Ventricular dysrhythmias, left ventricular hypertrophy, and sudden death

Left ventricular hypertrophy has been documented to be a powerful risk factor for sudden death, acute myocardial infarction, and other cardiovascular morbidity and mortality. The major determinant of left ventricular mass is the hemodynamic burden. However, the hypertrophic process is modified by demographic parameters (age, sex, race), nutritional parameters (salt intake, alcohol, obesity), and neuroendocrine factors (angiotensin, catecholamines, growth hormones, etc.). Ventricular ectopy and more serious arrhythmias are commonly seen in patients with left ventricular hypertrophy. Specific antihypertensive therapy will reduce left ventricular hypertrophy, although not all antihypertensive drugs are equipotent in this regard. A reduction in left ventricular hypertrophy has been shown to diminish left-ventricular-hypertrophy-associated arrhythmias. However, it remains to be shown that patients with left ventricular hypertrophy and ventricular ectopy are at a higher risk of sudden death than those without ventricular ectopy and that the reduction of left-ventricular-hypertrophy-associated ventricular ectopy indeed confers a clinical benefit that exceeds the one from the reduction in arterial pressure alone.Modified with permission. Messerli FH and Soria F: Left ventricular hypertrophy and ventricular ectopy. In Podrid PJ and Kower PR, eds.Arrhythmia: A Clinical Approach. ¢ Williams & Wilkins, 1994.     

Effect of alcohol septal ablation in patients with hypertrophic cardiomyopathy on the electrocardiographic pattern

Alcohol septal ablation (ASA) of patients with hypertrophic cardiomyopathy (HC) allows study of the electrocardiographic effects of myocardial necrosis confined to the base of the interventricular septum, a rare event in atherothrombotic coronary artery disease. Eighty-four consecutive patients were studied after ASA for HC. After excluding 20 with pacing before ASA and 6 with no available preprocedure electrocardiograms, the electrocardiograms of the remaining 58 patients were compared with those of 58 consecutive patients with anterior ST elevation myocardial infarctions who underwent primary intervention for left anterior descending coronary artery (LAD) occlusions. In 25 patients, the occlusions were proximal to the first septal perforator, and in 33 patients, the occlusions were more distal. All electrocardiograms were analyzed with respect to conduction abnormalities and ST-segment changes. Patients with HC developed right bundle branch block significantly more often than those with LAD occlusions (50% vs 14%, p = 0.001) Moreover, patients with HC required postprocedure pacing more frequently (14% vs 2%, p <0.05). A distinctive pattern of ST displacement was found. There was more frequent ST depression in leads I and aVF and greater ST elevation in lead V(1) in patients who underwent ASA, indicating a greater tendency toward a rightward direction than was true in patients with LAD occlusions. In conclusion, in addition to more frequent right bundle branch block after ASA, a distinctive a characteristic pattern of ST-segment deviation similar to but distinct from that produced by proximal LAD occlusion appeared.     

Preoperative staging of rectal cancer by endoluminal ultrasoundvs. magnetic resonance imaging

PURPOSE: The aim of this study was to compare the value of endoluminal ultrasonography (ELUS) with magnetic resonance imaging (MRI) for preoperative staging of rectal carcinoma. METHODS: Thirty-seven consecutive patients were examined by ELUS and MRI. Imaging results were compared with pathohistologic studies. A tumor extending beyond the bowel wall was considered to be positive and one within the bowel wall was considered negative. Lymph node involvement was considered present if nodes equal to or greater than 5 mm in diameter were found in the perirectal tissue. For evaluating the differences between the two methods, the Mc Nemar test was performed. RESULTS: T-Staging was correct in 88.2 percent (30/34) of patients by ELUS and in 82.3 percent (28/34) by MRI (difference not significant). N-Staging was correct in 80 percent (20/25) by ELUS and in 60 percent (15/25) by MRI (difference of borderline significance). A comprehensive preoperative staging (T + N) was made correctly in 68 percent (17/25) by ELUS and in 48 percent only (12/25) by MRI (difference not significant). CONCLUSIONS: We suggest that ELUS and MRI must be evaluated within the framework of established parameters when treatment modalities such as preoperative radiation therapy and local or radical surgical approach must be decided.     

Results after the adoption of a MELD/PELD‐based liver allocation policy in Argentina

In July 2005, Argentina switched from a categorical liver allocation system to a MELD/PELD‐based policy for patients with CLD. To analyze WL outcomes and survival after LT in children. From January 2000 to December 2010, 923 children were registered. Two consecutive five‐yr periods were analyzed and compared: Era I (January 2000–July 2005) (n = 379) and Era II (July 2005–December 31, 2010) (n = 544). All data were prospectively collected and analyzed using the Kaplan–Meier method. After adopting the MELD/PELD system, WL registrations increased by 44% (from 379 to 544) and the number of LT increased by only 24% (from 278 to 365). However, three‐month WL mortality rate (32% to 18%, p < 0.0001, HR 2.002 CI 95% 1.5–2.8) decreased significantly. No significant differences were observed between Era 1 and II in one‐yr post‐LT survival (77.5% vs. 84.1%, p = 0.3053) and in acute re‐LT rate (9% vs. 5%, p = 0.1746). Under the MELD/PELD‐based allocation system in Argentina, mortality on the WL significantly decreased in children with CLD without affecting post‐LT survival, although reduced access to LT was observed.     

Lupus arthropathy: historical evolution from deforming arthritis to rhupus

Systemic lupus erythematosus is an autoimmune and inflammatory disease with multiple clinical manifestations, including arthropathy. The clinical presentation of articular involvement is variable, ranging from arthralgia without erosions or deformity to an erosive arthropathy and severe functional disability. A subset of patients with this articular involvement have Jaccouds arthropathy, and others have an arthropathy with clinical findings similar to rheumatoid arthritis that has been called rhupus. In this paper we review the historical evolution of concepts of lupus arthropathy, from deforming arthritis to rhupus, and conclude that rhupus is not a combination of rheumatoid arthritis and lupus. Instead, rhupus arthropathy should be regarded as a variant of the arthropathy of systemic lupus erythematosus.     

SRC homology-2-containing protein tyrosine phosphatase-1 restrains cell proliferation in human medullary thyroid carcinoma

Medullary thyroid carcinoma (MTC) is a rare tumor originating from thyroid parafollicular C cells, where, in the inherited form, constitutive activation of the RET protooncogene is responsible for unrestrained cell proliferation. We previously demonstrated that somatostatin (SRIF) reduces cell growth in the human MTC cell line TT, which expresses all SRIF receptor (SSTR) subtypes and responds differently to selective SSTR agonists. The antiproliferative mechanism of SRIF and its analogs in MTC is still unclear. Src homology-2-containing protein tyrosine phosphatase-1 (SHP-1), a cytoplasmic protein tyrosine phosphatase (PTP), is activated by somatotropin release-inhibiting factor and reduces mutated RET autophosphorylation in a heterologous system. In this study, we explore the role of PTP activation, in particular of SHP-1, in TT cells, where RET is constitutively activated. In TT cells, SRIF stimulated the PTP activity of SHP-1, which was associated with proliferation inhibition and with reduction in the MAPK pathway activation. Blockade of PTP activity with sodium orthovanadate induced cell proliferation and MAPK phosphorylation and blunted the inhibitory effects of SRIF. Moreover, SHP-1 associates with SSTR2 depending on its activation. By using a MAPK kinase inhibitor, we demonstrated that TT cell growth depends on MAPK pathway activation. Furthermore, in TT cells overexpressing SHP-1, cell proliferation and MAPK signaling were strongly down-regulated, whereas in TT cells transfected with a dominant negative form of SHP-1, cell proliferation and MAPK signaling were markedly induced. Our data demonstrate that SRIF inhibitory effects on TT cell proliferation are mediated, at least in part, by SHP-1, which acts through a MAPK-dependent mechanism.     

Neuronal nitric oxide synthase and renin stimulation by sodium deprivation are dependent on the renal nerves

OBJECTIVE: The aim of the present study was to evaluate the role of the renal nerves in the regulation of neuronal nitric oxide synthase (nNOS) gene expression in normotensive rats on different sodium balance. METHODS: Thirty-six male Sprague-Dawley rats were divided into six experimental groups combining three diets with different NaCl content (normal, 0.4%; low, 0.04%; or high, 4.0%), and bilateral renal denervation or sham denervation. After 7 days of dietary treatment, all rats were sacrificed and plasma renin activity (PRA) measured. The nNOS and renin messenger RNA (mRNA) levels in the renal cortex were determined by semiquantitative polymerase chain reaction. RESULTS: PRA was higher in animals with low sodium diet compared with those with standard diet, while it was lower in animals with high sodium diet. Renal denervation decreased PRA in normal and low sodium groups, while it did not alter the PRA values in the high sodium group. The nNOS gene expression significantly increased in rats fed with the low sodium diet compared with the standard diet group, and it significantly decreased in rats with the high sodium diet. Renal denervation significantly reduced nNOS mRNA levels in rats receiving the low sodium diet, but did not significantly influence nNOS mRNA in normal and high sodium groups. Renin mRNA was influenced by diets and denervation in a parallel way to nNOS mRNA. CONCLUSION: The renal nerves mediate the increase of renin and nNOS mRNA during sodium restriction, while the suppression of nNOS and renin gene expression during a sodium load is independent of the presence of the renal nerves. The parallel changes in renin and nNOS mRNA during different sodium intakes suggest that nNOS can be part of the complex, and still largely unclarified, macula densa mechanism of renin regulation.     

Follicular lymphoma international prognostic index

The prognosis of follicular lymphomas (FL) is heterogeneous and numerous treatments may be proposed. A validated prognostic index (PI) would help in evaluating and choosing these treatments. Characteristics at diagnosis were collected from 4167 patients with FL diagnosed between 1985 and 1992. Univariate and multivariate analyses were used to propose a PI. This index was then tested on 919 patients. Five adverse prognostic factors were selected: age (> 60 years vs 60 years), Ann Arbor stage (III-IV vs I-II), hemoglobin level (< 120 g/L vs 120 g/L), number of nodal areas (> 4 vs 4), and serum LDH level (above normal vs normal or below). Three risk groups were defined: low risk (0-1 adverse factor, 36% of patients), intermediate risk (2 factors, 37% of patients, hazard ratio [HR] of 2.3), and poor risk ( 3 adverse factors, 27% of patients, HR = 4.3). This Follicular Lymphoma International Prognostic Index (FLIPI) appeared more discriminant than the International Prognostic Index proposed for aggressive non-Hodgkin lymphomas. Results were very similar in the confirmation group. The FLIPI may be used for improving treatment choices, comparing clinical trials, and designing studies to evaluate new treatments.