Is the Left Ventricular Lateral Wall the Best Lead Implantation Site for Cardiac Resynchronization Therapy?

GASPARINI, M., et al .: Is the Left Ventricular Lateral Wall the Best Lead Implantation Site for Cardiac Resynchronization Therapy? Short-term hemodynamic studies consistently report greater effects of cardiac resynchronization therapy (CRT) in patients stimulated from a LV lateral coronary sinus tributary (CST) compared to a septal site. The aim of the study was to compare the long-term efficacy of CRT when performed from different LV stimulation sites. From October 1999 to April 2002, 158 patients (mean age 65 years, mean LVEF 0.29, mean QRS width 174 ms) underwent successful CRT, from the anterior (A) CST in 21 patients, the anterolateral (AL) CST in 37 patients, the lateral (L) CST in 57 patients, the posterolateral (PL) CST in 40 patients, and the middle cardiac vein (MCV) CST in 3 patients. NYHA functional class, 6-minute walk test, and echocardiographic measurements were examined at baseline, and at 3, 6, and 12 months. Comparisons were made among all pacing sites or between lateral and septal sites by grouping AL + L + PL CST as lateral site (134 patients, 85%) and A + MC CST as septal site (24 patients, 15%). In patients stimulated from lateral sites, LVEF increased from 0.30 to 0.39   (P < 0.0001)   , 6-minute walk test from 323 to 458 m   (P < 0.0001)   , and the proportion of NYHA Class III–IV patients decreased from 82% to 10%   (P < 0.0001)   . In patients stimulated from septal sites, LVEF increased from 0.28 to 0.41   (P < 0.0001)   , 6-minute walk test from 314 to 494 m   (P < 0.0001)   , and the proportion of NYHA Class III–IV patients decreased from 75% to 23%   (P < 0.0001)   . A significant improvement in cardiac function and increase in exercise capacity were observed over time regardless of the LV stimulation sites, either considered singly or grouped as lateral versus septal sites. (PACE 2003; 26[Pt. II]:162–168)     

GST-7T and P-170 co-expression in multiple myeloma

Summary. Bone marrow samples from 40 patients affected by multiple myeloma either treated or untreated were examined for expression of glutathione-S-transferase n (GST-TT), P-glycoprotein and the protein product of ras oncogenes family, p-21, on plasma cells, by immuno-cytochemical detection. 72% of evaluated samples were positive for P-170 and 82% for GST-7T without any correlation with clinical or prognostic parameters. A significant relationship between GST-7T expression and P-l 70 positivity was found and co-expression was observed in 91% of evaluated samples.
Expression of P-170 and GST-TT was found both in treated and untreated patients. However, patients evaluated before and after therapy showed an increase in the percentage of plasma cells positive for GST-7T or P-170 or both. Expression of p-21 was not associated with these mechanisms of drug resistance.
These data suggest that different resistance mechanisms are present in multiple myeloma.     

In vitro cross-linking of calf lens α-crystallin by malondialdehyde

The effect of malondialdehyde on structural features of bovine x-crystallin has been investigated by absorption and fluorescence spectroscopy as well as by far-UV circular dichroism. Experimental evidence suggests the occurrence of intermolecular cross-linking induced by malondialdehyde. This cross-linking does not seem to affect the tryptophan environment, as suggested by intrinsic protein fluorescence. On the contrary, the time dependence of far-UV dichroic activity indicates that the cross-linking is accompanied by a secondary structure change. The formation of high molecular mass aggregates, evidenced by electrophoresis in denaturing conditions, leads to irreversible x-crystallin aggregation due to extensive intermolecular cross-linking. Since malondialdehyde is produced in vivo as a breakdown product of lipid peroxidation, the possible involvement of this molecule in the pathological mechanism of cataract formation has been briefly discussed. © Munksgaard 1994.     

Effects of different sleep duration on delta sleep in recovery nights

The study assessed the effects of different amounts of sleep restriction on slow wave sleep (SWS) in the ensuing recovery nights. After one adaptation night and an 8-hr baseline night, six healthy men were individually studied during and following five nights in which sleep was reduced to 5, 4, 3, 2, and 1 hr with a 1-week interval between conditions. Bach sleep reduction was followed by an 8-hr recovery night. Finally, a second 8-hr baseline night was recorded. A trend analysis revealed that SWS amount in recovery nights increases with decreasing previous sleep duration. Regression analyses showed that, within each participant, the rebound of SWS after a sleep reduction is predicted better by the total duration of sleep than by the specific amount of SWS lost.     

A New Case of Familial LCAT Deficiency

ABSTRACT. Twenty-eight patients with familial lecithin:cholesterol acyltransferase deficiency have been reported to date. We report a new Italian case who presents the clinical and biochemical characteristics of the disease. Typical disc-shaped high density lipoproteins (d= 1.063-1.21 g/ml) were detected by electron microscopy. An abnormal distribution of apolipoproteins in the different lipoprotein fractions was found by sodium dodecyl sulphate polyacrylamide electrophoresis.     

Cytotoxicity in patients with different clinical forms of Chagas' disease

There are few studies on cell-mediated cytotoxicity in human Chagas' disease. In the present study, we evaluated peripheral blood mononuclear cell (PBMC) cytotoxicity activity from chagasic patients with different clinical forms of disease. To verify the cytotoxic response, we performed cell lysis assays using ⁵¹Cr-labelled K562 cells as targets. Results are reported as lytic units (LU=number of cells required for 30% lysis) per million PBMC. Exposure of patients’ PBMC to Trypanosoma cruzi antigen led to an increase in cytotoxic activity compared with unstimulated patient cells against K562. Asymptomatic cardiomyopathy patients had higher responses (37.8±5.0 LU/10⁶ PBMC; mean±s.d.) than indeterminate (11.5±3.6 LU/10⁶) and symptomatic cardiomyopathy (7.8±2.5 LU/10⁶). Normal control PBMC stimulated with T. cruzi antigen had 4.36±1.31 LU/10⁶ PBMC against K562. Addition of recombinant interferon-gamma (IFN-γ) did not lead to significant increase in cytotoxicity in any group of patients. On the other hand, recombinant human IL-12 significantly increased cytotoxic responses from symptomatic cardiomyopathy patients and normal controls who presented low levels of cytotoxicity induced by T. cruzi antigen. The combined use of IL-12 and a neutralizing anti-IFN-γ antibody did not change IL-12-induced cytotoxic responses, showing the direct role of this cytokine on natural killer (NK) cells. NK cells were the main cells responsible for the lysis of K562 target cells as evidenced by testing cell subsets following magnetic cell sorting. These data demonstrate that chagasic patients with different clinical forms of disease have PBMC which respond to T. cruzi antigen with a cytotoxic response, and this response is up-regulated by IL-12.     

SYSTEMIC ADENOSINE INCREASE DURING COLD PRESSOR TEST IS DEPENDENT ON SYMPATHETIC ACTIVATION

1. Following local vasoconstriction-inducing stimuli, such as the cold pressor test (CPT), significant changes occur in haemodynamics, with a rise in arterial blood pressure and heart rate (HR) due to the activation of the sympathetic nervous system. Among the compensatory mechanisms to local ischaemia, the endogenous nucleoside adenosine (ADO) has been suggested to play a relevant role by contributing to sympathetic stimulation. The possibility was investigated that CPT-induced increases in plasma ADO levels were not only an expression of the increased production of ADO in the ischaemic area, but also a consequence of systemic sympathoexcitatory mechanisms, thus showing a bidirectional involvement of the mechanisms of ADO formation. 2. The CPT was performed in 15 volunteers and mean arterial blood pressure (MABP) and HR were evaluated, together with plasma levels of noradrenaline (NA) and ADO in the tested and contralateral arm. The 15 subjects were then divided into three groups of five that were treated with either 5 mg transdermal clonidine weekly, 100 mg atenolol daily or 600 mg aminophylline twice daily. After 1 week treatment, the same test was repeated in the respective groups. 3. The CPT induced a rise in MABP and HR and an increase in plasma levels of NA and ADO. Increases in ADO were more pronounced in the tested arm. Clonidine blunted the haemodynamic response and NA release, while increases in ADO increase were reduced to a greater extent in the contralateral arm rather than the tested arm. Atenolol only affected MABP and HR without any effect on NA and ADO levels. Theophylline did not show any effect on CPT-induced changes. 4. In conclusion, local vasoconstriction and ischaemia induced in one arm following CPT are associated with haemodynamic changes dependent on the activation of the sympathetic system. The observed increase in plasma levels of ADO seems to be, in part, a direct expression of local responses to ischaemia (pre-dominant in the tested arm), but also appears as the consequence of systemic sympathoexcitatory mechanisms. Such increases in ADO are not dependent on a beta 1-adrenoceptor-mediated mechanism. Finally, theophylline, at a therapeutic dose, has no effect on the response to CPT.     

EVALUATION OF TWO INHIBITORY TESTS (NOMIFENSINE AND L-DOPA + CARBIDOPA) FOR THE DIAGNOSIS OF HYPERPROLACTINAEMIC STATES

It has been reported that administration of nomifensine (Nom) or of L-dopa + carbidopa (L-dopa + Carb) potentiates central dopaminergic tonus, resulting in decreased prolactin (PRL) secretion. It has been proposed that these drugs would help to discriminate patients with PRL-secreting pituitary tumours from those with so-called 'functional' hyperprolactinaemia.
In this study, oral Nom (200 mg) was given to forty-three hyperprolactinaemic patients and L-dopa + Carb (50 mg Carb every 6 h for four doses followed by L-dopa 100 mg and Carb 35 mg) to thirty of them and both treatments to ten normal subjects. The hyperprolactinaemic patients were divided into four clinical groups. Group A, twenty patients with proven PRL-secreting pituitary tumours; Group B, thirteen women with elevated PRL levels (<100 ng/ml) without any radiological evidence of a pituitary tumour (hyperprolactinaemia of unknown aetiology or 'functional' hyperprolactinaemia); Group C, four women with polycystic ovarian disease and mildly elevated serum PRL; Group D, six patients with various other disorders associated with hyperprolactinaemia.
PRL levels decreased in the normal controls below the basal values by 61.3%±6.2 (SEM) after Nom and 77.6%± 4.2 after L-dopa + Carb. Decreases in serum PRL of at least 50% (in three consecutive determinations) were found in group A in 20% of patients after Nom and in 25% after L-dopa + Carb; in group B in 15% and 40% of cases; in most of the hyperprolactinaemic women in group C; and some in group D.
In conclusion, these two treatments did not discriminate between tumorous and non-tumorous causes of PRL hypersecretion.