Coexistence of antithrombin deficiency and suspected inferior vena cava atresia in an adolescent and his mother - case report and clinical implications.

BACKGROUND: Antithrombin deficiency (ATD) is an autosomal dominant thrombophilia presenting with varying phenotypes. In pediatric patients with ATD, thrombosis typically develops during the neonatal period or adolescence. However, to date there are no consistent recommendations on the therapeutic management of children with ATD. Inferior vena cava atresia (IVCA) belongs to a range of congenital or acquired vena cava malformations and is described as an independent risk factor for thrombosis. The present case report explores two cases of combined ATD and IVCA in an adolescent and his mother. CASE PRESENTATION: A 14-year-old male presented with extensive deep venous thromboses (DVTs) of both lower extremities as well as an IVCA. The patient had previously been diagnosed with an asymptomatic ATD without therapeutic consequences at that time. His mother was suffering from an ATD and had herself just been diagnosed with IVCA, too. The DVTs in the adolescent were treated by systemic anticoagulation and catheter-directed local thrombolysis causing favourable results. Yet, despite adequate oral anticoagulation the DVTs in both lower extremities reoccurred within 1 week after the patient was discharged from hospital. This time, thrombolysis could not be fully achieved. Surprisingly, probing and stenting of the IVCA was achieved, indicating an acquired IVCA which could have occurred after undetected thrombosis in early childhood. Genetic analyses showed the same mutation causing ATD in both son and mother: heterozygote missense mutation c.248 T > C, p.(Leu83Pro), within the heparin binding domain of antithrombin. This mutation was never reported in mutation databases before. CONCLUSIONS: To our knowledge this is the first case report discussing combined ATD and IVCA in two family members. Since ATDs present with clinical heterogeneity, taking a thorough family history is crucial for the anticipation of possible complications in affected children and decisions on targeted diagnostics and therapeutic interventions. Affected families must be educated on risk factors and clinical signs of thrombosis and need an immediate diagnostic workup in case of clinical symptoms. IVCA in patients with ATD could occur due to thrombotic occlusion at a very early age. Therefore, in case of family members with IVCA and ATD ultrasound screening in newborns should be considered.

Comprehensive assessments and related interventions to enhance the long-term outcomes of child, adolescent and young adult cancer survivors - presentation of the CARE for CAYA-Program study protocol and associated literature review.

BACKGROUND: Improved, multimodal treatment strategies have been shown to increase cure rates in cancer patients. Those who survive cancer as a child, adolescent or young adult (CAYA), are at a higher risk for therapy-, or disease-related, late or long-term effects. The CARE for CAYA-Program has been developed to comprehensively assess any potential future problems, to offer need-based preventative interventions and thus to improve long-term outcomes in this particularly vulnerable population. METHODS: The trial is designed as an adaptive trial with an annual comprehensive assessment followed by needs stratified, modular interventions, currently including physical activity, nutrition and psycho-oncology, all aimed at improving the lifestyle and/or the psychosocial situation of the patients. Patients, aged 15-39 years old, with a prior cancer diagnosis, who have completed tumour therapy and are in follow-up care, and who are tumour free, will be included. At baseline (and subsequently on an annual basis) the current medical and psychosocial situation and lifestyle of the participants will be assessed using a survey compiled of various validated questionnaires (e.g. EORTC QLQ C30, NCCN distress thermometer, PHQ-4, BSA, nutrition protocol) and objective parameters (e.g. BMI, WHR, co-morbidities like hyperlipidaemia, hypertension, diabetes), followed by basic care (psychological and lifestyle consultation). Depending on their needs, CAYAs will be allocated to preventative interventions in the above-mentioned modules over a 12-month period. After 1 year, the assessment will be repeated, and further interventions may be applied as needed. During the initial trial phase, the efficacy of this approach will be compared to standard care (waiting list with intervention in the following year) in a randomized study. During this phase, 530 CAYAs will be included and 320 eligible CAYAs who are willing to participate in the interventions will be randomly allocated to an intervention. Overall, 1500 CAYAs will be included and assessed. The programme is financed by the innovation fund of the German Federal Joint Committee and will be conducted at 14 German sites. Recruitment began in January 2018. DISCUSSION: CAYAs are at high risk for long-term sequelae. Providing structured interventions to improve lifestyle and psychological situation may counteract against these risk factors. The programme serves to establish uniform regular comprehensive assessments and need-based interventions to improve long-term outcome in CAYA survivors. TRIAL REGISTRATION: Registered at the German Clinical Trial Register (ID: DRKS00012504, registration date: 19th January 2018).

Quantitative electroencephalography supports diagnosis of natalizumab-associated progressive multifocal leukoencephalopathy.

Long-term treatment of multiple sclerosis with natalizumab (NTZ) carries the risk of a devastating complication in the form of an encephalopathy caused by a reactivation of a latent John Cunningham virus infection (progressive multifocal leucoencephalopathy, PML). Early diagnosis is associated with considerably better prognosis. Quantitative EEG as an objective, rater-independent technique provides high sensitivity (88%) and specificity (82%) for the diagnosis of NTZ-PML. Combination of diagnostic modalities addressing static morphological (brain MRI) as well as functional (EEG) pathologic changes may improve risk management programmes.

The Non-Langerhans Cell Histiocytoses (Rare Histiocytoses) - Clinical Aspects and Therapeutic Approaches.

Rare histiocytoses, also called non-Langerhans cell histiocytoses, include all proliferative disorders of histiocytes, macrophages and dendritic cells that are not classified as Langerhans cell histiocytosis (LCH) and do not belong to the hemophagocytic lymphohistiocytosis (HLH) group of diseases. Thus, the term includes numerous benign or malignant, localized or systemic, adult or pediatric diseases. The classification of the histiocytic disorders has been revised several times. Here, we follow the classification recently published by Jean Francois Emile and an international expert panel, defining subgroups of histiocytoses described as L-Group, C-Group, M-Group, R-Group, and H-Group, which stands for LCH-like, cutaneous or mucocutaneous, malignant, Rosai-Dorfman-Disease like and HLH like. Some of the diseases have an excellent prognosis after resection or even disappear spontanously, others progress rapidly, requiring intensive systemic therapies. The malignant non-Langerhans cell histiocytoses in general have a poor prognosis, here, complex chemotherapy protocols are usually applied, with inconsistant results. An interesting perspective in non-malignant rare histiocytoses might be small molecular inhibitors, in particular BRAF inhibitors, since BRAF mutations have been found in some subtypes of non-Langerhans cell histiocytoses. By prospective and retrospective collection of experiences in a new registry (the "International Rare Histiocytic Disorders Registry", IRHDR), knowledge about these rare diseases might hopefully be improved.

The German national registry for primary immunodeficiencies (PID).

In 2009, a federally funded clinical and research consortium (PID-NET, http://www.pid-net.org) established the first national registry for primary immunodeficiencies (PID) in Germany. The registry contains clinical and genetic information on PID patients and is set up within the framework of the existing European Database for Primary Immunodeficiencies, run by the European Society for Primary Immunodeficiencies. Following the example of other national registries, a central data entry clerk has been employed to support data entry at the participating centres. Regulations for ethics approvals have presented a major challenge for participation of individual centres and have led to a delay in data entry in some cases. Data on 630 patients, entered into the European registry between 2004 and 2009, were incorporated into the national registry. From April 2009 to March 2012, the number of contributing centres increased from seven to 21 and 738 additional patients were reported, leading to a total number of 1368 patients, of whom 1232 were alive. The age distribution of living patients differs significantly by gender, with twice as many males than females among children, but 15% more women than men in the age group 30 years and older. The diagnostic delay between onset of symptoms and diagnosis has decreased for some PID over the past 20 years, but remains particularly high at a median of 4 years in common variable immunodeficiency (CVID), the most prevalent PID.

Group therapy for patients with psychogenic nonepileptic seizures: a pilot study.

Great advances have been made in the diagnosis of people with psychogenic nonepileptic seizures (PNES) since the advent of video/EEG monitoring. However, treatment options for this population have lagged significantly. This pilot study was undertaken to evaluate whether group therapy done with a psychodynamic focus would offer a useful intervention. Twelve patients entered the study and seven completed at least 75% of the 32 weekly sessions. The Beck Depression Inventory and the Global Severity Index of the Symptom Checklist-90 showed improvement as well as an overall decrease in PNES frequency. The data suggest that group therapy focusing on interpersonal issues may benefit patients with PNES.

[Laparoscopic inguinal herniorrhaphy in children--experiences in a primary medical care center]. / Die laparoskopische herniorrhaphie des leistenbruches im kindesalter--erfahrungen in einem krankenhaus der grund--und regelversorgung.

AIM: Children undergoing laparoscopic herniorrhaphy may benefit from a minimally invasive access and the possible exploration of the contralateral groin. In this prospective feasibility study, the experiences and results after introduction of this method in a tertiary referral medical center are reported. METHODS: 50 laparoscopic herniorrhaphies were performed in 44 children (32 boys and 12 girls, range: 17 months-11 years) with open inner inguinal rings between January 2001 and March 2007. In 6 children (13.6 %) an additional contralateral open inner inguinal ring was detected. Laparoscopic access was obtained with a 5-mm laparoscope which was inserted transumbilically and two 2-mm needle holders were inserted through the inferolateral abdominal wall. The open inner inguinal rings were closed in 8 children using a resorbable Z-suture and in 36 children using a monofilamentous non-absorbable suture. Follow-up examinations included records of intra- and postoperative complications, recurrence rate and economic aspects. RESULTS: No intra- or perioperative complications occurred. Median operation time was 19 minutes. 43 / 44 operations were carried on an outpatient basis. Average material costs were about 20 Euro without any difference from the open access. During 36 months the follow-up rate was 91 %. Two children who had previously received an absorbable suture suffered from a recurring groin hernia within the first 6 months. CONCLUSION: Laparoscopic herniorrhaphy in children represents a safe and effective surgical method that can be recommended for tertiary referral medical centers with training facilities and experience in minimally invasive surgery.

Randomized clinical trial of the influence of intraperitoneal local anaesthesia on pain after laparoscopic surgery.

BACKGROUND: There is controversy about the effectiveness of intraperitoneal local anaesthesia (LA) in laparoscopic surgery. The aim of the present randomized clinical trial was to compare the analgesic effect of pre-emptive (preoperative) versus postoperative intraperitoneal LA in two different types of laparoscopic surgery. METHODS: Between July 2004 and January 2005, 133 consecutive patients scheduled to undergo laparoscopic fundoplication or hernia repair were randomly assigned to one of three treatments: placebo solution (50 ml 0.9 per cent saline) or LA (50 ml 0.5 per cent lidocaine) administered immediately after creation of the pneumoperitoneum, or LA (50 ml 0.5 per cent lidocaine) at the end of the operation. Analgesic requirements were analysed, and pain was assessed using a visual analogue scale (VAS) from 0 to 100 at 6, 12, 24 and 48 h after surgery. RESULTS: The duration of pneumoperitoneum (median 66 versus 46 min respectively; P < 0.001) and overall pain intensity (median VAS score 46.7 versus 6.5; P < 0.001) were higher for laparoscopic fundoplication than for hernia repair. Preoperative application of LA reduced abdominal pain (median 28.6 versus 74.9; P < 0.005), shoulder pain (median 24.3 versus 43.8; P = 0.004) and analgesic consumption (mean(s.d.) 11.1(5.0) versus 18.5(5.4) mg piritramide per 48 h; P = 0.002) after fundoplication, but had no analgesic effects after hernia repair. CONCLUSION: Pre-emptive application of LA reduced postoperative pain and analgesic requirements after laparoscopic fundoplication.

[Anti-reflux surgery in patients with adequate response to proton pump inhibitors - is there an indication?]. / Antirefluxchirurgie bei patienten mit adäquatem ansprechen auf protonenpumpeninhibitoren - sinnvoll oder übertherapiert?

BACKGROUND: The indication for anti-reflux-surgery in patients with gastroesophageal reflux disease (GERD) who are totally symptom-free under conservative treatment with proton pump inhibitors (PPI) is still seen controversially. Arguments for PPI-treatment include the missing trauma and few side-effects, arguments against include the life-time-long drug intake. We prospectively observed the indication of anti-reflux-surgery in symptom-free patients in comparison to patients with remaining symptoms under treatment with PPI. PATIENTS AND METHODS: Between January 1999 and December 2001, 317 patients with GERD were treated by laparoscopic hemifundoplication and grouped in patients with adequate response to PPI (n = 103) and patients with residual discomfort in spite of or by PPI (n = 214). Preoperative diagnostic included endoscopy, ph-testing, manometry and quality of life scoring by a standardized questionnaire. Peri- and postoperative morbidity as well as quality of life were analyzed and compared with healthy individuals (n = 50). RESULTS: Patient demographics and surgical procedures did not differ between the two groups. After a median follow-up of 49 months and a follow-up rate of 89.9 %, the recurrence rate was 2.5 % and perioperative complication rate was 6.3 % without any significant differences between the groups. Patients with GERD and adequate response to PPI showed preoperatively during PPI omission a significant lower incidence of esophagitis (3.9 % vs. 18.2 %) and higher quality of life score (93.7 +/- 11.3 vs. 75.3 +/- 12.6), which significantly decreased in comparison to healthy individuals (132.9 +/- 10.5). After anti-reflux surgery the quality of life has been increased in both groups (130.5 +/- 11.4 vs. 121.8 +/- 13.2). However, only patients with adequate response to PPI reached the quality of life score of healthy individuals. CONCLUSION: Patients with preoperatively adequate response to PPI profit of anti-reflux surgery in terms of postoperative quality of life. Concerning the indication for anti-reflux surgery in these patients, one has to balance between the individual inconvenience due to the long-lasting drug intake on the one hand and the operative risk, morbidity and outcome of a specialized surgical department on the other hand.

Late response to radiochemotherapy in pediatric glioblastoma: report on two patients treated according to HIT-GBM protocols.

High-grade gliomas in children are rare and the best treatment is undetermined. The German language group study HIT-GBM compares various induction protocols for subsequent patient cohorts. Currently, cisplatinum, etoposide, ifosfamide, and vincristine are given simultaneously with extended-field radiotherapy. Imaging is done 3 weeks after to define treatment response, followed by 6-weekly controls during consolidation with lomustine, vincristine, and prednisone. The authors report on 2 patients with incompletely resected glioblastoma multiforme in which response was lacking 3 weeks after radiochemotherapy but became evident 12 weeks later. This suggests that later time points are required to assess induction protocol response.

Modulation of the granzyme B inhibitor proteinase inhibitor 9 (PI-9) by activation of lymphocytes and monocytes in vitro and by Epstein-Barr virus and bacterial infection.

Proteinase inhibitor 9 (PI-9) is an intracellular serpin expressed in lymphocytes and monocyte-derived cells. It is the only known endogenous natural antagonist of granzyme B (GrB), and its proposed function is protection of cells from misdirected GrB. We have studied the regulation of PI-9 in primary peripheral blood mononuclear cells (PBMCs) following ex-vivo stimulation, and in PBMCs from patients suffering from viral or bacterial infections. By intracellular flow cytometry, we found identical PI-9 expression in all lymphocyte subsets, lower levels in monocytes and none in granulocytes. PI-9 was stable for 48 h in the presence of cycloheximide, indicating slow protein turnover. Incubation of PBMCs with several stimuli including lipopolysaccharide (LPS) led to up-regulation in the monocyte, but not the lymphocyte fraction, within 48 h, inhibitable by the NF-kappaB inhibitor pyrrolidin dithiocarbamate (PTDC). Up-regulation of PI-9 was observed in lymphocytes and monocytes of patients with acute Epstein-Barr virus (EBV), but not bacterial infection. Preterm infants had similar PI-9 expression as adults in monocytes, but lower in lymphocytes, decreasing during bacterial infection. Taken together, our data indicate that PI-9 is rapidly up-regulated upon stimulation of monocytes, but not lymphocytes. By protecting monocytes and macrophages from misdirected GrB in the inflammatory process, PI-9 might be involved in the regulation of antigen presentation.

Long-term experience of treating 185 patients with gastroesophageal reflux disease (GERD) by anti-reflux surgery respecting the functional-morphological restoration of the esophagus.

BACKGROUND: According to anatomical investigations the whole esophagus plays a crucial role as reflux barrier in the pathogenesis of gastroesophageal reflux disease (GERD). Morphologically, the spirally arranged muscle fibres present a tension-dependent "stretch closure" and in the event of any reduction of tension, as for example caused by an axial hiatus hernia, the organ may become inefficient. The aim of this study was to evaluate quality of life as the main success criterion after anti-reflux surgery based strictly on the restoration of functional morphology. METHODS: Between January 1999 and December 2000, 185 patients with GERD were treated by surgery in accordance with functional-morphological principles. After dissecting the mediastinum, the gastroesophageal junction was displaced into the abdomen with consecutive retensioning the esophagus. The esophageal hiatus was reconstructed with non-absorbable single knot sutures and strengthened with alloplastic material. The application of a 180 degrees fundus cuff around the posterior esophageal circumference served as a "spacer" and also restored the angle of His. Preoperatively, all patients underwent endoscopy, pH metry and manometry. During postoperative follow-up, recurrence rate and quality of life were evaluated via a disease-specific scale. RESULTS: Preoperatively, 85% of the patients had an elevated DeMeester Score with a median of 81.4; 64% had reflux esophagitis and 37% had reduced lower esophageal sphincter pressure. All 185 operations were performed without conversion in a median operating time of 74 min. In one patient a lesion of the esophagus was treated during the operation; two patients had lesions of the splenic capsule which were also dealt with during the operation. Postoperatively, pleural effusions occurred in 15 patients and puncture was deemed necessary in one subject. Ninety-three percent were followed up for a median of 45 months and the recurrence rate was 2.3%. The quality of life index was 81.6+/-12.4 points preoperatively, and had significantly improved to 125.2+/-12.7 points in the follow-up. CONCLUSION: Through the functional-morphological concept of anti-reflux surgery comprising the restoration of the tension-dependent "stretch closure" of the esophagus, significant long-term improvement in quality of life with a low recurrence rate and perioperative morbidity can be achieved.

AML bearing the translocation t(11;17)(q23;q21): involvement of MLL and a region close to RARA, with no differentiation response to retinoic acid.

We describe a case of acute myeloid leukemia (AML) bearing the translocation t(11;17)(q23;q21). The morphological phenotype represented a monoblastic leukemia, AML French-American-British (FAB) M5a. Further analysis of the translocation revealed an involvement of the mixed-lineage leukemia (MLL) gene and a region closely proximal to the retinoic acid (RA) receptor alpha (RARA) gene. AMLs involving both a rearranged MLL and the 17q21 region, in which the RARA gene is located, have only been described in some individual cases. The functional role of this translocation is still unknown. Rearrangements of the MLL (11q23) gene in AML are usually related to the morphological phenotype FAB M5. In general, they are associated with an adverse prognosis. In acute promyelocytic leukemia, the translocation (15;17)(q22;q11-21) involving the RARA leads to a maturation arrest that can be overcome by RA, often inducing remission. In other forms of AML, however, the effects of RA are limited and diverse. To study whether RA might have a therapeutical potential in our case, we performed an in vitro analysis of RA effects on AML cells. We found that RA leads to enhanced cell death and up-regulation of CD38 and CD117. However, no hints of RA-induced in vitro differentiation were visible. Our data indicate that in AML cells bearing the t(11;17)(q23;q21), a differentiation arrest that is overcome by RA is not present. On the contrary, RA induces alterations in cellular regulation that are similar to the RA-induced changes observed in early hematogenic progenitors; thus, a possible therapeutical benefit of RA in such cases remains open.

[Laparoscopic versus open appendectomy: which factors influence the decision between the surgical techniques?]. / Laparoskopische vs. offene Appendektomie: Welche Faktoren beeinflussen die Wahl der Operationsmethode?

BACKGROUND: Although in hospitals focussing on minimal invasive surgery laparoscopic appendectomy (LA) is widely practiced as method of choice in patients with acute appendicitis, the decision for the laparoscopic or the conventional technique (OA) is usually ensued by individual viewpoints. Aim of this prospective observation study was to analyse the decision algorithm for both procedures in patients with the presumptive diagnosis "appendicitis". PATIENTS AND METHODS: Between January 1996 and July 2001 512 patients with the presumptive diagnosis "acute appendicitis" underwent surgery and, assigned by intention-to-treat, were subdivided in a laparoscopic (I) and a conventional group (II). The choice of surgical procedure was analysed with regard to patient characteristics (age, gender, comorbidity), severity of appendicitis (clinical manifestation, preoperative inflammation signs), surgeon (clinical experience) and daytime (during the day, in the evening, at night). Furthermore, the outcome of either method was related to postoperative diagnosis, perioperative morbidity, analgesia, length of hospital stay and cosmetic results. RESULTS: In group I 265 patients and in group II 247 patients underwent surgery. Conversion from LA to OA was necessary in 6.4 %. Group I consisted of significantly more female (67.9 % vs. 45.7 %) and younger patients (21 yrs. vs. 30 yrs.) with less medical history as well as minor severity of tissue inflammation and significantly lower preoperative serum inflammation parameters (leukocytes (1000/ml): 10.6 +/- 4.3 vs. 13.5 +/- 4.9; CRP (mg/l): 2.3 +/- 3.3 vs. 5.6 +/- 7.5, I vs. II: p < 0.001). In group I more patients underwent surgery during day-time as well as by more laparoscopic-experienced surgeons. In the postoperative histopathologic evaluation there were significantly fewer cases with complicated appendicitis (33.2 % vs. 52.2 %, p < 0.001). Additionally, patients after LA revealed a lower postoperative complication rate (9.3 % vs. 18.3 %), length of hospital stay (median 3 vs. 4 days) and duration of analgesia (2.1 +/- 1.8 vs. 4.1 +/- 7.1 days). CONCLUSIONS: Important factors for decision algorithm between a laparoscopic or an open appendectomy include severity of appendicitis, gender, day-time as well as the surgeon's individual laparoscopic experience. With appropriate indication for each technique, both procedures are of equal value in the treatment of acute appendicitis. Furthermore the positive patient selection for laparoscopic appendectomy contributed to a better postoperative outcome in this study.

The relationship between social support, depression and treatment for depression in people with multiple sclerosis.

BACKGROUND: Studies have been fairly consistent in finding a relationship between social support and depression. However, little is known about the relationship between depression and social support in the context of treatment for depression. This study examined the effects of treatment for depression on social support among patients with multiple sclerosis (MS). METHOD: Sixty-three moderately depressed MS patients received 16 weeks of cognitive behaviour therapy (CBT), supportive expressive group psychotherapy (SEGP) or sertraline. Depression was measured using the Beck Depression Inventory and social support was measured using Arizona Social Support Interview Schedule. RESULTS: Treatment for depression was associated with significant increases in perceived social support, utilized social support and satisfaction with support, as well as reduction in need for emotional support. There were no significant changes in structural support or need for physical support. There were also no differences in change in social support across treatments. All changes in social support were fully explained by depression. Improvements in utilized social support and satisfaction with social support were fully mediated by improvements in depression. Baseline depression predicted improvements in perceived support and need for emotional support. CONCLUSIONS: These findings suggest that improvements in social support among MS patients during treatment for depression can be explained by depression. However, different domains of social support may be differentially sensitive to changes in depression.

Feasibility of surgical technique and evaluation of postoperative quality of life after laparoscopic treatment of intrathoracic stomach.

BACKGROUND: Because of the risk of life-threatening complications, the discovery of a complete intrathoracic stomach demands urgent surgery with the aim of repositioning the stomach and gastropexy, and secondarily, to improve life quality. In this study the feasibility of surgical technique and postoperative quality of life after laparoscopic treatment of complete intrathoracic stomach has been evaluated. METHODS: From June 1999 to December 2001 16 patients with an intrathoracic stomach (hiatus hernia Types IIB and III) were treated by laparoscopic techniques, including the repositioning of the stomach, hemi-fundoplication and anterior gastropexy. During the postoperative follow-up the recurrence rate and quality of life (Eypasch index) were evaluated. RESULTS: All operations were performed laparoscopically without conversion, with a mean operating time of 155 min. Pleural injuries occurred in 31% of patients and pleural effusions in 38%, which required puncture in three cases. Complete follow-up showed no recurrences at a median of 14 months. The median quality of life index was 84.6 preoperatively and had significantly improved to 117.8 after the operation. CONCLUSION: Laparoscopic access for the treatment of intrathoracic stomach represents a minimally invasive and safe treatment option for complete intrathoracic stomach, with a low level of perioperative morbidity and significant improvement in quality of life.

Long-term remission of APL with a second allogeneic BMT after CNS relapse following HLA-identical allogeneic BMT.

Second allogeneic bone marrow transplantation (BMT) for AML relapsing after an initial BMT has a poor prognosis, with a probability of a 2-y disease-free survival below 30 per cent, caused both by treatment-related mortality (TRM) and high relapse rate. While TRM is most likely due to heavy pretreatment, AML relapse after BMT may be due to resistant disease or to a poor graft-versus-leukaemia (GvL) effect of the transplant. The degree of GvL may depend on individual donor/recipient immunoreactivity. In most published cases of second allogeneic BMT, both transplants were performed from the same donor. Here, we describe a patient who was first transplanted for acute promyelocytic leukaemia (APL) (AML FAB M3v) from his HLA-identical brother and received intensive immunotherapy including donor lymphocytes and IL2. He remained free from GvHD >I degrees, but developed CNS relapse. After a second BMT from another HLA-identical brother, he spontaneously developed GvHD III degrees, and has now been disease free for nearly 3 years. In this patient, long-term remission of AML relapsing after BMT was achieved by combining remission induction using an individual chemotherapy protocol with a second BMT from an alternative matched related donor and transient GvHD III degrees, which probably conferred a GVL effect.

Terminal differentiation in vitro of patient-derived post-TMD megakaryoblastic AML cells.

Differentiation induction is a therapeutic principle in acute promyelocytic leukemia (AML) using all- trans retinoic acid. In cell lines with properties of AML M6/M7 (K562 and CMK), differentiation towards megakaryopoietic and erythropoietic phenotypes can be induced in vitro. Transitory myeloproliferative disorder (TMD) is a self-limited disorder of newborn infants with Down syndrome, phenotypically resembling acute myeloid leukemia of megakaryoblastic lineage. Despite spontaneous disappearance of blasts from blood and bone marrow, in about 10% of the patients, overt acute megakaryoblastic leukemia (AML M7) develops up to 4 years later. Recently, mutations of the GATA1 transcription factor have been identified in the megakaryoblastic leukemia of Down syndrome. Here, we studied cells from a patient suffering from megakaryoblastic AML at the age of 2.5 years after spontaneous remission of neonatal TMD. In vitro, terminal differentiation towards a megakaryocyte-like phenotype could be induced by phorbol myristate acetate (PMA), with typical morphological features, upregulation of platelet-specific and downregulation of erythroid antigens, going along with downregulation of c-myc. Whether spontaneous resolution of TMD is a process due to terminal differentiation is still open; however, here we give evidence that in vitro differentiation can be induced even in blasts deriving from an overt AML French-American-British (FAB) M7 after TMD.

Revictimization and information processing in women survivors of childhood sexual abuse.

This study examined the effect of sexual revictimization on information processing of trauma-related stimuli in a sample of child sexual abuse (CSA) survivors diagnosed with posttraumatic stress disorder (PTSD). Fifty-one treatment-seeking women participated in this study. Participants completed the Sexual Experiences Survey regarding sexual revictimization in the last 6 months and performed a modified emotional Stroop task in which they named the colors of neutral words (e.g., apple), general threat words (e.g., malignant and death), and sexual/victimization words (e.g., penis and abuser). As predicted, the revictimized participants (n = 16) took significantly longer to color-name sexual/victimization words than did the nonrevictimized participants. These results suggest that revictimization serves to prime preexisting "trauma" memory networks, thereby amplifying the impact of childhood sexual trauma on selective attention toward trauma-related stimuli.