Bernard–Soulier syndrome in pregnancy

Bernard–Soulier syndrome (BSS) is a rare autosomal recessively inherited bleeding disorder. Pregnancy in patients with BSS is characterized by ante‐, intra‐, or postpartum haemorrhage, which may be delayed and severe. There is no consensus in the management of BSS in pregnancy and so far only 16 pregnancies in nine patients have been described. We report a further three pregnancies in two women with the syndrome. We also outline our management of pregnant patients with BSS.     

Nationales Aktionsforum Diabetes mellitus (NAFDM)

NAFDM, the National Action Forum for Diabetes Mellitus, is an umbrella organisation for the leading diabetes organisations in Germany. Since its foundation at the end of 2004, NAFDM has brought together the activities of these organisations, which up to now were frequently working independently of each other, under a single ‘roof’. Supported by a central coordination unit, three project groups work successfully on the topics scientific research and healthcare research, patient care and prevention. Activities and results are shared and thus integrated into the network. The working groups are supported by NAFDM’s medical and health-policy steering groups. Apart from a number of successful events, two key publications have meanwhile come out: one on the status of prevention and one analysing the healthcare situation for diabetics in Germany. All people interested in diabetology are invited to join in and work with the NAFDM.     

Treatment of nasopharyngeal stenosis by prosthetic hollow stents: Clinical experience in eight patients.

OBJECTIVE: A series of nasopharyngeal appliance designs is presented that represents our evolving experience over a 20-year period in the adjunctive use of prosthetic stents in the surgical correction of nasopharyngeal stenosis. DESIGN: Retrospective assessment of effectiveness of two nasopharyngeal stenosis hollow stent designs in a consecutive series of patients for relief of nasal obstructive symptoms. SETTING: Tertiary academic medical center, Craniofacial Program at Children's Hospital. PATIENTS: Four patients with nasopharyngeal stenosis were treated with a preoperatively fabricated stent made from a clasped palatal appliance onto which hollow acrylic conduits were extended through surgically re-created pharyngeal ports. A subsequent set of four patients with nasopharyngeal stenosis were treated with intraoperatively-fashioned silastic grommets, as opposed to palatal appliances. INTERVENTIONS: Postoperative intraoral stenting of nasopharyngeal ports. MAIN OUTCOME MEASURES: Maintenance of pharyngeal port opening after 1 year, improvement in nasal airway obstructive symptoms. RESULTS: The palatal appliance stents were less well tolerated and had a lower maintenance of port patency after device removal (4 of 8, 50%). The silastic grommets provided better retention into the ports and increased patient tolerance, as well as better 1-year port maintenance (6 of 8, 75%). CONCLUSIONS: The grommet stent appliance offers numerous advantages over a conventional dental-clasped appliance for prosthetic nasopharyngeal stenting, including obviation of extensive preoperative preparation, ease of insertion and removal, and exchange of air during the stenting period. Improved nasopharyngeal patency with this device may be due to greater patient tolerance and subsequent longer use.     

Hepatic gene downregulation following acute and subchronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Chronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been shown to lead to the development of hepatotoxicity and carcinogenicity in the liver of female rats. In this study, we investigated hepatic gene downregulation in response to acute and subchronic TCDD exposure. We identified 61 probes which exhibited a downregulation of twofold or greater following subchronic (13 weeks) exposure to TCDD. Comparative analysis of the hepatic expression of these 61 probes was conducted with rats subchronically exposed to PeCDF, PCB126, PCB153, and a mixture of PCB126 and PCB153. PCB153 produced little or no alteration in these probes, while the binary mixture mimicked most closely the downregulation observed with TCDD. To discern if the repression of genes within this probe set occur as a primary response to TCDD exposure, we analyzed the early responsiveness of 11 genes at 6, 24, and 72 h following a single exposure to TCDD. We observed early repression of the 11 genes within this early time course, indicating that the repression of this subset of genes occurs as a primary response to TCDD exposure and not as a secondary response to 13 weeks of subchronic treatment. In addition, the gender, species, and AhR dependence of these responses were also investigated. Gender- and species-dependent repression was observed within this subset of genes. Furthermore, utilizing AhR knockout mice, we were able to determine the AhR-dependent downregulation of seven of 11 genes. Together these results assist efforts to understand the multitude of effects imposed by TCDD and AhR ligands on gene expression.     

Utility of exhaled nitric oxide as a noninvasive biomarker of lung inflammation in a disease model.

There is a great deal of interest in developing less invasive markers for monitoring airway inflammation and the effect of possible novel anti-inflammatory therapies that may take time to impact on disease pathology. Exhaled nitric oxide (eNO) has been shown to be a reproducible, noninvasive indicator of the inflammatory status of the airway in the clinic. The aim of the present study was to determine the usefulness of measuring eNO as a marker of the anti-inflammatory impact of glucocorticoid and an inhibitor of kappaB kinase-2 (IKK-2) inhibitor 2-[(aminocarbonyl)amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide (TPCA-1), in a pre-clinical model of airway inflammation. Rats were given vehicle, budesonide or TPCA-1 prior to exposure to lipopolysaccharide, previously shown to induce an increase in eNO and airway neutrophilia/eosinophilia. Comparison of the effect of the two compounds on inflammatory components demonstrated a significant correlation between the impact on eNO and inflammatory cell burden in the airway. The current study demonstrates the usefulness of profiling potential disease-modifying therapies on exhaled nitric oxide levels and the way in which an effect on this noninvasive biomarker relates to effects on pathological parameters such as lung cellularity. Information from studies such as the current one would suggest that the measurement of exhaled nitric oxide has potential for monitoring inflammatory status in lung tissue.     

Maximal inspiratory and expiratory pressure measurement in tracheotomised patients.

The present study compared four different sites and conditions for the measurement of maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) in 38 spontaneous breathing tracheotomised patients. Of the patients, 28 had chronic obstructive pulmonary disease (COPD). The four different conditions were: 1) through a cuff inflated cannula (condition A); 2) through the mouth with a deflated cannula (condition B); 3) through the mouth with a phonetic uncuffed cannula (condition C); and 4) through the mouth after stoma closure (condition D). Five trials in each condition were performed using a standardised method. The measurement of both MIP and MEP differed significantly depending on the condition of measurement. MIP taken in condition A was significantly higher when compared with conditions B, C and D. MEP in condition A was significantly higher when compared with condition B and D. In condition A the highest frequency of the best measurement of MIP and MEP was observed at the fourth and fifth effort, respectively. The same results were obtained after the selection of only COPD patients. In conclusion, respiratory muscle assessment differs significantly depending on measurement condition. Measurement through inflated cannula tracheotomy yields higher values of both maximal inspiratory and maximal expiratory pressure.     

Role of tumour necrosis factor-alpha receptor p75 in cigarette smoke-induced pulmonary inflammation and emphysema.

Chronic obstructive pulmonary disease (COPD) is characterised by a local pulmonary inflammatory response to respiratory pollutants and by systemic inflammation. Tumour necrosis factor (TNF)-alpha has been implicated in systemic effects of COPD and operates by binding the p55 (R1) and p75 (R2) TNF-alpha receptors. To investigate the contribution of each TNF-alpha receptor in the pathogenesis of COPD, the present study examined the effects of chronic air or cigarette smoke (CS) exposure in TNF-alpha R1 knockout (KO) mice, TNF-alpha R2 KO mice and wild type (WT) mice. CS was found to significantly increase the protein levels of soluble TNF-alpha R1 (by four-fold) and TNF-alpha R2 (by 10-fold) in the bronchoalveolar lavage of WT mice. After 3 months, CS induced a prominent pulmonary inflammatory cell influx in WT and TNF-alpha R1 KO mice. In TNF-alpha R2 KO mice, CS-induced pulmonary inflammation was clearly attenuated. After 6 months, no emphysema was observed in CS-exposed TNF-alpha R2 KO mice in contrast to WT and TNF-alpha R1 KO mice. CS-exposed WT and TNF-alpha R1 KO mice failed to gain weight, whereas the body mass of TNF-alpha R2 KO mice was not affected. These current findings suggest that both tumour necrosis factor-alpha receptors contribute to the pathogenesis of chronic obstructive pulmonary disease, but tumour necrosis factor-alpha receptor-2 is the most active receptor in the development of inflammation, emphysema and systemic weight loss in this murine model of chronic obstructive pulmonary disease.     

Characteristics and outcome of patients with active pulmonary tuberculosis requiring intensive care.

Severe tuberculosis (TB) requiring intensive care unit (ICU) care is rare but commonly known to be of markedly bad prognosis. The present study aimed to describe this condition and to determine the mortality rate and risk factors associated with mortality. Patients with confirmed TB admitted to ICU between 1990 and 2001 were retrospectively identified and enrolled. Clinical, radiological and bacteriological data at admission and during hospital stay were recorded. A multivariate analysis was performed to identify the predictive factors for mortality. A total of 58 TB patients (12 females, mean age 48 yrs) admitted to ICU were included. Mean Acute Physiology and Chronic Health Evaluation (APACHE) II score at admission was 13.1+/-5.6 and 22 of 58 (37.9%) patients required mechanical ventilation. The in-hospital mortality was 15 of 58 (25.9%); 13 (22.4%) patients died in the ICU. The mean survival of patients who died was 53.6 days (range 1-229), with 50% of the patients dying within the first 32 days. The factors independently associated with mortality were: acute renal failure, need for mechanical ventilation, chronic pancreatitis, sepsis, acute respiratory distress syndrome, and nosocomial pneumonia. These data indicate a high mortality of patients with tuberculosis requiring intensive care unit care and identifies new independently associated risk factors.