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Background Few population-based studies on the effects of environmental exposure variation exist. Aim Assessing respiratory symptom/disease incidence related to risk factor exposure changes. Methods A longitudinal general population sample from two surveys (PISA2:1991–1993; PISA3:2009–2011; no. = 970), aged ≥20 years at baseline, completed a questionnaire on respiratory symptoms/diseases, risk factor exposure and performed spirometry. 18-year follow-up cumulative incidence of respiratory symptoms/diseases and longitudinal changes (persistence, incidence, remittance) in risk factor exposure were computed. Results Cumulative incidence values were: 3.2% (corresponding to a 1.8‰/year incidence rate), asthma; 6.6% (3.8‰/year), asthma attacks; 4.5% (2.6‰/year), wheeze; 31.7% (21.0‰/year), allergic rhinitis-AR; 7.6% (4.4‰/year), chronic obstructive pulmonary disease-COPD; 16.1% (9.7‰/year), usual cough; 18.5% (11.3‰/year), usual phlegm; 30.7% (20.1‰/year), dyspnoea 1+; 13.9% (8.3‰/year), airway obstruction. The following associations emerged among respiratory symptom/disease cumulative incidence and risk factor exposure changes: a two-to-five fold higher risk for COPD, phlegm, cough, dyspnoea, asthma attacks, airway obstruction in persistent smokers; a two-to-three fold higher risk for COPD in remittent smokers; a two-fold higher risk for AR, phlegm and a four-fold higher risk for asthma in subjects with persistent occupational exposure; a two-fold higher risk for cough, phlegm, dyspnoea, AR in subjects with incident occupational exposure; a two-fold higher risk for AR, asthma attacks, COPD in subjects with incident traffic exposure. Conclusions Our study showed noteworthy respiratory symptom/disease incidence values and indicated that life-style and environmental exposure changes can differently influence onset. This information could be useful for primary prevention strategies in order to reduce the chronic disease burden in the general population.

Epidemiology An increasing number of inhabitants of Central America have developed a form of chronic kidney disease of unknown cause, named Mesoamerican nephropathy (MeN). Because similar epidemics have been reported in other parts of the world, such as Sri Lanka, India, Egypt, and Tunisia, this condition is currently called chronic kidney disease of uncertain origin (CKDu). Clinical presentation This disease is characterized by minimal proteinuria, leukocyturia, hyperuricemia, hypokalemia reduced glomerular filtration rate, and renal tubular dysfunctions. Pathology: The kidneys manifest tubulo-interstitial nephritis and glomerulosclerosis. Electron microscopy shows large dimorphic lysosomes with dark electron-dense aggregates. Potential causes: The cause(s) of this disease remain largely unknown. Several hypotheses have been proposed including infections, dehydration, global warming, hyperuricemia, exposure to agro-chemicals or heavy metals, and genetic susceptibility. This review addresses a mounting body of evidence suggesting that the disease may be the result of exposure to a variety of water contaminants combined with volume depletion. Therapy Absent a clear understanding of the causes of the disease, no specific therapeutic interventions can be recommended. Preliminary studies suggest that reduction of working hours, frequent rest in shaded area, and administration of purified water may reduce the risk of CKDu.

Introduction: COVID-19 has several overlapping phases. Treatment has focused on the late stage of the disease in hospital. Yet, the continuation of the pandemic is by propagation of the disease in outpatients. The current public health strategy relies solely on vaccines to prevent disease. Areas Covered: We searched the major national registries, pubmed.org, and the preprint servers for all ongoing, completed and published trial results with subject numbers of 100 or more on, and used a targeted search to find announcements of unpublished trial results. As of 2/15/2021, we found 111 publications reporting findings in human studies on 14 classes of agents, and on 9 vaccines. There were 62 randomized controlled studies, the rest retrospective observational analyses. Only 21 publications dealt with outpatient care, the rest all in hospitalized patients. Remdesivir and convalescent plasma have emergency use authorization for hospitalized patients in the U.S.A. There is also support for glucocorticoid treatment of the COVID-19 respiratory distress syndrome. Monoclonal antibodies are authorized for outpatients, but the supply is inadequate to treat all at time of diagnosis. Favipiravir, ivermectin, and interferons are approved in certain countries Expert Opinion: Worldwide vaccination is now underway. Vaccines and antibodies are highly antigen specific and new variants are appearing. There is a need for treatment of outpatients who contract the disease, in addition to mass immunization. We call on public health authorities to authorize treatments with known low risk and potential benefit for use in parallel with mass immunization.

COVID-19, caused by SARS-CoV-2, continues to be a major health problem since its first description in Wuhan, China, in December 2019. Multiple drugs have been tried to date in the treatment of COVID-19. Critical to treatment of COVID-19 and advancing therapeutics is an appreciation of the multiple stages of this disease and the importance of timing for investigation and use of various agents. We considered articles related to COVID-19 indexed on PubMed published January 1, 2020-November 15, 2020, and considered papers on the medRxiv preprint server. We identified relevant stages of COVID-19 including three periods: pre-exposure, incubation, and detectable viral replication; and five phases: the viral symptom phase, the early inflammatory phase, the secondary infection phase, the multisystem inflammatory phase, and the tail phase. This common terminology should serve as a framework to guide when COVID-19 therapeutics being studied or currently in use is likely to provide benefit rather than harm. (AIDS Rev. 2021;22:40-47)

BACKGROUNDThe spread of COVID-19 from Wuhan China, has been alarmingly rapid. Epidemiologic techniques succeeded in containing the disease in China, but efforts have not been as successful in the rest of the World, with a total of 29,155,581 confirmed cases of COVID-19, including 926,544 deaths worldwide as of September 15, 2020. Projections are for continued new infections and deaths if no effective therapeutic interventions can be initiated over the next several months. We performed a systematic review to determine the potential time course for development of treatments and vaccines, focusing on availability now and continuing in the last half of 2020.METHODSClinical TrialsWe reviewed up-to-date information from several sources to identify potential treatments for COVID-19: The Reagan-Udall Expanded Access Navigator COVID-19 Treatment Hub was used to track the efforts of companies to develop agents. We focused on trials completed as of September 1, 2020 on identified agents We used several different sources: (A) covid-trials.org, then validated results on (B) clinicaltrials.gov and the (C) World Health Organization’s International Clinical Trials Registry Platform (WHO ICTRP). We excluded studies which were clearly observational, with no randomization, control, or comparison group. We further set a cutoff of 100 for numbers of subjects, since smaller trial size could lack statistical power to establish superiority of the intervention over the control.PublicationsWe searched for published trial results on pubmed.gov and on medRxiv, the preprint server, and used a targeted Google™ search to find announcements of unpublished trial resultsRESULTSClinical Trials in RecruitmentAs of our cutoff date of April 1, 2020, we found 409 trials meeting our minimum requirement of 100 subjects. The WHO Solidarity megatrial for hospitalized patients was launched in over 100 countries, actively comparing hydroxychloroquine (HCQ), lopanovir/ritonavir (LPV/r) alone and in combination with interferon beta-1, and remdesivir. The LPV/r alone and HCQ arms have already been discontinued. Of these, only 9 were conducted on outpatients. A few vaccine trials are hoping to complete Phase 3 enrollment by the end of the third quarter 2020, but a prolonged follow-up of patients will likely be required.Clinical trials CompletedAs of September 1, 2020, there were 231 trials reporting completion, Of these, only 59 studies enrolled 100 or more subjects. There were 34 trials in hospitalized patients, 9 directed at outpatients, and 8 prevention studies,Published DataAs of September 1, 2020 we found 70 publications reporting findings in human studies on 13 classes of drugs and on 6 vaccines. There were 33 randomized placebo or active control studies; the rest were retrospective observational. Only seven publications dealt with outpatient care, the rest all in hospitalized patients.Available TreatmentsAt this time, remdesivir and convalescent plasma have been granted emergency use authorization in the U.S.A., solely for hospitalized patients. There is also support for glucocorticoid treatment of the COVID-19 respiratory distress syndrome. No treatments or prophylaxis are offered for outpatients.CONCLUSIONCOVID-19 is propagated primarily by infected ambulatory individuals. There have been no options brought forward for prevention and non-hospital treatment with only a few randomized, controlled outpatient studies expected to yield results in time to impact on the continuing pandemic by the end of 2020. It will be necessary for public health authorities to make hard decisions, with limited data, to prevent the continued spread of the disease. The choices will be hardest when dealing with possible early release of safe and effective vaccines which would, of course, be of greatest benefit to the World’s population.

An increase in FEV1 >=12% has been proposed in international guidelines as a clue to airway reversibility for diagnosing asthma in both adults and children. However, the validity of this cut-off has been questioned in the pediatric population. The aim of this study was to provide evidence that different cut-off values in BDR may be associated with better performance in discriminating among outpatient children with naïve asthma (A) and without asthma (NA). We compared three approaches: i) the conventional cutoff (12%); ii) the cut-off estimated by Youden's criteria; and iii) the cut-off based on a model-driven approach. we found that the conventional cut-off of 12% showed poor sensitivity in discriminating A and NA. The cut-off of 6.5% obtained maximizing Youden's J statistic showed higher sensitivity than the conventional one; however, the average correct classification rates obtained using the two criteria mentioned were less than 63%, highlighting poor discriminating performance. A model-based approach identifying three different categories of BDR - low (=14.7%) - yielded correct classification rates higher than 80%. The model-based approach made it possible to develop a dynamic nomogram, which graphically returns the prediction probability of asthma, overcoming the elevated risk of misclassification associated with the use of the conventional cut-off of 12%.

Hypertension and obesity in the young population are major risk factors for renal and cardiovascular events, which could arise in adulthood. A candidate-gene approach was applied in a cohort observational study, in which we collected data from 2638 high school adolescent students. Participants underwent anthropometric and blood pressure (BP) measurements, as well as saliva and urine sample collection for genomic DNA extraction and renal function evaluation, respectively. We tested whether candidate genes previously implicated in salt-sensitive hypertension in adults impact BP also among adolescents. Since inflammatory mechanisms may be involved in pathophysiology of hypertension and in endothelial dysfunction and atherosclerosis through reactive oxygen species, the baseline urinary excretion of inflammatory and oxidative stress markers in a subgroup of adolescents stratified according to ADD1 (alpha adducin) rs4961 genotypes was assessed. Regression analysis of BP values with genetic polymorphisms, highlighted an association with a missense variant of LSS (lanosterol synthase, rs2254524), a gene coding for an enzyme involved in endogenous ouabain synthesis. Higher diastolic and systolic BP were associated with LSS A allele ( P =0.011 and P =0.023, respectively). BP resulted associated with 5 more SNPs. The KL (klotho) rs9536314 missense variant was associated with 24 hour urinary Na + excretion ( P =0.0083). Urinary protein tests showed a greater excretion of IL1β (interleukin 1β) and interleukin 10 ( P ADD1 rs4961 T allele. In conclusion, 3 missense gene variants already implicated in adult hypertension impact BP or Na + excretion among adolescents, and, together with activated pro-inflammatory pathways, might predispose to early cardiovascular damage.

Hereditary angioedema (HAE) is a rare autosomic-dominant disorder characterized by a deficiency of C1 esterase inhibitor which causes episodic swellings of subcutaneous tissues, bowel walls and upper airways that are disabling and potentially life-threatening. We evaluated n = 17 patients with confirmed HAE diagnosis during attack and remission state and n = 19 healthy subjects. The samples were tested for a panel of IL (Interleukin)-17-type cytokines (IL-1β, IL-6, IL-10, granulocyte–macrophage colony stimulating factor (GM-CSF), IL-17, IL-21, IL-22, IL-23) and transforming growth factor-beta (TGF-β) subtypes. Data indicate that there are variations of cytokine levels in HAE subjects comparing the condition during the crisis respect to the value in the remission phase, in particular type 17 signature cytokines are increased, whereas IL-23 is unmodified and TGF-β3 is significantly reduced. When comparing healthy and HAE subjects in the remission state, we found a significant difference for IL-17, GM-CSF, IL-21, TGF-β1 and TGF-β2 cytokines. These results confirm and extend our previous findings indicating that in HAE there is operating an inflammatory activation process, which involves also T helper 17 (Th17) cytokines and TGF-β isoforms, associated with localized angioedema attacks and characterized by elevated bradykinin levels.

Vitamin D (25-OHD) has a role in bone health after treatment for cancer. 25-OHD deficiency has been associated with risk factors for cardiovascular disease, but no data focusing on this topic in childhood cancer survivors have been published. We investigated the 25-OHD status in children treated for acute lymphoblastic leukemia (ALL), and evaluated its influence on vascular function. 25-OHD levels were evaluated in 52 ALL survivors and 40 matched healthy controls. Patients were grouped according to 25-OHD level (

Hypertension is very prevalent among patients with chronic kidney disease (CKD) and end-stage kidney disease (ESRD). However, there are still several unsolved issues pertaining to the definition, variability, diagnosis and management of hypertension in these patients. This manuscript critically reviews the current challenges in clinical practice in defining, diagnosing and treating hypertension in CKD and ESRD patients. Moreover, the manuscript reviews the pharmacokinetics, pharmacodynamics and safety of most anti-hypertensive drugs used in the management of these patients.

Background: Few data are available on the temporal pattern of respiratory disease phenotypes in general population. Aim: To detect longitudinal patterns of disease phenotypes related to risk factors and physician visits. Methods: Pisan general population sample from 2 cross-sectional studies (PI1: 1991-93; PI2: 2009-11; n=1107), questionnaire-based data. Latent transition analysis (LTA) was performed to assess respiratory disease phenotypes at PI1 and PI2, labelled according to disease/symptom occurrence. Possible patterns were persistence, worsening and improvement of the phenotype. Multiple logistic regression models were estimated to assess the association among phenotype patterns, risk factors (smoking habits-SH and occupational exposure-OE) and physician visits, adjusting for age, sex and educational level. Results: 4 cross-sectional phenotypes were ranked by severity in PI1 and in PI2: healthy (H) (59 and 55%), allergic rhinitis (AR) (28 and 27%), cough/phlegm (CP) (11 and 15%), asthma (A) (3 and 4%). The longitudinal patterns were: persistent H (53%), persistent AR (27%), persistent CP (9%), improvement (2%), worsening (10%). Significant Associations: persistent CP with persistent SH (OR 5.9), persistent OE (OR 2.9) and incident OE (OR 2.2); persistent CP and worsening of phenotype with current visits of family physician (OR 5.4 and OR 4.7, respectively) and of specialist (OR 2.7 and OR 3.9, respectively). Conclusions: LTA allowed to identify four different phenotypes based on respiratory symptoms/diseases and their longitudinal patterns over 18 years. Such analysis brings new perspectives in the analyses of population-based data.

There are substantial doubts pertaining to the clinical usefulness of radiological and surgical interventions in the management of renovascular disease, particularly in patients with diffuse atherosclerotic vascular disease. This article reviews the current knowledge on advantages and limitations of interventional techniques in the management of patients with atherosclerotic renovascular disease. .

Importance Given that hypertension remains a leading risk factor for chronic disease globally, there are substantial ongoing efforts to define the optimal range of blood pressure (BP). Objective To identify a common threshold level above which BP rise tends to accelerate in progression toward hypertension. Design, Setting, and Participants This longitudinal, community-based epidemiological cohort study of adults enrolled in Framingham, Massachusetts, included 1252 participants (mean [SD] age, 35.3 [2.7] years) from the Framingham Original Cohort, of whom 790 (63.1%) were women. Each participant contributed up to 28 serial examinations of standardized resting BP measurements between 1948 and 2005. Exposures Age and systolic BP. Main Outcomes and Measures Via a segmented mixed model, we identified significant change points in the association between advancing age and increasing systolic BP among individuals categorized by their age at hypertension onset. Results Individuals maintained a relatively stable resting systolic BP level prior to hypertension onset. Systolic BP level began to rise at a more rapid rate after reaching a level of 123.2 mm Hg (95% CI, 122.7-130.1 mm Hg) in people with onset at 40 to 49 years; 122.0 mm Hg (95% CI, 120.3-123.9 mm Hg) in those with onset between 50 and 59 years, 124.9 mm Hg (95% CI, 120.2-127.9 mm Hg) in those with onset between 60 and 69 years, and 120.5 mm Hg (95% CI, 118.0-123.2 mm Hg) in those with onset between 70 and 79 years (P = .29 for between-group heterogeneity). Conclusions and Relevance We observed that individuals in the community generally maintained a systolic BP of less than 120 to 125 mm Hg, above which systolic BP increased at a relatively rapid rate toward overt hypertension. This trend was consistent whether the hypertension manifested earlier or later in life. Thus, a resting systolic BP that chronically exceeds the range of approximately 120 to 125 mm Hg may represent an important threshold of underlying vascular remodeling and signal incipient hypertension irrespective of age. Further investigations are needed to unravel the sequence of hemodynamic and vascular changes occurring prior to hypertension onset.

The use of biomaterials to treat anal fistula has drawn great interest. More recently, a porcine dermal matrix injection has been proposed as infill biomaterial to treat fistulas.We propose a novel approach consisting in non-cutting seton positioning followed by flap repair associated with dermal matrix injection into the fistula tracts after several weeks.We report our experience with this two-staged procedure on 11 consecutive patients with recurrent high trans-sphincteric fistulas with a minimum follow-up of 6 months.In our experience, this two-stage approach seems to be safe and effective.

Introduction: Bias may occur in randomized clinical trials in favor of the new experimental treatment because of unblinded assessment of subjective endpoints or wish bias. Using results from published trials, we analyzed and compared the treatment effect of hepatitis C antiviral interferon therapies experimental or control. Methods: Meta-regression of trials enrolling naïve hepatitis C virus patients that underwent four therapies including interferon alone or plus ribavirin during past years. The outcome measure was the sustained response evaluated by transaminases and/or hepatitis C virus-RNA serum load. Data on the outcome across therapies were collected according to the assigned arm (experimental or control) and to other trial and patient-level characteristics. Results: The overall difference in efficacy between the same treatment labeled experimental or control had a mean of +11.9% (p Conclusion: Our study indicates the same treatment is more effective when labeled “experimental” compared to when labeled “control” in a setting of trials using an objective endpoint and even after adjusting for patient and study-level characteristics. We discuss several factors related to design and conduct of hepatitis C trials as potential explanations of the bias toward the experimental treatment.

Introduction: Post-operative liver failure (PLF) occurs in approximately 10% of patients undergoing major hepatectomy. Partial portal vein arterialization (PPVA) enhances the regenerative capacity of the resected liver. The aim of this study was to investigate the impact of age on survival after PPVA for the treatment of post-operative liver failure in a rat model. Materials and Methods: 24 rats underwent extended liver resection, that leaded to PLF. 12 rats were divided in 2 groups treated with PPVA: group 1a-young rats (n=6, age 2 months) and group 2a-old rats (n=6, age 30 months). Two control groups of rats of the same age were not treated with PPVA: group 1b-young and group 2b-old. Results: on postoperative day 7, no significant differences were observed among all groups in terms of ALT levels, prothrombin activity and serum creatinine. As for the liver regeneration markers, the level of mitotic index was greater in the groups treated with PPVA compared to the control groups (without significant differences between young and old groups). The 75% (9/12) of the rats treated with PPVA survived up to 7 days, with no significant differences between young (5/6) and elderly rats 66.7% (4/6). Conclusion: PPVA treatment had the same beneficial effect both in young and old rats.

Background and Purpose— Higher low-density lipoprotein cholesterol is associated with more rapid chronic kidney disease progression; reduction in cholesterol with statins, in conjunction with statins’ pleiotropic effects, such as decreasing inflammation, may be renoprotective. The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial assessed the effect of statin treatment on the risk of nonfatal and fatal stroke in subjects with a noncardioembolic stroke or transient ischemic attack, no known coronary heart disease, and low-density lipoprotein cholesterol between 2.6 and 4.9 mmol/L (100–190 mg/dL). Methods— We explored the effect of randomization to atorvastatin 80 mg/d or placebo on the change in estimated glomerular filtration rate (eGFR; using the 4-component Modification of Diet in Renal Disease Study equation) in SPARCL subjects (n=4731) with (eGFR, 2 ; n=3119) and without (eGFR, ≥60 mL/min per 1.73 m 2 ; n=1600) chronic kidney disease overall and by glycemic status at baseline. Results— Mean baseline eGFR was similar between treatment groups (65.5±0.26 versus 65.6±0.26 mL/min per 1.73 m 2 atorvastatin versus placebo; 33% versus 34% had chronic kidney disease, respectively; P =0.55). After 60 months, eGFR increased 3.46±0.33 mL/min per 1.73 m 2 in those randomized to atorvastatin versus 1.42±0.34 mL/min per 1.73 m 2 in those randomized to placebo ( P 2 in the atorvastatin group and decreased 1.69±0.92 mL/min per 1.73 m 2 in placebo group during a period of 60 months ( P =0.016). Conclusions— This post hoc analysis suggests that atorvastatin treatment may improve renal function in patients with prior stroke or transient ischemic attack with and without chronic kidney disease, and that atorvastatin treatment may prevent eGFR decline in patients with stroke and diabetes mellitus. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00147602.

HMG-CoA reductase inhibitors (statins) have been shown to reduce cardiovascular morbidity in patients with normal and abnormal kidney function but not in patients with end-stage kidney disease. Evidence supports a role for statins in delaying the progression of kidney disease in a variety of experimental models in animals. However, the evidence that statins may retard CKD progression in humans is scant. In this review, we critically consider the available data supporting a role for statins in CKD progression in humans and the possibility that there might be differences among statins in regards to effects on the kidneys. Finally, we review the evidence that statins may increase the risk of acute kidney injury.

Catheter-based radiofrequency ablation technology to disrupt both efferent and afferent renal nerves has recently been introduced to clinical medicine after the demonstration of significant systolic and diastolic blood pressure reductions. Clinical trial data available thus far have been obtained primarily in patients with resistant hypertension, defined as standardized systolic clinic blood pressure ≥ 160 mm Hg (or ≥ 150 mm Hg in patients with type 2 diabetes) despite appropriate pharmacologic treatment with at least 3 antihypertensive drugs, including a diuretic agent. Accordingly, these criteria and blood pressure thresholds should be borne in mind when selecting patients for renal nerve ablation. Secondary forms of hypertension and pseudoresistance, such as nonadherence to medication, intolerance of medication, and white coat hypertension, should have been ruled out, and 24-h ambulatory blood pressure monitoring is mandatory in this context. Because there are theoretical concerns with regard to renal safety, selected patients should have preserved renal function, with an estimated glomerular filtration rate ≥ 45 ml/min/1.73 m(2). Optimal periprocedural management of volume status and medication regimens at specialized and experienced centers equipped with adequate infrastructure to cope with potential procedural complications will minimize potential patient risks. Long-term safety and efficacy data are limited to 3 years of follow-up in small patient cohorts, so efforts to monitor treated patients are crucial to define the long-term performance of the procedure. Although renal nerve ablation could have beneficial effects in other conditions characterized by elevated renal sympathetic nerve activity, its potential use for such indications should currently be limited to formal research studies of its safety and efficacy.

Hereditary angioedema (HAE) is a rare autosomal dominant disorder, due to C1-inhibitor deficiency, which causes episodic swellings of subcutaneous tissues, bowel walls and upper airways which are disabling and potentially life-threatening. We evaluated n = 17 patients with confirmed HAE diagnosis in basal and crisis state and n = 19 healthy subjects. The samples were tested for IL-17, FGFb, G-CSF and GM-CSF, using Bio-plex kit. Data analysis was performed via nonparametric Spearman’s correlations and two sets of linear mixed models. When comparing HAE subjects during basal and crisis states, we found out significantly (i.e., p value

We report a case of a 38-year old woman with a history of ulcerative colitis and Graves' disease who presented with pyoderma gangrenosum, microscopic hematuria, proteinuria, and positive myeloperoxidase ANCA. A renal biopsy revealed a focal proliferative glomerulonephritis with IgA deposits. All these manifestations are likely secondary to ulcerative colitis or to a common pathogenetic mechanism.

In the past decade, several new surgical tools have revived the hope for an improved technique to treat radically hemorrhoids with less postoperative pain. Among these radiofrequency (RF), excisional surgery seems to be safe, fast, and accompanied by less postoperative pain. The aim of this study was to evaluate and compare RF (ligasure TM) to conventional diathermy Milligan-Morgan hemorrhoidectomy (MMH).Between January 2003 and July 2009, 210 symptomatic patients were randomized to undergo RF (118 patients) or diathermy MMH (92 patients). Mean follow-up was 39 ± 16 months. Clinical outcome was assessed by validated questionnaire on postoperative symptoms and satisfaction. Primary endpoints were pain and wound healing. Secondary endpoints were operative time, early and late complications (including recurrences), and patient satisfaction. Data was analyzed using chi-squared test and Fisher's exact test.Despite postoperative pain was less after RF, this difference was significant only for severe pain (expressed as VAS score7). Significant differences were observed in terms of wound healing. The two techniques were similar in terms of early and late complications.RF hemorrhoidectomy is followed by reduced severe pain and better wound healing. However, in our experience, this is not followed by earlier return to daily activities.

There has been much recent interest in the role of aldosterone as an independent contributor to the progression of chronic kidney disease. Despite treatment with agents such as angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, many studies have shown that there is incomplete blockade of the renin-angiotensin cascade evidenced by persistent or rising plasma aldosterone levels despite therapeutic renin-angiotensin blockade. This phenomenon is commonly referred to as "aldosterone escape" and is thought to be one of the main contributors to chronic kidney disease progression despite conventional therapeutics. Animal models of the effects of exposure to exogenous aldosterone demonstrate the development of inflammation and fibrosis in both the myocardium and renal parenchyma. In limited human studies, aldosterone receptor antagonism is associated with decreased proteinuria and improved glomerular filtration rate. Although data support the addition of an aldosterone antagonist to conventional therapy when treating patients with chronic kidney disease, more studies are needed to determine the precise clinical indications and the appropriate safety monitoring.

End-stage renal disease (ESRD) is characterized by resting sympathetic overactivity. Baseline muscle sympathetic nerve activity (MSNA), which is governed by baroreflexes and chemoreflexes, is elevated in ESRD. Whether resting skin sympathetic nerve activity (SSNA), which is independent from baroreflex and chemoreflex control, is also elevated has never been reported in renal failure. The purpose of this study was to determine whether sympathetic overactivity of ESRD is generalized to include the skin distribution. We measured sympathetic nerve activity to both muscle and skin using microneurography in eight ESRD patients and eight controls. MSNA was significantly ( P = 0.025) greater in ESRD (37.3 ± 3.6 bursts/min) when compared with controls (23.1 ± 4.4 bursts/min). However, SSNA was not elevated in ESRD (ESRD vs. controls, 17.6 ± 2.2 vs. 16.1 ± 1.7 bustst/min, P = 0.61). Similar results were obtained when MSNA was quantified as bursts per 100 heartbeats. We report the novel finding that although sympathetic activity directed to muscle is significantly elevated, activity directed to skin is not elevated in ESRD. The differential distribution of sympathetic outflow to the muscle vs. skin in ESRD is similar to the pattern seen in other disease states characterized by sympathetic overactivity such as heart failure and obesity.

Despite the potentially life-threatening consequences of hyperkalemia, symptoms are often absent or mild. However, when hyperkalemia has been recognized, evaluation of vital signs is essential for determining hemodynamic stability and identifying the presence of cardiac arrhythmias related to the hyperkalemia. Quite commonly, and depending on the severity and rapidity of onset, hyperkalemia may be associated with substantial electrocardiographic (EKG) changes that can lead to death if proper interventions are not instituted. Through its effects on the resting membrane potential and threshold potential of excitable cells, hyperkalemia is a potentially life-threatening disorder. Symptoms and physical examination findings are often absent. Once identified, the entire clinical picture must be taken into account, including an assessment of hemodynamic stability, the presence of other electrolyte abnormalities, and an EKG evaluation. While there is a typical progression of EKG findings based on hyperkalemia severity, EKG manifestations are myriad and their evolution may be unpredictable.

Experimental evidence suggests that aldosterone contributes to progressive kidney disease. Angiotensin-converting enzyme inhibitors and angiotensin type 1 receptor antagonists suppress the renin-angiotensin system but they do not effectively reduce plasma aldosterone. Hence, administration of aldosterone receptor antagonists may provide additional renal protection. In the present prospective randomized open-label study, we evaluated the effects of spironolactone (25 mg/day for 1 year) on proteinuria and estimated glomerular filtration rate in 83 patients with chronic kidney disease already treated with angiotensin-converting enzyme inhibitors and/or angiotensin type 1 receptor antagonists. Eighty-two patients were treated with angiotensin-converting enzyme inhibitors and/or angiotensin type 1 receptor antagonists alone and served as controls. After 1 year of therapy, proteinuria decreased from 2.1+/-0.08 to 0.89+/-0.06 g/g creatinine (P0.001) in patients treated with spironolactone, but it did not change in control patients. Baseline aldosterone levels were significantly correlated with proteinuria (r=0.76, P0.0001), and predicted the degree of reduction in proteinuria with spironolactone (r=0.42, P0.0002). Baseline estimated glomerular filtration rate was similar in patients treated with spironolactone and controls (62.4+/-2.4 and 62.2+/-2.1 ml/min/1.73 m(2), respectively). After 1 month of therapy with spironolactone, estimated glomerular filtration rate decreased more in patients treated with spironolactone than in controls. However, by the end of 1 year the monthly rate of decrease in estimated glomerular filtration rate from baseline was lower in patients treated with spironolactone than in controls (0.323+/-0.044 vs 0.474+/-0.037 ml/min/1.73 m(2), P0.01). Spironolactone caused a significant rise in serum potassium levels (from 4.2+/-0.04 at baseline to 5.0+/-0.05 mEq/l after 12 months of treatment, P0.001). In conclusion, this study has shown that spironolactone may reduce proteinuria and retard renal progression in chronic kidney disease patients.

The prevalence of chronic kidney disease (CKD) and end-stage renal disease (ESRD) are steadily increasing. This phenomenon is in part linked to the aging of the US population, in part to the increasing prevalence of obesity, diabetes and related renal diseases. Some believe that renal ischemia may be a frequent cause of CKD and ESRD, but the prevalence of this condition is difficult to ascertain due to limitations of available diagnostic tools. The current definition of renal ischemia is also ground for confusion. Renal ischemia as a cause of progressive renal disease is commonly defined as a progressive decrease in glomerular filtration rate due to atherosclerosis of the main renal arteries. This definition however, is too restrictive and it does not take into account that functional and anatomical alterations of the renal microcirculation may also lead to progressive renal failure. In this review, we evaluate the clinical and pathophysiological aspects of ischemia-related progressive kidney disease.

Renal injury caused by the injection of phenol in the lower pole of one kidney increases blood pressure (BP), norepinephrine secretion from the posterior hypothalamic nuclei (PH), and renal sympathetic nerve activity in the rat. Renal denervation prevents these effects of phenol. We have also demonstrated that noradrenergic traffic in the brain is modulated by NO and interleukin-1β. In this study, we tested the hypothesis that the increase in sympathetic nervous system (SNS) activity in the phenol renal injury model is because of activation of reactive oxygen species. To this end, first we examined the abundance of several components of reduced nicotinamide-adenine dinucleotide phosphate oxidase (identified as the major source of reactive oxygen species), including gp91phox/Nox2, p22phox, p47phox, and Nox3 using real-time PCR. Second, we evaluated the effects of 2 superoxide dismutase mimetic, tempol (4-hydroxy-2,2,6,6-tetramethyl piperidinoxyl), and superoxide dismutase-polyethylene glycol on central and peripheral SNS activation caused by intrarenal phenol injection. Intrarenal injection of phenol raised BP, NE secretion from the PH, renal sympathetic nerve activity, and the abundance of reduced nicotinamide-adenine dinucleotide phosphate and reduced the abundance of interleukin-1β and neural-NO synthase mRNA in the PH, paraventricular nuclei, and locus coeruleus compared with control rats. When tempol or superoxide dismutase-polyethylene glycol were infused in the lateral ventricle before phenol, the effects of phenol on BP and SNS activity were abolished. The studies suggest that central activation of the SNS in the phenol-renal injury model is mediated by increased reactive oxygen species in brain nuclei involved in the noradrenergic control of BP.

The association between hypertension and chronic renal disease is well known. The pathogenesis of hypertension in patients with chronic kidney disease (CKD) is complex and multifactorial, which may explain why it is resistant to treatment. The traditional paradigm is that hypertension in CKD is due either to an excess of intravascular volume (volume dependent) or to excessive activation of the renin-angiotensin system in relation to the state of sodium/volume balance (renin-dependent hypertension). This review focuses on the importance of less established mechanisms, such as increased activity of the sympathetic nervous system, increased endothelin production, decreased availability of endothelium-derived vasodilators and structural changes of the arteries, renal ischemia, and sleep apnea.

HMG-CoA (3-hydroxy-3-methylglutaryl-CoA) reductase inhibitors (statins) have been shown to reduce serum cholesterol and cardiovascular morbidity and mortality. The mechanisms of these beneficial effects are reviewed. Altered inflammatory responses and improved endothelial function mediated by statins are thought to be, in part, responsible for the reduction in cardiovascular events. It has not been well established whether statins confer similar benefits to the kidney. In this review, we critically consider the available data whereby dyslipidemia mediates renal dysfunction by modulating the inflammatory response to diverse cytokines. We also review the emerging database suggesting that statins may modulate renal dysfunction by altering the response of the kidney to dyslipidemia, particularly in patients with end-stage renal disease (ESRD) and post-kidney transplant.

Experimental evidence suggests that aldosterone may contribute to progressive kidney disease. Although angiotensin-converting enzyme (ACE) inhibitors and angiotensin type 1 receptor antagonists (ARBs) suppress the renin-angiotensin system, these agents do not adequately control plasma aldosterone levels. Hence, administration of aldosterone receptor antagonists may provide additional renal benefits to the ACE inhibitors and ARBs.In the present uncontrolled pilot study, we evaluate the short-term (8 weeks) effects of spironolactone on proteinuria in 42 patients with chronic kidney disease (CKD) already treated with ACE inhibitors and/or ARBs.Spironolactone (25 mg/d for 8 weeks) decreased proteinuria from protein of 2.09 +/- 0.16 to 1.32 +/- 0.08 g/24 h after 2 weeks and 1.05 +/- 0.08 g/24 h after 8 weeks. Four weeks after discontinuation of spironolactone therapy, proteinuria returned to close to baseline values. Baseline proteinuria correlated significantly with plasma aldosterone level (r = 0.81; P0.0001). Moreover, baseline aldosterone level correlated significantly with degree of reduction in proteinuria after treatment with spironolactone (r = 0.70; P0.0001). Spironolactone caused a significant increase in serum potassium levels (from 4.4 +/- 0.1 mEq/L [mmol/L] at baseline to 4.8 +/- 0.1 mEq/L [mmol/L] after 8 weeks of treatment; P0.01).This study shows that spironolactone may effectively reduce proteinuria in patients with CKD. Concerns remain in regard to the risk for hyperkalemia in patients with CKD. Prospective randomized trials are necessary to confirm the efficacy and safety of antagonists of aldosterone on proteinuria and progression of CKD.

Pleiotropic, or non-lipid-dependent, effects mediated by 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have important clinical implications for the cardiovascular (CV) system. Atherosclerosis is an inflammatory process accompanied by increases in levels of plasma inflammatory markers and accumulation of immune cells within atherosclerotic plaques. Statins not only decrease serum lipid levels, but also inhibit signaling molecules at several points in inflammatory pathways. The anti-inflammatory effects and improved endothelial function associated with statin therapy are thought to be partly responsible for the reduction in CV morbidity and mortality. In analogy, patients with chronic kidney disease administered statins for CV risk reduction show evidence of improved renal function. However, whether statins confer similar protective benefits on the kidney has not been established. Several lines of evidence suggest that similar etiologic and pathological processes may be involved in CV and chronic kidney diseases. If inflammation and functional changes in the renovascular endothelium contribute to the progression of kidney disease, statins are likely to be effective in the treatment of renal disease. In this review, we critically consider emerging data indicating that statins may modulate renal function by altering the inflammatory response of the kidney and renal vasculature to dyslipidemia. Whether the amelioration of renal function by statins is separable from the lipid-lowering effects of these drugs still remains to be delineated. Other questions that remain to be addressed and issues that should be investigated also are presented.

In the United States, 50 million Americans are estimated to have hypertension. Over the past several decades, it has become clear that hypertension is both a cause and a consequence of kidney disease. In contrast to the striking decline in mortality rates from both stroke and coronary heart disease, the prevalence of hypertension as a cause of end-stage renal disease (ESRD) has increased such that it is now the second most common cause of ESRD in the United States. Hypertension and proteinuria occur in most patients with chronic kidney disease and are risk factors for faster progression of kidney disease. Antihypertensive agents reduce blood pressure and urine protein excretion and slow the progression of kidney disease. The level of blood pressure achieved and use of renin-angiotensin-aldosterone system-blocking agents is critical for delaying progression of renal disease in all ethnic groups.

Recent studies have implicated reactive oxygen species (ROS) in the pathogenesis of hypertension and activation of the sympathetic nervous system (SNS). Because nitric oxide (NO) exerts a tonic inhibition of central SNS activity, increased production of ROS could enhance inactivation of NO and result in activation of the SNS. To test the hypothesis that ROS may modulate SNS activity, we infused Tempol (4-hydroxy-2,2,6,6-tetramethyl piperidinoxyl), a superoxide dismutase mimetic, or vehicle either intravenously (250 microg x kg(-1) x min(-1)) or in the lateral ventricle (50 microg x kg body wt(-1) x min(-1)), and we determined the effects on blood pressure (BP), norepinephrine (NE) secretion from the posterior hypothalamus (PH) measured by the microdialysis technique, renal sympathetic nerve activity (RSNA) measured by direct microneurography, the abundance of neuronal NO synthase (nNOS)-mRNA in the PH, paraventricular nuclei (PVN), and locus coeruleus (LC) measured by RT-PCR, and the secretion of nitrate/nitrite (NO(x)) in the dialysate collected from the PH of Sprague-Dawley rats. Tempol reduced BP whether infused intravenously or intracerebroventricularly. Tempol reduced NE secretion from the PH and RSNA when infused intracerebroventricularly but raised NE secretion from the PH and RSNA when infused intravenously. The effects of intravenous Tempol on SNS activity were blunted or abolished by sinoaortic denervation. Tempol increased the abundance of nNOS in the PH, PVN, and LC when infused intracerebroventricularly, but it decreased the abundance of nNOS when infused intravenously. When given intracerebroventricularly, Tempol also reduced the concentration of NO(x) in the dialysate collected from the PH. Pretreatment with N(omega)-nitro-l-arginine methyl ester did not abolish the effects of intracerebral Tempol on BP, heart rate, NE secretion from the PH, and RSNA suggesting that the effects of Tempol on SNS activity may be in part dependent and in part independent of NO. In all, these studies support the notion that ROS may raise BP via activation of the SNS. This activation may be mediated in part by downregulation of nNOS and NO production, in part by mechanisms independent of NO. The discrepancy in results between intracerebroventricular and intravenous infusion of Tempol can be best explained by direct inhibitory actions on SNS activity when given intracerebral. By contrast, Tempol may exert direct vasodilation of the peripheral circulation and reflex activation of the SNS when given intravenously.

What, if anything, should physicians make of these apparently disparate hazards in a group of drugs that they prescribe so widely? The authors, and many of our colleagues, still believe that most patients clearly benefit from the judicious use of calcium antagonists. Reports of several large, powered prospective, randomized outcome studies including ALLHAT commend the use of long-acting calcium antagonists that, by virtue of their ability to attain more gradual and sustained plasma levels, do not evoke reactive sympathetic activation and consequently are safe. Concomitantly, such formulations should promote increased patient compliance and thereby favorably influence hypertension-related morbidity and mortality.

Background: It is important to test for microalbuminuria in patients with diabetes, hypertension and possible insulin resistance syndrome. Current screening methods are suboptimal. This study evaluates a new office screening test for microalbuminuria that utilizes a monoclonal antibody against human serum albumin (ImmunoDip®). Methods: 182 urine samples were collected from patients attending diabetes, nephrology or hypertension clinics. The ImmunoDip® screening test was carried out in the 182 samples after which albumin and creatinine concentrations were measured quantitatively in a reference laboratory. Results: Screening the 182 patient samples with ImmunoDip® and designating an albumin:creatinine ratio of ≧30 µg/mg as positive yielded a sensitivity of 96%, a specificity of 80%, a positive predictive value (PPV) of 66% and a negative predictive value (NPV) of 98%. The reduced specificity and PPV were not due to an intrinsic inaccuracy with ImmunoDip® screening of these samples, but rather was shown to be due to the discordance between the accepted upper limits of normal for the albumin:creatinine ratio (30 µg/mg) and the albumin concentration (20 mg/l), the latter corresponding to a ratio of 20 µg/mg. In 35 samples with albumin concentrations of 20–50 mg/l, ImmunoDip® screening yielded only one false negative (FN) result. Conclusions: ImmunoDip® is an excellent screening tool for microalbuminuria.