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Biomedical subjects

R E Clark

Publications and source records attributed to R E Clark.

At least 145 records · Page 8Linked to original sources
PubMed1994

Delayed commencement of granulocyte colony-stimulating factor following autologous bone marrow transplantation accelerates neutrophil recovery and is cost-effective.

It is known that Granulocyte colony-stimulating factor (G-CSF) accelerates neutrophil recovery following bone marrow transplantation (BMT), though the optimal timing is not clear. We have undertaken a pilot study in 19 recipients of autologous BMT for non-myeloid malignancy, in which G-CSF was commenced 10 (13 cases) or 7 (6 cases) days after BM infusion. These patients were compared with 18 historical controls, who did not receive G-CSF. The median time to achieve both 0.5 and 1.0 x 10(9) neutrophils/Litre was significantly shorter in the treated group (18 and 21 days respectively) than the control group (20.5 and 29 days; p = 0.03 and 0.02 respectively). No differences between the two groups were seen for the number of febrile days, days on antibiotics or the cost of the antibiotics. G-CSF-treated patients remained in hospital for significantly less time after marrow infusion (21 days compared to 29 days; p = 0.007). The cost of the G-CSF therapy was offset by the decreased bed utilisation, so that the median combined antibiotic, G-CSF and hospitalisation cost was 754 pounds less for G-CSF treated patients. It is concluded that delaying the commencement of G-CSF after autologous BMT accelerates neutrophil recovery, and may allow earlier discharge from hospital, whilst not adversely affecting the cost of the procedure.

Adult↗
PubMed1994

Thrombotic microangiopathy following bone marrow transplantation.

Thrombotic microangiopathy (TMA) is a well-recognised disorder which may occur in up to 6% of patients following bone marrow transplantation (BMT). Reported cases of post-BMT TMA vary widely in their reported clinical features, severity and response to therapy. Several factors are important in the aetiology, including cyclosporin A (CsA), graft-versus-host disease, irradiation, intensive conditioning chemotherapy and infection. A unifying pathogenetic mechanism is suggested, wherein these factors may interact to produce post-BMT TMA. On the basis of differences in clinical features and prognosis, we propose the classification of post-BMT TMA into four distinctive although overlapping subtypes: multifactorial fulminant TMA, conditioning-associated haemolytic-uraemic syndrome, CsA-associated nephrotoxicity with microangiopathic haemolytic anaemia (MAHA) and CsA-associated neurotoxicity with MAHA. Treatment of post-BMT TMA, especially of the poor-prognosis multifactorial fulminant subtype, is currently unsatisfactory, although occasional cases may respond to plasma exchange.

Anemia, Hemolytic↗
PubMed1994

Managing competition in public and private mental health agencies: implications for services and policy.

There were clear differences in our study between the management strategies employed by public agencies and those favored by private agencies. These differences, however, appeared to reflect the realities of financing rather than any fundamental differences in their orientation toward public service. There was no clear evidence that particular management practices affected an agency's performance on measures of financial access or acceptance of referrals from public hospitals. Government regulation and pressure from advocacy groups probably helped to maintain private agencies' focus on these and other public goals. From a public policy perspective, choosing a provider solely on the basis of ownership status is, at best, a naive approach to providing public mental health treatment. Not only is there great variation in process and practices within both private and public groups, but external factors such as competition from private practitioners may also exert a stronger influence on agency behavior than does ownership status. Because most current proposals for health care reform rely heavily on increased competition among providers to achieve their goals, the importance of ownership status as a predictor of conduct or performance may be further diminished. The emphasis on competition could increase differences between urban agencies and those in rural areas where there is less competition and, therefore, require different contracting approaches. As we move toward a health care system based on competition, administrators and policy makers will be forced to abandon their reliance on stereotypical public/private agency behavior as guides for policy decisions. Instead, they will have to consider more carefully the effects of political and market influences as well as agency characteristics when choosing community mental health providers.

Community Mental Health Centers↗
PubMed1994

Vogt-Koyanagi-Harada syndrome complicating allogeneic bone marrow transplantation.

Vogt-Koyanagi-Harada (VKH) syndrome is an uncommon acute ophthalmological disorder, characterised by bilateral serous retinal detachment with diffuse choroiditis, in association with specific extra-ocular manifestations. We describe a patient with unequivocal VKH syndrome arising 49 days after matched unrelated donor bone marrow transplantation (BMT) performed as treatment for severe aplastic anaemia. The visual symptoms and retinal changes responded well to corticosteroids. The haematological relevance of VKH syndrome is to distinguish it from retinitis due to cytomegalovirus, which requires different therapy and has a far worse visual prognosis.

Adult↗
PubMed1993

Relation between choice of prostheses and late outcome in double-valve replacement.

The purpose of this study was to determine if the combination of a mechanical and bioprosthetic valve in the aortic and mitral positions influences late morbidity and mortality when compared with patients who had dual mechanical or dual bioprosthetic valves inserted. We reviewed the course of 89 hospital survivors of combined aortic and mitral valve replacement. The mean postoperative follow-up interval was 6.6 years, with a total follow-up of 583 years (98% complete). At 12 months after operation, mean functional class decreased from 3.1 to 1.7 (p < 0.05) and mean cardiac index increased from 2.1 to 2.5 L.min-1.m-2 (p < 0.05). Actuarial survival for the 89 patients (exclusive of < 30-day or in-hospital mortality, 14%) was 70%, 51%, and 33% at 5, 10, and 15 years. Freedom from reoperation was 93%, 78%, and 68%, and freedom from combined thromboembolism and anticoagulant-related hemorrhage was 82%, 60%, and 50%. These results show that there was no difference in overall survival in patients with dual mechanical valves, dual bioprosthetic valves, or a combination of both types at 15 years. There was, however, a lower reoperation rate in the group with dual mechanical valves as compared with the group with dual bioprosthetic valves (p < 0.05 at 10 years) or with a combination of valves (p < 0.05 at 15 years). The higher the number of mechanical valves the higher the combined risk of thromboembolism and anticoagulant-related hemorrhage.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗
PubMed1993

Cardiopulmonary bypass and thyroid hormone metabolism.

Early investigations involving patient response to thyrotropin-releasing hormone during cardiac operations prompted researchers to consider that the cardiopulmonary bypass (CPB) procedure may affect this response. Results from several studies indicate that total T3 (active thyroid hormone) concentrations are significantly reduced during and after CPB (ie, the euthyroid sick syndrome). Inhibition of the monodeiodinase pathway during CPB, and subsequent inhibition of peripheral thyroxine to T3 conversion may partly explain these findings. These data prompted the investigation of intravenous T3 administration to patients undergoing CPB. Clinical trials to date have shown that intravenous T3 administered during or after CPB improves cardiac output and contractility. This article reviews the studies of thyroid hormone before, during, and after CPB operations.

Cardiopulmonary Bypass↗
PubMed1993

Operative treatment of pediatric obstructive hypertrophic cardiomyopathy: a 26-year experience.

We retrospectively reviewed the 26-year National Institutes of Health experience with operative treatment of obstructive hypertrophic cardiomyopathy in pediatric patients. Operative criteria were either severe obstructive symptoms (New York Heart Association functional class III or IV) or sudden death. Seventeen patients underwent 19 open procedures, of which the present study is comprised. Complete follow-up was available 10.1 +/- 1.4 years (mean +/- standard error; range, 0.8 to 26.2 years) after operation. The mean ages at diagnosis and operation were 11.9 +/- 1.3 years (range, 1 to 17 years) and 14.8 +/- 0.7 years (range, 9 to 17 years), respectively. The preoperative intraventricular septum mean dimension was 23.2 +/- 1.3 mm (range, 11 to 36 mm). The left ventricular outflow tract gradient was 74 +/- 9 mm Hg (range, 20 to 175 mm Hg) at rest and 94 +/- 7 mm Hg (range, 55 to 175 mm Hg) with provocation. Fifteen patients (88%) underwent left ventricular myotomy and myectomy, and 2 underwent mitral valve replacement. Two patients who initially received left ventricular myotomy and myectomy later underwent mitral valve replacement. There were one perioperative death (6%) and five late sudden deaths (31%) at 3.8, 8.7, 9.6, 14.1, and 21 years postoperatively. Kaplan-Meier survival was 86% +/- 8% at 5 years and 77% +/- 12% at 10 years. After operation, the left ventricular outflow tract gradient decreased almost 80% to 21 +/- 15 mm Hg (p = 0.0001). In 8 patients, the left ventricular outflow tract gradient completely resolved.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Late results after triple-valve replacement with various substitute valves.

The purpose of this study was to determine what influence various combinations of mechanical and bioprosthetic valves in the aortic, mitral, and tricuspid positions had on late morbidity and mortality of 40 hospital survivors of triple-valve replacement. At operation the patients ranged in age from 27 to 69 years; 73% were women. The mean postoperative follow-up interval was 8.3 years, with a total follow-up of 331 years (100% complete). At 12 months after operation, functional class decreased from 3.3 to 1.6 (p < 0.05), cardiac index increased from 2.0 to 2.6 L.min-1 x m-2 (p < 0.05), and pulmonary artery pressures decreased from 59/27 to 40/17 mm Hg (p < 0.05). There were no differences in preoperative variables between groups. Actuarial survival for the 40 patients (exclusive of 30-day or in-hospital mortality, which was 31%) was 78% and 74% at 5 and 10 years. At the same milestones, freedom from reoperation was 96% and 54%, freedom from combined thromboembolism and anticoagulant-related hemorrhage was 68% and 56%, and freedom from all late valve-related morbidity and mortality was 64% and 25%. Comparison of the patients with two or more mechanical prostheses with the patients having two or more bioprostheses indicated no significant differences in actuarial freedom from late death, thromboembolic events, or anticoagulant-related hemorrhage. However the actuarial freedom from reoperation in the groups with two or more mechanical valves was lower than that of the groups with two or more bioprosthetic valves (0/10 versus 13/30; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗
PubMed1993

Reversible lesions of the red nucleus during acquisition and retention of a classically conditioned behavior in rabbits.

Previous lesion, recording, and stimulation studies implicated the cerebellum and its associated brain-stem circuitry as essentially involved in classical conditioning of discrete, somatic muscle responses. This is a companion to our study of interpositus cooling, which showed that the formation of a memory was prevented. In the present study, we assess the red nucleus for its role in the plasticity associated with learning and memory by using local cooling as a reversible lesion technique. A cooling probe was implanted lateral to the red nucleus. Recording electrodes were implanted in the right red nucleus and the left interpositus nucleus. Animals were trained for 5 days with the cooling probe activated. No behavioral conditioned responses (CR) developed, and multiple unit recordings related to learning did not develop in the red nucleus. However, a learning related model did develop in the interpositus. After 5 days of training while cooling, animals were given 5 days of normal training (cooling probe inactive) to assess retention. Substantial savings were evident when normal training was given. CRs appeared quickly on the first day of normal training, and multiple unit models were present in both red nucleus and interpositus nucleus. These results support the idea that the red nucleus is a necessary efferent for the memory trace formed in the cerebellum.

Animals↗
PubMed1993

Substance abuse in schizophrenia: service utilization and costs.

Utilization and cost of institutional and outpatient services were prospectively measured over 1 year for three groups of schizophrenic patients: current substance abusers, past substance abusers, and those without a history of substance abuse. Current abusers had significantly greater utilization and cost of institutional (hospital and jail) services. Current abusers also had greater utilization of emergency services. There were no significant differences between the groups in utilization and cost of other services, including psychosocial rehabilitation, outpatient treatment (case management, psychotherapy, and psychiatric visits), and housing supports. The implications for developing cost-effective treatments for dually diagnosed individuals are discussed.

Adult↗
PubMed1993

Treatment of substance abuse in severely mentally ill patients.

Substance abuse is the most common comorbid complication of severe mental illness. Current clinical research converges on several emerging principles of treatment that address the scope, pace, intensity, and structure of dual-diagnosis programs. They include a) assertive outreach to facilitate engagement and participation in substance abuse treatment, b) close monitoring to provide structure and social reinforcement, c) integrating substance abuse and mental health interventions in the same program, d) comprehensive, broad-based services to address other problems of adjustment, e) safe and protective living environments, f) flexibility of clinicians and programs, g) stage-wise treatment to ensure the appropriate timing of interventions, h) a longitudinal perspective that is congruent with the chronicity of dual disorders, and i) optimism.

Activities of Daily Living↗
PubMed1993

Quantification of asymmetric valvular regurgitant jets by color Doppler ultrasound in vitro.

Accurate quantification of regurgitant jets in natural and prosthetic heart valves has been a goal of health care workers and researchers for many years. One promising new method applies the law of conservation of momentum transfer to velocities measured by color Doppler ultrasound to calculate the flow rate in the jet. One complicating factor is that regurgitant jets from real heart valves may be highly asymmetric. The purpose of this investigation was to determine whether the accurate calculation of the flow rate in asymmetric jets imaged by color Doppler requires an asymmetric formulation of the conservation of momentum transfer, combined with a method for imaging the jet in three dimensions. Asymmetric jets issuing from narrow slits were imaged in an in vitro, steady flow system. The ultrasound transducer was rotated around the jet axis to image the jet in three dimensions. The three-dimensional imaging confirmed that jets from slits are indeed asymmetric, but become relatively axisymmetric far from the orifice. Images were analyzed by computer and the calculated flows compared to measured flows. The accuracy of an asymmetric formulation of the conservation of momentum transfer method was compared to a simpler, axisymmetric formulation. If axisymmetry was assumed in asymmetric jets, significant errors in the calculated flow rates occurred. In these cases, the calculated flow also varied widely with distance from the orifice. When asymmetry was taken into account, the errors were considerably reduced. The results suggest that, in asymmetric jets, the momentum transfer is convected around the jet axis.

Blood Flow Velocity↗
PubMed1993

A framework for evaluating the economic impact of case management.

Confusion about the cost-effectiveness of case management stems partly from poorly defined assumptions about outcomes and unclear theories of how case management affects costs. The authors discuss how cost-effectiveness is influenced by the characteristics of various case management models, characteristics of the clients served, and contextual factors, including resources available in the treatment system and financial incentives built into various payment mechanisms. Important differences exist between case management models in the mechanisms favored for managing resources, including whether the client or the case manager is primarily responsible for directing the course of treatment, whether reduction in hospitalizations is a primary goal, whether team case management is used, and how the size of caseloads is determined.

Chronic Disease↗
PubMed1993

Long-term bone marrow cultures established from bone marrow transplant recipients.

Following bone marrow transplantation (BMT), the stroma remains host-derived, and has therefore been exposed to the high doses of chemoradiotherapy used in BMT conditioning. We have used long term bone marrow culture (LTBMC) to study the effect of this conditioning therapy on the stroma. Twenty-five BMT recipients were studied, comprising 13 allografts and 12 autografts. Marrow was aspirated prior to transplant (6 cases) and at 3, 6 or 12 months post-BMT. Fifteen haematologically normal subjects were studied in parallel. The stromal layer of LTBMC was visually assessed at weekly intervals and supernatant cells counted and assayed for colony forming unit-granulocyte/macrophage (CFU-GM). Five of the six cases studied both before and after BMT formed less confluent stroma following the procedure. A successive improvement in the proportion of patients forming good stroma was observed with increasing time from BMT. Supernatant cell and CFU-GM counts were not significantly different from normal following BMT. No clear relationship was observed between stromal confluence and any of the following: supernatant cell and CFU-GM counts, transplant type, underlying disease, conditioning regime or time to engraftment. These data support the view that BMT conditioning regimes cause stromal damage, and that this damage gradually improves with time.

Adult↗
PubMed1993

Redo cardiac surgery: late bleeding complications from topical thrombin-induced factor V deficiency.

Bovine thrombin-induced factor V deficiency was though to be a very rare acquired coagulopathy, with only three documented cases. We report a series of nine patients seen during a period of 32 months; these patients had normal preoperative coagulation profiles, and this unique coagulopathy developed 1 to 2 weeks after cardiovascular operations. The coagulopathy was characterized by a markedly elevated prothrombin time (40.9 +/- 5.8 seconds), an elevated activated partial thromboplastin time (96.3 +/- 12.2 seconds), a study positive for lupus anticoagulation (9/9), and markedly decreased levels of factor V (0.09 +/- 0.03 U/ml) and factor XI (0.04 +/- 0.02 U/ml), respectively. All patients had been exposed to commercially available bovine thrombin during prior cardiovascular or vascular operations and received a second bovine thrombin challenge during the latest procedure. Coagulopathic bleeding developed in four of the nine patients. Bleeding was unrelated to absolute fall in factor V level, but cessation of hemorrhage appeared to correlate with improvement in factor V level. Treatment with vitamin K, fresh frozen plasma, and platelet infusion were all unsuccessful in altering prothrombin time or factor V levels. Intravenous gamma globulin was used in three patients, two of whom were bleeding. All three patients showed a transient increase in factor V levels. Bleeding stopped in one of the two patients; the other continued to bleed and subsequently died. The third patient was treated prophylactically to increase factor V levels in preparation for flap reconstruction of his sternum. His factor V level increased from 0.26 to 0.49 U/ml, and he underwent the procedure without incident. Bovine thrombin-induced factor V deficiency may have been previously unrecognized. This deficiency should be suspected in patients who have undergone redo cardiovascular operations and in whom marked elevations in their prothrombin time occur 7 to 10 days after exposure to bovine thrombin. The resulting coagulopathy, although usually self-limited, has the potential to produce devastating bleeding complications. Intravenous gamma globulin (1 gm/kg during each of 2 days) has been used to increase factor V levels transiently but its role in therapy of this coagulopathy requires further investigation.

Administration, Topical↗
PubMed1993

Left ventricular function in experimental mitral regurgitation with intact chordae tendineae.

Left ventricular function in mitral regurgitation has typically been studied in models that either sever the chordae tendineae or create a ventriculoatrial shunt. These methods may have adverse effects on left ventricular function independent of the regurgitant lesion. An animal model of chronic mitral regurgitation was therefore developed that both preserves annuloventricular continuity and avoids the use of external shunts. A circular 0.16 to 0.24 mm/kg defect was created in the anterior mitral valve leaflet of weanling sheep under direct vision with the aid of cardiopulmonary bypass. Six animals were studied preoperatively and immediately postoperatively (acute regurgitation group), and 20 animals were studied 8.1 +/- 0.2 (mean +/- one standard deviation) months postoperatively (chronic regurgitation group). Animals with chronic mitral regurgitation were compared with an age- and weight-matched control group that was not operated on (n = 7). Volumetric data and ejection fraction were derived from digitalized cineangiographic images. Maximal elastance was calculated from pressure-volume loops obtained from the simultaneous recording of left ventricular pressure by micromanometer-tipped left ventricular catheters, and volumes were obtained from digitalized images of epicardial echocardiographic recordings. Mitral valve perforation resulted in 3+ to 4+ mitral regurgitation and a calculated regurgitant fraction of 37% +/- 7% (mean +/- one standard deviation). Acute mitral regurgitation was associated with an increase in left ventricular end-diastolic volume from 110 +/- 17 to 121 +/- 23 ml (p < or = 0.05) and no change in end-systolic volume. These changes were associated with an increase in fractional shortening, from 29% +/- 11% to 40% +/- 10% (p < or = 0.05), and an increase in velocity of circumferential shortening, from 1.5 +/- 0.7 to 2.9 +/- 0.7 circ/sec (p < or = 0.05). However, there was no change in maximal elastance, a load-independent index of left ventricular function. Conversely, animals with chronic mitral regurgitation exhibited an elevated end-diastolic volume (202 +/- 32 versus 145 +/- 34, p < or = 0.05), an elevated end-systolic volume (104 +/- 17 versus 63 +/- 20 ml, p < or = 0.05), and a reduced ejection fraction (48% +/- 6% versus 57% +/- 9%, p < or = 0.05) compared with controls.(ABSTRACT TRUNCATED AT 400 WORDS)

Acute Disease↗
PubMed1993

Periparotid lupus erythematosus panniculitis. Clinicopathologic correlation of two cases presenting as primary parotid disease.

Lupus erythematosus (LE) panniculitis, also called lupus profundus, is an uncommon but well-established manifestation of both chronic cutaneous (discoid) LE and systemic LE. Although LE panniculitis characteristically may involve the face, specific parotid and periparotid involvement has not, to the best of our knowledge, been previously reported. We describe the clinicopathologic correlation of two cases of LE panniculitis that presented as apparent primary parotid parenchymal disease; one as a neoplasm, the other as parotiditis. Failure to recognize LE panniculitis resulted in prolonged periods of inappropriate therapy and significant morbidity, including an unnecessary parotidectomy. Lupus erythematosus panniculitis has well-established histologic criteria that should be considered in the differential diagnosis of an unexplained parotid mass.

Adult↗