In through the out door: serology for atrophic gastritis

Gastric cancer remains the second biggest cause of cancer death worldwide. The most common type of gastric cancer, the intestinal type, is usually preceded by chronic atrophic gastritis. Gastritis serology is therefore of crucial importance for population-based screening and prevention studies. Helicobacter pylori serum antibodies can adequately diagnose inflammation of the gastric mucosa, but the serological diagnosis of atrophic gastritis is more hazardous. Many tests have been used for this purpose, either alone or in various combinations. Depending on the population, pepsinogens and gastrin often have a high specificity but low sensitivity for the diagnosis of atrophic gastritis, whereas antibodies against H. pylori or CagA have a high sensitivity but low specificity. A combination of two tests, e.g. H. pylori antibodies and pepsinogen I, may balance this issue and provide adequate screening tools, although there is a clear need for further improvement and simplification of serological testing for atrophic gastritis.     

Threshold effects of glucose transporter-4 (GLUT4) deficiency on cardiac glucose uptake and development of hypertrophy

The aim of this study was to investigate the metabolic and structural consequences of a decrease in glucose transporter-4 (GLUT4) levels on the heart. The CreLoxP system was utilised to delete GLUT4 in muscle tIssue including heart. The presence of the PGK-neoR cassette in the GLUT4-Lox mice resulted in reduced expression in all tIssues to levels 15-30% of wild-type control mice. In mice expressing Cre recombinase, there was a further reduction of GLUT4 in cardiac tIssue to almost undetectable levels. Cardiac glucose uptake was measured basally and during a euglycaemic/hyperinsulinaemic clamp using 2-deoxy-[1-(14)C]glucose. Insulin-stimulated glucose uptake was normal in hearts expressing 15% of normal GLUT4 levels but markedly reduced in mice with more profound reduction in GLUT4. Cardiac enlargement occurred only when GLUT4 levels were less than 5% of normal values. In heart there is a threshold level of GLUT4 above which insulin-stimulated glucose uptake is maintained. As little as 5% of normal GLUT4 levels expressed in heart is sufficient to prevent the development of cardiac hypertrophy.     

Rheopheresis in patients with ischemic diabetic foot syndrome: results of an open label prospective pilot trial

Rheopheresis is a specific application of membrane differential filtration, synonymous with double filtration plasmapheresis, for extracorporeal hemorheotherapy. Safety and efficacy of Rheopheresis for wound healing and skin oxygenation were investigated in patients with ischemic diabetic foot syndrome. Eight patients with type 2 diabetes mellitus and non-healing foot ulcers caused by severe ischemic diabetic foot syndrome were treated by a series of seven Rheopheresis sessions in a time span of 11 weeks. Wound healing had not been detectable under conditions of standardized wound care during at least 2 months. Wound status was classified by its morphology, severity and location, according to the criteria of Wagner. Transcutaneous oxygen pressure (tcPO2), laser Doppler flowmetry and vital capillary microscopy were repeatedly performed to monitor the effects of the Rheopheresis treatment series on microcirculation and skin blood flow. Laboratory parameters of blood rheology, endothelial function and inflammatory state were measured in addition to safety parameters. In four patients (baseline Wagner stage 2), Rheopheresis accelerated wound healing of foot ulcers and was associated with an improvement of Wagner stage and a pronounced increase in tcPO2. In two patients (baseline Wagner stage 2), wound healing was unchanged but mean tcPO2 increased, allowing successful minor amputation. Values of tcPO2 remained stable and enhanced for the 3 months follow-up period. In two patients (baseline Wagner stage 4 or 5), no improvements in foot lesions were observed within the treatment period. As an adjunct therapeutic option, Rheopheresis may preserve a functional lower extremity, delay amputation or reduce the extent of amputation.     

Autofluorescence bronchoscopy--a comparison of two systems (LIFE and D-Light)

BACKGROUND: Autofluorescense (AF) bronchoscopy is an established method to detect dysplasia and carcinoma in situ (CIS). Several different systems are currently available. OBJECTIVES: This study aimed to directly compare the LIFE system (Xillix Technologies, Vancouver, Canada) and the D-light system (Storz, Tuttlingen, Germany). METHODS: In a prospective study performed between May 1999 and October 2000, we examined patients with risk factors for lung cancer that underwent bronchoscopy with both (LIFE and D-light) systems in a crossover design. The findings were classified into normal, abnormal and suspicious lesions by independent investigators and then compared. RESULTS: This study comprised 332 patients (220 males, 112 females, mean age 62.7 years, range 40-85); 1,117 biopsies were studied (mean biopsy rate 3.4/patient). In 817 biopsies, mucosal areas were classified as normal with respect to control biopsy specimens, 113 as abnormal and 187 as suspicious using AF bronchoscopy. The histological examination showed normal tissue in 850 cases, in 55 cases scarring or inflammation, in 62 meta- or dysplasias, in 11 carcinomas in situ and in 127 invasive tumors. In only 5 cases, classifications were found to be different between the two systems (2 normal, 2 dysplasias, 1 invasive tumor). The mean time for the LIFE system examination amounted to 11.7 min (range 6.2-19.5) and for the D-light system to 7.4 min (range 4.3-11.9). This difference was statistically significant (p < 0.001). CONCLUSION: Both systems yielded comparable results. The examination time was significantly shorter with the D-light system, which may be explained by the more comfortable handling and the direct switch between white light and AF imaging. Different trials using either methodology could be compared directly.     

Left ventricular dyssynchrony predicts benefit of cardiac resynchronization therapy in patients with end-stage heart failure before pacemaker implantation

We evaluated patients with end-stage heart failure who have a high likelihood of response to cardiac resynchronization therapy (biventricular pacing). It appears that 20% of patients do not respond to this expensive therapy despite the use of selection criteria (dilated cardiomyopathy, heart failure, New York Heart Association class II or IV, left ventricular ejection fraction <35%, left bundle branch block, and QRS >120 ms). The presence of left ventricular dyssynchrony is needed to result in improvement after cardiac resynchronization therapy.     

Balloon angioplasty of coarctation of the aorta: a safe alternative for surgery in adults: immediate and mid-term results.

Patients with coarctation of the aorta can be treated either with surgery or with balloon angioplasty. So far, the last method has proved to be successful in children, but results of this treatment in (young) adults are virtually unknown. The aim of this study was to evaluate the immediate and mid-term follow-up results of balloon angioplasty of native coarctation in (mainly young) adults. Coarctation of the aorta was diagnosed by means of ultrasound or angiography, and defined as a stenosis with a pressure gradient greater than 20 mm Hg. The balloon angioplasty-procedure was carried out under complete anesthesia, and was considered to be successful, if the pressure gradient was reduced to less than 20 mm Hg. Nineteen consecutive adults (12 males, 7 females; aged 14-67 years, median 29) with native coarctation were treated from 1995-99. Mean pressure gradient decreased from 49.3+/- 20.8 to 4.8+/-8.2 mm Hg (P<0.0001). One patient showed a suboptimal result with a residual pressure gradient of 28 mm Hg. In one other patient a stent was placed on request of the referring physician. Follow-up was 100% complete and ranged from 3-47 months (mean 20.2+/- 12.9). At 1-year follow-up mean systolic blood pressure was reduced from 159.4+/-19.5 to 132.5+/-17.6 mm Hg (n = 18; P<0.0001), and mean ankle-arm pressure index improved from 0.73+/-0.09 to 0.96+/-0.05 (n = 18; P<0.0001). Anti-hypertensive medication could either be reduced or stopped in 7 patients (53.8%). With ultrasound or angiography or MRI, no patients had signs of aneurysm formation or worsening restenosis during follow-up. In adult patients with uncomplicated native coarctation of the aorta, balloon angioplasty (without stenting) would seem to be an excellent and safe alternative for surgery. In our hospital it has completely replaced surgical correction in such patients.     

Exercise and thrombosis

Long-term moderate or strenuous physical activity is associated with a considerable reduction in cardiovascular morbidity and mortality. This article reviews the evidence to suggest that part of the effect is mediated through the effects on thrombogenic factors. Fibrinogen has been convincingly shown to be an independent cardiovascular risk factor. Other hemostatic and fibrinolytic parameters that are predictive of coronary events include factor VII, platelet hyperreactivity, plasminogen activator inhibitor-1, and tissue-plasminogen activator. The effects of exercise on fibrinogen have been studied intensively. One randomized, controlled trial, two other intervention studies and a large number of population-based cross-sectional studies have consistently found an inverse relationship between various measures of sport activity or leisure activity and plasma levels of fibrinogen. The magnitude of the effect might be associated with a sizeable reduction in major coronary events. Relatively few data are available on endurance exercise and markers of the fibrinolytic system. Acute exercise leads to a transient activation of the coagulation system, which is accompanied by an increase in the fibrinolytic capacity in healthy subjects. However, patients with ischemic heart disease, who cannot increase their fibrinolytic potential, may be at considerable risk for acute ischemic events if they are exposed to unaccustomed strenuous physical exertion. It is concluded that physical activity has profound effects on thrombogenic factors and that these mechanisms could contribute to its beneficial cardiovascular effects.     

Prognostic significance of increased IL-10 production in patients prior to allogeneic bone marrow transplantation

IL-10 is a potent immunosuppressant which inhibits allo-antigen-specific T cell responses. In addition, IL-10 is a strong endogenous anti-inflammatory cytokine. To investigate the role of IL-10 in the induction of acute GVHD following allogeneic bone marrow transplantation (BMT) we performed a prospective study on spontaneous IL-10 production by peripheral blood mononuclear cells (PBMNC) in 84 patients admitted for allogeneic BMT. High spontaneous IL-10 production by PBMNC at the time of admission and prior to any preparative treatment correlated with a subsequent low incidence of GVHD and transplant-related mortality (8%), as compared to patients with low or intermediate IL-10 production (50%, P < 0. 01). Our data demonstrate the prognostic significance of increased IL-10 production in BMT patients and suggest a major role of IL-10 in maintaining immunobalance in the setting of allogeneic BMT. Bone Marrow Transplantation (2000) 25, 237-241.     

Acute pneumatosis cystoides intestinalis following allogeneic transplantation -- the surgeon's dilemma

Pneumatosis cystoides intestinalis (PCI) is still a poorly understood phenomenon, currently considered to result from primary mucosal insult from varying causes. We report a case of severe PCI in a patient with chronic GVHD after bone marrow transplantation (BMT) performed to treat secondary AML. Post BMT, the patient suffered acute intestinal and cutaneous GVHD, eventually developing intestinal and biopsy-proven cutaneous chronic GVHD, which necessitated continuous steroid therapy. Chronic pancreatitis associated with GVHD was diagnosed by explorative surgery in February 2000 on the basis of increasing epigastric discomfort, tumour marker (CA 125) increase and the CT finding of a suspicious mass in the pancreas. Readmission occurred in April 2000 for rapid onset of inferior abdominal pain with distinct peritoneal signs. Relaparotomy, deemed necessary on the grounds of both clinical and radiological findings, revealed marked PCI of the ascending and transverse colon and attached mesentery in an otherwise intact gastrointestinal tract. Post-operative reconvalescence was uneventful, with no clinical or radiological recurrence of PCI in the following 10 months. In the context of a review of the relevant literature, this case report illustrates the complex underlying pathophysiology, and difficulty in making a differential diagnosis and treating PCI.