Congenital nephrogenic diabetes insipidus arginine vasopressin receptor 2 gene mutation at new site: A case report

BACKGROUNDCongenital nephrogenic diabetes insipidus (CNDI) is a rare hereditary disorder. It is associated with mutations in the arginine vasopressin receptor 2 (AVPR2) gene and aquaporin 2 (AQP2) gene, and approximately 270 different mutation sites have been reported for AVPR2. Therefore, new mutations and new manifestations are crucial to complement the clinical deficiencies in the diagnosis of this disease. We report a case of a novel AVPR2 gene mutation locus and a new clinical mani-festation.CASE SUMMARYWe describe the case of a 48-d-old boy who presented with recurrent fever and diarrhea 5 d after birth. Laboratory tests showed electrolyte disturbances and low urine specific gravity, and imaging tests showed no abnormalities. Genetic testing revealed a novel X-linked recessive missense mutation, c.283 (exon 2) C>T (p.P95S). This mutation results in the substitution of a proline residue with a serine residue in the AVPR2 protein sequence. The diagnosis of CNDI was confirmed based on the AVPR2 gene mutation. The treatment strategy for this patient was divided into two stages, including physical cooling supplemented with appropriate amounts of water in the early stage and oral hydrochlorothia-zide (1-2 mg/kg) after a clear diagnosis. After follow-up of one and a half years, the patient gradually improved.CONCLUSIONAVPR2 gene mutations in new loci and new clinical symptoms help clinicians understand this disease and shorten the diagnosis cycle.     

Haemodynamic and neurohumoral effects of cold pressor test in severe heart failure

Summary. The effect of a cold pressor test (CPT) on haemodynamics in relation to general and regional sympathetic activity and arginin vasopressin (AVP), was studied in eleven patients with severe congestive heart failure (CHF). Compared to an age-matched control group (C), resting arterial plasma noradrenaline (NA) (419 ±77 vs. 182 ±15 pg ml^-1), and adrenaline (A) (142 ±28 vs 54 ±10 pg ml^-1) were higher (P<0.05) in CHF. AVP showed no significant difference (14±4 vs. 9±4 pg ml^-1). During CPT systolic and diastolic blood pressure and systemic vascular resistance increased (P<0.01), as did NA (δ 114±39 pg ml^-1, P<0.01), A (δ 33 ± 10 pg ml, P<0.01) and heart rate (δ 10 beats min^-1, P<0.01). The myocardial v-a difference of NA decreased (P<0.05), but was unchanged across the renal vascular bed during CPT. The a-v difference of NA in the hepatic vascular bed, and fractional extraction of A in the coronary sinus, renal and hepatic vascular beds remained unchanged during CPT. AVP did not change significantly and no change in cardiac index or left ventricular filling pressure was observed during CPT. These data suggest that despite an increased activation of the sympathetic nervous system at rest, a further increase in blood pressure and catecholamines took place during CPT. Thus, the effect of a CPT which activates the central sympathetic system seems not to be altered in patients with severe CHF.     

Role of the adrenal cortex in the natriuresis associated with vasopressin infusion

We have compared the effects of a 48-h continuous infusion of arginine vasopressin (AVP) given to four subjects (one subject studied twice) with that given to four patients lacking adrenocortical function and maintained on fixed doses of mineralocorticoid and glucocorticoid replacement therapy. Both patients and normal subjects were subjected to dietary salt and water restriction during the period of the infusion, and all participants were in balance on a low sodium diet at the start of the infusion period. Infusion of vasopressin in normal subjects was associated with an increase in fractional excretion of sodium by the kidney, which continued during the day after the infusion was stopped. The infusion was also associated with a fall in plasma aldosterone as well as falls in whole blood packed cell volume, plasma renin activity and plasma noradrenaline. Infusion of vasopressin in patients lacking adrenocortical function was associated with a smaller increase in fractional excretion of sodium by the kidney in comparison with that seen in normal subjects, and the increase in sodium excretion was confined to the period of the infusion. Mineralocorticoid activity was maintained constant during the infusion, although a fall in whole blood packed cell volume, plasma renin activity and plasma noradrenaline were noted, in similarity to the study made in normal subjects. We conclude that changes in mineralocorticoid activity are the main factors contributing to the increase in renal sodium excretion seen during, and after, the continuous infusion of vasopressin in salt- and water-restricted man.     

Influence of residual C-peptide secretion on the arginine vasopressin response to hypoglycaemia and metoclopramide in insulin-dependent diabetes

Abstract. Arginine vasopressin (AVP) hypersecretion in response to metoclopramide or to insulin-induced hypoglycaemia has been described in type I diabetes mellitus. In the present study, we examined whether residual endogenous insulin secretion may play a role in the control of this abnormal AVP secretory pattern. For this purpose, 21 insulin-dependent diabetic men and 10 age- and weight-matched normal men were tested with MCP (20 mg in an i.v. bolus). On a different occasion, subjects were tested with insulin (0.15IU kg^-1). The diabetic patients were subdivided into C-peptide negative patients (CpN, 11 patients without detectable endogenous pancreatic β cell activity) (group I) and C-peptide positive patients (CpP, 10 patients with residual endogenous insulin secretion) (group II). Experiments started after optimization of the metabolic status of the diabetic men by 3 days of treatment with continuous subcutaneous insulin infusion. The basal concentrations of AVP were similar in all groups. The administration of MCP induced a striking elevation in plasma AVP levels in the normal controls and in the diabetic subjects of groups I and II. However, the AVP rise was significantly higher in group I and group II than in normal controls. Furthermore, group I diabetics showed higher AVP increments than group II. Insulin induced a similar hypoglycaemic nadir in all subjects at 30 min, even though the diabetic subjects of groups I and II had a delayed recovery in blood glucose levels. The hypoglycaemic pattern was similar in group I and II. Hypoglycaemia induced a striking AVP increase in the normal controls. However, significantly higher AVP responses to hypoglycaemia were observed in the diabetic men of group I and group II than in the normal controls. Furthermore, group I diabetics showed higher AVP increments than group II. These data indicate that the hypothalamic-pituitary disorder affecting the AVP response to MCP and insulin-induced hypoglycaemia in well controlled type I diabetic men is inversely related to residual β-cell activity.     

儿童中枢性尿崩症的MRI诊断价值

目的：探讨磁共振成像（MRI）在儿童中枢性尿崩症（CDI）中的应用价值。材料和方法：对18例临床确诊为儿童CDI患者的MRI平扫及增强检查结果进行回顾性分析。结果：18例CDI患儿垂体后叶T1WI高信号均消失。其中颅咽管瘤7例，生殖细胞瘤2例，下丘脑-垂体区占位性病变3例，3例垂体柄和，或下丘脑漏斗部局限性梭形或球形增粗，单纯垂体后叶T1WI高信号消失者3例。结论：基于儿童CDI自身的特点，MRI平扫及增强扫描对诊断儿童CDI及寻找其病因具有重要价值。垂体后叶T1WI高信号消失是儿童CDI的非特异性MRI指标。     

Regulation of pain sensitivity in the central nervous system

Nociceptive information may be inhibited by stimulation of opiate receptors located presynaptically on primary afferent neurons. Sensory signals entering the spinal cord inhibit nociceptive signals by a non-opioid "gate" mechanism. Descending systems also modulate pain sensitivity at the spinal level. The descending 5-hydroxytryptamine (5-HT) system has a tonic inhibitory function, with diurnal fluctuations in intensity. The strong analgesic effects of electrical stimulation and morphine microinjections in certain brainstem structures is probably mediated by other descending systems. The ascending 5-HT system may influence the results of some complex tests for pain sensitivity by altering e.g. emotionality and habituation rate. Acupuncture analgesia involves opioid systems. In high frequency electroacupuncture and transcutaneous nerve stimulation, a non-opioid "gate" mechanism may predominate. Acute stress may produce analgesia by opioid as well as non-opioid mechanisms. The control of pain sensitivity is influenced by learning (e.g. biofeedback techniques and social factors), and may be affected in depression, mania and schizophrenia.     

A study of alpha1- and alpha2-adrenoceptor responsiveness in diabetic insipidus dogs

Summary— The present study was performed to investigate the participation of circulating vasopressin in alpha-adrenoceptor responsiveness. Thus, we compared the pressor responses induced by selective alpha1-or alpha2-adrenoceptor stimulation in two groups of conscious dogs: a) normal animals and b) animals with surgically-induced diabetes insipidus. In addition, platelet alpha2-adrenoceptors labelled with (³H)RX821002 were compared in the two groups. The pressor response to alpha1-adrenoceptor stimulation [ ie successive doses of noradrenaline (0.5, 1, 2, 4 μg/kg iv) after propranolol (1 mg/kg iv) plus yohimbine (0.5 mg/kg iv)] was significantly ( P < 0.05) less pronounced in diabetic insipidus than in normal dogs. In contrast, the magnitude of the pressor effects of alpha2-adrenoceptor stimulation [ ie noradrenaline after propranolol plus prazosin (1 mg/kg iv)] was the same in the two groups of animals. B_max and Kd values for (³H)RX821002 binding on platelets were similar in diabetic insipidus and normal dogs. This study shows that alpha1- (but not alpha2-) adrenoceptor responsiveness is decreased in diabetic insipidus suggesting the involvement of vasopressin in the mechanisms of the vascular alpha1 -adrenoceptor pressor response.     

Arginine vasopressin dissociates the diuresis and natriuresis due to atrial natriuretic factor in man

The possible interaction between arginine vasopressin (AVP) and atrial natriuretic factor (ANF) in the control of urinary sodium and water excretion was investigated in man. Nine healthy male volunteers undergoing stable maximal water diuresis were studied on four separate occasions. Atrial natriuretic factor 15 pmol kg-1 min-1 or placebo (P) was concomitantly administered against a background infusion of either AVP 0.003 pmol kg-1 min-1 or P; thus the combinations P + P, AVP + P, P + ANF and AVP + ANF were studied. Atrial natriuretic factor caused a significant increase in sodium excretion (UNaV) [+56%], urinary flow rate (V) [+17%] and free water clearance (CH2O) [+23%]; creatinine clearance (Ccr) did not change. Arginine vasopressin reduced V (-58%) and CH2O (-68%) but did not alter UNaV or Ccr. On the AVP + ANF study day, UNaV increased (+64%) as with P + ANF, but V (-44%) and CH2O (-52%) continued to decrease below baseline levels; analysis of variance showed this antidiuresis reflected the prevalent effect of AVP rather than any specific interaction. These results show that AVP is able to dissociate the natriuretic and diuretic effects of ANF.     

The combined effect of hypomagnesemia and hypokalemia inducing nephrogenic diabetes insipidus in a patient with type 1 diabetes mellitus

Nephrogenic diabetes insipidus (NDI) is rarely considered against more common differentials such as diabetes mellitus in patients presenting with polydipsia and polyuria. Hypokalemia and hypercalcemia are known to induce NDI, but not much is known about hypomagnesemia. Hypokalemia refractory to therapy should prompt consideration of hypomagnesemia.     

Progressive central hypovolaemia in man—resulting in a vasovagal syncope?

Summary. Hypotensive functional haemorrhage induced by venous pooling of blood in the legs has been reported to be characterized by a vasovagal reaction. In the present study these observations were extended by determination of the hormonal profile developed during progressive central hypovolaemia and an emotionally induced vasovagal syncope. In six subjects venous pooling resulted in normotensive central hypovolaemia, in one subject hypotensive central hypovolaemia was induced, and one subject experienced an emotionally induced vasovagal syncope. During normotensive central hypovolaemia heart rate increased from 58 ± 4 to 76 ± 4 beats min^-1 (P<0·05) and cardiac output fell from 6·1 ± 0·4 to 4·1 ± 0·21 min^-1. Pulse pressure and central venous pressure decreased from 64 ± 4 to 53 ± 4 mmHg, and from 8 ± 2 to 3 ± 2 mmHg, respectively. Adrenalin and noradrenalin increased from 87 ± 10 to 120 ± 20 pg/ml and from 196 ± 33 to 370 ± 50 pg/ml, respectively. Angiotensin II increased from 13 ± 4 to 36 ± 6 pg/ml and aldosterone from 63 ± 9 to 180 ± 27 pg/ml. In hypotensive central hypovolaemia the decrease in mean arterial pressure was accompanied by a decrease in heart rate and increments in the plasma concentrations of pancreatic polypeptide, indicating increased vagal activity and β-endorphin, while plasma noradrenalin was unchanged. In emotionally induced syncope heart rate decreased to cardiac arrest for 13 s, associated with increments in the plasma concentrations of pancreatic polypeptide and β-endorphin. It is concluded (1) that normotensive functional haemorrhage in man is associated with increased sympathetic activity and (2) that the qualitatively similar observations obtained during an emotionally and a hypovolaemic-induced hypotensive episode indicate that the hypotensive functional haemorrhage is characterized by a vasovagal reaction.     

Fluoxetine-induced pressor response in freely moving rats: a role for vasopressin and sympathetic tone

The present study was performed in order to assess, in freely moving rats, the cardiovascular effects of central administration of fluoxetine, a serotonin reuptake inhibitor. Two kinds of experiments were performed: 1) acute central administration of fluoxetine. and 2) chronic intraperitoneal administration of fluoxetine plus selegiline, a monoamine oxidase B inhibitor. Intracerebroventricular (i.c.v.) administration of fluoxetine (5-50 microg) induced an increase in blood pressure. This fluoxetine-induced pressor response reached its maximal 1 hour after injection without any significant change in heart rate. At the dose of 10 microg i.c.v., fluoxetine significantly increased mean blood pressure by 16 +/- 4 mmHg. This pressor response was reduced by an intravenous (i.v.) pretreatment with the alpha1-adrenoceptor antagonist, prazosin (500 microg kg(-1)) (+ 7 +/- 4 mmHg, P <0.05) or with the V1A-vasopressin receptor antagonist (20 microg kg(-1)) (+5 +/- 3 mmHg, P < 0.05). The pressor response was completely abolished by a concomitant pretreatment with prazosin plus the V1A-vasopressin receptor antagonist. Pretreatment with the beta-adrenoceptor antagonist, propranolol (1 mg kg(-1) i.v.), or the 5-HT2 receptor antagonist, ketanserine (5 mg kg(-1) i.v.), did not modify the fluoxetine-induced pressor response. In freely moving rats receiving fluoxetine (10 microg i.c.v.), vasopressin plasma levels were significantly higher (39 +/- 5 pg mL(-1) than in rats receiving 10 microL i.c.v. saline (14 +/- 4 pg mL(-1)). A 30 day intraperitoneal (i.p.) administration of fluoxetine in association with selegiline induced an increase in noradrenaline plasma levels and locomotor activity without any significant change in blood pressure and heart rate. These data suggest that, the pressor response elicited by central acute administration of fluoxetine is mediated by both an increase in sympathetic tone and vasopressin release. This observation could suggest the putative interest of alpha1-adrenoceptor and or V1A-vasopressin receptor antagonists in the treatment of "Serotonin Syndrome".     

Decreased insulin secretory capacity and normal pancreatic B-cell glucose sensitivity in non-obese patients with NIDDM

We investigated the dose-response characteristics of glucose-induced insulin release and the influence of hyperglycaemia on arginine-induced insulin secretion in eight non-obese subjects with NIDDM and in eight non-diabetic volunteers. Plasma C-peptide levels, achieved during 60 min hyperglycaemic clamps with and without the infusion of a primed continuous infusion of arginine (infusion rate 15 mg kg-1 min-1) during the last 30 min, were analysed with a modified Michaelis-Menten equation. The insulin secretory capacity (Vmax) for glucose-stimulated insulin release showed a trend towards a negative correlation with the fasting blood glucose in the NIDDM subjects (r = 0.68, P = 0.6); it was lower than the Vmax of non-diabetic controls (2.2 +/- 0.2 vs 4.2 +/- 0.4 nmol l-1 respectively; P less than 0.001). The ED50 (half maximal stimulating blood glucose concentration) of the second-phase glucose-stimulated insulin release (determined from the plasma C-peptide levels at 60 min) was not significantly different from the ED50 of the controls (11.9 +/- 0.8 vs 13.3 +/- 1.9 mmol l-1 respectively; P greater than 0.2). Combined glucose-arginine stimulation significantly increased insulin release. The Vmax for both phases were significantly lower in NIDDM patients than in controls (2.3 +/- 0.2 vs 5.0 +/- 0.9 and 3.8 +/- 0.5 vs 8.5 +/- 0.9 nmol l-1 respectively; P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

儿童中枢性尿崩症的病因及影像学检查的必要性

目的:分析儿童中枢性尿崩症的病因。材料与方法:复习180例儿童尿崩症的临床资料,对其中做过CT或MRI检查的105例中枢性尿崩症的临床及影像学进行回顾性分析研究。结果:原发性尿崩症59例,继发性尿崩症46例。结论:儿童中枢性尿崩症中继发性尿崩症占有相当高比例,一些开始诊断为原发性尿崩症者,若干年后可能出现鞍区肿瘤。鞍区影像学检查对儿童中枢尿崩症的病因分析起决定性作用,影像学随访也是非常必要的。     

Cardiovascular reflexes in patients with vascular headache

We have investigated the autonomic function of 75 patients with migraine by examining cardiovascular reflex function. The results were compared with those of 78 healthy volunteers. Measurements were made between attacks. Patients with migraine showed a smaller heart-rate response to deep breathing but a greater heart-rate response and higher blood pressure to standing when compared to controls. Migraine patients had a higher percentage of established sympathetic lesions (51% vs 17%) and severe (25% vs 5%) or atypical (24% vs 11.5%) global autonomic dysfunction. No significant differences were found among patients with migraine with aura, migraine without aura, and migraine with prolonged aura. Our findings indicate that patients with migraine have sympathetic hypofunction.     

Both plasma and renal endothelin-1 participate in the acute cardiovascular response to exercise

Plasma endothelin (ET-1) and renal endothelin are two distinct functional systems involved in maintaining blood volume. To investigate whether plasma and renal ET-1 participate in the cardiovascular response to exercise-induced hypovolaemia, we studied changes in plasma and urinary ET-1 in healthy non-professional athletes after 2 h of jogging performed both without and with drinking isotonic fluids. After the run, which caused a 13% plasma volume (PV) reduction, plasma and renal ET-1 (+117% and +118%) increased significantly (all P  < 0.01). Fluid loss restitution during the run significantly attenuated either the PV contraction (−1.2%) and plasma and renal ET-1 increase (+2 and +3%). At multiple regression analysis changes in AVP plasma concentration, and not in PRA or PV per se , were significantly related to ET-1 changes both in plasma and urine. The present findings indicate that both plasma and renal ET-1 participate in the cardiovascular response to hypovolaemia induced by long-lasting, dynamic exercise.     

Autonomic Function Testing in Patients with Migraine

SYNOPSIS
Autonomic nervous system function was studied in 62 patients with migraine. The Valsalva maneuver, deep breathing test, sustained handgrip test, orthostatic test and spectral analysis of heart rate variability in the supine and standing positions were performed in a group of 62 patients of both sexes, aged 21 to 50 years, and in an age-matched control group of 45 healthy volunteers.
Heart rate increase during sustained handgrip was significantly reduced in the headache group, when compared to the control group, while the results of the remaining cardiovascular tests did not significantly differ between the control and headache groups. In standing patients, the integrals of middle frequency bands of amplitude spectra were smaller in patients than in controls because the increase induced by standing was smaller in migraine patients. The results in patients with migraine with aura (21 patients) and migraine without aura (41 patients) did not differ significantly from each other. The same was true for the results of the female and male patients.
It is concluded that sympathetic function is impaired in migraine patients.     

Autonomic Function Testing in Patients with Tension-Type Headache

SYNOPSIS
Autonomic nervous system function was studied in 51 patients with tension-type headache. The Valsalva manoeuvre, deep breathing test, sustained handgrip test, orthostatic test and spectral analysis of heart rate variability in the supine and standing positions were performed in a group of 51 patients of both sexes aged 21 to 50 years and in an age-matched control group of 45 healthy volunteers.
Diastolic blood pressure increase and particularly heart rate increase during sustained handgrip were significantly reduced in the headache group, when compared to the control group, while the results of the remaining tests did not significantly differ between the control and headache groups. No significant differences were found between the episodic (19 patients) and chronic (32 patients) tension-type headache subgroups.
It is concluded that sympathetic function is impaired in tension-type headache patients.     

弥凝治疗经蝶垂体腺瘤术后中枢性尿崩症的临床研究

目的 观察口服弥凝片治疗经蝶垂体腺瘸术后中枢性尿崩症的疗效.方法 观察经蝶垂体腺瘤术后中枢性尿崩症患者口服弥凝片(0.1 mg,3次/d)2用前、后的尿量、尿渗透压等指标的变化.结果 34例患者口服弥凝前尿量为(7985.40±410.36)ml/d,血渗透压为(301.68±3.59))mOsm/kg;口服弥凝2周后,尿量较前减少至(2277.87±328.94)ml/d;血渗透压上升达(313.26±4.87)mOsm/kg,差异均有统计学意义(P均<0.01).用药期间无一例有不良反应.结论 口服弥凝片治疗经蝶垂体腺瘤术后尿崩症疗效明确,安全、方便.     

口服弥凝治疗鞍区肿瘤术后尿崩症的临床研究

目的观察口服弥凝片治疗鞍区肿瘤术后尿崩症的疗效。方法观察单剂量试验(单次口服弥凝片0.1mg)和两周试验(口服弥凝片0.1mg3次/天,口服两周)前后的尿量、尿渗透压等指标的变化。结果22例病人单次口服弥凝0.1mg后,尿量迅速下降,约为服药前的1/8,尿渗透压上升为服药前l0倍,此作用维持(12.52±3.81)h。服药两周后,尿量较前减少至(2155±360)ml/d;血渗透压上升达(312.32±5.26)mOsm/kg,单剂量和两周试验服药前后尿量和尿渗透压比较,差异有统计学意义,P<0.05。用药期间无一例有不良反应。结论口服弥凝片治疗鞍区肿瘤术后尿崩症疗效明确安全方便。     

Low plasma aldosterone despite normal plasma renin activity in uncomplicated type 1 diabetes mellitus: effects of RAAS stimulation

BACKGROUND: Data on levels and responsiveness of PRA and aldosterone in type 1 diabetes mellitus are conflicting. Earlier studies were not standardized with respect to the type of diabetes mellitus, the presence of diabetic complications or sodium intake. Therefore, we studied plasma renin activity and plasma aldosterone in uncomplicated type 1 diabetes mellitus by evaluating the effects of endogenous (sodium restriction) and exogenous (angiotensin I infusion) stimulation. DESIGN: Twenty-four type 1 diabetic patients and 24 matched healthy subjects were studied after 1 week of liberal sodium diet (200 mmol 24 h-1) and 1 week of low sodium diet (50 mmol 24 h-1). Angiotensin (Ang)I was infused at 4 and 8 ng kg-1 min-1 during both study days. RESULTS: During liberal and low sodium intake, plasma aldosterone was lower in type 1 diabetic patients compared with healthy subjects both at 08:00 h (P < 0.05) and after a 2-h euglycaemic clamp (P < 0.05), despite similar PRA levels. The correlations between changes in PRA and changes in plasma aldosterone when shifting sodium intake were similar in both groups. During liberal sodium intake, the aldosterone levels after AngI infusion were lower in type 1 diabetic patients, whereas during low sodium they were not different. CONCLUSIONS: Plasma aldosterone was deceased relative to PRA in uncomplicated type 1 diabetic patients, irrespective sodium intake. The responsiveness to sodium restriction was adequate and sodium restriction was able to overcome the decreased plasma aldosterone response to exogenous AngI, which was observed during liberal sodium in diabetic patients. The lower aldosterone is not secondary to diabetic complications and does not depend on the level of sodium intake.