Warm or cold ischemia in animal models of lung ischemia-reperfusion injury: is there a difference?
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Animals↗
Biomedical subjects
S Fischer
Publications and source records attributed to S Fischer.
Angiolymphoid hyperplasia with eosinophilia treated with anti-interleukin-5 antibody (mepolizumab).
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Aged↗
Immunosuppressive therapy after human lung transplantation.
In 2002, equal numbers of lung transplantation (LTx) were performed with or without induction therapy with antilymphocyte antibodies, monoclonal anti-CD3 antibody or anti-interleukin-2-receptor monoclonal antibodies. It remains to be established if induction therapy after LTx is beneficial or deleterious for long-term graft and patient survival. The vast majority of lung transplant recipients receive a triple-drug maintenance regimen including a calcineurin inhibitor, a cell-cycle inhibitor and steroids. Equal proportions receive cyclosporin A (CsA) and tacrolimus (Tac). There is also a trend to prescribe mycophenolate mofetil (MMF) instead of azathioprine (Aza). Steroid withdrawal is uncommon even 5 yrs after transplantation. The superiority of Tac over CsA as a maintenance agent has not been established to date, and the administration of MMF instead of Aza in combination with CsA and steroids did not improve graft or patient survival in a recent international, prospective, randomised, controlled trial. Shift from cyclosporin A to tacrolimus has emerged as the first treatment step of refractory acute rejection followed by high-dose steroids or antilymphocyte agents, total lymphoid irradiation or photopheresis. The treatment of chronic rejection remains deceptive and includes varied strategies such as modification of the maintenance regimen, addition of inhaled immunosuppressants and/or total lymphoid irradiation and photopheresis.
Cyclosporine↗
[Significance of triglycerides for other metabolic parameters in the familial metabolic syndrome].
BACKGROUND: The relationship between the various degrees of glucose tolerance and metabolic parameters have already been examined in various studies. Whether and to what extent the triglycerides (TG) affect other metabolic parameters in the different degrees of glucose tolerance is not certain. We therefore studied the importance of the triglycerides within a defined glycemic state in patients with an elevated familial risk for metabolic diseases. METHODS: We examined 866 patients (380 men, 486 women, mean age 44,4 years) in the "Familial Metabolic Syndrome Study" (FAMES). The patients were assigned to various degrees of glucose tolerance, according to the result of an oral glucose tolerance test. All degrees were divided into subgroups in respect of the triglyceride level (TG < 1,7 or TG >/= 1,7 mmol/l). In these subgroups we measured various metabolic parameters like fasting glucose, insulin resistance, insulin and proinsulin levels, HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), uric acid, HbA (1c), and free fatty acids (FFA). RESULTS: In patients with normal glucose tolerance the hypertriglyceridemia is already associated with other components of the metabolic syndrome like elevated HbA (1c), free fatty acids, proinsulin and insulin levels, worsened insulin sensitivity, elevated uric acid and LDL-C levels as well as a lowered HDL-C level. The patients with diabetes and hypertriglyceridemia also showed higher levels of FFA, proinsulin and insulin, a lower HDL-C level and a more prominent insulin resistance. CONCLUSION: Hypertriglyceridemia is an indicator for insulin resistance and elevated levels of other components of the metabolic syndrome within the various degrees of glucose tolerance.
Adult↗
Impact of preoperative aortic root diameter on long-term aortic valve function after valve sparing aortic root reimplantation.
BACKGROUND: Valve sparing aortic root reimplantation technique in patients with aortic root aneurysm have shown excellent mid-term results. In conjunction with the diameter of the aortic root the mechanical leaflet stress increase, which might have an impact on long-term aortic valve function after valve sparing aortic root reimplantation. METHODS AND RESULTS: From July 1993 to October 2001, 168 patients with aortic root aneurysm underwent valve sparing aortic root reimplantation. Patients with type A aortic dissection were excluded. Thus, 123 patients were analyzed. We identified 47 patients with an preoperative aortic root diameter exceeding 60 mm (group A), 58 patients with an diameter between 50 and 60 mm (group B), and 18 patients with a diameter less than 50 mm (group C). The groups were compared regarding mortality, long-term survival, freedom from reoperation, freedom from severe and moderate aortic valve insufficiency (AI), and postoperative morbidity. Mean follow-up (group A 43+/-26 months, group B 40+/-25 months, group C 23+/-19 months; group C versus group A, P=0.005; group C versus group B, P=0.011) was shorter in group C. Perioperative mortality (group A 2.2%, group B 1.9%, group C 5.2%; P=ns) was comparable between the groups with each one patient. The 3-year survival for group A was 98+/-2%, for group B 96+/-3%, and for group C 100+/-0% (P=ns). Freedom from reoperation for group A was 98+/-2%, for group B 96+/-3%, and for group C 88+/-8% (P=ns). Four patients developed severe or moderate AI, thus freedom from severe and moderate AI for group A was 100+/-0%, for group B 88+/-8%, and for group C 94+/-5% (P=ns). During follow-up no thromboembolic or bleeding events were noticed. CONCLUSIONS: Our data show that the preoperative diameter of the aortic root has no impact on the longevity of the repair. Thus, the reimplantation technique can be recommended for all patients presenting with an aortic root aneurysm and normal leaflets regardless of the aortic root diameter.
Adult↗
Efficiency of vibrational sounding in parasitoid host location depends on substrate density.
Parasitoids of concealed hosts have to drill through a substrate with their ovipositor for successful parasitization. Hymenopteran species in this drill-and-sting guild locate immobile pupal hosts by vibrational sounding, i.e., echolocation on solid substrate. Although this host location strategy is assumed to be common among the Orussidae and Ichneumonidae there is no information yet whether it is adapted to characteristics of the host microhabitat. This study examined the effect of substrate density on responsiveness and host location efficiency in two pupal parasitoids, Pimpla turionellae and Xanthopimpla stemmator (Hymenoptera: Ichneumonidae), with different host-niche specialization and corresponding ovipositor morphology. Location and frequency of ovipositor insertions were scored on cylindrical plant stem models of various densities. Substrate density had a significant negative effect on responsiveness, number of ovipositor insertions, and host location precision in both species. The more niche-specific species X. stemmator showed a higher host location precision and insertion activity. We could show that vibrational sounding is obviously adapted to the host microhabitat of the parasitoid species using this host location strategy. We suggest the attenuation of pulses during vibrational sounding as the energetically costly limiting factor for this adaptation.
Animals↗
[Peristomal dermatitis: a common condition and a differential diagnostic challenge].
Inflammation of the skin in the immediate neighborhood of a stoma (peristomal dermatitis) occurs--at least temporarily--in about two-thirds of all stoma patients. The often apparently uniform clinical presentation may conceal a variety of different pathological conditions, a knowledge of which is a must for the correct diagnosis and therapeutic strategy, which in turn is essential to prevent the development of a vicious circle of dermatitis and stomal insufficiency, which in the worst case may make a surgical intervention necessary.
Bacterial Infections↗
[Therapy decision based on the glucose triad. Drug treatment of type 2 diabetes].
For the treatment of type 2 diabetes we now have available a wide spectrum of oral antidiabetic agents and insulins that make it possible to offer the patient an individualized, pathophysiologically oriented therapy. Such treatment should be oriented to the two basic defects--insulin resistance and impaired early secretion of insulin--which can be assessed on the basis of fasting and postprandial blood sugar. Since monotherapy rarely suffices to correct the complex dysregulation, when close-to normalization of the glucose triad fasting blood glucose, postprandial blood glucose and HbA1C fails, early application of complementary combinations offer advantages, with preference being given to metformin in the overweight patient. This also applies to the combination with insulin.
1-Deoxynojirimycin↗
[Atopic eczema. Spectrum of provocation factors and possibilities for their effective reduction and elimination].
Atopic eczema forms together with extrinsic bronchial asthma and allergic rhinoconjunctivitis the classical atopic triad. Genetic predisposition is the crucial pathogenetic factor. The combination of genetic disposition and provocation factors leads to the clinical appearance of skin disease. In addition to therapy adjusted to the stage of the disease, modern management should include a search for relevant trigger factors and then their avoidance to reduce or even prevent flares of the disease. The spectrum of provocation factors ranges from simple measures such as appropriate clothing up to specific measures such as indoor aeroallergen reduction measures.
Adult↗
[Ross procedure with combined replacement of the ascending aorta: impact on autograft root function and distensibility].
BACKGROUND: The safety and effectiveness of combined aortic root autograft replacement in combination with ascending aorta replacement has been demonstrated recently. Replacement of the ascending aorta with a vascular prosthesis results in an increase in aortic root distension, and aortic root wall stress. In this study we aimed to assess the autograft root dimensions, distensibility, and autograft valve function in patients after Ross operation combined with replacement of the ascending aorta compared to patients who underwent Ross operation only. PATIENTS AND METHODS: Echocardiographic follow-up was performed on 28 patients after Ross operation with complete root replacement only (group R) and 12 patients who received an additional replacement of the ascending aorta (group R/A). The mean follow-up time was 24.9 +/- 17.2 months. Autograft root dimensions, root distensibility and valve function were assessed by echo-cardiography. The aortic root was measured at the level of the annulus, sinus of valsalva, and sinotubular junction. The distensibility was calculated as percent change of radius. RESULTS: The mean distensibility at the annulus level was higher in group R/A (18.4 +/- 6.8% vs 13.4 +/- 8.1%; p = 0.047); at the level of the sinus of valsalva and sinotubular junction no differences were observed. The autograft pressure gradient was within physiological limits in all patients. The majority of patients showed a competent autograft valve (group R: AI 0 degree; 83%, AI I degree; 14%, AI II degree; 3%; group R/A: AI 0 degree; 75%, AI I degree; 25%). CONCLUSIONS: Replacement of the ascending aorta with a non-compliant prosthesis does not effect root dimension, distensibility, and valve function.
Adult↗
Management of lung transplant recipients with bronchogenic carcinoma in the native lung.
Experience with lung transplantation for bronchogenic carcinoma is limited. In our experience, 3 of 6 patients died of recurrent carcinoma within 5 to 35 months after transplantation. Hence, we currently do not support lung transplantation for patients with pre-transplant diagnosis of bronchogenic carcinoma, with the exception of bronchioloalveolar carcinoma (BAC) confined to the lung. Patients with BAC should be staged thoroughly with chest and abdominal computerized tomography, brain magnetic resonance imaging, and bone scan repeated every 3 months while on the waiting list, and should undergo mediastinoscopy at the time of transplantation, with a plan for a backup recipient if metastatic lymph nodes are detected. Proposal for lung transplantation for patients with bronchogenic carcinoma, with the exception of BAC, probably should be performed in the setting of a clinical trial developed with input from the lung transplant community.
Carcinoma, Bronchogenic↗
Virulence of recent and former classical swine fever virus isolates evaluated by their clinical and pathological signs.
The clinical diagnosis of classical swine fever (CSF) still caused problems to the veterinarians during the last decade. The primary CSF outbreak was often detected too late and, meanwhile, the virus had spread. Consequently, the recent classical swine fever virus isolates (CSFV) were suspected to be of low virulence. The purpose of the study was to quantify the virulence of four recent CSFV by evaluating the clinical and pathological signs caused by different CSFV. Pigs of the same breed and age group were inoculated intranasally with CSFV from recent epidemics in European Union (EU) member states. The CSFV used are registered in the data base of the EU Reference Laboratory for CSF and belong to different genotypes: 2.1, 2.2 and 2.3 respectively. Clinical signs of CSF were evaluated by using a score system suggested previously (Mittelholzer et al., 2000: Vet. Microbiol. 74, 293). For the evaluation of pathological lesions, a new pathological score was introduced. The four CSFV tested here were classified as moderately virulent in general, although one CSFV may cause different clinical courses, ranging from highly virulent to avirulent. This indicates the importance of additional factors in the host animal for virulence. Differences in the clinical and pathological signs between these four recent CSFV were rather minor, emphasizing that the genetic typing of CSFV is absolutely essential. Differences towards former CSFV (e.g. reference virus strain Alfort 187) were more pronounced, especially regarding the onset and duration of the disease, the occurrence of skin haemorrhages and pathological lesions of kidney, subcutis and serosae. It is concluded that clinical diagnosis of CSF is rather difficult in pigs up to 14 days post-CSFV infection using these four CSFV, emphasizing the need for careful differential diagnosis and the laboratory investigation for CSF at an early stage.
Animals↗
Influence of treatment with acarbose or glibenclamide on insulin sensitivity in type 2 diabetic patients.
AIM: The aim of our double-blind, placebo-controlled study was to compare the effect of acarbose and glibenclamide on the insulin sensitivity in type 2 diabetes. METHODS: We investigated 77 patients (mean age 58.7 years, mean BMI 27.3 kg/m2), treated by diet alone for at least 4 weeks. The subjects were randomized into three treatment groups for 16 weeks: 100 mg t.i.d. acarbose (n = 25) or 1 mg t.i.d. glibenclamide (n = 27) or one t.i.d. placebo (n = 25). Before and after therapy, the levels of fasting plasma glucose, glycosylated haemoglobin, fasting insulin, plasma glucose and insulin 1 h after a standardized breakfast were measured and insulin sensitivity determined by euglycaemic hyperinsulinaemic clamp test. RESULTS: After the treatment period, BMI in the acarbose and placebo group decreased significantly, whereas in the glibenclamide group a significant increase was observed. Fasting plasma glucose was only significant reduced under glibenclamide. The postprandial glucose decreased significantly after acarbose (13.8 vs. 11.4 mmol/l, p < 0.05) and glibenclamide treatment (14.6 vs. 11.4 mmol/l, p < 0.05) and was unchanged under placebo (13.8 vs. 13.7 mmol/l). The fasting insulin levels remained unchanged in all three groups, whereas postprandial insulin values increased significantly under glibenclamide. Neither acarbose nor glibenclamide significantly changed insulin sensitivity [acarbose: glucose disposal rate before treatment 2.3 mg/kg body weight/min/insulin, after treatment 3.2; glibenclamide 2.2 vs. 2.1; placebo 2.6 vs. 3.0]. CONCLUSIONS: Our results show a more substantial improvement of glucose control under glibenclamide than under acarbose which, however, was not associated with an increase of insulin sensitivity.
Acarbose↗
Open regulation and practice in assisted dying.
The Netherlands, Oregon and Switzerland are the only areas in the world where assistance in dying has legally been practised in recent years. This article provides a detailed comparison of the history of the origins, legislation, monitoring systems and the extent of assistance in dying in these three places. It shows that the actual practice in Switzerland which, unlike Oregon, also allows assistance in suicide by means of infusions or gastric tubes, can today be technically quite similar to the permitted practice of active euthanasia on request in the Netherlands. Considering the preconditions restricting these practices, Swiss regulations are the most open, in that the law requires neither a medical second opinion (as in both the Netherlands and Oregon) nor the existence of a terminal illness (as in Oregon) as prerequisite to assistance in dying. In 2001, the proportion of assisted deaths (as reported to the authorities) in all deaths was almost ten times higher in the Netherlands (1.5% of all deaths) then in Oregon (<0.1% of all deaths) or Switzerland (0.2% of all deaths). The analysis of the different normative concepts underlying legislation reveals that in the Netherlands the basis for non-prosecution lies in the conflict of the physician's duties to respect life versus relief of suffering, while in the USA and in Switzerland the right-to-die concept plays a major role. These two concepts allow appreciation of distinctions between the roles of the physician in end-of-life practices and between assisted suicide and voluntary active euthanasia.
Euthanasia↗
Induction of antibodies to viscotoxins A1, A2, A3, and B in tumour patients during therapy with an aqueous mistletoe extract.
Mistletoe extracts exert immunomodulatory properties on immunocompetent cells of the innate as well as the specific immune system. These effects have been mainly ascribed to mistletoe lectin 1 (ML-1) present in most of the extracts. However, it became evident that also other components of these extracts may induce immunological reactions, and especially viscotoxins (VT) may be of relevance. Aim of the study was, therefore, to evaluate whether VT like ML-1 could activate B-cells and lead to the production of VT-specific antibodies. Sera from 26 patients with different tumours who were treated with the mistletoe extract ABNOBAviscum Mali (AM) 4 for at least 18 weeks were analysed before therapy and after 3, 6, 9, 12, and 18 weeks. Sera were tested by ELISA against the four viscotoxins A1, A2, A3, B, as well as against ML-1. Within the observation period twenty-four (92%) of the 26 patients developed antibodies to at least one of the four VT and 25 (96%) to ML-1. In most instances, anti-VT antibodies appeared after 6-9 weeks of treatment. The antibodies were predominantly of the IgG type belonging preferentially to the IgG1 and IgG3 subclass. IgE antibodies were found only to VT-B and to ML-1. There was no relation between the development of antibodies to VT and ML-1, and also cross-reactivity could be excluded with high probability. These data indicate that not only ML-1 but also VT induce immunological responses in patients treated with mistletoe extracts. Whether there is any relationship to the postulated anti-tumour effect of mistletoe extracts has, however, still to be evaluated.
Adjuvants, Immunologic↗
Hypoxia-induced hyperpermeability in brain microvessel endothelial cells involves VEGF-mediated changes in the expression of zonula occludens-1.
In vivo, hypoxia is known to damage the blood-brain barrier (BBB) leading to the development of vasogenic brain edema. Primary cultures of porcine brain derived microvascular endothelial cells were used as an in vitro BBB model to evaluate the mechanisms by which hypoxia regulates paracellular permeability. Paracellular passage across endothelial cell monolayers is regulated by specialized intercellular structures like the tight junctions (TJ). Zonula occludens-1 (ZO-1), a protein of the TJ, lines the cytoplasmic face of intact TJ. The continuity of the ZO-1 expression was disrupted during 24 h of hypoxia which correlated with a decrease of the protein level to 32 +/- 8% and with a twofold increase in the phosphorylation of ZO-1 in comparison to values determined at the start of the experiment. The localization and expression level of ZO-1 were maintained during hypoxia in the presence of a polyclonal antibody to vascular endothelial growth factor (VEGF) demonstrating that hypoxia-induced changes of the ZO-1 expression are mediated by VEGF. The effect of hypoxia on the ZO-1 distribution probably is not tissue- or cell-specific because similar changes of ZO-1 distribution were observed when the rat brain endothelial cell line RBE4 or the murine epithelial cell line CSG was used. Furthermore, ZO-1 changes correlated with small changes in actin distribution. These results suggest that hypoxia increases the paracellular flux across the cell monolayer via the release of VEGF, which in turn leads to the dislocalization, decreased expression, and enhanced phosphorylation of ZO-1. Science.
Actins↗
[Relaxation and the electromyographic identification of the recurrent laryngeal nerve].
INTRODUCTION: Electromyography for the identification of the recurrent laryngeal nerve is gaining ever more acceptance in thyroid surgery. Relaxation of the patient, e.g., to improve intubation conditions for anesthesia, carries a potential risk for error. METHOD: After definite identification of the recurrent laryngeal nerve and the vagus nerve (Neurosign 100, Magstim Co., Wales), ten consecutive patients were relaxed with mivacurium and atracurium besylate at a weight-dependent ED95 dosage. After peripheral relaxation was achieved (TOF-Watch, Organon Teknika Corp., at the adductor muscle of the thumb), the signal derived via the vocal muscle was assessed acoustically in 3-min intervals by the surgeon and graphically recorded by computer (EWACS, Inomed Co.). RESULTS: Complete peripheral relaxation was attained with mivacurium after 3-7 min and with atracurium after 7-11 min. A decrease in amplitude of the vocal muscle signal of >60% was recognized by the surgeon as a weakened signal and could be confirmed during an average duration of 13.3 min with mivacurium (maximum: 37 min) and 17.7 min with atracurium besylate (maximum: 23 min), respectively. Complete obliteration of the acoustic signal (<20% of the initial signal) occurred in three of six patients treated with mivacurium and in four of four patients treated with atracurium. CONCLUSIONS: The accuracy of electromyography of the recurrent laryngeal nerve can be substantially impaired by the administration of relaxants. If this medication cannot be dispensed with, the surgeon must be aware of the situation. In these cases, a peripheral relaxometer should also be employed to monitor relaxation as it subsides.
Adult↗
[Septic disease picture in a 33-year-old patient. Toxic shock syndrome].
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Adult↗