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Biomedical subjects

S Wagner

Publications and source records attributed to S Wagner.

At least 181 records · Page 10Linked to original sources

Percutaneous sonographic gastrostomy: method, indications, and problems.

OBJECTIVES: This study evaluated the application of ultrasound (US) guidance in the percutaneous placement of gastric feeding tubes in patients in whom endoscopic placement of a nutrition tube is not possible. METHODS: Thirty-eight patients with upper gastrointestinal obstruction were entered in a prospective study with US-guided nutrition tube application. Feasibility of placement, side effects, and nutritional states were monitored for a mean follow-up of 4 months. RESULTS: Ultrasound allowed rapid puncture after filling of the stomach with water through a nasal tube in 34/38 cases. In four cases a total upper gastrointestinal obstruction required an initial stomach insufflation through a direct puncture. Puncture-related major complications were not observed. Minor complications during the observation time were one late dislocation, five cases with broken material after about 6 months (four could be changed by using the Seldinger technique), and two minor local infections. The nutrition through feeding tubes stabilized body weight and body composition parameters. CONCLUSION: The percutaneous sonographic gastrostomy (PSG) is a safe and minimally invasive procedure for enteral nutrition in all cases with upper gastrointestinal obstruction when endoscopic placement of a feeding tube is not possible. Percutaneous sonographic gastrostomy may help to stabilize the nutritional parameters and general condition in patients with malignant diseases.

Adult↗

Hepatoma with severe non-islet cell tumor hypoglycemia.

We report a 22-yr-old male patient with chronic hepatitis B and a large, well differentiated hepatoma who developed episodes of symptomatic fasting hypoglycemia, which were caused by paraneoplastic secretion of unprocessed "big" insulin-like growth factor-II. Initially, the patient presented with normal liver function, which deteriorated during the clinical course. Therapeutic attempts to reduce tumor mass failed and the patient subsequently died because of metastases of the hepatoma. The pathophysiology of non-islet cell tumor hypoglycemia, differential diagnosis, and therapeutic options are discussed.

Adult↗

In vitro activities of terbinafine against cutaneous isolates of Candida albicans and other pathogenic yeasts.

Terbinafine is active in vitro against a wide range of pathogenic fungi, including dermatophytes, molds, dimorphic fungi, and some yeasts, but earlier studies indicated that the drug had little activity against Candida albicans. In contrast, clinical studies have shown topical and oral terbinafine to be active in cutaneous candidiasis and Candida nail infections. In order to define the anti-Candida activity of terbinafine, we tested the drug against 350 fresh clinical isolates and additional strains by using a broth dilution assay standardized according to the guidelines of the National Committee for Clinical Laboratory Standards (NCCLS) M27-A assay. Terbinafine was found to have an MIC of 1 microg/ml for reference C. albicans strains. For 259 clinical isolates, the MIC at which 50% of the isolates are inhibited (MIC50) of terbinafine was 1 microg/ml (fluconazole, 0.5 microg/ml), and the MIC90 was 4 microg/ml (fluconazole, 1 microg/ml). Terbinafine was highly active against Candida parapsilosis (MIC90, 0.125 microg/ml) and showed potentially interesting activity against isolates of Candida dubliniensis, Candida guilliermondii, Candida humicola, and Candida lusitaniae. It was not active against the Candida glabrata, Candida krusei, and Candida tropicalis isolates in this assay. Cryptococcus laurentii and Cryptococcus neoformans were highly susceptible to terbinafine, with MICs of 0.06 to 0.25 microg/ml. The NCCLS macrodilution assay provides reproducible in vitro data for terbinafine against Candida and other yeasts. The MICs for C. albicans and C. parapsilosis are compatible with the known clinical efficacy of terbinafine in cutaneous infections, while the clinical relevance of its activities against the other species has yet to be determined.

Antifungal Agents↗

Clinical outcome of transfemoral embolisation in patients with arteriovenous malformations of the liver in hereditary haemorrhagic telangiectasia (Weber-Rendu-Osler disease).

BACKGROUND: Arteriovenous malformations of the liver in Osler's disease may present as high output cardiac failure. A few case reports suggested that treatment with arterial embolisation may have beneficial effects in such patients. AIMS: To investigate the efficacy and safety of this treatment modality in a prospective pilot study. PATIENTS AND METHODS: Four women and one man (aged 39-59 years) with the dominant hepatic manifestation of Osler's disease presented with symptoms of cardiac failure and elevated cardiac output. Arteriovenous malformations were treated in three to five sessions with arterial embolisation using coils. The outcome was analysed by measurement of cardiac output and scoring of clinical symptoms. RESULTS: Embolisation was technically feasible in all patients and adequate occlusion of vascular malformations was achieved in four patients. After completion of therapy symptoms improved in four patients, while one patient suffered from abdominal pain due to cholangitis. One patient died seven months after the embolisation treatment from variceal bleeding. Mean cardiac output significantly decreased from 14.2 (range 12-17.3) l/min to 8 (range 5.9-10.6) l/min (p = 0.043). After a median follow up of 23 months (range 7-50 months), three of five patients had a long lasting improvement of clinical symptoms and cardiac function. CONCLUSIONS: This first treatment series of patients with dominant hepatic involvement in Osler's disease indicates that arterial embolisation may prevent cardiac failure by significantly lowering cardiac output.

Adult↗

Hereditary hemorrhagic telangiectasia: effective protocol for embolization of hepatic vascular malformations--experience in five patients.

PURPOSE: To develop a hepatic artery embolization protocol and investigate its efficacy in a prospective study treating patients with hereditary hemorrhagic telangiectasia and predominant hepatic involvement. MATERIALS AND METHODS: One man and four women with hereditary hemorrhagic telangiectasia presented with symptoms of high-output heart failure, abdominal angina, or severe portal hypertension. The hepatic arteries were embolized in stages in three to five sessions at 1- to 15-week intervals. After peripheral embolization with polyvinyl alcohol particles, proximal arteries were embolized with coils. Computed tomography and assessment of cardiac output were performed before and after therapy and at the end of follow-up (median, 25 months; range, 12-55 months). RESULTS: After embolization, analgesics and antiemetics were necessary for a median of 5 and 2 days, respectively. Other than ischemic cholangitis (one patient), no complications were observed. The mean cardiac output decreased significantly (P < .05) from 14.2 L/min to 8.0 L/min. Symptoms of high-output heart failure, abdominal angina, and portal hypertension resolved in all patients. Seven months after embolization, one patient died of postoperative sepsis after an unsuccessful surgical attempt to create a portacaval shunt. Delayed recurrence of symptoms was not noted in the other patients. CONCLUSION: In symptomatic patients with hereditary hemorrhagic telangiectasia and predominant hepatic involvement, embolization of the hepatic arteries in stages is well tolerated by the patients and results in good clinical improvement at midterm follow-up.

Adult↗

Impact of early risk stratification on the length of hospitalization in patients with acute Q-wave myocardial infarction. 'The 60-minutes myocardial infarction project'.

UNLABELLED: An assessment of individual risk factors may identify a subgroup of postinfarction patients at low risk, i.e. patients appropriate for early discharge. Using a large unselected population of the national registry, 'The 60-Minutes Myocardial Infarction Project', we (1) attempted to provide a retrospective analysis of clinical factors and in-hospital mortality in a population living on the 6th hospital day following admission to define a low-risk patient group with a residual in-hospital mortality of less than 1% eligible for early discharge, and (2) to analyze the current impact of risk stratification based on these clinical factors on the length of hospitalization. The study group consisted of 12,045 survivors on the 6th day after admission out of 14,980 patients of the registry with proven Q-wave myocardial infarction. Risk modeling was performed with multiple logistic regression. RESULTS: A total of 873 patients (7.3%) died after day 6 in hospital. The most important prognostic factors were cardiopulmonary resuscitation prior to admission (odds ratio, OR: 7.2, confidence interval, CI: 5.11-10.22), thrombolysis complicated by severe bleedings (OR: 6.2, CI: 1.2-31. 2) and age >70 years (OR 4.7, CI 3.51-6.39). The other more significant independent predictors of increased mortality were end-stage renal disease, age between 56 and 70 years, systolic blood pressure <95 mm Hg on admission, history of trauma </=2 months, cancer and left-bundle-branch block. Summarizing these nine groups of patients with the strongest association to in-hospital mortality, we defined a high-risk group comprising 79% of the AMI patients with a residual in-hospital mortality of 8.8%. On the other hand, by excluding these nine high-risk patient groups, a low-risk group of 21% of all AMI patients seems to be appropriate for early discharge (residual in-hospital mortality = 1.07%). However, in the current practice, there was no difference regarding the median length of hospital stay between the two risk groups. The low-risk patients were hospitalized 20 days compared to 22 days in the high-risk patients. CONCLUSION: Using a simple logistic regression model, which considers clinical factors of the early hospital phase, one fifth of the infarction patients can be stratified to be at low risk, and might be eligible for early hospital discharge. Currently, an individual risk stratification has no impact on the length of hospital stay in Germany.

Aged↗

Prevalence of Helicobacter pylori-associated gastritis in chronic urticaria.

BACKGROUND: Chronic urticaria and concurrent angioedema are frustrating problems for both physicians and patients. METHODS: 100 patients with chronic urticaria (mean duration 33.3+/-48.2 months) attending the urticaria consulting hour of our Department of Dermatology within 1 year were carefully analyzed for pathogenesis to avoid extensive unnecessary diagnostic approach in the future. RESULTS: In 43 cases a potential infectious trigger could be identified, 35 were of idiopathic origin, and 15 demonstrated pseudoallergic reactions to acetylsalicylic acid or food additives, 5 had antibodies to thyroid gland, and 2 had malignant diseases. Of patients with foci, 26 had Helicobacter pylori-associated gastritis, 9 chronic tonsillitis or sinusitis, 4 infections with Epstein-Barr virus or cytomegalovirus, 2 dental focal infections and 2 suffered from Yersinia infection. High prevalence of H. pylori gastritis was found since 47% of patients showed elevated H. pylori-specific IgA and/or IgG antibodies. 27 patients underwent endoscopy and in all but 1 (96%) antral H. pylori infection was found. In contrast, a prevalence rate of 37% among asymptomatic adults has been published. Disappearance (67%) or improvement of urticaria (24%) occurred in most antimicrobially treated patients after 3-12 weeks. In contrast, only 50% of untreated H. pylori-seropositive patients with chronic urticaria showed spontaneous remission or improvement within 12 weeks. Prevalence of H. pylori infection may even be underestimated since only 27/100 patients underwent endoscopy. It is suggested that H. pylori infection may be present at least in all seropositive subjects (47%). Moreover, we found H. pylori infection in 2 seronegative subjects demonstrating gastric complaints. CONCLUSIONS: Thus, measurement of H. pylori-specific antibodies and/or gastroscopy should be included in the diagnostic management of chronic urticaria to identify patients who may profit from eradication treatment with disappearance of long-standing and annoying urticaria symptomatology.

Adolescent↗

Ineffective cardiorespiratory function in hyperthyroidism.

Dyspnea on exertion is a common complaint in hyperthyroidism, and this thyroid dysfunction has been implicated as a primary cause of impaired effort tolerance. Using spirometry and spiroergometry, 42 patients with untreated hyperthyroidism were examined, and the condition was controlled 7 days later under propranolol monotherapy, as well as after 6 months in euthyroidism. While hyperthyroid, reduced forced vital capacity and tidal volume at the anaerobic threshold (AT) were observed in comparison to euthyroidism. Decreased oxygen (O2) pulse at AT (7 +/- 0.4 vs. 9.1 +/- 0.4 mL/beat, P = 0.0012) and at maximal exercise was noted in hyperthyroidism and was enhanced under propranolol (8.9 +/- 0.4 mL/beat, P = 0.0001). During exercise, the increment of minute ventilation (16.1 +/- 0.7 vs. 20.2 +/- 1.0 L/min, P = 0.0015), O2 uptake (9 +/- 0.5 vs. 11.4 +/- 0.5 mL/min/kg, P = 0.0022), O2 pulse (4.0 +/- 0.3 vs. 5.6 +/- 0.3 mL/beat, P = 0.0001), and heart rate (53 +/- 2 vs. 65 +/- 3 beat/min, P = 0.0004) was markedly lower in hyper- vs. euthyroidism. Work rate at AT and at maximum was reduced in hyper- vs. euthyroidism (107.4 +/- 3 vs. 141.1 +/- 4 watt, P = 0.0001). Negative correlations between free T3 and O2 pulse at AT (r = -0.59, P = 0.0005), delta O2 uptake (r = -0.54, P = 0.0007), delta minute ventilation (r = -0.48, P = 0.0007), and maximal work rate (r = -0.62, P = 0.0001) were noted. In hyperthyroidism, analysis of respiratory gas exchange showed low efficiency of cardiopulmonary function, respiratory muscle weakness, and impaired exercise capacity, which were reversible in euthyroidism.

Adult↗

Assessing information in T2-weighted MRI scans from secondary progressive MS patients.

BACKGROUND: Magnetic resonance imaging is used routinely for diagnosing MS and for objective assessment of the extent of disease as a marker of treatment efficacy in MS clinical trials. Nevertheless, in many clinical studies only weak correlations have been reported between MRI findings and clinical outcome measures. PURPOSE: The purpose of this study is to compare clinical outcome measures (neurologic scales) with MRI findings (evaluation of T2-weighted MRI scans using a semiautomated quantitative technique and with an independent assessment by a neurologist) in the context of a randomized clinical trial evaluating the efficacy of cladribine for treatment in secondary progressive MS. METHODS: Baseline, 6-month, and 12-month scans from 41 secondary progressive MS patients were examined and ranked in terms of lesion burden from the quantitative assessment and independently in terms of severity by neurologic evaluation. Comparison is made to monthly Expanded Disability Status Scale (EDSS) and Scripps Neurologic Rating Scale (SNRS) determinations in these patients with a nonparametric statistical procedure. RESULTS: Average rank correlations between any of the MRI assessment procedures and either clinical outcome measure were less than 0.15 in absolute magnitude. The average rank correlation between the two MRI assessment procedures was 0.10. There is only a weak degree of association between the MRI assessment procedures and the clinical parameters, although the study has statistical power in excess of 0.90 to find even a moderate level of association between them. CONCLUSIONS: Disease-related activity in T2-weighted scans of secondary progressive MS patients is a multidimensional construct, and is not summarized adequately solely by quantification of overall lesion burden or by assessment of severity. Neither method of summarizing information from T2-weighted scans is strongly related to measures of the clinical course of disease as assessed by the EDSS or SNRS.

Disease Progression↗

A rare case of bloody diarrhea: thrombosis of the V. mesenterica inferior following laparoscopic cholecystectomy.

Laparoscopic cholecystectomy has become the standard treatment for symptomatic cholecystolithiasis. The most common complications, as current experiences show, are bleeding, bile duct injury and non-technical complications like pneumonia. In some individual cases ischemic lesions of bowel by injury or thrombosis of intestinal vessels are described. Here we report the rare case of intestinal venous thrombosis following laparoscopic cholecystectomy. The complication clinically appeared within 24 h after operation starting with bloody diarrhea and mimicking inflammatory bowel disease. The patient, a 41-year old man, was treated with high-dose heparin and could be discharged after 44 days without complaints. Coloscopy six months after the event showed a restitution ad integrum.

Adult↗

[Enteroparesis caused by progressive fibrosis of the muscularis propria].

We would like to present the case of a 54-year-old patient who was admitted to the hospital with complaints of recurrent vomitus after food intake and associated weight loss. Endoscopy. barium X-ray of the small bowel and scintigraphy showed enteroparesis. Full-thickness biopsies achieved by explorative laparotomy revealed the pathological changes. The inner circular muscular layer was atrophic and replaced by fibrosis. The pathological findings were consistened with either visceral myopathy or isolated intestinal progressive systemic sclerosis. A sporadic nonfamilial type of visceral myopathy seems to be the most likely diagnosis in this case. Progressive systemic sclerosis seems to be unlikely as the patient presented with isolated gastrointestinal involvement and lack of appropriate autoantibodies. The diseases progression made an enteral supplementation impossible. Therefore a parenteral nutrition was started, which was characterized by a complicated clinical course. Persisting gastrointestinal complaints, recurrent port infections and lack of perspectives led to patient's diminished motivation for adequate sterile use of the port-system. This case report shows that besides the use of modern port-systems and antibiotics the psychological situation of patients treated with total parenteral nutrition is of great interest for optimal patient care.

Diagnosis, Differential↗

In vitro skewing of TCR transgenic CD4+ T cells from interleukin-2 deficient mice towards Th1 and Th2 in the absence of exogenous interleukin-2.

Previous experiments from several groups have indicated that in vitro priming for Th2 cells rigorously requires IL-4 but also depends on IL-2 [1-3]. On the other hand, IL-2 deficient mice characteristically have highly increased serum levels of the Th2-dependent isotypes IgG1 and IgE [4]. The overproduction of these isotypes is lost in IL-2 x IL-4 double deficient animals [5]. To readdress the question of a need for IL-2 for Th2 skewing in vitro we used T cells from IL-2-/- mice also transgenic for the DO11.10 TCR which is specific for OVA + IAd [6]. CD4+ cells from these mice were primed in vitro on IL-2-/- dendritic cells in the presence of OVA peptide and IL-4, IL-12 and IL-15, respectively. Following restimulation, cytokine production was analysed by intracellular staining with anti IL-4 and anti IFNgamma antibodies and flow cytometry. The data show that IL-4 primes IL-2-/- T cells for IL-4 production even in the absence of exogenous IL-2, while IL-12, as expected, polarises towards IFNgamma production. The ability to be primed for IL-4 production in the absence of IL-2 was also exhibited by naive CD4+CD62LlowTCR transgenic IL-2-/- cells and thus was not restricted to the CD44high CD62Llow cells which make up a high proportion of CD4+ cells in IL-2 deficient mice. We conclude that IL-2 is not absolutely required for in vitro skewing of naive T cells towards Th2.

Animals↗

The influence of tamoxifen on the maturation index of vaginal epithelium.

PURPOSE: The estrogenic effect of tamoxifen on vaginal epithelium in postmenopausal women with breast cancer was evaluated over a period of more than 48 months. METHODS: The tamoxifen group consisted of 118 postmenopausal patients, control group I of 30 postmenopausal women with breast cancer receiving no tamoxifen or hormonal replacement therapy and control group II of 40 postmenopausal women without breast cancer taking no hormones. We determined the maturation index of the vaginal epithelium. Pearson's chi-square-test and t-test for independent samples were used in the statistical analysis. RESULTS: The maturation index increased under tamoxifen therapy within the first 24 months from 0.4026 before taking tamoxifen (n = 64) to 0.6066 (n = 162, p < 0.0001) and in the following 24 months to 0.6325 (n = 122, p < 0.0001). Under tamoxifen intake of more than 48 months, an additional small increase of the maturation index to 0.6735 (n = 42, p < 0.0001) could be noticed. The maturation index in the tamoxifen group was statistically significantly higher (p < 0.0001) than in the control groups (control group I: 0.3975, p < 0.0001; control group II: 0.4102, p < 0.0001). CONCLUSION: An apparent increase in the maturation of the vaginal epithelium caused by the estrogenic effect of tamoxifen could be demonstrated.

Aged↗

Mechanisms of relaxation of rat aorta in response to progesterone and synthetic progestins.

OBJECTIVE: To compare the acute effects of progesterone, chlormadinone acetate (CMA), norethisterone acetate (NETA) and dienogest (DNG) with those of 17 beta-estradiol (17 beta-E2) on the vascular reactivity of male rat thoracic aorta. METHODS: Aortic rings with or without endothelium were placed in an organ bath for isometric tension recording. The integrity of the endothelium was assessed by the relaxant response of precontracted rings to acetylcholine (1 and 10 microM), which was diminished after mechanical removal of the endothelium. The concentrations of the steroid hormones were 0.01-10 microM. RESULTS: In vessels precontracted with phenylephrine (1 microM), CaCl2 (3 mM) or KCl (30 mM), progesterone, CMA and NETA (10 microM each) an endothelium-independent relaxation of 20-35% resulted, with a maximum response after 20-30 min, while DNG had a negligible effect in all experiments. The same concentration of 17 beta-E2 was twice as potent as the progestins. Indomethacin, the cyclooxygenase inhibitor and glibenclamide, an inhibitor of the ATP-sensitive potassium channels, did not affect the relaxant responses. The antagonists of progesterone receptors J 867 (1 microM) as well as of estrogen receptors ICI 182780 (1 microM) did not counteract the relaxation induced by progesterone and 17 beta-E2, respectively. Progesterone (10 microM) did not interfere with endothelium-dependent acetylcholine-induced relaxation of precontracted aortic rings. Pretreatment of the vessels with the hormones attenuated the maximal contractile response to phenylephrine. In the presence of verapamil (1 microM) or progesterone (10 microM) or 17 beta-E2 (1 and 10 microM) the concentration-response curves for calcium-induced contractions in K(+)-depolarized vessels were shifted to the right, with suppression of the maximum response. CONCLUSIONS: These studies suggest that in addition to 17 beta-E2 the progestins, progesterone, CMA and NETA caused a reduction of vascular tone, probably due to blockade of voltage-dependent and/or receptor-operated calcium channels.

Animals↗

Purine nucleoside phosphorylase. 1. Structure-function studies.

To probe the catalytic mechanism of human purine nucleoside phosphorylase (PNP), 13 active-site mutants were constructed and characterized by steady-state kinetics. In addition, microtiter plate assays were developed for both the phosphorolytic and synthetic reactions and used to determine the kinetic parameters of each mutant. Mutations in the purine binding site exhibited the largest effects on enzymatic activity with the Asn243Ala mutant resulting in a 1000-fold decrease in the kcat for inosine phosphorolysis. This result in combination with the crystallographic location of the Asn243 side chain suggested a potential transition state (TS) structure involving hydrogen bond donation by the carboxamido group of Asn243 to N7 of the purine base. Analogous to the oxyanion hole of serine proteases, this hydrogen bond was predicted to aid catalysis by preferentially stabilizing the TS as a consequence of the increase in negative charge on N7 that occurs during glycosidic bond cleavage and the associated increase in the N7-Asn243 hydrogen bond strength. Two residues in the phosphate binding site, namely His86 and Glu89, were also predicted to be catalytically important based on their alignment with phosphate in the X-ray structure and the 10-25-fold reduction in catalytic activity for the His86Ala and Glu89Ala mutants. In contrast, catalytic efficiencies for the Tyr88Phe and Lys244Ala mutants were comparable with wild-type, indicating that the hydrogen bonds predicted in the initial X-ray structure of PNP [Ealick, S. E., et al. (1990) J. Biol. Chem. 265, 1812-1820] were not essential for catalysis. These results provided the foundation for studies reported in the ensuing two manuscripts focused on the PNP catalytic mechanism [Erion, M. D., et al. (1997) Biochemistry 36, 11735-11748] and the use of mutagenesis to reverse the PNP substrate specificity from 6-oxopurines to 6-aminopurines [Stoeckler, J. D., et al. (1997) Biochemistry 36, 11749-11756].

Binding Sites↗

[Rare initial manifestation and differential diagnosis of primary sclerosing cholangitis].

BACKGROUND: Primary sclerosing cholangitis is most often diagnosed in middle-aged men who are suffering from inflammatory bowel diseases. CASE REPORT: A young, previously healthy woman presents with icterus of acute onset, high transaminases and positive hepatitis B virus serology. Ultrasound and nuclear magnetic resonance images demonstrate multiple liver tumors. After acute viral hepatitis as well as primary or secondary malignant liver tumors have been excluded as underlying diseases, diagnosis of primary sclerosing cholangitis is made. CONCLUSION: Differential diagnosis of primary sclerosing cholangitis should also be considered in cases with untypical primary presentation.

Acute Disease↗