Liver Assessment in Patients with Ataxia-Telangiectasia: Transient Elastography Detects Early Stages of Steatosis and Fibrosis.

Background: Ataxia-telangiectasia (A-T) is a rare autosomal-recessive multisystem disorder characterized by pronounced cerebellar ataxia, telangiectasia, cancer predisposition, and altered body composition. Liver diseases with steatosis, fibrosis, and hepatocellular carcinoma are frequent findings in older patients but sensitive noninvasive diagnostic tools are lacking. Objectives: To determine the sensitivity of transient elastography (TE) as a screening tool for early hepatic tissue changes and serum biomarkers for liver disease. Methods: Thirty-one A-T patients aged 2 to 25 years were examined prospectively from 2016-2018 by TE. In addition, we evaluated the diagnostic performance of liver biomarkers for steatosis and necroinflammatory activity (SteatoTest and ActiTest, Biopredictive, Paris) compared to TE. For calculation and comparison, patients were divided into two groups (<12, >12 years of age). Results: TE revealed steatosis in 2/21 (10%) younger patients compared to 9/10 (90%) older patients. Fibrosis was present in 3/10 (30%) older patients as assessed by TE. We found a significant correlation of steatosis with SteatoTest, alpha-fetoprotein (AFP), HbA1c, and triglycerides. Liver stiffness correlated significantly with SteatoTest, ActiTest, HbA1c, and triglycerides. Conclusion: Liver disease is a common finding in older A-T patients. TE is an objective measure to detect early stages of steatosis and fibrosis. SteatoTest and ActiTest are a good diagnostic assessment for steatosis and necroinflammatory activity in patients with A-T and confirmed the TE results.

Combination of broad molecular screening and cytogenetic analysis for genetic risk assignment and diagnosis in patients with acute leukemia.

We evaluated the impact of genetic analysis combining cytogenetics and broad molecular screening on leukemia diagnosis according to World Health Organization (WHO) and on genetic risk assignment. A two-step nested multiplex RT-PCR assay was used that allowed the detection of 29 fusion transcripts. A total of 186 patients (104 males (56%), 174 adults (94%), 12 children (6%), 155 AML (83%), 31 ALL (17%)) characterized by morphology and immunophenotyping were included. Of these 186 patients, 120 (65%) had a genetic abnormality. Molecular typing revealed a fusion transcript in 49 (26%) patients and cytogenetic analysis revealed an abnormal karyotype in 119 (64%). A total of 27 (14%) cases were genetically classified as favorable, 107 (58%) intermediate and 52 (28%) unfavorable. For 38 (20%) patients, there was a discrepancy in the genetic risk assignments obtained from broad molecular screening and cytogenetics. Cryptic fusion transcripts in nine (5%) patients changed the genetic risk assignment in four and the WHO classification in four patients. In 34 patients (18%), cytogenetics defined the risk assignment by revealing structural and numerical chromosomal abnormalities not detected by molecular screening. Broad molecular screening and cytogenetics are complementary in the diagnosis and genetic risk assignment of acute leukemia.

Pharmacokinetics of pamidronate in patients with bone metastases.

BACKGROUND: Pamidronate is a second-generation bisphosphonate used in the treatment of tumor-induced hypercalcemia and in the management of bone metastases from breast cancer, myeloma, or prostate cancer. The pharmacokinetics of pamidronate is unknown in cancer patients. PURPOSE: To determine the influence of the rate of administration and of bone metabolism, we studied the pharmacokinetics of pamidronate at three different infusion rates in 37 patients with bone metastases. METHODS: Three groups of 11-14 patients were given 60 mg pamidronate as an intravenous infusion over a period of 1, 4, or 24 hours. Urine samples were collected in the three groups of patients. Plasma samples were obtained only in the 1-hour infusion group. The assay of pamidronate in plasma and urine was performed by high-performance liquid chromatography with fluorescence detection after the derivatization of pamidronate with fluorescamine. RESULTS: The body retention (BR) at 0-24 hours of pamidronate represented 60%-70% of the administered dose and was not significantly modified by the infusion rate. In particular, the BR at 0-24 hours was not reduced at the fastest infusion rate. Among patients, a threefold variability in BR at 0-24 hours occurred, which was related directly to the number of bone metastases and, to some extent, to creatinine clearance. At 60 mg/hour, the plasma kinetics followed a multiexponential course characterized by a short distribution phase. The mean (+/- SD) half-life of the distribution phase was 0.8 hour (+/- 0.3), the mean (+/- SD) of the area under the curve for drug concentration in plasma x time at 0-24 hours was 22.0 +/- 8.8 mumol/L x hours, and the mean (+/- SD) of the maximum plasma concentration was 9.7 mumol/L (+/- 3.2). Pharmacokinetic variables remained unchanged after repeated infusions applied to four patients. Clinically, the three infusion rates were equally well tolerated without significant toxicity. CONCLUSIONS: The 1-hour infusion rate could be proposed as kinetically appropriate for the administration of pamidronate to patients with metastatic bone diseases.

[The plasma cell myeloma--molecular pathogenesis and target therapies]. / Das Plasmazell-Myelom--von der molekularen Pathogenese zu neuen gezielten Therapien.

The cells of the malignant clone of plasmacell myeloma have cytogenetic aberrations in a substantial number of cases. Many of these abnormal karyotypes are predictive for an unfavorable outcome. Gene mutations and abnormal gene expression, particularly of oncogenes and tumor suppressor genes, are often observed in myeloma cells. The cross talk between the myeloma cells and the bone marrow microenvironment plays an important role for growth and survival of the tumor cells. As a consequence of this cell-to-cell-interaction, several cytokines are secreted. The intracellular signaling, evoked by these cytokines, leads to continuous growth and proliferation and inhibition of apoptosis. Since these molecular pathways have been defined, many new targets for therapeutical interventions become obvious. Some molecules, directed against cytokines, are under early clinical investigation. Medicaments intervening in the cross talk between the myeloma cell and the bone marrow stroma as Thalidomide, Lenalidomide or Bortezomib are already available. Many of the myeloma patients suffer from bone disease. Some new drugs inhibiting the differentiation and activation of osteoclasts are evaluated in clinical trials. These molecules will be an important contribution against the painful bone disease of plasmacell myeloma.

Secondary malignancies in chronic myeloid leukemia patients after imatinib-based treatment: long-term observation in CML Study IV.

Treatment of chronic myeloid leukemia (CML) has been profoundly improved by the introduction of tyrosine kinase inhibitors (TKIs). Long-term survival with imatinib is excellent with a 8-year survival rate of ∼88%. Long-term toxicity of TKI treatment, especially carcinogenicity, has become a concern. We analyzed data of the CML study IV for the development of secondary malignancies. In total, 67 secondary malignancies were found in 64 of 1525 CML patients in chronic phase treated with TKI (n=61) and interferon-α only (n=3). The most common malignancies (n⩾4) were prostate, colorectal and lung cancer, non-Hodgkin's lymphoma (NHL), malignant melanoma, non-melanoma skin tumors and breast cancer. The standardized incidence ratio (SIR) for all malignancies excluding non-melanoma skin tumors was 0.88 (95% confidence interval (0.63-1.20)) for men and 1.06 (95% CI 0.69-1.55) for women. SIRs were between 0.49 (95% CI 0.13-1.34) for colorectal cancer in men and 4.29 (95% CI 1.09-11.66) for NHL in women. The SIR for NHL was significantly increased for men and women. An increase in the incidence of secondary malignancies could not be ascertained. The increased SIR for NHL has to be considered and long-term follow-up of CML patients is warranted, as the rate of secondary malignancies may increase over time.

Value of different modalities of granulocyte-macrophage colony-stimulating factor applied during or after induction therapy of acute myeloid leukemia.

PURPOSE: The hematopoietic growth factors (HGFs) introduced into induction chemotherapy (CT) of acute myeloid leukemia (AML) might be of benefit to treatment outcome by at least two mechanisms. HGFs given on days simultaneously with CT might sensitize the leukemic cells and enhance their susceptibility to CT. HGFs applied after CT might hasten hematopoietic recovery and reduce morbidity or mortality. MATERIALS AND METHODS: We set out to evaluate the use of granulocyte-macrophage colony-stimulating factor (GM-CSF; 5 microg/kg) in a prospective randomized study of factorial design (yes or no GM-CSF during CT, and yes or no GM-CSF after CT) in patients aged 15 to 60 years (mean, 42) with newly diagnosed AML. GM-CSF was applied as follows: during CT only (+/-, n = 64 assessable patients), GM-CSF during and following CT (+/+, n = 66), no GM-CSF (-/-, n = 63), or GM-CSF after CT only (-/+, n = 60). RESULTS: The complete response (CR) rate was 77%. At a median follow-up time of 42 months, probabilities of overall survival (OS) and disease-free survival (DFS) at 3 years were 38% and 37% in all patients. CR rates, OS, and DFS did not differ between the treatment groups (intention-to-treat analysis). Neutrophil recovery (1.0 x 10(9)/L) and monocyte recovery were significantly faster in patients who received GM-CSF after CT (26 days v 30 days; neutrophils, P < .001; monocytes, P < .005). Platelet regeneration, transfusion requirements, use of antibiotics, frequency of infections, and duration of hospitalization did not vary as a function of any of the therapeutic GM-CSF modalities. More frequent side effects (eg, fever and fluid retention) were noted in GM-CSF-treated patients predominantly related to the use of GM-CSF during CT. CONCLUSION: Priming of AML cells to the cytotoxic effects of CT by the use of GM-CSF during CT or accelerating myeloid recovery by the use of GM-CSF after CT does not significantly improve treatment outcome of young and middle-aged adults with newly diagnosed AML.

Detection of 16 p deletions by FISH in patients with inv(16) or t(16;16) and acute myeloid leukemia (AML).

Deletions of sequences centromeric to the p-arm breakpoint have been described in a subset of patients with inv(16) and acute myeloid leukemia (AML) and reported to be associated with a relatively good prognosis. We have investigated 16 p deletions in a cohort of 15 patients with AML and inv(16) or t(16;16) and compared non-deletion and deletion patients in terms of clinical course. Patients were studied by fluorescence in situ hybridization (FISH) using cosmid zit14 as a probe to detect the presence of 16 p deletions in metaphase chromosomes of leukemic cells. While seven patients (47%) revealed no evidence of a deletion, five patients (33%) presented 16 p deletions, thus bringing further support to the relatively frequent occurrence of this event in inv(16) patients. Remarkably, two patients with inv(16) and one patient with t(16;16) showed a mosaicism of deletion and non-deletion metaphases suggesting the presence of two distinct leukemic cell populations. Results let us assume that 16 p deletions are not restricted to inv(16) and may occur subsequently to inv(16) or t(16;16). The presence of a 16 p deletion in a case of inv(16) associated with CBFB-MYH11 transcript type E indicates that deletions are not limited to CBFB-MYH11 transcript type A rearrangements. Survival of deletion patients was compared with that of non-deletion and mosaic ones. No significant differences were observed. The advantage of FISH for enumerative and quantitative assessment of submicroscopic rearrangements of clinical significance is further emphasized.

Effect of long-term treatment with recombinant human interleukin-3 in patients with myelodysplastic syndromes.

In a phase II study, involving nine patients with refractory anemia or refractory anemia with ring sideroblasts, the effects of treatment with recombinant human interleukin-3 (IL-3) on hematopoietic function were assessed. Doses of IL-3 ranging from 60 micrograms/m2 during weeks 1-6 to 125 micrograms/m2 during weeks 7-12 were administered as subcutaneous bolus injections three times per week for 12 weeks. Platelet counts increased in six patients. Platelet increase correlated with stable or decreased serum tumour necrosis factor alpha (TNF-alpha) levels, while an increase of TNF-alpha levels during IL-3 therapy occurred in patients with no change or a decrease of platelet counts. Leukocyte counts increased in two patients and reticulocytes in three, without an effect on hemoglobin levels. Morphological analysis of the bone marrow revealed an expansion of the myeloid compartment in seven of eight evaluable patients, mainly due to stimulation of the precursor cells. No improvement of the in vitro growth of hematopoietic progenitor cells was observed. Sequential cytogenetic analyses indicate that IL-3 treatment does not act preferentially on either the cytogenetically abnormal or the normal clones. These results suggest that long-term treatment with low-dose IL-3 stimulates megakaryopoiesis with increase of platelet counts, but that additional later-acting cytokines probably will be required to augment neutrophil and erythrocyte counts.

Effect of combination therapy with all-trans-retinoic acid and recombinant human granulocyte colony-stimulating factor in patients with myelodysplastic syndromes.

Since all-trans retinoic acid (ATRA) and granulocyte colony-stimulating factor (G-CSF) not only enhance proliferation and differentiation of normal myeloid cells but also synergistically promote the differentiation of myeloid leukemic blast cells in vitro, we have started a pilot study of combined treatment with ATRA and G-CSF in patients with myelodysplastic syndrome, to analyze the effect of these drugs on hematopoietic differentiation. ATRA was given at 45 mg/m2/day p.o. from week 1-12 and G-CSF at 5 micrograms/kg/day s.c. from week 5-12 with dose modifications according to the absolute neutrophil counts (ANC). A total of 15 patients, predominantly with refractory anemia, were treated. During initial ATRA therapy, a bilineage response with increases of both ANC and platelet counts occurred in three patients. During combined ATRA/G-CSF therapy, ANC increased in all patients, and platelets increased in three out of 14 evaluable patients. An increase in hemoglobin concentration and a decrease in transfusion requirements occurred in one patient each. In the bone marrow, the myeloid-to-erythroid ratio increased during ATRA treatment and remained increased during concomitant G-CSF administration, while the maturation index of myeloid cells increased only in response to ATRA therapy, but returned to baseline during ATRA/G-CSF treatment. Cytogenetic analysis demonstrated persistence of the abnormal clones in all patients. The number of circulating progenitor cells CFU-GM increased in all patients studied. Serum concentrations of the soluble TNF receptor and IL-2 receptor both increased, while TNF-alpha--already elevated prior to therapy--and soluble ICAM-1 concentrations did not significantly change. Adverse effects included dermatitis and cheilosis in most patients, and a drop in platelet counts related to G-CSF in one patient. The pilot study demonstrates that the combination treatment with ATRA/G-CSF is well tolerated, leading to normalization of ANC in most, and improvement of platelets and red blood cells in a subgroup of patients.

The presence of an HLA-identical sibling donor has no impact on outcome of patients with high-risk MDS or secondary AML (sAML) treated with intensive chemotherapy followed by transplantation: results of a prospective study of the EORTC, EBMT, SAKK and GIMEMA Leukemia Groups (EORTC study 06921).

This report used the framework of a large European study to investigate the outcome of patients with and without an HLA-identical sibling donor on an intention-to-treat basis. After a common remission-induction and consolidation course, patients with an HLA-identical sibling donor were scheduled for allogeneic transplantation and patients lacking a donor for autologous transplantation. In all, 159 patients alive at 8 weeks from the start of treatment were included in the present analysis. In total, 52 patients had a donor, 65 patients did not have a donor and in 42 patients the availability of a donor was not assessed. Out of 52 patients, 36 (69%) with a donor underwent allogeneic transplantation (28 in CR1). Out of 65 patients, 33 (49%) received an autograft (27 in CR1). The actuarial survival rates at 4 years were 33.3% (s.e. = 6.7%) for patients with a donor and 39.0% (s.e. = 6.5%) for patients without a donor (P = 0.18). Event-free survival rates were 23.1% (s.e. = 6.2%) and 21.5% (s.e. = 5.3%), respectively (P = 0.66). Correction for alternative donor transplants did not substantially alter the survival of the group without a donor. Also, the survival in the various cytogenetic risk groups was not significantly different when comparing the donor vs the no-donor group. This analysis shows that patients with high-risk myelodysplastic syndrome and secondary acute myeloid leukemia may benefit from both allogeneic and autologous transplantation. We were unable to demonstrate a survival advantage for patients with a donor compared to patients without a donor.

Amyloid beta protein is internalized selectively by hippocampal field CA1 and causes neurons to accumulate amyloidogenic carboxyterminal fragments of the amyloid precursor protein.

A critical issue concerning Alzheimer's disease is its selectivity, which leads to cellular degeneration in certain brain areas but not in others, and whether this pathogenic selectivity involves products of the amyloid precursor protein (APP). Here, we show that the amyloid beta protein Abeta1-42 is accumulated gradually and is retained intact by field CA1, but not by other subdivisions, of organotypic hippocampal slice cultures. In contrast, the slightly shorter Abeta1-40 peptide was not sequestered selectively. Sequestration of Abeta1-42 was followed by the build-up of carboxyterminal fragments of the endogenous precursor protein that were identified by immunoprecipitation. Unlike the peptide uptake, this induction appeared to be stochastic at the cellular level. In addition, the APP fragments were distributed more broadly within the CA1 pyramidal neurons than the sequestered Abeta1-42, and they appeared to be localized to synaptic terminals in the molecular layer of the dentate gyrus and in the stratum lacunosum-moleculare of the subfield CA3. Concentrations of synaptophysin, a presynaptic marker, decreased as the number of neurons producing amyloidogenic species increased. These results indicate that exogenous Abeta1-42 sets into motion a sequence that involves 1) selective uptake of the peptide by vulnerable cells at risk in Alzheimer's disease, 2) markedly enhanced production of amyloidogenic precursor material, and 3) slow deterioration of central synapses.

Treatment of myelodysplastic syndromes with cytokines and cytotoxic drugs.

Clinical trials with hematopoietic growth factors (granulocyte-macrophage colony-stimulating factor [GM-CSF], granulocyte colony-stimulating factor [G-CSF], interleukin-3, erythropoietin] have been done in patients with myelodysplastic syndromes. Treatment with GM-CSF or G-CSF has resulted in an increase of neutrophil counts into the normal range in the vast majority of patients. Progression to acute leukemia does not appear to occur more frequently in the patients receiving GM-CSF or G-CSF. Increases in platelet counts and hemoglobin levels have been reported after treatment with interleukin-3 and erythropoietin, respectively, although the response is only seen in a minority of treated patients. Combination therapy with GM-CSF and low-dose cytosine arabinoside has been studied, but present data do not indicate an advantage over other treatment strategies. Cytogenetic and molecular genetic analyses demonstrate that both normal and malignant precursor cells are stimulated by cytokine therapy.

Transformations for within-subject designs: a Monte Carlo investigation.

We explored the use of transformations to improve power in within-subject designs in which multiple observations are collected for each S in each condition, such as reaction time and psychophysiological experiments. Often, the multiple measures within a treatment are simply averaged to yield a single number, but other transformations have been proposed. Monte Carlo simulations were used to investigate the influence of those transformations on the probabilities of Type I and Type II errors. With normally distributed data, Z and range correction transformations led to substantial increases in power over simple averages. With highly skewed distributions, the optimal transformation depended on several variables, but Z and range correction performed well across conditions. Correction for outliers was useful in increasing power, and trimming was more effective than eliminating all points beyond a criterion.

Ampakines reduce methamphetamine-driven rotation and activate neocortex in a regionally selective fashion.

It has been proposed that glutamatergic and dopaminergic systems are functionally opposed in their regulation of striatal output. The present study tested the effects of drugs that enhance AMPA-receptor-mediated glutamatergic transmission (ampakines) for their effects on dopamine-related alterations in cortical activity and locomotor behavior. Rats with unilateral 6-hydroxydopamine lesions of the ascending nigro-striatal dopamine system were sensitized to methamphetamine and then tested for methamphetamine-induced circling behavior in the presence and absence of ampakines CX546 and CX614. Both ampakines produced rapid, dose-dependent reductions in circling that were evident within 15 min and sustained through 1 h of behavioral testing. In situ hybridization maps of c-fos mRNA expression showed that in the intact hemisphere, ampakine cotreatment markedly increased c-fos expression in parietal, sensori-motor neocortex above that found in rats treated with methamphetamine alone. Ampakine cotreatment did not augment c-fos expression in frontal, sensori-motor cortex or striatum. Still larger ampakine-elicited effects were obtained in parietal cortex of the dopamine-depleted hemisphere where labeling densities were increased by approximately 60% above values found in methamphetamine-alone rats. With these effects, the hemispheric asymmetry of cortical activation was less pronounced in the ampakine-cotreatment group as compared with the methamphetamine-alone group. These results indicate that positive modulation of AMPA-type glutamate receptors 1) can offset behavioral disturbances arising from sensitized dopamine receptors and 2) increases aggregate neuronal activity in a regionally selective manner that is probably dependent upon behavioral demands.

Comparison of the effects of an ampakine with those of methamphetamine on aggregate neuronal activity in cortex versus striatum.

The present study used in situ hybridization to c-fos mRNA to compare the effects of an 'ampakine' (a positive modulator of AMPA type glutamate receptors) with those of methamphetamine on the balance of aggregate neuronal activity in the cortex versus striatum. Methamphetamine (n = 11) induced a marked increase in c-fos mRNA in the dorsomedial quadrant of the striatum and a 21% smaller, but still reliable, increase in the ventrolateral quadrant. The drug also elevated c-fos mRNA levels in the ventral and medial segments of the orbitofrontal cortex but had no detectable effects in motor and somatosensory neocortices. The ampakine (n = 11) caused a near inverse pattern of changes; i.e. a sizable increase in somatosensory labeling and a significant decrease in striatal labeling with statistically insignificant effects in motor and orbitofrontal cortex. Within-rat cortical and striatal values were correlated in both the vehicle (n = 11) and ampakine groups, and appropriate comparisons established that the ampakine caused 27-55% increases in the ratio of cortical to striatal labeling. These results are in accord with the idea that facilitation of glutamatergic transmission has 'network level' effects that are opposite in nature to those resulting from enhanced dopaminergic transmission. The potential relevance of ampakines alone or in conjunction with dopamine antagonists for the treatment of schizophrenia is discussed.

Peripheral blood stem cell transplantation as an alternative to autologous marrow transplantation in the treatment of acute myeloid leukemia?

The clinical use of autologous marrow transplantation in acute myeloid leukemia (AML) has been hampered by the inability to collect adequate numbers of cells after remission induction chemotherapy and the notably delayed hematopoietic regeneration following autograft reinfusion. Here we present a study in which the feasibility of mobilizing stem cells was investigated in newly diagnosed AML. Among 96 AML patients, 76 patients (79%) entered complete remission. Mobilization was undertaken with low dose and high dose schedules of G-CSF in 63 patients, and 54 patients (87%) were leukapheresed. A median of 2.0 x 10(6) CD34+ cells/kg (range 0.1-72.0) was obtained in a median of three leukaphereses following a low dose G-CSF schedule (150 microg/m2) during an average of 20 days. Higher dose regimens of G-CSF (450 microg/m2 and 600 microg/m2) given during an average of 11 days resulted in 28 patients in a yield of 3.6 x 10(6) CD34+ cells/kg (range 0-60.3) also obtained following three leukaphereses. The low dose and high dose schedules of G-CSF permitted the collection of 2 x 10(6) CD34-positive cells in 46% and 79% of cases respectively (P = 0.01). Twenty-eight patients were transplanted with a peripheral blood stem cell (PBSC) graft and hemopoietic repopulation was compared with the results of a previous study with autologous bone marrow. Recovery of granulocytes (>0.5 x 10(9)/l, 17 vs 37 days) and platelets (>20 x 10(9)/l; 26 vs 96 days) was significantly faster after peripheral stem cell transplantation compared to autologous bone marrow transplantation. These results demonstrate the feasibility of PBSCT in the majority of cases with AML and the potential advantage of this approach with respect to hemopoietic recovery.

Combined chloroquine/Fansidar-resistant falciparum malaria appears in East Africa.

The first two cases from East Africa of RII chloroquine- and Fansidar-resistant falciparum malaria are described. The first case occurred in a non-immune Swedish expatriate 2 weeks after arrival in Tanzania, and the second in a semi-immune Tanzanian soldier. Fansidar has not yet been marketed in Tanzania. The significance and etiology of the occurrence of combined chloroquine/Fansidar resistance in East Africa are discussed.

Weekly x 4 induction therapy with the anti-CD20 antibody rituximab: effect on circulating t(14;18)(+) follicular lymphoma cells.

Rituximab 375 mg/m(2) weekly x 4 has been reported to induce a 60% response rate in patients with relapsed follicular lymphomas (FL). Our aim was to examine the effect of this rituximab schedule on circulating FL cells in an ongoing multicenter study. One hundred fifty-four patients with FL were examined by nested polymerase chain reaction (PCR) at baseline for the presence of t(14;18) translocation-carrying lymphoma cells in bone marrow and/or blood. Sixty-four patients (42%) had PCR-detectable t(14;18)(+) FL cells. Pretreatment characteristics of these 64 patients were as follows: one had stage I, nine had stage II, 14 had stage III, and 40 had stage IV disease. Thirty-five patients had bulky disease (> or = 5 cm) and 25 patients had an elevated serum lactate dehydrogenase (LDH) level. Bone marrow was morphologically assessed in 64 patients, and 39 of these patients had an infiltration with FL cells. Blood samples from 51 patients were available for PCR analysis between weeks 8-12 after induction therapy, and 28 of these patients (55%) were PCR negative. Paired blood and bone marrow samples were available for PCR analysis from 39 patients between weeks 8-12 after induction therapy with rituximab. Thirteen of these patients (33%) did not have PCR-detectable cells in blood and bone marrow, while 26 patients (67%) still had circulating t(14;18)(+) cells in either bone marrow (eight patients), blood (one patient), or both (17 patients). PCR negativity in blood and bone marrow in 13 patients was statistically significantly associated with partial or complete response after induction therapy with rituximab (P = 0.006). However, clearance of PCR-detectable t(14;18)(+) cells in bone marrow and/or blood could not be associated with any low tumor burden pretreatment characteristics such as stages I/II, absence of morphological bone marrow infiltration or tumor bulk of > or = 5 cm, and normal serum LDH.

[Simple method for obtaining Toxocara canis antigen for the indirect immunofluorescence technic]. / Eine einfache Methode zur Gewinnung von Toxocara canis-Antigen für die indirekte Immunofluoreszenz-Technik

A simple method for the preparation of Toxocara canis antigen for the indirect immunofluorescent test is described: Embryonated Toxocara eggs are treated for 12 hours at room temperature with a 1:1 mixture of 2% NaHO and sodium hypochlorite (NaClO) solution with a concentration of 2% free chlorine in order to remove the outer layers of the egg shells. The larvae which are still enclosed in the lipid membrane are freed by mild ultrasonic treatment. Thereafter, the suspension of larvae is washed and purified in a modified Baermann apparatus. In this way large numbers of larvae in pure suspension were gained and used for the production of frozen sections for the indirect immunofluorescent test. Rabbits and mice experimentally infected with embryonated Toxocara canis eggs showed a positive serological reaction (titers between 1/10 to 1/320) in this test with Toxocara larvae as antigen, while in uninfected control animals no antibodies could be detected. The larval antigen exhibited only a weak cross reaction with sera of animals infected with Ascaris suum eggs.

Impaired emotional facial expression recognition in alcoholism compared with obsessive-compulsive disorder and normal controls.

Emotional facial expression (EFE) decoding skills have been shown to be impaired in recovering alcoholics (RA). The aim of the present study is to replicate these results and to explore whether these abnormalities are specific to alcoholism using two control groups: non-patient controls (NC) and patients with obsessive-compulsive disorder (OC). Twenty-two alcoholic patients at the end of their detoxification process (RA) were compared to 22 OC and 22 NC matched for age, sex and education level. They were presented with 12 photographs of facial expressions portraying different emotions: happiness; anger; and fear. Each emotion was displayed with mild (30%) and moderate (70%) intensity levels. Each EFE was judged on 8 scales labeled happiness, sadness, fear, anger, disgust, surprise, shame and contempt. For each scale, subjects rated the estimated intensity level. RA were less accurate in EFE decoding than OC and NC, particularly for anger and happiness expressions. RA overestimated the emotional intensity for mild intensity level expressions compared with both OC and NC while no significant differences emerged for moderate intensity level expressions. Deficits in EFE decoding skills seem to be specific to RA when compared with OC. Comparison with other psychopathological groups is still needed. Possible consequences of EFE decoding deficits in RA include distorted interpersonal relationships.