Outcome, comorbidity, hospitalization and 30-day mortality after closure of acute perforations and postoperative anastomotic leaks by the over-the-scope clip (OTSC) in an unselected cohort of patients.

BACKGROUND: Acute gastrointestinal (GI) wall defects contain a high risk of morbidity and mortality and may be closed endoscopically by a full-thickness over-the-scope clip (OTSC). METHODS: Unselected consecutive patients presenting with acute non-surgical perforations or postoperative anastomotic leaks or perforations underwent attempted OTSC placement as primary closure method after interdisciplinary consensus in three tertiary referral centres. Their clinical data and intervention characteristics were evaluated in an intention to treat analysis during a 24-month period to assess closure rates, 30-day mortality, hospitalization and comorbidity. RESULTS: In total, 34 patients (16 females, 18 males, 69.5 years) were included with 22 non-surgical perforations and 12 postoperative anastomotic leaks or perforations. Definitive closure of the perforations and leaks was achieved in 26/34 patients (76.5 %). Successful closure of the GI wall defect resulted in a significantly shorter hospital stay (8 days, p = 0.03) and was significantly correlated with comorbidity (r = 0.56, p = 0.005). In the group with OTSC failure, hospitalization was 18 days and 6 of 8 patients (75 %) required immediate surgery. Three deaths occurred in the group with successful OTSC closure due to comorbidity, while one death in the OTSC failure group was related to a refractory perforation. Favourable indications and locations for a successful OTSC procedure were identified as PEG complications, endoscopic or postoperative leaks of stomach, colon or rectum, respectively. CONCLUSIONS: In unselected patients, OTSC was effective for closure of acute GI wall defects in more than 75 % of all patients. Clinical success and short hospitalization were best achieved in patients without comorbidity, but closure of the perforation or the anastomotic leak was found to be not the only parameter relevant for patient outcome and mortality.

[Results of surgical treatment of hiatal hernia]. / Ergebnisse der operativen Therapie großer Hiatushernien.

BACKGROUND: Hiatus hernias are considered as the most prominent form of diaphragmatic hernias. The passage is defined through the oesophageal hiatus, resulting in a superdiaphragmatic displacement of parts of the stomach or the complete stomach, respectively. In our work we investigated the treatment of partial thoracic stomach with both open and minimally invasive surgical procedures emphasising the view on operating data, the success of the surgery and recurrence rates. Patients with mesh insertion for hernia defect closures were considered separately. MATERIAL AND METHOD: 94 Patients were treated in the period from 01.01.2003 to 01.06.2010. The ratio male/female was 2 : 1. The median age was 66 years. All data were prospectively collected by means of surgical protocols and data from the central patient records and analysed retrospectively. The statistical analyses were performed with SPSS 18.0 (SPSS Inc., Chicago, IL, USA). Any existing significances were determined using the T-test. RESULTS: Of the 94 patients, 65 were operated laparoscopically. In the case of nine patients an initial laparoscopic surgery had to be changed to an open procedure. The reasons for switching surgical procedures were splenic bleeding in the case of 2 patients, intestinal injury due to perforation by the trocar in one case and unclear surgical situs in 6 cases. The postoperative complication rate was 24 %. The main reasons were a delayed achievement of passage. The mortality rate was 0 %. The comparison between laparoscopic and open groups showed, by comparable complication and recurrence rates, a shorter recovery time in favour of patients operated on laparoscopically. Additionally it can be stated that a bridge closure with mesh (ePTFE) had no significant influence on the postoperative outcome. Therefore we cannot confirm the postulated poor postoperative results of other groups. CONCLUSION: In summary, the clear trend in the surgical treatment of hiatus hernias is to minimally invasive surgery. Only for patients with multiple previous operations, who are expected to have strong adhesions, the operation with comparable morbidity and mortality rates can also be planned primarily as open. In this case, however, longer postoperative recovery times must be expected. Large defects can be treated with comparable complication and recurrence rates by mesh insertion (ePTFE).

Acute interventional recanalisation of vertebrobasilar stenoses by angioplasty: complications and 12 months follow up.

INTRODUCTION: In acute symptomatic vertebrobasilar artery stenosis, the use of mechanical recanalisation remains controversial. The complication rate of acute interventional recanalisation (aIR) has to be considered, as evidence from randomised trials is lacking. In a single centre retrospective case series, we here describe complications and outcome after aIR. METHODS: We retrospectively assessed aIR in a tertiary care centre and included the following parameters: indication for aIR, national institute of health stroke scale (NIHSS) score on admission, recanalisation by thrombolysis in myocardial infarction score (TIMI) grades, post-interventional complications, mortality, NIHSS and modified Rankin scale at follow-up and rate of restenosis. RESULTS: We identified 14 aIR (14 percutaneous transluminal angioplasty with or without stent implantation in 12 patients; 6/12 with thrombolysis; n = 6 vertebral artery, n = 8 basilar artery; 4 women, mean age 67 years). Mortality was 25 % (3/12) after 7 days and 42 % (5/12) after 12 months. In 12/14, interventions are complete (TIMI 3, 86 %), in 2/14, a partial recanalisation (TIMI 2, 14 %) was achieved. In one case, a peri-interventional fatal intracerebral haemorrhage occurred (1/12, 8 %). At late follow-up (mean 342 days), one re-occlusion (1/7, 14 %) and one recurrent stroke (1/12, 8 %) were observed. CONCLUSIONS: In our single centre series of vertebrobasilar aIR recanalisation rate was high. However, procedural safety and clinical outcome varied considerably. The results of aIR need to be assessed in multicentric registers to define the procedural risk and outcome in the clinical setting.

[ALS and frontotemporal dementia - case report and review of the literature]. / ALS und frontotemporale Demenz - Fallbericht und Literaturübersicht.

The occurrence of cognitive decline in amyotrophic lateral sclerosis (ALS), especially in the form of frontotemporal dementia (FTD), has been described previously. Recent molecular biology and histopathology data suggest that both ALS and FTD may share common pathological pathways and may present two phenotypes of the same proteinopathy. The underlying pathophysiological mechanism may be defective RNA- and DNA-modulation, mediated by the proteins TDP43 and FUS. These findings are suggestive of a new disease category of TDP43-proteinopathies, which include ALS, FTD and overlap syndromes. While about half of the FTD cases are associated with TDP43-deposits, tau is found in the other half. A significant clinical overlap to other tauopathies exists here as well, for instance with corticobasal degeneration. In this paper, we present a case report and review the clinical spectrum and current pathogenetic concepts of FTD.

Differences in the treatment of young gastric cancer patients: patients under 50 years have better 5-year survival than older patients.

PURPOSE: In the literature, the manifestations of gastric cancer have been described based on all patients. In recent times, interest has focused on the subgroup of young patients. In the following analysis, the subgroup of young patients (< 50y) is compared with an older reference group (≥ 50y). MATERIAL AND METHODS: Between 01.01.1995 and 31.12.2005, 482 patients with a previously untreated gastric cancer underwent surgery. Fifty-six patients in this group were under 50 years of age, and the remaining 367 patients constituted the reference group. All data were recorded prospectively and analyzed retrospectively from the clinical cancer registry of the University of Erlangen. RESULTS: The analysis showed that the young patients had a similar tumor stage distribution. Diffuse tumor stages in the Laurén classification occurred significantly more often. The postoperative complication rate was similar, but the hospital mortality rate was significantly lower. The young patients had an obvious, but not significant, 5-year survival advantage in all tumor stages. CONCLUSIONS: Younger patients can be operated on with greater confidence as they have a significantly lower hospital mortality rate. They exhibit markedly better 5-year survival at all tumor stages. According to our data, there is nothing to support the general belief that young patients have a poorer disease course. Further clinical and experimental studies are necessary to investigate this group more precisely.

Systemic thrombolysis with rt-PA in patients under 40 years of age: a subgroup analysis of the Cologne Stroke Experience.

BACKGROUND: While the application of intravenous systemic thrombolysis (IVT) with rt-PA (recombinant tissue plasminogen activator) in older patients is currently moving into the focus of epidemiological studies, only few data are available regarding the application in young patients ≤40 years. Single-center data of a thrombolysis register were analyzed with respect to safety and efficacy of the treatment of young patients. METHODS: In a retrospective subgroup analysis of 450 patients treated by IVT within a 3-hour time window, patients ≤40 years were identified (n = 20). Clinical data [age, pretherapeutic stroke severity (National Institute of Health Stroke Scale, NIHSS), OTT (onset to-treatment time), rt-PA-dose, DNT (door[-]to[-]needle time), rate of symptomatic intracranial hemorrhages] and medical history were determined. The clinical outcome was assessed by the mRS (modified Rankin Scale). The results were compared to those of patients >40 years (n = 430). RESULTS: Twenty patients ≤40 years (mean age 32 years) out of 450 patients (4%) were treated by IVT. The percentage of predisposing diseases and vascular risk factors was significantly lower when compared to patients >40 years (p < 0.05). In contrast, the percentage of smokers was significantly higher (55 vs. 24%; p < 0.05). In comparison to patients >40 years, OTT, DNT and NIHSS at admission were not significantly different. After 3 months, 11 of 20 young patients (55%) showed a favorable outcome (mRS 0-1) and 80% were functionally independent (mRS 0-2). In the group of patients >40 years (n = 430), the respective percentages were significantly lower [p < 0.05; 34% (mRS 0-1) and 52% (mRS 0-2), respectively]. Symptomatic intracranial hemorrhages were not observed (in patients >40 years: 4%, p < 0.05). CONCLUSIONS: In comparison to the cohort of patients >40 years, IVT in young patients is safe and leads to a significantly better outcome after 3 months. Our data therefore encourage the use of IVT in young patients.

A giant bilateral calcified chronic subdural hematoma.

BACKGROUND: A calcified chronic subdural hematoma is a rare disease and its neuroradiological presentation is variable. The degree of calcification extends from thin calcified inner membranes to dense calcification and even ossification of the hematoma. Previous reports described a maximum of two hematoma cavities with calcified inner hematoma membranes. METHODS: Neuroimaging report with illustrative computerized tomography images. RESULTS: A patient with a bilateral symptomatic calcified chronic subdural hematoma, or so-called "armoured brain", was admitted to our intensive care unit with clinical signs of increased intracranial pressure. Computerized cranial tomography demonstrated multiple bilaterally located hematoma cavities with thin calcified inner membranes. After neurosurgical intervention by bilateral burr hole trepanation, clinical symptoms improved. CONCLUSIONS: Our case of a calcified chronic subdural hematoma presents with an uncommon imaging pattern with more than four hematoma cavities bounded by predominantly convex- and concave-configured thin calcified inner membranes.

Selective immune adsorption treatment of severe Guillain Barré syndrome in the intensive care unit.

BACKGROUND: The effectiveness of plasma exchange and intravenous application of immunoglobulins (IVIG) for the treatment of the Guillain Barré syndrome (GBS) has been demonstrated in large collectives. In contrast, there are only a few investigations in GBS patients with severe symptoms admitted to the intensive care unit (ICU) and treated with selective immune adsorption (SIA). We compared the efficacy and safety of SIA only versus SIA followed by IVIG in patients with severe GBS. METHODS: Patients with severe GBS admitted to the ICU were treated with SIA only or in combination with IVIG. Severity of symptoms was assessed using Hughes grades and severe GBS was defined as ≥ 3. Data were acquired retrospectively for the last 10 years (1998-2008). RESULTS: Data from 30 GBS patients (age 53 ± 16 years) with severe symptoms (Hughes grade 5: 30% [n = 9], grade 4: 57% [n = 17], grade 3: 13% [n = 4]) were analyzed. The mean Hughes grade at admission was 4.2 ± 0.7. Ten patients were treated by SIA only, 20 patients were treated sequentially with SIA followed by IVIG (30 g/d) over 3 days. The number of SIA sessions was 3.2 ± 0.8. Improvement of Hughes grade 4.2 ± 0.7 to 3.4 ± 0.9 (P < 0.001) occurred within 14.6 ± 15.5 days. Treatment with SIA only was as effective as the sequential therapy with IVIG. The Hughes grade decreased significantly in the group of patients where SIA was performed only (P = 0.008) and in the sequential treatment group (P < 0.001), respectively. In one patient SIA had to be terminated after one session due to ICU complications. Other severe side effects were not observed. CONCLUSIONS: In severely affected GBS patients admitted to ICU treatment with SIA seems to be safe and effective. In comparison to treatment with SIA only, sequential therapy with IVIG was not more effective.

[Cerebrotendinous xanthomatosis]. / Zerebrotendinöse Xanthomatose.

HISTORY AND CLINICAL FINDINGS: A 43-year-old woman had since childhood suffered from progressive dementia. Gait ataxia and mild polyneuropathy were noted in the neurological examination. She also had painful xanthomas of the achilles tendons. A bilateral cataract operation had been performed during adolescence. INVESTIGATIONS: An elevated concentration of cholestanol and a normal cholesterol level were found in the blood samples. The cerebral computed tomography revealed slight cerebral atrophy, predominantly affecting the cerebellum. Neurophysiological tests detected a sensory polyneuropathy in the legs. In addition the electroencephalogram showed a generalized slowing of electrical activity. DIAGNOSIS, TREATMENT AND COURSE: Clinical findings and laboratory values indicated the diagnosis of a cerebrotendinous xanthomatosis. After initiation of a drug therapy, based on a combination of an HMG-CoA-reductase inhibitor (simvastatin 20 mg/day) and a bile acid, chenodeoxycholic acid (15 mg/kg/day), further progression of the disease was prevented. CONCLUSION: The diagnosis of cerebrotendinous xanthomatosis is easily made in patients presenting all clinical symptoms expected in the disease. However, up to 30% of the patients do not show severe xanthomas. Especially in early stages of the disease the diagnosis may be difficult. Treatment can be efficacious and should be started as early as possible to prevent irreversible damage, particularly in the nervous system.

[Erysipel at the lower leg combined with a peripheral peroneus nerve palsy--an unusual occurrence]. / Ein Erysipel am Unterschenkel kombiniert mit einem peripheren Peroneusschaden--Ein seltenes Ereignis.

We present the clinical case of a fifty-year-old man who presented two times with a foot elevator paresis and an erysipel first on the right and after two months on the left side. Afterwards, we carried out a thorough case history with the help of clinical, radiological and magnetic resonance imaging. Even so the clinical pathology of the foot elevator paresis could not be manifested. A compartment syndrome could be discounted. In the context of the second stay during a neurology examination on both legs electromyography was performed and the nerve speed was tested. A peripheral peroneus paresis of unknown level and of unknown aetiology was demonstrated. The erysipel regressed rapidly under intravenous ampicillin antibiotics while the peroneus paresis was unchanged. The patent was released with a peroneus splint on both sides. With this case report we would like to point out the causes of peripheral peroneus paresis with regard to an additional erysipel. This case report is discussed regarding the possible aetiopathology and the current literature.

[Measuring fatigue in patients with multiple sclerosis with standardized methods in German speaking areas]. / Messbarkeit von Fatigue bei multipler Sklerose mithilfe standardisierter Methoden im deutschsprachigen Raum.

Fatigue describes the presence of a pronounced and advanced state of weariness. People with fatigue need more energy and it takes more effort to perform different activities than expected when compared to the patients disability. Fatigue can be observed in up to 92 % of patients suffering from multiple sclerosis. In the presented study, the German fatigue severity scale (dFSS) was established following the English "Fatigue Severity Scale". We enrolled 20 patients suffering from a primary relapsing multiple sclerosis and compared them to 20 healthy controls. Fatigue was detected if at least 4 points were reached in the dFSS. The dFSS demonstrated high validity and reliability. The dFSS is able to differentiate patients with fatigue from healthy controls. As consequence, the dFSS can be used to evaluate fatigue in German speaking individuals. The presented data demonstrated a good internal consistence. The scale is able to measure fatigue in an economic and rapid fashion. Therefore, it can be used in clinical situations for measuring fatigue in German speaking individuals.

Gender change and its impact on the course of multiple sclerosis.

We report the case of a 22-years old genotypic women suffering from a relapsing-remitting multiple sclerosis (MS) according to the Poser criteria. In this patient, a gender change had been performed by androgen-supplementation and surgical intervention. During gender change, the patient experienced further relapses. Different immunomodulatory and immunosuppressive treatment strategies did not stabilise the course of MS in this patient. Actually, an escalating therapy with mitoxantrone has been initiated. During the observation period the patient received long-term testosterone-supplementation. Testosterone levels were elevated in the serum of this genotypic female MS patient under such a hormonal treatment compared to normal ranges before. The clinical course of the patient is presented in this case. As there are several studies investigating an immunomodulatory impact of hormones on the course of MS or experimental allergic encephalomyelitis, we discuss the presented case and a possible influence of androgens in this patient.

[Glycogenesis Type II (M. Pompe). Selective failure of the respiratory musculature--a rare first symptom]. / Glykogenose Typ II (M. Pompe). Selektiver Befall der Atemmuskulatur --Eine seltene Erstmanifestation.

Late-onset Pompe's disease, a generalized lysosomal glycogen storage disease caused by acid maltase deficiency, usually presents as a slowly progressive muscular weakness of proximal muscles in lower limbs, followed by involvement of respiratory muscles. In the case presented here, however, respiratory failure was the first and selective symptom which caused the uncommon appearance of a patient entering our outpatient clinic on foot carrying his own artificial respirator. Intercostal muscle biopsy eventually led to the diagnosis.

[Complications and diagnostic limitations of chronic meningitis]. / Komplikationen und diagnostische Grenzen bei chronischer Meningitis. Eine Kasuistik.

HISTORY AND ADMISSION FINDINGS: A 37-year-old woman was admitted with total loss of vision of the left eye within 24 hours. Additionally, she complained about fatigue, headache, chills, fever, muscle pain and neck stiffness since 4 days. At admission, the body temperature was 38.7 degrees C. Neurological examination revealed papilledema and meningism. INVESTIGATIONS: Ophthalmologic findings were consistent with a papillitis. The vision was lost, the pattern-shift checkerboard visual evoked potentials were not measurable. MRI of the brain and the optical nerve was without pathological findings, meningeal or cerebral Gadolinium enhancement was not present. The CSF analysis yielded a lymphocytic meningitis with 249 cells/mm (3), the glucose ratio of cerebrospinal fluid and serum was normal. DIAGNOSIS, TREATMENT AND COURSE: The papillitis was treated unsuccessfully with high-dose methylprednisolone, the left eye remained blind. Persistence of the pleocytosis under initial treatment with aciclovir and ceftriaxone, reduction of the glucose ratio of cerebrospinal fluid and serum and intrathecal immunoglobuline A -- synthesis required a change of the diagnostic and therapeutic regimen. Various common and rare differential diagnoses were considered and ruled out, a chronic meningitis of unclear aetiology with the complication of amaurosis was diagnosed. In consideration of the most probable diagnosis, a tuberculostatic therapy was initiated. A prolonged reduction of the pleocytosis and normalization of cerebrospinal fluid parameters could be observed. CONCLUSIONS: A large number of aetiologies can cause chronic meningitis; this case report reviews the most important differential diagnoses and highlights the limitations of the diagnostic work-up although various methods are available. Clinical course and symptoms of chronic meningitis are mild to moderate and may even be absent, but it can cause severe complications.

Long-term persisting interferon beta-1b neutralizing antibodies after discontinuation of treatment.

OBJECTIVES: Neutralizing antibodies (NAB) against interferon beta (IFNB) with presumably negative impact on treatment outcome have been described in up to 42% of patients undergoing IFNB treatment. However, in most cases NAB decrease despite continuation of IFNB therapy. Observations on NAB after discontinuation of IFNB therapy are lacking. Here, we report for the first time on NAB which now persist for several years following discontinuation of IFNB treatment. MATERIALS AND METHODS: We present two multiple sclerosis patients followed over 8 and 10 years. NAB have been measured repeatedly and are presented together with clinical data. NAB developed after 2 years of treatment and persisted despite discontinuation of treatment at high titers for more than 4 years. CONCLUSION: Our data indicate that IFNB therapy may induce long-term NAB production which persists even after discontinuating IFNB treatment. Possible immunological mechanisms are discussed.

Expression of interleukin-6 and monocyte chemoattractant protein-1 by peritoneal sub-mesothelial cells during abdominal operations.

Cytokines and chemokines including interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) are secreted in response to major abdominal operations. The aim of this study was to identify the peritoneal cells that produce IL-6 and MCP-1. Samples of peritoneal tissue were taken from patients at the beginning and end of major abdominal operations. The samples were incubated in culture medium on microtitre plates for 5 h. The concentrations of IL-6 and MCP-1 were measured in culture supernatants by enzyme-linked immunosorbent assay (ELISA). In paraffin sections, cells that expressed IL-6 or MCP-1 were identified by combined in situ hybridization and immunohistochemistry. Antibodies against CD68, CD34, actin, and calretinin were included in these experiments. The median production of IL-6 increased significantly from 6256 pg/ml at the start of the operation to 20,000 pg/ml at the end. Production of MCP-1 rose from 7700 pg/ml to 11,820 pg/ml. IL-6 mRNA was mainly confined to endothelial cells. MCP-1 was expressed by a broader range of cells, consisting of actin-positive smooth muscle cells and endothelial cells, fibroblast-like cells, as well as occasional macrophages and mesothelial cells. Peritoneal endothelial cells contribute to the transient increase in concentrations of IL-6 in the circulation after surgical trauma. Recruitment of monocytes to the site of the trauma seems to be mainly effected by actin-positive smooth muscle cells and endothelial cells.

Early antithrombotic prophylaxis with low molecular weight heparin in neurosurgery.

BACKGROUND: Despite the high risk of venous thromboembolic events (VTE) in neuro-surgical patients, heparin prophylaxis has not been routinely established due to concern about bleeding complications. After initiating early low molecular weight heparin (LMWH) prophylaxis, we reviewed our patients in order to examine the viability of this practice. METHOD: Over a 3 year period, the records of patients admitted for elective neuro-surgery (ES), head injury (HI) or spontaneous intracranial haemorrhage (ICH) were analysed. Prophylaxis was performed with certoparin (3000 U anti-factor Xa s.c.) on the evening before ES and within 24 hours after surgery or admission whenever a CT did not show a progressive haematoma. Contraindications for LMWH were prothrombin time <70%, partial thrombo-plastin time >40 s, platelet count <100.000/ml, and platelet aggregation test sum <60%. The incidence of bleeding complications, VTE, and resulting morbidity/mortality was assessed. FINDINGS: 294 patients were admitted for ES, 344 for HI, and 302 for ICH. 155 of these were excluded because of contraindications. Intracranial bleeding was recorded in 1.5% (ES 1.1%, HI 3.5%, ICH 0%) and operative revision was performed in 1.1% (ES 0.7%, HI 2.8%) of patients. One case of moderate disability and no mortality occurred. The incidence of VTE and pulmonary embolism was documented in 0.2% and 0.1% of patients, with no associated mortality. No heparin induced thrombocytopenia was observed. INTERPRETATION: In neurosurgical patients, antithrombotic prophylaxis with certoparin was determined to be safe and efficacious when contraindications are carefully considered and a 12-hour time interval before and after surgery was guaranteed. This retrospective analysis should encourage a prospective trial of early LMWH prophylaxis.

[The diagnosis of brain death: medical and legal aspects with special reference to the German Transplantation Law (TPG)]. / Die Diagnose des Hirntodes: Medizinische und juristische Aspekte unter Berücksichtigung des Transplantationsgesetzes (TPG) der BRD.

The diagnosis of brain death following total and irreversible cessation of all cerebral functions is based on anthropological assumptions and conventions as well as on the exact medical diagnosis of total loss of brain function. The question whether individual life ends after cerebral function is irreversibly lost cannot be answered by medical definition alone. Clear and unrefutable legal definitions of death and the cessation of the rights of the individual must be provided before organs may be harvested from brain dead individuals. Acceptance of these definitions by the general population is of paramount importance for the practice of organ donation. In the first part of this article, the legal definition of death and the provisions of the German transplantation law are critically reviewed. The legal statements deal with the question of the definition of death and how death can be detected. The provisions of the German transplantation law are referenced with special attention to the provision of prior consent to the removal of organs following after the diagnosis of brain death. The provisions of the German constitution with respect to the preservation of the personal rights of the individual are discussed in the light of organ harvesting. The second part deals with the medical procedure of determining brain death in adults. The medical statements pertain to the diagnostic steps to be taken in the diagnosis and determination of brain death. The prerequisites for entering the diagnostic procedure to determine brain death are described. The clinical signs of total and irreversible cessation of brain function are listed, and the technical examinations to corroborate the clinical signs of brain death as accepted in Germany are delineated. In the perspective of the authors, individuals having suffered brain death still possess the protection of their personal human rights according to the German constitution since it cannot be conclusively demonstrated that total loss of brain function alone constitutes the cessation of life in the sense of the German constitution.

[Transient neonatal myasthenia gravis]. / Transiente neonatale Myasthenia gravis.

Ten to twenty percent of the offspring of mothers suffering from myasthenia gravis (MG) also develop transient neonatal MG, since maternal antibodies are able to cross the placenta. We report the course of two newborns of a mother with MG and a healthy father. The first pregnancy was complicated during the 3rd trimester by a hydramnion. The newborn presented with generalized muscle weakness, respiratory distress, weak sounding, anaemia, and poor sucking. Mechanical ventilation was necessary. Confirmation of the diagnosis was achieved by the result of repetitive muscle stimulation, showing a typical decrement in the EMG, and measurement of serum antiacetylcholin receptor antibodies. For 3 months, the infant was treated with neostigmin (cholinesterase inhibitor). After 26 days of hospitalization, the patient was released and followed up regularly. Myasthenic symptoms completely resolved. Side effects of the treatment were not observed. The course of the second pregnancy was normal. This second newborn was healthy. Our case report is remarkable for the very different presentation of two children of the same mother with MG during pregnancy and after delivery, with one child developing severe transient neonatal MG, initially requiring intensive care unit (ICU) treatment followed by quick recovery, and one child being healthy. We also present a score for monitoring the clinical course and adjusting anticholinesterase therapy accordingly.

The centromere1 (CEN1) region of Arabidopsis thaliana: architecture and functional impact of chromatin.

We have analysed the centromere 1 (CEN1) of Arabidopsis thaliana by integration of genetic, sequence and fluorescence in situ hybridisation (FISH) data. CEN1 is considered to include the centromeric core and the flanking left and right pericentromeric regions, which are distinct parts by structural and/or functional properties. CEN1 pericentromeres are composed of different dispersed repetitive elements, sometimes interrupted by functional genes. In contrast the CEN1 core is more uniformly structured harbouring only two different repeats. The presented analysis reveals aspects concerning distribution and effects of the uniformly shaped heterochromatin, which covers all CEN1 regions. A lethal mutation tightly linked to CEN1 enabled us to measure recombination frequencies within the heterochromatin in detail. In the left pericentromere, the change from eu- to heterochromatin is accompanied by a gradual change in sequence composition but by an extreme change in recombination frequency (from normal to 53-fold decrease) which takes place within a small region spanning 15 kb. Generally, heterochromatin is known to suppress recombination. However, the same analysis reveals that left and right pericentromere, though similar in sequence composition, differ markedly in suppression (53-fold versus 10-fold). The centromeric core exhibits at least 200-fold if not complete suppression. We discuss whether differences in (fine) composition reflect quantitative and qualitative differences in binding sites for heterochromatin proteins and in turn render different functional properties. Based on the presented data we estimate the sizes of Arabidopsis centromeres. These are typical for regional centromeres of higher eukaryotes and range from 4.4 Mb (CEN1) to 3.55 Mb (CEN4).