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Biomedical subjects

D M Simpson

Publications and source records attributed to D M Simpson.

At least 55 records · Page 3Linked to original sources
PubMed1999

Neuromuscular complications of the human immunodeficiency virus type 1 infection.

Neuromuscular disorders are the most frequent neurologic complications associated with human immunodeficiency virus (HIV) infection and AIDS. Although neurologic disorders are frequently overlooked, they add considerable morbidity and mortality to patients with HIV infection. It is critically important to properly diagnose and treat these neuromuscular complications, which leads to substantial improvement in patients' quality of life. Distal symmetric polyneuropathy is the most common form of peripheral neuropathy in HIV infection. It occurs mainly in patients with advanced immunosuppression and may also result from the neurotoxicity of several antiretroviral agents. Myopathy may occur at any stage of HIV disease and has also been described as a toxic side effect of zidovudine. Here we review the clinical features, diagnostic approach, and pathogenetic mechanisms of the neuromuscular complications of HIV infection. We also discuss management strategies and the results of clinical trials for the treatment of these disorders.

HIV Infections↗
PubMed1999

Thalidomide for the treatment of esophageal aphthous ulcers in patients with human immunodeficiency virus infection. National Institute of Allergy and Infectious Disease AIDS Clinical Trials Group.

A multicenter, double-blind, randomized, placebo-controlled clinical trial was conducted to determine the safety and efficacy of thalidomide for treating esophageal aphthous ulceration in persons infected with human immunodeficiency virus (HIV). Twenty-four HIV-infected patients with biopsy-confirmed aphthous ulceration of the esophagus were randomly assigned to receive either oral thalidomide, 200 mg/day, or oral placebo daily for 4 weeks. Eight (73%) of 11 patients randomized to receive thalidomide had complete healing of aphthous ulcers at the 4-week endoscopic evaluation, compared with 3 (23%) of 13 placebo-randomized patients (odds ratio, 13.82; 95% confidence interval, 1.16-823.75; P=.033). Odynophagia and impaired eating ability caused by esophageal aphthae were improved markedly by thalidomide treatment. Adverse events among patients receiving thalidomide included somnolence (4 patients), rash (2 patients), and peripheral sensory neuropathy (3 patients). Thalidomide is effective in healing aphthous ulceration of the esophagus in patients infected with HIV.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Human immunodeficiency virus-associated dementia: review of pathogenesis, prophylaxis, and treatment studies of zidovudine therapy.

Human immunodeficiency virus (HIV)-associated dementia (HIVD) has been reported in up to 15% of HIV-infected adult patients. Although the pathogenesis of HIVD remains unclear, HIV probably plays an important role in the syndrome, as evidenced by the correlation between cerebrospinal fluid (CSF) HIV load and neuropsychological functioning. Although a large number of antiretrovirals are used to treat HIVD, zidovudine is the best studied. Zidovudine therapy has been associated with reduced levels of HIV RNA in CSF, fewer HIV-related changes in brain tissue at autopsy, and time-limited improvements in neurological function among AIDS and HIVD patients. More recent studies have investigated the penetration into CSF of other antiretrovirals, including protease inhibitors, and the clinical efficacy of abacavir in the treatment of dementia. HIV encephalopathy may occur in 30%-60% of children with AIDS and causes significant disability. Zidovudine has been associated with improved neuropsychological functioning in children with progressive encephalopathy, but optimum dosing levels, duration of effect, and prophylactic potential remain to be demonstrated.

AIDS Dementia Complex↗
PubMed1999

HAART improves prognosis in HIV-associated progressive multifocal leukoencephalopathy.

Introduction of highly active antiretroviral therapy (HAART) has been associated with many changes in the complications of human immunodeficiency virus (HIV) infection. A cohort of 25 HIV patients with progressive multifocal leukoencephalopathy (PML) treated with HAART experienced a median survival of >46 weeks. This is an improvement in prognosis compared with recent historic experience and correlated with HIV RNA viral load reductions. We conclude that current HIV therapy is important in improving the outlook of PML in the setting of HIV.

Adult↗
PubMed1999

MR findings in AIDS-associated myelopathy.

BACKGROUND AND PURPOSE: The most common cause of spinal cord disease among patients with AIDS or those infected with HIV-1 is AIDS-associated myelopathy. The purpose of this study was to determine the MR characteristics of the spinal cord in this patient population and to correlate these findings with the clinical severity of myelopathy. METHODS: MR images of the spinal cord in 21 patients with documented HIV-1 infection or AIDS and a clinical diagnosis of AIDS-associated myelopathy were assessed retrospectively for atrophy, intrinsic signal abnormality, and abnormal enhancement. The clinical severity of myelopathy was graded by a neurologist on the basis of physical examination, and a qualitative correlation was made with the MR findings. RESULTS: MR findings were abnormal in 18 of the 21 patients. The most common feature was spinal cord atrophy (n = 15), typically involving the thoracic cord with or without cervical cord involvement, followed by intrinsic cord signal abnormality (n = 6), and normal-appearing cord (n = 3). Three patients had both cord atrophy and intrinsic cord signal abnormality. The cord signal abnormality was diffuse, without predilection for any specific distribution pattern. Enhancement was not seen in any of the 10 patients who received intravenous contrast material. Only one of 16 patients with moderate to severe myelopathy had normal MR findings, as compared with two of five patients with mild myelopathy. CONCLUSION: MR findings in the spinal cord are abnormal in the majority of patients with AIDS-associated myelopathy, typically showing spinal cord atrophy, with or without intrinsic cord signal abnormality. Patients with moderate to severe myelopathy have an increased frequency of spinal cord abnormalities, but a definite correlation between clinical severity of myelopathy and extent of MR abnormalities remains to be established.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Neuromuscular function in HIV infection: analysis of a placebo-controlled combination antiretroviral trial. AIDS Clinical Group 175/801 Study Team.

OBJECTIVE: To determine the frequency of peripheral neuropathy and myopathy in HIV-infected subjects enrolled in a combination antiretroviral treatment trial. DESIGN AND METHODS: AIDS Clinical Trial Group (ACTG) protocol 175 was a multicenter, double-blind, placebo-controlled, clinical trial. A total of 2467 subjects were randomized to one of four single or combination regimens, containing zidovudine (ZDV), didanosine (ddl), zalcitabine (ddC), and their respective placebos. Site investigators reported peripheral neuropathy, and the diagnosis of distal symmetrical neuropathy (DSP) was established by the study authors. Myalgia, muscle weakness and creatine phosphokinase (CPK) were prospectively assessed in a subset of the antiretroviral-naive cohort (n = 1067). RESULTS: Of 222 site diagnoses of neuropathy, 109 (49%) were DSP. There was a significant difference between treatment arms for rate of DSP and time to first grade 2 or higher DSP (ZDV-ddC, 6%; ZDV, 4%; ZDV-ddl, 4%; ddl, 3%; P = 0.029). Age and Karnofsky score were significant predictors of DSP. Fifty-six (54%) out of 104 patients with DSP remained on study medication at full (n = 29) or reduced (n = 27) dose within 6 months of developing neuropathy. There was no significant difference between treatment arms in the rate of myalgia or muscle weakness. The median CPK of subjects on ZDV-ddC was significantly higher than other study treatments, although CPK levels did not correlate with symptoms of myopathy. Only six subjects were diagnosed with myopathy during the study (one ZDV-ddl, one ZDV-ddC, and four ddl). CONCLUSIONS: DSP and myopathy may occur with current dosing regimens of combination antiretroviral therapy, and should be diagnosed using stringent criteria. ZDV-ddC was associated with the highest rate of DSP, although features of myopathy were not significantly different between treatment regimens.

Adult↗
PubMed1998

When acculturation hurts: the case of immunization.

The study examined the relationship between the acculturation of Mexican American mothers in Texas and immunization status of their children between 3 and 24 months of age. Mothers' acculturation, demographic characteristics, and immunization status of their children were assessed in in-person interviews with a sample of Mexican American respondents representative for Texas (n = 2193). Acculturation was measured with ten scales assessing oral and written language use, proficiency, and preference, music and TV viewing preferences, ethnic identity, place where a person was reared, and contacts with Mexico. Immunization status, defined according to the recommendation of the CDC Advisory Committee on Immunization Practices, was determined from official shot records obtained directly from respondents or, for respondents without records, obtained from their health care providers. Regression analysis revealed that acculturation significantly contributed to inadequate immunization status, even when socioeconomic status and other demographic covariates of acculturation were statistically controlled. Mediational analysis revealed that acculturation contributed to inadequate immunization through less positive attitudes toward immunization, a diminished sense of parental responsibility for children's immunization, and more perceived barriers to immunization. It is concluded that culture-specific beliefs encouraging childhood immunization should be fostered among Mexican Americans.

Acculturation↗
PubMed1998

AIDS-associated vacuolar myelopathy.

AIDS-associated vacuolar myelopathy (VM) is a common neurologic complication of AIDS. Pathologically, VM is characterized by vacuolization in the lateral and posterior columns of the thoracic spinal cord and has a striking similarity with the myelopathy of vitamin B12 deficiency. In autopsy series, 20% to 55% of patients with AIDS have evidence of spinal cord disease consistent with VM. The myelopathy usually manifests late in the course of HIV infection, with slowly progressive weakness of the lower extremities, gait disorder, sensory abnormalities in the legs, impotence in men, and urinary frequency and urgency. Its course is invariably progressive and leads to severe paralysis of the lower limbs, with loss of the ability to walk and of sphincter control. The differential diagnosis is extensive and includes metabolic, infective, and neoplastic spinal cord diseases. The diagnosis is based on the clinical observation and the exclusion of other causes of myelopathy via serologic, radiographic, and cerebrospinal fluid studies. The pathogenesis of VM is unknown. Attempts to detect HIV in the spinal cord have not yielded significant results, and there is no evidence of a relationship between the presence of HIV and the development of myelopathy. A metabolic disorder of the vitamin B12-dependent transmethylation pathway, induced by HIV or cytokine activation, is considered the possible cause of VM associated with AIDS. There is no known treatment for AIDS myelopathy and there is no evidence that antiretroviral drugs can improve the symptoms or slow the progression of VM. The symptomatic treatment includes antispasticity agents, management of sphincter dysfunction, and physical therapy. Experimental treatments are being tested in clinical trials.

Diagnosis, Differential↗
PubMed1998

A pilot study of L-methionine for the treatment of AIDS-associated myelopathy.

The pathogenesis of AIDS-associated vacuolar myelopathy (VM) may be related to abnormality of transmethylation mechanisms in the nervous system. To evaluate the safety and potential efficacy of the methyl-group donor L-methionine in AIDS-associated VM, we conducted a pilot clinical trial in 12 patients with VM. Seven of the nine patients who completed the study had clinical and electrophysiologic improvement. Controlled studies may be indicated to assess the efficacy and safety of L-methionine in AIDS-associated VM.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Lower extremity manifestations of neuromuscular diseases.

Neuromuscular disorders must be considered when a patient presents with a pes cavus deformity; lower extremity weakness; difficulty in walking; or cramps, stiffness, fatigue, pain, or paresthesia in the extremities. In those instances in which a neurologic disease is considered, distinctions between central and peripheral nervous system origin, focal versus generalized pathology, and static versus progressive course are critical in the diagnosis and treatment of the disorder. The complexities of the nervous system often result in missed or delayed diagnosis of these syndromes. Patients affected with neurologic diseases often require diagnostic and therapeutic interventions from various specialists. This article presents a systematic approach to the patient with a neurologic disorder, with special emphasis on neuromuscular manifestations in the lower extremities. Key observations to aid in the recognition of neuromuscular dysfunction are presented, along with an approach to diagnostic evaluation and management for these patients.

Foot Diseases↗
PubMed1997

Immunoblot studies of the acid-labile subunit (ALS) in biological fluids, normal human serum and in children with GH deficiency and GH receptor deficiency before and after long-term therapy with GH or IGF-I respectively.

OBJECTIVE: The aims of this investigation were (a) to study the presence of immunoreactive forms of the acid-labile subunit (ALS) in different human biological fluids, (b) to define the age dependence of serum ALS in normal children and adults and (c) to compare the regulation of ALS by GH or IGF-I in children with GH deficiency (GHD) and GH receptor deficiency (GHRD) before and after 1 year of therapy with GH or IGF-I, respectively. DESIGN AND PATIENTS: Selected human biological fluids from different consenting volunteers and serum from 68 normal children and 5 adults were analysed. Four children diagnosed as GHD and 7 children diagnosed as GHRD were treated with recombinant human (rh) GH at a dosage of 0.05 mg/kg/day s.c. or rhIGF-I at a dosage of 120 micrograms/kg twice daily s.c., respectively, for 12 months. MEASUREMENTS: Immunoreactive forms of ALS were studied by Western immunoblot using a specific rabbit antiserum derived against synthetic human ALS and quantified by laser densitometry analysis. Serum from children with GHD or GHRD were sampled before and at 6 and 12 months of therapy; serum from these patients had been also assayed at baseline for determination of IGF-I and IGF binding protein (IGFBP)-3 by radioimmunoassay and immunoradiometric assay, respectively. RESULTS: An immunoreactive 85 kDa doublet of ALS was detected in serum, plasma, follicular, peritoneal and synovial fluid, but not in urine, seminal plasma, amniotic or extra-embryonic coelomic fluids. Assessment of serum from newborns to adults revealed an age dependence; the ALS doublet was low, but detectable, in newborns, increased during adolescence and remained constant in adulthood. ALS levels were significantly lower in GHD (P = 0.02) and in GHRD children (P = 0.001) than in age-matched controls. Treatment with rhGH in GHD children produced a 2.7-fold increase in serum ALS concentrations at 6 months of therapy (P = 0.01), which was maintained after 1 year of treatment (P = 0.006), leading to normalization of ALS concentrations. In contrast, administration of rhIGF-I to GHRD children failed to increase and normalize serum ALS levels either at 6 or 12 months of therapy. CONCLUSIONS: Immunoreactive forms of acid-labile subunit are present in serum and plasma, as well as in follicular, peritoneal and synovial fluids, suggesting that acid-labile subunit can either cross the capillary barrier or be secreted locally. Acid-labile subunit concentrations are age-dependent with a sharp increase during adolescence, and are reduced in GH deficient and GH receptor deficient children. While treatment with rhGH is able to increase and normalize acid-labile subunit concentrations in GH deficient children, therapy with rhIGF-I fails to increase serum acid-labile subunit levels in GH receptor deficient patients. These data suggest that acid-labile subunit is directly GH-regulated, and that IGF-I cannot increase acid-labile subunit levels, as assessed by Western immunoblot.

Adolescent↗
PubMed1997

Errors and correlates in parental recall of child immunizations: effects on vaccination coverage estimates.

OBJECTIVE: We evaluated the accuracy of parental recall of children's immunization histories as compared with provider records and examined how errors in parental recall correlate with sociodemographic characteristics. DESIGN: The validation study was part of a population-based household survey designed to assess immunization levels among Texas children under age 2 years. For 72% (n = 3278), interviewers used vaccination records from the parent to copy dates for the diphtheria and tetanus toxoids and pertussis vaccine (DTP), oral polio vaccine (OPV), and measles, mumps, and rubella (MMR) shots. For parents without shot records (n = 1216), interviewers asked about each vaccine, whether the child had received the shot, how many, and at what age. Of these, 85% (n = 1029) were validated with health provider records. RESULTS: Measured against provider records, only 34% of parents accurately recalled the number of DTP shots a child had. More often (42%) parents underestimated the number of DTP shots than overestimated (24%). Agreement between parental recall and provider records was high (83%) for the single dose of MMR. Accuracy of parents' recall did not differ by race/ethnicity, education level, or type of health insurance coverage, but decreased as child's age increased. Having a vaccination record at home was associated with a higher immunization status. Hispanic, lower educated, and uninsured parents were more likely to have a vaccination record than non-Hispanic, higher educated, and privately insured parents. DISCUSSION: Validity of parental recall of children's immunization histories depends on the vaccine and the age of the child, which is highly correlated with the number of shots parents must recollect. Results suggest that inclusion of parent recall information from vaccination surveys underestimates DTP:OPV:MMR coverage. This underestimation is consistent across economic and race/ethnic groups. Thus, community surveys based on cards and recall should provide reliable conclusions about which groups need intensive program efforts. For the routine monitoring of vaccination coverage, reasonable estimates can be obtained by combining parent-held record and parent recall data. Caution is required when comparing coverage estimates from different surveys since the source of information and method of derivation will produce widely varying coverage rates.

Black or African American↗
PubMed1997

The impact of public assistance factors on the immunization levels of children younger than 2 years.

OBJECTIVES: This study examined how children's immunization status varied with enrollment in the Women, Infants, and Children (WIC); Aid to Families with Dependent Children (AFDC); food stamp; and Medicaid programs. METHODS: A statewide survey was used to determine the percentage of children less than 2 years of age who were up to date for diphtheria, tetanus, and pertussis; polio; and measles, mumps, and rubella vaccines. RESULTS: WIC and uninsured children were more likely and AFDC and Medicaid children less likely to be up to date than others. CONCLUSIONS: The higher immunization status of WIC and uninsured children suggests that integrating immunization practices with government programs may be effective.

Aid to Families with Dependent Children↗
PubMed1997

Botulinum toxin increases tearing in patients with Sjögren's syndrome: a preliminary report.

Three patients with Sjögren's syndrome (SS) who had severe xerophthalmia and blepharospasm received botulinum toxin injections for the treatment of their blepharospasm. They had a remarkable increase in tearing, measured by Schirmer's test, and a decrease in signs and symptoms of dry eyes after botulinum toxin injection periorbitally for blepharospasm. The mechanism for this increased tearing is unclear, but suggests a potential treatment for patients with severe xerophthalmia with SS.

Aged↗
PubMed1997

Traditional pharmacological treatments for spasticity. Part I: Local treatments.

Spasticity is a velocity-dependent increase in stretch reflex activity. It is one of the forms of muscle overactivity that may affect patients with damage to the central nervous system. Spasticity monitoring is relevant to function because the degree of spasticity may reflect the intensity of other disabling types of muscle overactivity, such as unwanted antagonistic co-contractions, permanent muscle activity in the absence of any stretch or volitional command (spastic dystonia), or inappropriate responses to cutaneous or vegetative inputs. In addition, spasticity, like other muscle overactivity, can cause muscle shortening, which is another significant source of disability. Finally, spasticity is the only form of muscle overactivity easily quantifiable at the bedside. Under the name pharmacological treatments of spasticity, we understand the use of agents designed to reduce all types of muscle overactivity, by reducing excitability of motor pathways, at the level of the central nervous system, the neuromuscular junctions, or the muscle. Pharmacologic treatment should be an adjunct to muscle lengthening and training of antagonists. Localized muscle overactivity of specific muscle groups is often seen in a number of common pathologies, including stroke and traumatic brain injury. In these cases, we favor the use of local treatments in those muscles where overactivity is most disabling, by injection into muscle (neuromuscular block) or close to the nerve supplying the muscle (perineural block). Two types of local agents have been used in addition to the newly emerged botulinum toxin: local anesthetics (lidocaine and congeners), with a fully reversible action of short duration, and alcohols (ethanol and phenol), with a longer duration of action. Local anesthetics block both afferent and efferent messages. The onset of action is within minutes and duration of action varies between one and several hours according to the agent used. Their use requires resuscitation equipment available close by. When a long-lasting blocking agent is being considered, we favor the use of transient blocks with local anesthetics for therapeutic tests or diagnostic procedures to answer the following questions: Can function be improved by the block? What are the roles played by overactivity and contracture in the impairment of function? Which muscle is contributing to pathologic posturing? What is the true level of performance of antagonistic muscles? A short-acting anesthetic can also serve as preparation to casting or as an analgesic for intramuscular injections of other antispastic treatment. Alcohol and phenol provide long-term chemical neurolysis through destruction of peripheral nerve. Experience with ethanol is more developed in children using intramuscular injection, while experience with phenol is greater in adults with perineural injection. In both cases, there are anecdotal reports of efficacy but studies have rarely been controlled. Side effects are numerous and include pain during injection, chronic dysesthesia and chronic pain, and episodes of local or regional vascular complications by vessel toxicity. In the absence of controlled studies, a theoretical comparison of neurolytic agents with botulinum toxin is proposed. Neurolytic agents may be preferred to botulinum toxin on a number of grounds, including earlier onset, potentially longer duration of effect, lower cost, and easier storage. Conversely, pain during injection, tissue destruction with chronic sensory side effects, and lack of selectivity on motor function with neurolytic agents may favor the use of botulinum toxin. Neurolytic agents and botulinum toxin may be used in combination, the former for larger proximal muscles and the latter for selective injection into distal muscles. In the future, neurolytic agents may prove more appropriate in very severely affected patients for whom the purposes of the block are comfort and hygiene. (ABSTRACT TRUNCATED)

Adult↗