Left ventricular mass and cardiovascular morbidity in essential hypertension: the MAVI study

OBJECTIVES

This study investigated the prognostic value of left ventricular (LV) mass at echocardiography in uncomplicated subjects with essential hypertension.

BACKGROUND

Only a few single-center studies support the prognostic value of LV mass in uncomplicated hypertension.

METHODS

The MAssa Ventricolare sinistra nell’Ipertensione study was a multicenter (45 centers) prospective study. The prespecified aim was to explore the prognostic value of LV mass in hypertension. Admission criteria included essential hypertension, no previous cardiovascular events, and age ≥50. There was central reading of echocardiographic tracings. Treatment was tailored to the single subject.

RESULTS

Overall, 1,033 subjects (396 men) were followed for 0 to 4 years (median, 3 years). Mean age at entry was 60 years, and systolic/diastolic blood pressure was 154/92 mm Hg. The rate of cardiovascular events (×100 patient-years) was 1.3 in the group with normal LV mass and 3.2 in the group (28.5% of total sample) with LV mass ≥125 g/body surface area (p = 0.005). After adjustment for age (p < 0.01), diabetes (p < 0.01), cigarette smoking (p < 0.01) and serum creatinine (p = 0.03), LV hypertrophy was associated with an increased risk of events (RR [relative risk] 2.08; 95% CI [confidence interval]: 1.22 to 3.57). For each 39 g/m² (1 SD) increase in LV mass there was an independent 40% rise in the risk of major cardiovascular events (95% CI: 14 to 72; P = 0.0013).

CONCLUSIONS

Our findings show a strong, continuous and independent relationship of LV mass to subsequent cardiovascular morbidity. This is the first study to extend such demonstration to a large nationwide multicenter sample of uncomplicated subjects with essential hypertension.     

Delayed clearance of serum HBsAg in compensated cirrhosis B: relation to interferon alpha therapy and disease prognosis

Objective: The aim of this study was to evaluate the incidence, prognostic factors and clinical significance of delayed clearance of serum HBsAg in compensated cirrhosis B.
Methods: This was a retrospective cohort study of 309 consecutive white patients with biopsy-proved compensated cirrhosis type B.
Results: During a mean follow-up of 68 months, HBsAg loss occurred in 32 patients, including 16 (8%) of 196 untreated patients (mean annual incidence 0.8%), 8 (10%) of 82 interferon (IFN) alpha–treated patients and eight patients who had been treated with other antivirals or steroids. The 5-yr probability of HBsAg loss was 4% and 16% for untreated and IFN-treated patients, respectively (   p = 0.0001  ). Cox's regression analysis identified hepatitis B e antigen–positivity at entry as the sole independent prognostic factor for HBsAg loss. Of the 32 patients who lost HBsAg, one (3%) subsequently developed hepatocellular carcinoma (HCC) and died, whereas, among the patients who remained HBsAg-positive, 11% developed HCC and 20% had died. The probability of HCC appearance was lower (   p = 0.0137  ) and survival was longer (   p = 0.0006  ) in patients who cleared HBsAg compared with patients with HBsAg persistence.
Conclusion: The incidence of HBsAg loss is about 0.8% in cirrhosis type B. Prognostic factors for clearance of HBsAg are initial HBeAg positivity and therapy with alpha interferon. Patients with cirrhosis type B, who lose HBsAg, have a low risk for liver cancer or liver-related death.     

Characterization of COR627 and COR628, two novel positive allosteric modulators of the GABA(B) receptor

The potential efficacy of GABA(B) receptor agonists in the treatment of pain, drug addiction, epilepsy, cognitive dysfunctions, and anxiety disorders is supported by extensive preclinical and clinical evidence. However, the numerous side effects produced by the GABA(B) receptor agonist baclofen considerably limit the therapeutic use of this compound. The identification of positive allosteric modulators (PAMs) of the GABA(B) receptor may constitute a novel approach in the pharmacological manipulation of the GABA(B) receptor, leading to fewer side effects. The present study reports the identification of two novel compounds, methyl 2-(1-adamantanecarboxamido)-4-ethyl-5-methylthiophene-3-carboxylate (COR627) and methyl 2-(cyclohexanecarboxamido)-4-ethyl-5-methylthiophene-3-carboxylate (COR628), which act as GABA(B) PAMs in 1) rat cortical membranes and 2) in vivo assay. Both compounds potentiated GABA- and baclofen-stimulated guanosine 5'-O-(3-[(35)S]thio)-triphosphate binding to native GABA(B) receptors, while producing no effect when given alone. GABA concentration-response curves in the presence of fixed concentrations of COR627 and COR628 revealed an increase of potency of GABA rather than its maximal efficacy. In radioligand binding experiments [displacement of the GABA(B) receptor antagonist, 3-N-[1-((S)-3,4dichlorophenyl)-ethylaminol]-2-(S)hydroxypropyl cyclo-hexylmethyl phosphinic acid ([(3)H]CGP54626)], both COR627 and COR628 increased the affinity of high- and low-affinity binding sites for GABA, producing no effect when administered alone up to a concentration of 1 mM. In vivo experiments indicated that pretreatment with per se ineffective doses of COR627 and COR628 potentiated the sedative/hypnotic effect of baclofen. In conclusion, COR627 and COR628 may represent two additional tools for use in investigating the roles and functions of positive allosteric modulatory binding sites of the GABA(B) receptor.     

Epidemiology of bacterial resistance in gastro-intestinal pathogens in a tropical area

During 1999-2000 a total of 4131 faecal specimens were collected and analysed at the medical centre St. Camille at Ouagadougou. Eight hundred and twenty-six (8.0%) grew significant bacteria. Escherichia coli (35%), Salmonella spp. (15%) and Shigella spp. (10%) were most frequently isolated. A large number of E. coli strains were resistant to aminopenicillins (>90%) and cotrimoxazole (80%); for Yersinia spp the resistance was 80 and 25%, respectively. Norfloxacin was the most active antibiotic but was rarely used. The study showed that it is necessary to create antibiotic-resistance surveillance centres in developing countries so that therapy may be appropriate and the spread of antibiotic resistance to other developed countries via increased emigration may be reduced.     

Hypertensive encephalopathy: antecedent to hippocampal sclerosis and temporal lobe epilepsy?

The authors describe three patients with refractory temporal lobe epilepsy (TLE) following an episode of hypertensive encephalopathy as their only identified antecedent event. All patients had typical MR features of hippocampal sclerosis (HS), and the two operated cases had typical HS histology and became seizure-free postoperatively. These cases suggest that hypertensive encephalopathy may be a rare form of initial precipitating injury, leading to TLE and HS.     

An ecologic study of geographical variation in multiple sclerosis risk in central Sardinia,Italy

We carried out an ecological study in the most archaic area of Sardinia to obtain a reliable estimate of the prevalence of multiple sclerosis (MS) and to investigate the geographical variation in the prevalence across the 100 administrative communes. To estimate the area-specific prevalence rate, we adopted a Bayesian approach that makes it possible to filter out the random variation from the estimates and to obtain a map that reflects the true geographical variation in MS prevalence. 428 resident cases were identified by the case register, including 69 multiplex families. The overall prevalence was 157 per 100,000 inhabitants. The Bayesian area-specific prevalence ranged from 143 to 262/100,000. The high prevalence and its moderate geographical variation in a genetically homogeneous population, as well as the high number of multiplex families observed in the communes with the highest prevalence, could be interpreted as representing a high susceptibility of the population to MS.     

The role of 99mTc-tetrofosmin Pinhole-SPECT in breast cancer axillary lymph node staging

The number of metastatic axillary nodes represents one of the most important prognostic factors in preoperative breast cancer patients. 99mTc-Tetrofosmin high resolution Pinhole (P)-SPECT was employed in 112 patients, 100 with breast cancer and 12 with benign mammary lesions, to ascertain axillary lymph node involvement. Axillary P-SPECT images were acquired utilizing specific software connected to a circular high resolution, single-head gamma camera equipped with a pinhole collimator with aperture size of 4.45 mm, rotating 180 degrees around the involved axilla. At the same time, patients also underwent conventional SPECT and planar acquisitions. Per-patient sensitivity and specificity were 100% and 93.6% for P-SPECT, 96.2% and 93.6% for SPECT and 56.6% and 100% for planar imaging, respectively. Moreover, P-SPECT detected more than 51% of lesions ascertained by histology, whereas SPECT and planar detected 32.6% and 20.3%, respectively. Only P-SPECT succeeded in identifying the exact number of metastatic axillary lesions in patients with multiple nodes; this procedure was able to correctly differentiate 88.67% of patients with 3 or less nodes from those with more than 3, thus giving important prognostic information. These data suggest 99mTc-Tetrofosmin P-SPECT is a reliable imaging method both for staging and prognostic purposes in breast cancer, and its routine use is recommended.     

Skin reaction in antiviral therapy for chronic hepatitis C: a role for polyethylene glycol interferon?

In the past decade, different modalities of antiviral therapy have been adopted aimed at eradicating hepatitis C virus infection. Initially, interferon was used in monotherapy, then interferon combined with ribavirin and amantadine. Recently, interferon has been conjugated with polyethylene glycol to allow optimization of its pharmacokinetic properties and to improve its antiviral activity. This study focused on the characteristics of the skin reactions that we observed in 27 patients with na?ve hepatitis C who received polyethylene glycol interferon-ribavirin-amantadine or polyethylene glycol interferon-ribavirin and in 10 previous non-responders to interferon monotherapy who were retreated with triple therapy. In 9 patients (7 on triple therapy) dermatitis-like lesions were observed, and in 5 the severity of the lesions necessitated withdrawal from therapy.     

Beta-endorphin elevations in the ventral tegmental area regulate the discriminative effects of Delta-9-tetrahydrocannabinol

beta-Endorphin is an endogenous opioid that produces behavioral effects similar to heroin and morphine and is released in the nucleus accumbens by cocaine, amphetamine and ethanol, suggesting a general involvement in the reinforcing effects of abused drugs. Here we show that, in rats, Delta-9-tetrahydrocannabinol (THC), the main psychoactive ingredient in cannabis, produces large increases in extracellular levels of beta-endorphin in the ventral tegmental area and lesser increases in the shell of the nucleus accumbens. We then used a two-lever choice THC-discrimination procedure to investigate whether THC-induced changes in endogenous levels of beta-endorphin regulate the discriminative effects of THC. In rats that had learned to discriminate injections of THC from injections of vehicle, the opioid agonist morphine did not produce THC-like discriminative effects but markedly potentiated discrimination of THC. Conversely, the opioid antagonist naloxone reduced the discriminative effects of THC. Bilateral microinjections of beta-endorphin directly into the ventral tegmental area, but not into the shell of the nucleus accumbens, markedly potentiated the discriminative effects of ineffective threshold doses of THC but had no effect when given alone. This potentiation was blocked by naloxone. Together these results indicate that certain psychotropic effects of THC related to drug abuse liability are regulated by THC-induced elevations in extracellular beta-endorphin levels in brain areas involved in opiate reward and reinforcement processes.