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Biomedical subjects

B Ford

Publications and source records attributed to B Ford.

At least 73 records · Page 4Linked to original sources

Cutaneous electromyographic silent period findings in brachial dystonia.

In this study we investigated the physiologic mechanisms in primary brachial dystonia by analyzing the cutaneous EMG silent period during isometric contraction of the opponens pollicis muscle. Results from the affected and unaffected arms of 11 patients with dystonia were compared to 7 patients with Parkinson's disease and 16 age-matched normal individuals (controls). The silent period onset latency, degree of EMG suppression during the silent period, and EMG rebound at the end of the silent period did not differ significantly between patients with dystonia and any other group. The duration of the silent period (the S-X interval), however, was significantly prolonged in dystonia (p<0.005) and in Parkinson's disease (p<0.001) in both affected and unaffected arms compared with controls. These findings suggest that mechanisms responsible for the initiation of the cutaneously induced silent period and the subsequent suppression depth of EMG activity are not affected in brachial dystonia, but the abnormally prolonged S-X intervals may reflect dysfunctional basal ganglia timing influences over spinal circuitry common to both dystonia and Parkinson's disease.

Adult↗

GABAergic neurons in the rat pontomesencephalic tegmentum: codistribution with cholinergic and other tegmental neurons projecting to the posterior lateral hypothalamus.

The present study was undertaken to determine the frequency and distribution of GABAergic neurons within the rat pontomesencephalic tegmentum and the relationship of GABAergic cells to cholinergic and other tegmental neurons projecting to the hypothalamus. In sections immunostained for glutamic acid decarboxylase (GAD), large numbers of small GAD-positive neurons (approximately 50,000 cells) were distributed through the tegmentum and associated with a high density of GAD-positive varicosities surrounding both GAD-positive and GAD-negative cells. Through the reticular formation, ventral tegmentum, raphe nuclei, and dorsal tegmentum, GAD-positive cells were codistributed with larger cells, which included neurons immunostained on adjacent sections for glutamate, tyrosine hydroxylase (TH), serotonin, or choline acetyltransferase (ChAT). In sections dual-immunostained for GAD and ChAT, GABAergic neurons were seen to be intermingled with less numerous cholinergic cells (approximately 2,600 GAD+ to approximately 1,400 ChAT+ cells in the laterodorsal tegmental nucleus, LDTg). Retrograde transport of cholera toxin (CT) was examined from the posterior lateral hypothalamus, where a major population of cortically projecting neurons are located. A small number of GABAergic cells were retrogradely labeled, representing a small percentage of all the GABAergic neurons (approximately 1%) and of all the hypothalamically projecting neurons (approximately 6%) in the tegmentum. The double-labeled GAD+/CT+ cells were commonly found ipsilaterally within 1) the deep mesencephalic reticular field, codistributed with putative glutamatergic projection neurons; 2) the ventral tegmental area, substantia nigra compacta, and retrorubral field, codistributed with dopaminergic projection neurons; 3) dorsal raphe, codistributed with serotonergic projection neurons; and 4) laterodorsal and pedunculopontine tegmental nuclei, codistributed with and in similar proportion to cholinergic projection cells (20-30% in LDTg). Acting as both projection and local neurons, the pontomesencephalic GABAergic cells would have the capacity to modulate the influence of the "ascending reticular activating system" and its chemically specific constituents upon cortical activation.

Acetylcholine↗

Differences in the prevalence of essential tremor among elderly African Americans, whites, and Hispanics in northern Manhattan, NY.

BACKGROUND: Until now there has been only one community-based study to examine interethnic differences in the prevalence of essential tremor (ET). The study suggested a higher prevalence among whites than African Americans. The present study is the first to examine differences in the prevalence of ET among Hispanics, African Americans, and whites. OBJECTIVE: To estimate the prevalence of essential tremor (ET) in a cohort of community-dwelling elderly of mixed ethnic background. METHODS: A random sample of 2117 Medicare recipients residing in Washington Heights-Inwood in northern Manhattan, NY, were interviewed. A standardized neurological assessment was performed on those who had neurological complaints and on a random sample of those who did not. Essential tremor was defined as a postural or kinetic tremor of the head or limbs. Diagnoses were independently confirmed by two neurologists based on videotaped examination. RESULTS: After age adjustment to the 1990 Washington Heights-Inwood census, the prevalence of ET was 40.2 per 1000 (95% confidence interval, 31.8 to 48.6). Among 46 cases with ET, ET was significantly more prevalent in men than in women (chi 2 = 5.0, P = .03). Prevalence increased significantly with age. The prevalence was higher in whites than African Americans. The prevalence in Hispanics was intermediate. CONCLUSION: The prevalence of ET increases with age and may be higher among men and whites. Prospective studies are needed to further examine these associations.

Black or African American↗

Short-term dichloroacetate treatment improves indices of cerebral metabolism in patients with mitochondrial disorders.

We performed a short-term, double-blind, placebo-controlled, crossover trial of sodium dichloroacetate (DCA) therapy in 11 patients affected by various primary mitochondrial disorders. Independent measures of oxidative metabolism (venous blood metabolites, exercise testing, phosphorus magnetic resonance [MR] spectroscopy of muscle, and proton MR spectroscopy of brain) were used in order to monitor metabolic responses to the drug. One week of DCA treatment produced significant decreases (p < 0.05) in blood lactate, pyruvate, and alanine at rest and after bicycle exercise. Proton MR spectra collected from a supraventricular volume of interest in brain of seven of 11 patients also showed significant changes. Brain lactate/creatine ratio decreased by 42% during DCA treatment (p < 0.05). Brain choline/creatine ratio (which is low in patients with myelinopathies) increased by 18% (p < 0.01) after therapy. N-Acetylaspartate/creatine ratio (an index of neuronal damage or loss) increased by 8% after treatment (p < 0.05). Proton MR spectra collected in two of 11 patients from a volume of interest including the basal ganglia showed similar results (decrease of 36.6% in lactate/creatine; increases of 16% in choline/creatine and 4.5% in N-acetylaspartate/creatine). Phosphorus MR spectroscopy of muscle and self-assessed clinical disability were unchanged. Our study indicates that short-term DCA treatment not only lowers blood lactate but also improves indices of both brain oxidative metabolism and neuronal and glial density or function.

Acetylcysteine↗

Peripherally induced EMG silent periods. Normal physiology and disorders of motor control.

Periods of relative or absolute EMG suppression induced by peripheral stimulation have been described using a variety of experimental paradigms in normal subjects and in conditions of abnormal motor control. Peripherally induced silent periods represent complex inhibitory modulations of muscle activity and can be reproducibly evoked by cutaneous or mixed nerve electrical or mechanical stimuli. Features of the electromyographic suppression which most easily permit analysis include the degree of EMG inhibition, the latency and duration of the response, and the timing of the return of normal EMG activity following the stimulus, or S-X interval. When exteroceptive reflexes in craniocervical muscles are studied, alternating periods of EMG inhibition and facilitation have been described. Experiments designed to isolate the various contributants to EMG silence have not revealed a unitary electrophysiological basis for all of the silent period responses elicited by peripheral means. Thus, silent periods share a multifactorial origin that depends upon segmental spinal mechanisms which are heavily influenced by descending suprasegmental pathways. Because these mechanisms are affected in a variety of central disorders of motor control, study of peripherally induced silent periods may provide a window on the abnormal physiology of selected CNS diseases. Further study is required to elucidate the electrophysiology of peripherally induced silent periods, and to clarify the alterations in these negative motor phenomena that occur in central disorders of motor control.

Dystonia↗

Engraftment of human hematopoietic precursor cells with secondary transfer potential in SCID-hu mice.

Human fetal bone fragments implanted subcutaneously in immunodeficient (SCID) mice maintain active human hematopoiesis. In this study, we show that this human hematopoietic microenvironment supports the engraftment and differentiation of HLA-mismatched, CD34+ primitive hematopoietic progenitor cells isolated from fetal and adult human bone marrow (BM). The BM CD34+ cells were depleted of CD2, CD14, CD15, CD16, glycophorin A, and CD19 lineage-committed cells (CD34+Lin-). Donor cell engraftment was manifested by the presence of B (CD19+) and myeloid (CD33+) cells of donor HLA phenotype. Successful engraftment was observed as early as 4 weeks after fetal BM donor cell injection and sustained for at least 12 weeks, with engraftment success rates of 100% (11/11 grafts) and 92% (11/12 grafts) at 8 and 12 weeks, respectively. Mixed BM chimerism of donor and endogenous cells was consistently observed in SCID-hu bones successfully engrafted with HLA-mismatched CD34+Lin- donor cells. Preconditioning of the SCID-hu bone with a single dose of sublethal (350 rad) whole body irradiation (WBI) immediately before cell injection enhanced the repopulation of the bone grafts with donor cells and, in some instances, resulted in complete repopulation. After WBI, as few as 500 fetal bone marrow CD34+Lin- cells injected in the human bone grafts resulted in donor-derived hematopoiesis. Donor progenitor cells recovered from the SCID-hu bone grafts 8 weeks postinjection had the capacity to repopulate secondary groups of HLA-disparate fetal human bones in SCID-hu mice with B and myeloid cells as well as CD34+ cells in some recipients. In addition, these cells repopulated fetal human thymus fragments in SCID mice with donor thymocytes including immature CD4+CD8+ and mature CD4+CD8- as well as CD4-CD8+ subsets. These results indicate that the fetal human bone implants of SCID-hu mice can support the maintenance of a cell population that has both multilineage potential and repopulating potential for periods of time as long as 16 weeks. The SCID-hu bone model consistently supported the engraftment of both fetal and adult CD34+Lin- cells without the administration of exogenous human cytokines to these animals. This model is currently being used to permit the isolation and characterization of candidate human hematopoietic stem cells (HSCs) and provide important information critical for human HSC therapy in humans.

Animals↗

Oral and genital tardive pain syndromes.

We report the development of chronic painful oral or genital sensations in 11 patients with tardive akathisia, tardive dyskinesias, or tardive dystonia. In each case, the pain syndrome became a source of profound distress for the patient, overshadowing all other concurrent neuropsychiatric symptoms, and requiring treatment. Agents effective in treating tardive dyskinesia and tardive akathisia, such as catecholamine depletors, proved effective in reducing the painful sensations. Our observations support the concept of tardive pain as a complication of chronic neuroleptic exposure.

Aged↗

Carcinogenicity, metabolism and Ki-ras proto-oncogene activation by 7,12-dimethylbenz[a]anthracene in rainbow trout embryos.

Field studies suggest that recent epizootics of hepatic neoplasms in some feral fish populations are associated with polycyclic aromatic hydrocarbon (PAH) exposure, but attempts to induce liver tumors in these species under laboratory conditions have been unsuccessful. Several studies have shown hepatic neoplasma to be inducible in laboratory fish species following PAH exposure at the free-swimming life stage. However, neither the susceptibility of the fish embryonic life stage to tumor induction by PAHs nor the potential of these carcinogens to induce oncogenic point mutations analogous to those reported in feral fish hepatic tumors have been clearly established. To address this, rainbow trout embryos were exposed by passive water uptake to 7,12-dimethylbenz[a]anthracene (DMBA), a potent model PAH in many mammalian tumor protocols. DMBA was rapidly absorbed by trout eggs and metabolized. The major non-polar metabolites identified were 12-hydroxymethyl-7-methylbenz[a]anthracene and 3,4-dihydroxy-3,4-dihydro-DMBA, whereas approximately 25% of the water soluble metabolites were identified as glucuronides by beta-glucuronidase treatment. Embryonic DNA adduction increased with time of DMBA exposure (2.2 +/- 0.3 pmol DMBA-equivalents/mg DNA at 24 h). Liver tumor incidence nine months after DMBA treatment was found to increase with DMBA concentration and exposure period (3.8% at 1 p.p.m./2 h; 23% at 5 p.p.m./2 h; 85% at 5 p.p.m./24 h). Stomach adenomas and nephroblastomas also were observed at low incidence in the DMBA-treated trout. Among 11 hepatic tumors examined, nine carried Ki-ras alleles with activating point mutations in codon 12 (4/11 GGA-->AGA; 4/11 GGA-->GTA) or codon 61 (1/11 CAG-->CTG). This spectrum differs substantially from those reported for DMBA-initiated mouse skin papillomas or hepatic tumors. These results may have important environmental implications because they suggest that even a brief exposure to PAHs during a sensitive stage of development may adversely affect some fish populations. They also indicate considerable variation in DMBA ras gene mutations among species and target organs.

9,10-Dimethyl-1,2-benzanthracene↗

Coenzyme Q10 with multiple vitamins is generally ineffective in treatment of mitochondrial disease.

We followed 16 patients with a variety of mitochondrial diseases over one to four periods of treatment (2 months each) with coenzyme Q10 plus vitamins K3 and C, riboflavin, thiamine, and niacin, using independent measures of oxidative metabolism to assess efficacy. There were large (> threefold) increases in serum coenzyme Q10 concentrations with treatment, but no measure of oxidative metabolism showed significant improvement with treatment for the group, nor did any individual patient show significant, reproducible, objective clinical improvement. The results suggest that coenzyme Q10 plus vitamin therapy does not significantly improve mitochondrial oxidative metabolism in patients with mitochondrial disease in general. Any clinical benefit that may follow from short-term administration appears slight.

Adenosine Triphosphate↗

Long-term follow-up of acute partial transverse myelopathy.

We carried out a prospective, long-term, combined clinical and MRI follow-up study on 15 patients hospitalized at the Montreal Neurological Institute between 1985 and 1988 with a diagnosis of acute partial transverse myelopathy of unknown etiology. Twelve of the 15 (80%) developed clinically definite or lab-supported definite multiple sclerosis (MS) by the end of a mean follow-up period of 38.5 months. The presence of CNS periventricular white matter lesions by cranial MRI at onset increased the likelihood of development of MS to 93%.

Acute Disease↗

AIDS-related beliefs and behaviours of Australian university students.

Parallel questionnaires that enquired into the beliefs and behaviours which related to the acquired immunodeficiency syndrome (AIDS) were administered by postal survey during August and September 1987 to two separate samples of students. Each sample comprised 300 students who were selected at random, were aged up to 30 years, and at the time were enrolled at The University of Sydney; the response rate was 70%. Results showed a high level of "correctness" of belief about AIDS and safer sexual practices. More than half the population had experienced sexual intercourse during 1987, 25% of whom had experienced sexual intercourse on a casual basis. A marked discrepancy was found between the knowledge of and the performance of safer sexual behaviours, as measured by two sets of key questions, which covered condom use in casual vaginal encounters and enquiry into a casual partner's history with regard to sexual experience, abuse of intravenous drugs and history of blood transfusions. A log-linear regression analysis showed no correlation between scores on the two sets of key questions on knowledge of safer sexual practices and the demographic variables of age, sex, sexual experience or religious commitment. It is suggested that an educational campaign that is directed at the problem of behavioural change will fail to be productive if it is focused narrowly on the knowledge of safer sexual techniques; in addition, it should take into account other attitudinal components, such as the perception of social pressures from peer-groups. Within this particular student population, the most-effective immediate stratagem may be to restructure the perceived personal and peer-group risks.

Acquired Immunodeficiency Syndrome↗

Emotional disorder and its assessment within the severe head injured population.

This study examined the usefulness of self-report measures of emotional disorder in a relatively acute, severely head injured population (i.e. individuals who had sustained their injuries within the previous two years). The General Health Questionnaire, the Leeds Scales of Depression and Anxiety, and Visual Analogue Scales of Depression and Anxiety were administered to 39 severely head injured subjects and 35 'close others' who were required to give their opinions on how they thought the head injured subjects were feeling. Twenty head injured subjects were re-tested within a week. Results indicated that the head injured are able to reliably complete self-report scales as indicated by the 'close others' similar reports. The head injured seem to be relatively aware of their overt behaviours and emotions, at least when utilizing the General Health Questionnaire and the Leeds Scale of Depression. According to the measures of emotional disposition used in the present study, emotional disorder was found to be common. From the results it was further suggested that lack of a close confiding relationship predicts emotional disorder and may be used to identify those subjects at risk. Overall, the results provide confidence for the use of self-report scales as a preliminary approach to the identification of emotional disorder in the severely head injured.

Adult↗

Hemi-inattention and the recovery patterns of stroke patients.

A series of stroke patients (n = 31) were assessed at four stages: 4 weeks, 8 weeks, 12 weeks and 18 months post-trauma. Significant recovery was noted at 8 weeks, although a trend towards recovery continued throughout the assessment phases. Patients presenting with hemi-inattention at the 4-week assessment achieved significantly poorer levels of functional ability at the final assessment although in some cases the inattention had resolved on neuropsychological tests.

Activities of Daily Living↗