Osmoregulation of vasopressin secretion is altered in the postacute phase of septic shock.

OBJECTIVE: To determine whether septic shock patients have an abnormal reponse to increasing osmolarity. DESIGN: Prospective interventional study. SETTING: Intensive care unit at Raymond Poincaré and Etampes Hospitals. PATIENTS: Normonatremic patients at > 72 hrs from septic shock onset. INTERVENTION: Osmotic challenge consisting of infusing 500 mL of hypertonic saline solution (with cumulative amount of sodium not exceeding 24 g) over 120 mins. MEASUREMENTS AND MAIN RESULTS: Plasma arginine vasopressin levels were measured 15 mins before the test and then four times every 30 mins. A slope of the relation between arginine vasopressin and plasma sodium levels of < 0.5 pg/mEq defined nonresponders. Among the 33 included patients, 17 (52%) were nonresponders. During osmotic challenge, variations throughout the test in plasma sodium levels, blood pressure, and central venous pressure were comparable between the two groups. Arginine vasopressin increased from 4.8 pg/mL [3.3-6.4 pg/mL] to 14.4 pg/mL [11.2-23.3 pg/mL] in responders but only from 2.8 pg/mL [2.3-4.0 pg/mL] to 4.0 pg/mL [3.1-5.3 pg/mL] in nonresponders (p < .0001). Responders had a higher plasma arginine vasopressin levels at baseline and a more severe hematosis alteration. Nonresponders had more frequently bacteremia and liver dysfunction, been referred from the ward and undergone surgery. Critical illness severity, hemodynamic alteration, hydroelectrolytic disturbances, treatment, and outcome did not differ between the two groups. CONCLUSION: Osmoregulation is dramatically altered in half of patients with prolonged septic shock.

A simplified method for the detection of Y chromosome microdeletions in infertile men using a multiplex sequence-tagged site-based amplification.

Sixteen sequence-tagged sites (STSs) were combined in five amplification reactions, to screen for deletions of DNA fragments located within the AZFa, AZFb, and AZFc regions of the Y chromosome. This multiplex strategy is fast and reliable, and most of the azoospermia-associated deletions reported so far are detected with this simplified method. Internal control STSs are included that allow discrimination between deletion and failure of amplification.

Thirst perception and osmoregulation of vasopressin secretion are altered during recovery from septic shock.

OBJECTIVE: Vasopressin (AVP) secretion during an osmotic challenge is frequently altered in the immediate post-acute phase of septic shock. We sought to determine if this response is still altered in patients recovering from septic shock. DESIGN: Prospective interventional study. SETTING: Intensive care unit (ICU) at Raymond Poincaré and Etampes Hospitals. PATIENTS: Normonatremic patients at least 5 days post discontinuation of catecholamines given for a septic shock. INTERVENTION: Osmotic challenge involved infusing 500 mL of hypertonic saline solution (with cumulative amount of sodium not exceeding 24 g) over 120 minutes. MEASUREMENTS AND MAIN RESULTS: Plasma AVP levels were measured 15 minutes before the infusion and then every 30 minutes for two hours. Non-responders were defined as those with a slope of the relation between AVP and plasma sodium levels less than < 0.5 ng/mEq. Among the 30 included patients, 18 (60%) were non-responders. Blood pressure and plasma sodium and brain natriuretic peptide levels were similar in both responders and non-responders during the course of the test. Critical illness severity, hemodynamic alteration, electrolyte disturbances, treatment and outcome did not differ between the two groups. Responders had more severe gas exchange abnormality. Thirst perception was significantly diminished in non-responders. The osmotic challenge was repeated in 4 non-responders several months after discharge and the abnormal response persisted. CONCLUSION: More than half of patients recovering from septic shock have an alteration of osmoregulation characterised by a dramatic decrease in vasopressin secretion and thirst perception during osmotic challenge. The mechanisms of this alteration but also of the relationship between haematosis and normal response remain to be elucidated.

Screening patients with hypertrophic cardiomyopathy for Fabry disease using a filter-paper test: the FOCUS study.

BACKGROUND: Patients with Fabry disease (FD) show left ventricular hypertrophy (LVH) mimicking hypertrophic cardiomyopathy (HCM) of sarcomeric origin and might benefit, if detected early, from specific enzyme replacement therapy. The prevalence of FD in patients with LVH of 13 mm or greater, screened using the leucocyte alpha-galactosidase A (α-gal A) activity test, a technique that is difficult to apply routinely, ranged from 0% to 6%. OBJECTIVE: To screen systematically for FD in patients with a diagnosis of HCM (LVH ≥15 mm) in primary cardiology practice, a validated, physician-friendly α-gal A assay was used on dried blood spots using a filter paper test. DESIGN AND PATIENTS: A cohort of 392 adults (278 men) followed for HCM were screened for FD. A standard blood test was used for confirmation in nine men in whom the α-gal A result was 40% or less. RESULTS: Four men (1.5%; 1.8% of men ≥40 years vs 0% <40 years; all with α-gal A <30%), but no women, were diagnosed with FD. Index cases presented with diffuse but asymmetric LVH, with severe obstruction in one case and frequent high-grade atrioventricular conduction block necessitating a pacemaker in three cases. Family screening identified eight additional cases. Genotyping was performed successfully on DNA extracted from the filter papers. CONCLUSION: In male patients diagnosed as having HCM, pure FD cardiac variants are not exceptional and can be specifically identified using a simple filter-paper test. The sensitivity of this test is low in female patients.

Molecular characterization of a novel mutation in the factor XIII a subunit gene associated with a severe defect: importance of prophylactic substitution.

A congenital FXIII A subunit deficiency was diagnosed in a male child because of umbilical bleeding at birth. Venous infusion was difficult and prophylactic FXIII infusion was delayed. At age 1, he suffered a spontaneous intracranial haemorrhage. Substitutive FXIII was initiated, and at age 12, no other significant bleeding event had occurred. His 5 years younger brother also bears the same FXIII deficiency. The younger brother's treatment was initiated at birth and never discontinued, and no bleeding occurred. Mutation gene analysis found a homozygous four bases insertion predicting a stop codon seven residues after PRO675. Antigen assay indicated that the mutant molecule is secreted. This case highlights the importance of prophylactic FXIII infusion.