Biomedical subjects

Michael R Clark

Publications and source records attributed to Michael R Clark.

12 recordsLinked to original sources

PubMed2006

Consensus guidelines: treatment planning and options. Diabetic peripheral neuropathic pain.

Despite the number of patients affected by diabetic peripheral neuropathic pain (DPNP), little consensus exists about the pathophysiology, best diagnostic tools, and primary treatment choices. Theories about the causes of DPNP are inextricably linked with the causes of diabetic neuropathles, yet most patients with such neuropathies do not experience pain. The factors that differentiate patients with pain from those without remain unknown and are the subject of much research. When choosing treatment for patients with DPNP, physicians are confronted with a myriad of choices, none of which has been shown to be effective for all patients. This article reviews the evidence for these treatments and attempts to guide physicians in choosing those treatments based on evidence from well-designed clinical trials to support their use. Two agents, duloxetine and pregabalin, are formally approved by the Food and Drug Administration for the treatment of DPNP. In addition, several other agents, including the tricyclic class of antidepressants, have been effective in clinical trials. Ultimately, treatment choice must also Include consideration of adverse effects, individual patient factors such as comorbidities, and often cost.

Analgesics, Opioid↗

PubMed2006

Psychogenic disorders: a pragmatic approach for formulation and treatment.

Four perspectives can provide a comprehensive yet flexible approach to the evaluation of a patient in distress with a psychogenic disorder. Each individual patient will have a different combination of the four perspectives that formulate the patient's problems. The perspectives identify the patient with a psychogenic disorder as a patient who is a composite of personal vulnerabilities and strengths but afflicted with diseases, struggling through life events, and motivated to behave for various reasons. Each individual perspective has its own logical process for evaluation and subsequently directed treatment. Although the perspectives are complementary, they each remain distinct and essential to the formulation of a patient's disability. This comprehensive and integrated formulation of a patient supports an approach to complex psychogenic cases that defy a simple list of diagnoses and nonspecific treatments. The patient does not have to fit into one theoretical approach to receive an available treatment. The treatments prescribed are now designed from the individual formulation and relevant perspectives.

Adult↗

PubMed2005

Intravascular survival of red cells coated with a mutated human anti-D antibody engineered to lack destructive activity.

Alloimmune feto-maternal destruction of blood cells is thought to be mediated by binding of alloantibodies to Fc receptors on effector cells. Blocking the antigen using inert antibodies might prolong cell survival. We have performed a "proof of principle" study in volunteers to measure the intravascular survival of autologous red cells coated with human recombinant IgG antibody containing a novel constant region, G1Deltanab, devoid of in vitro cytotoxic activity. RhD-positive red blood cells (RBCs), labeled with chromium-51 or technetium-99m, were separately coated to equal levels with wild-type IgG1 or G1Deltanab anti-D antibody (Fog-1). After re-injection, there was complete, irreversible clearance of IgG1-coated RBCs by 200 minutes, concomitant with appearance of radiolabel in plasma. Gamma camera imaging revealed accumulation in spleen and, at higher coating levels, in liver. In contrast, clearance of G1Deltanab-coated cells was slower, incomplete, and transient, with whole blood counts falling to 7% to 38% injected dose by about 200 minutes before increasing to 12% to 67% thereafter. There was no appearance of plasma radiolabel and no hepatic accumulation. These findings suggest that G1Deltanab-coated RBCs were not hemolysed but temporarily sequestered in the spleen and that our approach merits investigation in larger studies.

Antibodies, Monoclonal↗

PubMed2005

Function-blocking antibodies to human vascular adhesion protein-1: a potential anti-inflammatory therapy.

Human vascular adhesion protein-1 (VAP-1) is a homodimeric 170-kDa sialoglycoprotein that is expressed on the surface of endothelial cells and functions as a semicarbazide-sensitive amine oxidase and as an adhesion molecule. Blockade of VAP-1 has been shown to reduce leukocyte adhesion and transmigration in in vivo and in vitro models, suggesting that VAP-1 is a potential target for anti-inflammatory therapy. In this study we have constructed mouse-human chimeric antibodies by genetic engineering in order to circumvent the potential problems involved in using murine antibodies in man. Our chimeric anti-VAP-1 antibodies, which were designed to lack Fc-dependent effector functions, bound specifically to cell surface-expressed recombinant human VAP-1 and recognized VAP-1 in different cell types in tonsil. Furthermore, the chimeric antibodies prevented leukocyte adhesion and transmigration in vitro and in vivo. Hence, these chimeric antibodies have the potential to be used as a new anti-inflammatory therapy.

Amine Oxidase (Copper-Containing)↗

PubMed2004

A case-matching study of the analgesic properties of electroconvulsive therapy.

OBJECTIVE: Chronic pain improves with electroconvulsive therapy (ECT), yet few case reports account for treatment of comorbid major depression, a significant confounder of the analgesia of ECT. This study reports on the analgesia of ECT, controlling for treatment of depression. METHODS: This is a case-matching study comparing outcomes of inpatients with chronic pain and major depression in a multidisciplinary pain treatment unit treated with ECT and medications (cases) with those of inpatients treated with medications only (controls). Both groups received the same behavioral and pharmacological treatments for depression and chronic pain. Outcome measures included 0-10 pain rating scales and the Montgomery-Asberg Depression Inventory. Patients were matched on sex, age within 5 years, admission date within 6 months, psychiatric diagnoses, and, as much as possible, on race and pain syndrome diagnosis. Percentage changes in depression scores and pain scores were calculated from the beginning to the end of admission. RESULTS: There were nonsignificant differences in demographics, except in the proportion married. Twenty-five of 28 ECT patients were matched. Depression improvements were similar between cases and controls (55.9% vs 40.5%). Despite higher initial pain (8.1 vs 6.9 on a 10-point scale), the ECT group had less final pain (3.4 vs 5.5). The ECT group had a 59.8% drop in pain versus a 15.8% drop in the control group, P > 0.01. CONCLUSIONS: ECT has analgesic properties independent of its improvement of depression in patients with chronic pain and major depression. Improvements in depression were similar, while there was a significantly greater improvement in pain with ECT. The lower post-ECT treatment pain scores suggest a specific analgesic effect of ECT.

Analgesia↗

PubMed2004

Perspectives on pain and depression.

The health care system is often unsuccessful in the treatment of the patient experiencing chronic pain. Chronic pain is often complicated by a variety of psychiatric conditions that make it difficult to engage and treat patients. This generates frustration and pessimism in the physician. The patient may be afflicted by the syndrome of an affective disorder, demoralized by the unintended circumstances of their life, unable to meet the demands of stressors because of a lack of inherent capacities, or helplessly trapped by poor choices and repeated unproductive actions. The physician's interest and the patient's optimism can be restored and sustained by utilizing a systematic interdisciplinary approach utilizing the four perspectives of diseases, life stories, dimensions, and behaviors to evaluate the patient who is disabled by depression and chronic pain. The design of a comprehensive treatment plan involves the determination of each perspective's contribution to the patient's suffering. The process of formulation recognizes that the perspectives are distinct from one another but complementary in illuminating the various reasons for a patient's suffering. The perspectives offer a recipe for designing a rational treatment plan rather than trying to reduce the individual patient's complexity into a one-dimensional construct. This approach increases the probability of a successful outcome for both patient and physician.

Adaptation, Psychological↗

PubMed2004

Neurobiology of pain.

The neurobiology of pain has had extensive research directed at identifying the mechanisms of nociceptive transmission and integration. Clinical conditions of chronic pain including phantom limb pain cannot be explained without an understanding of the complex mechanisms of pain regulation. An overview of the neurobiological organization of the nociceptive system, from different pain fiber types to subcortical and cortical experiential centers, is presented, along with a brief description of the known cross talk within the system and between pain pathways and those for other information. Finally, interactions between affective, executive, and cognitive processes and pain experiences are described briefly.

Chronic Disease↗

PubMed2004

The effect of recombinant IgG antibodies against the leucine-33 form of the platelet beta3 integrin (HPA-1a) on platelet function.

Recombinant HPA-1a antibodies with Fc, mutated to remove destructive effector functions, have been developed as a potential therapy for fetomaternal alloimmune thrombocytopenia (FMAIT), via blockade of binding of human HPA-1a polyclonal antibodies to fetal HPA-1a1b platelets. We have assessed the effect of the IgG1 HPA-1a antibody B2G1 and two mutated derivatives in various functional assays in resting and agonist-stimulated platelets of the three HPA-1 genotypes. With HPA-1a1b platelets (fetal genotype), the antibodies did not activate signalling or CD62P expression in resting platelets, did not change in vitro bleeding time (IVBT), and did not inhibit platelet adhesion to collagen in flowing blood. Adhesion of HPA-1a1b platelets to fibrinogen was reduced by 20%, and aggregation induced by ADP by 50%, but collagen-related peptide (CRP-XL)-induced aggregation was normal. With HPA-1a1a platelets, aggregation to both ADP and CRP-XL was inhibited, with total blockade of adhesion to fibrinogen and of IVBT responses. Interestingly, a monovalent antibody fragment with identical specificity had no inhibitory effect on aggregation. In static adhesion assays using human alphaIIbbeta3 or alphaVbeta3 transfectants of HPA-1a (Leu(33)) phenotype, attachment to fibrinogen of the latter but not of the former was completely blocked by the HPA-1a antibodies. These observations are best explained by antibody-mediated blockade of the RGD binding site on beta3 by a mechanism of steric hindrance. As the effect on platelet function is modest with HPA-1a1b (fetal type) platelets, the mutated HPA-1a antibodies described here could be developed further for FMAIT therapy.

Antibodies↗

PubMed2003

Pain coping strategies play a role in the persistence of pain in post-herpetic neuralgia.

Post-herpetic neuralgia (PHN) is a neuropathic pain state that is often difficult to treat. Although frequently discussed in the clinical literature, little is known about the impact of pain on daily function and the extent to which psychosocial factors, in particular pain coping strategies, influence adaptation to this chronic illness. In the context of a crossover pharmacological trial, 68 patients with PHN completed a battery of psychological measures during a first drug-free baseline period. Following discontinuation of approximately 8 weeks of treatment, 49 of these patients completed data collection during a second drug-free assessment prior to beginning a second drug phase. Twice-weekly telephone pain ratings were combined with questionnaire measures of perceived interference due to pain, overall activity level, depressive symptoms, and pain coping strategies. Cross-sectional hierarchical regression analyses indicated that catastrophizing correlated with depressive symptoms but not pain, and coping self-statements were correlated with higher levels of overall activity. Prospective hierarchical regression analyses indicated that catastrophizing at baseline predicted level of pain 8 weeks later, an effect that was independent of baseline pain and depressive symptoms. Patients who reported increasing their activity in response to pain also reported more perceived interference due to pain 8 weeks later. Higher levels of ignoring pain sensations at baseline were prospectively correlated with more depressive symptoms 8 weeks later. These findings support a role for the continued investigation of cognitive-behavioral factors affecting the adaptation of elderly individuals experiencing PHN.

Adaptation, Psychological↗

PubMed2003

Academic psychiatry and health care reform: strategic initiatives for sustaining the clinical mission.

Health care reform has posed special challenges for departments of psychiatry in academic medical centers. This report describes one department's strategic responses to a marketplace with high penetration by managed care and provides examples of the kinds of faculty concerns that can arise when major departmental reorganizations are attempted. The department's successful adaptation to a radically altered professional environment is attributed to the following five initiatives: vertical integration and diversification of clinical programs, service line management, outcomes measurement, regional network development, and institutional managed care partnerships Although the authors did not design their adaptive efforts as a research study, they offer objective data to support their conclusion that the viability of their overall clinical enterprise has been sustained despite an external environment inhospitable to academic psychiatry.

Academic Medical Centers↗

PubMed2002

Refractory chronic pain.

Refractory chronic pain is a significant public health problem and frustrating to everyone affected by it. All physicians can participate in the care of these patients, but psychiatrists should take a leading role in their care. A comprehensive approach offers hope and increases the opportunities for successful treatment. Each perspective of an interdisciplinary formulation has a unique logic that defines specific methods for designing treatment for the patient with refractory chronic pain. The patient does not have to fit into one theoretic approach or model to receive and accept treatment. The patient's diagnoses are based on the formulation, which then directs treatment along rational directions. The linkages and interactions of a patient's diagnoses can then be investigated within a framework that includes the entire person and not just his or her biochemistry. If a patient's suffering persists, other factors must be considered that may have been overlooked before the treatment plan is abandoned or modified. Usually these factors are within one of the perspectives initially thought to be less important. A new combination of approaches is then required to treat the patient successfully. The perspectives appreciate not only that the patient is struggling through important life events but also that he is a person composed of vulnerabilities and strengths, having made many choices and afflicted by diseases.

Anxiety Disorders↗

PubMed1998

Pain coping strategies predict perceived control over pain.

Perceptions of control over pain and specific pain coping strategies are associated with a number of positive outcomes in patients with chronic pain conditions. Transactional models of stress have emphasized coping as a process that is both determined by, and influences appraisals of control. While perceptions of control and coping efforts are associated with better adjustment, little is known about the specific coping strategies that contribute to perceptions that pain is controllable. One hundred and ninety-five (65% female) individuals with chronic pain conditions admitted to an inpatient unit completed the Multidimensional Pain Inventory, the Survey of Pain Attitudes and the Coping Strategies Questionnaire. Stepwise multiple regression analyses were used to predict perceived pain control from measures of pain severity and coping. After controlling for pain severity and education, coping self-statements and reinterpreting pain sensations predicted greater perceptions of control over pain, whereas ignoring pain sensations predicted lower perceptions of control over pain. The coping strategies did not interact with pain severity in predicting perceptions of control. Coping flexibility, or the number of pain coping strategies reported at a high frequency, also predicted perceptions of control over pain and did not interact with pain severity. The present findings suggest that, regardless of pain severity, the use of specific cognitive pain coping strategies may increase perceptions of control over pain. Since the existing coping literature largely identifies maladaptive pain coping strategies, it is especially critical to establish which pain coping strategies are adaptive. Specific cognitive strategies, particularly coping self statements, are important components for cognitive-behavioral interventions for chronic pain management. Future research will need to determine whether other adaptive cognitive strategies such as reinterpreting pain sensations can be increased with cognitive interventions, since this strategy is infrequently used.

Adaptation, Psychological↗