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Biomedical subjects

D M Simpson

Publications and source records attributed to D M Simpson.

At least 73 records · Page 4Linked to original sources
PubMed1997

Traditional pharmacological treatments for spasticity. Part II: General and regional treatments.

Systemic pharmacologic treatments may be indicated in conditions in which the distribution of muscle overactivity is diffuse. Antispastic drugs act in the CNS either by suppression of excitation (glutamate) enhancement of inhibition (GABA, glycine), or a combination of the two. Only four drugs are currently approved by the US FDA as antispactic agents: baclofen, diazepam, dantrolene sodium, and tizanidine. However, there are a number of other drugs available with proven antispastic action. This chapter reviews the pharmacology, physiology of action, dosage, and results from controlled clinical trials on side effects, efficacy, and indications for 21 drugs in several categories. Categories reviewed include agents acting through the GABAergic system (baclofen, benzodiazepines, piracetam, progabide); drugs affecting ion flux (dantrolene sodium, lamotrigine, riluzole; drugs acting on monoamines (tizanidine, clonidine, thymoxamine, beta blockers, and cyproheptadine); drugs acting on excitatory amino acids (orphenadrine citrate); cannabinoids; inhibitory neuromediators; and other miscellaneous agents. The technique, advantages and limitations of intrathecal administration of baclofen, morphine, and midazolam are reviewed. Two consistent limitations appear throughout the controlled studies reviewed: the lack of quantitative and sensitive functional assessment and the lack of comparative trials between different agents. In the majority of trials in which meaningful functional assessment was included, the study drug failed to improve function, even though the antispastic action was significant. Placebo-controlled trials of virtually all major centrally acting antispastic agents have shown that sedation, reduction of global performance, and muscle weakness are frequent side effects. It appears preferable to use centrally acting drugs such as baclofen, tizanidine, and diazepam in spasticity of spinal origin (spinal cord injury and multiple sclerosis), whereas dantrolene sodium, due to its primarily peripheral mechanism of action, may be preferable in spasticity of cerebral origin (stroke and traumatic brain injury) where sensitivity to sedating effects is generally higher. Intrathecal administration of antispastic drugs has been used mainly in cases of muscle overactivity occurring primarily in the lower limbs in nonambulatory, severely disabled patients but new indications may emerge in spasticity of cerebral origin. Intrathecal therapy is an invasive procedure involving long-term implantation of a foreign device, and the potential disadvantages must be weighed against the level of disability in each patient and the resistance to other forms of antispastic therapy. In all forms of treatment of muscle overactivity, one must distinguish between two different goals of therapy: improvement of active function and improvement of hygiene and comfort. The risk of global performance reduction associated with general or regional administration of antispastic drugs may be more acceptable when the primary goal of therapy is hygiene and comfort than when active function is a priority.

Humans↗
PubMed1997

Clinical trials of botulinum toxin in the treatment of spasticity.

Botulinum toxin has been tested as a treatment for spasticity resulting from cerebral palsy, multiple sclerosis, traumatic brain injury, spinal cord injury, and stroke. The results of 18 studies are reviewed in this article. In both open label and double-blind, placebo-controlled trials, botulinum toxin has proven to be an effective measure for reduction of focal spasticity. Improvements have been documented in tone reduction, range of motion, hygiene, autonomic dysreflexia, gait pattern, positioning, and other criteria, though not all criteria tested showed improvement in all studies. In none of the studies were there significant adverse effects. Future trials may be improved by refinement of several design parameters, including patient selection, treatment timing, and selection of dose and injection site.

Anti-Dyskinesia Agents↗
PubMed1996

Insulin-like growth factor-binding proteins (IGFBPs) and their regulatory dynamics.

The IGFBPs are a family of homologous proteins that have co-evolved with the IGFs and that confer upon the IGF regulatory system both functional and tissue specificity. IGFBPs are not merely carrier proteins for IGFs, but hold a central position in IGF ligand-receptor interactions through influences on both the bioavailability and distribution of IGFs in the extracellular environment. In addition, IGFBPs appear to have intrinsic biological activity independent of IGFs. The current status of research on IGFBPs is reviewed herein. Following a brief introduction to the entire IGF/IGFBP system, separate sections for each of the six cloned mammalian IGFBPs, the most extensive for IGFBP3, cover selected topics that emphasize the dynamics of IGFBPs--that is, their regulation in cells, their functionally important post-translational modifications, and their interactions in the cellular microenvironment--and how these dynamics influence physiological function.

Animals↗
PubMed1996

Neurologic manifestations of HIV infection.

A wide spectrum of central and peripheral nervous system abnormalities may be associated with HIV infection. These disorders may be caused by HIV infection, result as secondary complications related to immunosuppression, or be a neurotoxic effect of therapeutic agents. The range of neurologic disorders includes dementia, focal cerebral mass lesions, myelopathy, peripheral neuropathies, and myopathy. Early diagnosis and therapy is critical, and may result in substantial improvement in patients' quality and quantity of life. This article reviews the approach to differential diagnosis of these neurologic disorders and presents theories of pathogenesis and current approaches to treatment.

Anti-Bacterial Agents↗
PubMed1996

Calculation of area of stabilometric signals using principal component analysis.

In stabilometry, the sway of the human body in an upright posture is studied by monitoring the displacement of its centre of pressure in the lateral (x) and anterio-posterior (y) directions. The area covered by this trace has been defined as that of an ellipse fitted to the data. Conventionally, its angle of inclination is found through linear regression (LR) on the data in the x-y plane. In the present paper, principal component analysis (PCA) is proposed as providing a more suitable basis for the estimation of angle and area. Results of simulations and stabilometric tests confirm large differences between area and angle estimates obtained by regression of x over y, and y over x, with PCA generally agreeing with either one or the other of the LRs. The PCA technique is therefore recommended as an improved basis for measuring area and inclination of stabilograms, or similar data sets.

Data Interpretation, Statistical↗
PubMed1996

Oxandrolone in AIDS-wasting myopathy.

OBJECTIVE: To evaluate oxandrolone, an oral anabolic steroid with potent anabolic activity and minimal androgenic effects, for the treatment of AIDS-associated myopathy and wasting. METHODS: In a multicenter, double-blind study, 63 HIV-seropositive men with > 10% loss of body weight were randomized to receive either placebo, 5 mg/day oxandrolone, or 15 mg/day oxandrolone for 16 weeks. Body weight, neuromuscular evaluation, and measures of well-being were repeatedly assessed. RESULTS: Patients who received 15 mg/day oxandrolone showed weight gain throughout the 16-week treatment period. Overall, the 5 mg/day oxandrolone group maintained their weight gain over the 16-week period, whereas the placebo group showed continual weight loss. At week 16, significantly more patients in the 15 mg/day dose group reported increases in appetite and activity than those receiving placebo. There were no consistent, dose-related, statistically significant differences from baseline in laboratory values or adverse events. CONCLUSION: Oxandrolone, at a dose of either 5 mg/day or 15 mg/day, in contrast to placebo, had a positive impact on the weight and well-being of HIV-seropositive patients suffering from wasting and weakness. Measurable improvement in muscle strength was not noted at the doses employed in this study. Oxandrolone was well tolerated in all the patients who were enrolled in the study. Based on the results reported here, additional studies using higher doses of oxandrolone seem warranted.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Improving the reporting of notifiable diseases in Texas: suggestions from an Ad Hoc Committee of providers.

In an effort to increase passive surveillance in Texas, an ad hoc committee of private and public health providers met to suggest changes in the list of reportable diseases and ways to improve provider participation. This group noted several reasons to make changes in the list of reportable diseases. Deletion was suggested for diseases whose reports did not warrant action from public health authorities or for previously common diseases, which were now rare and occurred as isolated events. Reasons to add a disease were recognition of new conditions of public health importance or the observation that a previously rare disease was now becoming common. It was the group's consensus that diseases reportable by law need to reflect realistic public health responses.

Disease Notification↗
PubMed1996

Extraocular muscle involvement in Becker muscular dystrophy.

We report limitation of gaze and slow saccadic eye movements by clinical examination and video-oculography in a patient with Becker muscular dystrophy. This rare association suggests that a dystrophinopathy should be considered in a patient with features characteristic of Becker muscular dystrophy even when mild impairment of eye movements is present.

Adult↗
PubMed1996

Botulinum toxin type A in the treatment of upper extremity spasticity: a randomized, double-blind, placebo-controlled trial.

Spasticity is a disorder of excess muscle tone associated with CNS disease. We hypothesized that botulinum toxin, a neuromuscular blocking agent, would reduce tone in spastic muscles after stroke. This randomized, double-blind, placebo-controlled, multicenter clinical trial evaluated the safety and efficacy of botulinum toxin type A (BTXA) in the treatment of chronic upper limb spasticity after stroke. Thirty-nine patients received IM injections of a total dose of either 75, 150, or 300 units of BTXA or placebo into the biceps, flexor carpi radialis, and flexor carpi ulnaris muscles. At baseline, patients demonstrated a mean wrist flexor tone of 2.9 and elbow flexor tone of 2.6 on the Ashworth Scale (0 to 4). Treatment with the 300-unit BTXA dose resulted in a statistically and clinically significant mean decrease in wrist flexor tone of 1.2 (p = 0.028), 1.1 (p = 0.044), and 1.2 (p = 0.026) points and elbow flexor tone of 1.2 (p = 0.024), 1.2 (p = 0.028), and 1.1 (p = 0.199) at weeks 2, 4, and 6 postinjection. In the placebo group, tone reduction at the wrist was 0.3, 0.2, and 0.0 and at the elbow was 0.3, 0.3, and 0.6 at weeks 2, 4, and 6 postinjection. BTXA groups reported significant improvement on the physician and patient Global Assessment of Response to Treatment at weeks 4 and 6 postinjection. There were no serious adverse effects. In this 3-month study, BTXA safely reduced upper extremity muscle tone in patients with chronic spasticity after stroke.

Adult↗
PubMed1996

Peptide T in the treatment of painful distal neuropathy associated with AIDS: results of a placebo-controlled trial. The Peptide T Neuropathy Study Group.

OBJECTIVE: To assess the safety and efficacy of Peptide T in the treatment of painful distal symmetrical polyneuropathy (DSP) associated with human immunodeficiency virus (HIV) infection. BACKGROUND: Painful DSP is a frequent complication of HIV infection, although its etiology and optimal treatment are unknown. Peptide T (D-(alpha 1)-Peptide T-amide) has been found in phase I trials and anecdotal reports to relieve neuropathic pain in AIDS patients. DESIGN/METHODS: In this multicentered, double-blind, randomized study, subjects received intranasal Peptide T 6 mg/day or placebo for 12 weeks. The primary outcome measure was change in the modified Gracely pain score. Secondary efficacy variables were results of neurologic examination, neuropsychological and electrophysiologic studies, global evaluation, and CD4 lymphocyte counts. RESULTS: Of 81 evaluable subjects, 40 received Peptide T and 41 received placebo. The change in pain scores was not significantly different (p = 0.32) in the Peptide T group (-0.24) as compared to placebo (-0.39). Group comparisons were not significantly different for change in any clinical examination or neuropsychologic measure, sural nerve amplitude or conduction velocity, or CD4 lymphocyte count. No significant drug-related adverse effects occurred in either group. CONCLUSION: Intranasal Peptide T is safe but ineffective in the treatment of painful DSP associated with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Clozapine-induced myotoxicity in patients with chronic psychotic disorders.

Muscle dysfunction related to clozapine treatment is largely unrecognized. We evaluated weekly creatine kinase (CK) levels in 37 consecutive clozapine-treated outpatients with chronic psychotic disorders. Those with CK elevations underwent clinical neurologic evaluation, electromyography (EMG), and nerve conduction studies. Patients with probable myopathy had a quadriceps muscle biopsy. Twenty control patients had a single CK level determination. Twenty-nine of 37 clozapine-treated patients had CK elevations. Three patients had extreme CK elevations (> 20,000 IU/L), without myoglobinuria. Mean CK levels were significantly greater in clozapine patients (194 IU/L) than in control patients (142.3, p = 0.033). Of 18 clozapine-treated patients evaluated clinically, 6 had mild proximal weakness. EMG in 13 patients was myopathic in 5, normal in 5, and neurogenic in 3. Muscle biopsy in 5 patients showed rare regenerating myofibers and mild acute denervation (1), mild type II fiber atrophy (1), minimal acute denervation (1), and normal muscle (2). In conclusion, clozapine therapy may be associated with CK elevations and, rarely, mild myopathy.

Chronic Disease↗
PubMed1996

The immunization status of Texas children aged 3 to 24 months: results of the 1994 Texas immunization survey.

Texas has no routine system to determine current immunization levels in preschoolers. To determine the current immunization status of Texas children younger than 2 years, the Texas Department of Health commissioned a household survey in 1994. The survey included 4552 in-person interviews with parents or legal guardians of children aged 3 to 24 months. Results showed a statewide up-to-date immunization level of 55%. The younger the children, the more likely they were to be up-to-date. Differences were marked among groups based on geography, race/ethnicity, and use of public assistance. Hispanic children, children enrolled in the Women, Infants, and Children program, and children living in border communities had higher levels of immunizations. Immunization levels were below the statewide average for African-Americans, children on Aid to Families with Dependent Children, and children on Medicaid. Children with no health insurance and children with private insurance had equivalent immunization levels. Although progress appears to have been made in getting children immunized according to recommended schedules, much work remains to be done to reach our state and national goals and to protect our youngest from outbreaks of vaccine-preventable diseases.

Diphtheria-Tetanus-Pertussis Vaccine↗
PubMed1995

Nucleoside analogue-associated peripheral neuropathy in human immunodeficiency virus infection.

Peripheral nerve disorders are among the most common neurological complications of HIV disease. Distal sensory polyneuropathy (DSP) is the most common form of neuropathy in patients with AIDS and can be caused by diverse mechanisms, including infectious, metabolic, inflammatory, nutritional, and toxic factors. Antiretroviral agents may cause or contribute to HIV-related DSP. Recognition of peripheral neuropathy has become increasingly important as more patients receive nucleoside analogue agents for the treatment of HIV disease. It is crucial to correctly distinguish between the neuropathies caused by toxic effects of nucleoside analogues and those that are primarily related to underlying HIV disease, because timely diagnosis and proper treatment of peripheral neuropathies may allow the continuation of antiretroviral therapy as well as improve the quality of life. The identification and treatment of peripheral neuropathies associated with use of the nucleoside drugs zalcitabine (ddC), didanosine (ddI), and stavudine (d4T) are reviewed.

Animals↗
PubMed1995

Mitochondrial abnormalities in human immunodeficiency virus-associated myopathy.

There is controversy as to whether zidovudine (ZDV) induces a mitochondrial myopathy that is distinguishable from human immunodeficiency virus (HIV)-associated myopathy in ZDV-naive patients. Mitochondrial abnormalities were evaluated in skeletal muscle obtained from 18 HIV-positive, ZDV-exposed patients, and 9 who were drug naive. All patients had clinical myopathy, and underwent neuromuscular evaluation with information recorded on timing and dosage of ZDV. All underwent muscle biopsies and samples were examined without knowledge of clinical history or ZDV status. Biopsy samples were evaluated by light and electron microscopy. Mitochondrial abnormalities were seen in ZDV-treated and -naive groups, and did not correlate with ZDV exposure or cumulative ZDV dosage. Mitochondrial abnormalities displayed significant correlation with the presence and severity of myofiber degeneration on biopsy, regardless of ZDV status. As mitochondrial abnormalities reflect myofiber degeneration, present in both patient groups, they may not be used as evidence of primary mitochondrial dysfunction. The etiology of myofiber degeneration in patients with HIV infection, whether ZDV-exposed or -naive, remains unclear.

Adult↗
PubMed1995

Assessment of nutritional, clinical, and immunologic status of HIV-infected, inner-city patients with multiple risk factors.

OBJECTIVE: To evaluate the nutritional, clinical, and immunologic factors associated with human immunodeficiency virus (HIV)-infected, inner-city patients with multiple risk factors. DESIGN: Prospective cross-sectional nutrition evaluation of patients with HIV infection. SETTING: Patients were interviewed at the outpatient clinic at Mt Sinai Medical Center, New York City, NY. SUBJECTS: Our subjects were men and women older than 18 years of age and at all stages of HIV infection (n = 56). OUTCOME MEASURES: Anthropometric measurements, history of weight changes (maintenance of preillness body weight or decrease from preillness weight status), 3-day food records, and clinical laboratory tests. STATISTICAL ANALYSES: Tests were used to compare patients who were at a stable weight with patients who had lost weight with regard to the anthropometric, dietary, and clinical variables. Spearman's rank correlation coefficient and chi 2 tests were applied to examine correlations between pairs and differences in proportions, respectively. RESULTS: Patients were classified into groups according to whether they were at a stable weight (n = 25) or had lost weight (n = 31). All anthropometric measurements, CD4 lymphocytes, and CD8 lymphocytes were significantly lower in the patients who had lost weight. No differences were observed between the groups for absolute lymphocyte count or transferrin, hemoglobin, and albumin levels. The mean energy intake of the 56 patients was 74% of the Recommended Dietary Allowance (RDA). Forty-seven patients (84%) took vitamin and/or mineral supplements within a range of 2% to 50,000% of the RDA. No significant positive correlations were observed between nutrient intake, CD4 cells, and absolute lymphocyte count. CONCLUSIONS/APPLICATIONS: All anthropometric measurements, CD4 lymphocytes, and CD8 lymphocytes were notably lower in patients with weight loss. The mean energy intake of the subjects was only 74% of the RDA. Megadoses of vitamin supplements were taken by a large number of patients, but no significant positive effects were observed for absolute lymphocyte count and CD4 cells. Although supplementation of micronutrients may influence the progression of HIV infection, a balanced, nutritious diet may be more beneficial in maintaining or improving the physiologic status of the patients. However, members of a high-risk population may benefit less from HIV-related social services and food or nutrition resources. With the growing number of injection-drug users in the acquired immunodeficiency syndrome population, it will be essential to develop comprehensive strategies to address the interconnected needs for medical and nutrition care. Ensuring that patients have adequate meals during an extended course of treatment in the outpatient clinic or that dietitians have meals available in group settings or through home-delivery service may be the most appropriate nutrition intervention in these high-risk patients.

Adult↗
PubMed1994

Neurologic manifestations of HIV infection.

PURPOSE: To review the clinical features, pathogenetic mechanisms, and management of neurologic manifestations of human immunodeficiency virus (HIV) infection. DATA SOURCES: Studies published from 1983 to 1994 identified by MEDLINE literature search; Centers for Disease Control and Prevention reports; recent communications and abstracts; and authors' published and unpublished data. STUDY SELECTION: We selected studies that described the clinical characteristics of neurologic disorders in the acquired immunodeficiency syndrome (AIDS), basic science studies addressing the mechanisms of direct or indirect neurologic damage in HIV infection, and clinical trials investigating the effects of therapeutic agents on the neurologic complications of AIDS. DATA EXTRACTION: We evaluated information and data on epidemiologic characteristics, clinical manifestations, pathogenetic mechanisms, and therapy for neurologic complications of HIV disease and outlined a practical approach to assess and manage these disorders. DATA SYNTHESIS: In the past decade, basic and clinical studies have provided considerable information about neurologic manifestations of AIDS. Dementia is the most important "primary" neurologic complication of HIV infection. Focal lesions of the central nervous system include cerebral toxoplasmosis, lymphoma, and progressive multifocal leukoencephalopathy. Other opportunistic infections include cytomegalovirus encephalitis, cryptococcal meningitis, and neurosyphilis. Various peripheral neuropathies and myopathies may occur in association with HIV infection or as toxic effects of antiretroviral agents. CONCLUSIONS: The prevalence of neurologic complications associated with HIV disease will increase as more effective therapies allow persons with AIDS to live longer. Early recognition and treatment of these disorders substantially affect patients' quality of life and survival.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Multifocal cytomegalovirus demyelinative polyneuropathy associated with AIDS.

A 47-year-old man with acquired immunodeficiency syndrome presented 3 months antemortem with the onset of lower extremity sensory abnormalities. A progressive course of multifocal weakness and sensory disturbances ensued. Electrophysiologic studies revealed a generalized asymmetric demyelinating polyneuropathy with secondary axonal loss. The patient was sequentially treated with plasmapheresis, high dose corticosteroids, intravenous immune globulin, and ganciclovir. His neuropathy progressed, and he died of a fulminant bronchopneumonia. At autopsy the patient had a multifocal cytomegalovirus polyradiculoneuropathy, with both demyelinative and necrotizing features. While cytomegalovirus may be associated with a variety of peripheral nerve syndromes, its clinical presentation as a primary demyelinating polyneuropathy is unusual. Its importance vis-à-vis potential therapy for AIDS-associated neuropathies is discussed.

Acquired Immunodeficiency Syndrome↗