Controlling Hypertension: Preventive Medicine At Its Best

Hypertension is a very common and important finding. The family physician is ideally suited to manage this problem on a long term basis. To do so, he must have an adequate practical plan of diagnosis and management. This article describes one approach to the problem.     

Global and regional myocardial oxygen consumption and blood flow in severe cardiomyopathy with left bundle branch block

OBJECTIVE: In patients with dilated cardiomyopathy (DCM), left bundle branch block (LBBB) is a common finding. The characteristic feature is an asynchronous septal wall motion and most frequently a delay of the lateral and/or posterior wall segments. With the onset of cardiac resynchronization therapy, there is a focus on the specific pathophysiology of a LBBB. However, quantitative data on regional myocardial oxygen consumption (MVO(2)) and blood flow (MBF) are missing. METHODS: We studied 31 patients with severe DCM and LBBB (ejection fraction 22.1+/-7.1%) and 14 patients with mild to moderate DCM without LBBB (ejection fraction 46.7+/-7.9%). Global and regional MVO(2) as well as MBF were determined from a dynamic (11)C-acetate positron emission tomography (PET) study. RESULTS: Global MVO(2) and MBF were lower in the DCM group with LBBB than in the control group (P<0.05). Regionally, the LBBB group revealed a higher (P<0.05) MVO(2) and MBF in the lateral wall than in the other walls. The control group did not show significant differences between the myocardial walls and demonstrated a smaller variability of the parameters. CONCLUSION: DCM patients with LBBB exhibit a more heterogeneous distribution of MVO(2) and MBF among the myocardial walls than DCM patients without LBBB. Due to the LBBB associated electromechanical alterations, the highest regional values of MVO(2) and MBF are found in the lateral wall.     

Ultrasound diagnosis of brain atrophy is related to neurodevelopmental outcome in preterm infants

BACKGROUND: Intraventricular haemorrhage and periventricular leukomalacia are associated with poor outcome of very preterm infants, while the role of more subtle cerebral alterations, as detected by cranial ultrasound, is less clear. AIM: In this study, we related periventricular echodensities and signs of brain atrophy to neurodevelopmental outcome at 3 y of age. PATIENTS AND METHODS: All preterm infants born in 1997 in our institution with a gestational age <32 wk or birthweight <1500 g were subjected to repeated standardized cranial ultrasound examinations until discharge. Survivors were examined at 3 y of age employing the Bayley Scales of Infant Development II. RESULTS: Eighty-seven infants were enrolled (birthweight 430-2500 g (median 1200 g), gestational age 24-34 wk (median 29 wk)). Periventricular echodensities were detected in 42 infants (48%); in 12 cases persisting <7 d, in 30 cases >7 d. At discharge, 18 infants (22%) had signs of brain atrophy. Neurodevelopmental outcome was assessed in 64 infants. Infants with signs of brain atrophy scored significantly lower on MDI (atrophy 91.8, no atrophy 101.9; p=0.02), PDI (atrophy 91.4, no atrophy 106.5; p=0.001) and Behaviour Rating Scale (atrophy 41.1, no atrophy 66.4; p=0.01) than infants without atrophy. Periventricular echodensities were not related to outcome. CONCLUSION: Our data show that infants with sonographic signs of brain atrophy at discharge achieve lower scores in neurodevelopmental testing at 3 y.     

Platelet adhesion assay--a new quantitative whole blood test to measure platelet function

At this time no practical laboratory method for the measurement of the current functional state of blood platelets is available. A new innovative platelet adhesion assay (PADA) is described here. With only a short time requirement and minimal equipment, the PADA provides quantitative measurements of platelet adhesiveness. Only 0.5 mL of freshly drawn citrated whole blood is needed, to which special polymer particles are added. A defined shear grade is induced by a short period of shaking the sample. Proteins of the blood sample, especially fibrinogen, and thereafter also activated platelets, bind to the specific polymer surface. Following platelet counts both in the sample and in a control (blood without particles), the adhesion index (AI) is calculated as a quantitative measure of platelet adhesiveness. In healthy volunteers, a mean AI of 52+/-12 was measured. AI was shown to be nearly independent of the number of platelets in the sample (100 to 350 k/ microL), the hematocrit (44 to 25%), and the fibrinogen content (1.5 to 5 g/L). Age of the volunteers had only a minor influence on the AI. PADA was shown to be a simple reliable laboratory method for the detection of disturbed platelet function. The test requires low analytical efforts compared with other diagnostic platelet function tests.     

Combination of low and high resolution sequences in two orientations for dynamic contrast-enhanced MRI of the breast: more than a compromise

The purpose was to combine T1-weighted 3D gradient echo sequences at low and high spatial resolution (and short and longer acquisition time, respectively) in two orientations without compromising signal/time curve analysis and to evaluate the incremental value of assessing architectural features in high resolution images in dynamic contrast-enhanced MR mammography. T1-weighted 3D-FLASH sequences in a 1.5-T scanner (512×256 pixel matrix at high resolution; 256×128 pixels at low resolution sequences, 72 slices, 1.7-mm slice thickness, TR 8.8 ms, TE 4.5 ms, flip angle 25°) were acquired in a special order during a single investigation. Three observers evaluated architectural features of 36 histopathologically proven lesions using high or low resolution images independently. Architectural features of each lesion were assessed by rating on two three-point scales. Kappa statistics verified the decrease of inter-observer variability. All observers improved assessment of architectural features regarding high resolution images in transversal and coronal orientation (observer A: eight positive, three negative corrections; B: 12/5; C: 16/4). Most positive corrections resulted from improved detection of morphologic criteria of malignancy. Mean inter-observer agreement significantly (P<0.05) increased from slight to moderate (mean weighted increased from 0.185 to 0.422). This protocol at the charge of slightly enlarged time for measurement offers an elegant way to improve analysis of architectural features in MRM.     

Occurrence and management of atrial arrhythmia after long-term Fontan circulation

OBJECTIVES: In patients after the Fontan operation, we determined risk factors for late failure and for intra-atrial re-entrant tachycardia at 15 to 20 years' follow-up. Midterm results after electrophysiologic ablation therapy for these tachycardias were also evaluated. METHODS: Current follow-up was available in 162 patients (2005 patient-years) with a wide range of underlying diagnoses operated on between February 1978 and May 1995. Risk factor analysis included patient-related and procedure-related variables, with late failure and the incidence of re-entrant tachycardia as outcome parameters. RESULTS: Forty late failures were observed (2.0 per 100 patient-years). At 15 years, Kaplan-Meier estimated survival was significantly (P =.007) better for patients with tricuspid atresia (93%) compared with that for patients with complex congenital malformation (71%). The sole multivariable risk factor for Fontan failure was the type of underlying diagnosis. At 20 years' follow-up, overall freedom from tachycardia was estimated to be 46% +/- 12%. Acute success of electrophysiologic ablation was seen in 25 (83%) of 30 patients, and Kaplan-Meier estimated freedom from recurrent tachycardia was 81% +/- 10% at 3 years. Multivariate analysis identified duration of Fontan circulation as the sole risk factor for re-entrant tachycardias. CONCLUSION: After the modified Fontan operation, long-term survival in patients with tricuspid atresia was significantly better compared with that in patients with complex congenital malformations. As first-choice therapy for atrial re-entrant tachycardias, we recommend electrophysiologic ablation therapy.     

A technical triade for proteomic identification and characterization of cancer biomarkers

Biomarkers are needed to elucidate the biological background and to improve the detection of cancer. Therefore, we have analyzed laser-microdissected cryostat sections from head and neck tumors and adjacent mucosa on ProteinChip arrays. Two differentially expressed proteins (P = 3.34 x 10(-5) and 4.6 x 10(-5)) were isolated by two-dimensional gel electrophoresis and identified as S100A8 (calgranulin A) and S100A9 (calgranulin B) by in-gel proteolytic digestion, peptide mapping, tandem mass spectrometry analysis, and immunodepletion assay. The relevance of these single marker proteins was evaluated by immunohistochemistry. Positive tissue areas were reanalyzed on ProteinChip arrays to confirm the identity of these proteins. As a control, a peak with low P was identified as calgizzarin (S100A11) and characterized in the same way. This technical triade of tissue microdissection, ProteinChip technology, and immunohistochemistry opens up the possibility to find, identify, and characterize tumor relevant biomarkers, which will allow the movement toward the clonal heterogeneity of malignant tumors. Taking this approach, proteins were identified that might be responsible for invasion and metastasis.     

Vaccination with hybrids of tumor and dendritic cells induces tumor-specific T-cell and clinical responses in melanoma stage III and IV patients

Hybrid cell vaccination was developed as therapeutic approach that aims at stimulating tumor-specific cytotoxic T-cell responses in cancer patients using hybrids of autologous tumor and allogeneic dendritic cells. We tested this concept and the efficacy of the vaccines in inducing clinical and immunologic responses in a clinical trial with melanoma stage III and IV patients. Of the 17 patients evaluated, 1 experienced a complete response, 1 a partial response and 6 stable disease with remarkably long survival times. In 11 of 14 patients analyzed, high-frequency T-cell responses to various tumor-associated T-cell epitope were induced and detectable in the peripheral blood. These immune responses were detected in clinical response patients as well as nonresponders. Failures of clinical responses in all the cases investigated correlated with loss of antigen expression and presentation. Hybrid cell vaccination thus proves effective in inducing tumor-specific T-cell responses in cancer patients.