Screening for Celiac Disease: A Prospective Study on the Value of Noninvasive Tests

Objective : Celiac disease is frequently diagnosed in patients with nonspecific ahdominal symptoms. Therefore, highly sensitive, specific, and simple noninvusive screening tests are needed. Methods : This study compared the usefulness of IgG- and IgA-antigliadin antibodies, IgA-endomysial antibodies, and intestinal permeability in diagnosing celiac disease in 102 adult patients with nonspecific ahdominal symptoms. In addition, all patients underwent small bowel biopsy as a gold standard for the diagnosis of celiac disease. Results : Forty-nine patients were ultimately diagnosed as having celiac disease because of flat mucosa. Flatulence and signs and symptoms dating back to childhood were more frequent and abdominal pain less frequent ( p < 0.05) in celiac disease but were not helpful for screening. IgA-endomysiul antibodies showed a sensitivity and specificity of 1(M)%; an altered intestinal permeability had also a 100% sensitivity, but only 55% specificity. IgG- and IgA-untigliadin antibodies' sensitivity (73% and 82%, respectively) and specificity (74% and 83%, respectively) were much lower. Combining the two antigliadiu antibodies did not significantly improve the sensitivity and specificity. Conclusion : Our data show the advantage of IgA-endomysial antibodies for screening of celiac disease except in the case of patients with IgA-deficiency or dermatitis herpetiformis. In these patients, the permeability test could improve noninvasive differential diagnosis.     

Beziehungen zwischen Chromosomenbefund und Prognose bei akuter nicht-lymphoblastischer Leukämie

Zusammenfassung Bei 48 Patienten mit akuter nicht-lymphoblastischer Leukämie, die einheitlich nach dem Protokoll 7421 der acute leukemia group B behandelt worden waren, wurden Remissionsrate und überlebenszeit mit der Chromosomenkonstitution der Knochenmarkzellen bei Diagnosestellung korreliert. 45,8 % der Patienten hatten nur normale Metaphasen (N-Patienten), 31,3% hatten normale und abnorme Metaphasen (AN-Patienten) und 22,9 % hatten nur abnorme Metaphasen (AA-Patienten). Eine Beziehung zwischen Patientenalter und Chromosomenbefund war nicht erkennbar. Die Remissionsrate der N-Patienten war 72,7%, der AN-Patienten 60% und der AA-Patienten 36,4%. Die entsprechenden mittleren überlebenszeiten betrugen 12,5, 8,5 und 4,0 Monate. Der Unterschied in den Remissionsraten und überlebenszeiten zwischen Patienten mit und ohne normale(n) Metaphasen war signifikant. Patienten, die in eine Remission kamen, hatten innerhalb der 3 Gruppen eine ähnliche Prognose. Die im Vergleich zu anderen Berichten bessere Prognose unserer AA-Patienten könnte mit einer effektiveren Chemotherapie zusammenhängen.Professor Dr. E. Scherer, Direktor der Universitätsstrahlenklinik gewidmet     

Effects of long-term strontium ranelate treatment on the risk of nonvertebral and vertebral fractures in postmenopausal osteoporosis: Results of a five-year, randomized, placebo-controlled trial

OBJECTIVE: This study was undertaken to assess the effect of strontium ranelate on nonvertebral and vertebral fractures in postmenopausal women with osteoporosis in a 5-year, double-blind, placebo-controlled trial. METHODS: A total of 5,091 postmenopausal women with osteoporosis were randomized to receive either strontium ranelate at 2 gm/day or placebo for 5 years. The main efficacy criterion was the incidence of nonvertebral fractures. In addition, incidence of hip fractures was assessed, by post hoc analysis, in the subset of 1,128 patients who were at high risk of fractures (age 74 years or older with lumbar spine and femoral neck bone mineral density T scores -2.4 or less). The incidence of new vertebral fractures was assessed, using the semiquantitative method described by Genant, in the 3,646 patients in whom spinal radiography (a nonmandatory procedure) was performed during the course of the study. Fracture data were analyzed using the Kaplan-Meier survival method. RESULTS: Of the 5,091 patients, 2,714 (53%) completed the study up to 5 years. The risk of nonvertebral fracture was reduced by 15% in the strontium ranelate group compared with the placebo group (relative risk 0.85 [95% confidence interval 0.73-0.99]). The risk of hip fracture was decreased by 43% (relative risk 0.57 [95% confidence interval 0.33-0.97]), and the risk of vertebral fracture was decreased by 24% (relative risk 0.76 [95% CI 0.65-0.88]) in the strontium ranelate group. After 5 years, the safety profile of strontium ranelate remained unchanged compared with the 3-year findings. CONCLUSION: Our findings indicate that treatment of postmenopausal osteoporosis with strontium ranelate results in a sustained reduction in the incidence of osteoporotic nonvertebral fractures, including hip fractures, and vertebral fractures over 5 years.     

Effect of cardiac resynchronization therapy on global and regional oxygen consumption and myocardial blood flow in patients with non-ischaemic and ischaemic cardiomyopathy.

AIMS: We studied the effects of cardiac resynchronization therapy (CRT) on global and regional myocardial oxygen consumption (MVO2) and myocardial blood flow (MBF) in non-ischaemic (NICM) and ischaemic dilated cardiomyopathy (ICM). METHODS AND RESULTS: Thirty-one NICM and 11 ICM patients, all of them acute responders, were investigated. MVO2 and MBF were obtained by 11C-acetate PET before and after 4 months of CRT. In NICM global MVO2 and MBF did not change during CRT, while the rate pressure product (RPP) normalized MVO2 increased (P=0.03). Before CRT regional MVO2 and MBF were highest in the lateral wall and lowest in the septum. Under therapy, MVO2 and MBF decreased in the lateral wall (P=0.045) and increased in the septum (P=0.045) resulting in a more uniform distribution. In ICM, global MVO2, MBF, and RPP did not change under CRT. Regional MVO2 and MBF showed no significant changes but a similar tendency in the lateral and septal wall to that in NICM. CONCLUSION: CRT induces changes of MVO2 and MBF on a regional level with a more uniform distribution between the myocardial walls and improved ventricular efficiency in NICM. Based on the investigated parameters, CRT appears to be more effective in NICM than in ICM.     

Sodium-Hydrogen Exchange and Platelet Function

On stimulation of platelets with agonists, for example, thrombin, a rapid rise in intracellular pH is observed. This alkalinization is mediated by an increase in transport activity of the Na⁺/H⁺ exchanger isoform NHE1. In addition to this Na⁺/H⁺ exchange mechanism, platelets express bicarbonate/chloride exchangers, which also contribute to pH_i homeostasis. The main functions of NHE1 in platelets include pH_i control, volume regulation, and participation in cell signaling. The isoform NHE1 is highly sensitive toward inhibition by EIPA, Hoe694, and Hoe642. The regulation of NHE1 activity is complex and is not completely understood. It includes the MAP kinase cascade, the Ca/calmodulin system, several heterotrimeric G proteins (G12, G13, Gq, and Gi), small G proteins (ras, cdc42, rhoA), and downstream kinases (e.g., p160ROCK). Volume challenges stimulate tyrosine phosphorylation of cytoplasmic proteins, which ultimately activate NHE1. Thrombin, thromboxane, platelet-activating factor, angiotensin II, endothelin, phorbol ester, and Ca²⁺ ionophors stimulate NHE1 activity in platelets. Blockade of platelet NHE1 can inhibit platelet activation. With the development of highly specific NHE1 inhibitors, detailed investigation of the relationships between NHE1 activity and platelet activation now becomes feasible.     

Bedeutung der stummen Myokardischämie für die Identifikation und optimale Therapie von Patienten mit latenter koronarer Herzkrankheit

Although percutaneous transluminal coronary angioplasty (PTCA) improves the symptomatic status and exercise capacity of patients with coronary artery disease and stale or unstable angina pectoris, a beneficial effect on long-term prognosis has not been convincingly demonstrated so far. In totally asymptomatic patients with coronary artery disease, however, decision to undertake PTCA is greatly influenced by prognostic considerations. Usually, detection of silent myocardial ischemia in non-invasive examinations (exercise stress testing, ambulatory electrocardiographic monitoring) precedes the angiographic diagnosis of coronary artery disease in these patients.     

Combination Therapy of Active HBsAg Vaccination and Interferon-α in Interferon-α Nonresponders with Chronic Hepatitis B

Treatment with interferon- leads to cessation of viral replication in 30–40% of patients with chronic hepatitis B. Preliminary data suggest that therapeutic vaccination in patients with chronic HBV infection may be beneficial. The present trial was conducted to assess the efficacy of combination therapy of interferon- with HBsAg vaccination in patients who previously failed to respond to interferon- alone. Eighteen patients positive for HBsAg and HBeAg were included. Mean ALT was 81 ± 23 units/liter and 7 (39%) patients had HBV-DNA levels >2000 pg/ml. Patients received 5 million IU interferon- 2b (Intron A) thrice weekly for six months and recombinant HBsAg (Gen H-B-Vax) at the beginning and 4 and 12 weeks after initiation of interferon therapy. No serious side effects were seen during the trial period. Loss of HBeAg was seen in 39% (7/18), HBV DNA was undetectable in 50% (9/18), and ALT was normal in 56% 10/18) of patients six months after completion of therapy. Simultaneous administration of interferon- and HBsAg vaccination in patients previously not responding to interferon alone appears to be safe, well-tolerated, and it achieved response rates similar to or even higher than interferon in treatment naive patients. This combination therapy seems to offer a new and promising approach for patients with chronic hepatitis B virus infection.     

Doctor-Patient Communication

PURPOSE: The purpose of the study was to examine the effect of communication on rectal cancer patients quality of life over four years. Previous studies have either used short follow-up periods or examined only certain aspects of quality of life, such as anxiety and depression. METHODS: In a prospective, observational study, rectal cancer patients, recruited by clinicians over a two-year period, were sent questionnaires over four years. The clinical details of these patients were recorded by the Munich Cancer Registry. The psychological scores from the European Organization for Research and Treatment of Cancer QLQ-C30 and CR38 were the main outcome variables. RESULTS: Thirty-nine percent of the sample reported that some aspect of the communication they received was unclear (incomprehensible or too little). More than 60 percent wished to speak more with their physician. Younger patients and those in larger hospitals were more likely to report unclear communication (P < 0.05). Analyses of covariance, controlled for age, gender, adjuvant therapy, stoma, education, clinic, and comorbidity, demonstrated that role, emotional, and social functioning scores were consistently lower in patients reporting unclear communication. Additionally, these patients experienced more problems sleeping, poorer body image, more financial worries, and a worse future perspective. Repeated measures analyses indicated that sleeping problems and emotional and social functioning difficulties persisted for at least three years. CONCLUSION: Reports of unclear communication were associated with poorer quality of life in rectal cancer patients without disease progression.     

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