Feasibility of peripheral blood stem cell (PBSC) and peripheral blood mononuclear cell (PBMNC) separation in children with a body weight below 20 KG.

Nine children from 10 to 76 months (median 28.0), weighing 8.5 to 19.7 kg (median 13.0 kg) underwent peripheral blood stem cell separation (PBSCS) or peripheral blood mononuclear cell separation (PBMNCS), after insertion of a double-lumen central venous catheter (8-10 French). Separations were performed with a continuous flow blood separator (Fen-wall CS 3000 plus), running a specially adopted separation-program. In 7 children (5 with neuroblastoma IV, 1 with multifocal Ewing's sarcoma, and 1 with rhabdomyosarcoma IV), stem cells were mobilized by application of G-CSF at a dosage of 15-27.7 micrograms/kg body weight (median 16.25) subcutaneously following high-dose chemotherapy, according to the disease-related protocols, whereas 2 children had PBMNCS to induce graft vs. leukemia (GvL)-reaction in the HLA-identical sibling suffering from relapsed chronic myelogenous leukemia (CML: n = 1), or chronic myelomonocytic leukemia (CMML: n = 1) after allogeneic BMT. In all cases, the collecting procedure was performed after filling the cell separator with priming solution consisting of 2 U of irradiated and washed packed red cells, 250 ml human albumin, and 0.9% NaCl. In the 7 patients with solid tumors between 0.45 and 62.7 x 10(6) CD-34 positive cells/kg body weight were separated; the patient who had the lowest yield was separated twice after another mobilizing course. Three patients (2 with neuroblastoma IV and 1 with multifocal Ewing's-sarcoma) underwent a double transplantation with 1-3 portions of the collected stem cells within a 5- to 6-week interval. Two children had a rapid engraftment on both peripheral blood stem cell transplantations (PBSCTs). The third child, who had the lowest yield and was separated twice had prompt engraftment at the first PBSCT but delayed and incomplete engraftment at the second PBSCT. One patient after adoptive immunotransfer with PBMNCs for relapsed CML is now 40 months in complete cytogenetic and molecular biological remission, whereas the other patient treated for relapsed CMML did not respond to the PBMNC-transfusion. The results indicate that PBSCS and PBMNCS can be performed in children with a body weight below 20 kg.

[Computer-assisted evaluation of a "medium resolution" HLA-DRB oligotyping of bone marrow donors]. / Computerunterstützte Auswertung einer "Medium resolution"-HLA-DRB-Oligotypisierung von Knochenmarkspendern.

One drawback of a 'medium resolution' generic dotblot oligonucleotide typing of the HLA-DRB locus has been the time consuming evaluation of the collected SSO-hybridisation datas. We developed a program on the basis of MS-ACCESS, written in visual basic, called HIDE (HLA Intelligent Data Evaluation) to manage this problem. HIDE offers a complete data management for the donor and the incoming sample, supports a membrane based data entry of the hybridisation-reactions and multiple testing of a sample. If an evaluation shows more than one matching allele combination, the result is summarized according to the main DRB-groups. The flexible structure of the program allows the entry of additional allelspecific reaction-patterns as well as the adaption to different SSO-typingsets.

Immunological and clinical response to immunosuppressive treatment in paraneoplastic cerebellar degeneration.

OBJECTIVE: To report the clinical and immunological response to immunosuppressive treatment with cyclophosphamide in two patients with paraneoplastic cerebellar degeneration. DESIGN: Case reports. Clinical and immunological follow-up data available for 4 1/2 years in the first patient and for 2 years in the second patient. SETTING: A 1500-bed university hospital and a 1200-bed university teaching hospital. INTERVENTION: Cyclophosphamide intermittent treatment. MAIN OUTCOME MEASURE: Clinical disability. RESULTS: One of the patients, who was treated from an early stage, recovered completely. The other patient showed a partial clinical response. While the two patients were receiving a maintenance regimen with cyclophosphamide, the conditions of both patients remained stable for at least 2 years. In both patients, intrathecal antibody synthesis declined considerably. CONCLUSION: Early induction of immunosuppressive therapy with cyclophosphamide should be tried in treating patients with paraneoplastic cerebellar degeneration.

[HLA class II typing of dialysis patients--a comparison of serologic and molecular biological typing procedures]. / HLA-Klasse-II-Typisierungen von Dialysepatienten--ein Vergleich zwischen serologischen und molekularbiologischen Typisierungsverfahren.

The typing results of 212 dialysis patients could be improved by 13%, using polymerase chain reaction and hybridization with SSOs for defining HLA DR B polymorphism. So far 19 organ donors were also typed using a more rapid method: PCR with SSP.

Cyclosporine versus azathioprine in the long-term treatment of multiple sclerosis--results of the German multicenter study.

In a double-blind controlled trial of 194 patients with clinically definite active multiple sclerosis, 98 were randomized to treatment with cyclosporine (CyA, 5 mg/kg/day), and 96 to treatment with azathioprine (Aza, 2.5 mg/kg/day). Eighty-five patients in the CyA group and 82 in the Aza group completed a treatment period of 24 to 32 months in accordance with the study protocol. No significant differences could be detected between the two treatment groups at the end of the trial. Assessment was done by serial quantitative neurological examinations and Kurtzke's Expanded Disability Status Scale. Frequency of relapse and patient self-evaluation also failed to show significant differences. Overall deterioration observed in both groups during the trial was only minor. The incidence of side effects in the CyA group was more than two times that in the Aza group. We conclude that CyA as a single agent cannot be the drug of final choice in long-term immunosuppressive treatment of relapsing-remitting and relapsing-progressive multiple sclerosis.

Geographical distribution of mortality rates for cerebrovascular disease in Lower Saxony (Federal Republic of Germany).

Using the official mortality statistics for the 46 districts of Lower Saxony (Federal Republic of Germany) for the years 1975-1977, the geographical distribution of mortality from cerebrovascular disease was studied. Only in women was a slight tendency towards higher rates in rural areas found. There were only moderate correlations with the rates for ischaemic heart disease and no statistically significant correlations with the rates for diseases of peripheral vessels.

Crossreacting idiotypes of kappa-monoclonal immunoglobulins M in sera of patients with Waldenström's macroglobulinemia.

Seventeen anti-idiotypic antisera (anti-Id) were prepared against kappa-monoclonal IgM from patients with Waldenström's macroglobulinemia. Their reactivity against homologous and heterologous IgM was tested using an ELISA. Crossreacting idiotypes were only found in two out of 289 investigated antigen-antibody reactions. One anti-Id IgG crossreacted with determinants on polyclonal IgM. These rare crossreactions were observed in Waldenström's macroglobulinemia patients with and without polyneuropathy. The scarcity of common idiotypes on different monoclonal IgM does, however, not constitute a decisive argument against common or related antibody specificities of such monoclonal IgM.

Polyneuropathy in Waldenström's macroglobulinaemia. Passive transfer from man to mouse.

To support the hypothesis of an immunopathogenesis of polyneuropathy in Waldenström's macroglobulinaemia (MW), serum IgM fractions of MW patients were applied intraperitoneally to mice for 17 days. Sections of liver, kidney, M. glutaeus maximus, central nervous system (CNS) and both Nn. ischiadici were examined for IgM, IgG, C3 and as control IgD with PAP-immunostaining. IgM deposits were found in every organ except the CNS. In peripheral nerves larger amounts were visualized in perineurium and endoneural space, whereas myelin lamellae and periaxon did not stain. Therefore, perhaps our investigation reveals a greater permeability of the blood-nerve barrier (BNB) compared with the blood-brain barrier (BBB). The involvement of the monoclonal IgM of MW, which has been shown to react in vitro with peripheral nerve constituents, appears possible in the pathogenesis of polyneuropathy.

Mollaret's meningitis: CSF-immunocytological examinations.

Mollaret's meningitis is a rare clinical entity consisting of recurrent attacks of meningeal irritation, which, after a sudden onset, last for a few days. The prognosis appears to be excellent, although the aetiology has not been established. In the CSF so-called endothelial cells are a typical finding, but their classification is not yet clear. In the present case immunocytological examination of CSF cells revealed that the so-called Mollaret cells are monocytes. The time course of changes in helper/suppressor ratio is similar to that in other infectious diseases of the central nervous system.

[Mycotic intracranial aneurysm in infective endocarditis of the mitral valve]. / Mykotisches intrakranielles Aneurysma bei infektiöser Endokarditis der Mitralklappe.

A 20-year-old woman suffering from mitral valve endocarditis due to streptococcus faecalis infection after blunt trauma and splenectomy complained of severe headache 18 days later. Cerebral angiography showed a left posterior artery aneurysm. A craniotomy was performed and the aneurysm could be successfully removed. The postoperative neurological status showed a mild transient right hemiparesis. The patient underwent mitral valve replacement with a St. Jude-Medical prosthesis 14 days after brain surgery. The patient was in stable neurologic and hemodynamic conditions at the time of discharge 3 weeks after valve replacement.

[Familial polyneuropathy with a disposition to pressure paralyses. A contribution to the differential diagnosis of mononeuropathies]. / Familiäre Polyneuropathie mit Disposition zu Druckparesen. Ein Beitrag zur Differentialdiagnose der Mononeuropathien.

When a young woman admitted for recurrent peripheral nerve palsies was suspected to suffer from hereditary polyneuropathy with liability to pressure palsies, 8 members of her family were examined diagnostically. Only one of these had a history of a transient mononeuropathy. A neurophysiological examination demonstrated peripheral nerve lesions not only in the patients father but also in 5 of her brothers and sisters. In presenting the data for this family the characteristics of hereditary polyneuropathy with liability to pressure palsies and the most important differential diagnostic aspects are discussed.

Primary germinoma of the brain. Immunocytochemical demonstration of tumour cells in the cerebrospinal fluid.

A patient is presented, who developed a suprasellar tumour. Stereotactical biopsy of the tumour revealed the diagnosis of a dysgerminoma. Immunocytochemical examination of the CSF showed neoplastic cells staining for human chorionic gonadotropin and for alpha-fetoprotein. The authors stress the possibility to diagnose primary intracranial germ cell tumours without operation.

Tobacco-alcohol amblyopia neuro-ophthalmological findings and clinical course.

The clinical picture of 40 patients with tobacco-alcohol amblyopia (TAA) is described. In 15 patients the course of the disease was studied longitudinally over a period of 31 months. In addition in six patients the acute development of the disease was studied during a period of four weeks in-patient treatment. TAA is characterised by distinct bilateral visual disturbances, symmetric scotomas, acquired disturbances of colour vision and mostly normal fundi. Visual acuity is usually grossly diminished. Central scotomas were present in 80% of the cases while the centrocecal from prevailed in the rest. The acquired disturbances of colour vision usually concerned the red-green sense (84%). The amplitudes of the visual evoked potentials were always reduced and deformed. In 33% we could not detect a P-100. In 5% the latency of the P-100 was prolonged. Full field stimulation was the best method of defining the P-100. By foveal stimulation the deformations of the amplitudes were more evident. The prognosis of the visual disturbances was unpredictable. The abnormalities improved in one half of the patients, but complete recovery was never reached despite substitution with vitamins.

[Tobacco-alcohol amblyopia. Clinical course in 33 patients]. / Tabak-Alkohol-Amblyopie. Klinischer Verlauf bei 33 Kranken.

The clinical data of 33 patients with tobacco-alcohol-amblyopia are described. Usually, the visual disturbance concerned both eyes and was not associated neither with headache nor with painful eye movements. The fundus was very often normal. In the static perimetry mostly relative or absolute central scotomas were found, sometimes centrocoecal scotomas and very seldom paracentral scotomas. The colour vision was very often disturbed, usually the red-green discrimination. In the rule the amplitudes of the visual evoked potentials were diminished, the P-100 latency was delayed in 39%. A follow-up of 25 patients revealed that the visus and the results of the static perimetry improved in 72% during vitamin substitution (B1, B2, B6, B12, folic acid). In a few cases this improvement could be observed even though the alcohol drinking was not ceased. In most cases the disturbance of the colour vision and the pathologic visual evoked potentials, however, did not change.

Reactivity of sera and isolated monoclonal IgM from patients with Waldenström's macroglobulinaemia with peripheral nerve myelin.

Sera of 23 patients with Waldenström's macroglobulinaemia and six monoclonal IgM paraproteins, which had been isolated from these sera, were examined for reactivity against peripheral nerve tissue. Of these 23 patients, 12 had clinical signs of peripheral polyneuropathy (PN). Using an indirect immunofluorescence method, all sera and monoclonal IgM preparations reacted with peripheral nerve structures, displaying a distinct granular fluorescence pattern with anti-IgM sera. The Waldenström sera reacted mainly with structures at the border of the myelin sheath, as well as between myelin and axon, and occasionally with the axon itself. There was no difference between sera of patients with PN and those without. Negative results were obtained in a complement fixation assay. Of the 23 sera, 15 reacted in an antibody-dependent lymphocyte-mediated cytotoxicity reaction (ADLC) with peripheral nerve myelin, and to a much lesser extent with myelin basic protein from CNS. Five of the six isolated monoclonal IgM preparations also gave positive ADLC reactions. These results constitute additional evidence for an immunological mechanism in the pathogenesis of PN in Waldenström's macroglobulinaemia.