Treatment of Parkinson's disease with controlled-release Carbidopa/L-DOPA.
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Adult↗
Biomedical subjects
R Pahwa
Publications and source records attributed to R Pahwa.
Diabetes mellitus presenting as paroxysmal kinesigenic dystonic choreoathetosis.
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Aged↗
Botulinum toxin treatment of essential head tremor.
We examined in a double-blind, placebo-controlled study the effects of botulinum toxin in 10 patients with essential head tremor. Each subject received two treatments approximately 3 months apart, one with botulinum toxin injections and another with normal saline injections into the sternocleidomastoid and splenius capitis muscles. The subjects were assessed before each treatment and at 2, 4, and 8 weeks after injections. There was moderate to marked improvement in clinical ratings in five subjects after botulinum toxin injections and in one subject after placebo. There was moderate to marked subjective improvement in five patients with botulinum toxin as compared with three subjects with placebo. Side effects were mild and transient. We conclude that botulinum toxin may be useful for patients with essential head tremor who have failed to benefit from oral medications.
Aged↗
Envelope glycoproteins of HIV-1 interfere with T-cell-dependent B cell differentiation: role of CD4-MHC class II interaction in the effector phase of T cell help.
T-cell-dependent B cell differentiation involves two phases: an inductive phase of T cell activation followed by an effector phase, which involves stimulation of B cells by activated T cells. We have previously demonstrated that anti-CD3 mAb and antigen-induced T-cell-dependent B cell functions are inhibited by HIV-1 envelope glycoprotein, gp120, at the inductive phase of T-cell-dependent B cell response. In this study we have investigated whether gp120 also inhibits the effector phase of interactions involved in T-cell-dependent-B cell differentiation response. For these studies, CD4+ T cells were first activated with antigen or pokeweed mitogen, cultured with soluble HIV-gp120 or medium for 2 hr, and washed. Coculture of gp120-treated preactivated T cells with autologous B cells resulted in impairment of IgG secretion, but did not affect IgM secretion significantly. The IgG secretion was restored by the addition of PMA (activator of protein kinase C) or forskolin (activator of adenylate cyclase), but not by the addition of ionomycin (inducer of intracellular calcium) to the T plus B cell cultures. A similar pattern of Ig secretion (IgM, no IgG) was observed with B cells of a patient with bare lymphocyte syndrome, indicating a requirement for MHC class II molecule interaction with T cells. These studies suggest that the effector phase of T-B cell interactions are impaired by gp120, and that the mechanism involves a signal transducing event(s), which is dependent upon cyclic AMP and/or protein kinase C. Furthermore, these latter reactions occur subsequent to T-B cell contact-dependent interactions at the effector phase, which involve MHC class II molecules on B cells and CD4 molecules on T cells.
Antigen Presentation↗
Treating motor fluctuations with controlled-release levodopa preparations.
A major problem in the long-term treatment of Parkinson's disease with chronic, intermittent levodopa therapy is fluctuations in motor response. Both peripheral and central pharmacokinetic properties of levodopa are important in determining the duration of response. The "wearing-off" phenomenon or "end-of-dose" deterioration is related directly to the level of plasma levodopa. Therefore, a principal strategy for the treatment of motor fluctuations has been the attempt to prolong levodopa plasma levels with the use of long-acting, controlled-release levodopa preparations. This paper reviews the available data on the two compounds that are commercially available: benserazide-levodopa hydrodynamically balanced system (Madopar HBS) and controlled-release carbidopa-levodopa (Sinemet CR).
Delayed-Action Preparations↗
Molecular basis of a multiple lymphokine deficiency in a patient with severe combined immunodeficiency.
We have previously reported that the T lymphocytes of a child with severe combined immunodeficiency are defective in the transcription of several lymphokine genes that include IL2, IL3, IL4, and IL5, which encode interleukins 2, 3, 4, and 5 (IL-2, -3, -4, and -5). To determine whether the defect in the patient's T lymphocytes involved a trans-acting factor common to the affected lymphokine genes, we examined the ability of nuclear factors from the patient's T lymphocytes to bind response elements present in the regulatory region of IL2. Nuclear factor NF-kB, activation protein 1 (AP-1), OCT-1, and NF-IL-2B binding activity were normal. In contrast, the binding of the nuclear factor of activated T cells (NF-AT) to its response element in the IL2 enhancer and to an NF-AT-like response element present in the IL4 enhancer was abnormal. To ascertain whether the abnormal NF-AT binding activity was related to an impaired function, we transfected patient and control T lymphocytes with constructs containing the reporter gene encoding chloramphenicol acetyl transferase (CAT) under the control of the entire IL2 regulatory region or of multimers of individual enhancer sequences. CAT expression directed by the IL2 regulatory region or by a multimer of the NF-AT-binding site was markedly lower in the patient relative to controls. In contrast, CAT gene expression directed by a multimer of the OCT-1 proximal (OCT-1p)-binding site was equivalent in patient and controls. These results indicate that an abnormality of/or influencing NF-AT may underlie the multiple lymphokine deficiency in this patient.
Cell Nucleus↗
Interactive video conferencing: a means of providing interim care to Parkinson's disease patients.
Inequity in health care delivery is attributable to a variety of factors including geographic isolation. Patients living far from major urban centers have limited access to medical specialists. In the instance of Parkinson's disease (PD), optimal assessment and care may depend upon availability of specialty health care providers. In order to broaden health care access, interactive video conference (IVC) units are being developed for medical use. IVC allows a patient at a distant site to be "seen and heard" by a hospital-based physician; simultaneously, the patient can "see and hear" the doctor. To establish the validity of this technology in the evaluation of PD, nine patients were independently examined and scored (UPDRS) by two movement disorder specialists. One examination was performed in-person by the usual physician. The other examination was performed on the same day via IVC over a distance of 350 miles by an examiner previously unfamiliar with the patients. Individual patient scores did not differ based on examiner (Spearman Rho Correlation Coefficients: UPDRS total scores r = 0.933, p < 0.0002; Hoehn and Yahr Scale r = 0.883, p < 0.001). A standardized exit interview was conducted to assess patients' perceptions of this application of video technology. Responses were favorable and virtually all patients viewed this as a means of accessing better health care. We conclude that valid motor assessments of PD patients can be made via IVC.
Aged↗
Is there a relationship between Parkinson's disease and essential tremor?
The issue of whether there is a relationship between essential tremor (ET) and Parkinson's disease (PD) is controversial partly due to the confusion regarding the accurate diagnosis of these conditions. The presence of postural tremor, which often occurs in PD, by itself is insufficient for the diagnosis of ET. Most epidemiological studies have shown that there is no association between these two conditions. Some studies, but not others have found a higher prevalence of tremor in family members of PD patients. Clinical, positron emission tomography scan, and neuropathological data have failed to show any relationship between these two conditions. It is concluded that there is no relationship between ET and PD and that when these two conditions are seen in the same patient, this represents a chance occurrence of two common diseases.
Humans↗
The relationship between hormonal mediators and systemic hypermetabolism after severe head injury.
The relationships of hormonal mediators to the systemic hypermetabolism and catabolism of head injury were studied in 15 patients with severe head injuries. Resting energy expenditure (REE), urinary nitrogen balance, and plasma glucose concentration were measured daily for the first 2 weeks after injury as the major indicators of hypermetabolism. These dependent variables were correlated with daily measurements of urinary epinephrine, norepinephrine, metanephrine, normetanephrine, dopamine, and cortisol, and with plasma levels of insulin, glucagon, and C-reactive protein. Urinary catecholamine and cortisol excretion were markedly elevated in these patients throughout the 2 weeks of study. Catecholamine excretion peaked between days 7 and 10, whereas cortisol excretion tended to be highest on day 5 after injury. Urinary levels of norepinephrine, normetanephrine, and cortisol were highest in the two patients with Glasgow Coma Scale scores of 4. Plasma insulin and glucagon concentrations were elevated on day 1 after injury and tended to increase throughout the 2-week period of study. The variables significantly associated with REE were the severity of injury, reflected by the GCS score, the urinary excretion of norepinephrine during the first 2 days after injury, and the urinary excretion of epinephrine and norepinephrine during days 3 to 7 after injury. A negative nitrogen balance was associated with the urinary excretion of epinephrine and norepinephrine, with caloric balance, and with plasma C-reactive protein during days 1 and 2 after injury. During days 3 to 7, a negative nitrogen balance was associated with the urinary excretion of epinephrine and norepinephrine and with caloric balance, and during days 8 to 14, a negative nitrogen balance was associated primarily with urinary cortisol excretion.
Adult↗
Clinical experience with controlled-release carbidopa/levodopa in Parkinson's disease.
We converted 158 Parkinson's disease (PD) patients on stable doses of standard carbidopa/levodopa (Std-L) to controlled-release carbidopa/levodopa (L-CR). Of the 141 patients who completed the study, 103 (73%) preferred L-CR, 26 (18.5%) preferred Std-L, and 12 (8.5%) had no preference. One hundred fourteen patients elected to continue L-CR, and we performed the primary data analysis on this group. Following conversion to L-CR, patients reported an increase in length of benefit from each dose and an increased "kick-in" time. There was a decrease in the total number of doses, "off" periods, sleep interruptions per night, dose failures, and sleep disturbances. Conversion to L-CR resulted in a significant increase in total levodopa dose. There was no significant change in the dyskinesias. However, early-morning dystonia resolved in eight of 14 patients. Our findings suggest that L-CR is particularly effective in decreasing motor fluctuations, reducing nocturnal problems, and minimizing levodopa dose failures in PD.
Adult↗
Prognostic significance of the onset mode in parkinsonism.
Early recognition of the prognosis in parkinsonism is important for both the management and studies aimed at preventing progression of disease. Less favorable prognosis is reported in early-onset postural instability and gait difficulty (PIGD) than in the tremor-onset cases, but the reasons for this are unknown. In 70 autopsy-verified cases, 11 (15.7%) had PIGD, and 34 (49%) had tremor onset. Improvement on levodopa was more common in the tremor-than the PIGD-onset cases (p < 0.05). The majority of tremor-onset cases had Lewy body disease, while the majority of PIGD-onset cases had other forms of pathology. Survival was shorter in the PIGD- than the tremor-onset cases (p < 0.05).
Adult↗
Double-blind controlled study of methazolamide in the treatment of essential tremor.
We studied the effect of the carbonic anhydrase inhibitor methazolamide in 25 patients with essential tremor (ET) in a double-blind, placebo-controlled trial. Tremor assessment included patient self-reporting of functional disability, clinical rating of motor tasks and tremor severity, and accelerometric measurements. There was no significant difference between methazolamide and placebo in any of the assessments. Side effects, paresthesias, sedation, headaches, and gastrointestinal symptoms were common. Only two patients elected to remain on the drug after the study. Methazolamide has only limited efficacy in the treatment of essential tremor.
Analysis of Variance↗
Identical twins with similar onset of Parkinson's disease: a case report.
The role of heredity in Parkinson's disease (PD) is controversial. We report a pair of monozygotic twins (confirmed by DNA fingerprints) concordant for PD. Their disease began when they were 62 and 63 years old. Both patients presented with left-side bradykinesia. One of the twins had a long history of depression. Both patients had typical manifestations of PD, which were responsive to dopaminergic therapy. The similar age of onset along with the similar clinical characteristics of these twins suggests that hereditary or genetic susceptibility may be important in the etiology of PD.
Diseases in Twins↗
A critical review of the neurotoxicity of styrene in humans.
Styrene monomer is an aromatic industrial solvent. It is used to make polystyrene, resins, rubber, reinforced material and boats. Humans are exposed to styrene in occupational situations mostly during spraying processes at work, most of which is inhaled. The major neurotoxic effects of styrene as reviewed are prenarcotic effects, electroencephalographic abnormalities, slowing of motor, sensory and distribution nerve conduction velocities that reveal the possibility of polyneuropathy, dysfunction of the autonomic nervous system, slowing of reaction times, and centrally-controlled otoneurotoxicity. In acute exposure situations reversal of adverse effects has been observed; however, the impact of long-term exposure needs further studies. Dopamine depletion has been reported as a neurochemical basis of the neurotoxicity of styrene. Styrene epoxide, a toxic intermediate metabolite, has also been reported to deplete glutathione and cause lipid peroxidation, possibly leading to neuronal membrane damage. Raised concentrations of glial fibrillary acidic protein has been reported as an indicator of neurotoxicity in rats, which may damage the brain through astrogliosis phenomenon. This damage is also correlated to the toxic effects of styrene epoxide. Recently decreased monoamine oxidase type B activity in peripheral blood cells has been investigated as biochemical indicator of neurotoxicity of styrene in workers. There is a need for long-term studies, consideration of confounding factors (smoking, alcohol, diet, drugs, working environment and exposure to other solvents), and the effects on different ethnic and racial groups. More electroencephalographic studies and computer tomographic investigations are desired. Further reduction of the exposure limit to below 50 ppm is recommended.
Animals↗
Effect of human immunodeficiency virus-1 envelope glycoprotein on in vitro hematopoiesis of umbilical cord blood.
Although hypercellularity is a common bone marrow finding in patients with human immunodeficiency virus type 1 (HIV-1) infection, the effect of HIV-1 on the hematopoietic system, which has been investigated in in vitro studies, is still controversial. In this study, we have investigated the effects of HIV-1 envelope glycoprotein, gp160, on the differentiation of hematopoietic progenitor cells derived from cord blood. Culture of cord blood mononuclear cells with gp160 resulted in enhancement of the in vitro growth of myeloid hematopoietic progenitors. To investigate the mechanism of the enhancement, adherent cells, T cells, or CD34-bearing hematopoietic progenitors were isolated and cultivated with gp160 in a variety of culture conditions. We have shown that gp160 had no direct effect on highly purified hematopoietic progenitors but exerted its enhancing effect indirectly via T cells, by induction of a humoral colony-stimulating factor(s). The activity of gp160 on T cells was abrogated by preincubation of gp160 with recombinant CD4 molecule and goat anti-gp120 antibody. These data provide evidence for a novel biological activity of HIV envelope glycoprotein, that of T-cell-mediated stimulation of myelopoiesis. Binding of gp160 with the cell surface CD4 molecule appears to be necessary for secretion of the colony-stimulating factor(s).
Antibodies↗
Superantigen staphylococcal enterotoxin B-induced T-helper cell activation is independent of CD4 molecules and phosphatidylinositol hydrolysis.
The role of the CD4 molecule in activation of T-helper cells was examined by investigating the effect of an anti-CD4 monoclonal antibody (Leu3a) in conventional peptide antigen-specific cloned T-helper cells that are also reactive to staphylococcal enterotoxin B (SEB). These T-helper cell clones are CD4+/CD45RO+/T-cell antigen receptor beta-chain variable region 12-positive and can respond to nominal peptide antigens and SEB by proliferation in the presence of class II major histocompatibility complex-expressing accessory cells. Although antigen and SEB were comparable in their ability to induce proliferative responses, interleukin 2 (IL-2) production, and IL-2 receptor alpha-chain expression, stimulation with SEB failed to trigger phosphatidylinositol hydrolysis or a rise in the intracellular free calcium ion concentration. Leu3a treatment inhibited antigen-induced proliferative responses of T cells with concomitant suppression of IL-2 production and IL-2 receptor expression. In contrast, SEB-induced responses were unaffected by Leu3a. These findings indicate that the functional consequences of binding (ligation) of conventional antigen and of superantigen with the T-cell receptor are distinct in the context of both signal transduction pathways and participation of CD4 molecules.
Antibodies, Monoclonal↗
The effect of acetazolamide on essential tremor: an open-label trial.
We studied the effect of the carbonic anhydrase inhibitor acetazolamide on 24 patients with essential tremor by patient self-evaluation of functional disability, rating of motor task function, and clinical rating of tremor severity. Acetazolamide significantly reduced tremor severity, but there was no statistically significant change in patient self-assessment of function or motor task rating. Although side effects were common, over half the patients elected to remain on the drug.
Acetazolamide↗
Olfactory function in essential tremor.
Olfactory function, assessed by the University of Pennsylvania Smell Identification Test, was normal in essential tremor (ET) patients and significantly reduced in patients with Parkinson's disease (PD). This finding further supports a lack of association between ET and PD.
Female↗