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Biomedical subjects

R J Lewis

Publications and source records attributed to R J Lewis.

At least 163 records · Page 9Linked to original sources
PubMed1996

Quality-of-life in patients receiving implantable cardioverter defibrillators at or before age 40.

As the use of ICDs increases, more young patients will be eligible to receive these devices. Such patients may have different concerns than older patients who more commonly receive ICDs. We investigated quality-of-life issues in patients followed by the Yale electrophysiology service who were < or = 40 years old (mean = 28) at the time of ICD implant. Mean time since ICD placement was 3.3 years. Each patient received a modified SF-36 health questionnaire; 16 (88%) of 18 responded. Nine were women; ten were married. The highest education level attained was high school for 6 (37%), and college or beyond for 10 (63%). Ten patients were employed; eight held the same job before and after ICD placement. Four women conceived after ICD implantation; one experienced ICD discharge during pregnancy. All delivered healthy infants. All patients felt their health was good to excellent, with 6 (38%) reporting an improvement in health since ICD placement. All felt capable of performing the activities of daily living, while 68% engaged freely in moderate physical activities. All patients felt they were average to very attractive. However, 63% worried about how their clothes fit with the ICD. Three quarters of the patients felt the ICD interfered with social interactions, while 50% were concerned about sexual encounters. Thus, even though these young patients have body image concerns and may limit their activities to some degree, they are productive, active members of society who have benefitted from ICD placement.

Adolescent↗
PubMed1996

New-onset atrial fibrillation: when is admission medically justified?

OBJECTIVE: To determine 1) the percentage of patients with new-onset atrial fibrillation for whom admission is medically justified and 2) whether those patients for whom hospitalization is medically justified can be reliably identified in the ED. METHODS: A retrospective, descriptive cohort analysis was performed using consecutive adult patients with new-onset atrial fibrillation seen in an urban, county hospital ED from 1987 through 1992. Admissions were categorized as medically justified if patients were hypotensive (systolic blood pressure < 90 mm Hg), had a diagnosis other than new-onset atrial fibrillation that warranted admission, or had a significant complication during the ED stay or during the subsequent hospitalization. The need for admission was considered to have been apparent during the ED evaluation if the patient fulfilled the above criteria for a medically justified admission while in the ED. RESULTS: Admission was medically justified for 143 of the 216 patients (66%; 95% CI 60-71%) admitted to our institution. For those patients whose admissions were medically justified, the most common concurrent conditions were congestive heart failure and chest pain suggestive of myocardial ischemia. The need for admission was apparent during the ED evaluation for 140 of the 143 patients (98%; 95% CI 94-100%) whose admissions were categorized as medically justified. CONCLUSION: Approximately one third of patients with new-onset atrial fibrillation may not require admission to the hospital. Most patients (98%) for whom admission is medically justified can be reliably identified during the ED evaluation.

Acute Disease↗
PubMed1996

Health and respirable particulate (PM10) air pollution: a causal or statistical association?

Numerous studies have reported weak but statistically significant acute health effects of particulate air pollution. The associations are observed at levels below the current U.S. standard of 150 micrograms/m3 (24 hr). Health effects include acute increased mortality from cardiopulmonary conditions and acute morbidity such as hospital admissions for related diseases. We reviewed recent epidemiology studies to evaluate whether criteria for causality are met, and we conclude that they are not. The weak associations are as likely to be due to confounding by weather, copollutants, or exposure misclassification as by ambient particulate matter (PM). The results from the same metropolitan areas are inconsistent, and PM explains such a small amount of the variability in mortality/morbidity that the association has little practical significance. Finally, experimental chamber studies of susceptible individuals exposed to PM concentrations well above 150 micrograms/m3 provide no evidence to support the morbidity/mortality findings. None of the criteria for establishing causality of the PM/mortality hypothesis are clearly met at ambient concentrations common in many U.S. cities.

Air Pollutants↗
PubMed1995

Managed care.

Explore the source record for details and available documents.

Antitrust Laws↗
PubMed1995

In vivo and in vitro studies on the neurotoxic potential of 6-hydroxydopamine analogs.

In an attempt to determine which physical and biological properties could best be correlated with neurotoxic potential, seven analogs of 1-(2,4,5-trihydroxyphenyl)-2-aminoethane (1), better known as 6-hydroxydopamine, were synthesized and compared to 1 in a variety of ways both in vivo and in vitro. The analogs, in combination with the standard 1, include all eight of the 2,4,5-trisubstituted-phenyl derivatives of phenethylamine and alpha-methylphenethylamine in which the substitution is of the trihydroxy or aminodihydroxy form. Low (60 nmol) and high (300 nmol) intracerebroventricular doses of all analogs produced long-term (7 day) reduction of mouse whole brain norepinephrine (NE) and lesser depletions of dopamine (DA), and effects on serotonin were varied. The analog 1-(5-amino-2,4-dihydroxyphenyl)-2-aminopropane (8) was both more complete and more selective than the standard 1 in depleting NE. Using a histofluorometric glyoxylic acid method and Fink-Heimer silver degeneration stain, it was determined that overt neural degeneration was produced by 8. In vitro, the ease of oxidation of the eight analogs was found to be represented by a formal potential range of -130 to -212 mV vs SCE. However, there was no obvious relationship between ease of oxidation and the extent of monoamine depletion from mouse brain. Using kinetic analysis of synaptosomal accumulation of [3H]NE and [3H]DA, it was found that the standard 1 is more potent in its interaction with the DA uptake site (Ki = 12 +/- 0 microM) than the NE uptake site (Ki = 51 +/- 1 microM). A correlation analysis was used to determine that differences in NE and DA depletion by each analog could not be explained by differences in potency for in vitro uptake blockade. However, there was a correlation between the Ki for [3H]NE uptake blockade and the EC50 for synaptosomal release of preloaded [3H]NE for the eight analogs (R2 = 0.96; for log:log plot, R2 = 0.54), indicating that the results for these two in vitro tests both reflect interaction with the same NE neuronal membrane transport site. A similar correlation between Ki and EC50 was shown for all eight analogs using [3H]DA (R2 = 0.92; for log:log plot, R2 = 0.52), indicating interaction with the same DA neuronal membrane transport site. These findings demonstrate that there is no single property that can account for selectivity of action and/or potency of catecholamine neurotoxins related to 6-hydroxydopamine.

Animals↗
PubMed1995

Informed consent in emergency research. Consensus statement from the Coalition Conference of Acute Resuscitation and Critical Care Researchers.

OBJECTIVE: A coalition conference of acute resuscitation researchers was held to discuss the feasibility of applying current federal research regulations regarding informed consent to the emergency setting. This article presents consensus recommendations for regulatory changes for consent in emergency research. PARTICIPANTS: Representatives from the Society for Academic Emergency Medicine and the American Heart Association identified several professional organizations as stakeholders in this issue, including research, clinical, bioethics, legal, and patient advocacy groups. The Office for Protection From Research Risks (OPRR), the Food And Drug Administration (FDA), and staff from specific legislative offices were also invited to observe. Forty-three participants attended, including representatives from 12 professional organizations, five medical institutions, and the FDA and OPRR. This was a closed meeting. Participants were self-funded or sponsored by their professional organizations. EVIDENCE: Before the meeting, a draft of a position statement was developed by the conference organizers based on the current literature and discussions with experts in the field. This draft, copies of the current federal research regulations, and supporting articles were distributed before the conference. CONSENSUS PROCESS: Participants rotated through moderated discussion sessions to comment on subsections of the draft. Following discussion, a working draft was developed and distributed to each participant and represented organizational board for final review. All comments were considered in the final version of the document. CONCLUSIONS: We believe there are circumstances when it is not feasible to obtain prospective or proxy consent for enrollment into an emergency research protocol. In these circumstances, patients are vulnerable, not only to research risks, but also to being denied potentially beneficial therapy when there is no known effective treatment for their life-threatening condition. We offer recommendations that should be met when the critical nature of the illness or injury or the need to apply an investigational therapy rapidly precludes prospective consent for participation in emergency research.

Consensus↗
PubMed1995

Cooliatoxin, the first toxin from Coolia monotis (Dinophyceae).

Coolia monotis is a benthic dinoflagellate previously thought to be non-toxic. We describe a new toxin, named cooliatoxin, purified from cultures of a strain of C. monotis isolated from Australia. Cooliatoxin is likely a mono-sulphated, polyether toxin (M = 1,062; i.p. LD50 = 1 mg/kg in mice) that induces hypothermia and respiratory failure in mice after a pronounced delay period during which there are no obvious signs of intoxication. These signs in mice are similar to those reported for the shellfish toxin named yessotoxin and the molecular weight of cooliatoxin corresponds to the mono-sulphated form of yessotoxin, suggesting that cooliatoxin may be an analogue of yessotoxin. Cooliatoxin has no effect on the mouse phrenic nerve or diaphragm musculature in vitro but causes initial stimulation and subsequent block of unmylenated nerves in vitro. In isolated guinea pig left atria, cooliatoxin (above 20 nm) induced a slow developing concentration dependent sustained inotropic response. Propranolol or tetrodotoxin reversed the positive inotropic effects, indicating that the majority of the cooliatoxin induced response was mediated by stimulation of nerves associated with the atrial musculature, resulting in the release of noradrenaline. Cooliatoxin induced transient contractions in isolated guinea pig vas deferens preparations. Atria and vas deferens preparations were tachyphylactic to a second equivalent dose of cooliatoxin applied after the effects of the first dose had diminished. The observed in vitro effects of cooliatoxin on peripheral nerves are unlikely to account for the lethal effects in mice and a central action of this toxin is suspected.

Adrenergic beta-Antagonists↗
PubMed1995

Sub-nanomolar concentrations of ciguatoxin-1 excite preganglionic terminals in guinea pig sympathetic ganglia.

The actions of low concentrations of ciguatoxin-1 (CTX-1, 0.2-0.8 nM) in guinea-pig sympathetic ganglia have been analysed using intracellular recording techniques in vitro. The effects of CTX-1 were graded with concentration but sensitivity varied markedly between neurones in the same preparation. Other than an initial transient (approximately 10 min) depolarization of some ganglion cells accompanied by an increase in input resistance, passive electrical properties did not significantly differ from controls. Amplitude and threshold of action potentials evoked by depolarizing current and threshold, latency and form of the initial responses to nerve stimulation were also not affected. Exposure to CTX-1 generated marked increases in the frequency of spontaneous excitatory synaptic potentials which often occurred in bursts (15-66 Hz) of similar amplitudes. Single stimuli to incoming nerves produced repetitive synaptic responses arising from preganglionic, but not from peripheral afferent, axons. Following brief (< 5 min) exposure to CTX-1, these effects declined over 30 min but, after longer exposure (> 15 min), they persisted for several hours despite continuous washing. All activity generated by CTX-1 was significantly reduced or abolished by d-tubocurarine (10(-5)-10(-4) M), hexamethonium (10(-5) M), tetrodotoxin (10(-7)-10(-6) M), omega-conotoxin (10(-7) M), reduced Ca2+ (0.1 mM)/raised Mg2+ (10 mM), raised Ca2+ (6 mM) or raised Mg2+ (25 mM). The data suggest that CTX-1 activates preganglionic axons by modifying the voltage sensitivity of a subpopulation of Na+ channels. Effects on these unmyelinated axons occur at much lower concentrations than have been reported to affect myelinated ones. Many of the symptoms of ciguatera poisoning might be explained by activity in autonomic and perhaps other unmyelinated nerve terminals.

Animals↗
PubMed1995

Lophozozymus pictor toxin: a fluorescent structural isomer of palytoxin.

Purified Lophozozymus pictor toxin (LPTX) shares many properties similar to palytoxin (PTX). LPTX and palytoxin isolated from Palythoa caribaeorum (C-PTX) have similar mol. wts of approx. 2680 on ionspray mass spectrometry (MS). In addition, antibodies against PTX could recognize and bind LPTX. Mixed mode high-performance liquid chromatography (HPLC) of LPTX, C-PTX and H-PTX (isolated from Palythoa tuberculosa) showed a major PTX component common to all three with the characteristic PTX-like UV spectrum at a retention time (Rt) of 17 min. However, LPTX exhibits fluorescence but PTX of equivalent toxicity does not. LPTX showed a unique peak at Rt of approx. 22 min on mixed mode HPLC. In addition, LPTX and C-PTX showed different ion fragmentation patterns on MS/MS. These results suggest that LPTX and the palytoxins are structural isomers, containing at least one difference which gives rise to fluorescence in LPTX.

Acrylamides↗
PubMed1995

Simultaneously stapled lobectomy: a safe technique for video-assisted thoracic surgery.

Currently, techniques for video-assisted thoracic surgery are being borrowed from the open conventional thoracotomy. However, these same techniques have made video-assisted lobectomy difficult, burdensome, and even dangerous. Simultaneously stapled lobectomy (simultaneous stapling of all hilar structures in their natural anatomic configuration) has been performed successfully in 16 patients. Every attempted simultaneously stapled lobectomy is included. The lesions included 14 malignant tumors, one giant benign pulmonary cyst, and one large necrotizing granuloma. Three right upper lobes, one right middle lobe, six right lower lobes, four left upper lobes, and two left lower lobes were resected uneventfully. Nine adenocarcinomas, two large cell carcinomas, and three squamous cell carcinomas ranging in size from 2.5 to 5 cm were removed. Lung fissures, the hilum, and the mediastinum were explored for lymph nodes in each patient. Median operative time was 110 minutes. Average blood loss was less than 100 ml. Median hospitalization was 6 days, although eight patients were discharged between 3 and 5 days. Three patients had air leaks for an average of 14 days and one patient had mild subcutaneous emphysema for 5 days. There was no surgical mortality. Median follow-up is 15 months (range 8 to 20 months). Simultaneously stapled lobectomy is not meant to replace conventional lobectomy by open thoracotomy. Indications are cardiac or renal problems, contralateral chest wall paralysis, neurogenic deficiencies, adamant refusal to undergo open lobectomy, psychologic aberrations, and pain from a previous thoracotomy. Contraindications include absent fissures, enlarged matted invasive nodes, fibrotic hilum, central or bulky lesions, calcific bronchi, chest wall invasion, and lesions crossing a fissure. Precedent for this technique will be discussed. When used with discretion in carefully selected patients, in whom an open lobectomy would be contraindicated, simultaneously stapled lobectomy might eventually prove to be another available option. Time and further experience will be necessary to determine its true merits.

Adenocarcinoma↗
PubMed1995

Is admission medically justified for all patients with acute stroke or transient ischemic attack?

STUDY OBJECTIVES: To determine whether admission to an acute care hospital is medically justified for all patients with acute stroke or transient ischemic attack (TIA) and whether those patients for whom admission is justified can be identified in the emergency department. DESIGN: Retrospective descriptive study. SETTING: Urban county teaching hospital. PARTICIPANTS: Consecutive adult patients seen in an ED with nonhemorrhagic stroke, TIA, or hemorrhagic stroke. METHODS: Admission to an acute care hospital was deemed medically justified when the patient had any of the following criteria: another diagnosis that warranted admission, an inadequate home situation, altered mental status, or an adverse event during hospitalization or if they underwent hospital-based treatment that could not be provided on an outpatient basis. RESULTS: One hundred sixty-eight patients were seen during a 1-year period: 120 had an ED diagnosis of nonhemorrhagic stroke, 22 had a diagnosis of TIA, and 26 had a diagnosis of hemorrhagic stroke. One hundred sixty-one patients (96%) were admitted to our hospital. Sixty-three of the 161 admissions (39%) were retrospectively categorized as medically justified. Seventeen of the 63 patients (27%) whose admissions were medically justified developed the criteria justifying their admission after leaving the ED. CONCLUSION: The practice of admitting all patients with nonhemorrhagic stroke, TIA, or hemorrhagic stroke to an acute care hospital is medically justified because the ED evaluation cannot reliably identify patients whose condition will worsen.

Acute Disease↗
PubMed1995

Total knee arthroplasty in human immunodeficiency virus-infected hemophiliacs.

Twenty-six knee arthroplasties were performed in 15 patients with hemophilia A and human immunodeficiency virus infection from 1984 to 1991. Patient age range was 27 to 48 years. After an average follow-up period of 6.4 years (range, 1-9 years) all patients were alive and none of the implants had become infected. T4 lymphocyte counts showed some deterioration, which was not clinically significant. All of the patients were improved following surgery. Nineteen implants were rated excellent, four good, and three fair. Infection with human immunodeficiency virus did not adversely affect the clinical outcome of knee arthroplasty at follow-up periods up to 9 years.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Electrical activity in rat tail artery during asynchronous activation of postganglionic nerve terminals by ciguatoxin-1.

1. The effects of ciguatoxin-1 (CTX-1) on the membrane potential of smooth muscle cells have been examined in rat proximal tail arteries isolated in vitro. 2. CTX-1 (> or = 10 pM) increased the frequency of spontaneous excitatory junction potentials (s.e.j.ps). At 100-400 pM, there was also a marked and maintained depolarization (19.7 +/- 1.4 mV, n = 14, at 400 pM). 3. In 20-400 pM CTX-1, perivascular stimuli evoked excitatory junction potentials (e.j.ps) which were prolonged in time course relative to control. 4. Although threshold and latency of the e.j.p. were not affected by CTX-1 (< or = 400 pM), propagated impulses were blocked at > or = 100 pM. 5. The spontaneous activity and the depolarization produced by CTX-1 were reduced in the presence of Ca2+ (0.1 mM)/Mg2+ (25 mM), omega-conotoxin (0.1 microM) or Cd2+ (50-100 microM). 6. All effects of CTX-1 were abolished by tetrodotoxin (0.3 microM). 7. Raised Ca2+ (6 mM) reduced the depolarization and spontaneous activity produced by CTX-1. 8. In 400 pM CTX-1, the membrane repolarized (17 +/- 3.2 mV, n = 4) following the addition of phentolamine (1 microM). S.e.j.ps and e.j.ps were selectively abolished by suramin (1 mM), and the membrane repolarized by 1.3 +/- 1.6 mV (n = 4). 9. We conclude that CTX-1 releases noradrenaline and ATP by initiating asynchronous discharge of postganglionic perivascular axons. In 100-400 pM CTX-1, the smooth muscle was depolarized to levels resembling those recorded in this artery during ongoing vasoconstrictor discharge in vivo.

Animals↗