Adequate cytogenetic examination in myelodysplastic syndromes: analysis of 529 patients

In myelodysplastic syndromes (MDS), the karyotype is one of the most significant prognostic markers with profound impact on differential diagnosis and therapeutic decisions. In a retrospective study, we examined karyotypes of bone marrow specimens of an oligocentric cohort comprising 529 patients with MDS to address the question how many metaphases need to be analyzed to detect even small cell clones with an appropriate expenditure. We found a statistically significant difference of the frequency of normal karyotypes in the patient group with 19 or less analyzed metaphases compared to the group with 20 or more metaphases analyzed (56% versus 47%, p=0.041). Furthermore, we demonstrate that the analysis of 25 or more metaphases can further improve the sensitivity of karyotype analysis and leads to the identification of additional clinically relevant abnormal clones or subclones in a substantial proportion of patients. In summary, our data suggest the examination of at least 20 metaphases in MDS.     

Inhibition of calpain prevents NMDA-induced cell death and β-amyloid-induced synaptic dysfunction in hippocampal slice cultures

Background and purpose:

Alzheimer''s disease (AD) is a multifactorial, neurodegenerative disease, which is in part caused by an impairment of synaptic function, probably mediated by oligomeric forms of amyloid-β (Aβ). While the Aβ pathology mainly affects the physiology of neurotransmission, neuronal decline is caused by excitotoxic cell death, which is mediated by the NMDA receptor. A comprehensive therapeutic approach should address both Aβ-induced synaptic deficits, as well as NMDA receptor-mediated neurodegeneration, via one molecular target. This study was designed to test whether calpain could be involved in both pathological pathways, which would offer a promising avenue for new treatments.

Experimental approach:

Application of the specific, water-soluble calpain inhibitor A-705253 was used to inhibit calpain in hippocampal slice cultures. We examined whether inhibition of calpain would prevent Aβ-induced deficits in neurotransmission in CA1, as well as NMDA-induced neuronal cell death.

Key results:

A-705253 dose-dependently prevented excitotoxicity-induced neurodegeneration at low nanomolar concentrations, determined by propidium iodide histochemistry. Inhibition of the NMDA receptor similarly protected from neuronal damage. Caspase staining indicated that calpain inhibition was protective by reducing apoptosis. Electrophysiological analysis revealed that inhibition of calpain by A-705253 also fully prevented Aβ oligomer-induced deficits in neurotransmission. The protective effect of calpain was compared to the clinically available NMDA receptor antagonist memantine, which was also effective in this model.

Conclusions and implications:

We suggest that inhibition of calpain exhibits a promising strategy to address several aspects of the pathology of AD that may go beyond the available therapeutic intervention by memantine.     

Embryoid bodies: an in vitro model of mouse embryogenesis

Embryonic stem (ES) cells are pluripotent cells isolated from the inner cell mass of blastocysts. ES cells are able to differentiate into the three primitive layers (endoderm, mesoderm and ectoderm) of the organism, including the germline. To study early stages of development, as well as to investigate the impact of a gene knock-out in vitro, ES cells are differentiated into three-dimensional structures called embryoid bodies, because of their ability to mimick post-implantation embryonic tissues. This review summarises the work on ES cell differentiation into haematopoietic and vascular cells, neuronal and glial cells, myocytes, and adipocytes, using this in vitro model of early embryogenesis. We also present the potential of this method to analyse the impact of genetic alterations in vitro.     

Surgical treatment strategies for giant inguinoscrotal hernia – a case report with review of the literature

Background

An inguinoscrotal hernia is defined as “giant” if descending below the midpoint of the inner thigh of a patient in upright position. In developed countries this is a rare entity. In the literature different surgical techniques have been reported so far to achieve a successful treatment.

Case presentation

We present the case of a 63 year-old man suffering from a giant inguinoscrotal hernia, whom we treated using a combined open transabdominal and inguinal approach following an unsuccessful laparoscopic attempt. Meshes were placed in a premuscular position (Lichtenstein’s procedure) and in a preperitoneal position. In addition, a reconstruction of the abdominal wall by modified components separation technique was performed. During the early postoperative period no complications were registered. Intensive care treatment was not necessary. The patient was discharged on postoperative day 8 in an excellent condition. Six months after surgery a scrotal hematocele was diagnosed and operatively removed. After a follow-up of 1.5 years neither hernia recurrence, nor chronic groin pain were recorded. The patient reported to be sexually active. His quality of life improved notably.Additionally, a Medline and PubMed database research was performed to create an overall picture of the existing surgical treatment strategies. Included were patients with diagnosis of primary giant inguinoscrotal hernia according to the given definition. Emergency interventions and cases without details of the surgical approach were excluded.

Conclusions

Firstly, this report describes a novel, successful surgical treatment of a giant inguinoscrotal hernia without administering preoperative progressive pneumoperitoneum therapy or visceral resection. Secondly, we summarize cases previously reported as a practical guide for possible surgical therapy approaches.

     

Double induction strategy for acute myeloid leukemia: the effect of high-dose cytarabine with mitoxantrone instead of standard-dose cytarabine with daunorubicin and 6-thioguanine: a randomized trial by the German AML Cooperative Group.

Early intensification of chemotherapy with high-dose cytarabine either in the postremission or remission induction phase has recently been shown to improve long-term relapse-free survival (RFS) in patients with acute myeloid leukemia (AML). Comparable results have been produced with the double induction strategy. The present trial evaluated the contribution of high-dose versus standard-dose cytarabine to this strategy. Between March 1985 and November 1992, 725 eligible patients 16 to 60 years of age with newly diagnosed primary AML entered the trial. Before treatment started, patients were randomized between two versions of double induction: 2 courses of standard-dose cytarabine (ara-C) with daunorubicin and 6-thioguanine (TAD) were compared with 1 course of TAD followed by high-dose cytarabine (3 g/m2 every 12 hours for 6 times) with mitoxantrone (HAM). Second courses started on day 21 before remission criteria were reached, regardless of the presence or absence of blast cells in the bone marrow. Patients in remission received consolidation by TAD and monthly maintenance with reduced TAD courses for 3 years. The complete remission (CR) rate in the TAD-TAD compared with the TAD-HAM arm was 65% versus 71% (not significant [NS]), and the early and hypoplastic death rate was 18% versus 14% (NS). The corresponding RFS after 5 years was 29% versus 35% (NS). An explorative analysis identified a subgroup of 286 patients with a poor prognosis representing 39% of the entire population; they included patients with more than 40% residual blasts in the day-16 bone marrow, patients with unfavorable karyotype, and those with high levels of serum lactate dehydrogenase. Their CR rate was 65% versus 49% (p =.004) in favor of TAD-HAM and was associated with a superior event-free survival (median, 7 v 3 months; 5 years, 17% v 12%; P =.012) and overall survival (median, 13 v 8 months; 5 years, 24% v 18%; P =.009). This suggests that the incorporation of high-dose cytarabine with mitoxantrone may contribute a specific benefit to poor-risk patients that, however, requires further substantiation. Double induction, followed by consolidation and maintenance, proved a safe and effective strategy and a new way of delivering early intensification treatment for AML.     

Zur Befunderhebung bei einem ausländischen Patienten

Ohne Zusammenfassung     

Avidity determination of IgG directed against tick-borne encephalitis virus improves detection of current infections

Recently, avidity determination of IgG has been introduced successfully into virus serology as an additional and specific means for confirmation or exclusion of current infections. This simple and highly reproducible method can compensate for problems arising by classical serology, which include lack of detectable IgM responses during primary infections and persistent IgM responses after past infections. We show that avidity determination can be applied successfully for serological diagnosis of TBEV infection. Using the urea denaturation method, primary TBEV infections showed anti-TBEV IgG of low avidity (avidity index < 0.4), whereas sera from individuals with past infections exhibited high avidity IgG. The retrospective analysis of cases with clinical symptoms of TBEV infection in the absence of detectable anti-TBEV IgM showed that a significant number of these cases (5/45) had anti-TBEV IgG of low avidity, indicating current infection. We recommend the use of avidity determination as a method for routine TBEV serology. J. Med. Virol. 51:242–251, 1997. © 1997 Wiley-Liss, Inc.     

食管切除术后病人的护理

在美国,食管癌是死亡率最高的恶性肿瘤之一,男性多于女性,其发病率随年龄增长而增加。食管癌临床表现早期食管癌临床表现不明显,吞咽困难是最常见的初始症状,但由于食管壁的柔韧性,病人到晚期才感觉到,从不能吞咽固体开始,进展到最终不能吞咽液体。此外,病人还可有吞咽时疼痛、体重减轻、营养不良和虚弱等表现。晚期表现还包括胸骨后疼痛、呃逆、呼吸困难、胃烧灼感、口臭、声音嘶哑、咳嗽、流涎过多及夜间误吸等。食管切除术后病人的护理食管切除术后24~48 h病人在重症监护室度过,通常带有气管插管等多种导管,护士应加强心肺及各方面的监护…