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Biomedical subjects

H Schuster

Publications and source records attributed to H Schuster.

At least 19 recordsLinked to original sources

Otitis media and a neck lump--current diagnostic challenges for Paragonimus-like trematode infections.

A 29 year-old Nigerian studying in the UK presented with a neck lump and otitis media. Paragonimus-like trematode eggs were found in the neck lump aspirate. Morphologically these eggs resembled Paragonimus uterobilateralis or Achillurbainia congolensis. We favoured the diagnosis of achillurbainiasis over extrapulmonary paragonimiasis on the basis of clinical features and because we could not amplify DNA sequences using PCR primers specific for Paragonimus species. We discuss current diagnostic challenges for this rare parasitic infection.

Adult↗

Dysbiosis and pouchitis.

BACKGROUND AND METHODS: The exact aetiology of pouchitis is unknown, but an association with dysbiosis has been suggested. This is a retrospective review of 17 studies published between 1985 and 2005, identified by a search of the Medline, Pubmed and Embase databases. RESULTS: The methodology of the studies varied widely. Many were performed at a time when the distinction between a healthy and an inflamed pouch was vague; misclassification of patients makes the analysis of data difficult and conclusions uncertain. CONCLUSION: The evidence that dysbiosis is a cause of pouchitis is poor. Nevertheless, available data allow the construction of an algorithm to aid management and suggest a structured approach for future research.

Algorithms↗

Tesaglitazar, a novel dual peroxisome proliferator-activated receptor alpha/gamma agonist, dose-dependently improves the metabolic abnormalities associated with insulin resistance in a non-diabetic population.

AIMS/HYPOTHESIS: Insulin resistance is associated with abnormalities in lipid and glucose metabolism, which are major components of metabolic syndrome and risk factors for vascular disease. This study examined the effect of tesaglitazar (Galida), a novel, dual-acting peroxisome proliferator-activated receptor alpha/gamma agonist, on lipid and glucose metabolism in patients with evidence of insulin resistance. METHODS: A 12-week, multicentre, randomised, double-blind, placebo-controlled, dose-finding study compared the efficacy and safety of oral tesaglitazar (0.1, 0.25, 0.5 and 1.0 mg/day) and placebo in 390 non-diabetic patients with hypertriglyceridaemia (plasma triglyceride concentration >1.7 mmol/l) and abdominal obesity (waist-to-hip ratio >0.90 for men and >0.85 for women). RESULTS: A 1.0-mg dose of tesaglitazar reduced fasting triglycerides (the primary endpoint) by 37% (95% CI: -43% to -30%; p<0.0001), non-HDL-cholesterol by 15% (95% CI: -20% to -10%; p<0.0001) and NEFA by 40% (95% CI: -51% to -27%; p<0.0001), and increased HDL-cholesterol by 16% (95% CI: 8 to -24%; p<0.0001). At the end of treatment there was a dose-dependent increase in patients with pattern A LDL particle diameter (40% at baseline vs 87% at 12 weeks for tesaglitazar 1.0 mg). Tesaglitazar produced significant reductions in fasting insulin concentration (-35%; p<0.0001) and plasma glucose concentration (-0.47 mmol/l; p<0.0001). Respiratory infection and gastrointestinal symptoms were the most common adverse events and were similarly frequent in all groups. CONCLUSIONS/INTERPRETATION: Tesaglitazar was well tolerated and produced significant, dose-dependent improvements in lipid and glucose metabolism and insulin sensitivity. Tesaglitazar may have the potential to prevent vascular complications and delay progression to diabetes in these patients.

Alkanesulfonates↗

Combined open and endovascular stent grafting of internal carotid artery fibromuscular dysplasia: long term results.

BACKGROUND: Symptomatic fibromuscular dysplasia (FMD) of the internal carotid artery (ICA) can present as thrombo-embolic ischemic events, spontaneous or post-traumatic dissection, aneurysmal degeneration or intracranial haemorrhage and needs definitive surgical treatment. PATIENTS AND METHODS: Six patients and nine ICA with FMD were revascularised using a carotid approach with minimal exposure of the common, external and internal carotid arteries for covered stent repair. All patients were female, the age ranged from 30 to 65 years (mean 44). RESULTS: One patient suffered from a perioperative transient neurological deficit. Duplex revealed a patent stent. The patient fully recovered after 5h, not showing any changes on repeat CT scans. One patient developed a recurrent laryngeal nerve palsy. The symptoms gradually resolved within 1 month. No perioperative strokes or deaths occurred. During a mean follow up of 48 months (range 13-63) no thromboembolic neurological events, graft occlusions or haemodynamically significant stenoses occurred. CONCLUSION: ICA FMD stent grafting is an alternative to open surgery or percutaneous endovascular intervention with excellent long-term results.

Adult↗

Comparison of rosuvastatin with atorvastatin, simvastatin and pravastatin in achieving cholesterol goals and improving plasma lipids in hypercholesterolaemic patients with or without the metabolic syndrome in the MERCURY I trial.

AIM: The metabolic syndrome (MS) increases the risk of coronary heart disease, yet few data are available on the effects of statin treatment in improving lipid measures in patients with the syndrome. This analysis compares the effects of statin therapy on plasma low-density lipoprotein cholesterol (LDL-C) goal achievement and lipid levels in hypercholesterolaemic patients with or without the MS. METHODS: The Measuring Effective Reductions in Cholesterol Using Rosuvastatin TherapY I (MERCURY I) trial compared rosuvastatin 10 mg with atorvastatin 10 mg and 20 mg, simvastatin 20 mg and pravastatin 40 mg over 8 weeks in patients with coronary or other atherosclerotic diseases or diabetes who had fasting levels of LDL-C of >or=2.99 mmol/l and triglycerides of <4.52 mmol/l. Modified National Cholesterol Education Program Adult Treatment Panel III (ATP III) criteria for the MS were met by 1342 (43%) of 3140 patients. RESULTS: LDL-C goal achievement rates and reductions in LDL-C, total cholesterol and non-high-density lipoprotein cholesterol (HDL-C) were similar in patients with and without the MS within statin treatment groups; triglycerides were reduced more and HDL-C tended to be increased more in patients with the MS, as expected. Treatment with rosuvastatin 10 mg was more effective in allowing patients with and without the MS to reach European and ATP III LDL-C goals, compared to atorvastatin 10 mg, simvastatin 20 mg and pravastatin 40 mg (p < 0.0001 for all comparisons); consistently produced greater reductions in LDL-C, total cholesterol and non-HDL-C, compared to these treatments; and produced similar or greater reductions in triglycerides and increases in HDL-C, compared to the other treatments. CONCLUSIONS: Statin therapy is effective in allowing LDL-C goal achievement and improving the lipid profile in hypercholesterolaemic high-risk patients with the MS. Rosuvastatin 10 mg presents significant advantages in goal achievement and lipid lowering over other statins at commonly used doses in patients both with and without the MS.

Aged↗

Ultrasound-guided percutaneous ethanol ablation of parathyroid hyperplasia: preliminary experience in patients on chronic dialysis.

OBJECTIVE: We report on a 3-year experience using single-shot, ultrasonography-guided, percutaneous ethanol ablation (PEA) of hyperplastic parathyroid glands in chronic dialysis patients suffering from secondary or tertiary hyperparathyroidism. MATERIALS AND METHODS: Seventeen uraemic patients (mean age 52 +/- 14 years) with hypercalcaemia and elevated serum levels of parathyroid hormone were assessed for ethanol ablation. Ten patients did not fulfil the inclusion criteria and underwent surgical parathyroidectomy. Seven patients were treated using PEA. RESULTS: All patients treated with PEA tolerated the procedure well, and no major complications were observed. Three out of seven patients underwent further ethanol ablation due to recurrent symptomatic hyperparathyroidism. Following the procedures, serum values of total calcium and parathyroid hormone remained within target range with concomitant medical therapy in all patients. CONCLUSION: PEA performed as a single-shot therapy can be used as a minimally invasive and safe supplement to medical therapy in the treatment of secondary or tertiary hyperparathyroidism in selected patients. In case of recurrence, treatment can be repeated without any problems.

Adult↗

Severe sporotrichoid infection with Mycobacterium szulgai.

Mycobacterium szulgai is a nontuberculous, acid-fast bacillus or atypical mycobacteria, which prior to 1972 was not thought of as a pathogen. Since then most cases reported in the literature have been of pulmonary disease with only a few case reports of cutaneous disease. Our patient, who had an underlying, uncategorized, immunosuppressive condition, presented with multiple severe ulcers spreading proximally up the arms in a sporotrichoid pattern with more scatttered lesions on his legs. He made a full recovery with appropriate antimicrobial treatment.

Adult↗

Improving lipid management--to titrate, combine or switch.

Despite the benefits of statin therapy, cholesterol management remains suboptimal and many patients do not achieve their recommended low-density lipoprotein cholesterol (LDL-C) goals. The use of insufficient doses, limited drug effectiveness and poor patient compliance may contribute to the treatment gap. Options for improving lipid management include dose titration, combination therapy or prescribing a more efficacious statin. LDL-C reductions are generally modest when patients' current statin dose is titrated, and there may be an increased potential for adverse effects. Combining statin therapy with another lipid-modifying agent can provide additional LDL-C reductions, but cost, tolerability and compliance should be considered. In general, switching to a more efficacious statin is a cost-effective way of enabling more patients to achieve recommended targets without increasing dosages. When considering the options available, physicians should balance efficacy, cost and safety to enable more patients to attain LDL-C goals and achieve greater therapeutic gain from statin treatment.

Cholesterol, LDL↗

Increased rates of pulmonary metastases following sham laparotomy compared to CO2 pneumoperitoneum and the inhibition of metastases utilizing perioperative immunomodulation and a tumor vaccine.

BACKGROUND: Subcutaneous tumor growth and establishment is increased after laparotomy; significantly smaller increases have been noted after CO2pneumoperitoneum (CO2 pneumo). Less is known about the impact of surgery on the fate of blood borne tumor cells. The extent of surgical abdominal wall trauma also correlates with the extent of early postoperative immunosuppression and the inflammatory response. These changes may favor lung metastases (mets) formation. This study's hypotheses were: (a) a reduction in surgical trauma or (b) a perioperative (periop) tumor vaccine or nonspecific immune up-regulation would limit lung mets formation. An intravenous tumor cell injection lung met model was used to test these hypotheses. METHODS: Study 1 determined the incidence of lung mets after sham laparotomy (OP) and CO2 pneumo. Three groups were studied (n=25/group) : Anesthesia control (AC), CO2 pneumo, and OP. 1 x 105 TA3Haushka adenocarcinoma cells were inoculated via tail vein injection into all mice immediately after surgery. Study 2 determined the impact of perioperative immunomodulation on lung mets formation. Five groups were studied (n=20/group) : AC, OP, OP + Monophosphoryl Lipid A (MPLA), OP + lysed tumor cells (LTC), or OP + MPLA + LTC. The vaccine consisted of 5 x 105 lysed TA3Ha tumor cells (LTC) and was given 5 times preop and once postop to the vaccine groups. MPLA, the nontoxic moiety of lipopolysaccharide, was used both as a vaccine adjuvant in the OP + MPLA + LTC group and as a nonspecific perioperative immune up-regulator in the OP + MPLA group. Five periop injections of MPLA were given to the OP + MPLA group. All mice were given tail vein injections of tumor cells after surgery. Fourteen days after surgery all mice were sacrificed, the lungs transected en bloc, and India ink injected into the trachea. The lungs were placed in Fekete's solution to counterstain the tumor foci white. The number of surface lung metastases was determined by two blinded observers, separately. RESULTS: In Study 1, there were significantly more lung tumors in the OP group (median=31.5) than the AC group (median=9; p<0.05) or the CO2 Pneumo group (median=6.5; p<0.05). There were no significant differences in the number of metastases between the AC and the CO2 Pneumo groups or in the incidence of animals in each group with 1 or more lung mets. In Study 2 significantly fewer metastases were noted for the Op + LTC group (median=3; p<0.05) and the OP + LTC + MPLA group (median=0; p<0.05) when compared to the OP group (median=20). Although the OP + MPLA group mice had fewer metastases (median=4) than the OP group, this difference was not significant. Significantly fewer of the OP + LTC + MPLA group mice developed one or more lung tumors than in the OP, OP + MPLA, and the OP + LTC groups. CONCLUSIONS: Full sham laparotomy was associated with more postoperative lung metastases than CO2 pneumo or anesthesia alone in this murine model. Up-regulation of the immune system in the perioperative period with lysed tumor cells, alone or in combination with MPLA, resulted in significantly fewer postoperative lung metastases. MPLA alone resulted in a less marked reduction of lung metastases.

Adenocarcinoma↗

Expansion of marginal zone B cells is not sufficient for the development of renal disease in NZBxNZW F1 mice.

The mechanisms which govern the production of autoantibodies and of tissue damage during systemic lupus (SLE) are still unclear. In the NZBxNZW F1 (BW) model of SLE glomerulonephritis, the activation and commitment of B cells are thought to play a major role in disease progression. Previous analysis has suggested that these mice have a substantial increase of marginal zone (MZ) B cells before the occurrence of the disease. Owing to the probable role of this B cell subset in autoantibody production, it was important to define the possible link between this abnormality and the occurrence of kidney damage. Using cytofluorometry analysis, we followed the splenic MZ B cell phenotype in different series of mice with shared autoimmune genetic background and histologically defined renal status. By comparing BW females and BW males, NZB and NZW mice, we confirm that BW mice have an increase in MZ B cells but this MZ B cells expansion is not directly linked to tissue lesions. Genetically modified BW female mice with a restricted repertoire of B and T cell antigen receptors, and which do not develop nephritis, exhibit the same increase of MZ B cells, suggesting that this increase does not depend on a specific set of antigens. Moreover, our analysis brings to light a pre-disease state in BW males, with autoantibody production and mesangial deposits.

Animals↗

Parasitic infections of the intestine.

Intestinal protozoal infections cause significant disease not only in the tropics but also in immunocompromised hosts and returning travellers in the developed world. Precise diagnosis of protozoal intestinal infection by microscopy can be difficult. Enzyme immunoassays for antigen detection are being used for some protozoal infections with some limitations which will, it is hoped, be overcome by molecular techniques. Nucleic acid amplification techniques could help improve detection of microsporidial species, which are difficult to detect microscopically and allow differentiation between Entamoeba histolytica and Entamoeba dispar. Definitive treatment for Cryptosporidium parvum infection remains elusive but new drugs are being evaluated. Cessation of thiabendazole production should not affect therapy of intestinal nematode infections as potent alternative therapy is available.

Animals↗

Efficient and cost-effective single nucleotide polymorphism detection with different fluorescent applications.

Three methods-5'nuclease assay with TaqMan, minisequencing, and oligonucleotide ligation assay (OLA)-were compared to detectfive single nucleotide polymorphisms (SNPs) in three separate genes. Each method had advantages and disadvantages. The 5' nuclease assay was the fastest and required only a single step. OLA was the most time consuming to optimize, but once running it was the least expensive method. Minisequencing was universal; however, the technique was also the most expensive. All three methods were reliable and highly effective. Investigators must consider their goals in terms of time, sample number, and expense when selecting among these genotyping techniques.

Base Sequence↗

Beta-2 adrenergic receptor gene variations and blood pressure under stress in normal twins.

We tested the hypothesis that blood pressure (BP) responses to physical and mental stress are associated with polymorphisms in the beta-2 adrenergic receptor (AR) gene. We studied normotensive, young, monozygotic (MZ) and dizygotic (DZ) twins. The subjects underwent automated BP measurements at the brachial and digital arteries and were subjected to mental arithmetic and cold pressor stress. We used allele-specific PCR to genotype four single nucleotide polymorphisms in the beta-2 AR gene. The most functionally relevant polymorphism in the beta-2 AR gene, Arg16/Gly, was associated with systolic and diastolic BP under resting conditions, during mental arithmetic, and during the cold pressor test, as well as with the increase in diastolic BP during both forms of stress. These findings support a role for the beta-2 AR gene in BP regulation. They also indicate that the beta-2 AR gene influences the level of not only resting but also stress-related BP.

Blood Pressure↗

Severely impaired baroreflex-buffering in patients with monogenic hypertension and neurovascular contact.

BACKGROUND: We identified a family with a monogenic syndrome of hypertension, brachydactyly, and neurovascular contact of the brain stem. Neurovascular contact of the ventrolateral medulla may lead to arterial hypertension by interfering with baroreflex function. METHODS AND RESULTS: In 5 patients with monogenic hypertension (18 to 34 years old), we conducted detailed autonomic function tests. Blood pressure during complete ganglionic blockade was 134+/-4.9/82+/-4.1 mm Hg and 90+/-6/49+/-2.4 mm Hg in patients and in control subjects, respectively. During ganglionic blockade, plasma vasopressin concentration increased 24-fold in control subjects and <2-fold in patients. In patients, cold pressor testing, hand-grip testing, and upright posture all increased blood pressure excessively. In contrast, muscle sympathetic nerve activity was not increased at rest or during cold pressor testing. The phenylephrine dose that increased systolic blood pressure 12.5 mm Hg was 8.0+/-2.0 microg in patients and 135+/-35 microg in control subjects before ganglionic blockade and 5.4+/-0.4 microg in patients and 13+/-4.8 microg in control subjects during ganglionic blockade. CONCLUSIONS: In patients with monogenic hypertension and neurovascular contact, basal blood pressure was increased even during sympathetic and parasympathetic nerve traffic interruption. However, sympathetic stimuli caused an excessive increase in blood pressure. This excessive response cannot be explained by increased sympathetic nerve traffic or increased vascular sensitivity. Instead, we suggest that baroreflex buffering and baroreflex-mediated vasopressin release are severely impaired.

Adolescent↗

A pathway model of lipid metabolism to predict the effect of genetic variability on lipid levels.

Complex phenotypes such as serum lipid concentrations involve numerous genes and require the analysis of the combined effects of these gene products. We modeled the interactions of six key lipid metabolism genes by means of differential equations. We tested the model by inserting the effects of known mutations in the low-density lipoprotein receptor gene and the lipoprotein lipase gene, as well as the effects of a high-fat diet, and observed that the predictions corresponded very well to published measurements. Models such as the one that we present here will become indispensable for analyzing and understanding the effects of variation in multiple genes.

Carrier Proteins↗

Secretion of MCP-1 and IL-6 by cytokine stimulated production of reactive oxygen species in endothelial cells.

Endothelial cells are known to produce reactive oxygen species by several mechanisms. Functional consequences of increased production of reactive oxygen species were investigated in vitro after stimulation with several proinflammatory cytokines. Time dependent increases in DCF-fluorescence as a measure of reactive oxygen load were quantified in single cells after incubation with TNF-alpha, IL-1 and IFN-gamma. The increased DCF-fluorescence was inhibited by cell permeant antioxidative substances Tiron and Tempol. NMMA, an inhibitor of nitric oxide synthase reduced endothelial DCF-fluorescence only marginally, indicating a minor participation of nitric oxide production in this detection system. Cytokine induced endothelial DCF-fluorescence increased in the presence of NADH, whereas coincubation with NADPH or xanthine was without effect. Flavoenzyme inhibitor diphenyliodonium abolished stimulated DCF-fluorescence. Cytokine induced release of MCP-1 and IL-6 by endothelial cells was completely inhibited in the presence of Tiron and Tempol, whereas NMMA was less effective. Collectively these data indicate that cytokine stimulated endothelial cells increase their reactive oxygen species production probably via NADH oxidase and this production may critically be involved in the secretion of MCP-1 and IL-6.

Antioxidants↗