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PubMed1984

Ophthalmological findings in nephropathia epidemica in Lapland.

We report ophthalmological findings in 15 cases of nephropathia epidemica. The patients, 13 men and 2 women, were 20 to 62 (mean 30) years of age. The onset of the disease was characterized by high fever, nausea, headache, abdominal pain, backache, somnolence, red throat, proteinuria, and oliguria. The symptoms subsided rapidly during the polyuria stage. Transitory myopia occurred in 8 patients (53%). Conjunctival injection and haemorrhages were seen in 3 patients (20%). One patient had acute glaucoma with oedema in the cornea and shallowing of the anterior chamber, with subsequent anterior uveitis and haemorrhages in the ocular fundus, and another patients had acute glaucoma. Three patients had photophobia which occurred in 2 patients without any glaucoma or anterior uveitis.

Adult↗
PubMedDate not supplied

The importance of egg protein in reduced protein diets designed for dogs with renal failure.

The effects of two reduced-protein diets and a canine maintenance diet on renal function, nutrition, serum and urine acid-base and electrolyte values, and divalent ion metabolism were compared in Beagle dogs with induced chronic renal failure. Two reduced-protein (18%) diets differed in their protein sources. One 18% protein diet was formulated using egg protein as the only protein source. The other 18% protein diet was formulated using a mixture of animal and vegetable proteins. The 42% protein diet contained a mixture of animal and vegetable protein sources. Results of this study indicate that the egg-based and mixed protein-based diets had similar effects on most clinical and laboratory evaluations in dogs with chronic renal failure. However, the egg protein diet appeared to promote hyperchloremic metabolic acidosis. Both reduced-protein diets were beneficial in reducing azotemia, polyuria, hypermagnesemia, and fractional excretion of phosphorus compared with the 42% protein diet.

Acid-Base Equilibrium↗
PubMedDate not supplied

Radioactive iodine treatment of a functional thyroid carcinoma producing hyperthyroidism in a dog.

Radioactive iodine (131I) was used in the treatment of a 12-year-old female dog with hyperthyroidism resulting from a large, unresectable (and metastatic) thyroid carcinoma associated with signs of severe inspiratory stridor and dyspnea. Hyperthyroidism was diagnosed on the basis of clinical signs (polyuria, polydipsia, polyphagia, weight loss, nervousness) and high basal serum thyroxine (T4) concentrations, as well as thyroid radioiodine kinetic studies that showed a high radioiodine uptake into the thyroid (% thyroid uptake) and markedly increased serum concentrations of protein-bound iodine-131 (PB131I) after 131I tracer injection. Thyroid imaging revealed diffuse radionuclide accumulation by the tumor, which involved both thyroid lobes. The dog was treated with three large doses of radioiodine (131I), ranging from 60 to 75 mCi, given at intervals of 5 to 7 months. The dog became euthyroid, and the size of the tumor decreased by approximately 25% after each 131I treatment, improving the severe inspiratory stridor and dyspnea, but both the hyperthyroid state and breathing difficulty recurred within a few months of each treatment. The dog was euthanatized 5 months after the last treatment because of progressive tracheal compression and pulmonary metastasis.

Animals↗
PubMedDate not supplied

Primary hypoadrenocorticism in ten cats.

Primary hypoadrenocorticism was diagnosed in ten young to middle-aged cats of mixed breeding. Five of the cats were male, and five were female. Historic signs included lethargy (n = 10), anorexia (n = 10), weight loss (n = 9), vomiting (n = 4), and polyuria (n = 3). Dehydration (n = 9), hypothermia (n = 8), prolonged capillary refill time (n = 5), weak pulse (n = 5), collapse (n = 3), and sinus bradycardia (n = 2) were found on physical examination. Results of initial laboratory tests revealed anemia (n = 3), absolute lymphocytosis (n = 2), absolute eosinophilia (n = 1), and azotemia and hyperphosphatemia (n = 10). Serum electrolyte changes included hyponatremia (n = 10), hyperkalemia (n = 9), hypochloremia (n = 9), and hypercalcemia (n = 1). The diagnosis of primary adrenocortical insufficiency was established on the basis of results of adrenocorticotropic hormone (ACTH) stimulation tests (n = 10) and endogenous plasma ACTH determinations (n = 7). Initial therapy for hypoadrenocorticism included intravenous administration of 0.9% saline and dexamethasone and intramuscular administration of desoxycorticosterone acetate in oil. Three cats were euthanatized shortly after diagnosis because of poor clinical response. Results of necropsy examination were unremarkable except for complete destruction of both adrenal cortices. Seven cats were treated chronically with oral prednisone or intramuscular methylprednisolone acetate for glucocorticoid supplementation and with oral fludrocortisone acetate or intramuscular injections of repository desoxycorticosterone pivalate for mineralocorticoid replacement. One cat died after 47 days of therapy from unknown causes; the other six cats are still alive and well after 3 to 70 months of treatment.

Addison Disease↗
PubMedDate not supplied

Acromegaly in 14 cats.

Acromegaly was diagnosed in 14 middle-aged to old cats of mixed breeding. Thirteen (93%) of the cats were male and one was female. The earliest clinical signs in the 14 cats included polyuria, polydipsia, polyphagia, all of which were associated with untreated diabetes mellitus. All developed severe insulin resistance within a few months; peak insulin dosages required to control severe hyperglycemia ranged from 20 to 130 U per day. Other clinical findings weeks to months after diagnosis included enlargement of one or more organs (e.g., liver, heart, kidneys, and tongue) (n = 14), cardiomyopathy (n = 13), increase in body size and weight gain (n = 8), nephropathy associated with azotemia and clinical signs of renal failure (n = 7), degenerative arthropathy (n = 6), and central nervous system signs (i.e., circling and seizures) caused by enlargement of the pituitary tumor (n = 2). The diagnosis of acromegaly was confirmed by demonstration of extremely high basal serum growth hormone concentrations (22 to 131 micrograms/l) in all cats. Computerized tomography disclosed a mass in the region of the pituitary gland and hypothalamus in five of the six cats in which it was performed. Two cats were treated by cobalt radiotherapy followed by administration of a somatostatin analogue (octreotide), whereas two cats were treated with octreotide alone. Treatment had little to no effect in decreasing serum GH concentrations in any of the cats. Eleven of the 14 cats were euthanized or died four to 42 months (median survival time, 20.5 months) after the onset of acromegaly because of renal failure (n = 2), congestive heart failure (n = 1), concomitant renal failure and congestive heart failure (n = 3), progressive neurologic signs (n = 2), persistent anorexia and lethargy of unknown cause (n = 1), the owner's unwillingness to treat the diabetes mellitus (n = 1), or unknown causes (n = 1). Results of necropsy examination in ten cats revealed a large pituitary acidophil adenoma (n = 10), marked left ventricular and septal hypertrophy (n = 7), dilated cardiomyopathy (n = 1), arthropathy affecting the shoulder, elbow, or stifle (n = 5), and glomerulopathy characterized by expansion of the mesangial matrix and variable periglomerular fibrosis (n = 10).

Acromegaly↗
PubMedDate not supplied

Fanconi's syndrome in a dog with primary hypoparathyroidism.

An 11-year-old castrated male mixed breed dog was referred for evaluation of muscle twitching, polyuria, polydipsia, anorexia, and periocular alopecia. Primary hypoparathyroidism was diagnosed by documenting decreased serum concentrations of parathyroid hormone and ionized calcium. Neurological, gastrointestinal, and dermatological signs resolved after calcium repletion. Initially, 1,25-dihydroxycholecalciferol PO was required to correct the hypocalcemia. Dihydrotachysterol, in combination with oral calcium supplementation, was used for long-term maintenance of normal serum calcium concentration. Aminoaciduria, glucosuria, and hyperchloremic metabolic acidosis were consistent with a diagnosis of Fanconi's syndrome. This diagnosis was further supported by the presence of hypokalemia and increased urinary fractional excretion of sodium, potassium, calcium, phosphorus, and magnesium. Renal tubular dysfunction resolved after oral supplementation with calcium and vitamin D3. Fanconi's syndrome in this dog may have been caused by decreased serum concentration of 1,25-dihydroxycholecalciferol, which was secondary to decreased parathyroid hormone production.

Animals↗
PubMedDate not supplied

Fanconi syndrome in a Labrador retriever.

A 2-year-old male Labrador Retriever was presented to the University of Missouri Veterinary Teaching Hospital with the primary complaints of polydipsia, polyuria, and joint or muscle pain. Low blood urea nitrogen concentration, hyperchloremia, and marked proteinuria were the only abnormalities in a serum biochemical profile and urinalysis. Decreased creatinine clearance and increased renal fractional excretion of sodium, potassium, calcium, and phosphorus were detected by renal clearance studies. Increased excretion of most amino acids was found by amino acid analysis of urine, but not all amino acids were lost with equal magnitude. Amino acids with secondary amino groups or basic side chains were lost at increased rates, whereas those with acidic side chains were not. These differences could be related to defects in specific renal amino acid transport mechanisms. Identification of these transport mechanisms may allow for pharmacologic intervention at the point of renal loss to alleviate clinical signs of disease.

Amino Acids↗
PubMedDate not supplied

Central diabetes insipidus in a dog with a pro-opiomelanocortin-producing pituitary tumor not causing hyperadrenocorticism.

Central diabetes insipidus was diagnosed by vasopressin measurements during hypertonic stimulation in a 9-year-old male giant Schnauzer with polyuria and polydipsia. The impaired release of vasopressin was believed to be caused by a large pituitary tumor, which was visualized by computed tomography. Studies of the function of the anterior lobe and the pars intermedia of the pituitary gland were conducted, and high concentrations of ACTH and alpha-melanotrophic hormone (alpha-MSH) were found without concomitant hyperadrenocorticism. Studies of the molecular size of the immunoreactive ACTH in plasma by gel filtration revealed that most of the circulating immunoreactivity was not ACTH but its precursor pro-opiomelanocortin (POMC) and low-molecular-weight POMC-derived peptides. The pituitary tumor of this dog probably originated from melanotrophic cells of the pars intermedia. The sensitivity of the pituitary-adrenocortical system for the suppressive effect of dexamethasone was unaffected.

Adrenocortical Hyperfunction↗
PubMed1991

The effect of 8-cyclopentyl-1,3-dipropylxanthine on the development of cyclosporin-induced acute renal failure.

The effect of the selective A1-adenosine receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (CPX, 0.1 mg kg-1 i.v.) administered twice daily to rats has been assessed on the development of renal dysfunction induced by four daily injections of cyclosporin (60 mg kg-1 i.p.). The series of cyclosporin injections resulted in a polyuria accompanied by a 64-70% increase in plasma urea and creatinine concentrations and a 50% reduction in inulin clearance. However, cyclosporin administration resulted in no change in p-aminohippurate clearance nor was there any evidence of tubular necrosis or vascular damage. CPX treatment did not improve any index of renal function perturbed by cyclosporin. The findings provide evidence that adenosine does not play a role in the pathophysiology of cyclosporin nephrotoxicity.

Acute Kidney Injury↗
PubMed2024

SLC12A1 variant c.1684+1 G>A causes Bartter syndrome type 1 by promoting exon 13 skipping.

BACKGROUND: Bartter syndrome type 1, an autosomal recessive genetic disorder, is caused by pathogenic loss-of-function variants in the SLC12A1 gene. It is characterized by metabolic alkalosis and prenatal-onset polyuria leading to polyhydramnios. METHODS: We identified pathogenic gene in a 12-day-old newborn boy with Bartter syndrome type 1 using whole-exome sequencing. Sanger sequencing validated the identified variants. A minigene assay was performed to investigate the effect of a novel splice site variant on pre-mRNA splicing. RESULTS: We found a compound heterozygous variants in the SLC12A1 gene, consisting of a known pathogenic missense mutation (NM_000338: c.769 G>A; p.Gly257Ser) and a novel splice site variant (c.1684+1 G>A). In silico predictions and an in vitro minigene splicing assay demonstrated that the splicing variant c.1684+1 G>A abolished a consensus splice donor site of SLC12A1 intron 13, resulting in complete exon 13 skipping, translational frameshift, and premature termination codon, ultimately leading to loss of SLC12A1 function. CONCLUSION: Using a cell-based in vitro assay, we revealed the aberrant effect of the pathogenic splicing variant SLC12A1 c.1684+1 G>A on pre-mRNA splicing. Our findings expand the gene mutation spectrum of Bartter syndrome type 1, providing a basis for genetic diagnosis and the development of genetic medicines.

Humans↗
PubMed1994

Epidermal growth factor as a diuretic in sheep.

1. Epidermal growth factor (EGF) has recently been shown to stimulate both polydipsia and polyuria and the aim of this study was to determine which was the primary response. Ewes received a continuous intravenous saline infusion (100 ml day-1) for 12 days (days 1-12) and EGF at doses of 0 (n = 6) or 10 micrograms h-1 (n = 6) over days 5-8. The supply of water was ad libitum during days 1-4 and 9-12, but was fixed at the pretreatment mean of days 1-4 for each ewe during days 5-8. 2. During the period of fixed water intake, the EGF-treated ewes experienced mild dehydration with elevated plasma osmolality, sodium, renin and arginine vasopressin (AVP) concentrations and slightly reduced plasma atrial natriuretic peptide (ANP) concentrations. 3. When the supply of water returned to ad libitum, the EGF-treated ewes increased their water intake by 105% (5.25 +/- 0.28 vs. 2.55 +/- 0.19 l day-1) and subsequently fluid balance was restored; plasma electrolyte and hormone responses also returned to normal. 4. This experiment demonstrates that EGF infused at a dose rate of 10 micrograms h-1 I.V. into sheep has a direct renal diuretic effect.

Animals↗
PubMed1966

Diabetes, a new mutation in the mouse.

Diabetes (db), which occurred in an inbred strain of mouse, is inherited as a unit autosomal recessive and is characterized by a metabolic disturbance resembling diabetes mellitus in man. Abnormal deposition of fat at 3 to 4 weeks of age is followed shortly by hyperglycemia, polyuria, and glycosuria. Accompanying morphological changes in the islets of Langerhans suggest neogenesis to compensate for insulin depletion.

Animals↗
PubMed1980

Functional development of grafted vasopressin neurons.

Vasopressin neurons, transplanted from normal rat fetuses into the third ventricle of adult Brattleboro rats, alleviate the polydipsia and polyuria of the hosts. Determination of the antidiuretic activity of grafted neurons in hosts with congenital diabetes insipidus provides a convenient model for analyzing the development, plasticity, and function of transplanted central nervous system neurons in mammals.

Animals↗
PubMed1989

Pharmacokinetics of foscarnet and distribution to cerebrospinal fluid after intravenous infusion in patients with human immunodeficiency virus infection.

To investigate the pharmacokinetics and effects of intravenous foscarnet, 13 relatively healthy male patients with human immunodeficiency virus infection and a mean CD4+ lymphocyte value of 0.45 x 10(-9) cells per liter were given a continuous intravenous infusion of foscarnet (0.14 to 0.19 mg/kg per min) for 8 to 21 days. Blood and urine samples were taken during and after drug administration to monitor foscarnet concentrations. Lumbar puncture was performed during the infusion in five patients. The concentrations in plasma showed large variations both within and between patients. The disposition of foscarnet could be explained by a triexponential equation (t1/2 lambda 1, 0.40 to 2.52 h; t1/2 lambda 2, 3.20 to 16.7 h; t1/2 lambda 3, 36 to 196 h). Renal clearance accounted for most of the plasma clearance, the difference probably reflecting the passage of foscarnet into bone. Up to 20% of the cumulative dose may have been deposited in bone 7 days postinfusion. Foscarnet was distributed to the cerebrospinal fluid in a concentration varying from 13 to 68% of the simultaneous concentration in plasma. Polyuria and polydipsia were recorded in all patients. There appears to be an association between the degree of malaise, including symptoms such as nausea, vomiting, fatigue, and headache, and concentrations in plasma above 350 mumol/liter.

Acquired Immunodeficiency Syndrome↗
PubMed1978

Congenital nephrogenic diabetes insipidus in a baby girl.

A 6-week-old girl with fever, hypernatraemia, dehydration, and polyuria failed to concentrate urine in response to exogenous vasopressin administration. There was no family history of nephrogenic diabetes insipidus. When she was 15 months old, the infusion of vasopressin did not produce an increase in urinary cyclic-AMP.

Cyclic AMP↗
PubMed1982

Effect of indomethacin on clinical progress and renal function in cystinosis.

Three children with nephropathic cystinosis were treated with indomethacin 3 mg/kg a day for periods ranging from 9 to 18 months. The drug produced worthwhile clinical improvement in all, with marked beneficial effects on polyuria, polydipsia, and general wellbeing. Clearance studies performed under conditions of maximal water diuresis showed that proximal tubular sodium reabsorption was increased in all children, with consequent reduction in sodium delivery to the distal nephron leading to reduced free water clearance and distal tubular cation exchange. Plasma sodium and potassium concentrations became normal in all patients, with improvement in phosphate and bicarbonate concentrations in one. Renal function continued to deteriorate, but without obvious acceleration of the process by the drug. We were unable to demonstrate a beneficial effect on growth; nevertheless, indomethacin is a useful adjunct to the symptomatic treatment of children with severe nephropathic cystinosis.

Body Water↗
PubMed1986

DDAVP and urine osmolality in refractory enuresis.

A double blind crossover trial of 20 micrograms intranasal 1-deamino-8-d-arginine vasopressin (DDAVP) versus placebo was carried out in 17 children with intractable enuresis aged between 6 and 13 years who had failed to respond to drugs and an enuresis alarm. Fluid intake was not restricted. There was a significant reduction in the number of wet nights. Seven children (41%) were cured or showed considerable improvement, with strong evidence against any placebo effect. The best response was seen in children aged 10 years or over and if urine osmolality after DDAVP reached beyond 1000 mmol/kg or was already at this concentration. The degree of overnight rise in urine osmolality after treatment with DDAVP was not predictable but correlated well with the clinical improvement in nocturnal diuresis present in eight of the children. A further 12 children with equally refractory enuresis were given 20 micrograms of the active drug to take during their school journeys or holidays. Six of them had previously normal overnight urine osmolalities with only two successes, but of the six who had nocturnal diuresis before treatment, five became dry, suggesting that DDAVP acts largely by anti-diuresis and might be most useful in children with nocturnal polyuria.

Adolescent↗
PubMed1986

Oral desmopressin in central diabetes insipidus.

Seven paediatric patients with central diabetes insipidus were studied in an open dose ranging study in hospital followed by a six month study on an outpatient basis to assess the efficacy and safety of peroral administration of DDAVP (desmopressin) tablets. In the dose ranging study a dose dependent antidiuretic response was observed. The response to 12.5-50 mcg was, however, less effective in correcting baseline polyuria than were doses of 100 mcg and above. Patients were discharged from hospital on a preliminary dosage regimen ranging from 100 to 400 mcg three times daily. After an initial adjustment in dosage in three patients at one week follow up, all patients were stabilised on treatment with tablets and reported an adequate water turnover at six months. As with the intranasal route of administration dosage requirements varied from patient to patient, and a dose range rather than standard doses were required. A significant correlation, however, was found for the relation between previous intranasal and present oral daily dosage. No adverse reactions were reported. No clinically significant changes were noted in blood chemistry and urinalysis. All patients expressed a preference for the oral over existing intranasal treatment. Treatment with tablets offers a beneficial alternative to the intranasal route, particularly in patients with chronic rhinitis or impaired vision.

Administration, Intranasal↗