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Biomedical subjects

R Lewis

Publications and source records attributed to R Lewis.

At least 181 records · Page 10Linked to original sources
PubMed1992

Pharmacokinetic strategies for cyclosporin therapy in organ transplantation.

Marked interindividual variations in cyclosporin (CsA) produce disparate clinical results in organ transplant recipients. In an attempt to eliminate marked deviations of insufficient or excessive CsA concentrations consequent to the administration of uniform drug doses, test dose pharmacokinetics were performed on each potential organ transplant candidate. An intravenous 3 mg/kg test dose delivered over 3 h proved to be readily performed, namely 53% perfect studies, and relatively reliable, namely 73% of observed concentrations within 10% of the predicted values. Furthermore, the use of CsA doses predicted by pretransplant studies reduces the incidence of delayed graft function, early rejection episodes and transplant loss. The oral test dose study predicted a suitable amount of CsA to achieve sufficient gastrointestinal absorption but was less accurate than the iv prediction method: namely, 40% of observed post-transplant concentrations were within 10% of the predicted target value. Furthermore, patients who received oral doses predicted by the test dose strategy showed no improvement in the incidence of acute rejection episodes between 7 and 60 days, and only modestly improved serum creatinine values. The lower accuracy of predictions from oral test dose studies may reflect the impact of non-linear oral (as opposed to iv) drug pharmacokinetics, of variable diet, and/or of altered postoperative gastrointestinal function.

Administration, Oral↗
PubMed1992

A trial of the prostaglandin E1 analogue, enisoprost, to reverse chronic cyclosporine-associated renal dysfunction.

Cyclosporine (CYA) reduces the renal synthesis of prostaglandins of the E series (PGE). Analogue of PGE1 have been shown to mitigate the vasoconstriction and abnormal renal function of experimental acute CYA nephrotoxicity. We examined the hypothesis that the orally bioavailable PGE analogue enisoprost (EP) would improve renal function in renal transplant recipients chronically exposed to CYA. In a randomized double-blind study, 40 patients at two centers who were being monitored for 3 to 30 months after renal transplantation, were allocated to receive either EP 100 micrograms orally four times daily or placebo (P) for 2 weeks. CYA dosing was fixed at existing levels. There could be no evidence of concurrent acute renal injury, including that of acute rejection. Glomerular filtration rate (GFR) was measured by the clearance of radiolabeled DTPA, while effective renal plasma flow (ERPF) was measured as the clearance of p-aminohippuric acid (PAH). The acute effects of EP were examined twice, by comparing immediate postdose to predose values for GFR and ERPF on day 1 and again on day 14. Chronic effects were examined by comparing baseline (predose) values only for GFR and ERPF between days 1 and 14 and by an examination of creatinine clearances (CCR) on days 0, 14, and 21. At enrollment, patients were well matched for renal function (CCR:EP 47 +/- 5 v P 49 +/- 4 mL/min/1.73 m2; P = NS). Baseline demographics were similar, although patients treated with EP were older (46 +/- 2 v 36 +/- 3 years, mean +/- SEM, P = 0.003). CYA doses and blood levels did not change significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Sonographic changes during hepatic interstitial laser photocoagulation. An investigation of three optical fiber tips.

RATIONALE AND OBJECTIVES: Interstitial laser photocoagulation (ILP) destroys tumors thermally, using laser energy delivered from implanted optical fibers. The objectives of the study are to identify a fiber tip/delivered energy combination which produces lesions of useful size, visible on ultrasound (US) during ILP, and to compare ILP lesions and their US images. METHODS: Hepatic ILP was performed at laparotomy in six pigs, using three different fiber tips (cylindrical diffusing, spherical diffusing, plane-cut). US images were obtained during ILP, immediately after ("early" images), and before the animals were killed (2-2.5 hours, "late" images). Actual lesions were assessed histopathologically. RESULTS: Few US changes were seen around cylindrical diffusing and spherical diffusing tips until tip destruction. Plane-cut tips, at 1.5 to 2.0 W, produced prominent US images of the 1- to 2-cm thermal lesions. Early images tended to overestimate necrosis. Late images approximated necrosis. CONCLUSION: For US-controlled ILP, plane-cut tips are better than currently available cylindrical diffusing or spherical diffusing tips. Lesion image growth periods might enable control of lesion size. Further studies are needed to determine the consistency of the described relationship between lesion images and actual lesions.

Animals↗
PubMed1992

Clinical versus administrative data bases for CABG surgery. Does it matter?

This study compared the ability of a clinical and administrative data base in New York State to predict in-hospital mortality and to assess hospital performance for coronary artery bypass graft surgery. The results indicated that the clinical data base, the Cardiac Surgery Reporting System, is substantially better at predicting case-specific mortality than the administrative data base, the Statewide Planning and Research Cooperative System. Also, correlations between hospital mortality rates that are risk-adjusted using the two systems were only moderately high (0.75 to 0.80). The addition of new risk factors from the Statewide Planning and Research Cooperative System improved the predictive power of both systems but did not diminish the difference in effectiveness of the two systems. The three unique clinical risk factors in the Cardiac Surgery Reporting System (ejection fraction, reoperation, and more than 90% narrowing of the left main trunk) seemed to account for much of the difference in effectiveness of the two systems.

Coronary Artery Bypass↗
PubMed1992

The ability of pretransplant test-dose pharmacokinetic profiles to reduce early adverse events after renal transplantation.

Pretransplant test-dose pharmacokinetic profiles were used to determine individual cyclosporine drug bioavailability and clearance rates in renal transplant patients. Assuming a linear relation between dose and area under the concentration curve (AUC), starting i.v. and p.o. CsA doses were computed from the test-dose results. Target values were 400 ng/ml steady-state concentration (Css) during continuous intravenous infusion, and 500 ng/ml average drug concentration (Cavss = AUC/dosing interval) after oral administration, based upon measurements with the specific monoclonal antibody 3H-tracer radioimmunoassay. The outcomes after dose individualization with a 1-(n = 32), 2-(n = 38), or 3-(n = 41) hr i.v. infusion test dose and a p.o. test dose (n = 111) were compared with 228 historical control patients who received a uniform protocol of CsA i.v. at 2.5 mg/kg/day and p.o. at 14 mg/kg/day. The observed Css after i.v. CsA was within 10% of the target concentration in 73% of recipients tested with the 3-hr protocol, a significantly greater fraction than achieved with either the uniform dose (14%), or the 1-(34%) and 2-(25%) hr protocols. Patients in the 3-hr protocol group showed reduced incidences of delayed graft function, early graft loss, and rejection episodes, and a lower mean serum creatinine value, particularly at 7 but also at 30 days posttransplantation. Administration of the predicted oral dose produced a peak concentration of greater than or equal to 700 ng/ml drug absorption in 60% of recipients at 3 days, 90% at 5 days, and 98% at 7 days. The test-dose method less effectively predicted the appropriate oral CsA dose to produce target Cssav and failed to reduce the 90-day rejection incidence. Despite its limitations with the more-complicated p.o. route, the test-dose method successfully predicts i.v. CsA doses, thereby reducing the incidence of early adverse events.

Administration, Oral↗
PubMed1992

Mechanisms and amelioration of acute renal allograft failure in the cyclosporine era.

The fairly wide-ranging spectrum of tactics under investigation for ameliorating acute renal allograft dysfunction caused by harvest/preservation-related ischemia, acute CsA nephrotoxicity, and acute immunologic crises reflect the fact that no single approach has emerged as universally useful for mitigating the vasomotor nephropathy produced by the combined effects of each of these vectors of vasomotor renal allograft injury. Given the clinical heterogeneity of patients and allografts, it is the author's bias that, in addition to careful donor and recipient hemodynamic management, induction immunosuppressive regimens should be individualized on the basis of allograft function in the immediate postreperfusion period (judged by rate of diuresis, intraoperative parenchymal tone, renal scan profiles, and rate of decline of serum creatinine concentration) as well as patient-specific immunologic and general medical risk factors. Promising laboratory and clinical investigations of such agents as calcium channel blockers, substances promoting intrarenal vasodilator vs. vasoconstrictor prostaglandin formation, and atriopeptins have the potential to provide clinically helpful options with regard to adjunctive therapy for ameliorating acute renal allograft dysfunction associated with INF and ACR.

Acute Kidney Injury↗
PubMed1992

Boundary fighting: territorial conflicts in health organizations.

If health institutions are to be healthy places to work and study, managers in these institutions will have to take the lead to revamp old tradition-based boundaries. Health problems now rarely require the exclusive care of one specialist. Health care and rehabilitation require that many health care specialists work together. And, prevention crosses all disciplinary boundaries. Similarly, our changing society requires a more flexible workplace with job sharing, teaming, multicompetent personnel, and an environment that is dedicated more to meeting the needs of consumers than those of health professionals. Boundaries in health institutions must change if these institutions are to meet the needs of a changing society and attract and retain health care professionals who want to experience the opportunities of new, more permeable boundaries without the ordeal of warfare.

Conflict, Psychological↗
PubMed1992

Paradoxical emboli in elderly patients.

We report two elderly patients who each had a patent foramen ovale (PFO) and were considered to have had paradoxical emboli. In one patient the PFO was detected by contrast two-dimensional echocardiography, whereas in the other it was demonstrated at post-mortem examination. This is an unusual but treatable condition, particularly difficult to diagnose in older people and probably occurring more frequently than is generally suspected.

Aged↗
PubMed1991

Haemodynamic significance of incompetent calf perforating veins.

A total of 149 consecutive unselected patients (221 limbs) who presented with signs and symptoms of chronic venous problems (varicose veins with or without ankle oedema, skin changes and leg ulcers) have been studied by clinical examination, ascending deep to superficial venography, Doppler ultrasound and ambulatory venous pressure measurements. Of the limbs, 180 (82 per cent) had varicose veins without obstruction in the deep veins or reflux in the popliteal or femoral veins while 41 (18 per cent) had deep venous disease. Of the 180 limbs with 'primary' varicose veins 110 (60 per cent) did not have incompetent calf perforating veins (group A) while 70 (40 per cent) did (group B). On the basis of the ambulatory venous pressure after calf muscle exercise and the refilling time, the incompetent calf perforating veins of limbs in group B belonged to three subgroups of different haemodynamic significance. In 20 limbs (30 per cent) they were found to be of no haemodynamic significance, in 25 (35 per cent) of moderate haemodynamic significance and in 25 (35 per cent) of major haemodynamic significance. The last were, on clinical examination, indistinguishable from limbs with deep venous disease although they had patent deep veins with competent popliteal valves.

Humans↗
PubMed1991

Adolescent coping: the different ways in which boys and girls cope.

In order to investigate the ways in which boys and girls cope with their concerns, 650 Year 11 and Year 12 students from seven post-primary schools in Melbourne, Australia were asked to describe how they cope with the main concerns in their lives. In addition to elicitation of spontaneous responses, a modified form of the Ways of Coping Checklist (Folkman and Lazarus, 1980; 1985b) was also administered to obtain an assessment of students coping strategies. Clear differences were found between the ways in which boys and girls cope. Girls seek more social support and generally are more likely than boys to focus on relationships. They also employ more strategies related to hoping for the best and wishful thinking. The question of how boys and girls can develop their coping repertoire so as to increase the adaptability of their responses in difficult situations is also addressed.

Adaptation, Psychological↗
PubMed1991

Behavior problems and adaptive functioning in children with mild and severe closed head injury.

Assessed behavior problems and adaptive functioning in children with mild or severe closed head injuries, on average more than 2 years postaccident. To ensure that any problems detected in the present study were not merely preexisting problems, potential subjects were excluded if there was a history of preexisting CNS damage, significant developmental delay, or behavior problems. Children with severe head injuries had an excessive rate of behavior problems and impaired adaptive functioning. Children with mild head injuries also had an excessive rate of behavior problems (comparable to that of children with severe head injuries) but did not have impaired adaptive functioning. Results are discussed in terms of six alternative ways brain injury and behavior problems can be related functionally.

Activities of Daily Living↗
PubMed1991

Magnesium deficiency may be an important determinant of ventricular ectopy in digitalised patients with chronic atrial fibrillation.

Digitalised patients with chronic atrial fibrillation (AF) have a high prevalence of ventricular premature beats (VPB); magnesium deficiency may be a contributory factor. We have used a magnesium loading-test to examine the relationship between ventricular ectopy and magnesium status in 14 digitalised patients with chronic AF. Among seven patients with infrequent VPB (less than 250 24 h-1; mean 107 24 h-1) mean magnesium retention was 10.1% and four subjects retained no significant quantities of magnesium, indicating magnesium repletion. Among the remaining seven patients, mean magnesium retention was significantly higher (33.1%, P less than 0.02) and all patients retained 20% or more of the load given. There was an overall relationship between Mg retention and numbers of VPB (rs = 0.54; P less than 0.05). Magnesium deficiency may be determinant of ventricular ectopy in digitalised patients with chronic AF.

Aged↗
PubMed1991

Long-term follow-up of patients with nonischemic dilated cardiomyopathy and ventricular tachyarrhythmias treated with implantable cardioverter defibrillators.

We analyzed our 10-year cumulative experience of 40 consecutive patients with idiopathic dilated cardiomyopathy and associated ventricular tachyarrhythmias, treated with implantable cardioverter defibrillators. Dilated cardiomyopathy was defined as left ventricular ejection fraction (EF) less than or equal to 50% with no defineable etiology. Patient characteristics included: 24 male, mean age 52 years, mean EF = 33%, New York Heart Association Class I-III, presenting syndrome--cardiac arrest (n = 28), syncope/near syncope (n = 12). At 2.5 years mean follow-up, there were 16 deaths: one operative, three sudden, two incessant ventricular tachycardia/ventricular fibrillation (VT/VF), six heart failure, and four noncardiac. The actuarial mortality at 1 and 4 years was 0% and 14% for sudden death, 11% and 34% for cardiac death. The projected mortality was 52% and 78% for same time intervals (P less than 0.01). No useful baseline variable predicted who would or would not receive an ICD shock in follow-up. ICD therapy appears effective in reducing sudden death mortality in this high risk population.

Cardiomyopathy, Dilated↗
PubMed1991

Exogenous nerve growth factor reverses age-related structural changes in neocortical neurons in the aging rat. A quantitative Golgi study.

The role of chronic exogenous intracerebroventricular administration of nerve growth factor (NGF) on the morphology of layer V pyramidal cell dendrites in aging rats was quantified using Golgi impregnations. Both dendritic branching and dendritic spines from the basilar tree of randomly selected pyramidal neurons of the frontal cortex were evaluated in young control (4-month-old) Fischer 344 rats, in old controls (24-month-old), and in 24-month-old rats administered NGF for 4 weeks. Sholl analysis of basilar dendritic trees showed that neuronal branching in older rats was significantly greater than that in young rats (probably due to compensatory dendritic hypertrophy). The extent of dendritic material in aged rats receiving NGF, however, was identical to that in young rats, that is, the dendritic tree had regressed in size. Dendritic spine response to NGF treatment depended on the region of the dendritic tree sampled. Normal aging resulted in spine loss. However, NGF treatment restored dendritic spine densities to those seen in young controls on terminal tip segments ("plastic" regions). Internal branch segments ("nonplastic" regions) showed no response to NGF. As dendritic spines are thought to represent the neuroanatomic basis of learning and memory, results suggest that NGF can influence the morphology of cortical neurons (probably indirectly via the basal forebrain projections) and therefore may play an efficacious role in the treatment of geriatric cognitive dysfunction and even perhaps in Alzheimer's disease.

Aging↗
PubMed1991

The hand-held, voice-controlled terminal: medical information interface of the future.

In its push to cross the barrier of fixed-site, fixed-format information displays, Texas Instruments is busy working on prototypes of a small device that healthcare knowledge workers can carry with them onsite or offsite to enter orders, display test results, view images, listen to audio comments and record other patient data. TI won't specify a delivery date, and they say it's still several years away. Vision must precede form.

Computer Communication Networks↗
PubMed1991

Packaging matters--part II: material selection.

The second part of this two-part article discusses material selection for medical device packaging. Part I analyzed the design of the pack and concluded that the package and the device should be designed together. In Part II, the constraints on material choice are discussed in relation to the overall device package, and the properties that device packaging must exhibit are defined.

Equipment Design↗