[A Pair of Siblings with a rare R5H-Mutation in Exon 1 of the MAPT-Gene]. / Ein Geschwisterpaar mit einer seltenen Tau-Gen-Mutation (MAPT R5H).

We report on a female patient presenting with primary progressive aphasia (PPA) and her brother presenting with psychosis. Both siblings had an R5H-mutation in exon 1 of the MAPT-gene. The PPA patient presented for the first time at the age of 72 years with a 4-year-history of language impairment. After a progressive course the patient died at the age of 76 years. The R5H-MAPT-gene mutation detected in the siblings has been described only once in 2002 by Hayashi et al. [1]. In this previous case from Japan, a 75-year-old patient initially displayed amnesia and disorientation. He became bedridden, with progressive mutism and rigidity of the upper extremities. Noteworthy are the manifold signs and symptoms in R5H-mutations and the late age of onset. For future trials, the detection of biomarkers for frontotemporal lobar degeneration in presymptomatic cohorts like the genetic frontotemporal dementia initiative (GENFI) is of help for stratifying subjects at risk.

Hypertriglyceridemia as a possible risk factor for prostate cancer.

We retrospectively studied anthropometric and laboratory parameters (including serum triglycerides, cholesterol), as well as comedication in 504 patients diagnosed with prostate cancer between January 1997 and August 2002 at a single referral center, and compared these patients with 565 age-matched patients with benign prostatic hyperplasia. A positive correlation was found between serum triglycerides and prostate cancer (odds ratio: 1.148/mmol/l; 95% confidence interval (CI) 1.003-1.315; P<0.05) after correcting for age, body mass index, diabetes and comedication with statins. Hypertriglyceridemia may increase the risk of prostate cancer, and the prognostic relevancy of serum triglycerides should be studied prospectively.

[Errors in pharmacotherapy]. / Fehler in der Pharmakotherapie.

The article discusses step by step the drug-prescription process from the assessment of a patient's medical history to the administration or intake. Practical examples illustrate common errors which could lead to complications in the inpatient as well as outpatient setting.

Conventional caries removal and sealed caries in permanent teeth: a microbiological evaluation.

OBJECTIVES: The aim of this study was to compare microbiological infection after conventional carious dentine removal with incomplete carious dentine removal and sealing. METHODS: Eighty-seven patients (12-50 years of age) under treatment at the Dental Clinics of the Federal University of Rio Grande do Sul (UFRGS), Brazil, participated in the study. The patients presented 90 posterior permanent teeth with primary caries. The lesions were coronal, active, and reached at least the middle third of the dentine. None of the teeth exhibited spontaneous pain, sensitivity to percussion or apical pathology (detected through radiographic exams). Pulp sensibility was confirmed by the cold test. The lesions were divided into 2 experimental groups: complete caries removal (CCR) based on hardness criteria (n=60 lesions) and incomplete caries removal (ICR) and sealing (n=32 lesions). Microbiological samples were obtained from the initial demineralized dentine, after CCR and after ICR-Seal. RESULTS: The number of anaerobic and aerobic bacteria, lactobacilli, and mutans streptococci decreased at the end of treatment (p<0.05). Significantly less anaerobic bacteria (p<0.01), aerobic bacteria (p=0.02), and mutans streptococci (p<0.01) growth was observed after ICR-Seal compared to CCR. The difference in lactobacilli was insignificant (p=0.08). The amount of bacteria detected after conventional caries removal was higher than that which remained in sealed caries lesions. CONCLUSIONS: The results suggest it is not necessary to remove all carious dentine before the restoration is placed because over time, sealing of carious dentine results in lower levels of infection than traditional dentine caries removal. CLINICAL SIGNIFICANCE: The results of this study indicate that sealed carious dentine was less infected than the remaining dentine left after conventional caries removal and sealing. Our results support treatment of deep carious lesions in one session with incomplete removal of carious dentine.

Multilumen central venous catheters increase risk for catheter-related bloodstream infection: prospective surveillance study.

BACKGROUND: Catheter-related bloodstream infections (CRBSI) are a leading cause of nosocomial infections associated with significant mortality and costs. The objective of this study was to determine the rate of CRBSI in two large Swiss hospitals and to identify risk factors for this condition. PATIENTS AND METHODS: During 1 year all central venous catheter (CVC)-inserted in patients admitted for visceral, orthopedic or urologic surgery at the cantonal hospital in St Gallen and cantonal hospital in Chur were included in the study. Catheters were followed for the duration of their insertion. Blood cultures and semiquantitative cultures from catheters were drawn in the presence of local or systemic signs of infection. Primary endpoint was CRBSI defined as definite if (a) the same pathogen grew in at least one blood culture and from the distal segment of the catheter or (b) the same pathogen grew in at least one peripherally and centrally drawn blood culture and the differential time to positivity of central blood culture vs peripheral blood culture was > 120 min. CRBSI was defined as probable if at least one blood culture was positive with a recognized pathogen in the absence of another site of infection. Data were analyzed using univariate and multivariate time-to-event methods. RESULTS: During the study period, 1,396 CVCs were prospectively studied in 1,162 patients. Incidence density of all CRBSIs (definite n = 29, probable n = 7) was 2.5 (95% CI: 1.8-3.5) per 1,000 catheter-days. The lowest rate of CRBSI was found in subclavian catheters, the adjusted hazard ratio (HR) for jugular catheters was 2.2 (95% CI: 1.1- 4.3; p = 0.03) and for femoral catheters 2.9 (95% CI: 0.6-14.4; p = 0.19). Each additional lumen increased the risk (HR = 4.4; 95% CI: 2.5-7.7; p < 0.001), whereas the permanent blocking of additional lumens was protective (HR = 0.3; 95% CI: 0.1-0.7; p = 0.006). The most commonly isolated organism were coagulase-negative staphylococci with a rate of 28%. CONCLUSION: Number of lumens and site of access were independent risk factors for CRBSI. The use of catheters with multiple lumens should therefore be restricted as far as possible. If a catheter cannot be removed, the permanent closure of unneeded lumens may reduce the risk of CRBSI.

Function, osteoarthritis and activity after ACL-rupture: 11 years follow-up results of conservative versus reconstructive treatment.

ACL-reconstruction aims to restore joint stability and prevent osteoarthritis; however, malfunction and osteoarthritis are often the sequelae. Our study asks whether ACL-reconstruction or conservative treatment lead to better long-term results. In this retrospective cohort study, 136 patients with isolated ACL-rupture who had been treated by bone-ligament-bone transplant or conservatively were identified. Twenty-seven of these were excluded because of a revision operation in the 11.1 years follow-up period, leaving 109 patients (60 reconstructions and 49 conservatively treated) for evaluation based on clinical, radiological and internationally accepted knee-scores (Tegner, IKDC, Kellgren and Lawrence). An individual cohort study is classified as EBM level 2b according to the Oxford Centre of EBM. We observed significantly better knee-stability (P = 0.008) but more osteoarthritis (Grade II or higher) after ACL-reconstruction (42% vs. 25%). Physical activity levels were similar in both groups during the follow-up period (P = 0.16). Eleven years after ACL-rupture the physical activity levels are similar for both groups. After ACL-reconstruction, stability is higher as is osteoarthritis, whereby the result is not necessarily perceived as better subjectively. Specifically, this retrospective study yielded a 24% incidence of oseoarthrits 11 years after conservative management of ACL-rupture in patients not needing secondary surgery. The risk of secondary meniscal tears is reduced after ACL reconstruction, which reduces the negative effects of OA after surgery. The ultimate objective would be to achieve a good subjective outcome by conservative treatment followed by a rehabilitation program designed to keep secondary meniscus tears at a low level.

[Spontaneous bacterial peritonitis: diagnostic and prognostic aspects]. / Die spontane bakterielle Peritonitis: diagnostische und prognostische Aspekte.

Spontaneous bacterial peritonitis (SBP) is a frequent complication of cirrhosis with ascites. As clinical symptoms are often mild or lacking, the condition may not be perceived in otherwise severely ill patients. This study focuses on diagnostic and prognostic aspects in 25 patients with 26 episodes of SBP. A microbiological diagnosis was established in 18 patients by positive culture of ascitic fluid or positive gram stain. In 8 episodes the diagnosis was presumed on the basis of an elevated polymorphonuclear leukocyte (PMN) count in the ascitic fluid (> 250 PMN/microliters). The mean (+/- SD) age of the 11 women and 14 men was 55 +/- 14 years; 16 were attributed to Child grade C, 9 to Child grade B liver dysfunction. In 19 cases, cirrhosis was confirmed histologically. The underlying liver disease was Laennec's cirrhosis in 13 cases, hepatitis-B virus associated chronic liver disease in 7 cases and primary biliary cirrhosis in 2 cases. At the time of diagnosis, 6 of 25 patients had no fever, 13 of 25 patients had no abdominal pain, 10 of 24 patients showed no abdominal tenderness upon palpation and 5 of 26 patients had no fever or abdominal pain. 17 of 26 patients showed signs of portosystemic encephalopathy. The total white blood cell count in the ascitic fluid was 3627 +/- 3978/microliters with 71 +/- 29% polymorphonuclear cells in the group with microbiologically proven peritonitis and 5105 +/- 2860 cells/microliters (80 +/- 13%) in the group with negative ascitic fluid culture, respectively. Gram stains were positive in 8 cases and culture in 16 of 25 patients. E. coli was cultured in 8 episodes and Str. pneumoniae in two. In-hospital mortality was 61% in the group with microbiologically proven peritonitis and 14% in the group with negative ascitic fluid culture (p = 0.062); 6-month mortality rate was 78% and 86% respectively (p = 0.91). Prognosis was worse in patients Child grade C (p = 0.027), in patients lacking symptoms or signs of peritoneal irritation (p = 0.017), in patients with septic shock (p = 0.018) and in patients with elevated serum-creatinin levels at the time of diagnosis (p = 0.05). SBP is a treatable complication with high mortality of advanced liver disease. Clinical manifestations may be non-specific or absent. We recommend that diagnostic paracentesis be performed in all patients with cirrhosis and ascites if their clinical condition is rapidly worsening.

Sleep-related laryngospasm.

The term "sleep-related laryngospasm" refers to episodic, abrupt interruption of sleep accompanied by feelings of acute suffocation followed by stridor. The condition is included in the diagnostic and coding manual of the American Sleep Disorders Association (ASDA), but there are few references in the peer-reviewed literature. Our description of the distinct clinical picture associated with this condition is based on an analysis of the histories of a series of 10 patients. The patients and their families gave precise, uniform accounts of the dramatic attacks. Diagnostic work-up included pulmonary and gastroenterological assessment. All patients reported sudden awakening from sleep due to feelings of acute suffocation, accompanied by intense fear. Apnoea lasting 5-45 s was followed by stridor. Breathing returned to normal within minutes. Patients were left exhausted by the attacks. Nine of our 10 patients had evidence of gastro-oesophageal reflux and six responded to antireflux therapy. We conclude that the nocturnal choking attacks (and the occasional daytime attacks experienced by some of the patients) are caused by laryngospasm. The pathogenesis of the apparent underlying laryngeal irritability is unknown. The condition may be related to a gastro-oesophageal reflux.

Microvesicular steatosis, hemosiderosis and rapid development of liver cirrhosis in a patient with Pearson's syndrome.

BACKGROUND/AIMS: Pearson's marrow-pancreas syndrome consists of refractory sideroblastic anemia with vacuolization of marrow precursors and exocrine pancreas dysfunction. Patients with this disease usually have large deletions of the mitochondrial genome. We report a patient with Pearson's syndrome who had predominantly hepatic manifestations such as microvesicular steatosis, hemosiderosis and rapidly developing cirrhosis. METHODS: Analysis of the mitochondrial and nuclear genomes, determination of enzyme activities and of the hepatic iron content were performed using standard techniques of molecular biology and biochemistry. RESULTS: The patient had typical ringed sideroblasts in a bone marrow smear and a 7436-bp deletion of the mitochondrial genome in all tissues investigated, compatible with Pearson's syndrome. He died within 3 months after birth due to liver failure. Histopathological analysis of the liver revealed complete cirrhosis with signs of chronic cholestasis, microvesicular steatosis and massive hemosiderosis. In addition, the patient was heterozygous for the C282Y and H63D mutations of the hemochromatosis gene. CONCLUSIONS: Pearson's syndrome should be added to the list of neonatal diseases which can cause microvesicular steatosis, hepatic accumulation of iron and liver cirrhosis.