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Biomedical subjects

R M Jones

Publications and source records attributed to R M Jones.

At least 19 recordsLinked to original sources

Hepatitis due to nitrofurantoin.

OBJECTIVE: To report three cases of hepatitis related to the use of nitrofurantoin. CLINICAL FEATURES: Two patients who had been taking nitrofurantoin for several years, presented with severe liver failure. In both, the drug had been continued despite evidence of liver injury. A third patient presented with acute hepatitis after six weeks of nitrofurantoin therapy. INTERVENTION AND OUTCOME: One of the patients with liver failure died and the other underwent a successful liver transplantation. The third patient recovered after withdrawal of the drug. CONCLUSION: These cases emphasise the potential for serious hepatic reactions with nitrofurantoin, the danger of continuing the drug once liver damage has occurred and the need for careful monitoring of liver function during long-term therapy.

Adult

Oxygen-derived free radicals and hemolysis during open heart surgery.

Reperfusion injury occurs during open-heart surgery after prolonged cardioplegic arrest. Cardiopulmonary bypass also is known to cause hemolysis. Since reperfusion of ischemic myocardium is associated with the generation of oxygen free radicals, and since free radicals can attack a protein molecule, it seems reasonable to assume that hemolysis might be the consequence of free radical attack on hemoglobin protein. The results of this study demonstrated that reperfusion following ischemic arrest caused an increase in free hemoglobin and free heme concentrations, simultaneously releasing free iron and generating hydroxyl radicals. In vitro studies using pure hemoglobin indicated that superoxide anion generated by the action of xanthine oxidase on xanthine could release iron from the heme ring and cause deoxygenation of oxyhemoglobin into ferrihemoglobin. This study further demonstrated that before the release of iron from the heme nucleus, oxyhemoglobin underwent deoxygenation to ferrihemoglobin. The released iron can catalyze the Fenton reaction, leading to the formation of cytotoxic hydroxyl radical (OH.). In fact, the formation of OH. in conjunction with hemolysis occurs during cardiac surgery, and when viewed in the light of the in vitro results, it seems likely that oxygen-derived free radicals may cause hemolysis during cardiopulmonary bypass and simultaneously release iron from the heme ring, which can catalyze the formation of OH..

Cardiac Surgical Procedures

Water balance and lung fluids in rats at high altitude.

A disturbed water and electrolyte homeostasis is not generally held to be a primary mechanism in the pathogenesis of acute mountain sickness (AMS) and high altitude pulmonary edema (HAPE), but the association of oliguria and weight gain with AMS and HAPE has led to the hypothesis that water retention may be a facilitative mechanism, possibly caused by an effect of hypoxia to release antidiuretic hormone (ADH). To examine the problem, normal Long-Evans rats (N) and the strain with congenital diabetes insipidus (DI) were exposed to hypobaric hypoxia (0.5 atm) for 4 days, and fluid balance in the whole animals and in their lungs was studied. Both strains reduced water intake and were oliguric on acute exposure, but the N rats gained body weight and increased lung water, while the DI rats increased neither body weight nor lung water. Neither strain increased lung blood at high altitude. The oliguria in the DI rats could not have been due to a release of antidiuretic hormone, and was attributed to the diminished water intake in both strains. The protection against HAPE in the DI rats was probably due to their more severe dehydration that exists already in normoxia, and its further increase in hypoxia, compared with N rats.

Altitude Sickness

Recovery characteristics using isoflurane or propofol for maintenance of anaesthesia: a double-blind controlled trial.

We studied 114 female patients (ASA 1 or 2) who were within 20% of ideal body weight and who were scheduled to undergo gynaecological laparoscopy which required supplementation with an opioid (groups IA and PA), or dental procedures which did not require opioid supplementation (groups IO and PO). A computerised package of psychomotor tests was performed before surgery. Anaesthesia was induced with propofol 2.5 mg.kg-1 and all patients received atracurium 0.3 mg.kg-1 and 67% nitrous oxide in oxygen. Patients in group IA received isoflurane 1% (inspired), and alfentanil 10 micrograms.kg-1 as a bolus and 10 micrograms.kg-1.h-1 as an infusion. Patients in group PA received propofol 9 mg.kg-1.h-1 as an infusion, decreasing to 6 mg.kg-1.h-1 after 15 min, together with alfentanil 10 micrograms.kg-1.h-1. Patients in groups IO and PO received isoflurane and propofol in the regimens described for groups IA and PA, but without alfentanil. Recovery was assessed by a blinded observer who recorded times to awakening (eye opening) and orientation (giving date of birth), and who repeated the psychomotor tests at 1, 3 and 5 h. Linear analogue scales of mood, nausea and pain were obtained and other side effects were noted in the succeeding 48 h. A matched control group of 25 females (who were not anaesthetised) underwent psychomotor testing on four occasions in order to assess the 'learning effect' of repeated recovery testing. The analysis of recovery tests did not assume a normal distribution.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Mivacurium chloride: a study to evaluate its use during propofol-nitrous oxide anaesthesia.

We assessed the neuromuscular and cardiovascular effects of mivacurium chloride, a neuromuscular blocking agent, in 33 patients during propofol-nitrous oxide anaesthesia. Neuromuscular function was assessed with supramaximal stimuli of the ulnar nerve, using surface electrodes at the wrist, with repeat trains of four. Mivacurium given as a bolus of 0.15 mg.kg-1 (ED95 x 2) was found to be haemodynamically stable. Intubating conditions assessed at 2 and 2.5 min were either good or excellent. All patients developed a block of 100% in a mean (SD) time of 105 (34) s. There were mean (SD) intervals of 12 (2.4) min before the reappearance of the first twitch of the train of four (T1) following the bolus dose, and 15.8 (3.1) min for the T1 to reach 25% of its control value (TC). Seventeen patients received an infusion of mivacurium to maintain neuromuscular blockade (T1:TC 10-20%) with a mean (SD) infusion rate of 6.9 (2.2) micrograms.kg-1.min-1. Recovery from neuromuscular blockade was assessed with spontaneous offset or augmented with edrophonium following either the initial bolus or an infusion. Following a bolus it took a mean (SD) of 26.2 (3.7) min for the fourth twitch of the train of four (T4):T1 ratio to reach 0.7. In patients receiving an infusion with spontaneous offset it took a mean (SD) time of 12.0 (2.2) min to reach the T4:T1 ratio of 0.7 from a T1:TC value of 8.8. Edrophonium significantly decreased the recovery time in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

A putative anaerobic coproporphyrinogen III oxidase in Rhodobacter sphaeroides. I. Molecular cloning, transposon mutagenesis and sequence analysis of the gene.

A mutant of Rhodobacter sphaeroides, N1, has been isolated which is incapable of photosynthetic growth and, instead of synthesizing bacteriochlorophyll, N1 excretes coproporphyrin III into the growth medium. Using conjugative gene transfer, several clones were isolated from a R. sphaeroides gene library which restored normal pigment synthesis and photosynthetic growth to N1. Using transposon Tn5 mutagenesis, the gene was located to a 1.05 kb EcoRI fragment. Sequence and transcription analysis defined the position and expression of an open reading frame of approximately 920 bp, which is proposed as the anaerobic coproporphyrinogen III oxidase dedicated to bacteriochlorophyll biosynthesis.

Amino Acid Sequence

Perforated peptic ulcer. A further application of laparoscopic surgery.

A case of perforated peptic ulcer in a patient with cervical myelopathy due to osteophyte cervical canal stenosis complicated by the sudden onset of abdominal pain is described. Diagnostic laparoscopy revealed a perforated peptic ulcer in the anterior wall of the duodenal cap. Laparoscopic treatment was suitable for this condition.

Aged

An investigation of cognitive style and alcohol/work-related problems among Naval personnel.

This study examines the relationship between cognitive style (i.e., information, normative, and diffuse orientation, and commitment) and alcohol/work-related problems. A random sample of Naval personnel (n = 2000) with less than two years of service toward their first enlistment was sent a questionnaire to assess cognitive style [1] and alcohol/work-related problems. A total of 899 respondents (45.0%) returned their questionnaires. Findings support prevention strategies that incorporate problem-solving, decision-making, and coping strategies, particularly among participants who employ diffuse problem-solving/coping strategies (lack of exploration and commitment, avoidance of problems). Correlations between cognitive style and alcohol/work-related problems are theoretically compatible. Diffuse orientation scores are positively related to both alcohol- and work-related problems, while norm and information orientation scores are negatively related to both measures. Collectively, cognitive style measures explain 11.4 percent of the variability in alcohol-related problems, and 14.0 percent of the variability in work-related problems.

Adaptation, Psychological

Preconditioning of heart by repeated stunning: adaptive modification of myocardial lipid membrane.

Recent studies indicate that preconditioning of a heart by repeated stunning protects it from subsequent ischemic injury. Such myocardial preservation is likely to be due to adaptive modification of lipid composition and dynamic structure of cellular membrane. To test this hypothesis, swine heart was subjected to four episodes of 5 min stunning by LAD occlusion, followed by 10 min of reperfusion after each stunning. Heart was then made regionally ischemic for 60 min by LAD occlusion, followed by 6 h reperfusion. Control heart was perfused for 60 min, followed by 60 min ischemia and 6 h reperfusion. Free fatty acids (FFA) accumulated in control heart during ischemia as expected, which was further enhanced by reperfusion. The FFA level was also enhanced during ischemia in stunned myocardium. However, this FFA level was almost restored during reperfusion. The levels of polyunsaturated fatty acids (PUFA) such as oleate, linoleate, and arachidonate followed a similar pattern. Membrane fluidity, monitored by fluorescence polarization, was decreased during ischemia and reperfusion in the unstunned heart, with the corresponding increase in microviscosity. The increased microviscosity was significantly reduced by stunning. Since FFA are presumably generated from membrane phospholipids, these results suggest that stunning may cause the incorporation of a greater proportion of PUFA in membrane phospholipids, leading to preservation of membrane phospholipids and maintaining the membrane fluidity, which may be at least partially responsible for the attenuation of ischemic reperfusion injury.

Adaptation, Physiological

Enhanced responses to endothelin during perfusion of ischemic myocardium. Myocardial response to endothelin.

Although endothelin perfusion at 50 pM did not reduce the coronary flow, at 200 pM, it reduced the coronary flow to a similar extent in both normal and ischemic hearts. Endothelin at 50 pM concentration enhanced the myocardial levels of inositol-1,4,5-triphosphate (IP3) and diacyl glycerol (DG) in ischemic, but not in normal, hearts. On the other hand, endothelin at 50 pM concentration enhanced the activities of membrane protein kinase C (PKC) and calmodulin dependent (CaM-PK) kinases in normal, but not in ischemic, hearts. The corresponding loss of cytosolic PKC, but not of CaM-PK, suggests a translocation of PKC and an activation of CaM-PK by endothelin. These results suggest that pM concentrations of endothelin activate membrane kinases in normal hearts and enhance PIP2, breakdown in ischemic hearts. The greater CK release and myocardial levels of nonesterified fatty acids by 200 pM concentrations of endothelin in ischemic hearts, as compared to control hearts, suggests that: (1) the myocardial cellular injury and phospholipid breakdown induced by pM concentrations of endothelin are enhanced during reperfusion; and (2) both IP3 and membrane kinase (PKC and CaM-PK) dependent biochemical cascades of reaction, rather than kinases alone, may be involved in the endothelin-induced myocardial cellular injury.

Analysis of Variance

Colon carcinoma immunoscintigraphy by monoclonal anti-CEA antibody labeled with gallium-67-aminooxyacetyldeferroxamine.

Previous experimental results in nude mice showing that radiolabeling the monoclonal antibody anti-CEA 35 with 67Ga-aminooxyacetyldeferroxamine could give better tumor localization than radioiodination prompted us to initiate the present clinical study. The 67Ga-labeled antibody anti-CEA 35 (185 MBq, 0.7-1.7 mg) was injected preoperatively into 14 patients for colorectal carcinoma imaging. The same antibody labeled with 125I (3.7 MBq, 0.25 mg) was injected simultaneously to compare the 67Ga and 125I dose recoveries in surgical specimens. Twelve of 14 primary tumors gave a positive 67Ga scintigraph. The mean %ID/g recovered in all tumors 3-9 days after injection was significantly higher for 67Ga (0.019%) than for 125I (0.005%) (p < 0.001, paired t test). The tumor-to-normal tissue ratios were generally higher for 67Ga, with the exception of liver. We conclude that 67Ga-aminooxyacetyldeferroxamine improved immunoscintigraphy outside the liver, particularly in the pelvic region. We also show that deferroxamine infusion accelerates the excretion of 67Ga in eight patients and propose that this could lead to further improvement of immunoscintigraphy.

Aged

Preconditioning of heart by repeated stunning. Adaptive modification of antioxidative defense system.

Previous studies demonstrated that preconditioning of a heart by repeated stunning can reduce the cellular injury to the heart from subsequent acute ischemic insult. To examine the possible biochemical mechanism for such myocardial preservation afforded by preconditioning, swine heart was subjected to four episodes of 5 min. stunning by occluding the left anterior descending coronary artery (LAD), followed by 10 min. of reperfusion after each stunning. Heart was then made regionally ischemic for 60 min. by LAD occlusion, followed by 6 hrs. reperfusion. Control heart was perfused for 60 min., followed by 60 min. ischemia and 6 hrs. reperfusion. The results of our studies indicated the stimulation of a number of antioxidative enzymes, including Mn-superoxide dismutase (Mn-SOD), catalase, glutathione peroxidase, and glutathione reductase, after repeated stunning and reperfusion. In addition, a number of new proteins were expressed after preconditioning the heart, including some oxidative-stress related proteins and 72 kDa heat-shock protein. These results suggest that preconditioning of a heart by repeated stunning may lead to strengthening of the oxidative defense system of the heart, which is likely to play a role in myocardial preservation during subsequent ischemic and reperfusion injury.

Adaptation, Physiological