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Biomedical subjects

A Schaffner

Publications and source records attributed to A Schaffner.

At least 19 recordsLinked to original sources

[Fever--useful or noxious symptom that should be treated?].

Fever is a phylogenetically ancient host reaction to invading microorganisms and other noxious stimuli. Poikylothermic organisms can reach febrile temperatures by seeking a hot environment in response to a higher set point in their thermoregulatory center. Endothermic organisms produce febrile temperatures through endogenous heat production at the expenditure of a higher metabolic rate. Nevertheless, fever has been conserved during evolution through millennia, obviously because of its advantage for host defense. Despite of these arguments most doctors, nurses and patients treat fever with antipyretics. The role of fever for the recovery from low risk infections is marginal at best. A large study of ibuprofen in patients with severe sepsis could not establish a positive or negative role on the course or final outcome of the infection in an intensive care setting. These clinical observations seemingly contradict findings in severe experimental bacterial infections in rodents but it has to be taken into consideration that these animals, in contrast to patients, received no antibiotic treatment. In patients with influenza-like illnesses non-steroidal antirhumatics (NSAR) improve fever and wellbeing with little or no evidence for undesired side-effects. It therefore appears appropriate to treat patients with these and similar infections with NSAR. Antipyretic therapy in special patient groups such as brain injury victims, patients with cardiac or respiratory failure or dementia has not been established to be indicated to overcome a worsening of these organs to fail during infections. In children with a history of fever convulsions prevention or lowering of fever does not reduce recurrence. In patients with strokes it appears advisable however to use antipyretics in case of fever despite of a present lack of a proven beneficial effect. In conclusion symptomatic antipyretic therapy should be considered for low risk infections if patient suffering from fever. For more severe infections antipyretic therapy can be applied on an individual basis without too much hope to improve outcome or cause a severe worsening of prognosis.

Analgesics, Non-Narcotic↗

Rapid detection of pathogenic fungi from clinical specimens using LightCycler real-time fluorescence PCR.

In the study presented here a LightCycler real-time PCR system was used for the diagnosis of fungal infections from clinical tissue samples. Nine specimens were investigated from six patients with suspected or proven invasive fungal infections. Seven of nine samples were positive in a broad-range fungal PCR assay. In four samples, Aspergillus fumigatus was detected both by a species-specific hybridization assay as well as by sequencing of amplification products. In addition, the broad-range fungal PCR assay and PCR sequencing detected and identified, respectively, the following organisms in the specimens noted: Candida albicans in a culture-negative liver biopsy, Histoplasma capsulatum in a bone marrow sample, and Conidiobolus coronatus in a facial soft tissue specimen. Real-time PCR is a promising tool for the diagnosis of invasive fungal infections in human tissue samples and offers some advantages over culture methods, such as rapid analysis and increased sensitivity.

Aspergillus fumigatus↗

Marginal and subgingival plaque--a natural habitat of Tropheryma whipplei?

BACKGROUND: DNA of Tropheryma whipplei, the etiologic agent of Whipple's disease, has recently been detected in the saliva of healthy subjects. In this pilot study we searched for the habitat of T. whipplei within the oral cavity. MATERIALS AND METHODS: Samples from different oral sites were obtained from periodontically healthy volunteers, patients with progressive periodontitis and Chinese subjects with necrotizing ulcerative gingivitis or gingivitis. Quantitative real-time PCR was performed using T. whippleispecific primers, human beta-globin-specific primers to control for tissue DNA extraction and PCR reaction and broad-range eubacterial primers to control for bacterial DNA extraction. T. whipplei specificity of multiple amplicons was confirmed by sequencing. The detection limit of the method was 10 ag of T. whipplei DNA, corresponding to one to five bacteria under reference assay conditions. RESULTS: T. whipplei was found in the oral cavity of four out of ten healthy individuals from hospital staff and in three out of nine periodontitis patients, but in none of the individuals from China. All positive samples derived from subgingival and gingival sulcus plaque containing between 10(3) and 5 x 10(5) cells ml(-1) of plaque suspension, whereas saliva, smooth surface plaque and samples from the tongue or cheeks were negative. CONCLUSION: Our results suggest that T. whipplei colonizes the human body via the oral cavity and that bacterial plaques of the gingival crevice and the gingival sulcus/pocket may serve as a natural primary habitat.

Actinomycetales↗

Effects of standardization of whole milk with dry milk protein concentrate on the yield and ripening of reduced-fat cheddar cheese.

Commercial milk protein concentrate (MPC) was used to standardize whole milk for reduced-fat Cheddar cheesemaking. Four replicate cheesemaking trials of three treatments (control, MPC1, and MPC2) were conducted. The control cheese (CC) was made from standardized milk (casein-to-fat ratio, C/F approximately 1.7) obtained by mixing skim milk and whole milk (WM); MPC1 and MPC2 cheeses were made from standardized milk (C/F approximately 1.8) obtained from mixing WM and MPC, except that commercial mesophilic starter was added at the rate of 1% to the CC and MPC1 and 2% to MPC2 vats. The addition of MPC doubled cheese yields and had insignificant effects on fat recoveries (approximately 94% in MPC1 and MPC2 vs. approximately 92% in CC) but increased significantly total solids recoveries (approximately 63% in CC vs. 63% in MPC1 and MPC2). Although minor differences were noted in the gross composition of the cheeses, both MPC1 and MPC2 cheeses had lower lactose contents (0.25 or 0.32%, respectively) than in CC (0.60%) 7 d post manufacture. Cheeses from all three treatments had approximately 10(9) cfu/g initial starter bacteria count. The nonstarter lactic acid bacteria (NSLAB) grew slowly in MPC1 and MPC2 cheeses during ripening compared to CC, and at the end of 6 mo of ripening, numbers of NSLAB in the CC were 1 to 2 log cycles higher than in MPC1 and MPC2 cheeses. Primary proteolysis, as noted by water-soluble N contents, was markedly slower in MPC1 and MPC2 cheeses compared to CC. The concentrations of total free amino acids were in decreasing order CC > MPC2 > MPC1 cheeses, suggesting slower secondary proteolysis in the MPC cheeses than in CC. Sensory analysis showed that MPC cheeses had lower brothy and bitter scores than CC. Increasing the amount of starter bacteria improved maturity in MPC cheese.

Animals↗

Brugada syndrome.

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Anticoagulants↗

Introduction to the Immunocompromised Host Society consensus conference on epidemiology, prevention, diagnosis, and management of infections in solid-organ transplant patients.

Infectious complications are still a significant cause of morbidity and death in solid-organ transplant patients, with significant infection being found in up to two-thirds of these individuals. The risk of infection in the organ transplant patient, particularly of opportunistic infection, is largely determined by 3 factors: the net state of immunosuppression, the epidemiologic exposures the patient encounters, and the consequences of the invasive procedures to which the patient is subjected. The most important principles of patient treatment are prevention, early diagnosis, and specific therapy. This issue is designed as a position paper by a group of experts on epidemiology, prevention, diagnosis, and management of infections in solid-organ transplant patients. We feel that our efforts may serve as an important first step in the development of guidelines in this area.

Anti-Infective Agents↗

Pretransplant evaluation for infections in donors and recipients of solid organs.

The risk of infectious disease reactivation in recipients of and transmission by solid-organ transplants remains, and thorough screening and testing of recipient and donor is especially important. In conceiving screening strategies, it is crucial to consider the sensitivity and specificity of individual diagnostic tests in the context of their use. Furthermore, recognition of special risks for infectious complications of transplantation will help to guide preventive, diagnostic, and therapeutic steps in the control of infectious complications in individual patients. The acceptability of risks for infectious complications after transplantation depends also on the urgency of transplantation of a vital organ as well as the availability of organs. Although these principals are well accepted, standards for the extent of screening and criteria for inappropriate donors and exclusion of unfit recipients remain controversial to some extent.

Communicable Diseases↗

Comparison of effects of amphotericin B deoxycholate infused over 4 or 24 hours: randomised controlled trial.

OBJECTIVE: To test the hypothesis that amphotericin B deoxycholate is less toxic when given by continuous infusion than by conventional rapid infusion. DESIGN: Randomised, controlled, non-blinded, single centre study. SETTING: University hospital providing tertiary clinical care. PATIENTS: 80 mostly neutropenic patients with refractory fever and suspected or proved invasive fungal infections. INTERVENTION: Patients were randomised to receive 0.97 mg/kg amphotericin B by continuous infusion over 24 hours or 0.95 mg/kg by rapid infusion over four hours. MAIN OUTCOME MEASURES: Patients were evaluated for side effects related to infusion, nephrotoxicity, and mortality up to three months after treatment. Analysis was on an intention to treat basis. RESULTS: Patients in the continuous infusion group had fewer side effects and significantly reduced nephrotoxicity than those in the rapid infusion group. Overall mortality was higher during treatment and after three months' follow up in the rapid infusion than in the continuous infusion group. CONCLUSION: Continuous infusions of amphotericin B reduce nephrotoxicity and side effects related to infusion without increasing mortality.

Adolescent↗

Tetrahydrobiopterin increases myocardial blood flow in healthy volunteers: a double-blind, placebo-controlled study.

OBJECTIVES: Tetrahydrobiopterin (BH4) is a regulatory cofactor for the activity of nitric oxide synthases. Vasodilating properties of BH4 have been reported in vitro and in vivo. The influence of BH4 on myocardial blood flow (MBF), however, is largely unknown. We therefore performed a double-blind, placebo-controlled study to investigate the effect of intravenous BH4 on MBF in healthy volunteers. METHODS AND RESULTS: Resting MBF was assessed in 15 subjects receiving either intravenous BH4 (10 mg/kg) or placebo using positron emission tomography (PET) and [13N]ammonia. From a mean baseline MBF of 0.91 +/- 0.09 ml/min/g, MBF increased to 1.18 +/- 0.10 ml/min/g after BH4 (n = 10; p = 0.0042). In contrast, in the group receiving placebo mean MBF remained unchanged (non-significant decrease from 0.97 +/- 0.19 to 0.84 +/- 0.11 ml/min/g; n = 5; p = 0.36). Systemic haemodynamics and ECGs remained unaffected in both groups. BH4 was very well tolerated. CONCLUSION: Systemically administered BH4 is safe and effectively increases resting MBF in healthy volunteers.

Adult↗

Reactive hypoglycaemia due to late dumping syndrome: successful treatment with acarbose.

Reactive hypoglycaemia is a rare disease which occurs postprandially in everyday life involving blood glucose levels below 2.5 to 2.8 mmol/l. We report on a 66-year-old patient who developed symptomatic reactive hypoglycaemia due to late dumping syndrome 10 years after oesophagectomy with cervical anastomosis. A 75 g sucrose load revealed a plasma glucose level of 9.4 mmol/l after one hour, followed by symptomatic hypoglycaemia with a plasma glucose level of 1.8 mmol/l after three hours. Concomitantly, high concentrations of insulin (3216 pmol/l at a glucose level of 9.4 mmol/l and 335 pmol/l at a glucose level of 1.8 mmol/l) and glucagon-like peptide 1 (GLP-1) (375 pmol/l at a glucose level of 9.4 mmol/l and 85 pmol/l at a glucose level of 1.8 mmol/l) were measured. While the patient was under treatment with acarbose, another sucrose load did not provoke symptomatic hypoglycaemia (plasma glucose nadir of 4.6 mmol/l after two hours). Insulin and GLP-1 levels increased much less, to peak levels of 375 pmol/l and 75 pmol/l respectively, after one hour when plasma glucose was 6.8 mmol/l. We conclude that in patients with reactive hypoglycaemia due to gastrointestinal surgery, acarbose decreases rapid glucose absorption associated with hyperglycaemia and GLP-1 secretion, and thus diminishes excessive insulin release. Acarbose is therefore a successful treatment modality for reactive hypoglycaemia due to late dumping syndrome.

Acarbose↗

Two novel genes FIND and LIND differentially expressed in deactivated and Listeria-infected human macrophages.

Deactivation of macrophage functions plays an important role in human infectious and inflammatory diseases. In this study, differential-display RT-PCR was used to analyze the gene expression of human mononuclear phagocytes deactivated with interleukin (IL)-4, IL-10, and dexamethasone (DEX), in the absence and presence of infection with Listeria monocytogenes (Listeria). Two novel differentially expressed mRNA species were discovered: FIND (IL-Four INDuced) was upregulated with IL-4 but down-regulated with DEX, and is predicted to code for an M(r) 53,000 transmembrane protein. LIND (Listeria INDuced) was induced by Listeria infection, and is predicted to code for an M(r) 39,000 nuclear or cytoplasmic protein containing three coiled-coil domains. In addition, we report several novel effects of deactivators and infection on the expression of known genes: (1) IL-4 caused pronounced upregulation of ABCG2, coding for an ATP-binding cassette transporter highly expressed in the placenta, which mediates multidrug resistance of cancer cells, but is otherwise of unknown function; (2) both DEX and IL-4 downregulated osteopontin, an important factor of host resistance against intracellular infections; (3) inhibition of the CC-chemokine I-309 mRNA expression by all three deactivators in the presence of Listeria infection, and (4) upregulation by Listeria infection of the interferon-stimulated gene ISG20 of unknown function, whose product localizes with nuclear dots/PML bodies.

Adaptor Proteins, Signal Transducing↗

Bone marrow involvement in Whipple's disease: rarely reported, but really rare?

Infection with Tropheryma whippelii, the causative agent of Whipple's disease, involves nearly every organ. Involvement of bone marrow may be an overlooked area of Whipple's disease. We report a case of lymphoma-like Whipple's disease with bone marrow involvement together with a brief review of the literature on this topic. Despite minimal documentation, bone marrow may be commonly involved in Whipple's disease and, although not specific, diastase-resistant periodic acid-Schiff (PAS)-positive macrophages in bone marrow may offer an important clue to diagnosis using PAS histology of upper endoscopic biopsies, polymerase chain reaction or electron microscopy.

Adult↗

Effects of trimethoprim and co-trimoxazole on the morphology of Listeria monocytogenes in culture medium and after phagocytosis.

The purpose of this study was to compare the extra- and intracellular activity of antifolates on Listeria monocytogenes. The fortuitous discovery of elongated bacteria in response to trimethoprim revealed a novel effect on the morphology of Listeria in cell culture medium and after phagocytosis. This phenomenon permitted the quantification of trimethoprim activity, revealing comparable activity intra- and extracellularly. Subinhibitory concentrations of trimethoprim resulted in bacterial elongation, which was reversed after removal of trimethoprim. We attribute this effect of trimethoprim to an inhibition of cell wall synthesis and/or cell separation of Listeria.

Animals↗