Is 44-hour better than 24-hour ambulatory blood pressure monitoring in hemodialysis?

The aim of this study is to evaluate if hemodialysis (HD) patients with similar blood pressure (BP) in the whole inter-HD period could have different target organ lesions and survival if the behavior of BP differs from the first to the second day of the inter-HD period. The present study compares 44-hour ambulatory BP monitoring (ABPM) patterns in 45 HD patients. Three BP patterns emerged: group A (n = 15) had similar BPs throughout (138 +/- 11/88 +/- 12 in the first 22 h vs. 140 +/- 11/87 +/- 12 mm Hg in the second 22-hour period); group B (n = 15) had a significant systolic BP rise from the first to the second period (132 +/- 15/80 +/- 12 vs. 147 +/- 12/86 +/- 13 mm Hg, p < 0.05); group C (n = 15) had significantly higher BPs (p < 0.05) than the other 2 groups throughout the whole inter-HD period, with no significant change between the 2 halves (172 +/- 14/108 +/- 12 vs. 173 +/- 18/109 +/- 14 mm Hg). Ventricular mass and survival during the 30-month follow-up period were statistically significantly better in group A, intermediate in group B and worse in group C. The data suggest that a 44-hour ABPM is more accurate than a 24-hour one in evaluating organ lesion and prognosis in HD patients.

Association between hypervolemia and ventricular hypertrophy in hemodialysis patients.

BACKGROUND: Left ventricular hypertrophy (LVH) is a well-known predictor of cardiovascular mortality in patients who have end-stage renal disease and are maintained on hemodialysis (HD), and LVH is not always correlated with the severity of hypertension in these patients. The purpose of this study was to investigate the role of other factors contributing to LVH. METHODS: A total of 50 patients with HD were classified in three groups according to whether their LV mass index (LVMI) was higher than (n = 15), equal to (n = 20), or lower than (n = 15) that predicted by a formula based on their ambulatory blood pressure monitoring (ABPM). RESULTS: Subjects with higher LVMI than predicted had significantly greater inter-HD weight gain (3.4 +/- 0.8 v 2.7 +/- 0.8 and 2.6 +/- 05 kg, respectively, in the other two groups, P < .05), and subjects with lower LVMI than predicted had a tendency toward a more pronounced nocturnal dipping pattern of BP (P = .07 v the other two groups), although daytime and night-time average BP levels did not differ between groups. All other clinical and laboratory parameters were similar among the three groups except higher cardiac output and various indices of LVH, which were more pronounced in the group with higher LVMI by ABPM. This group had also the lowest survival rate over the 2 to 3 years of follow-up, with five deaths versus two in each of the other two groups. CONCLUSIONS: The data suggest that correct management of inter-HD weight gain by nutritional counseling and shorter inter-HD intervals may prevent LVH and improve survival independently of BP control.

Effects of hypertension on maternal adaptations to pregnancy: experimental study on spontaneously hypertensive rats.

CONTEXT: Animal models for essential hypertension have been used for understanding the human pathological conditions observed in pregnant hypertensive women. OBJECTIVE: To study the possible effects of pregnancy on hypertension and of hypertension on pregnancy in spontaneously hypertensive rats (SHR), and in their normotensive Wistar-Kyoto (WKY) counterparts. TYPE OF STUDY: Comparative study using laboratory animals. SETTING: Animal Research Laboratory of Clinical Medicine at the Medical School of Botucatu, São Paulo State University, Brazil. SAMPLE: Ten to twelve-week-old virgin female normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). The animals were separated into four groups: 15 pregnant spontaneously hypertensive rats (SHR-P), 10 non-pregnant spontaneously hypertensive rats (SHR-NP), 15 pregnant normotensive rats (WKY-P), and 10 non-pregnant normotensive rats (WKY-NP). MAIN MEASUREMENTS: The blood pressure was evaluated by the tail cuff method, in rats either with or without prior training for the handling necessary for tail cuff measurements. The maternal volume expansion was indirectly evaluated by weight gain, and by systemic parameters as hematocrit, hemoglobin, total protein, albumin and sodium retention. The perinatal outcome of pregnancy was evaluated by analysis of resorptions, litter size, rate of low weight and number of stillbirths. RESULTS: The late fall in blood pressure in the pregnant SHR strain and in the normotensive WKY strain can only be detected in rats previously trained to accept the handling necessary for the tail cuff measurement. During pregnancy the body weight gain was significantly higher in WKY than in SHR rats. Systemic parameters were significantly lower in pregnant WKY rats than in non-pregnant WKY rats, while no differences were observed between pregnant and non-pregnant SHR groups. In pregnant WKY rats the sodium retention was higher from the 13th day onwards, while in SHR rats this occurred only on the 21st day. The characteristics of reproductive function such as number and weight of fetus, perinatal mortality and the resorption rate were significantly affected in the SHR strain. CONCLUSION: The SHR strain may be considered as a model for chronic hypovolemic maternal hypertension, with the fetal growth retardation being determined by this hypovolemic state.

Renal artery clipping attenuates the progression of adriamycin nephropathy.

This study was designed to analyze the impact of diminished renal perfusion pressure due to renal clipping on the rat model of adriamycin nephropathy. Male Wistar rats, divided into four groups (n = 9 per group) were injected with saline as control (C), adriamycin 3 ml/kg (Ad), saline with the left renal artery clipped (Rv), and adriamycin plus clip (AdRv). After 24 weeks mean arterial pressure (MAP), inulin, and p-aminohippurate (PAH) clearances were performed to evaluate renal function. Morphologic analysis included histologic criteria of percentage of glomerulosclerosis and tubulointerstitial lesion index (TILI). The MAP (mm Hg) was similar between Rv (143+/-13) and AdRv (154+/-20), but higher (P < .05) than C (120 +/-8) and Ad (124+/-11). Inulin clearance (mL/min/ 100 g) in Ad (0.2+/-0.05) was smaller than in C (0.53+/-0.17) and Rv (0.4+/-0.01) (P < .05), and was at an intermediate level in AdRv (0.33+/-0.2). The level of PAH (mL/min/100 g) was normal at 1.76 in C, and diminished more in Ad (0.58) than in Rv (1.06) and AdRv (1.18) (P < .05). Both Ad and the AdRv nonclipped kidneys had the highest degree of glomerulosclerosis (33% and 25%) and TILI (7% and 8%), respectively, compared with C and Rv (both 0%), whereas the clipped kidneys displayed intermediate degrees (9% and 5%) (P < .05 v nonclipped). The data suggest that diminished perfusion pressure of the clipped kidney, by decreasing the intraglomerular pressure, protects the glomerulus from damage and attenuates the evolution of adriamycin nephropathy.

[Efficacy and tolerability of the captopril and hydrochlorothiazide combination in the treatment of mild to moderate hypertension. Multicenter study]. / Eficácia e tolerabilidade da associação captopril + hidroclorotiazida no tratamento da hipertensão arterial leve a moderada. Estudo multicêntrico.

PURPOSE: To evaluate the antihypertensive efficacy and tolerability of captopril 50 mg + hydrochlorothiazide 25 mg daily in mild to moderate primary hypertension. METHODS: Out-patients (n = 471) with mild to moderate hypertension, diastolic blood pressure (DBP) 95-115 mmHg, with 15 days of washout, were included to the treatment initially with half tablet of the association of captopril 50 mg + hydrochlorothiazide 25 mg once daily, for 30 days. After this period, patients with DBP > 90 mmHg had the dosage duplicated, while the others had the same dosage for 60 days more. Evaluation was performed 15 days before and then every month during active drug. RESULTS: Twenty six patients were withdrawn, 13 (2.7%) by adverse effects and 13 by protocol violation. At the end of the wash-out period, the blood pressure (BP), 162 +/- 16/103 +/- 6 mmHg decreased significantly at the 30th day to 146 +/- 14/92 +/- 8 mmHg (p < 0.001 vs 0th day); 139 +/- 12/86 +/- 7 mmHg at the 60th day, (p < 0.001 vs 30th day), and further to 136 +/- 11/84 +/- 5 mmHg, (p < 0.001 vs day 0) till the end of the 90th day. Antihypertensive efficacy (DBP < or = 90 mmHg and decreased of the DBP > or = 10 mmHg) was obtained in 82% of the patients. There was no difference in BP control considering race, hypertension level, previous antihypertensive treatment and obesity. Cough (4%) was the main adverse event. CONCLUSION: Captopril + hydrochlorothiazide was effective and safe in the treatment of mild to moderate hypertension. The favorable response was observed in 82% of the patients independently of race, hypertensive level, previous antihypertensive treatment and obesity. Low incidence of side effects was reported, with no difference from others reported in the literature.

[Treatment of mild and moderate hypertension with fosinopril. Comparison of adverse effects with other antihypertensive agents]. / Tratamento da hipertensão arterial leve e moderada com fosinopril. Comparação de efeitos adversos com outros anti-hipertensivos.

PURPOSE: To evaluate the adverse reactions of fosinopril with other antihypertensives used as monotherapy. METHODS: Out-patients (n = 2,568) with diagnostic of mild to moderate hypertension, diastolic blood pressure (DBP) 95-115mmHg, with no antihypertensive treatment for 15 days, were included to treatment initially with fosinopril (F) 10mg, once daily, for six weeks. After this period, patients with DBP > 95mmHg had the dosage, once daily, increased to 20mg, while the others were maintained with the same dosage for six more weeks. Adverse reactions of 822 patients treated as monotherapy were grouped as absent, musculoskeletal, cardiovascular, cough, gastrointestinal, neurological, genital-urinary dysfunctions and dermatological and compared with 1,568 with F. Monotherapy consist in alpha-methyldopa (100 patients); beta-blocker (129); calcium blocker (106); diuretic (394); and another ACE inhibitors (93). RESULTS: At the end of the period without treatment, the blood pressure (BP), 165 +/- 16/105 +/- 7mmHg decreased significantly at 6th week to 144 +/- 15/91 +/- 9mmHg (p < 0.05 vs week 0) with further lowering to 139 +/- 13/86 +/- 7mmHg till the end of 12th week. BP response (DBP < or = 90mmHg) was obtained in 89% of the patients with F. Absence of adverse reactions were > or = 70% in patients with F compared to other drugs. CONCLUSION: Fosinopril has demonstrated therapeutic efficacy and less adverse reactions compared to antihypertensives used previously as monotherapy.

Killing acanthamoebae with polyaminopropyl biguanide: quantitation and kinetics.

The two Acanthamoeba species most often implicated in corneal keratitis, A. castellanii and A. polyphaga, were exposed as cysts to polyaminopropyl biguanide (PAPB), a commonly used antimicrobial agent. Killing of amoeba cysts was rapid and extensive, with fewer than 2% of either species surviving 30 s of exposure to > or = 45 ppm of PAPB. Killing kinetics were biphasic, and further exposures of 15 min to 1 h killed greater than 90% of those surviving initial killing. This potency of PAPB, together with its low toxicity to humans when ingested or applied topically, underscores the potential of PAPB as an antiamoebic agent.

[Comparative and double-blind study of the efficacy and safety of cilazapril compared to nifedipine retard in the treatment of mild and moderate arterial hypertension]. / Estudo comparativo duplo-cego da eficácia e segurança do cilazapril comparadas à nifedipina "retard" no tratamento da hipertensão arterial leve e moderada.

PURPOSE: To evaluate the antihypertensive efficacy and safety of cilazapril compared to nifedipine retard in mild to moderate hypertension. METHODS: forty randomized out-patients with mild moderate hypertension, diastolic pressure (DP) between 95 and 115 mmHg, with placebo for 15 days were randomized and allocated for treatment, double-blind, once daily with cilazapril 2.5 mg (n = 20) or nifedipine retard 20 mg (20 = n) for four weeks. The non-responders (DP > 90mmHg) had the dosage increased twice, b.i.d., while responders were maintained up to 10 weeks. Clinical visits were performed before, at baseline and every two weeks and the laboratory test was performed after placebo run-in, 4th and 10th weeks of treatment. RESULTS: The blood pressure (BP) were similar between groups at the end of the placebo (cilazapril 151 +/- 14/103 +/- 5 - nifedipine 157 +/- 17/108 +/- 7mmHg, p > 0.05). DP decreased already at second weeks (cilazapril 95 +/- 9 - nifedipine 96 +/- 11mmHg, p < 0.05, compared to week 0) in both groups at the end of study with no difference inter groups. BP normalization was obtained in 58% of the patients with cilazapril and in 61% in the nifedipine group. Adverse biochemical effects were not observed in any group. Six (16%) patients of the cilazapril and 15 (39%) of nifedipine related collateral events, although no difference were observed between groups. CONCLUSION: Cilazapril 2.5 to 25mg normalized BP in 58% of mild and moderate hypertension patients, and this efficacy was similar to sustained-release nifedipine 20 to 40mg. Cilazapril had no adverse effects on the biochemical parameters with low incidence of collateral effects.

Topoisomerase mutations affect the relative abundance of many Escherichia coli proteins.

The relative abundance of 88 proteins was measured in extracts from three strains of Escherichia coli K-12 that are isogenic except for the topA and gyrB genes. Mutations in these genes slightly raise or lower, respectively, steady-state DNA supercoiling levels but have little effect on growth rate. Altered protein abundances were observed in the mutant strains relative to wild type. Many proteins exhibited minimum abundance at wild-type supercoiling levels, and other proteins exhibited maximal abundance at relaxed levels. A smaller number showed maximal abundance at elevated levels of supercoiling. These data suggest that small, non-lethal changes in DNA supercoiling can have widespread effects on patterns of gene expression.

[An open comparative study of captopril + hydrochlorothiazide versus chlorthalidone for the treatment of mild and moderate primary hypertension]. / Estudo aberto comparativo captopril + hidroclorotiazida versus clortalidona para tratamento da hipertensão primária leve e moderada.

PURPOSE: To compare the antihypertensive and metabolic effects of captopril combined with hydrochlorothiazide (C+HCTZ) versus chlorthalidone (CT) in mild and moderate primary hypertensive patients. METHODS: Fifty five patients, without treatment or treated with 15 days placebo were randomized for treatment with the combination of captopril 50mg and hydrochlorothiazide 25mg (n = 29) against chlorthalidone (n = 26). The clinical evaluation was done during placebo and monthly throughout three months, and the laboratory tests were done before and at the end of the study. RESULTS: The blood pressure were similar between groups during placebo period (C + HCTZ: 161 +/- 25/102 +/- 6-CT: 155 +/- 18/101 +/- 6 mmHg); the diastolic blood pressure decreases significantly at first month already in the group C + HCTZ (89 +/- 8 mmHg) compared to group CT (94 +/- 8 mmHg, p < 0.05). The percentile diastolic and mean blood pressure dropped, in average, 12% in C + HCTZ group and in CT varied between 7 (1st and 2nd month) to 11% (3rd month). Without statistical difference, the blood pressure normalization was obtained in 69% of the patients with the association captopril and diuretic and in 50% of the patients in the chlorthalidone group. It was observed a significant reduction of potassium in patients treated with chlorthalidone (4.2 +/- 0.7 to 3.7 +/- 0.4 mEq/L, p < 0.01) that was not observed with the captopril and the thiazide associated. The last treatment also significantly reduced the cholesterol levels (219 +/- 39 mg/dl to 202 +/- 39 mg/dl, p < 0.04). CONCLUSION: Our results indicate that captopril combined with low diuretic dose normalize the blood pressure in 69% mild to moderate primary hypertensive patients, and acts faster than chlorthalidone in this control. In addition has metabolic benefits reducing cholesterol levels with no alteration in potassium levels.

[Captopril in mild and moderate hypertension resistant to diuretics: predictive value of the efficacy by captopril acute test]. / Captopril na hipertensão arterial leve e moderada resistente a diurético: valor preditivo da eficácia através do teste agudo do captopril.

PURPOSE: To evaluate if acute blood pressure response with captopril can be applied as a predictive test of treatment efficacy in hypertensive patients uncontrolled with large dose of diuretics. METHODS: Mild and moderate 120 uncontrolled hypertensive patients treated with hydrochlorothiazide 100 mg, were submitted to captopril (25 mg) test. The systolic (SBP) and diastolic (DBP) blood pressure acute and chronic responses were correlated and the linear discriminate function (LDF) and qui-square were applied to test the treatment efficacy. Previously two groups (G) patients were obtained as bad responders (G1) and good responders (G2) respectively, if the mean arterial pressure fall less or equal/more than 15% at the end of the associated treatment with diuretic and captopril. RESULTS: Mean arterial pressure values during placebo were 168 +/- 2/109 +/- 1 mmHg. This values after diuretic and associated captopril treatment were, respectively, 151 +/- 1/101 +/- 1 and 137 +/- 1/90 +/- 1 mmHg, all significant different (p < 0.05). Blood pressure normalization was obtained in 58% of patients. The calculated LDF formula were: LDF = 7.92 - % SBP +/- 1.21 delta % DBP. The G1 LDF mean value was 192 and 361 to G2. The value 276 represents the separation medium point between both groups. As far the distance from the separation medium point for a calculated LDF for a calculated LDF for a problematic patient, as more will be the probability for this patient to belong to this group. LDF and qui-square classified correctly, respectively, 80% and 47% of patients in G1. To G2 good responders patients, LDF and qui-square agreed, respectively, in 72 and 77%. CONCLUSION: The results obtained suggest that captopril test, could be useful as an auxiliary methodology to select hypertensive patients, uncontrolled with diuretic treatment, which might benefit with the association of converting enzyme inhibitors drugs.

[Captopril in mild and moderate arterial hypertension resistant to diuretic therapy. A multicenter study]. / Captopril na hipertensão arterial level e moderada resistente à diureticoterapia. Estudo multicêntrico.

PURPOSE: To evaluate the antihypertensive effect of captopril in mild and moderate hypertensive patients uncontrolled with diuretics. METHODS: Low dose of captopril (25 to 50 mg) bid were associated during 9 weeks in 120 patients previously treated with 100 mg of hydrochlorothiazide. A subgroup of patients (74) were followed additionally for 3 weeks with the same dose of the drugs administered as a single dose. The patients were clinically evaluated after two weeks placebo, and each three weeks of active drugs. Blood pressure normalization were considered when diastolic arterial pressure was < or = 90 mmHg. Laboratory tests were measured before diuretic, before captopril and at the end of combined twelve weeks treatment. RESULTS: After 15 days washout, the baseline supine arterial pressure, 168 +/- 2/ 109 +/- 1 mmHg decrease significantly with diuretic to 151 +/- 1/ 101 +/- 1 mmHg and the drop was further increased with captopril b.i.d., with a mean dose of 44 +/- 1 mg, to 137 +/- 1/ 90 +/- 1 mmHg. Blood pressure normalization was obtained in 58% patients with captopril b.i.d. and in 63% as single dose. Blood pressure normalization was achieved in 63% of non-white patients and in 56% patients over 45 years old. Plasmatic potassium decreased significantly with diuretic and did not recovered when captopril was associated. CONCLUSION: Our results indicate that the addition of low dose of captopril twice or once a day may result in a marked additional blood pressure reduction in cases of insufficient control by the diuretic alone.

D-value determinations are an inappropriate measure of disinfecting activity of common contact lens disinfecting solutions.

Determination of a D value for specific test organisms is a component of the efficacy evaluation of new contact lens disinfecting solutions. This parameter is commonly defined as the time required for the number of surviving microorganisms to decrease 1 logarithmic unit. The assumption made in establishing a D value is that the rate of kill exhibits first-order kinetics under the specified conditions. Such exponential kill rates are seen with thermal contact lens disinfection system. A comparison of the death rate kinetics for a variety of chemical contact lens disinfecting solutions was undertaken to ascertain the suitability of D-value determination for these chemical disinfectants. The active agents of these different solutions included hydrogen peroxide, thimerosal, chlorhexidine, tris(2-hydroxyethyl)tallow ammonium chloride, thimerosal, polyaminopropyl biguanide, and polyquaternium-1. The solutions were challenged with 10(6) CFU of either Pseudomonas aeruginosa, Serratia marcescens, or Staphylococcus hominis per ml, and survival rate was determined. This study clearly demonstrates the nonlinear nature of the inactivation curves for most contact lens chemical disinfecting solutions for the challenge organisms. D-value determination is, therefore, an inappropriate method of reporting the biocidal activity of these solutions.

Gyrase inhibitors can increase gyrA expression and DNA supercoiling.

Treatment of bacterial cells with inhibitors of gyrase at high concentration leads to relaxation of DNA supercoils, presumably through interference with the supercoiling activity of gyrase. Under certain conditions, however, the inhibitors can also increase supercoiling. In the case of coumermycin A1, this increase occurs at low drug concentrations. Oxolinic acid increases supercoiling in a partially resistant mutant. We found that increases in chromosomal DNA supercoiling, which were blocked by treatment with chloramphenicol, were accompanied by an increased expression rate of gyrA. This result is consistent with gyrase being responsible for the increase in supercoiling. In wild-type cells, increases in gyrA expression were transient, suggesting that when supercoiling reaches sufficiently high levels, gyrase expression declines. Oxolinic acid studies carried out with a delta topA strain showed that drug treatment also increased plasmid supercoiling. The levels of supercoiling and topoisomer heterogeneity were much higher when the plasmid contained one of several promoters fused to galK. Since oxolinic acid causes an increase in gyrA expression, it appears that gyrase levels may be important in transcription-mediated changes in supercoiling even when topoisomerase I is absent.

Rifampin and rpoB mutations can alter DNA supercoiling in Escherichia coli.

Two cases are described which indicate that RNA polymerase could alter DNA supercoiling. One occurred in a topA mutant in which abnormally high levels of plasmid supercoiling were lowered by rifampin, an inhibitor of the beta subunit of RNA polymerase. The second case involves suppression of a temperature-sensitive gyrB mutation by a rifampin-resistant allele of rpoB, the gene encoding the beta subunit of RNA polymerase. Measurements of chromosomal DNA supercoiling show that the rpoB mutation reduced DNA relaxation.

DNA gyrase on the bacterial chromosome. Oxolinic acid-induced DNA cleavage in the dnaA-gyrB region.

Oxolinic acid forms complexes with gyrase and DNA in such a way that subsequent denaturation of gyrase reveals DNA cleavage. Cleavage sites were mapped in a 10,000 base-pair region of the Escherichia coli chromosome containing the dnaA, dnaN, recF, and gyrB genes. Twenty-four cleavage sites were identified. The sites were cleaved at different frequencies, with the most frequent cleavage occurring within gyrB. Not all sites were equally sensitive to oxolinic acid concentration, some sites exhibited an altered cleavage frequency when the gyrB225 delta topA mutant strain DM800 was compared with wild-type cells, and coumermycin selectively changed the cleavage frequency at a few sites in the mutant strain DM800. These perturbations appear to alter the frequency of cleavage at a site but not the location of the site. The availability of many sites of differing strengths may be an important factor in the ability of gyrase to fine-tune the level of supercoiling or provide local swivels in bacterial DNA.