deamino-arginine-vasopressin and Chronic-Disease

Hypopituitarism refers to deficiency of one or more hormones produced by the anterior pituitary or released from the posterior pituitary. Hypopituitarism is associated with excess mortality, a key risk factor being cortisol deficiency due to adrenocorticotropic hormone (ACTH) deficiency. Onset can be acute or insidious, and the most common cause in adulthood is a pituitary adenoma, or treatment with pituitary surgery or radiotherapy. Hypopituitarism is diagnosed based on baseline blood sampling for thyroid stimulating hormone, gonadotropin, and prolactin deficiencies, whereas for ACTH, growth hormone, and antidiuretic hormone deficiency dynamic stimulation tests are usually needed. Repeated pituitary function assessment at regular intervals is needed for diagnosis of the predictable but slowly evolving forms of hypopituitarism. Replacement treatment exists in the form of thyroxine, hydrocortisone, sex steroids, growth hormone, and desmopressin. If onset is acute, cortisol deficiency should be replaced first. Modifications in replacement treatment are needed during the transition from paediatric to adult endocrine care, and during pregnancy.

Topics: Acute Disease; Adenoma; Adrenocorticotropic Hormone; Chronic Disease; Deamino Arginine Vasopressin; Gonadal Steroid Hormones; Gonadotropins, Pituitary; Hormone Replacement Therapy; Human Growth Hormone; Humans; Hydrocortisone; Hypophysectomy; Hypopituitarism; Pituitary Gland; Pituitary Hormones, Anterior; Pituitary Irradiation; Pituitary Neoplasms; Prolactin; Radiotherapy; Thyrotropin; Thyroxine; Vasopressins

People with thrombocytopenia due to bone marrow failure are vulnerable to bleeding. Platelet transfusions have limited efficacy in this setting and alternative agents that could replace, or reduce platelet transfusion, and are effective at reducing bleeding are needed.. To compare the relative efficacy of different interventions for patients with thrombocytopenia due to chronic bone marrow failure and to derive a hierarchy of potential alternative treatments to platelet transfusions.. We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (the Cochrane Library 2016, Issue 3), MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1980) and ongoing trial databases to 27 April 2016.. We included randomised controlled trials in people with thrombocytopenia due to chronic bone marrow failure who were allocated to either an alternative to platelet transfusion (artificial platelet substitutes, platelet-poor plasma, fibrinogen concentrate, recombinant activated factor VII (rFVIIa), desmopressin (DDAVP), recombinant factor XIII (rFXIII), recombinant interleukin (rIL)6 or rIL11, or thrombopoietin (TPO) mimetics) or a comparator (placebo, standard of care or platelet transfusion). We excluded people undergoing intensive chemotherapy or stem cell transfusion.. Two review authors independently screened search results, extracted data and assessed trial quality. We estimated summary risk ratios (RR) for dichotomous outcomes. We planned to use summary mean differences (MD) for continuous outcomes. All summary measures are presented with 95% confidence intervals (CI).We could not perform a network meta-analysis because the included studies had important differences in the baseline severity of disease for the participants and in the number of participants undergoing chemotherapy. This raised important concerns about the plausibility of the transitivity assumption in the final dataset and we could not evaluate transitivity statistically because of the small number of trials per comparison. Therefore, we could only perform direct pairwise meta-analyses of included interventions.We employed a random-effects model for all analyses. We assessed statistical heterogeneity using the I. We identified seven completed trials (472 participants), and four ongoing trials (recruiting 837 participants) which are due to be completed by December 2020. Of the seven completed trials, five trials (456 participants) compared a TPO mimetic versus placebo (four romiplostim trials, and one eltrombopag trial), one trial (eight participants) compared DDAVP with placebo and one trial (eight participants) compared tranexamic acid with placebo. In the DDAVP trial, the only outcome reported was the bleeding time. In the tranexamic acid trial there were methodological flaws and bleeding definitions were subject to significant bias. Consequently, these trials could not be incorporated into the quantitative synthesis. No randomised trial of artificial platelet substitutes, platelet-poor plasma, fibrinogen concentrate, rFVIIa, rFXIII, rIL6 or rIL11 was identified.We assessed all five trials of TPO mimetics included in this review to be at high risk of bias because the trials were funded by the manufacturers of the TPO mimetics and the authors had financial stakes in the sponsoring companies.The GRADE quality of the evidence was very low to moderate across the different outcomes.There was insufficient evidence to detect a difference in the number of participants with at least one bleeding episode between TPO mimetics and placebo (RR 0.86, 95% CI 0.56 to 1.31, four trials, 206 participants, low-quality evidence).There was insufficient evidence to detect a difference in the risk of a life-threatening bleed between those treated with a TPO mimetic and placebo (RR 0.31, 95% CI 0.04 to 2.26, one trial, 39 participants, low-quality evidence).There was insufficient evidence to detect a difference in the risk of all-cause mortality between those treated with a TPO mimetic and placebo (RR 0.74, 95%CI 0.52 to 1.05, five trials, 456 participants, very low-quality evidence).There was a significant reduction in the number of participants receiving any platelet transfusion between those treated with TPO mimetics and placebo (RR 0.76, 95% CI 0.61 to 0.95, four trials, 206 participants, moderate-quality evidence).There was no evidence for a difference in the incidence of transfusion reactions between those treated with TPO mimetics and placebo (pOR 0.06, 95% CI 0.00 to 3.44, one trial, 98 participants, very low-quality evidence).There was no evidence for a difference in thromboembolic events between TPO mimetics and placebo (RR 1.41, 95%CI 0.39 to 5.01, five trials, 456 participa. There is insufficient evidence at present for thrombopoietin (TPO) mimetics for the prevention of bleeding for people with thrombocytopenia due to chronic bone marrow failure. There is no randomised controlled trial evidence for artificial platelet substitutes, platelet-poor plasma, fibrinogen concentrate, rFVIIa, rFXIII or rIL6 or rIL11, antifibrinolytics or DDAVP in this setting.

Topics: Benzoates; Bone Marrow Diseases; Chronic Disease; Deamino Arginine Vasopressin; Hemorrhage; Hemostatics; Humans; Hydrazines; Platelet Transfusion; Pyrazoles; Randomized Controlled Trials as Topic; Receptors, Fc; Recombinant Fusion Proteins; Thrombocytopenia; Thrombopoietin; Tranexamic Acid

Hypothermia has been demonstrated to induce pancytopenia in animals, but whether this association exists in humans is unknown. The authors report the case of an 8-year-old girl in whom hypothermia (temperature 33 degrees C-35 degrees C) is the cause of pancytopenia. The patient developed thermoregulatory dysfunction subsequent to surgical resection of a craniopharyngioma. Her recurrent cytopenias could not be explained by any etiology except chronic hypothermia. The pancytopenia improved upon rewarming the patient to a temperature of 36 degrees C. This association between hypothermia and pancytopenia has rarely been reported in humans and may be underdiagnosed especially in cases of transient or milder presentations. The authors recommend careful hematologic monitoring of patients with thermoregulatory dysfunction.

Topics: Adrenal Insufficiency; Blood Cell Count; Cerebral Infarction; Child; Chronic Disease; Consciousness Disorders; Craniopharyngioma; Deamino Arginine Vasopressin; Dehydration; Diabetes Insipidus; Female; Frontal Lobe; Humans; Hyponatremia; Hypophysectomy; Hypopituitarism; Hypothalamus; Hypothermia; Hypothyroidism; Pancreatitis; Pancytopenia; Pituitary Neoplasms; Postoperative Complications; Seizures; Sleep Stages

Bleeding during functional endoscopic sinus surgery always been a challenge for the quality of surgical field for surgeons. This study aimed to evaluate the effect of local nasal desmopressin premedication on blood loss and the quality of surgical field in functional endoscopic sinus surgery.. This study was conducted on 90 patients with chronic rhinosinusitis who were candidate for endoscopic sinus surgery. They were randomly assigned to two study groups. One group received a single puff of local desmopressin (10 μg) in each side of nasal cavity 30 min before the surgery and the other received normal saline instead. Blood loss and the quality surgical field were determined in 15, 30, 60 and 90 min during the surgery (scoring by BOEZAART grading system). All data were analyzed.. Blood loss was significantly lesser in the desmopressin group (mean ± SD, 16.289 ± 5.605 ml) than in the control group (24.289 ± 5.2722 ml, P < 0.001).Surgeons were more satisfied with the surgical field in the desmopressin group than control group in all cutoff points (15, 30, 60, and 90 min during the surgery, P < 0.001). No side effects were observed using local desmopressin.. Premedication with local desmopressin can reduce bleeding effectively and clear the surgical field during functional endoscopic sinus surgery.

Topics: Adult; Blood Loss, Surgical; Chronic Disease; Deamino Arginine Vasopressin; Drug Monitoring; Endoscopy; Female; Hemostatics; Humans; Intraoperative Care; Male; Middle Aged; Premedication; Rhinitis; Sinusitis; Treatment Outcome

Relapse after cessation of desmopressin is an important problem in treating patients with enuresis. Structured withdrawal of desmopressin tablets has been shown to decrease relapse rates. However, scientific data are lacking on the structured withdrawal of the fast melting oral formulation of desmopressin. We compared relapse rates of structured withdrawal using placebo and direct cessation in a population of patients with enuresis who were desmopressin responders.. Patients diagnosed with enuresis and responding to desmopressin from 13 different centers were involved in the study. Patients were randomized into 4 groups. Two different structured withdrawal strategies were compared to placebo and direct withdrawal. Sample size was estimated as 240 (60 patients in each group), with a power of 0.80 and an effect size of 30%. Randomization was performed using NCSS statistical software (NCSS, Kaysville, Utah) from a single center. The relapse rates of the groups were compared using chi-square testing. Logistic regression analysis was performed to define the independent factors having an effect on relapse rates.. Desmopressin treatment was initiated in 421 patients, and 259 patients were eligible for randomization. Relapse rates were 39 (1%) and 42 (4%) for the structured withdrawal groups, which were significantly less than for direct withdrawal (55, 3%) and placebo (53, 1%). Logistic regression analysis revealed that initial effective dose of 240 μcg, greater number of wet nights before treatment and nonstructured withdrawal were associated with higher relapse rates.. We found that structured withdrawal with the fast melting oral formulation of desmopressin results in decreased relapse rates. Application of a structured withdrawal program was also an independent factor associated with reduced relapse rates, together with lower initial effective dose and number of wet nights per week. Relapse after cessation of desmopressin is an important problem, and in this study structured withdrawal was observed to be associated with decreased relapse rates compared to placebo and direct withdrawal.

Topics: Antidiuretic Agents; Child; Chronic Disease; Deamino Arginine Vasopressin; Enuresis; Female; Humans; Male; Prospective Studies; Secondary Prevention; Single-Blind Method

Primary monosymptomatic nocturnal enuresis (PMNE) is often not openly discussed in Asian societies. We report the parental view of PMNE in Singapore, its impact on patients and their families and the traditional beliefs and its influence on subsequent management. A screening questionnaire was used in evaluating 30 children enrolled in a clinical trial on the use of oral Desmopressin for the treatment of PMNE. Primary monosymptomatic nocturnal enuresis was familial in 56.7% of patients. Fifty per cent of them were previously unevaluated. Earlier remedial attempts included bedtime fluid restriction and voiding (100%), incentive measures (43.3%), traditional practices (26.7%), punishment (20%), drugs (16.7%), psychotherapy (100%) and bladder training (3.3%). Perceived causes of PMNE were maturational delay (50%), deep sleep (50%), familial (43.3%), behavioural problems (43.3%) and excessive fluid intake (26.7%). Reasons for seeking treatment included restricted outdoor activities (90%), parental fatigue (86.7%), disrupted sleep for the household (46.7%) and fear of underlying pathology (26.7%). Perceived adverse effects on patients included social stigma (83.3%), disrupted sleep (33.3%) and impaired school performance (13.3%). Primary monosymptomatic nocturnal enuresis can thus be a chronic distressing problem in Asian communities.

Topics: Adolescent; Asia; Attitude to Health; Child; Chronic Disease; Deamino Arginine Vasopressin; Enuresis; Female; Humans; Male; Parents; Renal Agents; Singapore; Surveys and Questionnaires

Ten patients with chronic schizophrenia completed a 3-month double-blind, placebo-controlled trial with a vasopressin analogue. Modest improvement occurred, but several patients also experienced significant fluid and electrolyte imbalance.

Topics: Adolescent; Adult; Chronic Disease; Clinical Trials as Topic; Deamino Arginine Vasopressin; Double-Blind Method; Female; Humans; Male; Placebos; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology; Water-Electrolyte Imbalance

Desmopressin acetate 0.3 microgram/kg was given intravenously to nine patients with chronic liver disease and to a further six such patients in a double blind controlled study versus placebo. Desmopressin acetate significantly shortened the bleeding time compared with basal values in both groups and compared with placebo. There was also a significant decrease in partial thromboplastin time (but not prothrombin time) and significant increases in factor VIII and its components, von Willebrand factor and ristocetin cofactor activity, but not in factors VII, IX, X, XI, or XII. Increased fibrinolysis could be blocked by concomitant administration of tranexamic acid. No important side effects were seen. The multimer pattern of von Willebrand factor was studied for the first time in chronic liver disease. It was normal, but after administration of desmopressin acetate the percentage of multimers of higher molecular weight increased significantly. This may be an important mechanism in the shortening of the bleeding time in cirrhosis, as has been shown in uraemia and other conditions after administration of desmopressin acetate. Desmopressin acetate may be useful in correcting defects in primary haemostasis in chronic liver disease.

Topics: Bleeding Time; Chronic Disease; Clinical Trials as Topic; Deamino Arginine Vasopressin; Double-Blind Method; Humans; Liver Cirrhosis; Random Allocation; von Willebrand Factor

A vasopressin derivative or placebo was administered to 21 chronic schizophrenia patients for 3 weeks in a randomized crossover double-blind design. The patients were divided into those above and below the median on baseline memory measured by the Wechsler memory scale. Vasopressin treatment did not improve memory either in those patients with below median baseline memory or in the group as a whole.

Topics: Adult; Chronic Disease; Clinical Trials as Topic; Deamino Arginine Vasopressin; Double-Blind Method; Female; Humans; Male; Memory Disorders; Middle Aged; Random Allocation; Schizophrenia; Vasopressins

Topics: Antidiuretic Agents; Chronic Disease; Deamino Arginine Vasopressin; Humans; Hyponatremia

To describe the natural history of patients with nocturnal enuresis (NE) during a 10-year period and to evaluate possible impact of comorbid conditions on the persistence of NE.. Ninety-five children (male to female ratio [M:F] 65:30), aged at first visit between 6 and 21 years were included in this study. Of study subjects 75 had primary monosymptomatic nocturnal enuresis (PMNE), 3 had secondary monosymptomatic nocturnal enuresis (SMNE) and 17 had non-mono­symptomatic nocturnal enuresis (NMNE). Demographic and NE-related details were assessed from electron­ic medical records and by telephone interview at the times 3, 6, 12 months and 3, 5, 10 years after the first examination. Sixty-seven of 95 patients were enrolled, of whom 57 had PMNE (M:F ratio 39:18, mean age 9.35 ± 2.81 years, mean age at improvement 11.5 ± 4.08 years), 8 had NMNE (M:F ratio 4:4, mean age 10.1 ± 2.64 years, mean age at improvement 12.6 ± 1.68 years) and 2 had SMNE (M:F ratio 1:1, mean age 12 years, mean age at improvement 13.5 ± 2.12 years).. The mean duration of follow up was 7.2 ± 2.5 years. All of the 67 children had 5 years follow up. Only 29 of 67 patients (19 with PMNE, 8 with NMNE and 2 with SMNE) had 10 years follow up and 4 of 19 with PMNE were still affected by NE. Out of 57 patients with PMNE 12 (2/12 with language disorders, 1/12 varicocele and 1/12 cryptorchidism) and out of 8 patients with NMNE 1 were still enuretic while all patients with SMNE were in remission.. We observed that language disorders and testicular pathology in NE children could be comor­bidities associated with persistence of NE and treatment resistance.

Topics: Adolescent; Antidiuretic Agents; Child; Chronic Disease; Comorbidity; Cryptorchidism; Deamino Arginine Vasopressin; Female; Follow-Up Studies; Functional Laterality; Humans; Language Disorders; Male; Nocturnal Enuresis; Remission Induction; Remission, Spontaneous; Time Factors; Varicocele; Young Adult

A recent study has revealed that acute and chronic administration of the vasopressin V2 receptor (V2R) agonist dDAVP induced a marked increase of urinary albumin excretion (UAE) in healthy rats and humans (Bardoux P et al. Nephrol Dial Transplant 2003; 18: 497-506). The occurrence of an elevation of UAE among patients with chronic syndromes of inappropriate antidiuresis has not been reported.. We looked for the elevation of UAE in 24-h urine samples of the following patients: nine chronic SIADH patients, two patients with acute post-operative SIADH, three patients of the same family with nephrogenic syndrome of inappropriate antidiuresis (NSAID) and two patients with hyponatraemia due to surdosage of dDAVP in the setting of central diabetes insipidus.. There was no elevation of UAE in our patients (whether they presented with hyponatraemia or not), apart from a patient treated with supra-physiological doses of dDAVP. When she received 80 microg/day of dDAVP, her UAE was 42 mg/day. In this patient, UAE returned to the normal range (21 mg/day) when doses of dDAVP were tapered (20 microg/day).. The present study shows that chronic V2R stimulation generally does not result in a rise in UAE. The discrepancy between our results and those of the above-mentioned study could be explained by a dose-dependent effect of V2R stimulation on UAE.

Topics: Adult; Aged; Aged, 80 and over; Albuminuria; Antidiuretic Agents; Chronic Disease; Circadian Rhythm; Deamino Arginine Vasopressin; Diabetes Insipidus; Dose-Response Relationship, Drug; Female; Humans; Hyponatremia; Inappropriate ADH Syndrome; Incidence; Male; Middle Aged; Mutation; Receptors, Vasopressin

This paper presents an ongoing study of children with chronic ITP in Sweden that addresses four specific questions: is there a subgroup of children with chronic ITP that have impaired platelet function? Do children in this subgroup have antibodies directed against surface glycoproteins that are crucial for platelet function? Can desmopressin improve the impaired platelet function in this subgroup? Do children with chronic ITP show signs of cell-mediated cytotoxicity?

Topics: Adolescent; Autoantibodies; Blood Platelets; Child; Chronic Disease; Deamino Arginine Vasopressin; Humans; Immunity, Cellular; Membrane Glycoproteins; Platelet Adhesiveness; Platelet Aggregation; Platelet Function Tests; Purpura, Thrombocytopenic, Idiopathic; Sweden

Little is known of the fibrinolytic host immune mechanisms responsible for induction of chronic allograft nephropathy (CAN), defined as a loss in glomerular filtration rate (GFR) caused by tubular atrophy and interstitial fibrosis, often with fibrous intimal thickening in the small arteries. However, chronic rejection has been reported to be associated with decreased activity of the fibrinolytic system. In our previous study, [Deamino-Cys1, D-Arg8]-vasopressin (dDAVP) induced urokinase-type plasminogen activator (uPA) release from human peripheral T lymphocytes via arginine vasopressin (AVP) V2-receptor-mediated reaction enhanced by an AVP V1-receptor antagonist. Therefore, we examined the level of uPA released from peripheral T lymphocytes by AVP in transplant patients with CAN in comparison with control groups.. In this study, we evaluated in vitro uPA releasing activity of lymphocytes obtained from renal allograft patients with well-functioning grafts (n = 9), CAN (n = 5), or acute rejection episodes (n = 5) compared with lymphocytes from healthy volunteers with normal renal function (n = 12) or patients with renal insufficiency (n = 5).. Lymphocytes prepared from patients with chronic allograft nephropathy showed a significantly lower increase in uPA release induced by the combination of the V1-receptor antagonist and dDAVP compared with those from the other groups.. This finding suggested that a decrease in uPA release from human peripheral blood lymphocytes by AVP-related peptides may be potentially involved in the pathophysiology of CAN.

Topics: Adult; Arginine Vasopressin; Chronic Disease; Deamino Arginine Vasopressin; Female; Humans; Kidney Transplantation; Lymphocytes; Male; Middle Aged; Transplantation, Homologous; Urokinase-Type Plasminogen Activator

Two patients with a long history of unexplained thrombocytopenia, eventually diagnosed with von Willebrand's disease (vWD) type 2B are reported. In one patient with platelet counts of 80 x 10(9)/l 1-desamino-8-D-arginine vasopressin (DDAVP) had a favourable effect during bleeding episodes. The second patient received intermediate purity von Willebrand's factor (vWF)/factor VIII concentrate (Haemate HS), which helped haemostasis during tooth extraction. It increased platelet counts from 15 to 30 x 10(9)/l, whereas platelet transfusions produced no increase, nor prevented severe bleeding during abdominal surgery. Thus the treatment of vWD type 2B might depend on the degree of thrombocytopenia. It is recommended that in patients with mild to moderately decreased platelet counts, DDAVP treatment can be tried, whereas in patients with severely decreased platelet counts intermediate purity vWF/factor VIII concentrate substitution is preferred. In addition, vWD type 2B should be considered in the differential diagnosis of any child with chronic thrombocytopenia as the treatment strategy is different.

Topics: Adolescent; Child; Chronic Disease; Deamino Arginine Vasopressin; Factor VIII; Humans; Male; Thrombocytopenia; von Willebrand Diseases; von Willebrand Factor

We reported 4 cases of lymphocytic infundibuloneurohypophysitis. All four patients had diabetes insipidus as initial symptoms without anterior pituitary dysfunction. All patients showed pituitary stalk swelling and two patients showed enlargement of the pituitary gland. No patients were operated on for a histological diagnosis. No patients received corticosteroid treatment for this pathology. The mean follow-up period was 36 months. The diabetes insipidus continued in all cases, but radiological findings showed improvement in all cases. In one case, adrenal insufficiency occurred after 10 months, but had disappeared 6 months later. We think lymphocytic infundibuloneurohypophysitis can be diagnosed without histological examinations and can be treated conservatively without corticosteroid treatment. It seems to be a self-limiting disease. This disease can be distinguished from lymphocytic adenohypophysitis, but in some cases, both the anterior and posterior pituitary glands are invaded, and in this situation lymphocytic hypophysitis may be an appropriate name. Even if the initial symptom is diabetes insipidus, careful follow-up is needed for the duration of the disease.

Topics: Aged; Chronic Disease; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Humans; Inflammation; Lymphocytes; Magnetic Resonance Imaging; Male; Middle Aged; Pituitary Diseases; Pituitary Gland

The efficacy of desmopressin, a drug that reduces nocturnal urine volume with no side effects, was evaluated in a group of 21 patients.. 20 boys and 1 girl with primary nocturnal enuresis were treated with intranasal desmopressin (DDAVP) for a period of 12 weeks.. An improvement in 80.95% was achieved. Following treatment enuresis recurred, but to a lesser degree than before therapy.. DDAVP is useful in the treatment of primary nocturnal enuresis whose etiology is not organic or functional.

Topics: Adolescent; Child; Chronic Disease; Deamino Arginine Vasopressin; Drug Evaluation; Enuresis; Female; Humans; Male; Recurrence; Time Factors

Previous studies have demonstrated that in adult rats with chronic hyponatremia, both symptoms of encephalopathy and mortality largely depend upon the gender of the animal and the presence of elevated plasma levels of vasopressin (AVP). Since effects of AVP on blood vessels may be gender dependent, the present study was designed to compare the effects of chronic (4 days) hyponatremia on cerebral blood flow (CBF), cerebral oxygen consumption (CMRO2), and cerebral perfusion index (CPI) in adult male and female rats. CBF (intra-arterial 133Xe injection method) and CMRO2 (arteriovenous difference of cerebral oxygen contentxCBF) were measured in normonatremic and hyponatremic (hyponatremia induced with 140 mmol/L glucose and either AVP or desmopressin [dDAVP], plasma sodium = 100 to 110 mmol/L) adult rats of both genders. The CPI was assessed from magnetic resonance imaging of the transit of magnetic susceptibility contrast agent through the brain. Female rats with AVP-induced chronic hyponatremia had a 36% decrease in CBF and a 60% decrease in CMRO2. In male animals, both parameters were not different from control values. AVP-induced hyponatremia resulted in a 45% decrease in CPI in female rats, but hyponatremia induced with dDAVP did not affect CPI in either male or female rats. Chronic (4 days) administration of AVP did not affect CPI in either male or female normonatremic rats. When rats with AVP-induced chronic hyponatremia were pretreated with estrogen, the CPI in males was not different from that in females. Our results demonstrate that during AVP-induced chronic hyponatremia in female rats, there is significant depression of both oxygen utilization and blood flow in the brain.

Topics: Animals; Arginine Vasopressin; Blood Pressure; Brain; Brain Diseases; Cerebrovascular Circulation; Chronic Disease; Deamino Arginine Vasopressin; Estrogens; Female; Hyponatremia; Magnetic Resonance Imaging; Male; Oxygen Consumption; Potassium; Rats; Sex; Sodium

Previous studies from this laboratory showed that both acute and chronic hyponatremia impaired active brain buffering. These studies were performed to determine whether correcting the plasma sodium restored normal buffering in hyponatremic rats. Acute (1- and 2-day) and chronic (7- and 14-day) hyponatremia was induced in male Sprague-Dawley rats by constant desmopressin administration combined with a liquid diet. Plasma sodium was corrected by stopping desmopressin for 6 h, substituting solid chow, and allowing free access to water. Studies were performed 24 h later. Uncorrected hyponatremic rats who continued to receive desmopressin and liquid diet served as controls. Brain pH was determined by [31P]NMR in rats anesthetized with N2O and paralyzed with pancuronium. Brain buffering was determined by the response to CO2 loading. Resting brain pH was the same in corrected and uncorrected rats, but the two groups responded differently to CO2 loading. Thus, 55 min after ventilation with 20% CO2, corrected rat brain pH was 0.13 pH units higher than in uncorrected rats despite statistically similar changes in CO2 tension and arterial pH in both groups. Moreover, 15 min into recovery from CO2 exposure, brain pH in corrected rats overshot resting pH by 0.07, whereas no overshoot occurred in uncorrected rats. Buffering in corrected rats was identical to that shown previously in normonatremic rats. The complete restoration of late-phase buffering achieved by normalizing the plasma sodium of hyponatremic rats indicates that at least some portion of active hydrogen ion transport is sodium dependent in the brain.

Topics: Acute Disease; Animals; Brain Chemistry; Buffers; Carbon Dioxide; Chronic Disease; Deamino Arginine Vasopressin; Diet; Hydrogen-Ion Concentration; Hyponatremia; Male; Rats; Rats, Sprague-Dawley; Sodium

The present studies evaluated whether previously observed impairments in brain buffering during acute hyponatremia were maintained during chronic hyponatremia as well and whether the impairment was due in part to changes in brain water, brain perfusion, or activation of arginine vasopressin (AVP) V1 receptors. Acute (1 and 2 day) and chronic (7 and 14 day) hyponatremia was induced in male Sprague-Dawley rats by constant desmopressin administration in combination with a liquid diet. Brain pH was determined by 31P nuclear magnetic resonance (NMR) in rats anesthetized with N2O and paralyzed with pancuronium. Brain buffering was evaluated by the response to CO2 loading, and brain perfusion was evaluated by 19F-NMR using trifluoromethane washout. Compared with normonatremic controls fed the same diet, brain pH in both acute and chronic hyponatremics was 0.12 pH units lower after 55 min ventilation with 20% CO2 despite identical decreases of approximately 0.35 units in all groups during the first 15 min. Moreover, in the recovery period brain pH overshot basal levels only in normonatremic controls. Brain water content in chronic hyponatremic rats was equal to controls, and brain perfusion was identical in the five groups during CO2 exposure. These results are analogous to those reported during acute hyponatremia induced with AVP and show that the impairment of active brain buffering is maintained during chronic hyponatremia and is unrelated to brain water content, perfusion, tissue catabolism, or AVP V1 receptor activation.

Topics: Acute Disease; Administration, Inhalation; Animals; Brain; Buffers; Carbon Dioxide; Cerebrovascular Circulation; Chronic Disease; Deamino Arginine Vasopressin; Hydrogen-Ion Concentration; Hyponatremia; Magnetic Resonance Spectroscopy; Male; Phosphorus; Rats; Rats, Sprague-Dawley

A patient with benign monoclonal IgG lambda paraproteinemia, acquired von Willebrand syndrome (AVWS), and chronic melena successfully responding to high-dose intravenous immunoglobulin (lvlg) is reported. Coagulation parameters at admission were APTT (ratio) 1.68; VIII:C 11 IU/dL; vWF:Ag 7 IU/dL:Ricof less than 3 IU/dl. RIPA was greater than 1.8 mg/ml, and bleeding time (BT) was prolonged (18 min). No evidence for an in vitro inhibitor against the VIII/vWF complex was observed. VIII/vWF measurements showed a short-lived increase after both DDAVP and Hemate P, and BT was transiently normalized. After intravenous Ig (1 g/kg for 2 days), VIII/vWF measurements, hemostatic parameters and multimeric pattern were completely corrected (VIII/C 106 IU/dl, vWF:Ag 168 IU/dl, RiCof 147 IU/dl, APTT ratio 0.89, BT 5'), with a return to pre-infusion values after 15 days. Hemoccult test became negative and packed red cell transfusions, of which 130 units were administered during the last year, were no longer required. After 18 months the patient is on maintenance treatment with repeated courses of Ig, at 3 to 4-week intervals based on VIII/vWF and BT monitoring.

Topics: Bleeding Time; Chronic Disease; Deamino Arginine Vasopressin; Dose-Response Relationship, Drug; Factor VIII; Humans; Immunoelectrophoresis; Immunoglobulins, Intravenous; Male; Melena; Middle Aged; Paraproteinemias; von Willebrand Diseases; von Willebrand Factor

Glomerular filtration rate (GFR) and tubular involvement were studied in 74 patients with serologically verified nephropathia epidemica (NE). Increased levels of serum creatinine and serum beta 2-microglobulin were documented in 96% and 99% of the patients, respectively. The mean of the lowest estimated GFR was 26 ml/min. Proximal tubular reabsorptive capacity was assessed by urinary loss of beta 2-microglobulin and cell damage by urinary activity of N-acetyl-beta-D-glucosaminidase. Both of these parameters were elevated in most of the patients during the acute phase of the disease. Increased serum levels of Tamm-Horsfall-specific IgG and/or IgA occurred in 72 of 74 patients. No patient required dialysis and there was no mortality. Six months after discharge only three patients had a GFR less than 80 ml/min as estimated by [51Cr]EDTA clearance; two of these had underlying chronic diseases and one had suffered clinically severe NE. Desmopressin tests showed decreased urine osmolarity in three patients 8 months after discharge. These three had chronic diseases, which may have contributed to the impaired tubular function. Thus, there was a markedly decreased GFR and a tubular dysfunction in the acute phase of NE. Most patients recovered within a few months and none showed evidence of chronically impaired renal function due to NE.

Topics: Acetylglucosaminidase; Acute Disease; Adolescent; Adult; Aged; beta 2-Microglobulin; Chronic Disease; Creatinine; Deamino Arginine Vasopressin; Female; Glomerular Filtration Rate; Hemorrhagic Fever with Renal Syndrome; Humans; Immunoglobulin A; Immunoglobulin G; Kidney Tubules; Male; Middle Aged; Mucoproteins; Osmolar Concentration; Uromodulin

The purpose of this study was to determine how acute hyponatremia might augment the excretion of ammonium in dogs with chronic metabolic acidosis. The excretion of ammonium was higher during hyponatremia because the proportion of ammonium produced that was excreted in the urine increased from 66% in controls to 77%. Effects on the production of ammonium are more complex. The rate of renal ammoniagenesis was not increased during hyponatremia in absolute terms nor when expressed per millimole of oxygen consumption. In contrast, this rate was somewhat higher during hyponatremia if expressed per millimole of sodium reabsorbed (9.8 vs. 10.3 mumol). The rate of oxygen consumption by the kidney did not fall, as anticipated, during hyponatremia; when this rate was expressed per millimole of sodium reabsorbed it rose from 46 to 55 mumol. There was no significant change in the rate of extraction of glutamine by the kidney, but there was a significant decrease in the rate of release of alanine during hyponatremia. Hence there appears to be more oxidation (yielding more ammonium) and less transamination of glutamine. We conclude that the renal events which led to a higher rate of excretion of ammonium during hyponatremia were a larger than expected rate of ammonium production owing to a greater rate of oxygen consumption together with lesser rate of transamination of the glutamine extracted by the kidney. In addition, more of the ammonium produced was transferred to the urine.

Topics: Acidosis; Acute Disease; Ammonia; Animals; Chronic Disease; Deamino Arginine Vasopressin; Dogs; Glomerular Filtration Rate; Glutamine; Hypotonic Solutions; Kidney; Osmolar Concentration; Sodium; Sodium Chloride

Ten chronic undifferentiated schizophrenics, 6 men and 4 women, aged 28-63, with 6- to 31-year histories of the disease were given DDAVP to observe the effects of this neuropeptide on the prevalent negative symptoms of their illness. Patients were maintained on neuroleptic therapy and first given a 20-day course of placebo followed by 20 days of DDAVP i.m., 4 micrograms Andreasen Scale for assessment of negative symptoms, the Brief Psychiatric Rating Scale, the NOSIE Rating Scale and the Luria-Nebraska Rating Scale were administered to monitor negative symptomatology, behavior and memory before the study began, after placebo and after DDAVP administration. Patients were also given a growth hormone-clonidine test and in addition plasma basal concentrations of 3-methoxy-4-hydroxyphenylglycol (MHPG), homovanillic acid, 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA) were measured at the same intervals. DDAVP therapy induced a significant improvement of negative symptomatology and a trend toward improvement of short- to medium-term memory. No changes in homovanillic acid, MHPG, 5-HIAA and DOPAC, nor of growth hormone response to clonidine stimulation were observed.

Topics: Adult; Aggression; Brain; Chronic Disease; Deamino Arginine Vasopressin; Dopamine; Female; Hallucinations; Humans; Male; Memory; Mental Recall; Middle Aged; Norepinephrine; Psychiatric Status Rating Scales; Receptors, Adrenergic; Schizophrenia; Schizophrenic Psychology; Serotonin; Thinking

An early diagnosis of renal dysfunction is particularly important in patients with chronic abuse of analgesics. First morphological changes in cases of analgesic nephropathy are found in the renal medulla. Therefore, urinary osmolarity as well as the urinary excretion of cyclic adenosine monophosphate (AMP) and kallikrein were measured after application of desamino-D-arginine vasopressin (DDAVP) as parameters of the renal tubular function in 21 patients with normal creatinine clearance and a regular, excessive use of analgesics. The results were compared with those of 17 healthy volunteers and 8 patients with chronic renal insufficiency after analgesic nephropathy. In patients with analgesic nephropathy the urine osmolarity after 12 h of thirst was 367 +/- 28 mOsm/kg and did not increase after DDAVP. The results obtained from healthy volunteers were 781 +/- 39 mOsm/kg. Half of the patients with chronic misuse of analgesics had lower values of urine osmolarity after thirst and DDAVP compared to the reference area of healthy subjects. Similar results were found when the effect of DDAVP under conditions of water-loading was tested. The excretion of cyclic AMP as a second messenger of DDAVP and of kallikrein did not differ between patients with chronic abuse of analgesics and healthy volunteers. The excretion of kallikrein in patients with manifest analgesic nephropathy, however, was decreased. Thus the renal concentration test with DDAVP proved to be useful in early diagnosis of renal dysfunction caused by analgesics.

Topics: Adult; Analgesics, Opioid; Chronic Disease; Cyclic AMP; Deamino Arginine Vasopressin; Female; Humans; Kallikreins; Kidney Diseases; Male; Middle Aged; Osmolar Concentration; Substance-Related Disorders; Time Factors

The role of vasopressin in the regulation of body water volume and its distribution to intravascular, interstitial and intracellular compartments, and the importance of particular body water compartments in the pathogenesis of DOCA-salt hypertension were studied in young Brattleboro rats. Vasopressin-deficient, vasopressin-synthesizing and vasopressin-deficient rats chronically supplemented with deamino-8-D-arginine vasopressin (dDAVP) were compared with water-drinking controls. The chronic DOCA-salt treatment caused a marked hypertension in vasopressin-synthesizing animals; in these animals body water was slightly increased due to the expansion of extra-cellular fluid volume whereas intracellular water tended to decrease, so that the ratio of extracellular fluid volume to intracellular water rose significantly. The development of DOCA-salt hypertension was attenuated in the vasopressin-deficient rats, which had a similar level of total body water, slightly increased intracellular water and significantly decreased extracellular fluid volume compared with the hypertensive vasopressin-synthesizing rats. Consequently, in the vasopressin-deficient rats, the ratio of extracellular fluid volume to intracellular water did not differ from that of controls. A vasopressin deficiency was associated with a failure to expand the interstitial fluid volume although plasma volume was increased. Unaltered total body water together with elevated plasma osmolality indicated an extracellular water deficiency in DOCA-salt-treated vasopressin-deficient rats. Chronic dDAVP supplementation restored the body fluid pattern and the hypertensive response of the DOCA-salt-treated vasopressin-deficient rats. In conclusion, the antidiuretic effects of vasopressin are necessary for the interstitial fluid volume expansion that is essential for a full development of DOCA-salt hypertension.

Topics: Animals; Body Water; Chronic Disease; Deamino Arginine Vasopressin; Desoxycorticosterone; Heterozygote; Homozygote; Hypertension; Nephrectomy; Rats; Rats, Brattleboro; Sodium Chloride; Vasopressins

1-deamino-8-D-arginine vasopressin (DDAVP) was administered intranasally in a dose of 2 micrograms/kg BW to 17 uremic patients (16 maintained on chronic hemodialysis and 1 treated conservatively). The bleeding time was significantly shortened 120 minutes after DDAVP administration (from 18.1 +/- 7.5 minutes to 12.3 +/- 6.4 minutes p less than 0.001). Factor VIII related antigen (VIII: Ag) did not change. Factor VIII ristocetin cofactor activity (VIII: RCof) significantly increased (from 251.2 +/- 162.0 to 336.5 +/- 167.2 p less than 0.025). Platelet count decreased significantly after DDAVP (from 174.9 +/- 43.8 X 10(9)/l to 155.6 +/- 45.9 X 10(9)/l 30 minutes p less than 0.01 and 129.8 +/- 45.2 X 10(9)/l p less than 0.005 120 minutes after DDAVP). Antithrombin III concentration, and hematocrit did not change. Our data indicate that further clinical studies of intranasal DDAVP in uremic patients during episodes of bleeding are warranted.

Topics: Administration, Intranasal; Adult; Bleeding Time; Chronic Disease; Deamino Arginine Vasopressin; Factor VIII; Female; Humans; Male; Middle Aged; Platelet Count; Platelet Function Tests; Uremia

Twenty-three chronic undifferentiated schizophrenics, 13 women and 10 men, aged 37-64 years with 15-to 40-year histories of the disease were given either thyrotropin-releasing hormone (TRH) (10 subjects) or DDAVP (13 subjects) with the aim to improve the negative symptoms of the disease and memory. TRH (600 micrograms i.v.) and DDAVP (4 micrograms i.m.) were administered every other day for 30 days. Negative symptoms were monitored by the Andreasen rating scale and by the Honingfeld NOSIE rating scale, memory by the Folstein 'Mini mental State' rating scale and by the Luria-Nebraska rating scale before therapy and then at days 15, 16, 30 and 31 of treatment. Both therapies significantly improved negative symptoms. Memory was significantly improved in all the patients treated with TRH and in 9 of the 13 patients treated with DDAVP, who presented less severe cognitive impairments. A peripheral mechanism of action of DDAVP was excluded by the observation that plasma electrolytes and osmolality, blood pressure, ECG patterns, 24-hour urine volume and specific gravity, basal plasma cortisol and growth hormone levels and weight of the patients were unchanged during therapy. TRH treatment induced a transient borderline hyperthyroidism at day 15 and a progressive decrease of the thyrotropin response to TRH stimulation. A common mechanism of action of the two peptides on the central noradrenergic system is suggested.

Topics: Adult; Affective Symptoms; Attention; Behavior; Chronic Disease; Deamino Arginine Vasopressin; Female; Humans; Language; Male; Memory; Middle Aged; Psychiatric Status Rating Scales; Schizophrenia; Thyrotropin-Releasing Hormone

Topics: Administration, Intranasal; Adult; Carbamazepine; Chlorpropamide; Chronic Disease; Deamino Arginine Vasopressin; Diabetes Insipidus; Diuresis; Drug Evaluation; Humans; Pituitary Hormones, Posterior; Vasopressins

Topics: Adult; Aged; Arginine Vasopressin; Blood Coagulation; Blood Coagulation Disorders; Chronic Disease; Deamino Arginine Vasopressin; Female; Humans; Liver Cirrhosis; Male; Middle Aged

1. Urinary and plasma levels of adenosine 3':5'-cyclic monophosphate (cyclic AMP) after an intravenous injection of bovine parathyroid hormone (PTH) were measured in 12 patients on long-term lithium treatment and in nine control subjects. The maximum urine osmolality (Umax.) after an intravenous injection of desamino-D-arginine vasopressin (DDAVP) was also measured. 2. In all the control subjects and six of the patients, the Umax. after DDAVP exceeded 700 mosmol/kg. The cyclic AMP responses in these two groups did not differ significantly. 3. In the remaining six patients whose Umax. did not reach 700 mosmol/kg, the cyclic AMP response to PTH was significantly less than that of the controls. 4. A strong correlation was demonstrated in the patients between the urinary cyclic AMP response after PTH and the maximum osmolality after the administration of DDAVP. 5. These observations are consistent with the hypothesis that reduced adenylate cyclase activity contributes to the development of nephrogenic diabetes insipidus in patients on long-term lithium treatment.

Topics: Adult; Aged; Chronic Disease; Cyclic AMP; Deamino Arginine Vasopressin; Female; Humans; Kidney Concentrating Ability; Kidney Diseases; Kidney Function Tests; Lithium; Male; Middle Aged; Mood Disorders; Parathyroid Hormone; Time Factors

Renal concentration tests were carried out on 45 healthy volunteers and 106 patients with chronic renal disease of moderate degree involving impaired concentrating ability. Each subject served as his own control. The control experiment involved a total of 36 hr of "dehydration" (no fluids per os or food with a high fluid content such as fruit) in which 4 hr clearance periods were started from the 12th and continued to thd 36th hr. The first 12 hr involved an overnight period from 20.00 hr. One week later the same subjects were given 10 micrograms demopressin (dDAVP) at the 13th hr and a subsequent 4 hr clearance period provided blood and urine samples to compare desmopressin-induced urine concentration with various stages of concentration during oral fluid withdrawal alone. The drug was given intranasally. We measured urine osmolality and concentrations of urea. Na, K and calculated the U/P creatinine concentration ratios and creatinine clearances (CCr). Using Uosm as the criterion, the dDAVP experiment at 12 hr gave the same results as 24 hr of fluid withdrawal alone. With the U/PCr ratio as the criterion, dDAVP + 12 hr gave the same results as 36 hr of fluid withdrawal alone. Between 32 and 36 hr dehydration, CCr decreased - otherwise it remained unchanged in both healthy and ill subjects, with and without dDAVP. The only side-effect was the discomfort of more than 12 hr dehydration. This would appear to simplify a potentially useful diagnostic and prognostic test.

Topics: Adolescent; Adult; Aged; Arginine Vasopressin; Chronic Disease; Creatinine; Deamino Arginine Vasopressin; Electrolytes; Female; Humans; Kidney Concentrating Ability; Kidney Diseases; Kidney Function Tests; Male; Middle Aged

Intranasal administration of DDAVP (1-deamino-8-D-arginine vasopressin), a synthetic analogue of vasopressin, followed by measurement of urine osmolaity 6 h afterwards, represents a convenient, reliable and simple method for the estimation of renal concentrating capacity in children. The DDAVP-test is as accurate and reproducible as the water deprivation test, irrespective of the degree of concentrating capacity. Mean urine osmolality after DDAVP in children without renal disease was found to be 984 +/- 218 mosmol/kg water (m +/- 2 SD). In children with recurrent pyelonephritis, urine osmolality after DDAVP was decreased. The values were significantly lower with bilateral changes than with unilateral changes of chronic pyelonephritis in the i.v. urograms. In chronic pyelonephritis the concentrating capacity appears to be earlier impaired than other parameters of renal function.

Topics: Adolescent; Arginine Vasopressin; Child; Child, Preschool; Chronic Disease; Deamino Arginine Vasopressin; Humans; Infant; Kidney Concentrating Ability; Osmolar Concentration; Pyelonephritis; Time Factors; Urinary Tract Infections; Urine