deamino-arginine-vasopressin and Syndrome

The acquired von Willebrand syndrome (AVWS) is a bleeding disorder that is frequently unrecognized or is misdiagnosed as von Willebrand disease. AVWS is characterized by structural or functional defects of von Willebrand factor (VWF) that are secondary to autoimmune, lymphoproliferative or myeloproliferative, malignant, cardiovascular, or other disorders. VWF abnormalities in these disorders can result from (1) antibody-mediated clearance or functional interference, (2) adsorption to surfaces of transformed cells or platelets, or (3) increased shear stress and subsequent proteolysis. Diagnosis can be challenging as no single test is usually sufficient to prove or exclude AVWS. Furthermore, there are no evidence-based guidelines for management. Treatments of the underlying medical condition, including chemo/radiotherapy, surgery, or immunosuppressants can result in remission of AVWS, but is not always feasible and successful. Because of the heterogeneous mechanisms of AVWS, more than one therapeutic approach is often required to treat acute bleeds and for prophylaxis during invasive procedures; the treatment options include, but are not limited to, desmopressin, VWF-containing concentrates, intravenous immunoglobulin, plasmapheresis or recombinant factor VIIa. Here, we review the management of AVWS with an overview on the currently available evidence and additional considerations for typical treatment situations.

Topics: Animals; Deamino Arginine Vasopressin; Factor VIIa; Hematologic Diseases; Hemostatics; Humans; Immunoglobulins, Intravenous; Plasmapheresis; Recombinant Proteins; Syndrome; von Willebrand Diseases; von Willebrand Factor

Nocturia is common in the elderly population and, aside from being a nuisance, it is associated with morbidity and mortality. Nocturia results from the complex interactions of several factors: changes in the urinary system and renal function with aging, the effects of sleep on renal function, changes in sleeping patterns associated with aging, and the presence of concurrent diseases and medications. Nocturia in the elderly can be caused by many conditions; a common cause is the syndrome of nocturnal polyuria. Although the pathophysiology of nocturnal polyuria remains obscure, some investigators believe that low night-time levels of antidiuretic hormone are involved. Proper management of nocturia requires identification of the specific underlying causes. This Review provides an overview of the mechanisms, evaluation and treatment of nocturia for the practicing nephrologist.

Topics: Aged; Aging; Antidiuretic Agents; Circadian Rhythm; Comorbidity; Deamino Arginine Vasopressin; Depression; Glomerular Filtration Rate; Humans; Kidney; Nocturia; Polyuria; Sleep; Sleep Apnea Syndromes; Sleep, REM; Syndrome; Urinary Bladder; Urination; Urodynamics

Nocturia is a common condition in the elderly that profoundly influences general health and quality of life. It appears to predict a higher risk of death. One consequence of nocturia is sleep deterioration, with increased daytime sleepiness and loss of energy and activity. Accidents, e.g. falls, are increased both at night and during the day in elderly persons with nocturia. Nocturia is caused by nocturnal polyuria, reduced voided volumes, or a combination of the two. Nocturnal polyuria can be caused by numerous diseases, e.g. diabetes insipidus, diabetes mellitus, congestive heart failure, and sleep apnoea. A disorder of the vasopressin system, with very low or undetectable vasopressin levels at night, is manifested as an increased nocturnal urine output, which in the most extreme cases reaches 85% of the 24-h diuresis: the prevalence of low or undetectable vasopressin levels at night has been estimated to be 3-4% in those aged >or= 65 years. Treatment of nocturia may include avoiding excessive fluid intake and use of diuretic medication in the afternoon rather than the morning, oral desmopressin at bedtime in cases of nocturnal polyuria, and antimuscarinic agents in the case of overactive bladder or impaired storage capacity of the bladder.

Topics: Age Factors; Aged; Circadian Rhythm; Deamino Arginine Vasopressin; Diuresis; Health Status; Humans; Life Style; Polyuria; Renal Agents; Sleep Wake Disorders; Syndrome; Urination Disorders

In the kidney, the fine control of NaCl absorption takes place in the distal nephron and is controlled by aldosterone and vasopressin. This review summarizes the effects of vasopressin on Na+ transport mediated by the amiloride-sensitive epithelial sodium channel (ENaC) and the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel in immortalized or primary cultured cortical collecting duct cells, expressing either the wild-type ENaC subunits, or mutations, or deletions of the PY domain of the beta- or gamma-ENaC subunits responsible for Liddle's syndrome, an inherited form of hypertension due to excessive salt absorption.

Topics: Absorption; Aldosterone; Amiloride; Animals; Cells, Cultured; Chlorides; Cystic Fibrosis Transmembrane Conductance Regulator; Deamino Arginine Vasopressin; Epithelial Sodium Channels; Humans; Hypertension; Ion Transport; Kidney Tubules, Collecting; Mice; Mice, Mutant Strains; Models, Biological; Natriuresis; Oocytes; Protein Subunits; Recombinant Fusion Proteins; Sodium Channels; Sodium Chloride; Syndrome; Vasopressins; Water-Electrolyte Balance; Xenopus laevis

Acquired von Willebrand syndrome (AVWS) is a rare acquired bleeding disorder similar to the congenital von Willebrand disease (VWD) in terms of laboratory findings. Diagnosis of AVWS can be very difficult, with treatment normally taking an empirical form. Although more than 200 cases have been reported since 1968, no retrospective or prospective studies are available on AVWS. Recently, an International Registry on AVWS, gathering data directly from worldwide Departments of Haematology-Oncology and Haemophilia Centres, has been organised by a group working on behalf of the Subcommittee on VWF in the Scientific Standardisation Committee (SSC) of International Society on Thrombosis and Haemostasis (ISTH). Information about an additional 211 AVWS patients is now available, with more detailed data on demography, type of haemorrhage, diagnostic tests for AVWS and management of bleeding episodes. The additional 211 AVWS cases are associated with lymphoproliferative (47%) or myeloproliferative (19%) disorders, cardiovascular diseases, neoplasia (7%) and other miscellaneous diseases (14%). Bleeding episodes of AVWS patients were managed by different compounds including desmopressin (22%), FVIII/VWF concentrates (26%) and high-dose immunoglobulin (10%), plasmapheresis (2%), steroids (5%) and immunosuppressive drugs (20%). Based on complied data, we can conclude that none of the therapeutic approaches proposed are 100% effective in all AVWS cases. Therefore, treatment must be customized for each patient according to the underlying disorder, as well as to the type and the severity of bleeding episode and must be targeted to each specific case.

Topics: Coagulants; Deamino Arginine Vasopressin; Glucocorticoids; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Plasmapheresis; Syndrome; von Willebrand Diseases; von Willebrand Factor

Transient diabetes insipidus (DI) is a disease of late pregnancy, that has been reported with increasing frequency. Although initially thought to be nephrogenic, the etiology of this syndrome is most likely excess vasopressinase activity. The disease is associated with preeclampsia with liver involvement. Infants of mothers with the syndrome are predominantly male. Management may be with deamino D arginine vasopressin (dDAVP) during gestation and postpartum since vasopressinase does not break down dDAVP. The copious urine output may disguise preeclampsia. Fluid restriction should be avoided as it will lead to dehydration and hemoconcentration.

Topics: Adult; Cystinyl Aminopeptidase; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Humans; Hypertension; Infant, Newborn; Liver; Polyuria; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Syndrome

Topics: Blood Platelets; Blood Vessels; Chemical Phenomena; Chemistry; Deamino Arginine Vasopressin; Diagnosis, Differential; Female; Genes, Dominant; Genes, Recessive; Genetic Counseling; Humans; Syndrome; von Willebrand Diseases; von Willebrand Factor

This study looked at whether oral desmopressin, by decreasing kidney urine production, would prolong bladder filling-time thereby increasing the time to reach maximum capacity, thus reducing overactive bladder (OAB) symptoms, and providing an alternative method of treatment to OAB sufferers.. An investigator-initiated, 2-week, multi-national, multi-centre, "proof-of-concept," phase IIb, double-blind, placebo-controlled, prospective, randomized, cross-over study was conducted using 0.2 mg of oral desmopressin in adults suffering with OAB. Patients were included in the trial period if they had >or=4 voids in the first 8-hr of the day after rising, excluding the first morning void. The primary endpoint was evaluation of effectiveness of desmopressin in increasing the time to the first OAB symptom episodes during the first 8-hr following treatment.. Time to first void was 8-min later on the drug than on placebo (P = 0.27). However, the drug led to one less void (3.2 vs. 4.2) in the same period (P < 0.001). There was an increase in the time to first urgency episode with a decrease in the number of urgency episodes in the drug days compared to placebo (P < 0.003). There was a subjective improvement in frequency and urgency and overall quality-of-life as measured by the ICIQ-OAB. Twenty-seven people reported adverse events which were all mild, headache being the commonest and no hyponatremia was recorded.. Antidiuresis, using oral desmopressin tablets, is a novel, feasible and safe (short-term basis) method of treatment for adults with OAB, and could be considered in the armamentarium of drugs available for the treatment of OAB.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Antidiuretic Agents; Cross-Over Studies; Deamino Arginine Vasopressin; Double-Blind Method; Europe; Female; Humans; Kidney; Male; Middle Aged; Prospective Studies; Quality of Life; Syndrome; Tablets; Time Factors; Treatment Outcome; Urinary Bladder, Overactive; Urination; Urodynamics; Young Adult

In children with congenital heart disease (CHD), excessive perioperative bleeding is associated with increased morbidity and mortality, thus making adequate perioperative hemostasis crucial. We investigate the prevalence of acquired von Willebrand syndrome type 2A (aVWS) in CHD and develop a treatment algorithm for patients with aVWS and CHD (TAPAC) to reduce perioperative blood loss.. Retrospective cohort study.. Single-center study.. A total of 627 patients with CHD, undergoing corrective cardiac surgery between January 2008 and May 2017.. The evaluation of perioperative bleeding risk was based on the laboratory parameters von Willebrand factor (VWF) antigen, ristocetin cofactor activity, platelet function analyzer (PFA) closure time adenosine diphosphate, and PFA epinephrine. According to the bleeding risk, treatment was performed with desmopressin or VWF.. aVWS was confirmed in 63.3 %, with a prevalence of 45.5% in the moderate and 66.3 % in the high-risk group. In addition, prevalence increased with ascending peak velocity above the stenosis (v max ) from 40.0% at less than or equal to 3 m/s to 83.3% at greater than 5 m/s. TAPAC reduced mean blood loss by 36.3% in comparison with a historical control cohort ( p < 0.001), without increasing the number of thrombotic or thromboembolic events during the hospital stay. With ascending v max , there was an increase in perioperative blood loss in the historical cohort ( p < 0.001), which was not evident in the TAPAC cohort ( p = 0.230).. The prevalence of aVWS in CHD seems to be higher than assumed and leads to significantly higher perioperative blood loss, especially at high v max . Identifying these patients through appropriate laboratory analytics and adequate treatment could reduce blood loss effectively.

Topics: Adenosine Diphosphate; Algorithms; Blood Loss, Surgical; Child; Deamino Arginine Vasopressin; Epinephrine; Heart Defects, Congenital; Humans; Retrospective Studies; Syndrome; von Willebrand Diseases; von Willebrand Factor

Topics: Deamino Arginine Vasopressin; Demyelinating Diseases; Humans; Hyponatremia; Magnetic Resonance Imaging; Sodium; Syndrome

Orbital apex syndrome (OAS) manifests as multiple cranial nerve palsies caused by an abnormal nerve response to inflammation or other processes. Central diabetes insipidus (CDI) is characterized by deficient synthesis or secretion of antidiuretic hormone. A 62-year-old woman underwent myringotomy for otitis media with effusion. Two months after the procedure, symptoms of hearing loss had not improved, and she underwent left tympanoplasty and mastoidectomy. After surgery, she presented with left ocular pain and visual loss. Neurologic examination revealed ptosis, total ophthalmoplegia, and a relative afferent pupillary defect on the left eye. Magnetic resonance imaging showed an asymmetric contrast-enhancing lesion in the left orbital apex and left cavernous sinus, with adjacent dural thickening and enhancement. OAS was diagnosed, and steroid treatment was started. During the regular follow-up period, she reported polyuria, and CDI was diagnosed. Treatment with intranasal desmopressin 10 μg twice daily was started, and symptoms greatly improved. The mechanism underlying the association of CDI with OAS is unclear, and further research is needed. The present case suggests that polyuria in OAS should alert neurologists and ophthalmologists to possible CDI.

Topics: Administration, Intranasal; Cavernous Sinus; Deamino Arginine Vasopressin; Diabetes Insipidus, Neurogenic; Diffusion Magnetic Resonance Imaging; Female; Humans; Middle Aged; Ophthalmoplegia; Otitis Externa; Polyuria; Prefrontal Cortex; Pupil Disorders; Syndrome; Treatment Outcome

We describe a three-year-old boy who had a growth and psychomotor retardation associated with inappropriate lack of thirst and vasopressin secretion in the presence of chronic plasma hyperosmolarity. Computed brain tomography revealed bilateral supratentorial sub-ependymal and cortical calcifications. Dissociation in the plasma vasopressin response to osmotic change was demonstrated in this patient. Treatment with a vasopressin analogue, desamino-D-arginine vasopressin (DDAVP) and forced intake of water restored plasma osmolality and serum sodium levels to normal.

Topics: Antidiuretic Agents; Brain; Child, Preschool; Deamino Arginine Vasopressin; Humans; Hypernatremia; Male; Osmolar Concentration; Sodium; Syndrome; Thirst; Tomography, X-Ray Computed

Topics: Deamino Arginine Vasopressin; Demyelinating Diseases; Diabetes Insipidus, Neurogenic; Female; Humans; Hyponatremia; Saline Solution, Hypertonic; Syndrome; Young Adult

Topics: Adult; Antidiuretic Agents; Brain Edema; Deamino Arginine Vasopressin; Diabetes Insipidus, Neurogenic; Humans; Hyponatremia; Magnetic Resonance Imaging; Male; Myelinolysis, Central Pontine; Syndrome

Acquired von Willebrand syndrome (AVWS) usually mimics von Willebrand disease (VWD) type 1 or 2A. However, in rare cases, the characteristics of other VWD types can predominate in AVWS that might require careful consideration of differential treatment options. The diagnosis and the treatment of a case of type 2B-like AVWS are discussed. Diagnosis of AVWS was ascertained by determining ristocetin cofactor activity, ristocetin-induced platelet aggregation, von Willebrand factor antigen, collagen binding and characterization of von Willebrand factor (VWF) multimers. Inhibitor presence was sought through mixing experiments, the Bethesda method, and calculation of the in-vivo recovery and plasma half-life of VWF after administration of factor VIII/VWF concentrate. Mutations in the A1 domain of VWF were ruled out by sequencing of exon 28 of the VWF gene. A 34-year-old male patient, putatively diagnosed with type 2B VWD, and undergoing laparoscopic cholecystectomy, did not respond adequately to perioperative hemostatic treatment with desmopressin and high doses of factor VIII/VWF concentrate, requiring the administration of recombinant activated factor VII. Further diagnostic workup revealed AVWS mimicking type 2B VWD, most likely owing to an autoantibody developed in the course of underlying monoclonal gammopathy of undetermined significance. The presence of AVWS should be considered before a diagnosis of type 2B VWD is made, especially in patients with a history atypical for inherited disease.

Topics: Adult; Autoantibodies; Bleeding Time; Cholecystectomy, Laparoscopic; Collagen; Deamino Arginine Vasopressin; Diagnosis, Differential; Exons; Factor VII; Factor VIII; Humans; Male; Paraproteinemias; Platelet Aggregation; Protein Binding; Recombinant Proteins; Ristocetin; Sequence Analysis; Syndrome; von Willebrand Disease, Type 2; von Willebrand Factor

Inherited disorders of platelets constitute a group of rare diseases that give rise to bleeding syndromes of variety severity, with more severe cases being first diagnosed during infancy and childhood. To appropriate diagnose a platelet function disorder during early childhood the knowledge of the physiological characteristics of platelets in the paediatric population is mandatory. Apart from thrombocytopenia which is quite common in neonates and children the present overview is aimed to focus on inherited platelet function disorders. Furthermore, knowledge on platelet maturation and reference values according to age are given, and a diagnostic strategy specifically adapted to a pediatric population is presented on the bases of plasmatic and molecular laboratory methodologies. Finally, therapeutic approaches are briefly summarized (antifibrinolytic agents, Desmopressin, HLA-matched platelets, recombinant factor VIIa).

Topics: Antifibrinolytic Agents; Blood Platelet Disorders; Child; Deamino Arginine Vasopressin; Diagnosis, Differential; DNA Mutational Analysis; Factor VIIa; Hemorrhagic Disorders; Humans; Infant; Infant, Newborn; Molecular Motor Proteins; Myosin Heavy Chains; Partial Thromboplastin Time; Platelet Count; Platelet Function Tests; Platelet Transfusion; Recombinant Proteins; Syndrome; Thrombocytopenia; von Willebrand Diseases; von Willebrand Factor

Hyponatraemia is among the more common electrolyte abnormalities encountered in the ED. Both the primary disturbance and its correction can result in life-threatening neurological sequelae. Osmotic myelinolysis syndrome is one such complication and is associated with the rapid correction of hyponatraemia. The present case report describes the mechanism of severe hyponatraemia in a patient taking deamino arginine vasopressin, and the subsequent development of both central pontine and extrapontine myelinolysis after rapid correction of sodium levels. Implications for the emergency management of such patients are discussed.

Topics: Adult; Deamino Arginine Vasopressin; Female; Humans; Hyponatremia; Myelinolysis, Central Pontine; Osmosis; Sodium; Syndrome

There is still no medical treatment available for the so-called fish-odour syndrome (trimethylaminuria). A recent coincidental observation points to a possible therapy with desmopressin. Theoretical considerations about the possible mechanism can explain the observed effects.

Topics: Antidiuretic Agents; Child, Preschool; Deamino Arginine Vasopressin; Fish Products; Humans; Male; Metabolism, Inborn Errors; Methylamines; Odorants; Oxygenases; Syndrome

Topics: ADAM Proteins; ADAMTS13 Protein; Administration, Intranasal; Child; Deamino Arginine Vasopressin; Enuresis; Female; Hemostatics; Humans; Purpura, Thrombotic Thrombocytopenic; Recurrence; Syndrome; Thrombosis

Topics: Adenocarcinoma; Anesthesia, Intravenous; Anesthetics, Intravenous; Anticoagulants; Aprotinin; Bernard-Soulier Syndrome; Colectomy; Colonic Neoplasms; Coronary Artery Bypass; Deamino Arginine Vasopressin; Drainage; Erythrocyte Transfusion; Extracorporeal Circulation; Genes, Dominant; Hemorrhagic Disorders; Hemostatics; Heparin; Humans; Leukopenia; Male; Middle Aged; Molecular Motor Proteins; Myosin Heavy Chains; Peptic Ulcer Hemorrhage; Plasma; Platelet Count; Platelet Transfusion; Pleural Effusion; Postoperative Complications; Postoperative Hemorrhage; Propofol; Sclerotherapy; Syndrome

Liddle's syndrome is a genetic form of hypertension linked to Na(+) retention caused by activating mutations in the COOH terminus of the beta or gamma subunit of the epithelial sodium channel (ENaC). In this study, we used the short-circuit current (I(sc)) method to investigate the effects of deamino-8-d-arginine vasopressin (dDAVP) on Na(+) and Cl(-) fluxes in primary cultures of cortical collecting ducts (CCDs) microdissected from the kidneys of mice with Liddle's syndrome carrying a stop codon mutation, corresponding to the beta-ENaC R(566) stop mutation (L) found in the original pedigree. Compared to wild-type (+/+) CCD cells, untreated L/+ and L/L CCD cells exhibited 2.7- and 4.2-fold increases, respectively, in amiloride-sensitive (Ams) I(sc), reflecting ENaC-dependent Na(+) absorption. Short-term incubation with dDAVP caused a rapid and significant increase (approximately 2-fold) in Ams I(sc) in +/+, but not in L/+ or L/L CCD cells. In sharp contrast, dDAVP induced a greater increase in 5-nitro-2-(3-phenylpropamino)benzoate (NPPB)-inhibited apical Cl(-) currents in amiloride-treated L/L and L/+ cells than in their +/+ counterparts. I(sc) recordings performed under apical ion substituted conditions revealed that the dDAVP-stimulated apical secretion of Cl(-), which was absent in cultured CCDs lacking CFTR, was 1.8-fold greater in L/+ and 3.7-fold greater in L/L CCD cells than in their +/+ CCD counterparts. After the basal membrane had been permeabilized with nystatin and a basal-to-apical Cl(-) gradient had been imposed, dDAVP also stimulated larger Cl(-) currents across L/L and L/+ CCD layers than +/+ CCD layers. These findings demonstrate that vasopressin stimulates greater apical CFTR Cl(-) conductance in the renal CCD cells of mice with Liddle's syndrome than in wild-type mice. This effect could contribute to the enhanced NaCl reabsorption observed in the distal nephron of patients with Liddle's syndrome.

Topics: Animals; Cells, Cultured; Chloride Channel Agonists; Chloride Channels; Chlorides; Codon; Cystic Fibrosis Transmembrane Conductance Regulator; Deamino Arginine Vasopressin; Electrophysiology; Epithelial Sodium Channels; Hypertension; Kidney Tubules, Collecting; Mice; Mice, Knockout; Nephrons; Nystatin; Organ Culture Techniques; Phenotype; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sodium; Sodium Channels; Syndrome; Vasopressins

More than 700 children aged between 5 and 15 years were treated at the University of Vienna Department of Urology during the last 10 years. The therapeutic approach was based on a complex diagnostic scheme to define the individual problem of each enuretic child. Generally speaking the enuresis problem turned out to be a symptom of delayed maturation of fine motor control [1] or sleep and hormone secretion rhythm during day and night hours. In a high percentage of enuretic children, no major physical problem or disease could be found, but the possibility of a physical problem, especially a neurourological problem, should not be ignored. Nonneurogenic discoordinated voiding in children can be treated by cognitive flow-triggered feedback training [2, 3] while overproduction of urine during sleep is reduced by antidiuretic hormone therapy with desmopressin (DDAVP; 1-deamino-8-D-arginine-vasopressin), a synthetic analogue of antidiuretic hormone.

Topics: Adolescent; Austria; Child; Deamino Arginine Vasopressin; Enuresis; Humans; Renal Agents; Retrospective Studies; Syndrome; Toilet Training; Treatment Outcome

The paper describes a patient with Asperger disorder, Neurogenic Diabetes Insipidus (NDI) and Primary Empty Sella (ES). His response to vasopressin treatment suggested a concomitant presence of primary polydipsia. This is the first reported case of an autistic spectrum disorder associated with NDI or ES. The implications of the observed co-occurrence of these relatively rare disorders are discussed in relation to diagnosis and pathogenesis.

Topics: Adult; Autistic Disorder; Comorbidity; Deamino Arginine Vasopressin; Diabetes Insipidus; Drinking; Empty Sella Syndrome; Humans; Magnetic Resonance Imaging; Male; Pituitary Gland, Posterior; Syndrome; Water Intoxication

The effect of the synthetic vasopressin derivative 1-desamino-8D-arginine vasopressin (DDAVP = desmopressin) on bleeding time was studied in three patients with Hermansky Pudlak syndrome. A good response was observed in this type of storage pool disease. DDAVP might be useful in managing the bleeding disorder found in patients with the Hermansky-Pudlak syndrome.

Topics: Adolescent; Adult; Albinism; Bleeding Time; Blood Coagulation Factors; Blood Platelet Disorders; Blood Platelets; Child; Child, Preschool; Deamino Arginine Vasopressin; Female; Humans; Male; Platelet Function Tests; Platelet Storage Pool Deficiency; Serotonin; Syndrome

We describe three patients who have polydipsia and polyuria due to an abnormality in the osmoregulation of thirst. The clinical manifestations of the syndrome are similar to those of neurogenic diabetes insipidus. Thus, under basal conditions the patients have thirst, normal to high normal levels of plasma osmolality, and low levels of plasma vasopressin. Moreover, antidiuretic therapy greatly reduces thirst and polydipsia as well as polyuria. The only clinically distinguishing feature of the response is that thirst and water intake decrease less rapidly than water excretion. As a consequence, the patients with this syndrome develop variable degrees of dilutional hyponatremia and hypoosmolemia during treatment. The plasma vasopressin response to osmotic stimulation is relatively normal. In most of the patients, the osmotic threshold for vasopressin release is at the upper limit of normal, but this finding only explains their modest elevation in basal plasma osmolality. Thirst and water intake also change as a function of plasma osmolality. However, the threshold or "set" of the thirst osmostat appears to be abnormally low. The degree of downward resetting varies from patient to patient, but is always sufficient to stimulate thirst and water intake at levels of plasma osmolality below the normal range. This abnormality can account not only for the thirst and polyuria under basal conditions but also for the overhydration that occurs during antidiuretic therapy. The pathogenesis of the osmoregulatory abnormality is unknown but may be due to disruption of one or more of the afferent pathways that regulate the "set" of the thirst and vasopressin osmostats.

Topics: Adult; Body Weight; Deamino Arginine Vasopressin; Diabetes Insipidus; Drinking; Female; Humans; Male; Syndrome; Thirst; Urine; Vasopressins; Water-Electrolyte Balance

The multimeric and subunit patterns of plasma von Willebrand factor (vWF) were analyzed in eight patients with myeloproliferative syndrome (MS) in order to investigate the possible existence of heterogeneity in the "in vivo" proteolytic cleavage of the protein, previously observed in this entity. Six patients lacked large vWF multimers, five of them having normal bleeding times (BT) and clinically documented episodes of thrombotic origin, whereas one patient had long BT and bleeding symptoms. Seven patients showed a relative increase in the 176 kDa subunit fragment while the 189 kDa polypeptide was increased in only one. In addition, another patient (and prior to any therapy) showed the presence of a new fragment of approximately 95 kDa which disappeared after Busulfan therapy. The collection of blood from these patients with proteinase inhibitors did not correct the abnormalities. The infusion of DDAVP to two patients with abnormal vWF was accompanied by: the appearance of larger vWF multimers which disappeared rapidly from plasma; an increase in the relative proportion of the satellite bands of each multimer and a further increase of the 176 kDa fragment. These data point to some heterogeneity in the vWF abnormality present in MS which may be related in part to a variable degree of proteolysis of vWF occurring "in vivo" rather than "in vitro", and which may be associated to either a thrombotic or a bleeding diathesis. They also suggest that despite the presence of abnormal, already proteolyzed vWF, DDAVP-enhanced proteolysis occurs in MS to a similar extent to what is described in normal individuals.

Topics: Deamino Arginine Vasopressin; Hemorrhage; Humans; Myeloproliferative Disorders; Protein Conformation; Syndrome; Thrombosis; von Willebrand Factor

The Gray platelet syndrome is a rare disorder characterised by the absence of platelet alpha-granules and their contents. We describe a new patient and the effects of infusions of 1-deamino-8-arginine vasopressin (DDAVP). The patient had a prolonged skin bleeding time and his platelets had reduced numbers of alpha-granules, increased vacuolation and reduced retention on glass beads. Platelet von Willebrand factor antigen (vWf:Ag) was undetectable and levels of platelet fibrinogen, beta-thromboglobulin, platelet factor 4 and thrombospondin were reduced. All tests of plasma coagulation factors were normal, including Factor VIII (F.VIII:C), vWf:Ag, ristocetin cofactor (R:CoF) and botrocetin cofactor. Platelet ATP, ADP, platelet albumin, surface membrane glycoproteins and 14C-serotonin uptake were also normal. Infusions of DDAVP increased plasma F.VIII:C, vWf:Ag and R:CoF and shortened the bleeding time on two occasions. This suggests that DDAVP shortens the bleeding time by releasing vWf:Ag and/or other proteins from cellular storage sites other than the platelet.

Topics: Adult; Bleeding Time; Blood Platelet Disorders; Blood Platelets; Deamino Arginine Vasopressin; Humans; Male; Syndrome; von Willebrand Factor

The prolonged partial thromboplastin time observed in the plasma of a 36 year old asymptomatic man was related to the reduced prekallikrein activities (coagulant; antigenic; and amidolytic) and the absence of coagulant and immunologic activities of high molecular weight kininogen (HMWKg). The patient's plasma also exhibited impaired surface-mediated fibrinolysis and impaired generation of kallikrein. The coagulation defect was identified as the "Fitzgerald trait". The levels of CH50, C2, C4 and C-1 inactivator were normal. Venous occlusion in the patient gave rise to a normal release of extrinsic plasminogen activator from the vascular endothelium. The administration of DDAVP led to a FVIII/VWF response which was similar to that obtained in healthy subjects. No alteration could be observed in the contact phase proteins after DDAVP administration.

Topics: Adult; Blood Coagulation Disorders; Deamino Arginine Vasopressin; Humans; Kallikreins; Kininogens; Kinins; Male; Prekallikrein; Protein Precursors; Syndrome; Tourniquets

A case of transient vasopressin-resistant diabetes insipidus is reported which developed during the seventh gestational month. Polyuria reached 4-6 L daily and urine osmolality remained dilute despite 21 hours of water deprivation followed by 5 U intramuscularly of aqueous pitressin, as well as four days of treatment with intranasal DDAVP (0.1-0.5 mL every 12 hours). Urinary excretion of prostaglandin E2, 1384 ng/24 hours, was fourfold that in nongravid subjects and a plasma arginine vasopressin level of 12 pg/mL was recorded. Indomethacin had no effect on urine osmolality but decreased urine volume markedly. Hydrochlorothiazide, also, decreased urine volumes, and this drug was used to manage the patient until delivery. The syndrome remitted in the puerperium, the patient concentrating her urine to 938 mOsm/kg when tested several months postpartum.

Topics: Adult; Deamino Arginine Vasopressin; Diabetes Insipidus; Drug Resistance; Female; Humans; Hydrochlorothiazide; Osmolar Concentration; Pregnancy; Pregnancy Complications; Syndrome

The mechanisms of metabolic acidosis and hyperkalemia were investigated in a patient with chronic mineralocorticoid-resistant renal hyperkalemia (5.3-6.9 mmol/l), metabolic acidosis (arterial blood pH 7.27, total CO2 17 mmol/l), arterial hypertension, undetectable plasma renin activity (less than 0.10 ng/ml/h), high plasma aldosterone level (32-100 ng/dl), and normal glomerular filtration rate (131 ml/min/1.73 m2). During the hyperkalemic period, urine was highly acidic (pH 4.6-5.0), urinary NH4 excretion (10-13 microEq/min) and urinary net acid excretion (19-24 microEq/min) were not supernormal as expected from a chronic acid load. During NaHCO3 infusion, the maximal tubular HCO3 reabsorption was markedly diminished (19.8 mmol/l glomerular filtrate), and the fractional excretion of HCO3 (FE HCO3) when plasma HCO3 was normalized was 20%. Urine minus blood PCO2 increased normally during NaHCO3 infusion (31 mm Hg), and the urinary pH remained maximally low (less than 5.3) when the buffer urinary excretion sharply increased after NH4Cl load. When serum K was returned toward normal limits, metabolic acidosis disappeared, urinary NH4 excretion rose normally after short NH4Cl loading while the urinary pH remained maximally low (4.9-5.2), the maximal tubular HCO3 reabsorption returned to normal values (24.8 mmol/l glomerular filtrate), and FE HCO3 at normal plasma HCO3 was 1%. Nasal insufflation of 1-desamino-8-D-Arginine Vasopressin (dDAVP) resulted in an acute normalization of the renal handling of K and in an increase in net urinary acid excretion. We conclude that: the effect of dDAVP on renal handling of K may be explained by the reversal of the distal chloride shunt and/or an increase in luminal membrane conductance to K; the distal acidification seems to be normal which in the event of distal chloride shunt impairing distal hydrogen secretion might be explained by the presence of systemic acidosis which is a potent stimulus of hydrogen secretion, and metabolic acidosis in the steady state was accounted for by the diminution of bicarbonate reabsorption and ammonia production in the proximal tubule secondary to chronic hyperkalemia.

Topics: Acid-Base Equilibrium; Acidosis, Renal Tubular; Adult; Aldosterone; Deamino Arginine Vasopressin; Drug Resistance; Humans; Hyperkalemia; Kidney; Male; Potassium; Renin-Angiotensin System; Syndrome

The mechanisms of metabolic acidosis and hyperkalemia were investigated in a patient with chronic mineralocorticoid-resistant renal hyperkalemia (5.3 to 6.8 mM), metabolic acidosis (arterial blood pH 7.27, total CO2 17 mM), arterial hypertension, undetectable plasma renin activity (less than 0.10 ng/ml/hr), high plasma aldosterone (32 to 100 ng/dl), normal GFR (131 +/- 2.5 ml/min/1.73 m2). During hyperkalemic period, urine was highly acidic (pH 4.6 to 5.0), urinary NH4 excretion (13 mumoles/min) and urinary net acid excretion (24 mumoles/min) were not supernormal as expected from a chronic acid load. During NaHCO3 infusion, maximal tubular HCO3 reabsorption (Tm HCO3) was markedly diminished (19 mmoles/liter GF), fractional excretion of HCO3 (FE HCO3) when plasma HCO3 was normalized, was 20%. Urine-minus-blood PCO2 increased normally (31 mmHg) during NaHCO3 infusion, and urinary pH remained maximally low (less than 5.3) when buffer urinary excretion sharply increased after NH4Cl load. When serum K was returned toward normal limits, metabolic acidosis disappeared, urinary NH4 excretion rose normally after short NH4Cl loading while urinary pH remained maximally low (4.9 to 5.2), Tm HCO3 returned to normal value (24.8 mmoles/liter GF), and FE HCO3 became nil. The renal handling of K was improved with acute NaHCO3 loading and normalized after DDAVP nasal insufflation.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acidosis, Renal Tubular; Adult; Aldosterone; Deamino Arginine Vasopressin; Humans; Hyperkalemia; Male; Syndrome

Two new cases of Wolfram's syndrome associated with progressive urinary tract dilatation are reported. The possibility of anatomic outlet obstruction or neurogenic bladder was eliminated radiologically and urodynamically. Dilatation of the urinary tract was considered to be a consequence of high diuresis associated with diabetes insipidus. A very important improvement in bilateral urinary tract distension was achieved with bladder drainage while dDAVP therapy dramatically decreased the daily urinary output. A review of diabetes insipidus and its urological implications is presented.

Topics: Adolescent; Blindness; Child; Deamino Arginine Vasopressin; Diabetes Complications; Diabetes Insipidus; Dilatation, Pathologic; Female; Humans; Male; Optic Atrophy; Syndrome; Urodynamics; Urologic Diseases

A patient with lifelong severe polyuria and polydipsia had normal serum antidiuretic hormone (ADH) levels and responded to water deprivation with a prompt increase in urine osmolality and maintenance of normal plasma osmolality (less than 290 mOsm/kg), despite extreme thirst. When treated with desmopressin acetate and allowed free access to water, she was able to reduce plasma osmolality below 270 mOsm/kg, and her compelling thirst disappeared. The disorder is interpreted to be the result of excessive fluid intake in response to a thirst stimulus that was not inhibited by normal plasma osmolality. This study indicates that osmoreceptor control of ADH secretion is normal. Continued administration of vasopressin has relieved the symptoms and has not resulted in water intoxication.

Topics: Adult; Deamino Arginine Vasopressin; Female; Humans; Osmolar Concentration; Polyuria; Pregnancy; Syndrome; Thirst; Vasopressins