Specific inhibition of the renin-angiotensin system: A key to understanding blood pressure regulation

The availability of specific inhibitors of the renin-angiotensin system has made it possible to evaluate precisely the contribution of this system to the maintenance of normal blood pressure and of various hypertensive situations encountered in animal models and in man. Furthermore, by combining the blockade of the renin system with accurate measurements of sodium balance, it is possible to expose and quantify latent or manifest abnormalities in renal sodium handling that operate directly or by interacting with the renin system.Experimental and clinical observations made with these inhibitors support the hypothesis that the level of blood pressure, normal or abnormal, is largely determined by two components: (1) the renin system (i.e., the angiotensin II-vasoconstrictor factor) and (2) the sodium extracellular and intravascular volume factor, which in the longer term may be indirectly supported by the renin system via angiotensin-induced aldosterone secretion.Normally, without threat to the homeostasis, the sodium volume component appears to be the main factor determining blood pressure and sustaining renal perfusion via adequate or—if necessary—increased blood pressure. However, whenever renal perfusion is compromised due to such events as hemorrhage, sodium depletion, upright posture, exercise, cardiac failure, cirrhosis, or renal vascular impairment, renin is secreted by the kidney. It seems that the renin-angiotensin system is the main vasoconstrictor system used by the body to support the sodium volume component to maintain or restore adequuate renal perfusion. There is little evidence that the catecholamines and the nervous system play any major or direct role in sustaining blood pressure, although indirectly they may be critically involved in monitoring renal renin release.Two models of renal hypertension have served as the experimental basis for development of this concept. Established two-kidney Goldblatt hypertension (one renal artery clipped, contralateral kidney intact) was found to be renin-dependent, since angiotensin II blockade induced a marked fall in blood pressure. Clinical counterparts to this predominantly “vasoconstrictor” type of hypertension are renovascular hypertension with unilateral renal artery stenosis, malignant and essential hypertension with high renin levels, and possibly normotensive situations with reduced “effective” blood volume such as cirrhosis and congestive heart failure.Chronic one-kidney Goldblatt hypertension (one renal artery clipped, contralateral nephrectomy) under conditions of unrestricted sodium intake appeared on the other hand to be predominantly sodium-volume-dependent, so that angiotensin II blockade did not alter the pressure level. However, sodium (and volume) depletion did not lower the blood pressure either in this model but resulted instead in a compensatory rise of renin release, and thus in a transition from a sodium-volume to vasoconstrictor-maintained type of hypertension. Accordingly, under conditions of sodium depletion, angiotensin II blockade did markedly reduce the blood pressure. Clinical counterparts to this model in which simultaneous sodium depletion plus blockade of the renin system are necessary to reduce blood pressure appear to be most patients with normal renin essential hypertension, chronic renal failure with normal or low renin levels, renovascular hypertension with bilateral renal artery stenoses, and possibly coarctation of the aorta.In contrast to these two model situations, low-renin essential hypertension as well as the hypertension induced by an excess of various mineralocorticoids appears to represent a pure volume type of hypertension, in which a diuretic-induced volume reduction does not result in a compensatory rise in renin release and a shift to vasoconstrictor support but instead results in a parallel reduction of blood pressure.     

Patient-Rated Access to Needed Care: Patient-Centered Medical Home Principles Intertwined

Background

Primary care teams can facilitate access to care by helping patients to determine whether and when care is needed, and coordinating care across multiple clinicians and settings. Appointment availability metrics may or may not capture these contributions, but patients' own ratings of their access to care provide an important alternative view of access that may be more closely related to these key functions of care teams.

Expression of nesfatin-1/NUCB2 in rodent digestive system

AIM: To observe the regional distributions and morphological features of nesfatin-1/nucleobindin-2 (NUCB2) immunoreactive (IR) cells in the rodent digestive system. METHODS: Paraffin-embedded sections of seven organs (pancreas, stomach, duodenum, esophagus, liver, small intestine and colon) dissected from sprague-dawley (SD) rats and institute of Cancer Research (ICR) mice were prepared. The regional distributions of nesfatin-1/NUCB2 IR cells were observed by immunohistochemical staining. The morphological ...     

New insights into Brunner syndrome and potential for targeted therapy

We report two families with Brunner syndrome living in one state of Australia. The first family had a predicted protein‐truncating variant of monoamine oxidase A (MAOA) (p.S251KfsX2). Affected males had mild intellectual disability (ID), obsessive behaviour, limited friendships and were introverted and placid during clinical interview. The family disclosed episodic explosive aggression after a diagnosis was made. The second family had a missense variant in MAOA (p.R45W). Affected males had borderline‐mild ID, attention deficit disorder and limited friendships. One had a history of explosive aggression in childhood and episodic symptoms of flushing, headaches and diarrhoea. Their carrier mother had normal intelligence but similar episodic symptoms. Characteristic biochemical abnormalities included high serum serotonin and urinary metanephrines and low urinary 5‐hydroxyindoleacetic acid (5‐HIAA) and vanillylmandelic acid (VMA). Symptomatic individuals in the second family had particularly high serotonin levels, and treatment with a serotonin reuptake inhibitor and dietary modification resulted in reversal of biochemical abnormalities, reduction of ‘serotonergic’ symptoms and behavioural improvement. Brunner syndrome should be considered as a cause of mild ID with paroxysmal behavioural symptoms. It can be screened for with serum/urine metanephrine and serotonin measurement. Cautious treatment with a serotonin reuptake inhibitor, dietary modifications and avoidance of medications contraindicated in patients on monoamine oxidase inhibitors can improve symptoms.     

Pedunculated Brunner＇s gland hamartoma of the duodenum causing upper gastrointestinal hemorrhage

A case of pedunculated Brunner＇s gland hamartoma （BGH） of the duodenum causing upper gastrointestinal （GI） hemorrhage is reported. The patient was a 47-year-old man who visited our hospital for further evaluation of tarry stools and shortness of breath. Endoscopic examination of the upper digestive tract revealed a large peduncular polyp with bleeding, about 30 mm in diameter, arising from the wall of the second portion of the duodenum. GI bleeding occurred from the base of the stalk of the polyp. Endoscopic polypectomy was performed. Histological examination of the specimen revealed that the main body of the polyp contained several Iobules of mature Brunner＇s gland with areas of cystic dilatation. The surface epithelium consisted of normal duodenal mucosa with areas of focal ulceration. This polyp was diagnosed as a BGH. The symptom of tarry stools resolved after endoscopic resection. Our case shows that treatment is necessary for duodenal BGH if GI bleeding occurs.     

Is the renin system necessary?

Numerous studies have been carried out to assess the role of the renin system in sustaining abnormally high blood pressure and in contributing to various other cardiovascular disorders such as congestive heart failure, ascites, and shock. The clinical use of potent and specific inhibitors of the renin-angiotensin system has produced important application in the treatment of high blood pressure, severe congestive cardiac failure and experimental hemorrhagic shock. Only in the state of considerable sodium depletion does blockade of the renin system produce any untoward effect, i.e. hypotension. These results are very similar to those obtained previously in patients with bilateral nephrectomy. They raise the question whether under conditions of our present salt-eating habits the renin system is really necessary.     

Brunner’s gland adenoma is a rare cause of upper gastrointestinal bleeding: A case report and literature review

Brunner’s gland adenoma is a rare benign tumour that arises from Brunner’s glands in the duodenum. Lesions are usually incidentally discovered during oesophagogastroduodenoscopy. However, in some cases, they may present clinically with vague abdominal symptoms or bleeding. We present the case of a 54-year-old male who complained of progressive fatigue and intermittent melena for 3 months. Clinical examination findings were unremarkable. Routine blood tests showed microcytic hypochromic anaemia. Oesophagogastroduodenoscopy showed normal oesophageal and gastric mucosa as well as a pedunculated polyp on the anterior wall of the duodenal bulb. Endoscopic ultrasound (EUS) revealed a duodenal hyperechoic mass arising from the submucosal layer of the anterior wall of the duodenal bulb with central cystic degeneration. Both endoscopic- and EUS-guided biopsies were non-diagnostic. Endoscopic mucosal resection was performed after the patient provided consent. Histopathological examination revealed hyperplastic mucosal lobules containing Brunner’s glands and smooth muscle cells; malignant cells or Helicobacter pylori infection were not evident. Brunner’s gland adenoma is a rare lesion of the duodenum and should be considered in the differential diagnosis of upper gastrointestinal bleeding. EUS is helpful in the diagnosis and detection of the layer of origin. However, the final diagnosis is usually made after lesion removal.     

Clinical and immunologic studies in identical twins discordant for systemic lupus erythematosus

Middle-aged female identical twins, one of whom had systemic lupus erythematosus (SLE), were evaluated for immunologic reactivity to previous antigenic challenges, including primary immunization with a foreign antigen, keyhole limpet hemocyanin (KLH). These two women had lived together for all of their 58 years and neither was receiving anti-inflammatory or immunosuppressive drugs at the time of these studies. Both twins demonstrated comparable 7S and 198 humoral antibody response to KLH, as well as similar viral antibody titers. However, the twin with SLE was anergic to common antigens, streptokinase-streptodornase, Trichophyton and Candida; furthermore delayed hypersensitivity to KLH did not develop after immunization. This observed discrepancy between humoral and cellular immunity in genetically similar subjects may be significant in the pathogenesis of SLE.     

Brunner's gland hyperplasia: treatment of severe diffuse nodular hyperplasia mimicking a malignancy on pancreatic-duodenal area

Brunner's gland hyperplasia is a benign tumor of the duodenum and it is rarely associated with clinical symptoms. We report on a 64-yr-old man with Brunner's gland hyperplasia who had undergone a duodenocephalo-pancreatectomy. The reason is that he presented upper gastrointestinal obstructive symptoms and the esophagogastroduodenoscopic finding revealed the lesion to be an infiltrating type mass on the second portion of the duodenum with luminal narrowing. An abdominal computed tomography showed a 2.5 cm-sized mass in the duodenal second portion with a suspicious pancreatic invasion and 7 mm-sized lymph node around the duodenum. Duodenocephalopancreatectomy was successfully performed. Histological examination revealed a Brunner's gland hyperplasia. The final diagnosis was the coexistence of Brunner's gland hyperplasia and pancreatic heterotopia with a pancreatic head invasion. The literature on Brunner's gland hyperplasia is reviewed.