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Mark S Wallace

Publications and source records attributed to Mark S Wallace.

At least 19 recordsLinked to original sources
PubMed2007

Recommendations for the management of herpes zoster.

The objective of this article is to provide evidence-based recommendations for the management of patients with herpes zoster (HZ) that take into account clinical efficacy, adverse effects, impact on quality of life, and costs of treatment. Systematic literature reviews, published randomized clinical trials, existing guidelines, and the authors' clinical and research experience relevant to the management of patients with HZ were reviewed at a consensus meeting. The results of controlled trials and the clinical experience of the authors support the use of acyclovir, brivudin (where available), famciclovir, and valacyclovir as first-line antiviral therapy for the treatment of patients with HZ. Specific recommendations for the use of these medications are provided. In addition, suggestions are made for treatments that, when used in combination with antiviral therapy, may further reduce pain and other complications of HZ.

2-Aminopurine↗
PubMed2006

A randomized, double-blind, placebo-controlled study of intrathecal ziconotide in adults with severe chronic pain.

Safety and efficacy data from a study of slow intrathecal (IT) ziconotide titration for the management of severe chronic pain are presented. Patients randomized to ziconotide (n = 112) or placebo (n = 108) started IT infusion at 0.1 microg/hour (2.4 microg/day), increasing gradually (0.05-0.1 microg/hour increments) over 3 weeks. The ziconotide mean dose at termination was 0.29 microg/hour (6.96 microg/day). Patients' baseline Visual Analogue Scale of Pain Intensity (VASPI) score was 80.7 (SD 15). Statistical significance was noted for VASPI mean percentage improvement, baseline to Week 3 (ziconotide [14.7%] vs. placebo [7.2%; P = 0.036]) and many of the secondary efficacy outcomes measures. Significant adverse events (AEs) reported in the ziconotide group were dizziness, confusion, ataxia, abnormal gait, and memory impairment. Discontinuation rates for AEs and serious AEs were comparable for both groups. Slow titration of ziconotide, a nonopioid analgesic, to a low maximum dose resulted in significant improvement in pain and was better tolerated than in two previous controlled trials that used a faster titration to a higher mean dose.

Adult↗
PubMed2006

The effect of intravenous ketorolac on capsaicin-induced deep tissue hyperalgesia.

Preclinical and clinical studies have emphasized that persistent small afferent input will induce a state of central facilitation that can be attenuated by systemically administered nonsteroidal antiinflammatory drugs. However, these studies have been performed using cutaneous models of hyperalgesia. In this study we evaluated the effects of IV ketorolac on an experimental model of deep tissue hyperalgesia using IM capsaicin. We used a double-blind, placebo-controlled, crossover design. Ten subjects received 60 mg of ketorolac or placebo in 2 sessions separated by 1 wk. Capsaicin (100 microg in 10 microL) was then injected into the flexor carpi ulnaris muscle of the left forearm. After injection, spontaneous pain scores, pressure pain scores, gripping pain, pain distribution, and pain quality were recorded at 0, 5, 10, 15, 20, and 25 min. Cutaneous allodynia and dysesthesia were then mapped and thermal and mechanical thresholds were measured. The IM injection of capsaicin resulted in a reliable report of pain, hyperalgesia, and referred pain. Ketorolac had no effect on spontaneous pain, elicited pain, pain distribution, or secondary hyperalgesia induced by capsaicin. The findings of this study support the feasibility of further pharmacological studies using the IM capsaicin pain model.

Adult↗
PubMed2006

Ziconotide: a new nonopioid intrathecal analgesic for the treatment of chronic pain.

Ziconotide is a new nonopioid intrathecal agent recently approved for the treatment of chronic pain. Ziconotide is indicated for the management of severe chronic pain in patients for whom intrathecal therapy is warranted and who are intolerant of or refractory to other treatment, such as systemic analgesics, adjunctive therapies or intrathecal morphine. Ziconotide blocks the N-type calcium channels located in the superficial dorsal horn of the spinal cord, resulting in potent analgesia. The efficacy of ziconotide has been demonstrated in three randomized, placebo-controlled trials in over 500 patients. In addition, its safety has been demonstrated in over 1200 subjects. Ziconotide is a potent analgesic with a narrow therapeutic window. The drug requires a slow titration in order to achieve analgesia while avoiding dose-limiting side effects. This review examines the currently available information on this new analgesic.

Analgesics↗
PubMed2006

Intradermal capsaicin causes dose-dependent pain, allodynia, and hyperalgesia in humans.

BACKGROUND: Intradermal capsaicin is a human pain model that produces reliable pain and sensitization. This model facilitates controlled testing of analgesic efficacy via a crossover design while minimizing confounding variables in clinical pain states and retaining sufficient power with small samples. METHODS: To determine the lowest dose of capsaicin that produces consistent neurosensory measures, we administered 0.1, 1, 10, or 100 microg to healthy volunteers in a blinded manner (N = 19). Pain scores were recorded at 0, 5, 10, 15, and 60 minutes on a visual analog scale from 0 to 100. Areas and intensities of mechanical allodynia (foam brush stimulus) and pinprick hyperalgesia (von Frey test) were quantified at 15 and 60 minutes, as were flare areas. RESULTS: Capsaicin produced dose-dependent increases in spontaneous pain (p = .013), the area and intensity of mechanical allodynia (p = .006 and p < .001, respectively), the area and intensity of pinprick hyperalgesia (p = .010 and p = .014, respectively), and the flare area (p = .010). The 10 microg dose produced greater spontaneous pain than the 1 microg dose (p = .017). The 100 microg dose produced greater spontaneous pain than the 10 microg, but the difference was not statistically significant. CONCLUSION: The 10 and 100 microg capsaicin doses produced robust pain measures across a range of modalities, and lower doses produced minimal effects. Whereas most studies use 100 microg, using a lower dose is reasonable and may facilitate detection of subtle analgesic effects--particularly with nonopioid analgesics--and drugs can be tested in lower doses, minimizing adverse side effects.

Adult↗
PubMed2005

NanoStore: a concept for logistical improvements of compound handling in high-throughput screening.

Small molecule screening, the systematic encounter of biology space with chemical space, has provoked the emergence of a whole industry that recreates itself by constant iterative improvements to this process. The authors describe an approach to tackle the problem for one of the most time-consuming steps in the execution of a screening campaign, namely, the reformatting of high-throughput screening test compounds from master plates to daughter assay plates used in the execution of the screen. Through an engineered storage procedure, they prepare plates ahead of the screening process with the respective compounds in a ready-to-use format. They show the biological inertness of the method and how it facilitates efficient recovery of compound activity. This uncoupling of normally interconnected processes provides time and compound savings, avoids repeated freeze-thaw cycles of compound solutions, and removes the problems associated with the DMSO sensitivity of certain assays types.

Automation↗
PubMed2005

Qualitative and quantitative characterization of the thermal grill.

Concurrent applications to the skin of spatially adjacent bands of innocuous warm and cool stimuli would elicit a peculiar sensation, known as the 'thermal grill illusion'. To validate the thermal grill as a research tool, this two-phase study qualitatively characterizes this peculiar sensation and further quantitatively establishes the temperature matching of the most intense/noxious thermal grill stimulations at two different time points. The temperature combinations (degrees C) tested were: 18/18, 42/42, 18/42, 20/20, 40/40, 20/40, 22/22, 38/38, 22/38, 24/24, 36/36 and 24/36. None of the subjects reported pain with single temperature combinations. However, hot associated with pain and burning sensations were reported in all mixed temperature combinations tested. The VAS scores for pain were significantly elevated for 20/40 and 18/42 in comparison to 22/38 and 24/36 (P<0.007). At the 3-second time point, the matching temperatures (+/-SD) of 20/40 and 18/42 were 45.7+/-1.8 (range 44-48) and 46.6+/-1.5 (range 44-48) degrees C, respectively, whereas the matching temperatures for the single temperature combinations were similar to the set temperatures. Importantly, at the 10-second time point, none of the combinations were significantly greater than the highest of the pair of stimuli. The time course variation in the perception of the combined stimuli suggests an adaptation occurred in central processing.

Adolescent↗
PubMed2005

Diagnosis and treatment of neuropathic pain.

PURPOSE OF REVIEW: Neuropathic pain accounts for 25-50% of pain clinic visits with an estimated prevalence of 4 million. Neuropathic pain is often difficult to diagnose and treat with few pharmacologic options currently available. This review summarizes the latest research on the pathophysiology, diagnosis and treatment of neuropathic pain. RECENT FINDINGS: The diagnosis of neuropathic pain relies on an evaluation of information given by the patient and physical findings obtained by the health provider. There are several validated questionnaires that can be used. Neuropathic pain is associated with a number of different cellular and molecular mechanisms. These include abnormalities in ion channels; exaggerated responses to cytokines, enzymes and neuropeptides; and abnormal communications between large/small fibers and sympathetic/small fibers. An understanding of these mechanisms has led to mechanistic directed treatments including topical treatments, antiepileptics, antidepressants, opioids and other drugs in development that are more mechanistically driven. SUMMARY: Neuropathic pain is common, underdiagnosed and undertreated. Diagnosing and understanding the basic mechanisms of neuropathic pain will lead to better treatments of this difficult health care problem.

Journal Article↗
PubMed2004

Intrathecal ziconotide in the treatment of refractory pain in patients with cancer or AIDS: a randomized controlled trial.

CONTEXT: Ziconotide (formerly SNX-111) selectively blocks N-type voltage-sensitive calcium channels and may be effective in patients with pain that is refractory to opioid therapy or those with intolerable opioid-related adverse effects. OBJECTIVE: To assess the safety and efficacy of intrathecal ziconotide in patients with pain that is refractory to conventional treatment. DESIGN, SETTING, AND PATIENTS: Double-blind, placebo-controlled, randomized trial conducted from March 12, 1996, to July 11, 1998, at 32 study centers in the United States, Australia, and the Netherlands. Patients were 111 individuals ages 24 to 85 years with cancer or AIDS and a mean Visual Analog Scale of Pain Intensity (VASPI) score of 50 mm or greater. Patients were randomly assigned in a 2:1 ratio to receive ziconotide or placebo treatment. INTERVENTIONS: Intrathecal ziconotide was titrated over 5 to 6 days, followed by a 5-day maintenance phase for responders and crossover of nonresponders to the opposite treatment group. MAIN OUTCOME MEASURE: Mean percentage change in VASPI score from baseline to the end of the initial titration period. RESULTS: Of the evaluable population, 67 (98.5%) of 68 patients receiving ziconotide and 38 (95%) of 40 patients receiving placebo were taking opioids at baseline (median morphine equivalent dosage of 300 mg/d for the ziconotide group and 600 mg/d for the placebo group; P =.63, based on mean values), and 36 had used intrathecal morphine. Mean (SD) VASPI scores were 73.6 (1.8) mm in the ziconotide group and 77.9 (2.3) mm in the placebo group (P =.18). Mean VASPI scores improved 53.1% (95% confidence interval [CI], 44.0%-62.2%) in the ziconotide group and 18.1% (95% CI, 4.8%-31.4%) in the placebo group (P<.001), with no loss of efficacy of ziconotide in the maintenance phase. Pain relief was moderate to complete in 52.9% of patients in the ziconotide group compared with 17.5% in the placebo group (P<.001). Five patients receiving ziconotide achieved complete pain relief, and 50.0% of patients receiving ziconotide responded to therapy compared with 17.5% of those receiving placebo (P =.001). CONCLUSION: Intrathecal ziconotide provided clinically and statistically significant analgesia in patients with pain from cancer or AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed2004

Lack of effect of two oral sodium channel antagonists, lamotrigine and 4030W92, on intradermal capsaicin-induced hyperalgesia model.

Preclinical studies have emphasized that persistent small afferent input will induce a state of central facilitation, which can be regulated by systemically administered sodium channel blockers. We have extended these preclinical studies to the human volunteers by examining the effects of lamotrigine and 4030W92, two structurally related voltage-sensitive sodium channel antagonists, on acute sensory thresholds and facilitated processing induced by intradermal capsaicin. Fifteen healthy subjects received 4030W92, lamotrigine, and placebo in a randomized order using double-blinded crossover design methodology in three sessions each separated by a 7-day washout period. In each session, baseline neurosensory testing was performed on the volar aspect of the subject's left forearm. Subjects were then dosed with either lamotrigine (300 mg), 4030W92 (100 mg), or placebo, followed 2 h later by capsaicin (100 microg) injected intradermally on the volar aspect of the left forearm. Pain scores, blood pressure, heart rate, and respiratory rate were measured at the time of injection and every 5 min for 15 min. Fifteen minutes after the capsaicin injection, the hyperalgesic area was determined by von Frey hair, stroking, and heat; the flare response was outlined; and neurosensory testing again was performed halfway between the edge of the hyperalgesic area and the capsaicin injection site. While capsaicin significantly decreased the hot pain and VF pain thresholds, oral lamotrigine and 4030W92 failed to alter this response to capsaicin, relative to placebo treatment. Similarly, oral lamotrigine or 4030W92 did not alter the pain scores reported from mechanical pain stimuli at any time postcapsaicin. This study showed a lack of effect of two structurally similar sodium channel antagonists on a human experimental pain model using intradermal capsaicin, which is consistent with other studies on the effects of sodium channel antagonists of capsaicin-induced pain and hyperalgesia. This lack of effect stands in contrast to reported effects of sodium channel antagonists on preclinical models of cutaneous hyperalgesia or effects of lamotrigine on clinical neuropathic pain.

Administration, Oral↗
PubMed2003

Advances in neuropathic pain: diagnosis, mechanisms, and treatment recommendations.

Chronic neuropathic pain, caused by lesions in the peripheral or central nervous system, comes in many forms. We describe current approaches to the diagnosis and assessment of neuropathic pain and discuss the results of recent research on its pathophysiologic mechanisms. Randomized controlled clinical trials of gabapentin, the 5% lidocaine patch, opioid analgesics, tramadol hydrochloride, and tricyclic antidepressants provide an evidence-based approach to the treatment of neuropathic pain, and specific recommendations are presented for use of these medications. Continued progress in basic and clinical research on the pathophysiologic mechanisms of neuropathic pain may make it possible to predict effective treatments for individual patients by application of a pain mechanism-based approach.

Analgesics↗
PubMed2003

Tutorials in clinical research: part VII. Understanding comparative statistics (contrast)--part A: general concepts of statistical significance.

OBJECTIVES/HYPOTHESIS: The present tutorial is the seventh in a series of Tutorials in Clinical Research. The specific purpose of the tutorial (Part A) and its sequel (Part B) is to introduce and explain three commonly used statistical tools for assessing contrast in the comparison between two groups. STUDY DESIGN: Tutorial. METHODS: The authors met weekly for 10 months discussing clinical research studies and the applied statistics. The difficulty was not in the material but in the effort to make the report easy to read and as short as possible. RESULTS: The tutorial is organized into two parts. Part A, which is the present report, focuses on the fundamental concepts of the null hypothesis and comparative statistical significance. The sequel, Part B, discusses the application of three common statistical indexes of contrast, the chi2, Mann-Whitney U, and Student t tests. CONCLUSIONS: Assessing the validity of medical studies requires a working knowledge of research design and statistics; obtaining this knowledge need not be beyond the ability of the busy surgeon. The authors have tried to construct an accurate, easy-to-read, easy-to-apply, basic introduction to comparing two groups. The long-term goal of the present tutorial and others in the series is to facilitate basic understanding of clinical research, thereby stimulating reading of some of the numerous well-written research design and statistical texts. This knowledge may then be applied to the continuing educational review of the literature and the systematic prospective analysis of individual practices.

Bias↗
PubMed2003

Tutorials in clinical research: VII. Understanding comparative statistics (contrast)--part B: application of T-test, Mann-Whitney U, and chi-square.

OBJECTIVE: This tutorial on comparative statistics has been written in two complementary segments. The first paper (part A) focused on explaining the general concepts of the null hypothesis and statistical significance. This second article (part B) addresses the application of three specific statistical tests. These two articles should be read sequentially and the first article should be available for reference while one reads the second. STUDY DESIGN: Tutorial. METHODS: The authors met weekly for 10 months to discuss clinical research articles and the applied statistics. The difficulty was not the material but the effort to make it easy to read and as short as possible. RESULTS: The article discusses the application of three common statistical indexes of contrast, chi2, Mann-Whitney U, and Student t-test and other concepts, such as sample size, degrees of freedom, errors, power, and confidence intervals. CONCLUSIONS: Statistical tests generate a number known as a statistic (chi2, U, t), which is sometimes called a "critical ratio" because it helps us to make a decision. This number is then associated with a probability, or P value. Sample size is a crucial element in the initial design of a research project and in the subsequent ability of the results to show statistical significance if the difference is clinically important. The example data used in this paper demonstrate the application of the three specific tests and illustrate the effect of sample size on the results.

Biomedical Research↗
PubMed2002

Treatment options for refractory pain: the role of intrathecal therapy.

Intraspinal drug delivery represents an important treatment option for the management of chronic pain. Selection of candidates for this type of therapy requires careful evaluation of the patient, possibly including psychological screening. Although determining the efficacy of long-term intraspinal drug therapy has been challenging, several classes of agents have been identified to provide benefits in patients with a variety of pain types. Such agents include opioids, alpha(2)-agonists, sodium channel antagonists, and gamma-aminobutyric acid agonists. In addition, combinations of agents with distinct mechanisms of action may be therapeutically advantageous because many clinical pain states result from more than one mechanism.

Analgesics↗
PubMed2002

A multicenter, double-blind, randomized, placebo-controlled crossover evaluation of a short course of 4030W92 in patients with chronic neuropathic pain.

Several lines of evidence suggest that neuropathic pain is mediated in part by an increase in the density of voltage-sensitive sodium channels in injured axons and the dorsal root ganglion of injured axons. The purpose of this study was to examine the safety, analgesic efficacy, and tolerability of oral 4030W92 (a new novel sodium channel blocker) in a group of subjects with chronic neuropathic pain. This study used a randomized, double-blind, placebo-controlled, crossover design in 41 subjects with neuropathic pain with a prominent allodynia. Each subject received a 2-week course of 4030W92 (25 mg/day) and placebo separated by a 2-week washout period. At baseline, postdose day 1, day 7, and day 14, the following were measured: (1) spontaneous and evoked pain scores, (2) dynamic and static allodynia mapping, (3) Short Form McGill Pain Questionnaire, and (4) blood sample for 4030W92 assay. At baseline and day 14 the following were measured: (1) thermal testing in the painful area, (2) Medical Outcomes Study Short Form 36 Questionnaire, and (3) patient global satisfaction. Allodynia severity was significantly lower (P = .046) on treatment day 1, postdose for 4030W92 compared to placebo. However, this was not maintained on treatment day 7 or 14. The area of static allodynia was significantly smaller (P = .03) on treatment day 7 for 4030W92 compared to placebo. However, this was not maintained to treatment day 14. There was no significant effect of 4030W92 on any other efficacy measure. Side effects were minimal. 4030W92, at 25 mg/day, produced a nonsignificant reduction in pain without treatment limiting side effects. The maximum analgesic effect of this drug remains unknown.

Clinical Trial↗
PubMed2002

The effect of chronic oral desipramine on capsaicin-induced allodynia and hyperalgesia: a double-blinded, placebo-controlled, crossover study.

UNLABELLED: The tricyclic antidepressants are often used for the treatment of neuropathic pain. In this study, we evaluated one of these drugs on human cutaneous experimental pain. A randomized, double-blinded, placebo-controlled, crossover design methodology was conducted. Subjects participated in 2 14-day study sessions separated by a 7-day washout period. One session was with desipramine and one with placebo. At baseline, Day 7, and Day 15, quantitative sensory testing was performed to thermal and mechanical stimuli. On Day 15 only, intradermal capsaicin was injected on the volar aspect of the forearm followed by an assessment of pain and hyperalgesia. Oral desipramine had no significant effect on acute sensory thresholds, pain, secondary hyperalgesia, or flare response induced by intradermal capsaicin. Mean peak plasma levels of desipramine were within the therapeutic range for the treatment of depression. This study further supports a lack of effect of the tricyclic antidepressants on acute nociception and experimentally-induced secondary hyperalgesia. IMPLICATIONS: Human experimental pain models have recently been developed; however, the efficacy of the tricyclic antidepressants (TCA) in these models has not been systematically studied. This investigation provides further validation of human experimental pain models and demonstrates that the chronic delivery of a TCA has no effect on human experimental pain.

Adult↗
PubMed2002

Tutorials in clinical research: part IV: recognizing and controlling bias.

OBJECTIVE: This is the fourth of a series of Tutorials in Clinical Research (1-3). The objectives of this article are to heighten reader awareness of biases and of methods to reduce their impact and to provide an easy reference document for the reader during future journal reading. STUDY DESIGN: Tutorial. METHODS: The authors met weekly for 4 months discussing clinical research articles and biases for which they might be at risk. Liberal use of reference texts and specific articles on bias were reviewed. Like the example by Sackett, biases were catalogued to create an easily understood reference. Articles were chosen to demonstrate how understanding bias might facilitate assessment of the validity of medical publications. RESULTS: The article is organized into three main sections. The first section introduces specific biases. Two tables serve as rapid reference tools. The second section describes the most common biases linked to specific research approaches and reviews techniques to minimize them. The last section demonstrates the application of the information to an article in a manner that can be applied to any article. CONCLUSIONS: Assessing the validity of a medical publication requires an awareness of bias for which the research is inherently at risk. A review of the publication to determine what steps the authors did or did not undertake to minimize the impact of biases on their results and conclusions helps establish the validity. This article should be of assistance in this critical review task.

Bias↗