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Biomedical subjects

R J Lewis

Publications and source records attributed to R J Lewis.

At least 199 records · Page 11Linked to original sources
PubMed1993

VATS-Argon Beam Coagulator treatment of diffuse end-stage bilateral bullous disease of the lung.

Diffuse bullous disease of the lungs remains an unrelentless, debilitating, terminal disease. Intensive medical therapy can give transient relief of symptoms. Thoracotomy and resection has not always been successful and can be associated with an increased mortality and morbidity. Eight patients with end-stage bullous disease, unresponsive to medical therapy and not considered to be candidates for a thoracotomy, underwent unilateral video-assisted thoracic surgical ablation of bullae using the Argon Beam Coagulator. Six men and 2 women ranging in age from 28 to 71 years reported a decrease in dyspnea. Three patients restudied had an increase in forced expiratory volume in 1 second of 34%. Postoperatively, 7 patients had an air leak, pneumonia developed in 2 patients, and 3 patients had massive subcutaneous emphysema after parietal pleurectomy. Hospitalization averaged 13.6 days. All patients made a complete recovery, and each was subjectively improved. Steroid use decreased, oxygen requirements decreased, dyspneic episodes decreased, infections decreased, and endurance increased. In 3 patients with a limited follow-up evaluated postoperatively, video-assisted thoracic surgery and the Argon Beam Coagulator seemed to be beneficial for treating advanced, generalized bullous disease.

Adult↗
PubMed1993

Ciguatoxin-2 is a diastereomer of ciguatoxin-3.

Ciguatoxin-2, a major ciguatoxin present in the flesh and viscera of ciguateric fishes, has been shown by 1H nuclear magnetic resonance studies (2-dimensional homonuclear Hartman Hahn, nuclear Overhauser effect and decoupling difference experiments) to be a diastereomer of ciguatoxin-3, differing only in stereochemistry at carbon 52 (a quaternary carbon). This difference accounts for the significant changes in the chemical shift of resonances for protons in this region of ciguatoxin-2. Differences between ciguatoxin-1, -2 and -3 involve modifications at only one end of the ciguatoxins (ring M) and modest differences in potency, indicating that this ring contributes to, but is not critical for, high affinity binding of the ciguatoxins to voltage-dependent sodium channels. It is proposed that ciguatoxin-2 originates from a different precursor to the precursor (presumably gambiertoxin-4b) for ciguatoxin-1 and -3, and that both precursors are produced by a common biosynthetic pathway in Gambierdiscus toxicus.

Base Sequence↗
PubMed1993

Comparative action of three major ciguatoxins on guinea-pig atria and ilea.

The actions of pure ciguatoxin-1, ciguatoxin-2 and ciguatoxin-3 were assessed on the contractile activity of isolated guinea-pig left atria and ilea. Low concentrations of each ciguatoxin caused transient positive inotropy, whereas moderate concentrations induced transient and sustained positive inotropic phases. The transient positive inotropic phase was inhibited by tetrodotoxin or atenolol, indicating this phase stems from indirect effects of the ciguatoxins via the stimulation of intrinsic adrenergic nerves. On atria pretreated with atropine and alpha- and beta-adrenoceptor antagonists to block neural actions of the ciguatoxins, moderate concentrations of each ciguatoxin induced only slowly developing, sustained positive inotropy. ED50s for the indirect positive inotropic phase were 2.7 x 10(-11), 1.6 x 10(-10) and 1.4 x 10(-11) M and for the direct positive inotropic phase were 1.6 x 10(-10), 1.4 x 10(-9) and 1.5 x 10(-9) M for ciguatoxin-1, -2 and -3, respectively, indicating that their effects on neurons are 10-fold (ciguatoxin-1 and -2) to 100-fold (ciguatoxin-3) more potent than those directly on the myocardium. High concentrations of each ciguatoxin additionally induced sustained negative inotropy which could be reversed by lidocaine. On guinea-pig ilea, each ciguatoxin induced a transient contracture which could be abolished by atropine. Each ciguatoxin significantly reduced the contractile response of ilea to nicotine, without affecting the contractile response to acetylcholine. We conclude that ciguatoxin-1, -2 and -3 activate similarly the voltage-dependent Na+ channels in neuronal and myocardial tissues, but vary in their relative affinity for the Na+ channels in these tissues.

Acetylcholine↗
PubMed1993

Ciguatera and mannitol: in vivo and in vitro assessment in mice.

Mannitol (1 g/kg i.v.) is currently the treatment of choice for acute ciguatera, but confirmation of this treatment's apparent efficacy awaits further experimental or controlled clinical evidence. In mice, mannitol (1 g/kg i.v.) administered before or after i.p. ciguatoxin did not influence the signs of intoxication or the time to death. The effects of oral ciguatoxin differed from those following i.p. ciguatoxin, but again i.v. mannitol provided no detectable benefit. Development of hypothermia was rapid in mice receiving i.p. or oral ciguatoxin and was unaffected by i.v. mannitol. A sublethal i.p. dose of ciguatoxin initially retarded (day 0-4) but then accelerated (day 4-12) the growth of mice. Mannitol (i.v.) had no influence on these effects of ciguatoxin on the growth of mice. Ciguatoxin inhibited responses of isolated diaphragms to nerve stimulation (ED50 = 9 x 10(-11) M), while directly stimulated diaphragms were inhibited by five-fold higher concentrations. Mannitol (50 mM) added to the organ bath did not influence the ciguatoxin-induced inhibition of diaphragm responses to nerve stimulation in vitro. Responses of isolated diaphragm to nerve stimulation were normal in preparations removed from ciguatoxin-treated mice displaying pronounced dyspnoea (gasping). However, responses to nerve stimulation were reduced in preparations removed from mice immediately following death from ciguatoxin. Mannitol (i.v.) partially protected the phrenic nerve-diaphragm from this effect of ciguatoxin in vivo. We conclude that the lethal effects of ciguatoxin in mice probably stem from a central action, and suggest that species differences may account for the absence of any marked beneficial effect of i.v. mannitol in the mouse model for ciguatera in humans.

Animals↗
PubMed1993

Recovery of ciguatoxin from fish flesh.

A mouse bioassay, validated for the quantification of ciguatoxin in up to 20 mg of ether extract from fish flesh, revealed that 63 +/- 14% of spiked ciguatoxin was recovered using a standard extraction procedure. Except for extracts from the least toxic of ciguateric fish (0.1-0.5 nmol ciguatoxin-1/kg fish), signs in mice of intoxication by ciguatoxin (hypothermia to below 33 degrees C as well as at least severe diarrhoea or lachrymation or hypersalivation) could be distinguished from the toxic reaction that follows administration of ciguatoxin-free ether extracts. Ciguatoxin recovery was similar for four variants of the ether-water partition, with the 2 M NaC1/ether partition extracting half the contaminants. The method described is selective for ciguatoxin and could be used to quantify natural levels ciguatoxin in the flesh of fish in the absence of a validated in vitro test.

Animals↗
PubMed1993

Origin and transfer of toxins involved in ciguatera.

1. Ciguatera is a disease caused by sodium channel activator toxins and results from the consumption of warm water fish contaminated by the ciguatoxin class of polyether toxins. 2. Other toxins, including okadaic acid and maitotoxin, have no proven role in causing human illness associated with ciguatera. 3. Ciguatera often affects only a discrete region of a reef, with flare-ups of ciguatera being both temporally and spatially unpredictable. 4. The ciguatoxins likely arise through the biotransformation and acid-catalysed spiroisomerisation of gambiertoxin-4A produced by Gambierdiscus toxicus and it is unlikely that other toxic benthic dinoflagellates are involved. 5. Events leading to a ciguatera outbreak are initiated by environmental and genetic factors that favour the proliferation of gambiertoxins, with an apparent role for anthropomorphic effects; however, the precise factors involved are yet to be determined. 6. The gambiertoxins and/or ciguatoxins are transferred from the benthos to herbivorous species (fish, invertebrates etc) and then to carnivorous fish via marine food chains. 7. Factors influencing the concentration of ciguatoxins that accumulate in fish include the rate of dietary intake, the efficiency of assimilation, the degree and nature of any toxin biotransformation, the rate of depuration, and the rate of growth of fish.

Animals↗
PubMed1993

An introduction to the Bayesian analysis of clinical trials.

Although most clinical trials comparing therapies are analyzed using classical hypothesis testing and P values, such methods do not yield the information most useful to the clinician, that is, the probability that one treatment is more efficacious than another. Bayesian inference can yield this probability but only if we quantify our prior beliefs about the possible efficacies of the treatments studied. This article gives a brief introduction to Bayesian methods and contrasts them with classical hypothesis testing. It shows that the quantification of prior beliefs is a common and necessary part of the interpretation of clinical information, whether from a laboratory test or published clinical trial. Advantages of Bayesian analysis over classical analysis of clinical trials include the ability to incorporate prior information regarding treatment efficacies into the analysis; the ability to make multiple unscheduled inspections of accumulating data without increasing the error rate of the study; and the ability to calculate the probability that one treatment is more effective than another. Because it is likely that Bayesian methods will be used more often in the analysis of future clinical trials, investigators and readers should be aware of the two schools of statistical thought and the strengths and weaknesses of each.

Bayes Theorem↗
PubMed1993

Clinical predictors of post-traumatic seizures in children with head trauma.

STUDY OBJECTIVES: To determine the clinical characteristics associated with early post-traumatic seizures in children with head trauma. DESIGN, SETTING, AND TYPE OF PARTICIPANTS: Retrospective chart review; urban trauma center/pediatric emergency department. Trauma patients aged 3 months to 15 years given discharge diagnosis ICD-9-CM codes indicating head trauma and seen from 1988 to 1990 were eligible for the study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 194 patients, 96% suffered blunt trauma and 53% had a loss of consciousness. Fifty-one percent of 141 computed tomography (CT) scans of the head were abnormal, most frequently demonstrating skull fractures (34%), subdural hematomas (15%), and cerebral contusions (14%). Eighteen patients (9.3%) suffered post-traumatic seizures. A loss of consciousness, a low Glasgow Coma Scale (GCS) score (3 to 8), and an abnormal CT scan were associated with post-traumatic seizures (P < .02, .001, and .02, respectively). However, only a low GCS score was predictive of post-traumatic seizures when these factors were considered simultaneously (P < .001), with 38.7% of patients with low GCS scores suffering post-traumatic seizures and 3.8% of patients with high GCS scores suffering post-traumatic seizures. In children with low GCS scores, treatment with phenytoin was associated with a decrease in post-traumatic seizures. CONCLUSION: In the pediatric head trauma patient, a GCS score of 3 to 8 appears to be predictive of post-traumatic seizures. The data from this retrospective study are consistent with the hypothesis that prophylactic phenytoin reduces post-traumatic seizures in the pediatric head trauma patient with a low GCS score.

Adolescent↗
PubMed1993

An introduction to the use of interim data analyses in clinical trials.

During a controlled clinical trial, data accumulate that contain information on the relative efficacy of the two treatments, yet these data often are not inspected or analyzed until the planned sample size has been reached and the trial has been terminated. This type of fixed-sample-size trial design, with a single terminal data analysis, has the ethical disadvantage that more patients than are necessary to obtain a reliable result may be randomized to the less efficacious treatment, whichever one that turns out to be. Thus, it often is desirable to schedule one or more analyses of the data, to be conducted before planned termination, to see if a reliable conclusion may be drawn from the data and the trial terminated early. Such analyses are called interim analyses. When interim analyses occur after each of severe relatively large groups of patients, the trial is called a group-sequential trial. Interim data analyses must be planned in advance to avoid increasing the risk of committing a Type I error and to achieve adequate power. This article introduces the statistical issues involved in the planning of interim data analyses and the design of group-sequential clinical trials.

Bias↗
PubMed1993

Isolation and purification of Aeromonas sobria cytotonic enterotoxin and beta-haemolysin.

Aeromonas sp., grown in tryptone soya broth supplemented with yeast extract, 0.6%, pH 7.5, and incubated with agitation at 100 oscillations/min for 15 h at 37 degrees C produced optimal amounts of beta-haemolysin and cytotonic enterotoxin. More prolonged incubation resulted in the loss of enterotoxic activity and anion exchange chromatographic analysis indicated the presence of a moiety capable of breaking down the toxin. Anion exchange fast protein liquid chromatography resulted in a single peak of haemolytic activity and two peaks with enterotoxic activity. The cytotonic enterotoxin was purified from the fraction most active in the infant mouse assay; the second peak, which did not cross-react immunologically, may represent a second cytotonic enterotoxin. Neither peak was observed in the chromatographic fractions of filtrates from strains devoid of activity in the infant mouse assay. Purified enterotoxin, estimated to have a mol. wt of 15 kDa by SDS-PAGE, caused fluid accumulation in the infant mouse assay, was non-haemolytic to rabbit erythrocytes, caused an increase in cAMP activity in tissue culture cells and did not cross-react immunologically with components of cholera toxin or the whole toxin. Purified beta-haemolysin had an estimated mol. wt of 55 kDa, lysed rabbit erythrocytes and did not cause fluid accumulation in the infant mouse test.

Aeromonas↗
PubMed1992

One hundred consecutive patients undergoing video-assisted thoracic operations.

Video-assisted thoracic surgery is a new modality that allows visualization of and access to the intrathoracic organs without making a thoracotomy incision. One hundred consecutive patients underwent 113 thoracic procedures using this technique. Eight wedge resections for metastatic lesions, 6 pericardial windows, 1 bronchogenic cystectomy, 4 explorations of the aortopulmonary window, 1 decortication, 5 pleural scleroses, 8 bullous ablations, 25 lung biopsies, 19 wedge resections for carcinoma, 9 explorations of the thorax, 3 lobectomies, 1 esophageal cystectomy, 14 wedge resections for benign lesions, 4 pleurectomies, 1 excision of a neurogenic tumor, 3 mediastinal explorations, and 1 imaged axillary dissection were performed. There was no mortality. Ten patients had complications from which they recovered completely. Patients undergoing video-assisted thoracic operations seem to have reduced postoperative pain, shorter hospitalization, and quicker recovery times. Currently, this new modality appears to have beneficial value for patients; however, only further experience will determine its true merits.

Adolescent↗
PubMed1992

Imaged thoracic lobectomy: should it be done?

Imaged thoracic surgery is a new modality that is rapidly gaining acceptance from thoracic surgeons. Procedures that traditionally required a thoracotomy can now be done successfully using this technique in some patients. Three patients with primary carcinoma of the lung have undergone lobectomy using imaged thoracic surgery.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed1992

Imaged thoracoscopic surgery: a new thoracic technique for resection of mediastinal cysts.

Previously, intrathoracic organs have been approached by either thoracotomy or thoracoscopy. A technique, imaged thoracoscopic surgery, using video optics and projection of images on a screen provides another option for the thoracic surgeon. Two patients with mediastinal cysts, one bronchogenic and one esophageal, underwent surgical removal using imaged thoracoscopic surgery. Postoperative pain was markedly reduced, hospitalization shortened, and recovery accelerated. Numerous complex surgical procedures can be performed using imaged thoracoscopic surgery.

Adult↗
PubMed1992

Action of ciguatoxin on human atrial trabeculae.

This report describes the action of ciguatoxin-1, the major ciguatoxin present in fishes that cause ciguatera, on the contractile activity of human cardiac musculature. Ciguatoxin-1 caused a large, sustained and concentration-dependent positive inotropy in human atrial trabeculae that were obtained during coronary artery bypass surgery from otherwise healthy hearts. Atenolol (a beta 1-adrenoceptor selective antagonist without local anaesthetic-type activity) or low concentrations of tetrodotoxin abolished the positive inotropy caused by ciguatoxin-1, indicating that ciguatoxin-1 stimulated neural elements present in this tissue to release noradrenaline. The positive inotropic action of ciguatoxin-1 did not stem from a significant direct action on myocardial voltage-dependent sodium channels, nor did it stem from significant alpha 1- or beta 2-adrenoreceptor stimulation. Ciguatoxin-1 caused positive inotropy in preparations stimulated at between 0.02 and 2.0 Hz. Mannitol, currently the treatment of choice for ciguatera, did not significantly reverse the positive inotropy induced by ciguatoxin-1 in human atrial trabeculae.

Adult↗
PubMed1992

Multiple ciguatoxins in the flesh of fish.

Most cases of ciguatera (fish poisoning) result from consumption of the flesh of fishes contaminated with ciguatoxin(s); however, the relatively low toxicity of ciguateric fish flesh has hindered attempts to identify these ciguatoxin(s). Utilising high performance liquid chromatography, mass spectroscopy and mouse bioassay signs we have determined that ciguatoxin-1 (MH+ m/z = 1112), ciguatoxin-2 and ciguatoxin-3 are the major ciguatoxins present in the flesh of ciguateric fish. Ciguatoxin-1, -2 and -3 were present in yields of 0.19, 0.09 and 0.02 microgram/kg flesh, respectively, in Scomberomorus commersoni; 0.08, 0.09 and 0.07 microgram/kg flesh, respectively, in Plectropomus spp. and; 0.67, 0.61 and 0.06 microgram/kg flesh, respectively, in Pomadasys maculatus. Two minor toxins, which may be further oxidised analogues of ciguatoxin-1 and ciguatoxin-2, were also identified. The presence of multiple ciguatoxins in fish flesh has important consequences for the detection of ciguateric fish and may be a contributing factor to the observed variability in the symptoms of ciguatera.

Animals↗
PubMed1992

Ciguatoxins are potent ichthyotoxins.

The ciguatoxins are lipid soluble polyether compounds which have structural and biochemical features in common with the brevetoxins. Pure ciguatoxin-1, ciguatoxin-2 or brevetoxin-2 added to water containing Gambusia affinis induced similar signs, including pronounced opercular movement and uncoordinated swimming preceding death. The estimated LD50s (48 hr) to G. affinis for ciguatoxin-1, ciguatoxin-2 and brevetoxin-2 were 0.5, 2.1 and 10 nmoles/litre, respectively, indicating that the ciguatoxins were up to 20-fold more potent than the brevetoxins in this assay. Previous studies reveal that the ciguatoxins are more potent than the brevetoxins in both i.p. lethality to mammals and affinity for voltage-dependent sodium channels. However, relative to their affinity for the voltage-dependent sodium channel, brevetoxin-2 is 4-fold more potent to fish than the ciguatoxins, whereas the ciguatoxins are up to 11-fold more potent to mice than brevetoxin-2. This study found that only 3.4% of administered ciguatoxin-1 was accumulated by G. affinis. Ciguatoxin-1 may be biotransformed by G. affinis. The lethal effects of the ciguatoxins in fish may impose an upper limit on the levels of ciguatoxin carried by fish, which could contribute to the low incidence of human fatality associated with ciguatera.

Animals↗
PubMed1992

Treatment of prolonged ventricular fibrillation. Immediate countershock versus high-dose epinephrine and CPR preceding countershock.

BACKGROUND: Early countershock of ventricular fibrillation has been shown to improve immediate and long-term outcome of cardiac arrest. However, a number of investigations in the laboratory and in the clinical population indicate that immediate countershock of prolonged ventricular fibrillation most commonly is followed by asystole or a nonperfusing spontaneous cardiac rhythm, neither of which rarely respond to current therapy. The use of epinephrine in doses greater than those currently recommended has recently been shown to improve both cerebral and myocardial perfusion during cardiopulmonary resuscitation (CPR). The purpose of this study was to compare cardiac resuscitation outcome between immediate countershock of prolonged ventricular fibrillation with high-dose epinephrine therapy and conventional CPR before countershock of prolonged ventricular fibrillation in a canine model. METHODS AND RESULTS: After sedation, intubation, induction of anesthesia, and instrumentation, ventricular fibrillation was electrically induced in 28 dogs. After 7.5 minutes of ventricular fibrillation, animals were randomly allocated to two treatment groups: group 1, immediate countershock followed by recommended advanced cardiac life support (ACLS) interventions, or group 2, 0.08 mg/kg epinephrine and manual closed-chest CPR before countershock and ACLS. In both groups, ACLS was continued until a spontaneous perfusing rhythm was restored or for 20 minutes (total arrest time, 27.5 minutes). A spontaneous perfusing rhythm was restored in three of 14 group 1 animals and in nine of 14 group 2 animals (p = 0.014 by sequential analysis method of Whitehead). Coronary perfusion pressure (aortic minus right atrial pressure during CPR diastole) before countershock was significantly greater in group 2 (21 +/- 7 mm Hg) when compared with mean circulatory pressure in group 1 (9 +/- 8, p less than 0.01). CONCLUSIONS: The findings of this study suggest that a brief period of myocardial perfusion before countershock improves cardiac resuscitation outcome from prolonged ventricular fibrillation.

Animals↗