Beta-adrenergic receptor density and function in left ventricular hypertrophy in young essential hypertensives

A sympathetic overactivity has been reported in the early stages of essential hypertension and has been involved in the pathogenesis of left ventricular hypertrophy (LVH) in essential hypertension. The state of beta2-adrenergic receptors as related to the presence of this complication was investigated in a group of 15 essential hypertensive patients and compared to 10 normotensive control subjects. Left ventricular mass index was determined by bidimensional echocardiography. Plasma catecholamine levels were measured by a radioenzymatic assay. beta2-adrenoceptor density was measured in intact lymphocytes by radioligand binding assay, using the hydrophilic ligand CGP 12177. beta2- adrenoceptor function was assessed by measuring intracellular cAMP levels in isoproterenol-stimulated lymphocytes. Left ventricular mass index (P < 0.05), body mass index (P < 0.01), plasma noradrenaline levels (P < 0.05) and beta2-adrenoceptor density (P < 0.05) were higher in hypertensives than in controls. Left ventricular mass index correlated with body mass index both in normotensives and hypertensives, as well as with plasma noradrenaline levels only in normotensives. Left ventricular mass index also showed a positive correlation with mean arterial pressure and an inverse relationship with beta2-adrenoceptor density and response only in hypertensive patients. In conclusion, left ventricular hypertrophy in young essential hypertensives is associated to a reduced beta2-adrenoceptor density and function, probably as a compensating mechanism of the hypertrophied myocardiocyte secondary to the increased sympathetic outflow.Journal of Human Hypertension (2000) 14, 17-21.     

Treatment of systemic sclerosis with recombinant interferon-gamma. A phase I/II clinical trial.

OBJECTIVE. A phase I/II trial to examine the safety and efficacy of interferon-gamma (IFN gamma) therapy for patients with systemic sclerosis (SSc). METHODS. An 18-week open-label study was performed. Eighteen patients with rapidly progressive SSc were enrolled, 14 of whom completed at least 16 weeks of the study. These 14 patients had a mean age of 40 years and had been diagnosed as having SSc an average of 10.1 months prior to study entry. Recombinant IFN gamma was injected intramuscularly 3 times weekly for 18 weeks. Six patients received a 0.1 mg/m2 dose, while 8 patients received a 0.5 mg/m2 dose. Patients who completed the 18-week trial were offered maintenance therapy at a dose of up to 0.5 mg/m2. The effects of IFN gamma on skin involvement were assessed by 2 methods: 1) evaluation of skin thickness, by scoring 15 zones according to a 0 (normal skin) to 3 (hidebound skin) scale; and 2) determination of the total body surface area involved, by using 2-dimensional body diagrams to indicate areas affected, and then having a second, "blinded," assessor calculate the area score with a planimeter. RESULTS. The mean skin thickness score decreased from a baseline of 25.9 to 19.1 (P < 0.03), and the mean area scores declined from 33.1 to 19.6 (P < 0.02) after 18 weeks of IFN gamma treatment. Ten patients had a > 25% decrease in area score. Five patients had a > or = 70% decrease in area score, and 3 of them have not experienced disease recurrence for 6 to 17 months after discontinuation of IFN gamma. Five patients withdrew before the study ended. Three of these patients developed renal crisis, which may reflect the severity of the SSc in the study group, although an adverse effect of IFN gamma in SSc cannot be excluded. CONCLUSION. IFN gamma was associated with a beneficial effect on the skin involvement in most of this series of patients with rapidly progressive SSc. A placebo-controlled study will be necessary to confirm these results.     

The epidemiology of Entamoeba histolytica in Mexico City. A pilot survey I

Stocks of intestinal amoebae isolated from hospital patients in Mexico City and grown in monoxenic culture were compared among themselves and with those already described (Sargeaunt & Williams, 1979), using the electrophoretic patterns of four enzymes: glucose phosphate isomerase (GPI), phosphoglucomutase (PGM), L-malate:NADP⁺ oxido-reductase (oxalacetate-decarboxylating) (ME) and hexokinase (HK). New isoenzyme groups (Sargeaunt & Williams, 1979) of all the amoebae, including Entamoeba histolytica have been demonstrated. Amongst these have been found seven more groups of E. histolytica, two new groups of E. hartmanni, one new group of Dientamoeba fragilis and one new group of E. coli. Of the seven new groups of E. histolytica three are known to originate from patients with clinical amoebiasis whilst the remainder are from asymptomatic subjects. Only 11·2% of the 125 isolations were associated with clinical amoebiasis, and these are clearly distinguished from the isolations from asymptomatic patients by their electrophoretic isoenzyme pattern.     

Global and local variations in antimicrobial susceptibilities and resistance development in the major respiratory pathogens

Acute respiratory tract infections, such as bacterial pneumonia and acute exacerbations of chronic bronchitis, have been identified by the World Health Organisation as the leading global infectious cause of death. An increasing prevalence of antibiotic resistance has been identified worldwide in the three major bacterial respiratory pathogens -Streptococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenzae. The selection and spread of resistance is to some degree inevitable and the importance of monitoring its progress has led to the instigation of numerous international, regional and national surveillance programmes. The results from surveillance studies show wide variations in susceptibility rates, both geographically and over time, highlighting the need for local resistance prevalence data in order to guide empirical prescribing and to identify areas in which medical need for new agents is greatest.     

Early involvement of the spinal cord in diabetic peripheral neuropathy

OBJECTIVE: The pathogenesis of diabetic peripheral neuropathy (DPN) is poorly understood. We have recently reported a significant reduction in spinal cord cross-sectional area at the stage of clinically detectable DPN. In this study, we investigated whether spinal cord atrophy occurs in early (subclinical) DPN. RESEARCH DESIGN AND METHODS: Eighty-one male type 1 diabetic subjects, 24 nondiabetic control subjects, and 8 subjects with hereditary sensory motor neuropathy (HSMN) type 1A underwent detailed clinical and neurophysiological assessments. Diabetic subjects were subsequently divided into three groups based on neuropathy severity (19 with no DPN, 23 with subclinical DPN, and 39 with clinically detectable DPN). All subjects underwent magnetic resonance imaging of the cervical spine and cord area measurements at disc level C2/C3. RESULTS: Mean corrected spinal cord area index (SCAI) (corrected for age, height, and weight) was 67.5 mm [95% CI 64.1-70.9] in diabetic subjects without DPN. Those with subclinical (62.4 mm [59.5-65.3]) and clinically detectable DPN (57.2 mm [54.9-59.6]) had lower mean SCAIs compared with subjects with no DPN (P = 0.03 and P < 0.001, respectively). No significant difference was found between diabetic subjects without DPN and nondiabetic control subjects (69.2 mm [66.3-72.0], P = 0.47). Mean SCAIs in subjects with HSMN type 1A (71.07 mm [65.3-76.9]) were not significantly different from those for nondiabetic control subjects and diabetic subjects without DPN. Among diabetic subjects, SCAI was significantly related to sural sensory conduction velocities and the Neuropathy Composite and Symptom Scores. CONCLUSIONS: Spinal cord involvement occurs early in DPN. There is also a significant relation between reduction in SCAI and neurophysiological assessments of DPN.     

Bone augmentation in rabbit calvariae: comparative study between Bio-Oss and a novel beta-TCP/DCPD granulate

AIM: In the present in vivo study, we compare the bone regeneration capacity of a novel brushite cement synthesized in our laboratory (DTG) with Bio-Oss using rabbits as an animal model. METHODS: The study was performed in a group of 14 adult New Zealand rabbits using the bone conduction model. Two titanium cylinders were fixed into perforated slits made on the parietal cortical bone of each rabbit. One cylinder was left empty (negative control) and the other was filled with either Bio-Oss or brushite set-cement granules (test cylinder). Four weeks after the intervention, the animals were sacrificed and biopsies were taken. The following parameters were analysed: bone tissue augmentation, bone mineral density and biomaterial resorption. The comparison of data between the different groups was performed using the Mann-Whitney test with a significance level of p<0.05. RESULTS: The mean bone mineral density and augmented mineral tissue inside the test cylinders were similar but higher than those of negative controls. Material resorption and bone tissue augmentation were significantly higher in the defects treated with the brushite-based set cement (p<0.05). CONCLUSIONS: Brushite cement granules were more resorbable and generated more bone tissue than Bio-Oss inside the titanium cylinders placed in the rabbit calvaria.     

Poly(ADP-ribose) polymerase-1 inhibitor 3-aminobenzamide enhances apoptosis induction by platinum complexes in cisplatin-resistant tumor cells

Cisplatin is one of the most widely used antitumor drugs. However, as all the anticancer drugs currently used in clinic, cisplatin shows the phenomenon of drug resistance (intrinsic or acquired) against a wide variety of tumors. Poly (ADP-ribose) polymerase-1 is an enzyme involved in DNA repair and apoptotic cell death, which may be inhibited to increase cisplatin chemosensitivity of tumor cells so that cisplatin resistance may be circumvented. In the present study we report that PARP-1 inhibitor 3-aminobenzamide (3-AB) increases the cytotoxic activity of the platinum compounds cisplatin, trans-[PtCl(2)(4-picoline)(piperazine)] and transplatin against CH1cisR cisplatin-resistant ovarian tumor cells. In fact, a concentration of 3-AB of 1 mM not only increases the cytotoxic activity of these platinum complexes but also switches the mode of cell death from necrosis to apoptosis. Altogether, these data suggest that pharmacological modulation of PARP-1 by inhibitors may be a suitable strategy to fight against tumor resistance to platinum drugs.