Determination of sensitivity of fresh leukemia cells to immunotoxins.

In clinical practice, sensitivity of malignant cells to a given immunotoxin remains hypothetical, since standard test systems such as the protein synthesis inhibition assay or the cloning assay are not appropriate. This study evaluated the feasibility of a semi-routine procedure based on dye exclusion assay enumerating the percentage of living cells after fluorescein diacetate-propidium iodide staining. The validity of the method was evaluated using five different subclones derived from the CEM cell line, which expressed a wide range of sensitivity to T101 A-chain immunotoxin. The comparison between dye exclusion assay and standard test systems suggested that this method might allow an easy and reproducible semi-quantitative evaluation of the sensitivity of leukemia cells. In a series of 21 patients suffering from various blood diseases in which the malignant cells expressed the T65 antigen, dye exclusion assay could detect clear T101 immunotoxin cell sensitivity in about 50% of the cases. The mean density of T65 antigen on malignant cells was found to influence dramatically the sensitivity of target cells to T101 immunotoxin.

Prognostic significance of karyotype in de novo adult acute myeloid leukemia. The BGMT group.

A group of 201 adult patients, 127 younger and 74 older than 55 years, with de novo acute myeloid leukemia were investigated to determine the prognostic significance of karyotype on early death (toxic or aplastic death occurring before hematopoietic recovery), drug resistance, continuous complete remission (CCR) and survival probabilities at 5 years. A good prognostic impact was found for t(8;21), t(15;17) and inv(16). The best factor proved to be t(8;21) (5-year survival probability: 50%), followed by t(15;17) (5-year survival probability: 39%) and by inv(16) (5-year survival probability: 43%). An intermediate outcome was found in patients with trisomy 8 (27% alive at 5 years) and in patients with numerical abnormalities other than -7 and +8 (33% in CCR and 62% alive at 5 years). Normal karyotypes had a different prognostic impact according to age: intermediate in young and good in older patients. A poor outcome was observed among patients with del(5q)/-5 (median survival: 1 month), with 11q23 rearrangements (median survival: 1.5 months) and with del(7q)/-7 (median survival: 10 months). The 'other structural change' group was also found to be a poor risk population (5-year survival probability: 5%) whereas complex karyotypes were predictive of short survivals only in older patients. Conversely, del(7q)/-7 and +8 as secondary changes, had no prognostic impact.

Richter's syndrome. Evidence for the clonal origin of the two proliferations.

A case of Richter's syndrome was investigated by several technics: light and electron microscopy, surface markers, immunohistological studies and immunoelectron microscopy. On light microscopy lymph node proliferation was composed of large lymphoid cells, some exhibiting Reed-Sternberg like features. On electron microscopy many intermediary cells, from small lymphocytes to immunoblasts and plasma cells, were noted. The circulating small lymphocytes were characterized as B cells (SIg +; MRBC+). The lymph node cells shared the same SIg phenotype (IgMK) but the percentage of MRBC was slightly lower. Immunohistological studies showed that lymph node cells were stained exclusively by anti micron and anti kappa antisera. These results are indicative of the B clonal origin of the two cell proliferations. Immunoelectron microscopy showed three staining patterns: 1) cells presenting only surface staining, 2) cells with diffuse staining presumably related to ribosomal fixation, 3) cells with endoplasmic reticulum staining. The significance of these three patterns is discussed with regard to B lymphocyte differentiation.

Bone marrow involvement in anaplastic large cell lymphoma. Immunohistochemical detection of minimal disease and its prognostic significance.

Bone marrow involvement by anaplastic large cell anaplastic large cell (ALC) lymphoma can be difficult to detect on routine morphologic examination alone. In a series of 42 patients with ALC lymphoma, the authors analyzed: (1) the usefulness of a limited panel of monoclonal antibodies directed against CD30 (Ber-H2, HRS4) and epithelial marrow involvement on routinely processed biopsy specimens; and (2) the prognostic significance of bone marrow involvement as detected on both morphologic and immunohistochemical grounds. On conventional examination, 17% of the patients were found to have bone marrow involvement at diagnosis. However, after immunohistochemical analysis, occult malignant cells were detected in 23% of the patients with negative bone marrow biopsy on routine histology. The low percentage of positive cases on routine morphologic examination compared to immunohistochemical examination was related to: (1) the scarcity of neoplastic cells which were scattered among hematopoietic cells; (2) the difficulty of distinguishing malignant cells from immature hematopoietic elements; and (3) the absence of alteration of the reticulin network. The authors observed a significant association between marrow infiltration and the presence of hematologic abnormalities (mostly anemia or cytopenias) at diagnosis, both in children and adult patients. More importantly, a significant lower survival was seen in patients with bone marrow involvement compared to those without bone marrow involvement. Immunohistochemistry with anti-CD30 and anti-EMA antibodies should be performed systematically in bone marrow biopsies from patients with ALC lymphoma to reliably identify the presence of bone marrow involvement that appears to carry a poor prognosis.

Influence of naloxone on antidepressant drug effects in the forced swimming test in mice.

The influence of naloxone on the effects of several antidepressant drugs, atropine and caffeine was studied in the forced swimming test in mice. Naloxone itself has no effect in this test, but significantly reduces that of two tricyclic antidepressants, clomipramine (20 and 30 mg/kg) and desipramine (20 and 30 mg/kg). Except for clorgyline at the high dose of 60 mg/kg, no significant reduction of activity by naloxone was observed with other antidepressants (pargyline, nomifensine and mianserin), nor with caffeine and atropine. These results are discussed in terms of the pharmacological characteristics of each drug and of the test used. No straightforward interaction between cholinergic or monoaminergic and endorphinic systems is evident. Possible action at opiate receptor sites is discussed.

Naloxone inhibits clomipramine in mouse forced swimming test.

Naloxone inhibited the effect of clomipramine on duration of immobility of mice in the forced swimming test. This test is proposed as an antidepressant study model. It had previously been shown that naloxone inhibited the analgesic effect of the antidepressant clomipramine. Several hypotheses are considered for the mechanism of the naloxone-clomipramine antagonism.

Influence of naloxone and methysergide on the analgesic effect of clomipramine in rats.

The effects of the tricyclic antidepressant clomipramine were studied in two analgesic tests in rats: (1) vocalization threshold response; and (2) scored behavioral response to electric shock to the tail. Clomipramine (20-50 mg/kg i.p.) produced analgesia, decreasing behavioral response scores and increasing vocalization threshold. Morphine also reduced the response scores in the second test. Naloxone (0.8 mg/kg i.p) or methysergide (20 mg/kg i.p.) (no effect when given alone) abolished the analgesic effect of clomipramine as evaluated by vocalization threshold response. Naloxone alone (0.6 or 2 mg/kg i.p.) increased the behavioral response at 20 and 30 V but did not modify the score at 40 V. Naloxone reduced the analgesic effect of clomipramine or morphine in the behavioral test. These results suggest that the analgesic effect of clomipramine could involve both serotonergic and endorphin central systems.

Morphine pretreatment reduces clomipramine effect in mouse forced-swimming test.

It had previously been shown that naloxone inhibits the effect of clomipramine both in a pain test in the forced-swimming test in mice which is proposed as an antidepressant study model. Evidence is reported of a decrease in activity of clomipramine in the forced-swimming test in mice after morphine pretreatment. The hypothesis of an interaction with mu-opiate receptors is considered.

Efficacy and tolerance of calcium alginate versus vaseline gauze dressings in the treatment of diabetic foot lesions.

BACKGROUND: The study aimed at comparing the efficacy and tolerance of an alginate wound dressing with a vaseline gauze dressing in the treatment of diabetic foot lesions. METHODS: This open-label randomized multicenter controlled study was designed to assess the effect of an up to 6-week treatment with either calcium alginate or vaseline gauze dressings. Lesions were either acute or chronic, under cleansing, and with a surface area of 1-50 cm(2); osteomyelitis and severe hypovascularization were non-inclusion criteria. Dressings were changed every day then, once granulation had occurred, every 2 to 3 days. Primary outcome was the proportion of patients with granulation tissue over 75% of the wound area and having a 40% decrease in wound surface area; secondary outcomes were pain on dressing changes, the number of dressing changes, and adverse events. RESULTS: Seventy-seven patients were enrolled. Due to the premature cessation of treatment in 13 patients, it was decided to reduce the period of the efficacy analysis to 4 weeks (without revising the criteria of efficacy). The success rate was of 42.8% in the calcium alginate group and of 28.5% in the vaseline gauze group (not significant difference). A subsequent analysis of granulation tissue surfaces covering the wounds at week 4 (all surfaces taken together) showed a superiority of calcium alginate (p=0.04). Pain on dressing change was lower in the calcium alginate group (p=0.047) and the total number of dressing changes tended also to be lower (p=0.07). Adverse events, which occurred 4 times in the calcium alginate group and 6 times in the other, were judged independent of the treatments. CONCLUSIONS: As compared with vaseline gauze, calcium alginate appears to be more appropriate for topical treatment of diabetic foot lesions in terms of both healing and tolerance.

Activities of five antidepressants in a behavioral pain test in rats.

Various clinical and experimental reports indicate that antidepressant drugs can have analgesic properties. The authors tested successively the anti-nociceptive activity of desipramine, clomipramine, maprotiline, viloxazine and nomifensine on the acute experimental pain model designed by Charpentier. At 25 mg/kg, desipramine showed a marked antalgic action. Clomipramine and maprotiline had a similar though much weaker action. On the other hand, nomifensine and viloxazine did not reduce pain perception; their effects on the parameters studied were variable. The usefulness of the test itself is discussed and suggestions are made regarding the relations between the analgesic potency of the drugs and the main neurotransmitter system they are assumed to act on.

Chronic administration of clomipramine inhibits morphine hot plate analgesia.

Clomipramine, chronically administered in mice, for 3 days, inhibits partially but significantly morphine analgesia in the hot plate test, when used at dose of 10 mg/kg/day, i.p.; 2.5 and 5 mg/kg/day were ineffective. Neither higher doses (20 and 40 mg/kg/day) nor longer duration of pretreatment (8 and 16 days) modified the intensity of this inhibition. Reduction in morphine analgesia was obtained after a 24h delay between the last injection of clomipramine and that of morphine (30 min before testing), while clomipramine did not induce any antinociceptive effect and clomipramine and desmethylclomipramine plasma and brain levels were low or undetectable. These results provide new evidence for the interaction between clomipramine and the endogenous opiate system. A pharmacokinetic interaction between clomipramine and morphine was excluded; involvement of change in opiate and 5 HT2 receptors by chronic administration of clomipramine is discussed.

Computer generation of surface distribution maps of measures of brain activity.

A laboratory computer system in described which will rapidly generate gray-scale maps showing the distribution of measures derived from the electrical activity of the brain, such as the electroencephalogram (EEG) or other biological measures. The system allows flexible description of electrode number and placement, mapping onto any shaped space and rapid generation of maps by integration with the data collection software.

[Panic attack caused by biguanides]. / Attaque de panique déclenchée par les biguanides.

We report the case of a patient born in 1923 who had been treated with metformin since 1977 and experienced panic attacks. Lactic acid levels, measured during an attack for the first time since metformin was prescribed, were found to be elevated on two occasions. Metformin was discontinued, and during a 9-month follow-up period the patient was free from any psychiatric disorder. The role of lactic acid in the triggering of panic attacks is discussed.

[Dexamethasone test in cluster headache]. / Test à la dexaméthasone dans l'algie vasculaire de la face.

Cluster headache and manic depressive illness share in common similarities like: periodic symptomatology, accessibility to lithium therapy, abnormalities in circadian rhythm of cortisol. Though, in contrast to periodic depression, D.S.T. was found normal in 9 patients with cluster headache.

[Functional assessment scales and lower limb amputation]. / Echelles d'évaluation fonctionnelle et amputation du membre inférieur.

INTRODUCTION: This paper is a review of the literature on assessment tools in lower limb amputees. MATERIAL AND METHODS: The authors have research on Medline(R) data base the different tools with keys words "lower limb amputee or amputation, functional evaluation or outcome assessment tools, activity of daily living", and have completed the research with the references of papers. RESULTS: A comprehensive approach of the consequences of an amputation and of the outcome of prosthetic care should include an evaluation of gait, use of the prosthesis in activities of daily life, acceptability and satisfaction with the device. DISCUSSION: Functional assessment tools that are validated are recent, and most of them were developed in English. They take into account the use and the acceptance of the device, but there is no study using them for an important sample population. CONCLUSION: It is now necessary to translate the recent tools into French, and to confirm their validity and sensitivity to change.

[Clinical and pharmacologic aspects of the analgesic effect of tricyclic antidepressants]. / Aspects cliniques et pharmacologiques de l'effet antalgique des antidépresseurs tricycliques.

Although tricyclic antidepressants have now been used for more than 20 years in the treatment of chronic pain, controlled studies of their effectiveness are quite recent. The best results are obtained in pain due to peripheral nerve lesions, and high doses are recommended. In contrast with the slow onset of their effect on depression, these drugs promptly relieve pain, which suggests two different mechanisms of action. The analgesic mechanism is unknown; some data indicate that serotonin is involved but an action on the adrenergic system cannot be ruled out. The arguments supporting the recent endorphin hypothesis are reviewed, ad a possible relationship between tricyclic antidepressants and endorphins is envisaged.

Evaluation of a wheelchair prototype with non-conventional, manual propulsion.

OBJECTIVE: To evaluate the results of a user satisfaction questionnaire on a new type of lever-propelled wheelchair designed to avoid the discomfort and potential repetitive strain injuries related to conventional hand-rim propulsion. METHODS: Seventeen participants filled out a questionnaire to rate their conventional wheelchair and the prototype (after 2 days' use) in terms of comfort, adjustability, steering/ride, manoeuvrability, stability when crossing obstacles, safety, weight, size, portability and appearance. Overall satisfaction was also scored. RESULTS: According to the user questionnaire results, the lever-propelled prototype chair was rated as significantly superior than conventional wheelchairs in terms of comfort, safety and overall satisfaction. The prototype was rated significantly inferior in terms of size, adaptability, appearance and crossing obstacles. CONCLUSION: We conclude that the prototype wheelchair is highly acceptable and comfortable and can be recommended to disabled sportspersons. The prototype's weak points are mainly related to ergonomic aspects, which could be improved in future models.