Cefoxitin: An alternative to carbapenems in urinary tract infections due to extended-spectrum beta-lactamase-producing Enterobacteriaceae.

BACKGROUND AND OBJECTIVES: Infections caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) have become a major public health issue worldwide. Cefoxitin is a second-generation cephalosporin and is associated with a strong in vitro activity against ESBL. PATIENTS AND METHODS: We conducted a prospective monocentric cohort study from 2012 to 2015 to evaluate the clinical efficacy and safety of cefoxitin in 15 patients treated for urinary tract infection (UTI) caused by ESBL-E, without any severity criteria. RESULTS: We included 15 patients; 11 were male patients with defined risk factors for ESBL-E. Ten patients presented with male UTI, three with pyelonephritis, and two with cystitis. Escherichia coli was the predominant pathogen. All patients had a positive outcome with a good tolerance (a skin rash without any sign of severity was observed in one patient). Microbiological cure was obtained in 9 patients out of 10 at the end of treatment. CONCLUSION: Cefoxitin is an alternative treatment to carbapenems for urinary tract infections caused by ESBL-producing Enterobacteriaceae.

[Renal failure after gastrointestinal hemorrhage: case 10/2012]. / Akutes Nierenversagen nach gastrointestinaler Blutung - Fall 10/2012.

HISTORY AND ADMISSION FINDINGS: We report on a 78-year-old female patient, who presented to the emergency department with nausea and vomiting. INVESTIGATIONS: Endoscopy of the upper gastrointestinal tract revealed gastric erosions and duodenal ulcers. The patient had iron deficiency anemia. DIAGNOSIS, TREATMENT AND COURSE: Following treatment with a proton pump inhibitor (PPI) the patient developed fever, signs of inflammation and oliguric renal failure. In the urine-dipstick there was minimal hematuria and leukocyturia. Urinary protein-differentiation revealed tubular proteinuria with excretion of α1-microglobulin. Renal biopsy showed interstitial nephritis with infiltration of eosinophilic granulocytes. After stopping treatment with PPI and commencing glucocorticoid therapy, the patient recovered fully from renal failure. CONCLUSIONS: Allergic interstitial nephritis following PPI treatment is an important differential diagnosis of renal failure of unknown cause and has a good prognosis when promptly diagnosed and treated.

Exercise-induced albuminuria is associated with perivascular renal sinus fat in individuals at increased risk of type 2 diabetes.

AIMS/HYPOTHESIS: Microalbuminuria represents an established surrogate marker of early diabetic nephropathy and glomerular microangiopathy. Increasing evidence is emerging of a role of perivascular adipose tissue (PVAT) as an important link between obesity, insulin resistance and both macro- and microangiopathy. It is not known whether perivascular renal sinus fat (RSF) has an impact on microalbuminuria in the prediabetic stage. We investigated whether RSF quantified by MRI is associated with microalbuminuria before or after exercise. METHODS: Non-diabetic individuals at increased risk of type 2 diabetes were recruited into the Tübingen Lifestyle Intervention Program (TULIP); 146 participants took part in the analysis. RSF was measured in axial MRI sections at the level of the renal artery. Urine was collected before and after exercise stress testing. RESULTS: Participants (age 47 ± 12 years; mean ± SD) reached a mean exercise load of 176 ± 49 W, with a mean arterial peak pressure (MAPP) of 112 ± 14 mmHg. After adjusting for sex, age, visceral adipose tissue (VAT) and MAPP during exercise, RSF was significantly associated with postexercise albumin/creatinine ratio (ACR; p = 0.006). No association between RSF and baseline BP could be observed after adjusting for confounders (p = 0.26), and there was no association between RSF and baseline ACR either (p = 0.2). CONCLUSIONS: RSF is associated with exercise-induced albuminuria independently of sex, age, VAT and MAPP in a non-diabetic cohort at diabetic risk. We conclude that PVAT in the renal sinus may play a role in the pathogenesis of microalbuminuria.

[Triage systems in the emergency department]. / Triagesysteme in der Notaufnahme.

Emergency department (ED) triage systems facilitate the categorization of emergency patients according to their disease severity and determine both treatment priority and treatment location. Four different five-level triage systems are internationally accepted. The Australasian Triage Scale (ATS, Australasia) allows categorization based on symptoms using specific descriptors. The Manchester Triage System (MTS, UK) uses defined presentational flow charts combined with indicators. The Canadian Triage and Acuity Scale (CTAS, Canada) is based on the ATS, but also includes diagnoses. The Emergency Severity Index (ESI, USA) first excludes life-threatening and severe disease before stratification according to estimated resource utilization. The goal of all triage systems is to reduce the in-hospital mortality and to minimize time to treatment, length of stay, and resource utilization.

Student tutors are able to teach basic sonographic anatomy effectively - a prospective randomized controlled trial.

PURPOSE: Ultrasound is a widely used diagnostic tool. In medical education, it can be used to teach sonographic anatomy as well as the basics of ultrasound diagnostics. Some medical schools have begun implementing student tutor-led teaching sessions in sonographic abdominal anatomy in order to meet the growing demand in ultrasound teaching. However, while this teaching concept has proven to be feasible and well accepted, there is limited data regarding its effectiveness. We investigated whether student tutors teach sonographic anatomy as effectively as faculty staff sonographers. MATERIALS AND METHODS: 50 medical students were randomly assigned to one of two groups. 46 of these could be included in the analysis. One group was taught by student tutors (ST) and the other by a faculty staff sonographer (FS). Using a pre/post-test design, students were required to locate and label 15 different abdominal structures. They printed out three pictures in three minutes and subsequently labeled the structures they were able to identify. The pictures were then rated by two blinded faculty staff sonographers. A mean difference of one point in the improvement of correctly identified abdominal structures between the pre-test and post-test among the two groups was regarded as equivalent. RESULTS: In the pre-test, the ST (FS) correctly identified 1.6 ± 1.0 (2.0 ± 1.1) structures. Both the ST and FS group showed improvement in the post-test, correctly identifying 7.8 ± 2.8 vs. 8.9 ± 2.9 structures, respectively (p < .0001 each). Comparing the improvement of the ST (6.2 ± 2.8 structures) versus the FS (6.9 ± 3.2) showed equivalent results between the two groups (p < .05 testing for equivalence). CONCLUSION: Basic abdominal sonographic anatomy can be taught effectively by student tutors.

[Retroperitoneal masses: two case reports--Case 11/2009]. / Retroperitoneale Raumforderungen: Zwei Kasuistiken--Fall 11/2009.

HISTORY AND ADMISSION FINDINGS: A 35-year old patient (male, headaches, visual impairment, 170/100 mmHg, case 1) and a 61-year old patient (female, headaches, epistaxis, 230/110 mmHg, case 2) were investigated in our hospital. INVESTIGATIONS: Laboratory findings in case 1 verified acute renal failure (serum creatinine 23 mg/dl, urea 146 mg/dl, pH 7.19). Bilateral obstructive uropathy was seen in sonography, and CT showed periureteral, retroperitoneal masses (RPM). In case 2, the lab showed a marked hyperreninism with secondary hyperaldosteronism, and ultrasound revealed a lowered right renal resistance-index. The MRI showed a retroperitoneal mass with long-segmental compression of the right renal artery (no lymphomas). CT-guided biopsy revealed grade 2 adenocarcinoma. No metastases were seen in the PET-CT. DIAGNOSIS, TREATMENT AND COURSE: In case 1, Morbus Ormond with post-renal failure owing to obstructive uropathy was assumed. After drainage of obstructive uropathy, immunsuppressive therapy (glucocorticoids and azathioprine) was started, and renal function recovered completely in the patient who was free of complaints in the further clinical course. In case 2, cancer disease progressed to osteoblastic metastases under palliative chemotherapy. CONCLUSIONS: RPM generally cause symptoms at rather late stages of the underlying disease. A total of 75% of RPM are based on idiopathic retroperitoneal fibrosis (M. Ormond). Common causes of secondary RPM are drugs, neoplasms, infectious diseases and former therapies in the retroperitoneum (surgery, radiotherapy). Histological investigation is recommended for RPM with atypical location, clinical suspicion of underlying neoplastic or infectious diseases and lacking response to glucocorticoids. The standard therapy for M. Ormond includes glucocorticoids, tamoxifene or methotrexate (or combinations of glucocorticoids with either tamoxifene or methotrexate). In case of secondary RPM, therapy depends on the cause of RPM.

Effects of a supplementary final year curriculum on students' clinical reasoning skills as assessed by key-feature examination.

BACKGROUND: The final year of medical education is considered crucial in making students 'fit for purpose'. Studies have shown that many students leave medical school without having experienced sufficient preparation for their upcoming professional life. AIM: The aim of this study was to examine the effectiveness of a supplementary internal medicine final year curriculum on clinical reasoning skills. METHOD: Final year internal medicine students from two universities participated in the study which was based on a static-group design. The experimental group (n = 49) took part in a final year student curriculum with interactive case-based seminars and skills training sessions. The comparison group (n = 25) did not receive any additional training beyond working on the ward. Clinical reasoning skills were assessed using a key-feature pre-post test. RESULTS: Prior to their clinical rotation, the two groups did not differ in the key-feature examination (p < 0.924). The experimental group performed significantly better than the comparison group (p < 0.028) in the post-intervention key-feature examination. CONCLUSIONS: Supplementary interactive case-based seminars and skills training sessions are effective and significantly improve the clinical reasoning skills of final year students in internal medicine. Further study is warranted and should look to examine the effectiveness of a final year student curriculum on other performance measures.

Protein kinase C iota mediates lipid-induced apoptosis of human coronary artery endothelial cells.

Apoptosis is involved in the development and progression of atherosclerotic lesions. Protein kinase C (PKC) signalling is of importance in atherosclerosis as well as apoptosis. Therefore, we tested the involvement of PKC in lipid-induced apoptosis of human coronary artery endothelial cells (HCAEC). Protein expression of PKC isoforms alpha, beta I, delta, epsilon, and iota was detected, whereas no relevant protein amounts of PKC isoforms beta II, gamma, eta, theta, and zeta were found. Inhibition of classical and novel PKC isoforms by treatment with bisindolylmaleimide or PKC down-regulation by long-term treatment with 12-O-tetradecanoyl phorbol-13-acetate (TPA) could not prevent apoptosis induced by palmitate or stearate. In contrast, a specific myristoylated, cell-permeable PKC zeta/iota pseudosubstrate prevented lipid-induced apoptosis in HCAEC. Furthermore, saturated fatty acids activated PKC iota as evidenced by PKC iota down-regulation upon long-term treatment with stearate. Our data provide evidence that PKC iota is activated by saturated fatty acids and mediates lipid-induced apoptosis of HCAEC.

Genetic variability of procolipase associates with altered insulin secretion in non-diabetic Caucasians.

AIMS: Procolipase (CLPS) is secreted from the exocrine pancreas into the gastrointestinal tract and becomes proteolytically cleaved into colipase and the pentapeptide enterostatin. While colipase is an indispensable cofactor for pancreatic lipase, enterostatin acts as a hormone that inhibits insulin secretion and confers satiety signals to the brain, thereby restricting further food intake in animal models. As both high fat diet and obesity contribute to insulin resistance, we investigated whether genetic variability of CLPS associates with metabolic traits in non-diabetic humans at diabetes risk. METHODS: Tagging single nucleotide polymorphisms (SNPs) in the human CLPS locus on chr6p21.1 were selected using HapMap data. 498 humans, phenotyped for different glucose and lipid metabolic traits, were genotyped by bidirectional sequencing and multivariate linear regression analyses were undertaken. RESULTS: 2 tagging SNPs (rs3748050 in the Kozak sequence: A/G and rs3748051 in intron 1: A/G), covering 100% of CLPS variability including 8 kb of its promoter, were genotyped for association analyses. The minor alleles of both tagging SNPs associated significantly with a reduced insulin secretion (-20.2%, both SNPs) in various estimation models derived from the oral glucose tolerance test (OGTT; rs3748050/51: 30 min C-peptide levels: p=0.001/0.01, insulinogenic index: p=0.02/0.02, AUC C-peptide/AUC glucose: p=0.01/0.01) after adjustment for relevant covariates. No significant associations with fasting total cholesterol (c), HDL-c, LDL-c, triglycerides and free fatty acids were found (all p > 0.11). CONCLUSIONS: CLPS genetic variability associates with insulin secretory function in non-diabetic humans and may represent a novel candidate gene for development of type 2 diabetes.

[Nephropathia epidemica as the result of a Puumala virus infection in a pregnant patient]. / Nephropathia epidemica als Folge einer Puumala-Virus-Infektion bei einer schwangeren Patientin.

HISTORY AND ADMISSION FINDINGS: A 29-year-old woman in the early stage of pregnancy ( approximately 6 (th) week) presented in our hospital with influenza-like symptoms of fever, headache, aching limbs and tenderness over the costovertebral angle. Acute oliguric renal failure occurred within a few days. INVESTIGATIONS: Ultrasonography revealed symmetrically enlarged kidneys with a small amount of perirenal fluids. The blood count showed thrombocytopenia, and viral serology verified a recent infection with Puumala virus (species of Hantavirus). TREATMENT AND COURSE: Epidemic nephropathy was diagnosed. The patient underwent one session of hemodialysis and soon recovered without any residual renal damage. The pregnancy continued without any further complications. CONCLUSIONS: There are only few reports on infections with Puumala virus during pregnancy are. None of theses described any fetal abnormalities causes by the maternal infection, as in our patient. Hantavirus infections should be considered in differential diagnosis of acute renal failure in endemic regions.

Integration of role-playing into technical skills training: a randomized controlled trial.

INTRODUCTION: Recently, efforts have been undertaken to enhance the face validity of technical skills training by introducing role-plays and standardised patients. Since little is known about the effects of role-playing with respect to the realism of a training situation and students' objective performance, we performed a randomized controlled trial. METHODS: 36 medical students participated in videotaped small group skills-lab sessions on the topics of Doppler sonography and gastric tube insertion. One half of the students participated in role-plays and the other half practised without role-playing. Realism of the training situation was analysed by means of post-intervention self-selected student survey evaluations. Technical performance and patient-physician communication were assessed by independent ratings of the videotaped sessions. RESULTS: The physician's role was regarded to be significantly more realistic when performing role-plays. Assessment of videotaped sessions showed that practising technical skills by performing role-plays resulted in significantly better patient-physician communication whereas students' technical performance did not differ between groups. CONCLUSION: Introducing role-plays enhances the realism of technical skills training and leads to better patient-physician communication. Students do not seem to be overstrained by practising clinical technical skills using role-plays. We conclude that role-playing is a valuable method in practising technical skills.

Role of AMP-activated protein kinase gamma 3 genetic variability in glucose and lipid metabolism in non-diabetic whites.

AIMS/HYPOTHESIS: AMP-activated protein kinase (AMPK) is a heterotrimeric enzyme that acts as an intracellular fuel sensor, directing multiple metabolic pathways in a catabolic direction in times of nutrient shortage. In humans, three different gamma-subunits (gamma(1), gamma(2), gamma(3)) have been identified as AMPK regulators. The AMPKgamma3 (protein kinase, AMP-activated, gamma 3 non-catalytic subunit, PRKAG3) isoform plays a role in gene regulation in glucose/lipid metabolism and skeletal muscle glycogen content. We investigated whether PRKAG3, in addition to being expressed in skeletal muscle, is also expressed in human liver. We also investigated whether genetic variance in PRKAG3 is associated with glucose and/or lipid metabolism in non-diabetic whites. MATERIALS AND METHODS: After sequencing a screening cohort (n = 50) in the PRKAG3 locus, we genotyped 1061 participants for frequently found single nucleotide polymorphisms (SNPs). Association analyses between genotypes/haplotypes and metabolic traits were carried out. RESULTS: We detected PRKAG3 expression in human liver and skeletal muscle. Two SNPs (rs692243, rs6436094) with minor allele frequencies of 0.16 and 0.26 respectively and in moderate linkage disequilibrium (D' = 0.92; r (2) = 0.47) were found. rs692243 (C/G) confers a Pro71Ala mutation, while rs6436094 (A/G) is located in the 3' untranslated region. No associations with prediabetic traits such as body fat distribution, insulin resistance or insulin secretion were found (p > 0.15 for all). However, the minor alleles of both SNPs were significantly associated with higher serum LDL-cholesterol and apolipoprotein (Apo) B-100 levels (rs692243: CG:LDL 4.3%, ApoB-100 3.4%; GG:LDL 7.6%, ApoB-100 5.4%; p = 0.008 and p = 0.01 respectively; rs6436094: AG:LDL 3.3%, ApoB-100 1.7%; GG:LDL 11.3%, ApoB-100 11.1%; p = 0.009 and p = 0.05 respectively; dominant model). The GG/GG diplotype homozygous for both minor SNP alleles displayed the highest LDL-cholesterol among all frequent diplotypes (p = 0.059). CONCLUSIONS/INTERPRETATION: While genetic variability in PRKAG3 does not seem to have a major effect on glucose metabolism, it may play an important role in lipoprotein metabolism in humans.

An innovative model for teaching complex clinical procedures: integration of standardised patients into ward round training for final year students.

OBJECTIVES: Ward rounds are an essential activity for doctors in hospital settings and represent complex tasks requiring not only medical knowledge but also communication skills, clinical technical skills, patient management skills and team-work skills. However, although the need for ward round training is emphasized in the published literature, there are currently no reports of ward round training in a simulated setting with standardized patients. METHODS: 45 final year students participated in a ward round training session lasting two hours with three standardized patient scenarios and role-plays. Final year students assumed the role of either doctor, nurse or final year student with role-specific instructions and provided each other with peer-feedback during the training session. Training was assessed using final year student focus groups and semi-structured interviews of standardized patients. Written protocols of the focus group as well as the interviews of standardized patients were content analysed. RESULTS: In the course of five focus groups, 204 individual statements were gathered from participating final year students. Ward round training proved to be a feasible tool, well accepted by final year students. It was seen to offer a valuable opportunity for reflection on the processes of ward rounds, important relevant feedback from standardized patients, peer group and tutors. Semi-structured standardized patient interviews yielded 17 central comments indicating that ward rounds are a novel and exciting experience for standardized patients. CONCLUSION: Ward round training with standardized patients is greatly appreciated by final year students and is viewed as an important part of their education, easing the transition from observing ward rounds to conducting them on their own.

The Par6alpha/aPKC complex regulates Akt1 activity by phosphorylating Thr34 in the PH-domain.

A single nucleotide polymorphism in the partitioning defective protein-6alpha (Par6alpha) promoter is coupled with lower Par6alpha expression and better insulin sensitivity, whereas overexpression of Par6alpha in C2C12 myoblasts inhibits insulin-induced protein kinase B/Akt1 activation and glycogen synthesis. Here we show that a direct interaction of Par6alpha with atypical protein kinase C (aPKC) is crucial for this inhibition. A DeltaPB1-Par6alpha deletion mutant that does not interact with aPKC neither increased aPKC activity nor interfered with insulin-induced Akt1 activation in C2C12 cells. Further, T34 phosphorylation of Akt1 through aPKC is important for inhibition of Akt1. When Par6alpha was overexpressed, activation of wild-type Akt1 (-59.3%; p=0.049), but not T34A-Akt1 (+2.9%, p=0.41) was reduced after insulin stimulation. The resistance of T34A-Akt1 to Par6alpha/aPKC-mediated inhibition was also reflected by reconstitution of insulin-induced glycogen synthesis. In summary, Par6alpha-mediated inhibition of insulin-dependent glycogen synthesis in C2C12 cells depends on the direct interaction of Par6alpha with aPKC and on aPKC-mediated T34 phosphorylation of Akt1.

Fatal multidrug-resistant Acinetobacter baumannii sepsis in a patient with travel history and recent onset of systemic lupus erythematosus: a case report.

Severe infections are a common cause of death in patients suffering from systemic lupus erythematosus (SLE). We here report on a fatal multidrug-resistant Acinetobacter baumannii sepsis in a patient with newly diagnosed SLE, who had to be treated with immunosuppressants due to lupus nephritis. Detailed analysis of the patient's history revealed that colonisation probably had occurred during a recent hospitalisation of the patient in the Mediterranean region. E-test analysis indicated that resistance to carbapenems was mediated by a plasmid-encoded metallo-beta-lactamase. We conclude that travel history including previously visited health care facilities always should be carefully considered for decisions on anti-infective therapy, as travel activities increasingly facilitate spread of antimicrobial resistances.

[Early systolic notched peripheral Doppler flow pattern as an indicator of functional obstruction of the common iliac artery after iatrogenic aortic dissection: a case report]. / Frühsystolisch eingekerbte periphere Dopplerflusssignale als Hinweis auf eine funktionelle Obstruktion der Arteria iliaca communis bei iatrogener Aortendissektion: ein Fallbericht.

We report on a 57-year-old male patient with typical claudication localised in the right thigh, following aortic valve replacement. The ankle brachial index under resting conditions is within normal range on both sides. A conspicuous monomorphic double-humped peripheral Doppler flow pattern with an early systolic notch extending to the baseline can be registered in all the arteries of the right lower limb. The flow patterns of all other peripheral arteries are properly configured and of triphasic morphology. As the underlying cause of the pathologically altered Doppler flow morphology, aortic dissection Type A can be detected, extending from the former cannulation site of the ascending aorta into the right common iliac artery. Its dissection membrane functionally occludes the right common iliac artery in the early systole, the effect being brief and reversible. The pathogenesis of this morphologically altered Doppler flow pattern and potential differential diagnoses are discussed in this case report, also considering the current literature.

An innovative model for final-year students' skills training course in internal medicine: 'essentials from admission to discharge'.

Clerkships are generally seen as a very favourable learning environment for final-year students. However, in recent years the clinical experience of final-year students has been reported to decline progressively. It was decided, therefore, to introduce an innovative skills training model in internal medicine. Sixty final-year students received four consecutive days of training during their first week, consisting of three-hour sessions on each day. The skills training course reflected a patient history from admission to discharge and included all required routine procedures, typical forms/files and computer interactions. Acceptability was measured with self-administered surveys post-intervention and again 16 weeks later; self-assessment was measured pre-/post-intervention. The skills training course was well accepted by the students and led to a significant improvement in self-assessment. It was considered to be very helpful for work on the wards in both the immediate and the long-term retrospective evaluation. The final-year skills training course allows students to learn how to handle specific tools and applications for their work on the ward. It possesses face validity and is easy to integrate.