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Biomedical subjects

R E Clark

Publications and source records attributed to R E Clark.

At least 37 records · Page 2Linked to original sources
PubMed2001

Family support and substance use outcomes for persons with mental illness and substance use disorders.

This paper explores the relationship between direct support from family members and friends and substance use outcomes for people with co-occurring severe mental illness and substance use disorders. Data are from a 3-year randomized trial of 203 patients in treatment for dual disorders. Informal (family) caregivers for 174 participants were asked about economic assistance and direct care that they provided to participants. Associations between family support and substance use outcomes were examined with bivariate comparisons of abstainers and nonabstainers and with regression models using change in substance use and cumulative substance use as dependent measures. Family economic support was associated with substance abuse recovery in bivariate and regression analyses. Caregiving hours were significantly associated with substance use reduction but not with cumulative substance use. Informal support was not associated with changes in psychiatric symptoms. The findings suggest that direct family support may help people with dual disorders to reduce or eliminate their substance use. Further research is needed to confirm this connection and to establish the mechanisms by which support is useful.

Activities of Daily Living↗
PubMed2001

A decade's experience with quality improvement in cardiac surgery using the Veterans Affairs and Society of Thoracic Surgeons national databases.

OBJECTIVE: To review the Department of Veteran Affairs (VA) and the Society of Thoracic Surgeons (STS) national databases over the past 10 years to evaluate their relative similarities and differences, to appraise their use as quality improvement tools, and to assess their potential to facilitate improvements in quality of cardiac surgical care. SUMMARY BACKGROUND DATA: The VA developed a mandatory risk-adjusted database in 1987 to monitor outcomes of cardiac surgery at all VA medical centers. In 1989 the STS developed a voluntary risk-adjusted database to help members assess quality and outcomes in their individual programs and to facilitate improvements in quality of care. METHODS: A short data form on every veteran operated on at each VA medical center is completed and transmitted electronically for analysis of unadjusted and risk-adjusted death and complications, as well as length of stay. Masked, confidential semiannual reports are then distributed to each program's clinical team and the associated administrator. These reports are also reviewed by a national quality oversight committee. Thus, VA data are used both locally for quality improvement and at the national level with quality surveillance. The STS dataset (217 core fields and 255 extended fields) is transmitted for each patient semiannually to the Duke Clinical Research Institute (DCRI) for warehousing, analysis, and distribution. Site-specific reports are produced with regional and national aggregate comparisons for unadjusted and adjusted surgical deaths and complications, as well as length of stay for coronary artery bypass grafting (CABG), valvular procedures, and valvular/CABG procedures. Both databases use the logistic regression modeling approach. Data for key processes of care are also captured in both databases. Research projects are frequently carried out using each database. RESULTS: More than 74,000 and 1.6 million cardiac surgical patients have been entered into the VA and STS databases, respectively. Risk factors that predict surgical death for CABG are very similar in the two databases, as are the odds ratios for most of the risk factors. One major difference is that the VA is 99% male, the STS 71% male. Both databases have shown a significant reduction in the risk-adjusted surgical death rate during the past decade despite the fact that patients have presented with an increased risk factor profile. The ratio of observed to expected deaths decreased from 1.05 to 0.9 for the VA and from 1.5 to 0.9 for the STS. CONCLUSION: It appears that the routine feedback of risk-adjusted data on local performance provided by these programs heightens awareness and leads to self-examination and self-assessment, which in turn improves quality and outcomes. This general quality improvement template should be considered for application in other settings beyond cardiac surgery.

Cardiac Surgical Procedures↗
PubMed2001

Trace and delay eyeblink conditioning: contrasting phenomena of declarative and nondeclarative memory.

We tested the proposal that trace and delay eyeblink conditioning aref fundamentally different kinds of learning. Strings of one, two, three, or four trials with the conditioned stimulus (CS) alone and strings of one, two, three, or four trials with paired presentations of both the CS and the unconditioned stimulus (US) occurred in such a way that the probability of a US was independent of string length. Before each trial, participants predicted the likelihood of the US on the next trial. During both delay (n = 20) and trace (n = 18) conditioning, participants exhibited high expectation of the US following strings of CS-alone trials and low expectation of the US following strings of CS-US trials--a phenomenon known as the gambler's fallacy. During delay conditioning, conditioned responses (CRs) were not influenced by expectancy but by the associative strength of the CS and US. Thus, CR probability was high following a string of CS-US trials and low following a string of CS-alone trials. The results for trace conditioning were opposite. CR probability was high when expectancy of the US was high and low when expectancy of the US was low: The results show that trace and delay eyeblink conditioning are fundamentally different phenomena. We consider how the findings can be understood in terms of the declarative and nondeclarative memory systems that support eyeblink classical conditioning.

Adolescent↗
PubMed2001

Implementing evidence-based practices for persons with severe mental illnesses.

Extensive empirical research, summarized in several reviews and codified in practice guidelines, recommendations, and algorithms, demonstrates that several pharmacological and psychosocial interventions are effective in improving the lives of persons with severe mental illnesses. Yet the practices validated by research are not widely offered in routine mental health practice settings. As part of an effort to promote the implementation of evidence-based practice, the authors summarize perspectives on how best to change and sustain effective practice from the research literature and from the experiences of administrators, clinicians, family advocates, and services researchers. They describe an implementation plan for evidence-based practices based on the use of toolkits to promote the consistent delivery of such practices. The toolkits will include integrated written material, Web-based resources, training experiences, and consultation opportunities. Special materials will address the concerns of mental health authorities (funders), administrators of provider organizations, clinicians, and consumers and their families.

Community Mental Health Services↗
PubMed2001

Implementing dual diagnosis services for clients with severe mental illness.

After 20 years of development and research, dual diagnosis services for clients with severe mental illness are emerging as an evidence-based practice. Effective dual diagnosis programs combine mental health and substance abuse interventions that are tailored for the complex needs of clients with comorbid disorders. The authors describe the critical components of effective programs, which include a comprehensive, long-term, staged approach to recovery; assertive outreach; motivational interventions; provision of help to clients in acquiring skills and supports to manage both illnesses and to pursue functional goals; and cultural sensitivity and competence. Many state mental health systems are implementing dual diagnosis services, but high-quality services are rare. The authors provide an overview of the numerous barriers to implementation and describe implementation strategies to overcome the barriers. Current approaches to implementing dual diagnosis programs involve organizational and financing changes at the policy level, clarity of program mission with structural changes to support dual diagnosis services, training and supervision for clinicians, and dissemination of accurate information to consumers and families to support understanding, demand, and advocacy.

Counseling↗
PubMed2001

Single-cue delay eyeblink conditioning is unrelated to awareness.

We examined the importance of awareness for eyeblink conditioning by directly comparing single-cue delay eyeblink conditioning and single-cue trace eyeblink conditioning. During single-cue delay conditioning, participants who became aware of the stimulus contingencies early in the conditioning session conditioned no better than those who became aware later in the session or did not become aware. Thus, the level of awareness was unrelated to the overall level of conditioning across the session. In contrast, awareness of the stimulus contingencies early in the session predicted the success of single-cue trace conditioning. These data, together with earlier findings, show that awareness is irrelevant to single-cue delay eyeblink conditioning but is critical for single-cue trace eyeblink conditioning. The findings from the present study are related to previous findings for differential (CS+ and CS-) eyeblink conditioning and awareness.

Aged↗
PubMed2000

Impaired recognition memory in rats after damage to the hippocampus.

Rats with radio-frequency or ibotenic acid lesions of the hippocampus and rats with radio-frequency lesions of the fornix were tested on the visual paired comparison task (VPC), a test of recognition memory. Memory was assessed at five different delay intervals ranging from 10 sec to 24 hr. All operated groups performed normally at the shorter delays (10 sec and 1 min). Across longer delays, the two groups with hippocampal damage were impaired. Rats with fornix lesions performed well on the VPC task but were impaired on a spatial task (spontaneous alternation). The results show that the hippocampus is essential for normal recognition memory. Moreover, fornix lesions need not mimic the effects of direct damage to hippocampal tissue. The findings are discussed in the context of the contribution of the hippocampus to recognition memory.

Animals↗
PubMed2000

Biochemical markers of bone turnover following high-dose chemotherapy and autografting in multiple myeloma.

The effect of high-dose chemotherapy and autografting on bone turnover in myeloma is not known. A study of 32 myeloma patients undergoing blood or marrow transplant (BMT), conditioned with high-dose melphalan, was done. Bone resorption was assessed by urinary free pyridinoline (fPyr) and deoxypyridinoline (fDPyr), expressed as a ratio of the urinary creatinine concentration. Bone formation was assessed by serum concentration of procollagen 1 extension peptide (P1CP) and bone-specific alkaline phosphatase (BSAP). Eighteen cases had normal fPyr and fDPyr at transplant, and in all but one of these cases the level remained normal throughout subsequent follow-up. In contrast, in 14 cases urinary fPyr and fDPyr levels were increased at transplant. In these cases, both fPyr and fDPyr fell to normal levels over the next few months (P = .0009 and.0019, respectively). fPyr and fDPyr levels at transplant and their trends post-BMT were unrelated to the use of pre-BMT or post-BMT bisphosphonate or post-BMT interferon. Nine cases had elevated P1CP or BSAP at transplant, which rapidly normalized. In most patients there was an increase in P1CP and/or BSAP several months post-transplant. In conclusion, increased osteoclast activity may be present even in apparent plateau phase of myeloma. High-dose chemotherapy with autografting may normalize abnormal bone resorption, although the effect may take several weeks to emerge and may be paralleled by increased osteoblast activity. The findings provide biochemical evidence that autografting may help normalize the abnormal bone turnover characteristic of myeloma. (Blood. 2000;96:2697-2702)

Adult↗
PubMed2000

Oligodeoxynucleotide 5mers containing a 5'-CpG induce apoptosis through a mitochondrial mechanism in T lymphocytic leukaemia cells.

A chimeric methylphosphonodiester/phosphodiester 15mer oligodeoxynucleotide of randomly selected sequence was observed to rapidly induce apoptosis in MOLT-4 and Jurkat E6 T lymphocytic leukaemia cells following intracytoplasmic delivery. A series of further methylphosphonate substitutions and mutations and truncations of the oligodeoxynucleotide served to establish that the phosphodiester-linked sequence CGGTA present in the 15mer was responsible for this biological activity. End-protected CpG oligodeoxy-nucleotide 5mers of sequence type CGNNN exhibited a range of apoptosis-inducing potencies, with CGTTA being the most active. The latter was shown to significantly reduce the rate of RNA synthesis in MOLT-4 cells within 1 h; DNA laddering and redistribution of phosphatidylserine to the outer surface of the plasma membrane were marked by 160 min and mitochondrial transmembrane potential collapsed over roughly the same time scale. Pro-caspase 8 was reduced within 130 min and the proteolytically activated caspase 8 substrate Bid was also down by this time, implicating release of cytochrome c from mitochondria by the active 15 kDa fragment of Bid. Substantial proteolytic activation of pro-caspase 3 was relatively delayed. These findings support a mitochondrial amplification mechanism for apoptosis triggered by CpG 5mers.

Apoptosis↗
PubMed2000

Impaired recognition memory in monkeys after damage limited to the hippocampal region.

Monkeys with lesions limited to the hippocampal region (the hippocampus proper, the dentate gyrus, and the subiculum) were impaired on two tasks of recognition memory: delayed nonmatching to sample and the visual paired-comparison task. Recognition memory was impaired in five different groups of monkeys, whether the lesions were made by an ischemic procedure, by radio frequency, or by ibotenic acid. The finding that the hippocampal region is essential for normal recognition memory performance is considered in the context of current ideas about the role of the hippocampus in declarative memory.

Animals↗
PubMed2000

Awareness predicts the magnitude of single-cue trace eyeblink conditioning.

Studies of differential eyeblink conditioning (CS+ and CS-) have demonstrated that successful conditioning requires awareness of the stimulus contingencies and that delay conditioning does not. Two experiments were carried out to determine whether awareness is also important for single-cue trace eyeblink conditioning. In experiment 1, participants who performed a secondary, attention-demanding task emitted significantly fewer conditioned eyeblink responses than participants who watched a silent movie during the conditioning session. In experiment 2, participants who became aware of the stimulus contingencies early in the conditioning session emitted significantly more conditioned responses during the remainder of the session than participants who became aware later in the session or who never became aware. These results indicate that awareness is important for single-cue trace eyeblink conditioning, just as it is for differential trace conditioning. The relationship between awareness and trace eyeblink conditioning is discussed in the light of these and other recent findings.

Aged↗
PubMed2000

Mechanical bridge to recovery in fulminant myocarditis.

A patient with acute fulminant lymphocytic myocarditis and cardiogenic shock was successfully treated by mechanical off loading of the left ventricle. A nonpulsatile left-heart bypass was undertaken with an implantable centrifugal blood pump. Careful weaning resulted in device removal on the seventh day. Left and right ventricular function is sustained at 7 months. Widespread application of this method depends on the availability of an inexpensive user friendly blood pump, appropriate weaning protocols and emerging strategies to promote sustainable myocardial recovery.

Adult↗
PubMed2000

Antisense therapeutics in chronic myeloid leukaemia: the promise, the progress and the problems.

DNA sequences which are complementary or 'antisense' to a target mRNA can inhibit expression of that mRNA's protein product. Antisense therapeutics has therefore received attention for inhibiting oncogenes in haematological malignancy, in particular in chronic myeloid leukaemia. However, it is now becoming clear that antisense therapeutics is considerably more problematic than was naively initially assumed. In this article, some of these difficulties are discussed, together with the achievements in CML so far. Considerable further research is required in order to define an optimal antisense therapeutics strategy for clinical use.

Animals↗
PubMed2000

b3a2 BCR-ABL fusion peptides as targets for cytotoxic T cells in chronic myeloid leukaemia.

Peptide sequences spanning the BCR-ABL protein junction potentially constitute novel leukaemia-specific antigens. 9-mer b3a2 fusion peptides have been reported to bind with high affinity to HLA-A3, -A11 and -B8. We have studied the effect of b3a2 BCR-ABL junctional peptides on the cytotoxic T-cell (CTL) response against normal and chronic myeloid leukaemia (CML) cells. Antigen-presenting cells (APCs) were prepared from HLA-A3- or -B8-positive peripheral blood mononuclear cells (PBMCs) by incubation with phytohaemagglutinin (PHA) and interleukin (IL)-2 for 7 d. These APCs were pulsed with the respective b3a2 junctional peptide in the presence of beta2-microglobulin and were then used to challenge autologous PBMCs at 7-d intervals in the presence of IL-2, IL-6, IL-7 and IL-12. On subsequent exposure to target cells (either further pulsed normal APCs or unpulsed CML cells), specific HLA-restricted CTL responses were observed against all HLA-A3/-B8 matched normal target cells tested, but not to targets that were HLA mismatched. Cytotoxicity was also induced against HLA-A3/-B8 unpulsed CML cells, but not against unmatched CML cells. These data indicate (i) that endogenous BCR-ABL junctional peptides may be presented by CML cells and (ii) that exogenous peptides are potential stimulators of autologous antileukaemic CTLs.

Antigen-Presenting Cells↗
PubMed1999

Risk stratification for cardiac valve replacement. National Cardiac Surgery Database. Database Committee of The Society of Thoracic Surgeons.

BACKGROUND: The Society of Thoracic Surgeons National Database Committee is committed to risk stratification and assessment as integral elements in the practice of cardiac operations. The National Cardiac Surgery Database was created to analyze data from subscribing institutions across the country. We analyzed the database for valve replacement procedures with and without coronary artery bypass grafting to determine trends in risk stratification. METHODS: The database contains complete records of 86,580 patients who had valve replacement procedures at the participating institutions between 1986 and 1995, inclusive. The 1995 harvest of data was conducted in late 1996 and available for evaluation in 1997. These records were used to conduct an in-depth analysis of risk factors associated with valve replacement and to provide prediction of operative death by using regression analysis. Regression models were made for six subgroups. RESULTS: Adverse patient risk factors, including diabetes, hypertension and reoperation, but not ventricular function, increased over time. There were trends with regard to increasing age of the various population subsets. The types of prostheses used remained similar over time, with more mechanical prostheses than bioprostheses used for both aortic and mitral valve replacement. There was a trend toward increased use of bioprostheses in aortic replacements and decreased use in mitral replacements between 1991 and 1995 than between 1986 and 1990. The mortality rate was determined by patient subset for primary operation and reoperation and by urgency status. The modeling showed that the predicted and observed mortality correlated for all age groups and within patient subsets. CONCLUSIONS: Risk modeling is a valuable tool for predicting the probability of operative death in any individual patient. This large, multiinstitutional database is capable of determining modern operative risk and should provide standards for acceptable care. The study illustrates the importance of risk stratification for early death both for the patient and the surgeon.

Adult↗
PubMed1999

The AB-180 circulatory support system: summary of development and plans for phase I clinical trial.

BACKGROUND: The AB-180 circulatory support system is a small, durable, efficient centrifugal pump with low thrombogenic potential. The device was designed to provide a fully implantable, left ventricular assist system for short-term support to address the issues of systemic anticoagulation, thrombus formation, infection, and cost. METHODS: Extensive bench and animal studies were performed to validate the mechanical integrity of the device and its functionality as an implant. RESULTS: These studies demonstrated anticoagulation requirements, established operating guidelines, incorporated safety systems, and demonstrated safety and efficacy. CONCLUSIONS: The AB-180 fulfills the stated goals on initial evaluation. A phase I human trial is underway.

Adult↗