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Biomedical subjects

A Mackowiak

Publications and source records attributed to A Mackowiak.

10 recordsLinked to original sources

Pathologic laughing and intractable hiccups can occur early in multiple sclerosis.

Pathologic laughing occurs in approximately 10% of patients with multiple sclerosis (MS), especially when patients have entered the chronic stage. We describe four patients with MS who, at an early stage, developed pathologic laughing associated, in two cases, with intractable hiccups. In two patients, MRI showed an enhanced lesion in the medulla oblongata and the mesencephalon, two regions suspected of being involved in pathologic laughing and intractable hiccups.

Adolescent↗

Antiapoptotic effects of budipine.

Apoptosis is one essential step for neuronal death in the nigrostriatal region in patients with Parkinson's disease. Cytotoxic tumor necrosis factor-alpha (TNF-alpha) and the proinflammatory cytokine interleukin-6 (Il-6) provide a proapoptotic environment. We investigated the influence of the antiparkinsonian compound budipine on the release of TNF-alpha and Il-6 in peripheral blood mononuclear cells (PBMC) and on the degree of cisplatin induced apoptotic cell death in SH-SY 5Y human neuroblastoma cells. 10(-7), 10(-8), 10(-9) mol/l of budipine significantly reduced release of TNF-alpha and Il-6 in PBMC and decreased apoptotic cell death after 50 hours and 74 hours in the SH-SY 5Y cells. Our results suggest, that budipine administration provides an antiapoptotic environment and slows neuronal apoptotic and inflammatory mediated loss of neurons.

Anti-Inflammatory Agents, Non-Steroidal↗

[General practitioners' approach to relapsing multiple sclerosis].

Management of multiple sclerosis depends on close multidisciplinary collaboration but general practitioners play a particularly important role, especially in case of relapse, due to their close relationship with the patient. The purpose of this work was to conduct a survey of general practitioners' knowledge of relapsing multiple sclerosis and ascertain their main difficulties in patient management. One hundred seventy-seven practitioners answered a written questionnaire with two headings, diagnostic criteria for relapse and therapeutic approaches. Analysis of the results showed that this common event is under recognized. While 55.9 p.cent of the general practitioners stated they diagnosed relapse by themselves, only 2.8 p.cent knew its exact definition. Differential diagnosis accounted for a large number of mistakes. Our survey also underlined the use of certain therapeutic options (low-dose oral corticosteroid therapy) for which the effectiveness has not been demonstrated. It would be important to propose specific education on relapsing multiple sclerosis for general practitioners and improve cooperation with specialists. An integrated care network might be useful.

Adrenal Cortex Hormones↗

[Primary progressive forms of multiple sclerosis: application of the new diagnostic criteria in French].

Approximately 15 p.100 of all cases of multiple sclerosis (MS) are primary progressive multiple sclerosis (PPMS). Diagnosis is however frequently delayed due to the lack of relapse. The commonly used Poser criteria established in 1983 are not directly applicable to this subgroup of MS patients. In 2000, Thompson et al proposed new diagnostic criteria for PPMS. The aim of our study was to apply retrospectively these new criteria to a cohort of patients from northern France (G-SEP cohort). The cohort included 184 patients (94 women and 90 men, sex ratio=1.04). Mean age at disease onset was 40.3 years (18-67 years) and mean follow-up was 9.9 (1-39 years). Only one patient was older than 65 years but 13 patients (7.1 p.100) were younger than 25 years. Patients were classed as having definite, probable or possible PPMS on the basis of clinical, MRI, cerebrospinal fluid and visual evoked potential (VEP) data. Most of the patients (61.4 p.100) had one symptom at onset; spastic paraparesis was frequent (79 p.100). Mean delay to diagnosis was 4.4 years. Ten patients (5.4 p.100) were surgically treated for cervic arthrosic myelopathy. Mean EDSS score at the end of follow-up was 5.8 (3-10). MRI was positive in 87.3 p.100 of the patients. Oligoclonal bands were found in 78.2 p.100. VEPs ware abnormal in 79.9 p.100 of the patients. Applying the Thompson criteria, 57.7 p.100 of the patients had definite PPMS, 38.7 p.100 probable PPMS. Our results are very similar to previous studies and confirm the usefulness of the new proposed criteria, which however should be prospectively tested to determine sensitivity and specificity in a new cohort of patients.

Adolescent↗

[Late onset of type I familial amyloid neuropathy: results of biopsy from accessory salivary glands].

Familial amyloidotic polyneuropathy (FAP) type I is usually characterized by onset in the third decade, autonomic nervous system failure, and heart block conduction occurring after the onset of neurological symptoms. A 74-year-old woman, with past medical history of a third degree heart block treated by a pace-maker, was hospitalized because of an axonal sensory-motor polyneuropathy, without autonomic dysfunction. There was no familial history. Because she complained of mouth dryness, biopsies of the labial salivary glands were performed, showing amyloid deposits. Immuno-histochemicals studies confirmed the presence of transthyretin. We analysed the transthyretin gene of the patient and her asymptomatic son, and found in both cases, the point mutation leading to the single amino acid substitution of a methionine for valine at position 30, which is typical of type I FAP. This case revealed the clinical variation of FAP type I and the interest of biopsies of the labial salivary glands in the diagnosis of polyneuropathies.

Age Factors↗

Influence of melanoma B16 on the pharmacokinetics of mitoguazone in mice.

In this study, the influence of different stages and transplantation routes of the experimentally widely used solid tumor melanoma B16 on the pharmacokinetics of the antineoplastic agent mitoguazone was investigated in B6D2F1 mice. It could be shown that changes of the pharmacokinetic parameters as well as the distribution pattern of this drug were clearly influenced and dependent on the tumor stage but not by the tumor inoculation route. Advanced melanoma (d16) led to a sharp decrease in the terminal elimination half-life as well as to decreased spleen levels and increased initial liver concentrations of the drug. With respect to the results obtained in leukemia P388-bearing mice it can be concluded that the tumor stage as well as the tumor model are to be considered as important factors in which way and to which extent a tumor may alter the pharmacokinetics of antineoplastic agents.

Animals↗

Distribution of cisplatin in tumor-free versus tumor-bearing B6D2F1 mice.

In healthy as well as in leukemia P388- or melanoma B16-bearing B6D2F1 mice the platinum concentrations in liver, serum and kidneys were determined after i.v. administration of 10 mg/kg cisplatin. In a tumor stage related to about 40% of the mean survival time (MST) no differences in platinum distribution between tumor-bearing and healthy animals could be observed. In the tumor stage related to about 70% of the MST, elevated platinum levels in serum of both tumor models and in kidneys only in melanoma-bearing but not in leukemia-bearing mice could be found. These results confirm those of other authors that tumor stages less than 50% of the MST exert no marked influence on the distribution pattern of cisplatin in rodents. Moreover, in advanced tumor stages distributional differences of antineoplastic agents may be expected between healthy and tumor-bearing mice as well as between animals bearing different neoplasias.

Animals↗

Influence of leukemia P388 on the pharmacokinetics of mitoguazone in B6D2F1 mice.

The aim of the present study was to investigate the influence of different stages of leukemia P388 on the pharmacokinetics of the antineoplastic agent mitoguazone in mice. It could be shown that, independent of the tumor stage investigated, the total clearance of mitoguazone is slightly reduced reflecting a moderate increase of AUC in the serum of leukemia-bearing animals. Furthermore, in an advanced tumor stage the drug levels in kidneys, liver, spleen and serum were found to be elevated to some extent in comparison to tumor-free controls in contrast to an earlier stage of leukemia. In conclusion, the tumor stage has to be considered as an important factor to which extent a neoplasia may alter the pharmacokinetics of drugs used for anticancer chemotherapy.

Animals↗