Repetitive magnetic stimulation of cortical motor areas in Parkinson's disease: implications for the pathophysiology of cortical function.

We investigated the neurophysiological and clinical effects of repetitive magnetic stimulation (rTMS) delivered to the cortical motor areas in healthy subjects and patients with Parkinson's disease. rTMS was delivered with a high speed magnetic stimulator (Cadwell, Kennewick, WA) through a figure-eight coil centred on the primary motor area at a stimulus intensity of 120% motor threshold. Trains of 10 stimuli were delivered at frequencies of 5 Hz while subjects were at rest and during a voluntary contraction of the contralateral first dorsal interosseous muscle. In normal subjects at rest, the muscle evoked responses (MEPs) to each stimulus in a train of magnetic stimuli progressively increased in size during the train. rTMS left the MEPs unchanged in patients off therapy and had a small facilitatory effect in those on therapy. In normal subjects and patients, 5-Hz rTMS trains delivered during a voluntary contraction of the target muscle left the MEP unchanged in size. MEPs were followed by a silent period that increased in duration during the course of the train. The silent period duration increased to a similar extent in patients and controls. The reduced rTMS-induced facilitation of MEPs in patients with Parkinson's disease reflects a decreased facilitation of the excitatory cells in the cortical motor areas.     

Non-invasive estimation of the diastolic elastic and viscoelastic properties of the left ventricle

The present study applies a non-invasive method to the quantitative evaluation of left ventricular stiffness in normal subjects and in patients with ischaemic heart disease (IHD). We have studied 20 patients with IHD and 25 healthy subjects. The third heart sound (S3) was detectable in all patients. We have correlated the energy spectrum of S3, divided into 15 Hz bands, with a series of echocardiographic parameters. The existence of a significant correlation between the spectrum energy and the diameter and thickness of the left ventricle at the moment of S3 allowed us to explore the possibility of interpreting the origin of S3 based on a mathematical model. Our hypothesis has been that, once the left ventricle starts vibrating, it behaves as a simple physical model composed of a mass and an elastic element. To this purely elastic model one can add a factor accounting for viscosity, with a damping effect, to obtain a more complex viscoelastic model. The stiffness coefficient 'k' was computed in both models from the peak frequency of S3 and the left ventricular mass at the moment of S3. Furthermore, in the viscoelastic model, the damping element 'c' was also computed. Both parameters--k and c--were significantly increased in the group with IHD compared with the control group. Although a simplification of the vibrating system, these models make it possible to obtain non-invasively information on the characteristics of the left ventricle through the combined use of echocardiography and spectral analysis of S3.     

Brain tissue microarrays in dementia research: White matter microvascular pathology in Alzheimer's disease

Tissue microarrays (TMA) consist of up to 1000 cylindrical tissue cores from different donor paraffin blocks relocated into one recipient block, allowing for efficient histopathological studies by fluorescence in situ hybridization, RNA in situ hybridization or immunohistochemistry. On the background of the increasing interest of the TMA technique in cancer research and the suggestion of its application also in studies of non‐neoplastic intracranial disorders, the technique was applied to pathologic white matter in AD brains. Eight cases with AD and concomitant white matter pathology were neuropathologically diagnosed on whole brain coronal slides. The TMA technique was used to grade severity of white matter pathology and to quantify small vessels with traditional staining and immunohistochemical markers. These measurements were compared with the whole brain neuropathological assessment. The technique produced good results with preserved tissue structures as confirmed by the whole brain evaluation. Severity of white matter pathology evaluated on the TMA cores correlated negatively with small vessel quantities, and statistically significant differences in vessel quantities paralleled different grades of white matter pathology. It is concluded that the TMA technique could be further utilized in studies of dementing disorders, and may have its advantages in large, clinically well‐characterized materials (e.g. in quantitative mapping of white matter changes).     

Abnormal sensorimotor integration is related to disease severity in Parkinson's disease: a TMS study.

Hyperexcitability of the motor system has been reported in Parkinson's disease (PD). We evaluate how cutaneous afferents modulate motor excitability in PD patients and whether abnormal modulation is correlated to parkinsonian symptoms. Digital stimulation causes abnormal enhancement of motor responses in patients. This effect may be one of the features of motor hyperexcitability in PD. Cutaneomotor hyperexcitability correlates with clinical scores, suggesting that abnormal processing of cutaneous inputs might contribute to the pathogenesis of parkinsonian symptoms.     

A cross-reactive idiotype in scleroderma

Autoantibodies to centromere proteins (anti-CENPs) and to topoisomerase-I are highly specific for scleroderma. Unlike most autoantibodies in other diseases, these autoantibodies are mutually exclusive. We have analysed the idiotypes (Ids) expressed by anti-CENP-B, antitopoisomerase-I, and IgGs from 20 scleroderma patients. Rabbit anti-Ids were prepared to antitopoisomerase-I from two scleroderma patients, and to anti-CENP-B from four patients. These six anti-Ids were used to study the purified autoantibodies from 20 scleroderma patients: four antitopoisomerase-I, 10 anti-CENP-B, and six purified IgG from scleroderma patients who were negative for both autoantibodies. In addition, we studied sera from 40 normal autoantibody-negative controls, and sera and purified immunoglobulins from 17 systemic lupus erythematosus (SLE) patients containing high titres of anti-double-stranded DNA, and/or autoantibodies to extractable nuclear antigens (ENA). Using direct binding, and competitive inhibition ELISAs and immunoblots, we identified an Id present in the heavy chains of all the affinity-purified antitopoisomerase-I, and anti-CENP-B. Interestingly, this Id was also present in the immunoglobulins of the scleroderma patients who had neither of the two autoantibodies. By contrast, cross-reactive Id-EM was not found in the sera or immunoglobulins from 17 SLE patients, or in the sera from 40 normal subjects. Several samples from two patients showed that this cross-reactive Id-EM was stable over time. The scleroderma disease-specific autoantibodies may be identified through a common structural feature at the variable region of the heavy chain: cross-reactive Id-EM.     

Recombinant human erythropoietin in the treatment of cancer-related anaemia

Abstract: The efficacy and safety of recombinant human erythropoietin (rhEPO) were tested when given subcutaneously (s.c.) in an escalating dose of 2000–10,000 units (U) daily in 60 patients with cancer-related anaemia (CRA). A positive response, defined as an increase in haemoglobin more than 2 g/dl and independence of blood transfusions, was observed in 23 of 48 evaluable patients (48%) within a median of 8 wk. In detail, rhEPO corrected anaemia in 11 of 14 patients (79%) with malignant lymphoma, in 8 of 15 patients (53%) with multiple myeloma and in 4 of 10 patients (40%) with a solid tumour. The median dose of rhEPO in successful cases was 5000 U daily. Four patients with agnogenic myeloid metaplasia and 5 with myelodysplastic disorder failed to respond to rhEPO. No patient had any severe side effects. Pretreatment serum erythropoietin levels appeared to be a weak predictor for response to rhEPO treatment. In conclusion, rhEPO seems to be safe and effective in correcting CRA in certain groups of patients.     

Effect of chronic oral domperidone therapy on gastrointestinal symptoms and gastric emptying in patients with parkinson's disease

This study investigated whether domperidone could improve gastrointestinal symptoms in patients with Parkinson's disease who were receiving levodopa therapy. A total of 11 patients were studied. Following a baseline gastric emptying test, patients were treated with a starting dose of domperidone 20 mg p.o. q.i.d. A follow-up gastric emptying test was repeated at least 4 months after starting domperidone therapy. At the beginning and at each 3-month follow-up visit, symptoms of nausea, vomiting, anorexia, abdominal bloating, heartburn, regurgitation, dysphagia, and constipation were evaluated and scored on a scale of 0–3. The overall mean follow-up period was 3 years. Compared with their baseline evaluation, patients experienced a significant improvement in all symptoms (p < 0.05) except dysphagia and constipation. Gastric emptying of an isotope-labeled solid meal was significantly faster, with a baseline result of 60.2 ± 6.4% retention of isotope 2 h after the meal compared with 37.0 ± 2.2% retention during domperidone therapy (p < 0.05). Patients' global assessment of Parkinson's disease remained stable or improved. Serum prolactin was elevated in all patients after domperidone therapy (p < 0.05). Domperidone therapy significantly reduces upper gastrointestinal symptoms and accelerates gastric emptying of a solid meal, but does not interfere with response to antiparkinsonism treatment.     

Periodontal status of a subject sample of Yemen

Abstract From August to October 1991, the periodontal status of 1001 Yemenis representing the age groups 12-14, 15-19, 20-24 and 35-44 years was recorded and evaluated with preference to the CPITN, the calculus index and clinical attachment levels. The impact of chewing khat, the leaves of a cultivated, alkaloid shrub, and of using the traditional miswak chewing stick for oral hygiene purposes were investigated. The results show that 6.9% of the juvenile probands (15-19 years) had healthy periodontal tissue (CPITN 0). whereas bleeding on probing and calculus (CPITN 1+2) were registered in 86.2%. In the 35-44 year age group. 1.7% were periodontally healthy, whereas 84.5% displayed plaque retention or shallow pocketing (CPITN 2-3) and 12.5% deep pocketing (CPITN 4). The treatment needs in all age groups are confined primarily to calculus removal and instruction in oral hygiene. The clinical attachment level and the calculus index revealed age-related attachment loss and calculus formation, primarily among male probands. The higher khat consumption among the male population is reflected in its detrimental effect on the periodontal tissue, especially among younger probands. Oral hygiene aids have also an influence on periodontal status, with a toothbrush proving more efficient than the miswak. WHO efforts directed towards prophylactic programs need to be intensified but can be staffed by dental hygienists.     

A newly recognized point mutation in the cytochrome b558 heavy chain gene replacing alanine57 by glutamic acid,in a patient with cytochrome b positive X-linked chronic granulomatous disease

Molecular genetic analysis was performed in a patient with cytochrome b positive X-linked chronic granulomatous disease. A previous Southern blot study, using a cytochrome b heavy chain cDNA as probe, revealed a Pst I restriction fragment pattern for the cytochrome b heavy chain gene (CYBB) different to that of normal individuals. Since restriction length polymorphism with Pst I has never been observed in control individuals and no abnormal restriction fragment patterns in the patient's CYBB was detected with seven other enzymes used, we focussed on the single Pst I site in the CYBB cDNA as being the only mutation site responsible for his disease. A fragment of the patient's cDNA which included the Pst I site was amplified by reverse polymerase chain reaction, and loss of the Pst I site in the fragment was confirmed by incubation with Pst I. Subsequent sequence analysis of the fragment revealed a point mutation in the Pst I site (cytosine to adenine), substituting glutamic acid for alanine at position 57.