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Biomedical subjects

A Gerber

Publications and source records attributed to A Gerber.

At least 19 recordsLinked to original sources
PubMed2006

[Intermittent fever: rare expression of an adenocarcinoma of the ampulla of Vater].

PURPOSE: Prolonged intermittent fevers are frequently seen in internal medicine and they constitute a real diagnosis challenge. Infection, auto-immune disease and neoplasy are the most common causes. EXEGESIS: We report here a 48 year-old man with a prolonged intermittent fever. At first, all his assessments were negative and it's only secondary, as clinical and biological disturbances occur that the diagnosis of adenocarcinoma of the ampulla has been done. CONCLUSION: Neoplasms represent a rare cause of intermittent prolonged fever, but we must always keep them in mind. In this case, any specific symptom was initially present to end up quickly to the solution.

Adenocarcinoma↗
PubMed2006

[Pneumococcal septic arthritis revealing a multiple myeloma].

INTRODUCTION: The most common presenting features of multiple myeloma are bone pain, anemia, renal failure or hypercalcemia. Bacterial infection as the initial presentation of this desease is rare. CLINICAL CASE: We report the case of a 62-year-old man with pneumococcal septic arthritis of the knee revealing a multiple myeloma. DISCUSSION: Pneumococcal infection should lead to a suspicion of underlying illness and especially the multiple myeloma.

Arthritis, Infectious↗
PubMed2006

Prevalence of chlamydiae in semen and genital tracts of bulls, rams and bucks.

Chlamydiae infect male genital organs of ruminants. However, little is known about their prevalence. Hence, we investigated fresh and cryopreserved semen (bulls: n=304; rams: n=78; bucks: n=44) by polymerase chain reaction (PCR), as well as genital organs (bulls: n=13; rams: n=10; bucks: n=6) by immunohistochemistry (IHC) and PCR. Sera from bulls (n=104) and small ruminants (n=61) were tested by LPS and rMOMP (recombinant major outer membrane protein) ELISA and competitive ELISA (cELISA), respectively. Three PCR assays were compared in this study for detection of chlamydial DNA in semen: 16S rRNA, IGS-S (intergenic spacer 16S/23S-short), and IGS-L (intergenic spacer 16S/23S-long) PCRs. PCR sensitivity and inhibitory effects were determined by spiking semen with Chlamydophila (Cp.) abortus DNA. In bull semen, detection limits of the 16S, IGS-S and IGS-L PCRs were 10, 10, 100 templates, respectively. However, PCR sensitivity was reduced in ram and buck semen suggesting the presence of potential PCR inhibitors. Of 304 bull semen samples, the 16S PCR revealed DNA of chlamydiae in 20 samples (6.6%), including Cp. abortus (n=2), Cp. psittaci (n=1), Chlamydia suis (n=2), and Chlamydia-like organisms (n=15). In rams, one semen sample was positive for Chlamydia-like organism. All investigated male genital organs were negative for Chlamydia. Serology revealed 47.1% (49/104) positive bulls by LPS ELISA. Of these, 30 samples were positive by rMOMP ELISA, predominantly for Cp. pecorum. In small ruminants, cELISA displayed 34.8% (16/46) and 60% (9/15) positivity for Cp. abortus in rams and bucks, respectively. There was no correlation between serology and PCR of semen. The presence of chlamydiae in semen suggests the possibility of venereal transmission, although risk may be low in Switzerland.

Animals↗
PubMed2006

[Intravenous midazolam-ketamine anaesthesia for closed reduction of forearm fractures in children: impact of additional axillary plexus anaesthesia].

BACKGROUND: The aim of this study was to compare ketamine requirements in children undergoing closed reduction of forearm fractures under midazolam-ketamine anaesthesia with or without axillary plexus anaesthesia. METHODS: With hospital ethical committee approval, we retrospectively analyzed the records of children who received midazolam-ketamine anaesthesia in the years 2000-2001 (group A) and midazolam-ketamine anaesthesia combined with axillary plexus anaesthesia in the years 2002-2004 (group B) for closed reduction of forearm fractures. Requirements for ketamine and postoperative analgesics were noted. Groups were compared with the Mann-Whitney U-test or T-test and the chi2-test (p<0.05). RESULTS: A total of 455 children (group A 225/group B 230) were included in this study. The total amounts of ketamine were not statistically different between the two groups (p=0.154). However, ketamine requirements became less if the time interval between start of axillary plexus anaesthesia and start of intervention became more than 15 min (p<0.05). Patients in group B requested fewer analgesics in the postoperative period (p<0.01). CONCLUSIONS: In the clinical routine of an emergency department the combination of midazolam-ketamine anaesthesia with axillary plexus anesthesia for closed reduction of forearm fractures in children did not result in lower requirements of ketamine.

Adolescent↗
PubMed2006

Cost-benefit analysis of a plant sterol containing low-fat margarine for cholesterol reduction.

For decreasing the risk of coronary heart disease (CHD) it has been proposed to enrich food such as margarine with plant sterol esters which have been shown to reduce total and LDL cholesterol concentrations, two of the major risk factors. A Markov model was developed to assess the costs and benefits of consuming a low-fat plant sterol containing margarine (PS margarine). A health insurer's perspective was taken with a time frame of 10 years. Transition probabilities for CHD and CHD-related death were calculated on the basis of the Framingham risk equations. These were applied to a representative sample of the German population. The alteration in cholesterol levels after intake of PS margarine was estimated based on a meta-analysis of ten randomized controlled trials with parallel or crossover design that found a reduction of 5.7% in total cholesterol. Average annual costs of CHD were assumed to be at 3,000 euro. Costs for "no CHD" and "CHD-related death" were set to 0 euro since the intervention would solely be paid by the consumers. Sensitivity analyses were performed with regard to annual costs, risk estimation, PS margarine reduction in total cholesterol, discount factor, and risk of CHD-related death. The 10-year CHD risks are 6.1% (PS margarine) vs. 6.5% (control). Thus expected 10-year CHD costs are 696 euro (PS margarine) vs. 748 euro (control). The cost savings of 52 euro varied between 32 euro and 74 euro in the sensitivity analysis. A projection at the level of the population for which evidence (randomized controlled trials) exists that plant sterols lower cholesterol (25.35 million) leads to a reduction of 117,000 CHD cases over 10 years and a cost reduction of 1.3 billion euro for this time period (sensitivity analysis 0.8-1.9 billion euro).

Adolescent↗
PubMed2005

Therapeutic actions of insulin-like growth factor I on APP/PS2 mice with severe brain amyloidosis.

Transgenic mice expressing mutant forms of both amyloid-beta (Abeta) precursor protein (APP) and presenilin (PS) 2 develop severe brain amyloidosis and cognitive deficits, two pathological hallmarks of Alzheimer's disease (AD). One-year-old APP/PS2 mice with high brain levels of Abeta and abundant Abeta plaques show disturbances in spatial learning and memory. Treatment of these deteriorated mice with a systemic slow-release formulation of insulin-like growth factor I (IGF-I) significantly ameliorated AD-like disturbances. Thus, IGF-I enhanced cognitive performance, decreased brain Abeta load, increased the levels of synaptic proteins, and reduced astrogliosis associated to Abeta plaques. The beneficial effects of IGF-I were associated to a significant increase in brain Abeta complexed to protein carriers such as albumin, apolipoprotein J or transthyretin. Since levels of APP were not modified after IGF-I therapy, and in vitro data showed that IGF-I increases the transport of Abeta/carrier protein complexes through the choroid plexus barrier, it seems that IGF-I favors elimination of Abeta from the brain, supporting a therapeutic use of this growth factor in AD.

Amyloid beta-Peptides↗
PubMed2005

[Cost-effectiveness of prevention of coronary disease in Germany].

It is generally accepted that the incidence of coronary heart disease can effectively be reduced by strengthening prevention. At the same time, it is still unclear how large the effects of life-style oriented preventive measurements such as diet and exercising are in everyday life. Furthermore, there is an ongoing debate on what measurements are effective. Thus, against the background of dwindling financial resources in health care the input of health economic evaluation is explicated. General issues of health economic evaluation are presented. After that, an overview on the current findings of cost-effectiveness in primary prevention of coronary heart disease is given. Risk factors are separately discussed. It is demonstrated that preventive measurements dealing especially with hypertension and hypercholesterolemia can be cost-effective.

Coronary Artery Disease↗
PubMed2005

Evidence-based medicine: why do opponents and proponents use the same arguments?

There is quite some ethical controversy on Evidence-based Medicine (EbM) with regard to issues of physician autonomy as well as its allocative implications. Yet, there are some shortcomings in the current debate. First of all, some of the arguments brought up against EbM are similarly defaults of "classical medicine" as well, for instance its negligence of social aspects of medicine. Second, it is often maintained that EbM is just a tool to attain cost containment. This argument is false in two regards for neither is there any idea of cutting costs in the roots of EbM nor does EbM once practiced necessarily lead to less costs as there can be underuse as well as overuse. Third, both opponents and proponents of EbM come up with the same arguments against each other. Both maintain that the other way of practicing medicine does not allow for physicians' autonomy and free judgment. Therefore, we are going to search for the different presuppositions on which these "reproaches" rely. In this way we can demonstrate that both opponents and proponents rely on different notions of autonomy and free judgment in their argument. Finally, we hope to show that some of the ethical criticism may be raised against classical medicine as well and that allocation in terms of costs is not primarily an aim of EbM.

Attitude of Health Personnel↗
PubMed2005

Overweight and obesity associated with a missense polymorphism in fatty acid amide hydrolase (FAAH).

BACKGROUND: The brain endogenous cannabinoid system modulates reward and craving pathways and consequently may affect body weight. A naturally occurring missense polymorphism in the gene encoding fatty acid amide hydrolase (FAAH), the primary enzyme for inactivation of endocannabinoids, is associated with problem drug use. AIMS: To investigate the relationship between the FAAH cDNA 385 A/A (P129T) polymorphism and overweight disorders in subjects of multiple ethnic backgrounds attending a medical screening clinic. SUBJECTS: A total of 2667 subjects of white, black and Asian ancestry were genotyped and stratified by a standardized clinic-based assessment of body mass index (BMI, weight in kilograms/(height in meters)(2) or kg/m(2)). METHODS: Subjects were genotyped for the FAAH cDNA 385 C --> A polymorphism using allele-specific oligonucleotide hybridization methods by investigators blinded to all clinical information. BMI was calculated based on exact clinical measurements and World Health Organization ranges were used to stratify subjects. Statistical methods included the Fisher exact test, Mann-Whitney U-test and multivariable logistic regression analysis. RESULTS: The homozygous FAAH 385 A/A genotype was significantly associated with overweight and obesity in white subjects (P=0.005) and in black subjects (P=0.05) but not in a small group of Asians. The median BMI for all subjects was significantly greater in the FAAH 385 A/A genotype group compared to heterozygote and wild-type groups (P=0.0001). In white subjects, there was an increasing frequency of the FAAH 385 A/A genotype with increasing BMI categories of overweight (P=0.02) and obese (P=0.006) with the same trend in black subjects. CONCLUSIONS: These results suggest a role for the FAAH 385 A/A missense polymorphism as an endocannabinoid risk factor in overweight/obesity and may provide indirect evidence to support cannabinoid antagonist treatment strategies in overweight disorders.

Adult↗
PubMed2005

Regulation of in vitro and in vivo immune functions by the cytosolic adaptor protein SKAP-HOM.

SKAP-HOM is a cytosolic adaptor protein representing a specific substrate for the Src family protein tyrosine kinase Fyn. Previously, several groups have provided experimental evidence that SKAP-HOM (most likely in cooperation with the cytosolic adaptor protein ADAP) is involved in regulating leukocyte adhesion. To further assess the physiological role of SKAP-HOM, we investigated the immune system of SKAP-HOM-deficient mice. Our data show that T-cell responses towards a variety of stimuli are unaffected in the absence of SKAP-HOM. Similarly, B-cell receptor (BCR)-mediated total tyrosine phosphorylation and phosphorylation of Erk, p38, and JNK, as well as immunoreceptor-mediated Ca(2+) responses, are normal in SKAP-HOM(-/-) animals. However, despite apparently normal membrane-proximal signaling events, BCR-mediated proliferation is strongly attenuated in the absence of SKAP-HOM(-/-). In addition, adhesion of activated B cells to fibronectin (a ligand for beta1 integrins) as well as to ICAM-1 (a ligand for beta2 integrins) is strongly reduced. In vivo, the loss of SKAP-HOM results in a less severe clinical course of experimental autoimmune encephalomyelitis following immunization of mice with the encephalitogenic peptide of MOG (myelin oligodendrocyte glycoprotein). This is accompanied by strongly reduced serum levels of MOG-specific antibodies and lower MOG-specific T-cell responses. In summary, our data suggest that SKAP-HOM is required for proper activation of the immune system, likely by regulating the cross-talk between immunoreceptors and integrins.

Adaptor Proteins, Signal Transducing↗
PubMed2004

Proteasome inhibitors modulate chemokine production in lung epithelial and monocytic cells.

Proteasome inhibition has become a target for antitumour and anti-inflammatory therapy. The present study investigated the influence of cysteine proteinase and proteasome inhibitors on chemokine production in lung epithelial cells and monocytic cells. The lung carcinoma cell lines A549, SK-MES, NCI-H727, virus-transformed bronchial epithelial cell line BEAS-2B, primary lung epithelial cells, and the acute monocytic leukaemia cell lines Mono-Mac-6 and THP-1 were incubated with proteasome (N-acetyl-L-leucyl-L-leucyl-L-norleucinal (ALLN), beta-lactone) or cysteine proteinase inhibitor (L-trans-Epoxysuccinyl-Leu-3-methylbutylamide-ethyl ester) and the influence on chemokine production (interleukin-8: IL-8, monocyte chemoattractant protein-1, RANTES) was quantified at protein and mRNA levels. Inhibition of proteasome activity by ALLN and beta-lactone resulted in significantly increased IL-8 secretion (5- to 22-fold). Cysteine proteinase inhibitors did not influence chemokine production. The simultaneous rise in IL-8 mRNA was caused by an increased half-life of mRNA and increased RNA synthesis. Moreover, analysis of transcription factor activation revealed induction of activator protein-1 (c-Jun) activity by proteasome inhibition, whereas nuclear factor-kappaB (p50 and p65) was not activated. The significant increase in IL-8 production after proteasome inhibition was also observed in primary lung epithelial cells and in monocytic cells. In addition, the secreted IL-8 was biologically active as shown by the neutrophil chemotaxis assay. In conclusion, it was shown that proteasome inhibitors stimulate interleukin-8 secretion in lung epithelial cells and monocytic cells, thus recruiting neutrophils.

Analysis of Variance↗
PubMed2002

Pressurized bag pump and syringe pump arterial flushing systems: an unrecognized hazard in neonates?

OBJECTIVE: Hand-held flushing of radial arterial lines at 0.5 ml/s in neonates can result in retrograde embolization of flush solution into the central arterial circulation. We studied flush flow velocities during intermittent arterial line purging using a flow regulating device with an infusion bag pump and a syringe pump system. MEASUREMENTS AND INTERVENTIONS: In this in vitro experiment we simulated flushing of a 24- and a 22-G cannula against a mean arterial pressure of 45 mmHg. Fluid flow velocities were gravimetrically measured during flushing from an infusion bag system pressurized to 100, 200, and 300 mmHg and from a syringe pump flush system after initialization of boluses of 0.5, 1.0, 1.5, 2.0, and 2.5 ml. The flow regulating device was opened for 1, 2, and 5 s. RESULTS: Both flush systems tested allowed delivery of flush flow velocities exceeding 0.5 ml/s (e.g., 22-G cannula; bag system, pressure 300 mmHg up to 0.64+/-0.08 ml/s; syringe pump, 2 ml bolus up to 0.74+/-0.05 ml/s). In syringe pump systems the main determinant of flow velocity was bolus size, in bag pump systems flushing time and bag pressure. CONCLUSIONS: Based on data about critical flow velocities through an radial arterial cannula in neonates, both tested flushing systems carry the risk of exceeding the critical value of 0.5 ml/s. They are likely to cause retrograde embolization of flushing solution into the central arterial circulation with the associated risk of clot and air embolization. In vivo studies should identify margins of safety to minimize the risk of retrograde flushing into the central arterial circulation.

Catheters, Indwelling↗
PubMed2002

Prospective epidemiologic survey of patients with community-acquired pneumonia requiring hospitalization in Switzerland.

BACKGROUND: Community-acquired pneumonia (CAP) is a common problem and the principal infection requiring hospitalization, but its treatment is complicated by the difficulty in microbiological diagnosis and the increasing incidence of antibiotic resistance among respiratory pathogens. The purpose of this paper is to present the main epidemiologic features of patients with CAP requiring hospitalization in our country. METHODS: We enrolled three hundred and eighteen adult patients with CAP requiring hospitalization in seven large medical centers in Switzerland during two winter periods. The patients' mean age was 70.4 years. This study describes the epidemiology of these patients. Clinical, radiologic and microbiological evaluations were performed at study entry during treatment, and at 4 weeks post-therapy. For microbiological diagnostic purposes, sputum culture, throat swab culture, PCR, blood cultures, Legionella urinary antigen and serologic evaluations were also performed. RESULTS: Despite the higher mean age, the overall mortality rate was 8%, lower than in other comparable studies. The most common underlying diseases present at study entry were cardiac failure (23%), chronic obstructive pulmonary disease (20%), renal failure (15%), and diabetes (12%); 40% of the patients were smokers. Although dyspnea, cough and positive pulmonary auscultation findings were present in about 90% of patients, fever >38 degrees C was present in only 64%. The most frequently isolated respiratory pathogens were Streptococcus pneumoniae (12.6%), Haemophilus influenzae (6%), Staphylococcus aureus (1.6%), and Moraxella catarrhalis (1.6%). Atypical pathogens were frequently found, with the following distribution: Mycoplasma pneumoniae, 7.5%; Chlamydia pneumoniae, 5.3%; and Legionella pneumophila, 4.4%. The mean duration between onset of symptoms and hospital admission was 4.8 days, and the mean treatment duration was 12.1 days. Two weeks after the start of therapy, although clinical symptoms were absent, radiologic infiltrates were still present in 24% of patients. CONCLUSIONS: The microbiological diagnosis in CAP can be established in only about 50% of cases with the combination of several diagnostic tools. Epidemiologic surveys of CAP should be performed on a regular basis, regionally, as a way to improve the management of these infections.

Aged↗
PubMed2002

[Screening for aneuploidy by first trimester nuchal translucency measurement: results from a prospective trial including 1980 cases in a single center in Switzerland].

AIM: The purpose of this study was to evaluate the efficiency of first trimester screening for chromosomal abnormalities using the sonographically determined thickness of nuchal translucency (NT) combined with maternal age. PATIENTS AND METHODS: Risk screening was offered to all patients with a fetal crown rump length (CRL) between 45 and 84 mm after extensive counselling. For the risk assessment the software provided by the Fetal Medicine Foundation was used. In accordance with the recommendation of the Swiss Working Group on First Trimester Screening a cut-off risk of 1 : 400 was chosen. RESULTS: A total of 1980 consecutive pregnancies participating in the risk screening programme with due dates prior to May 1, 2001 were included. Mean maternal age was 30.1 yrs and 522 (26.4 %) patients were 35 yrs or older. A positive risk screening result was obtained in a total of 219 (11.1 %) pregnancies including 33 of the 37 (1.9 %) cases with unbalanced chromosomal abnormalities. CONCLUSIONS: The detection rate for unbalanced chromosome abnormalities in general (89.2 %) as well as the one for trisomy 21 (93.3 %) in particular are very high with a moderate false-positive rate (9.6 %) in this series. As a comparison in the series presented here, traditional "maternal age screening" (cut-off age 35 yrs) would have yielded detection rates of 64.9 % for all unbalanced chromosome abnormalities and 73.3 % for trisomy 21 at a false-positive rate of 25.0 %. Reducing the false-positive rate by raising the cut-off age to 38 yrs would yield detection rates of 40.5 % for all unbalanced chromosome abnormalities and 46.7 % for trisomy 21 at a false-positive rate of 8.9 %. The number of invasive procedures performed to detect one unbalanced chromosome count may be calculated as 21.75 using the cut-off age of 35 yrs as compared to 6.4 using NT measurement and maternal age. The outcome of this ongoing study is in good accordance with the earlier observation that the main benefit of the addition of first trimester NT measurements to the risk screening protocol is a very high detection rate at a moderate false-positive rate.

Adult↗
PubMed2001

Cathepsin K--a marker of macrophage differentiation?

Cathepsin K is a cysteine protease with high matrix-degrading activity. Initially, cathepsin K was described as being expressed exclusively by osteoclasts. It was suggested that cathepsin K expression is a specific feature of cells involved in bone remodelling. The aim of this study was to investigate the hypothesis that cathepsin K is expressed not only in bone-resorbing macrophages, but also more generally in specifically differentiated macrophages, such as epithelioid cells and multinucleated giant cells in soft tissues. Specimens obtained from different organs and anatomical locations of patients suffering from sarcoidosis, tuberculosis, granulomas caused by foreign materials, and sarcoid-like lesions were investigated for the expression of cathepsins B, K, and L. Immunohistochemistry and in situ hybridization showed cathepsin K in epithelioid cells and multinucleated giant cells irrespective of the pathological condition and anatomical location, but not in normal resident macrophages. By immunoelectron microscopy, cathepsin K was discovered in cytoplasmic granules of multinucleated giant cells. In contrast, cathepsin B and cathepsin L were expressed ubiquitously in CD68-positive tissue macrophages, epithelioid cells, and multinucleated giant cells. The results demonstrate that cathepsin K, but not cathepsin B or cathepsin L, differentiates specific phenotypes of macrophages independently of the anatomical site. Its enzymatic characteristics, particularly its high matrix-degrading activity, suggest that cathepsin K-positive epithelioid cells and multinucleated giant cells are characterized by an enhanced specific proteolytic capability.

Adult↗