Losartan and amlodipine on myocardial structure and function: a prospective, randomized, clinical trial.

AIMS: To compare the effects of losartan and amlodipine on myocardial structure and function in hypertensive patients with Type 2 diabetes and left ventricular hypertrophy. METHODS: After a 4-week placebo period, patients were randomized to losartan 50 mg (n = 90) or amlodipine 5 mg (n = 91) for 12 months, with a doubling of the dose in patients who did not respond after 4 weeks. Blood pressure was measured in the clinic every month, while conventional echocardiography and acoustic densitometry (integrated backscatter analysis) were performed at the end of the placebo period and after 12 months of treatment. RESULTS: Both drugs reduced systolic/diastolic blood pressure to a comparable extent. Losartan significantly reduced left ventricular mass index (-19%, P < 0.001), interventricular septal thickness (-16.6%, P < 0.01) and left ventricular posterior wall thickness in diastole (-13.7%, P < 0.01). Amlodipine also decreased such measurements (-10%, P < 0.01 for left ventricular mass index, -9.3%, P < 0.05 for interventricular septal thickness in diastole and -10.1%, P < 0.05 for posterior wall thickness in diastole), but to a lesser extent than losartan. Both drugs significantly increased the ratio of peak filling velocity at early diastole to that at atrial contraction (E/A ratio) and decreased isovolumetric relaxation time: +13.7% and -8.5% with losartan,(both P < 0.01), and +7.9% and -4.9%, with amlopidine (both P < 0.05). Losartan, but not amlodipine, significantly reduced the relative integrated backscatter compared to baseline of the intraventricular septum (-10%, P < 0.01), and of the left ventricular posterior wall (-12%, P < 0.01), while increasing the cyclic variation of integrated backscatter of both the intraventricular septum (+35%, P < 0.001) and the left ventricular posterior wall (+32%, P < 0.001). CONCLUSIONS: Losartan provided a greater attenuation of left ventricular hypertrophy than amlodipine, seemingly as a result of a greater reduction of myocardial fibrosis.

The representation of tool use in humans and monkeys: common and uniquely human features.

Though other species of primates also use tools, humans appear unique in their capacity to understand the causal relationship between tools and the result of their use. In a comparative fMRI study, we scanned a large cohort of human volunteers and untrained monkeys, as well as two monkeys trained to use tools, while they observed hand actions and actions performed using simple tools. In both species, the observation of an action, regardless of how performed, activated occipitotemporal, intraparietal, and ventral premotor cortex, bilaterally. In humans, the observation of actions done with simple tools yielded an additional, specific activation of a rostral sector of the left inferior parietal lobule (IPL). This latter site was considered human-specific, as it was not observed in monkey IPL for any of the tool videos presented, even after monkeys had become proficient in using a rake or pliers through extensive training. In conclusion, while the observation of a grasping hand activated similar regions in humans and monkeys, an additional specific sector of IPL devoted to tool use has evolved in Homo sapiens, although tool-specific neurons might reside in the monkey grasping regions. These results shed new light on the changes of the hominid brain during evolution.

Listeria monocytogenes in two different poultry facilities: Manual and automatic evisceration.

Listeriosis is a serious foodborne disease caused by Listeria monocytogenes, a pathogen often found in food processing plants. Poultry meat and its derivatives may harbor L. monocytogenes even if good manufacturing practices are implanted in abattoirs. Little information exists in Brazil on the frequency of L. monocytogenes contamination, even though the country is considered the top poultry meat exporter in the world. This study attempted to compare 2 exporters poultry facilities following same the standards but differing only in manual (plant M) or automatic (plant A) evisceration. Eight hundred fifty-one samples from food, food contact and non-food contact surfaces, water, and workers' hands were collected from cage to finished products over a 1-yr period. In plant A, 20.1% of the samples were positive for L. monocytogenes, whereas in plant M, 16.4% was found. The greatest incidence of contamination with the pathogen in plant A was found in non-food contact surfaces (27.3%), while in plant M, it was found in products (19.4%). The most prevalent serovars were 1/2a or 3a (plant M) and 4b, 4d, or 4e (plant A). Despite having proper hygiene and good manufacturing practices, controlling the entry and persistence of L. monocytogenes in processing facilities remains a formidable task.

Measurement of Dysprosium Stark Width and the Electron Impact Width Parameter.

In this work, we suggest a methodology to determine the impact parameter for neutral dysprosium emission lines from the characterization of the plasma generated by laser ablation in a sealed chamber filled with argon. The procedure is a combination of known consistent spectroscopic methods for plasma temperature determination, electron density, and species concentration. With an electron density of 3.1 × 1018 cm-3 and temperature close to 104 K, we estimated the impact electron parameter for nine spectral lines of the neutral dysprosium atom. The gaps in the impact parameter data in the literature, mainly for heavy elements, stress the importance of the proposed method.

Epidemiological Survey of Listeria monocytogenes in a gravlax salmon processing line.

Listeria monocytogenes is a cause of concern to food industries, mainly for those producing ready-to-eat (RTE) products. This microorganism can survive processing steps such as curing and cold smoking and is capable of growing under refrigeration temperatures. Its presence in RTE fish products with extended shelf life may be a risk to the susceptible population. One example of such a product is gravlax salmon; a refrigerated fish product not exposed to listericidal processes and was the subject of this study. In order to evaluate the incidence and dissemination of L. monocytogenes 415 samples were collected at different steps of a gravlax salmon processing line in São Paulo state, Brazil. L. monocytogenes was confirmed in salmon samples (41%), food contact surfaces (32%), non-food contact surfaces (43%) and of food handlers' samples (34%), but could not be detected in any ingredient. 179 L. monocytogenes isolates randomly selected were serogrouped and typed by PFGE. Most of L. monocytogenes strains belonged to serogroup 1 (73%). 61 combined pulsotypes were found and a dendrogram identified six clusters: most of the strains (120) belonged to cluster A. It was suggested that strains arriving into the plant via raw material could establish themselves in the processing environment contaminating the final product. The wide dissemination of L. monocytogenes in this plant indicates that a great effort has to be taken to eliminate the microorganism from these premises, even though it was not observed multiplication of the microorganism in the final product stored at 4°C up to 90 days.

Quantitative evaluation of Listeria monocytogenes in fresh and processed surubim fish (Pseudoplatystoma sp).

L. monocytogenes is a foodborne psychrotrophic bacterial pathogen of special importance for minimally processed foods. In this work, it was enumerated in samples of surubim fish by MPN technique. The population of L. monocytogenes was estimated as < 0.012 MPN/cm(2) in fresh and < 0.03 MPN/g in minimally processed fish.

Is bupropion useful in the treatment of post-stroke thalamic apathy? A case report and considerations.

Post-stroke apathy is considered to be one of the clinical consequences of lesions affecting the structures of the prefrontal cortex, basal ganglia, thalamus and limbic system. However, there is no current consensus on the treatment of post-stroke apathy, which mainly depends on the underlying etiology and comorbidities. A 62-year-old man, affected by hemorrhagic stroke in the left thalamus, presented with mood depression, anhedonia, hyporexia and marked apathy. The patient underwent clinical evaluation before and after receiving two different pharmacological therapies: escitalopram and bupropion. Only after treatment with the latter drug did the patient show changes: high motivation and willingness to pursue activities, greater interest in the external environment and social life activities, and an overall reduction of apathy. On the basis of our observations in this case, we hypothesize that the thalamic lesion resulted in disconnection of the fronto-striatal-thalamic circuits, and that loss of the dopaminergic striatal innervation caused the patient's apathetic state. The resolution of the apathetic disorder may be attributable to the action of the dopaminergic drug bupropion on the mesocortical pathway.

Triple-combination therapy in the treatment of hypertension: a review of the evidence.

Hypertension is a serious public health concern with inadequate control of blood pressure (BP) worldwide. Contributing factors include low efficacy of drugs, underuse of combination therapies, irrational combinations, physicians' therapeutic inertia and poor adherence to treatment. Current guidelines recommend the use of initial (dual) combination therapy in high-risk patients for immediate BP response, better short- and long-term BP control, and continued/improved patient adherence. This article aims to review the existing evidence of triple-combination therapies with respect to efficacy, safety and adherence to treatment. It is estimated that three drugs are required to achieve BP control in approximately one-fourth to one-third of patients. Randomised controlled trials (RCTs) have shown that triple combinations of amlodipine/valsartan/hydrochlorothiazide, amlodipine/olmesartan/hydrochlorothiazide and amlodipine/telmisartan/hydrochlorothiazide produce greater BP reductions, with greater proportions of patients achieving BP control compared with dual therapies. Further evidence also demonstrates that triple-combination therapy is efficacious for moderate to severe hypertension, with substantial additional BP reduction over dual regimens. Both RCTs and post-marketing observational studies have shown consistent and comparable efficacy in both the general population and high-risk hypertensive subgroups. Triple therapies are generally well tolerated with adverse event profiles similar to dual regimens. In addition, fixed-dose combinations used as single pill improve patient adherence leading to better long-term BP control. Depending on regional circumstances, they may also be cost effective. Thus, single-pill triple combinations of different classes of drugs with complementary mechanisms of action help to treat patients to goal with improved efficacy and better adherence to treatment.

Effect of telmisartan/hydrochlorothiazide vs lisinopril/hydrochlorothiazide combination on ambulatory blood pressure and cognitive function in elderly hypertensive patients.

The aim of this study was to compare the effects of telmisartan/hydrochlorothiazide (HCTZ) vs lisinopril/HCTZ combination on ambulatory blood pressure and cognitive function in elderly hypertensive patients. A total of 160 patients, 76 men and 84 women, aged 61-75 years, with sitting diastolic blood pressure (DBP)>90 mmHg and <110 mmHg and systolic blood pressure (SBP)>140 mmHg were randomized to receive temisartan 80 mg/HCTZ 12.5 mg o.d. or lisinopril 20 mg/HCTZ 12.5 mg o.d. for 24 weeks, according to a prospective, open-label, blinded end point, parallel-group design. At the end of a 2-week wash-out period and after 12 and 24 weeks of active treatment, 24-h noninvasive ambulatory BP monitoring (ABPM) was performed and cognitive function was evaluated through six different tests (verbal fluency, Boston naming test, word-list memory, word-list recall, word-list recognition and Trails B). Both treatments significantly reduced ambulatory BP. However, the telmisartan/HCTZ combination produced a greater reduction in 24-h, day-time and night time ABPM values. Lisinopril/HCTZ did not induce significant changes in any of the cognitive function test scores at any time of the study, whereas at both 12 and 24 weeks telmisartan/HCTZ significantly improved the word-list memory score (+17.1 and +15.7%, respectively, P<0.05 vs baseline), the word-list recall score (+13.5 and +16.9%, P<0.05) and the Trails B score (-33 and -30.5%, P<0.05). These results suggest that in elderly hypertensive patients treatment with telmisartan/HCTZ produces a slightly greater reduction in ambulatory BP than lisinopril/HCTZ combination and, unlike this latter, improves some of the components of cognitive function, particularly episodic memory and visuospatial abilities.

Hydrochlorothiazide added to valsartan is more effective than when added to olmesartan in reducing blood pressure in moderately hypertensive patients inadequately controlled by monotherapy.

This study was undertaken to evaluate the effects on blood pressure of hydrochlorothiazide (HCTZ) 12.5 mg added to valsartan 160 mg or to olmesartan 20 mg in hypertensive patients. After a 2-wk placebo period, 130 patients, aged 35 to 75 y, with diastolic blood pressure (DBP) >or=99 and 110 mm Hg were randomly assigned to olmesartan 20 mg once daily or to valsartan 160 mg once daily according to a prospective, parallel-arm study design. After 4 wk of monotherapy, patients whose BP was not controlled (DBP >or=90 mm Hg) were given combination treatment with HCTZ 12.5 mg for an additional 4 wk. At the end of the placebo period and at the end of each treatment period, clinical and ambulatory BP measurements were recorded. At the end of the combination therapy period, venous blood samples were drawn 2, 4, and 24 h after drug intake for evaluation of HCTZ plasma concentrations. Both combinations induced a greater ambulatory BP reduction than monotherapy. However, mean reduction from baseline in the valsartan/HCTZ-treated patients (-21.5)-14.6 mm Hg for 24 h, -21.8/-14.9 mm Hg for daytime, and -20.4/-13.7 mm Hg for nighttime systolic blood pressure [SBP]/DBP) was greater than in the olmesartan/HCTZ-treated patients )-18.8/-12.3 mm Hg for 24 h, -19.3/-12.8 mm Hg for daytime, and 17.4/-10.6 mm Hg for nighttime SBP/DBP). The difference between the effects of the 2 treatments was significant (P<.01). In particular, compared with monotherapy, the add-on effect of HCTZ 12.5 mg was significantly greater in the valsartan group than in those treated with olmesartan; the difference was more evident for nighttime BP values. Plasma concentrations of HCTZ were significantly greater with valsartan than with olmesartan at each determination time (P<.05). These findings suggest that the addition of HCTZ 12.5 mg to valsartan 160 mg monotherapy produces a greater BP reduction than the addition of the same dose of HCTZ to olmesartan 20 mg monotherapy.

A new model of experimental choroidal neovascularization in the rat.

Choroidal neovascularization in rat eyes was induced by krypton laser photocoagulation. Lesions were studied weekly by ophthalmoscopy, fundus photography, and fluorescein angiography. Morphologic correlation was provided by serial sectioning of lesions for light and transmission electron microscopy. In addition, vascular casts were prepared for scanning electron microscopy. Choroidal neovascularization occurred in 25 (60%) of 42 lesions, as evidenced by growth of capillaries through breaks in Bruch's membrane. In addition, 24 (28%) of 86 lesions studied by fluorescein angiography demonstrated leakage. This study provides the most complete angiographic, histologic, and ultrastructural documentation of experimental choroidal neovascularization in the rat. This model may be useful for in vivo studies of choroidal angiogenesis and its modulation via drug therapy.

Recessive dystrophic epidermolysis bullosa.

Recessive epidermolysis bullosa dystrophica (REBD), a bullous disorder of the skin and mucous membranes, is frequently associated with ocular complications. A 40-year-old woman presented with lid ulcerations, chronic conjunctivitis, diffuse subepithelial corneal scarring, corneal ulceration, and cataracts. Management with intensive lubricant therapy, soft-bandage contact lenses, and cataract extraction successfully restored her sight. Histologic examination via light and electron microscopy revealed blister formation and scarring beneath the epithelial basement membrane of both the skin and cornea, confirming the diagnosis of REBD. The ultrastructure of the skin and cornea and the ocular complications of the major forms of epidermolysis are described herein. To our knowledge, successful ocular management of a confirmed case of REBD with complete ocular histopathologic features has not been documented.

Erbium-YAG laser surgery on experimental vitreous membranes.

We used a pulsed erbium-YAG laser emitting in the midinfrared region (2.94 microns) to cut experimental vitreous membranes in rabbits via an intraocular fiberoptic delivery system. Thirty-four membranes were cut at distances of 500 to 3600 microns from the retina. All 34 of the membranes treated were effectively cut. Sixteen cases had no evidence of retinal injury, including one in which the membrane was only 800 microns from the retina. Retinal injuries in the remaining cases consisted of small (less than 300 microns) retinal burns and hemorrhages. In 94% of the cases with retinal injury, the fiberoptic was within 2000 microns of the retina. We conclude that a pulsed erbium-YAG laser allows near tractionless cutting of vitreous membranes and may have potential for clinical use if further studies show it to be efficacious and safe near the retina.

Retinal manifestations of neurofibromatosis. Diagnosis and management.

Five patients presented with vision-threatening retinal tumors and systemic signs of neurofibromatosis, including neurofibromatosis type 1 (four patients) and familial cafe-au-lait spots (one patient). These tumors included large retinal astrocytic hamartomas, multiple retinal capillary hemangiomas, and combined hamartomas of the retina and retinal pigment epithelium, which resulted in rubeotic glaucoma, vitreous hemorrhage, and retinal detachment. Surgical therapy included retinal cryopexy, xenon and argon photocoagulation, scleral buckling, and pars plana vitrectomy with excisional retinal biopsy. Retinal tumors may result in marked visual loss in patients with neurofibromatosis, and vitreoretinal surgery may restore useful vision in some of these patients.

Ambulatory blood pressure monitoring in normotensive and hypertensive type 2 diabetes. Prevalence of impaired diurnal blood pressure patterns.

To assess the prevalence of an impaired diurnal blood pressure (BP) pattern in a population of both normotensive and hypertensive diabetics, noninvasive ambulatory BP monitoring (SpaceLabs 5200, Redmond, WA) was performed in 96 outpatients with type 2 diabetes (47 normotensives and 48 hypertensives) and in 103 control subjects without diabetes (50 normotensives and 53 hypertensives). Mean 24 h and daytime (06:00 to 22:00) BP and heart rate (HR) were not statistically different in diabetic patients compared to nondiabetic ones. Nighttime (22:00 to 06:00) BP and HR tended to be higher in both normotensive and hypertensive diabetics, although not significantly. Heart rate, diastolic BP (DBP), and especially the nocturnal systolic BP (SBP) decrease, were less marked in both normotensive and hypertensive diabetics, with a consequent increase in rate-pressure. A significant correlation was found between the percent decrease in nighttime SBP and the decrease in orthostatic SBP in casual BP measurements. The analysis of individual recordings allowed us to detect an impaired circadian pattern (the disappearance of the nocturnal BP decrease or a paradoxical BP increase) in 30% of the normotensive and 31% of the hypertensive diabetics (v 6% of the normotensive and 6.4% of the hypertensive nondiabetic subjects). As the absence of a nocturnal BP fall has been associated with the increased prevalence of left ventricular hypertrophy and atherosclerotic cardiovascular disease, its detection by ambulatory monitoring might be of prognostic and therapeutic importance.

Incidence and significance of Listeria in fish and fish products from Latin America.

The incidence and importance of Listeria spp. in fish and fishery products in Latin American countries is reviewed. There are very few papers dealing with this subject, however it is known that Listeria can be an important problem even for fisheries of tropical countries. The importance of GMP and HACCP implementation is also discussed.

Incidence of Listeria species in raw and pasteurized milk produced in São Paulo, Brazil.

The present study evaluated the incidence of Listeria spp. in raw and pasteurized milk from a Brazilian dairy plant. Ten samples of each type of milk (raw types B and C and pasteurized types B and C) were collected monthly from October 1989 to September 1990 (except in December), comprising 440 samples (110 samples of each type of milk). The recovery of Listeria spp. was carried out using LPM (lithium chloride phenylethanol moxalactam) and MOX (modified Oxford) agars, after a two-step enrichment procedure in Listeria enrichment broth (LEB) and Fraser broth. Overall, 12.7% of raw milk samples, 0.9% of pasteurized milk samples and 6.8% of total of milk samples were positive for Listeria spp., while 9.5% of raw milk samples, none of the pasteurized milk samples and 4.8% of total milk samples, were positive for Listeria monocytogenes. Raw milk also contained L. innocua (9.5%), L. welshimeri (0.9%) and L. grayi (0.4%). Pasteurized milk contained only L. innocua (0.9%).

Evaluation of motility enrichment on modified semi-solid Rappaport-Vassiladis medium (MSRV) for the detection of Salmonella in foods.

The detection and identification of Salmonella spp. is still troublesome and time consuming to the food industry. Employing the modified semi-solid Rappaport-Vassiliadis medium (MSRV), presumptive results for Salmonella can be obtained in 48 h, representing an interesting alternative to the standard methods. The specificity and sensitivity of the MSRV method were evaluated in this research. The efficiency of this method was also compared with the methodology recommended by the US Food and Drug Administration (FDA) using bismuth sulfite agar, XLT4 agar and Rambach agar. A total of 146 food samples comprised of 41 chicken thighs, 35 Brazilian fresh pork sausages, 35 samples of cocoa powder and/or granulated cocoa and 35 samples of grated fresh coconut, were examined. Overall, the rapid method (direct + indirect) and the standard culture detected 96.1% and 84.6% of the positive samples, respectively. No Salmonella was detected in the coconut or cocoa samples by any of the methods. Eighteen (43.9%) chicken thigh samples were contaminated with the microorganism. The rapid method (direct + indirect) and the standard culture detected 94.4% and 88.9% of these, respectively. Salmonella was detected in eight (22.8%) fresh pork sausage samples. The MSRV method detected Salmonella in all eight samples, while the standard gave positive results in six (75%). When compared with the standard method, the indirect method showed 86.4% sensitivity and 96.8% specificity, while the direct MSRV showed a sensitivity of 71.4% and specificity of 99.2%. Combined, both MSRV methods showed 95.5% sensitivity and 96.8% specificity. The MSRV medium also reduces the time necessary for the isolation of Salmonella from foods.

Incidence of Listeria spp. and Salmonella spp. in horsemeat for human consumption.

The incidence of Salmonella spp., Listeria spp. and Listeria monocytogenes in horsemeat for human consumption was investigated. One-hundred and twenty-one samples of frozen horsemeat collected from two Brazilian abattoirs were analysed over a period of 1 year. Twenty-two samples (18.2%) were positive for Listeria spp. with nine (7.4%) containing L. monocytogenes. None of the samples harbored Salmonella spp.

Characterization and evaluation of some virulence markers of Listeria monocytogenes strains isolated from Brazilian cheeses using molecular, biochemical and serotyping techniques.

A total of 207 L. monocytogenes strains isolated from different types of cheeses commercialized in the city of Rio de Janeiro, Brazil, were serotyped and evaluated for their ability to produce beta-haemolysin and lecithinase and to adsorb Congo red dye. Of the 207 strains, 59.9, 27.5 and 12.6% belonged to serotypes 1/2a, 1/2b and 4b, respectively. In addition, 175 strains of L. monocytogenes produced lecithinase while strains of the other species did not. Some of the non-L. monocytogenes strains adsorbed the dye Congo red, while some L. monocytogenes did not. Statistical analysis of the results showed significant differences (P < 0.05) amongst the virulence tests and the three serotypes found. In the present study, 32 L. monocytogenes strains were also analyzed by RAPD (randomly amplified polymorphic DNA). RAPD analysis allowed the discrimination among strains of different serotypes, as well as among strains of the same serotype. It is important to emphasize that the use of more than one primer is needed for characterization of L. monocytogenes strains. With RAPD the strains were grouped into six different profiles, some of them common for strains belonging to different serotypes. The results also indicated a close genetic relationship among strains of different serotypes.