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Biomedical subjects

H W Clark

Publications and source records attributed to H W Clark.

At least 19 recordsLinked to original sources

A recombinant fragment of human SP-D reduces allergic responses in mice sensitized to house dust mite allergens.

C57Bl6 mice sensitized to Dermatophagoides pteronyssinus and challenged with D. pteronyssinus allergen extract given intranasally followed by treatment with intranasal applications of a 60-kDa truncated, trimeric recombinant form of human SP-D (rfhSP-D) showed a significant reduction in serum IgE, IgG1, peripheral blood eosinophilia and airway hyperresponsiveness compared to saline or bovine serum albumin-treated controls. Intracellular cytokine staining of lung and spleen homogenates showed increases in interleukin (IL)-12 production in lung tissue and normalization of IL-12 and interferon (IFN)-gamma in spleen tissue. In previous studies we demonstrated the effectiveness of native SP-D and rfhSP-D in down-regulating allergic responses to allergens of Aspergillus fumigatus. The results reported here indicate that rfhSP-D can suppress the development of allergic symptoms in sensitized mice challenged with allergens of the common house dust mite.

Animals↗

Violent traumatic events and drug abuse severity.

We examined the occurrence of violent traumatic events, DSM-III-R diagnosis of posttraumatic stress disorder (PTSD), and PTSD symptoms, and the relationship of these variables to drug abuse severity. One-hundred fifty opioid-dependent drug abusers who were participants in a randomized trial of two methadone treatment interventions were interviewed using the Diagnostic Interview Schedule, the Addiction Severity Index, and the Beck Depression Inventory. Twenty-nine percent met diagnostic criteria for PTSD. With the exception of rape, no gender differences in the prevalence of violent traumatic events were observed. The occurrence of PTSD-related symptoms was associated with greater drug abuse severity after controlling for gender, depression, and lifetime diagnosis of PTSD. The high rate of PTSD among these methadone patients, the nature of the traumatic events to which they are exposed, and subsequent violence-related psychiatric sequelae have important implications for identification and treatment of PTSD among those seeking drug abuse treatment.

Adult↗

Methadone maintenance vs 180-day psychosocially enriched detoxification for treatment of opioid dependence: a randomized controlled trial.

CONTEXT: Despite evidence that methadone maintenance treatment (MMT) is effective for opioid dependence, it remains a controversial therapy because of its indefinite provision of a dependence-producing medication. OBJECTIVE: To compare outcomes of patients with opioid dependence treated with MMT vs an alternative treatment, psychosocially enriched 180-day methadone-assisted detoxification. DESIGN: Randomized controlled trial conducted from May 1995 to April 1999. SETTING: Research clinic in an established drug treatment service. PATIENTS: Of 858 volunteers screened, 179 adults with diagnosed opioid dependence were randomized into the study; 154 completed 12 weeks of follow-up. INTERVENTIONS: Patients were randomized to MMT (n = 91), which required 2 hours of psychosocial therapy per week during the first 6 months; or detoxification (n = 88), which required 3 hours of psychosocial therapy per week, 14 education sessions, and 1 hour of cocaine group therapy, if appropriate, for 6 months, and 6 months of (nonmethadone) aftercare services. MAIN OUTCOME MEASURES: Treatment retention, heroin and cocaine abstinence (by self-report and monthly urinalysis), human immunodeficiency virus (HIV) risk behaviors (Risk of AIDS Behavior scale score), and function in 5 problem areas: employment, family, psychiatric, legal, and alcohol use (Addiction Severity Index), compared by intervention group. RESULTS: Methadone maintenance therapy resulted in greater treatment retention (median, 438.5 vs 174.0 days) and lower heroin use rates than did detoxification. Cocaine use was more closely related to study dropout in detoxification than in MMT. Methadone maintenance therapy resulted in a lower rate of drug-related (mean [SD] at 12 months, 2.17 [3.88] vs 3.73 [6.86]) but not sex-related HIV risk behaviors and in a lower severity score for legal status (mean [SD] at 12 months, 0.05 [0.13] vs 0.13 [0.19]). There were no differences between groups in employment or family functioning or alcohol use. In both groups, monthly heroin use rates were 50% or greater, but days of use per month dropped markedly from baseline. CONCLUSIONS: Our results confirm the usefulness of MMT in reducing heroin use and HIV risk behaviors. Illicit opioid use continued in both groups, but frequency was reduced. Results do not provide support for diverting resources from MMT into long-term detoxification.

Adult↗

Collectins and innate immunity in the lung.

Evidence from both in vitro and in vivo studies suggests that the collectins are important elements in host innate immune defences against infectious agents. Study of the collectins in specific disease settings now raises the prospects of developing therapies exploiting these mechanisms of innate immunity.

Animals↗

Premorbid brain size is a determinant of functional reserve in abstinent crack-cocaine and crack-cocaine-alcohol-dependent adults.

Studies of Alzheimer's disease patients show that individuals with larger premorbid brains have a later onset of disease, or a lessened severity of cognitive impairment, or both. This may be due to a "functional reserve" associated with the greater number of neurons and synapses available in larger brains. We used magnetic resonance imaging and the MicroCog Assessment of Cognitive Functioning to examine the association between intracranial volume (premorbid brain size) and neuropsychological function in abstinent crack-cocaine and crack-cocaine-alcohol dependent individuals. There were no significant differences between the crack-only and the crack-alcohol dependent participants in neuropsychological performance or in intracranial volume. The abstinent cocaine-dependent individuals (both crack-only and crack-alcohol) were significantly impaired in many neuropsychological domains. Intracranial volume accounted for a significant proportion of the variance in neuropsychological performance. This result is consistent with the finding in the Alzheimer's literature that larger brains can maintain function to a greater degree, or for a longer period of time, in the face of cerebral disease or insult. Functional reserve may be a heretofore little recognized protective mechanism of the brain that has consequences for the severity of expression of cerebral disease or insult throughout life.

Adult↗

Self-efficacy and illicit opioid use in a 180-day methadone detoxification treatment.

Self-efficacy ratings coincided with illicit opioid use across the 3 phases of a 180-day methadone detoxification treatment. Efficacy ratings increased after patients received their first dose of methadone, did not change while they were maintained on a stable dose of methadone, and declined during the taper as they attempted to face high-risk situations without the full benefit of methadone. Efficacy ratings measured at a point before a phase of treatment predicted illicit opioid use across that phase. For clarification of the relation between self-efficacy and illicit opioid use, 3 conceptual models proposed by J.S. Baer, C.S. Holt, and E. Lichtenstein (1986) were tested. Self-efficacy influenced subsequent drug use in parallel with previous behavior, but this influence was found only at the start of the stabilization phase and immediately before the start of the taper phase. These findings highlight the usefulness of the self-efficacy concept for the treatment of opioid addiction.

Adult↗

Treatment research with crack-cocaine-dependent male veterans: the efficacy of different recruitment strategies.

Crack cocaine dependence rapidly leads to physical deterioration and severe social consequences. There is no widely accepted standard of treatment. As such, it is important to attract broad samples of patients into treatment research to improve efficacy and to establish generalizability. Better understanding of what attracts different subgroups of cocaine users into treatment, particularly research-based treatment, is needed. This article assesses the efficacy of six different recruitment strategies for attracting different populations of male veterans into treatment for crack cocaine dependence. New directions are outlined for the examination of recruitment strategies.

Adolescent↗

Continuity of care and desipramine in primary cocaine abusers.

The objective of this research was to determine the efficacy of enhanced continuity of care and desipramine in increasing treatment attendance and abstinence from cocaine in primary cocaine abusers. Study design was a random assignment, placebo-controlled factorial with assessments at baseline and at 3 (first week of outpatient treatment), 8, and 12 weeks after start of study. Desipramine blood levels were taken at weeks 2 (inpatient), 3, and 8. Subjects (N = 94 men) were recruited on an inpatient ward and assigned to increased continuity of care or to standard treatment, and to active or placebo drug. Main outcome variables were toxicology-verified reports of cocaine use, and attendance at counseling sessions. Enhanced continuity of care increased abstinence from cocaine at week 3 and increased attendance at individual counseling sessions throughout the 12 weeks of the study. There were no main effects for desipramine. Blood levels above 123 ng/ml at week 2 predicted longer stays in outpatient. We conclude that enhanced continuity of care is a low cost intervention that improves early treatment outcome and attendance; desipramine effects do not warrant its therapeutic use.

Adult↗

Needle exchange programs and social policy.

The specter of AIDS will continue to dominate the concerns of clinicians, policy-makers, and social scientists into the next century. In addition to being a biological issue, HIV disease is a political issue. As a result of this, interest groups have mobilized to restrict certain interventions aimed at stopping the spread of HIV. Among those restricted interventions is the exchange of sterile needles and syringes for "dirty" needles and syringes with injection drug users (IDUs). Increasing the availability of clean equipment by removing the laws restricting their availability, and/or by funding needle exchange programs, would appear to be a much needed and rational public health policy. However, needle exchange programs have been viewed as fostering drug addiction or enabling drug addicts, thus marginalizing it as an early stage of treatment for addicts and as a demonstrated public health intervention. There is no empirical evidence to support this conclusion. In the absence of better knowledge about how to prevent the use of illicit injection drugs and how to effectively treat IDUs, we believe that needle exchange programs (NEPs) need to be implemented for several key reasons. First, they can help slow the spread of HIV infection. Second, they can be cost-effective when compared to the higher health care costs that result without needle exchange programs. Third, they can act as a precursor to treatment, or recovery, for addicts.

Cost-Benefit Analysis↗

Opioid use in the treatment of chronic pain: assessment of addiction.

Addiction medicine specialists, besieged with the adverse consequences of opioids, not unreasonably develop reservations about their use. Opioid prohibition may be appropriate when working with addicts, but drug abstinence is not always the most appropriate nor optimal treatment of pain patients. Consultation concerning the management of chronic pain patients may require an attitude adjustment of challenging proportions for the addiction medicine specialist; it is a role substantially different from that usually assumed in treating alcohol- and drug-dependent patients. Rather than relentlessly pursuing psychotropic drug abstinence as the treatment goal, restoration of function should be the primary treatment goal for the chronic pain patient. Unlike the chemically dependent patient whose level of function is impaired by substance use, the chronic pain patient's level of function may improve with adequate, judicious use of medications, which may include opioids. Evaluating for addiction in a patient who is prescribed long-term opioids for pain control is often problematic. While the concept of addiction may include the symptoms of physical dependence and tolerance, physical dependence and/or tolerance alone does not equate with addiction. In the chronic pain patient taking long-term opioids, physical dependence and tolerance should be expected, but the maladaptive behavior changes associated with addiction are not expected. Thus, it is the presence of these behaviors in the chronic pain patient that is far more important in diagnosing addiction.

Chronic Disease↗

Opioids, chronic pain, and the law.

As the United States continues its "War on Drugs," physicians who prescribe opioids for the purpose of pain control must recognize that legal issues are an important part of the prescription process. Physicians who do not correctly prescribe opioids may mark their patients as drug abusers and themselves as misprescribers. Efforts are under way to characterize appropriately the conditions under which opioids should be prescribed for the management of pain. California and Texas have passed intractable pain laws, which permit the prescribing of opioid medication for chronic pain patients. These laws were necessary because claims were made against prescribers who legitimately administered opioids to chronic pain patients. Physicians must be aware that once a patient has been diagnosed an addict, it is not legal to prescribe opioids for the purpose of maintaining or detoxifying that patient; treatment of pain is still permissible, however. It is clear that new standards of care must be developed to reduce the liability of legitimate prescribers from sanctions in either criminal or civil settings. With new standards of care, prescriptions for opioids written in good faith for the treatment of pain should survive legal scrutiny.

Chronic Disease↗

Laboratory tests for rapid screening of drugs of abuse in the workplace: a review.

The use of rapid, on-site drug detection devices is reviewed. These tests permit the detection of various psychoactive substances in urine, and are easily used by nonskilled personnel. Saliva tests are available for detection of alcohol. These rapid tests have varying degrees of accuracy, and it is recommended that positive outcomes for all rapid tests be verified by standard laboratory procedures. The tests have potential use in the emergency room, doctor's office, drug treatment program, and the work place. When access to formal laboratory testing is limited by either time or location, an easily portable test can give critical information. A number of commercially available tests are reviewed for method, accuracy, advantages and disadvantages. Consequently, the interested practitioner should be able to find a suitable screening test from among the tests reviewed.

Humans↗

The role of physicians as medical review officers in workplace drug testing programs. In pursuit of the last nanogram.

In discussing the role of physicians in workplace drug testing programs, I focus on the recent Department of Transportation regulations that require drug testing in such regulated industries as interstate trucking, air transportation, mass transit, and the railroads. These regulations require that applicable drug testing programs employ physicians as medical review officers to evaluate positive tests that have been screened and confirmed by different techniques to determine if there is a legal medical explanation for the result. The drug testing program tests for the presence of amphetamine, cocaine, tetrahydrocannabinol, opiates, and phencyclidine. If an employee testing positive has an acceptable medical explanation, the result is to be reported as negative. Little practical advice exists for medical review officers, and they must be aware of key elements of the regulations and potential trouble spots.

Confidentiality↗