Accuracy and 'range of uncertainty' of oscillometric blood pressure monitors around the upper arm and the wrist

BACKGROUND: Although they have been marketed widely, few data about the diagnostic accuracy of blood pressure monitors are available. METHODS: Repeated measurements of blood pressures in 85 patients were performed in random sequence with two oscillometric blood pressure monitors around the upper arm (Visomat OZ2) and the wrist (Omron R3( and with a standard sphygmomanometer. The oscillometric blood pressure monitors were validated according to protocols of the British Hypertension Society (BHS) and the American Association for the Advancement of Medical Instrumentation (AAMI). Subsequently, sensitivity and specificity of these monitors for the diagnosis of hypertension or exclusion of the possibility of its presence in a general medical outpatient population were calculated. RESULTS: Sphygmomanometric readings exceeded oscillometric blood pressure measurements by 3.7+/-7.5/4.8+/-5.6 mmHg (systolic/diastolic) for the upper arm and 5.7+/-6.2/6.8+/-6.8 mmHg for the wrist. Deviations occurred in both directions and were higher for blood pressures in the hypertensive range. Oscillometric blood pressure measurements at the upper arm, but not at the wrist, satisfied validation criteria of BHS and AAMI protocols. Optimal sensitivity and specificity for the diagnosis of hypertension, defined as blood pressure > 140/90 mmHg with a standard sphygmomanometer, was achieved with blood pressure limits of 133/82 mmHg for the Visomat OZ and 131/80 mmHg for the Omron R3. CONCLUSIONS: Average sphygmomanometer values exceed oscillometrically measured blood pressure values but individual disagreements cannot be predicted. Measurements at the upper arm are more accurate than are those at the wrist according to the validation protocols of the BHS and AAMI. Additional appraisal of sensitivities and specificities and of a 'range of uncertainty' for the diagnosis of hypertension may allow better judgement of accuracy of individual oscillometric blood pressure measurements.     

Geldanamycin-induced Lyn dissociation from aberrant Hsp90-stabilized cytosolic complex is an early event in apoptotic mechanisms in B-chronic lymphocytic leukemia

Lyn, a tyrosine kinase belonging to the Src family, plays a key role as a switch molecule that couples the B-cell receptor to downstream signaling. In B-CLL cells, Lyn is overexpressed, anomalously present in the cytosol, and displays a high constitutive activity, compared with normal B lymphocytes. The aim of this work was to gain insights into the molecular mechanisms underlying these aberrant properties of Lyn, which have already been demonstrated to be related to defective apoptosis in B-cell chronic lymphocytic leukemia (B-CLL) cells. Herein, Lyn is described to be in an active conformation as integral component of an aberrant cytosolic 600-kDa multiprotein complex in B-CLL cells, associated with several proteins, such as Hsp90 through its catalytic domain, and HS1 and SHP-1L through its SH3 domain. In particular, Hsp90 appears tightly bound to cytosolic Lyn (CL), thus stabilizing the aberrant complex and converting individual transient interactions into stable ones. We also demonstrate that treatment of B-CLL cells with geldanamycin, an Hsp90 inhibitor already reported to induce cell death, is capable of dissociating the CL complex in the early phases of apoptosis and thus inactivating CL itself. These data identify the CL complex as a potential target for therapy in B-CLL.     

Radiologische Diagnostik der Sigmadivertikulitis und Stadieneinteilung

Background and objectives

Radiological imaging is of central importance for diagnosing acute and chronic diverticular disease. The indications for the various radiological imaging modalities and their most important findings are discussed in this review article.

Methods

The current literature on this topic was reviewed and summarized.

Results

Contrast-enhanced computed tomography of the abdomen is the method choice in cases of suspected acute diverticulitis and should enable a differentiation between complicated and uncomplicated forms. In suspected chronic diverticular disease virtual colonoscopy represents an equivalent alternative to classical colonoscopy.

Conclusion

Based on imaging findings therapeutic decisions can be made and the radiological findings can have some prognostic value in the follow-up of patients.

     

Newly diagnosed hepatocellular carcinoma in patients with advanced hepatitis C treated with DAAs: A prospective population study

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The response of autologous T cells to a human melanoma is dominated by mutated neoantigens

Our understanding of pathways leading to antitumor immunity may depend on an undistorted knowledge of the primary antigenic targets of patients' autologous T cell responses. In the melanoma model derived from patient DT, we applied cryopreserved short-term autologous mixed lymphocyte-tumor cell cultures (MLTCs) in combination with an IFN-gamma enzyme-linked immunospot (ELISPOT) assay to cDNA expression screening. We identified three previously unknown peptides processed from melanosomal proteins tyrosinase (presented by HLA-A(*)2601 and -B(*)3801) and gp100 (presented by HLA-B(*)07021) and five neoantigens generated by somatic point mutations in the patient's melanoma. The mutations were found in the genes SIRT2, GPNMB, SNRP116, SNRPD1, and RBAF600. Peptides containing the mutated residues were presented by HLA-A(*)03011, -B(*)07021, and -B(*)3801. Mutation-induced functional impairment was so far demonstrated for SIRT2. Within MLTC responder populations that were independently expanded from the patient's peripheral blood lymphocytes of different years, T cells against mutated epitopes clearly predominated. These results document a high degree of individuality for the cellular antitumor response and support the need for individualizing the monitoring and therapeutic approaches to the primary targets of the autologous T cell response, which may finally lead to a more effective cancer immunotherapy.     

Assessing the demand for psychological care in chronic diseases: development and validation of a questionnaire based on the example of inflammatory bowel disease

BACKGROUND: This study was designed to develop and validate the ADAPT (Assessment of the Demand for Additional Psychological Treatment), a questionnaire assessing the demand for disease-oriented counseling (DOC), integrated psychosomatic care (IPC), and psychotherapy (PT) in chronically ill patients on the example of inflammatory bowel diseases (IBDs). METHODS: After its development, the ADAPT was distributed to 39 IBD patients along with the Hospital Anxiety and Depression scale (HAD), the Rating Form of IBD Patient Concerns (RFIPC), and a questionnaire on social support (SOZU-K22). For construct validity, 19 hypotheses were made on how DOC, IPC, and PT should correlate with HAD, RFIPC, SOZU-K22, and disease-related variables. To analyze interindividual responsiveness, patients were classified according to their bio-psycho-social state, and DOC, IPC, and PT scores were compared between these classes. The test-retest method with a 4-week time lapse was used to analyze reliability and intraindividual responsiveness. DOC, IPC, and PT scores between baseline and follow-up were compared separately for patients classified as "stable" or "changed" according to changes in HAD and disease activity. RESULTS: Observed correlations were largely in agreement with the 19 hypotheses. DOC, IPC, and PT achieved significantly different scores between different patients. After 4 weeks, DOC, IPC, and PT revealed stable scores in patients with "stable" HAD and revealed significantly different scores in patients with "changed" HAD. Changed disease activity was not associated with significant changes of the ADAPT. CONCLUSIONS: The ADAPT is the first questionnaire to assess subjective demand for additional psychological care in chronically ill patients. The first application of the ADAPT to 39 IBD patients suggests its validity, reliability, and responsiveness.     

Plasma ghrelin levels in patients with short bowel syndrome

Ghrelin is a novel peptide hormone which was identified as an endogenous growth hormone secretagogue. It is mainly secreted in the stomach, but important sites of its secretion are other parts of the gastrointestinal tract. Ghrelin is thought to be involved not only in regulation of growth hormone secretion but also in regulation of food intake and nutritional status. This study was aimed to investigate the changes in plasma ghrelin levels in patients with short bowel syndrome. Twenty-four patients with malnutrition due to short bowel syndrome and eleven healthy controls were included in the study. They underwent clinical examination and assessment of plasma or serum levels of ghrelin leptin, soluble leptin receptor, IGF-I, IGFBP-1 and IGFBP-3. Plasma ghrelin levels were decreased in patients with short bowel syndrome (p<0.01). Furthermore, decreased serum levels of IGF-I (p<0.01) and IGFBP-3 (p<0.001) were found in patients with short bowel syndrome. Other laboratory differences between both groups were not significant. No relationship between ghrelin and other determined variables was found. We conclude that plasma ghrelin levels are decreased in the group of patients with short bowel syndrome. It is probably because of a decrease in the tissue mass that is able to secrete ghrelin.     

Administration of glutathione in patients with type 2 diabetes mellitus increases the platelet constitutive nitric oxide synthase activity and reduces PAI-1

Several studies suggest that nitric oxide (NO) production is impaired in diabetes mellitus. Reduced levels of NO could contribute to cardiovascular mortality. Furthermore, NO synthesis is impaired in glutathione (GSH)-depleted human umbilical vein endothelial cells and GSH is reduced in patients with type 2 diabetes mellitus (T2DM). We tested the hypothesis that treatment with GSH may improve platelet constitutive NO sinthase (cNOS) activity in patients with T2DM. Fifteen patients with T2DM underwent a treatment with GSH 600 mg/day i.m. for 10 days. With respect to the basal values on the 10th day of treatment, the red blood cell GSH concentration and platelets cNOS increased (1.4+/-0.1 vs 1.9+/-0.1 micromol/10(10) RBC, p<0.001 and 0.7+/-0.1 vs 2.9+/-0.2 fmol x min(-1) x 10(-9) PLTs, p<0.001, respectively) and the plasma PAI-1 levels diminished (81.4+/-3.7 vs 68.7+/-4.0 ng/ml, p<0.002). A negative correlation between the cNOS and the PAI-1 was found on the basal values. After a wash-out of 30 days the values of red blood cell GSH concentration, platelet cNOS activity and PAI-1 Ag returned to the basal levels. These data suggest that the administration of GSH, in patients with T2DM, is able to improve platelet cNOS activity together with a reduction of PAI-1.     

Chronic treatment with pirenzepine decreases growth hormone secretion in insulin-dependent diabetes mellitus

We and others previously reported that nocturnal GH secretion in patients with insulin-dependent diabetes mellitus is blunted by acute cholinergic muscarinic blockade with pirenzepine. In this study, we investigated whether this inhibitory effect on GH secretion persists during chronic pirenzepine administration, and if pirenzepine administration affects glycemic control. Nocturnal GH secretion was studied from 2300-0800 h before and after one month of pirenzepine administration (100 mg/day, orally, given at 2300 h) in 13 diabetic patients receiving their usual insulin treatment. GH secretion (GH area under curve) was blunted after pirenzepine administration [mean, 877 +/- 215 (+/- SE) vs. 1407 +/- 311 micrograms/L.min; P less than 0.002]. During pirenzepine administration, hemoglobin A1c significantly decreased (P less than 0.02), and 4 of the 13 patients had lower daily insulin requirements (5-23 U/day), but there was no significant change for the group as a whole. These results indicate that the inhibitory effect of pirenzepine on GH secretion persists when pirenzepine is given chronically and that pirenzepine seems to improve the metabolic control of the patients.