Measurement of arginine vasopressin.

Arginine vasopressin (AVP) is a peptide hormone synthesised in the hypothalamus and secreted from nerve terminals within the posterior pituitary gland. Secretion is primarily under osmoregulatory control and levels rise in plasma in response to a body water deficit and are suppressed in response to water overload. The responsive end organ in osmoregulation is the kidney, and an increase in plasma AVP normally results in urine concentration while a decrease results in urine dilution and a diuresis. The hormone is present in urine. The level of AVP in urine is directly related to the prevailing plasma concentration, but is also influenced by urine concentration, osmolal clearance, and renal metabolism. The measurement of AVP in plasma and urine is by radioimmunoassay (RIA). Prior extraction of the hormone is required to remove interfering substances and, particularly for plasma measurements, to concentrate the assayed sample. The secretion of AVP by the posterior pituitary gland is also stimulated by non-osmoregulatory factors such as reduced blood volume, reduced blood pressure, and nausea and is acutely suppressed by an oropharyngeal reflex. Plasma AVP measurement has a role in delineating complex osmoregulatory dysfunction, but protocols for study need to control the non-osmoregulated stimulatory and inhibitory factors. The urine AVP excretion rate corrected for osmolal clearance has a role in the assessment of renal responsiveness to its action.

Free radical-mediated lipid peroxidation and systemic nitric oxide bioavailability: implications for postexercise hemodynamics.

BACKGROUND: The metabolic vasodilator mediating postexercise hypotension (PEH) is poorly understood. Recent evidence suggests an exercise-induced reliance on pro-oxidant-stimulated vasodilation in normotensive young human subjects, but the role in the prehypertensive state is not known. METHODS: Nine prehypertensives (mean arterial pressure (MAP), 106 ± 5 mm Hg; 50 ± 10 years old) performed 30 minutes of cycle exercise and a nonexercise trial. Arterial distensibility was characterized by simultaneously recording upper- and lower-limb pulse wave velocity (PWV) via oscillometry. Systemic vascular resistance and conductance were determined by MAP/Q and Q/MAP, respectively. Venous blood was assayed for indirect markers of oxidative stress (lipid hydroperoxides (LOOH); spectrophotometry), plasma nitric oxide (NO) and S-nitrosothiols (fluorometry), atrial natriuretic peptide (ANP), and angiotensin II (ANG-II) (radioimmunoassay). RESULTS: Exercise reduced MAP (6mm Hg) and vascular resistance (15%) at 60 minutes after exercise, whereas conductance was elevated (20%) (P < 0.05). The hypotension resulted in a lower MAP at 60 and 120 minutes after exercise compared with nonexercise (P < 0.05). Upper-limb PWV was also 18% lower after exercise compared with baseline (P < 0.05). Exercise increased LOOH coincident with the nadir in hypotension and vascular resistance but failed to affect plasma NO or S-nitrosothiols. Exercise-induced increases in LOOH were related to ANG-II (r = 0.97; P < 0.01) and complemented by elevated ANP concentrations. CONCLUSIONS: These data indicate attenuated vascular resistance after exercise with increased oxidative stress and unchanged NO. Whether free radicals are obligatory for PEH requires further investigation, although it seems that oxidative stress occurs during the hyperemia underlying PEH.

An acute bout of self-myofascial release increases range of motion without a subsequent decrease in muscle activation or force.

Foam rolling is thought to improve muscular function, performance, overuse, and joint range of motion (ROM); however, there is no empirical evidence demonstrating this. Thus, the objective of the study was to determine the effect of self-myofascial release (SMR) via foam roller application on knee extensor force and activation and knee joint ROM. Eleven healthy male (height 178.9 ± 3.5 cm, mass 86.3 ± 7.4 kg, age 22.3 ± 3.8 years) subjects who were physically active participated. Subjects' quadriceps maximum voluntary contraction force, evoked force and activation, and knee joint ROM were measured before, 2 minutes, and 10 minutes after 2 conditions: (a) 2, 1-minute trials of SMR of the quadriceps via a foam roller and (b) no SMR (Control). A 2-way analysis of variance (condition × time) with repeated measures was performed on all dependent variables recorded in the precondition and postcondition tests. There were no significant differences between conditions for any of the neuromuscular dependent variables. However, after foam rolling, subjects' ROM significantly (p < 0.001) increased by 10° and 8° at 2 and 10 minutes, respectively. There was a significant (p < 0.01) negative correlation between subjects' force and ROM before foam rolling, which no longer existed after foam rolling. In conclusion, an acute bout of SMR of the quadriceps was an effective treatment to acutely enhance knee joint ROM without a concomitant deficit in muscle performance.

A family with hyponatremia and the nephrogenic syndrome of inappropriate antidiuresis.

Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is an X-linked disorder caused by activating mutations in arginine vasopressin receptor 2 (AVPR2), resulting in persistently concentrated urine. We report on a family affected by NSIAD with the known mutation R137C, an arginine to cysteine substitution at amino acid 137. The spectrum of symptoms varied markedly and ranged from infrequent voiding to incidentally noted hyponatremia to recurrent admissions with hyponatremic seizures. There was evidence for physiologic compensatory mechanisms: most affected members intuitively compensated for the concentrated urine by curtailing their fluid intake. Before the genetic diagnosis, these members had recognized each other by their infrequent voiding, which especially suited one patient, a London cab driver. Interestingly, after water deprivation, urine osmolality was significantly lower in patients compared with unaffected members, suggesting desensitization of the downstream signaling pathway with persistent AVPR2 activation. Urine osmolality was as low as 241 mOsm/kg (241 mmol/kg) in patients, which could obfuscate the diagnosis. The development of symptoms of hyponatremia was strikingly different in the 2 male patients: one patient was asymptomatic with a plasma sodium level of 120 mEq/L (120 mmol/L), whereas another experienced seizures with similar values. Investigations of such genetically defined patients show clues for the understanding of human physiology and inform diagnosis and clinical management.

Quantitating nocturia: a study into the recording of solute and water excretion to determine causation.

BACKGROUND: Nocturia is common but the clinical assessment of its severity and cause rarely involves any biochemical analysis. Investigating the cause of nocturia needs to be informed by the overall 24 h fluid and solute excretion patterns. The aim of this study was to establish a practical method of monitoring the renal excretion of water and solutes over a complete 24 h cycle. METHODS: The excretion patterns of sodium, volume and osmoles were assessed in 89 healthy control subjects over a 24 h period by sampling each voiding from the 24 h collection and then using the total urine creatinine as the denominator. A group of 21 patients under investigation for sleep-disordered breathing (SDB: a group of disorders known to increase the risk of nocturia) were also studied to determine comparative excretion patterns. RESULTS: Reference excretion patterns of sodium, volume and osmoles were described. Patients under investigation for SDB had overall a significant (P < 0.001) increase in urine sodium excretion at night (nocturnal natriuresis) matched by an increased osmotic excretion and accompanied by a significantly increased nocturnal urine volume (P < 0.001). CONCLUSION: Breaking down a 24 h urine collection into voided aliquots provides practical information on the pattern of water and solute excretion. Such patterns may assist in identifying the underlying mechanism of significant nocturia in individual patients presenting with this symptom, and could be used as a method of monitoring treatment.

Thiazolidinediones and the renal and hormonal response to water immersion-induced volume expansion in type 2 diabetes mellitus.

Thiazolidinediones cause sodium retention and edema by a direct effect on the kidneys. The aim of this study was to use the technique of head-out water immersion to investigate the effects of rosiglitazone on sodium and volume homeostasis in subjects with type 2 diabetes mellitus. The volume expansion response to water immersion was compared with the response on a non-immersion control day in 12 nondiabetic male subjects and 8 diet-controlled male type 2 diabetic subjects with hourly blood and urine sampling over a 4-h period. This was repeated after both groups had taken 4 mg of rosiglitazone daily for 7 days. Immersion produced a natriuresis in both groups (P < 0.001). An impairment of this natriuresis was seen in the diabetic subjects (P = 0.006). However, when rosiglitazone was taken, there was no significant difference in immersion-induced natriuresis compared with nondiabetic controls (P = 0.2). There was an immersion-induced rise in atrial natriuretic peptide (ANP) and urinary cyclic guanosine monophosphate (cGMP), in the healthy subjects (ANP P = 0.001, cGMP P = 0.043), which was not seen in the diabetic subjects (ANP P = 0.51, cGMP P = 0.74). Rosiglitazone restored the immersion-induced increase in cGMP excretion and rise of ANP in the diabetic group (ANP P = 0.048, cGMP P = 0.009). This study confirms that type 2 diabetic subjects have an impaired natriuretic response to acute volume expansion, which appears to be enhanced rather than diminished by rosiglitazone. This may be related to its effects in increasing natriuretic peptides and restoring the impaired cGMP excretion to volume expansion.

The impact of an out-reach clinic on referral of patients with renal impairment.

BACKGROUND: Early diagnosis and prompt treatment of a number of renal diseases may delay renal failure, obviate the need for renal replacement therapy and reduce co-morbidity. The aim of this study was to examine the impact of out-reach renal clinics on patterns of referral of patients with renal impairment to a nephrologist. METHODS: The number of patients with renal impairment was determined as defined by serum creatinine levels >150 micromol/l in three centres within a single NHS trust over two separate 1-week periods. None of the centres studied has a local nephrologist, however one centre (hospital A) has renal out-reach clinics, another is geographically close to a renal unit (hospital B), while the third unit (hospital C) has no nephrology presence and is geographically furthest from the renal unit. In addition, retrospective as well as follow-up data on the renal function of all patients with renal impairment was collected. RESULTS: In hospital A, there was a lower proportion of patients with unreferred renal impairment than in the other two hospitals. Within the unreferred patient group there were significantly more patients whose renal function improved during the follow-up period. A considerable proportion of patients with documented deterioration in renal function remained unknown to nephrology services 6 months after initial presentation. Other than the presence of an onsite nephrology service, the only other factor found to be significantly different in those patients not referred to nephrologists was age: as in all three centres, those not referred were significantly older. CONCLUSION: Inequity of access to renal services is an important obstacle to early referral of patients with impaired renal function. Out-reach renal services provide a model which significantly improves referral patterns.

Plasma atrial natriuretic peptide in fetuses with cardiac disease.

OBJECTIVE: To investigate atrial natriuretic peptide (ANP) levels in fetuses with cardiac defects and to evaluate the relationships between plasma ANP levels and the presence of polyhydramnios. METHODS: Plasma ANP levels were measured by radioimmunoassay in 27 fetuses with cardiac abnormalities and in 14 normal healthy fetuses. RESULTS: Fetal plasma ANP levels were similar in the two studied groups (p = 0.18) but they were significantly higher in a subset of cases with cardiac disease and polyhydramnios (n = 7) than in those with cardiac disease and normal amniotic fluid (n = 20; p = 0.036) and controls (p = 0.01). CONCLUSION: Polyhydramnios in fetuses with heart conditions might be explained by increased fetal diuresis secondary to increased ANP production.

Using iron deficiency tests for colorectal cancer screening: a feasibility study in one UK general practice.

Iron deficiency is common at presentation in colorectal cancer. Testing for it may complement other screening tests such as faecal occult blood testing and sigmoidoscopy. We therefore examined the feasibility of offering iron deficiency testing to patients in a primary care setting in the UK, offering testing to all 1240 patients aged 55-74 years in one general practice in South Wales, UK. Patients with abnormal results were assessed and offered further investigations. Five hundred and fifty-one people (44.4%) attended for iron deficiency blood tests, of whom 26 patients (4.7%) were iron deficient and offered endoscopic assessment. This identified two cases of benign neoplasia amenable to treatment and no cases of cancer. Iron deficiency testing in a screening context appeared feasible although uptake may be low.

Addition of candesartan to angiotensin converting enzyme inhibitor therapy in patients with chronic heart failure does not reduce levels of oxidative stress.

BACKGROUND: Angiotensin II exerts a number of harmful effects in patients with chronic heart failure (CHF) and, through an increase in oxidative stress, is thought to be critical in the development of endothelial dysfunction. Angiotensin II may be elevated in CHF despite treatment with angiotensin converting enzyme (ACE) inhibitors, producing a rationale for adjunctive angiotensin receptor blockade. We investigated whether the addition of angiotensin antagonism to ACE inhibition would reduce oxidative stress and improve endothelial function and exercise tolerance in patients with chronic heart failure. METHODS AND RESULTS: Twenty-eight heart failure patients, who were on stable ACE inhibitor therapy, were randomised to receive adjunctive therapy with candesartan or placebo. Plasma lipid-derived free radicals, TBARS and neutrophil O2-generation, markers of oxidative stress, were measured in venous blood. Arterial endothelial function was assessed as the response of the brachial artery to flow-related shear stress. Exercise capacity was determined by cardiopulmonary exercise testing. Compared with placebo, candesartan had no effect on changes in lipid derived free radicals (-0.1+/-1.2 vs. -0.1+/-1.0 units, respectively, P=NS), TBARS (-2.2+/-1.1 vs. -2.6+/-2.2 micromol/l, respectively, P=NS) or neutrophil O2-generating capacity (-7.3+/-5.1 vs. -8.4+/-7.9 mV/5x10(5) neutrophils, respectively, P=NS). There was no effect on changes in brachial artery flow-mediated dilatation (0.5+/-1.0 vs. 0.8+/-1.3%, respectively, P=NS) nor peak VO2 (1.6+/-0.7 ml/kg per min vs. 1.8+/-0.6 ml/kg per min; P=NS). CONCLUSION: The addition of the candesartan to ACE inhibitor therapy had no effect on oxidative stress and did not improve endothelial function or exercise capacity in patients with CHF.