supine position were similar to those seen in non-pregnant subjects, but there was a significant reduction in LOSP and BrP in the lithotomy position unrelated to any change in intragastric pressure. It is concluded that the lithotomy position is associated with increased risk of regurgitation in early pregnancy.

Adolescent↗

Effects of beta-adrenoceptor antagonism on the cardiovascular and catecholamine responses to tracheal intubation.

The catecholamine and cardiovascular responses to laryngoscopy and tracheal intubation were studied in 20 patients who underwent elective gynaecological surgery and who were allocated randomly to receive either practolol 10 mg or saline intravenously prior to induction of anaesthesia. Anaesthesia was induced with fentanyl and thiopentone; atracurium was administered and the lungs were ventilated artificially with 67% nitrous oxide in oxygen. Tracheal intubation was performed when muscle relaxation was adequate. Arterial pressure, heart rate, plasma noradrenaline and adrenaline concentrations were measured before and after tracheal intubation. A significant increase in catecholamine concentrations occurred in both groups in response to tracheal intubation but the magnitude of the increase in adrenaline was greater in the practolol group. There were no significant differences in arterial pressure or heart rate changes between the groups. We conclude that pretreatment with practolol is of no value in the attenuation of the hypertensive response to direct laryngoscopy and tracheal intubation in previously normotensive patients.

Adult↗

Midwive's assessment of the upper sensory level after epidural blockade.

The ability of midwives to assess accurately the level of epidural blockade after a short period of instruction was examined. Seventy-two midwives estimated the upper level bilaterally in 100 patients, by detection of the loss of sensation to a cold stimulus. The midwife and anaesthetist were in complete agreement over the level of block in 71.5% of cases; the midwife overestimated the height of the block in 9.5% of cases, and underestimated in 19%. The midwife underestimated by three spinal segments in 1.5% of cases, and never by more. The technique was acceptable to patients and midwives alike. This procedure should enable safe management of obstetric analgesia, whoever administers top-ups; accurate detection of a block that recedes below therapeutic levels should facilitate earlier top-ups and thus reduce pain for the patient in labour.

Anesthesia, Epidural↗

Bile acid secretion and pool size during phenobarbital induced hypercholeresis.

An increase in bile flow after phenobarbital administration occurs in the rat and other species; however, the mechanism(s) of the choleretic effect is incompletely understood and the role of the increase in liver weight is controversial. We therefore measured bile flow, bile acid secretion and pool size in male Sprague-Dawley rats pretreated with phenobarbital (75 mg/kg/day) for 6 days; liver weight, liver cell volume and DNA content were also evaluated. Phenobarbital treatment increased liver weight and mean hepatocyte volume by 39 and 26%, respectively, while total DNA content did not change, thus indicating that the hepatomegaly results principally from hypertrophy rather than hyperplasia. Bile flow was significantly higher in treated rats when expressed per unit of body weight (64.6 +/- 2.4 (S.E.) vs 53.3 +/- 1.6 microliter/min/kg; P less than 0.05) but was unchanged when expressed per gram of liver (1.40 +/- 0.04 vs 1.37 +/- 0.06 microliter/min/g; P greater than 0.5). The initial bile acid secretion rate and pool size were both significantly reduced in the phenobarbital group compared to controls (1224.2 +/- 110.4 vs 1656.6 +/- 163.2 nmol/kg/min and 562.8 +/- 41.5 vs 814.3 +/- 78.3 mumol/kg; both P less than 0.05), whereas the basal synthetic rate was unchanged. These findings suggest that the enlarged, phenobarbital-treated hepatocyte produces more bile than the normal cell, despite the decreased secretion of bile acids. Therefore, the drug-induced choleresis involves a selective increase in the bile acid-independent fraction of bile flow.

Animals↗