原发性醛固酮增多症(原醛症)是继发性高血压的常见病因之一,部分患者亦可伴有低血钾,醛固酮瘤及特发性醛固酮增多症是其主要的病理亚型.原醛症的诊断包括筛查、确诊及分型诊断3个步骤,传统影像学结合体位刺激的方法进行分型诊断,假阳性及假阴性率均较高,肾上腺静脉插管采血可作为影像学检查的补充.醛固酮瘤及原发性肾上腺增生患者应予手术治疗,特发性醛固酮增多症患者多采用药物治疗,螺内酯是其首选药物。

Primary aldosteronism

The treatment of testicular cancer is a success story in oncology. With available methods, 95% of men with this condition can be cured. Emphasis is shifting toward maintaining high cure rates and reducing or effectively managing late effects of treatment.

https://www.nejm.org/doi/pdf/10.1056/NEJMra1407550

Testicular Cancer — Discoveries and Updates

What is new

Cardiovascular disease is a major contributor to global morbidity and mortality and is the common end point of many chronic diseases. The endothelins comprise three structurally similar peptides of 21 amino acids in length. Endothelin 1 (ET-1) and ET-2 activate two G protein-coupled receptors — endothelin receptor type A (ETA) and endothelin receptor type B (ETB) — with equal affinity, whereas ET-3 has a lower affinity for ETA. ET-1 is the most potent vasoconstrictor in the human cardiovascular system and has remarkably long-lasting actions. ET-1 contributes to vasoconstriction, vascular and cardiac hypertrophy, inflammation, and to the development and progression of cardiovascular disease. Endothelin receptor antagonists have revolutionized the treatment of pulmonary arterial hypertension. Clinical trials continue to explore new applications of endothelin receptor antagonists, particularly in treatment-resistant hypertension, chronic kidney disease and patients receiving antiangiogenic therapies. Translational studies have identified important roles for the endothelin isoforms and new therapeutic targets during development, in fluid-electrolyte homeostasis, and in cardiovascular and neuronal function. Novel pharmacological strategies are emerging in the form of small-molecule epigenetic modulators, biologics (such as monoclonal antibodies for ETB) and possibly signalling pathway-biased agonists and antagonists. Endothelin 1 is the most potent vasoconstrictor in the human cardiovascular system. In this Review, Dhaun and Webb discuss the biology of the endothelins and endothelin receptors and how these pathways can be therapeutically targeted in cardiovascular and renal diseases.

Endothelins in cardiovascular biology and therapeutics.

Acid-sensing ion channels (ASICs) and the epithelial Na(+) channel (ENaC) are both members of the ENaC/degenerin family of amiloride-sensitive Na(+) channels. ASICs act as proton sensors in the nervous system where they contribute, besides other roles, to fear behaviour, learning and pain sensation. ENaC mediates Na(+) reabsorption across epithelia of the distal kidney and colon and of the airways. ENaC is a clinically used drug target in the context of hypertension and cystic fibrosis, while ASIC is an interesting potential target. Following a brief introduction, here we will review selected aspects of ASIC and ENaC function. We discuss the origin and nature of pH changes in the brain and the involvement of ASICs in synaptic signalling. We expose how in the peripheral nervous system, ASICs cover together with other ion channels a wide pH range as proton sensors. We introduce the mechanisms of aldosterone-dependent ENaC regulation and the evidence for an aldosterone-independent control of ENaC activity, such as regulation by dietary K(+) . We then provide an overview of the regulation of ENaC by proteases, a topic of increasing interest over the past few years. In spite of the profound differences in the physiological and pathological roles of ASICs and ENaC, these channels share many basic functional and structural properties. It is likely that further research will identify physiological contexts in which ASICs and ENaC have similar or overlapping roles.

https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1111/bph.13533

The function and regulation of acid-sensing ion channels (ASICs) and the epithelial Na(+) channel (ENaC): IUPHAR Review 19.

Background Significant variability exists for the relative risk (RR) of testicular malignancy in isolated cryptorchidism. Objective To perform a meta-analysis to clarify the true magnitude of this risk, allowing clinicians to better counsel patients and their families. Setting Secondary research conducted by undergraduate researchers, clinical academics and a clinical statistician. Design, data sources, and methods A search of the English literature was performed for studies relating to testicular cancer and cryptorchidism, published between 1 January 1980 and 31 December 2010, using Embase and Medline databases. 735 papers were identified and analysed by four authors independently in accordance with our inclusion and exclusion criteria. Studies reporting an association between cryptorchidism and subsequent development of testicular malignancy were included. Genetic syndromes or other conditions which predisposed to the development of cryptorchidism were excluded. Pooled estimates and 95% CIs for the RRs were calculated. Results Nine case–control studies and three cohort studies were selected. The case–control studies included 2281 cases and 4811 controls. Cohort studies included 2 177 941 boys, with a total of 345 boys developing testicular cancer (total length of follow-up was 58 270 679 person-years). The pooled RR was 2.90 (95% CI 2.21 to 3.82) with significant heterogeneity (p 2 =89%). Conclusion Boys with isolated cryptorchidism are three times more likely to develop testicular cancer. The limitations of this study must be acknowledged, in particular, possible publication bias and the lack of high-quality evidence focusing on the risk of malignancy in boys with isolated cryptorchidism.

https://adc.bmj.com/content/archdischild/98/1/20.full.pdf

A meta-analysis of the risk of boys with isolated cryptorchidism developing testicular cancer in later life

Among the environmental factors that affect blood pressure, dietary sodium chloride has been studied the most, and there is general consensus that increased sodium chloride intake increases blood pressure. There is accruing evidence that chloride may have a role in blood pressure regulation which may perhaps be even more important than that of Na+. Though more than 85 % of Na+ is consumed as sodium chloride, there is evidence that Na+ and Cl− concentrations do not go necessarily hand in hand since they may originate from different sources. Hence, elucidating the role of Cl− as an independent player in blood pressure regulation will have clinical and public health implications in addition to advancing our understanding of electrolyte-mediated blood pressure regulation. In this review, we describe the evidence that support an independent role for Cl− on hypertension and cardiovascular health.

https://link.springer.com/content/pdf/10.1007%2Fs00424-015-1690-8.pdf

The hidden hand of chloride in hypertension

Concerns exist regarding the potential increased cardiovascular risk from lowering diastolic blood pressure (DBP) in hypertensive patients. We analyzed 30-year follow-up data of 10 355 hypertensive patients attending the Glasgow Blood Pressure Clinic. The association between blood pressure during the first 5 years of treatment and cause-specific hospital admissions or mortality was analyzed using multivariable adjusted Cox proportional hazard models. The primary outcome was a composite of cardiovascular admissions and deaths. DBP showed a U-shaped association (nadir, 92 mm Hg) for the primary cardiovascular outcome hazard and a reverse J-shaped association with all-cause mortality (nadir, 86 mm Hg) and noncardiovascular mortality (nadir, 92 mm Hg). The hazard ratio for the primary cardiovascular outcome after adjustment for systolic blood pressure was 1.38 (95% CI, 1.18–1.62) for DBP <80 compared with DBP of 80 to 89.9 mm Hg (referrant), and the subdistribution hazard ratio after accounting for competing risk was 1.33 (1.17–1.51) compared with DBP ≥80 mm Hg. Cause-specific nonfatal outcome analyses showed a reverse J-shaped relationship for myocardial infarction, ischemic heart disease, and heart failure admissions but a U-shaped relationship for stroke admissions. Age-stratified analyses showed DBP had no independent effect on stroke admissions among the older patient subgroup (≥60 years of age), but the younger subgroup showed a clear U-shaped relationship. Intensive blood pressure reduction may lead to unintended consequences of higher healthcare utilization because of increased cardiovascular morbidity, and this merits future prospective studies. Low on-treatment DBP is associated with increased risk of noncardiovascular mortality, the reasons for which are unclear.

Diastolic Blood Pressure J-Curve Phenomenon in a Tertiary-Care Hypertension Clinic.

Genomics of Blood Pressure and Hypertension: Extending the Mosaic Theory Toward Stratification

Aims Hypertension and diabetes mellitus (DM) frequently cluster together and synergistically increase cardiovascular risk. Among those who develop DM during treatment for hypertension (new-onset diabetes, NOD), it is unclear whether NOD reflects a separate entity associated with increased risk or merely reflects accelerated presentation of DM.

Methods and results We analysed data on 15 089 hypertensive patients attending the Glasgow Blood Pressure Clinic. The date at first hospital encounter either with diagnosis of diabetes or prescription of anti-hyperglycaemic medication were considered as the onset of diabetes. Cox proportional hazard models (including propensity score matching) were employed to study associations between diabetes status, early and late NOD (diagnosis 10 years from first clinic visit) and cause-specific mortality. There were 2516 patients (16.7%) with DM, of whom 1862 (12.3%) had NOD [early NOD = 705 (4.6%); late NOD = 1157 (7.6%)]. The incidence rate of NOD was 8.2 per 1000 person-years. The total time at risk was 239 929 person-years [median survival: 28.1 years (inter-quartile range: 16.2–39.9)]. Compared with non-diabetic individuals, prevalent DM [hazard ratio (HR) = 1.8, 95% confidence interval (CI): 1.4–2.2] and time varying NOD status (HR: 1.09, 95% CI: 1.06–1.17) were associated with increased adjusted all-cause mortality. Early NOD (HR: 1.39, 95% CI: 1.2–1.6) was associated with increased in mortality risk, but not late NOD (HR: 0.92, 95% CI: 0.83–1.01). Results were consistent in the propensity score matched analyses.

Conclusion Although 1-in-8 hypertensive patients develop NOD, mortality is increased only in the 1-in-20 who develop early NOD. Further studies are warranted to determine if early identification of such individuals should provide an alert for intensification of therapeutic interventions.

/pdf/contrasting-mortality-risks-among-subgroups-of-treated-31myrwcl2d.pdf

Stefanie Lip

Papers

A meta-analysis of the risk of boys with isolated cryptorchidism developing testicular cancer in later life

The hidden hand of chloride in hypertension

Diastolic Blood Pressure J-Curve Phenomenon in a Tertiary-Care Hypertension Clinic.

Genomics of Blood Pressure and Hypertension: Extending the Mosaic Theory Toward Stratification

Contrasting mortality risks among subgroups of treated hypertensive patients developing new-onset diabetes.