Search PubMed⌕ Search

Biomedical subjects

A M Moses

Publications and source records attributed to A M Moses.

At least 37 records · Page 2Linked to original sources
PubMed1989

Osmotic thresholds for AVP release with the use of plasma and urine AVP and free water clearance.

Eleven hydrated normal subjects were infused with hypertonic saline so that plasma osmolalities (POsmol) ranged from 280 to 306 mosmol/kg. Linear relationships were calculated between POsmol and plasma and urine arginine vasopressin (AVP) in the 11 individual subjects. There was an excellent linear correlation between POsmol and plasma and urine AVP, with the latter as concentration or rate of excretion. The highest correlation coefficient occurred when urine AVP was expressed as microunits of AVP per 100 milliliters of glomerular filtrate. The smallest coefficient of variation of the slopes occurred when urine AVP was expressed as microunits of AVP per minute. The osmotic thresholds obtained by abscissal intercepts from relating POsmol to urine AVP per minute or per 100 milliliters of glomerular filtrate were 285.9 and 285.5 mosmol/kg, respectively. These values did not differ from the mean osmotic threshold obtained by traditional free water clearance changes (285.8 mosmol/kg). Analysis of the relationship between plasma osmolality and plasma AVP resulted in the greatest variation in slope and osmotic threshold, with the latter being significantly lower than that obtained by free water clearance changes. The data also demonstrated a much more rapid rise of urine than of plasma AVP under the stated conditions of osmotic stimulation.

Adult↗
PubMed1988

Two distinct pathophysiological mechanisms in congenital nephrogenic diabetes insipidus.

V1 and V2 vasopressin receptor functions were studied in 2 patients with congenital nephrogenic diabetes insipidus. V1 receptor-mediated functions (increase in urinary prostaglandin E2 excretion and plasma cortisol levels) and Gs (guanine nucleotide-binding stimulatory protein) activity of erythrocyte membranes were normal in both patients. After infusion of 0.4 micrograms/kg dDAVP, a 57-yr-old male patient had no increase in plasma factor VIII coagulant, ristocetin cofactor, or fibrinolytic activity or change in von Willebrand factor multimers. In addition, he had no vasodilatory response to dDAVP, a response that occurs in normal subjects and patients with central diabetes insipidus. In contrast, a 25-yr-old female patient had normal hemostatic and vasodilatory responses to the infusion of dDAVP. These observations indicate that the cellular abnormalities in patients with congenital nephrogenic diabetes insipidus may be either at the V2 receptor or in the postreceptor (and Gs activity) cascade of events that mediate vasopressin-induced antidiuresis. Therefore, heterogeneity exists in the biochemical cause(s) of congenital nephrogenic diabetes insipidus in man.

Adult↗
PubMed1986

Urinary and metabolic clearances of arginine vasopressin in normal subjects.

Synthetic arginine vasopressin (AVP) was infused into 11 hydrated normal subjects at five different infusion rates ranging from 10 to 350 microU X kg-1 X min-1. Each infusion rate was continued for 1 h, and urinary determinations were made on the 30- to 60-min specimens during which time there was no further rise in plasma AVP. Urinary AVP concentrations (microU/ml) and excretion rates (microU/min) increased linearly with increasing infusion rates, and the concentration of AVP in urine increased 120 times more rapid than plasma. Urinary and metabolic clearances of AVP also increased linearly with the maximum urinary clearance being 60.6% of the creatinine clearance. The total metabolic clearance of AVP (including urinary clearance) was 17.8 times that of the urinary clearance of AVP alone. These data clarify the relationships between plasma and urinary AVP in normal hydrated subjects during AVP infusion under steady-state conditions and emphasize the potential advantage of measuring urinary AVP as a monitor of endogenous AVP secretion.

Adolescent↗
PubMed1986

Evidence for normal antidiuretic responses to endogenous and exogenous arginine vasopressin in patients with guanine nucleotide-binding stimulatory protein-deficient pseudohypoparathyroidism.

In six patients with pseudohypoparathyroidism (PHP) who were deficient in guanine nucleotide-binding stimulatory protein (Ns) activity, the response to endogenous arginine vasopressin (AVP) was tested during water deprivation. Hourly plasma osmolality (Posm), urinary osmolality (Uosm), and urinary AVP (UAVP) values were compared to those in normal subjects. The Uosm vs. Posm and the UAVP vs. Uosm relationships of the patients were all within the normal range. Four patients with Ns-deficient PHP were subjected to maintained water loads and infused with AVP at three different rates for 1 h each to assess their responses to exogenous AVP. Urinary volume and osmolality values from the final 30 min of each infusion rate were measured. All volume values except 1 were within 1.6 SD of normal, and all osmolality values except 1 were within 1.1 SD of normal. In conclusion, these studies indicate that these six patients with Ns-deficient PHP are not resistant to the antidiuretic (cAMP-mediated) action of endogenous or exogenous AVP, in contrast to the previously documented resistance of patients with Ns-deficient PHP to the actions of PTH, TSH, glucagon, and gonadotropins.

Adolescent↗
PubMed1985

Antidiuretic and PGE2 responses to AVP and dDAVP in subjects with central and nephrogenic diabetes insipidus.

Vasopressin stimulates renal prostaglandin (PGE2) production at several loci and in turn PGE2 modulates the antidiuresis. We have found the time courses of increased urinary PGE2 in subjects with central diabetes insipidus (DI) parallel the antidiuretic responses to AVP and dDAVP. The antidiuretic response to 4 micrograms dDAVP in these subjects was far greater than the response to 5 U (12.5 micrograms) AVP, but the PGE2 response to the dDAVP was only marginally greater than that which followed the AVP. Therefore, dDAVP disproportionately stimulates antidiuresis in relation to PGE2 production, whereas the reverse holds for AVP. In subjects with nephrogenic DI 12.5 micrograms AVP caused no antidiuresis but stimulated PGE2 excretion as well as in subjects with central DI. There was an intermediate relationship between antidiuresis and PGE2 excretion in subjects with central DI given AVP and subjects with nephrogenic DI injected with dDAVP. In summary, 1) the normal PGE2 response to AVP in subjects with nephrogenic DI is consistent with other evidence that non-antidiuretic actions of vasopressin are not impaired in these subjects. 2) The limited capability of dDAVP to stimulate PGE2 may be a factor in the augmented antidiuretic response to dDAVP in subjects with central DI. 3) Antidiuretic and PGE2 responses to vasopressin can be dissociated, thus allowing further consideration of mechanisms by which each may be independently controlled and interrelated.

Adult↗
PubMed1985

Inhibition of hormonal activation of hepatic phosphorylase by chlorpropamide: evidence for an intracellular site of drug action.

Phosphorylase a activity was measured in hepatocytes from fed rats, some of which received ip chlorpropamide injections for 5 days preceding death (20 mg/100 g BW X day for 5 days). Chlorpropamide treatment significantly depressed basal phosphorylase a activity and lessened the increments in the activity of this enzyme induced by 10(-10) -10(-8) M glucagon and arginine vasopressin. The reductions in phosphorylase a activity after treatment with chlorpropamide were more than sufficient to explain the accompanying decreases in hepatic glucose production. Since glucagon and arginine vasopressin stimulate alternate pathways of phosphorylase activation and since chlorpropamide antagonizes both hormones, it is likely that the drug acts at or distal to the intracellular site (phosphorylase kinase) at which the two activation pathways converge.

Animals↗
PubMed1984

Marked hypotonic polyuria resulting from nephrogenic diabetes insipidus with partial sensitivity to vasopressin.

We studied two women with severe hypotonic polyuria whose symptoms dated from infancy. We eliminated the possibility of central diabetes insipidus (DI) and primary polydipsia, and established the presence of nephrogenic DI on the basis of: 1) the interrelationships between plasma osmolality, urine osmolality, and urinary AVP; and 2) impaired antidiuretic responses to AVP and 1 deamino-8-D-arginine vasopressin. Though 25-50 times as resistant to 1 deamino-8-D-arginine vasopressin nasal spray as patients with central DI, these patients could be treated effectively with large doses of the nasal spray. One patient has been so treated for more than a year with dramatic improvement in her polydipsia, polyuria, and sense of well-being.

Administration, Intranasal↗
PubMed1984

Parathyroid hormone infusion test in children and adolescents.

10 children with short stature were infused with parathyroid hormone (PTH). The results were compared to those obtained from a study of 28 normal adult volunteers. As expected, the children had higher basal serum phosphorus levels than the adults. PTH administration increased urinary excretion of cyclic AMP, sodium, potassium, bicarbonate, phosphate clearance, and reabsorption of calcium. The responses of the children were indistinguishable from those of the adults. Infusion of PTH to 3 children with hypoparathyroidism produced exaggerated cyclic AMP, phosphate, calcium, potassium, and bicarbonate responses. When given to a patient with pseudohypoparathyroidism, it did not increase urinary excretion of cyclic AMP and potassium or phosphate clearance, but did induce normal sodium and bicarbonate excretion. We conclude that the values obtained from normal adults are applicable to children and are useful in the evaluation of hypocalcemia in childhood.

Adolescent↗
PubMed1983

Evidence for bone remodeling but lack of calcium mobilization response to parathyroid hormone in pseudohypoparathyroidism.

Twenty-eight patients with hypoparathyroidism were classified into PTH-deficient (HP; n = 14) or PTH-resistant [pseudohypoparathyroid (PHP); n = 14] groups on the basis of serum PTH level and urinary cAMP response to PTH infusion. Bone density (BD; bone mineral content/bone width) was determined by 125I photon absorptiometry in the distal third of the radius of each patient. After 3 days of equilibration on a constant diet, fasting serum Ca, 1,25-dihydroxyvitamin D [1,25-(OH)2D] and 24-h urinary hydroxyproline (OHP) were measured during 4 control days and 4 treatment days [Lilly Parathyroid Extract (PTE); 100 U, im, every 6 h]. In HP, the mean BD was 0.772 +/- 0.016 (+/- SE) g/cm2, which was similar to the value obtained in a normal control group matched for age, sex, and race. In PHP, the mean BD was 0.633 +/- 0.017 g/cm2, which was 15 +/- 2% less than the normal value (P less than 0.005). Diminished BD was present in all patients with PHP, even in the absence of radiographic changes. Mean basal OHP excretion in PHP was more than twice that in HP (34.9 +/- 5.5 vs. 13.8 +/- 1.3 mg/day; P less than 0.005). Both groups had significant and comparable increases in urinary OHP excretion in response to PTE (9.1 +/- 2.1 mg/day for HP; 8.1 +/- 2.2 mg/day for PHP; P less than 0.005 for each). However, unlike the patients with HP, those with PHP did not have increases in serum 1,25-(OH)2D or a normal calcemic response to PTE. Thus, the bone-remodeling response to PTH remains intact in the majority of patients with PHP, but the mineral mobilization response, which may require 1,25-(OH)2D, is defective.

Adolescent↗
PubMed1982

Deficiency of hormone receptor-adenylate cyclase coupling protein: basis for hormone resistance in pseudohypoparathyroidism.

Pseudohypoparathyroidism is an inherited disorder associated with resistance to the action of several hormones, including parathyroid hormone, thyroid-stimulating hormone, follicle-stimulating hormone, and luteinizing hormone. The disorders described under this designation are heterogeneous in regard to the underlying genetic defects, the phenotypic manifestation, and the severity of the defects in hormone action. The majority of affected individuals who also have the characteristic skeletal changes (heredity osteodystrophy) have a defect in the guanine nucleotide regulatory protein (G protein) that is essential for coupling certain cell-surface hormone receptors to the adenylate cyclase system. This defect is probably the cause for resistance to the action of multiple hormones. In the remaining patients the cause for hormone resistance has not been identified.

Adenylyl Cyclases↗
PubMed1982

Further studies on the mechanism by which chlorpropamide alters the action of vasopressin.

The injection of chlorpropamide into Brattleboro homozygous rats (di/di) has previously been shown to result in enhanced activation of renal medullary adenylate cyclase activity and increased renal medullary content of cAMP in response to 1-desamino-8-D-arginine vasopressin (dDAVP). In contrast, in vivo chlorpropamide did not alter GTP, guanylylimidodiphosphate, or fluoride-stimulated adenylate cyclase activities in these renal membranes. We have now found that the effect of in vivo chlorpropamide in enhancing dDVAP-stimulated adenylate cyclase activity involves lowering the Km for ATP. We have also found that dDAVP increases urinary prostaglandin E2 (PGE2) excretion, and treatment with chlorpropamide causes an even greater PGE2 response to dDAVP. In contrast, in vivo chlorpropamide treatment did not increase vascular responses to arginine vasopressin (AVP) in the perfused kidney preparation and, in fact, inhibited the AVP-induced decrease in the glomerular filtration rate. Chlorpropamide, therefore, enhances the renal responses to dDAVP in terms of the cAMP and PG systems, while not increasing responses to postreceptor stimuli of the adenylate cyclase system or vascular responses to AVP. These observations support the concept that in vivo chlorpropamide acts at the receptor of the vasopressin-sensitive part of the tubule to augment responsiveness to vasopressin. In addition, in vivo chlorpropamide may inhibit certain vascular responses to AVP.

Adenylyl Cyclases↗
PubMed1982

Altered osmotic threshold for vasopressin release and impaired thirst sensation: additional abnormalities in Kallmann's syndrome.

Seven subjects with Kallmann's syndrome were studied to determine whether they had disturbances of fluid homeostasis. Simultaneous measurements of urine and plasma osmolality (Uosm and Posm, respectively) were made during free access to fluids. The Uosm-Posm relationship was abnormal in five patients on at least one occasion. Patient 2 was frequently overhydrated (Posm less than or equal to 280 mosmol/kg) and patient 5 excreted a dilute urine when his Posm was 290 mosmol/kg. The three subjects (1, 5, and 7) tending to have an increased Psom (greater than or equal to 300 mosmol/kg) were able to concentrate their urine (Uosm greater than 800 mosmol/kg) and denied polyuria and polydipsia. Their elevated Posms could be explained by impairment of thirst, rather than increased excretion of water, because the patients concentrated their urines at normal Posms during fluid deprivation. The osmotic threshold for vasopressin release was decreased (Posm = 270.6 mosmol/kg) in one patient and increased (Posm greater than or equal to 295 mosmol/kg) in two others of the seven patients. The elevated osmotic threshold was not due to chronic hyperosmolality or a generalized defect in vasopressin secretion. In the patient with the highest osmotic threshold (Posm = 296 mosmol/kg) and Posms between 289--301 mosmol/kg during free access to fluid, the osmotic threshold decreased to only 293 mosmol/kg after 6 weeks of adequate hydration and desmopressin acetate. However, in response to hypotension induced by trimethaphan, he increased his plasma vasopressin from 1--26 microU/ml. In conclusion, some patients with Kallmann's syndrome may have osmoreceptor dysfunction and abnormal thirst regulation, indicating more extensive hypothalamic involvement than previously appreciated.

Adolescent↗
PubMed1982

Secondary hyperparathyroidism caused by oral contraceptives.

Secondary hyperparathyroidism developed on two separate occasions in a patient taking an oral contraceptive (OC) in a mixture of norethindrone and mestranol (Ortho-Novum 1/80). The probable cause of this condition is an estrogenic inhibition of the calcium mobilizing effect of parathyroid hormone (PTH) or vitamin D. The possible consequences of OC therapy in this patient and patients like her include those of milk hypocalcemia, moderate hypophosphatemia, or the neurotoxic actions of excessive levels of circulating PTH. One should also consider the possible role of OC therapy in patients with unexplained parathyroid hyperplasia and with tertiary hyperparathyroidism.

Adult↗
PubMed1981

Simplifying the diagnosis of diabetes insipidus in children.

We simplified the procedures for identifying children with diabetes insipidus by using the relationship between urine and plasma osmolality (Uosm and Posm). We defined the normal Uosm-Posm relationship as the area within the 95% confidence regions for pairs of osmolality measurements obtained from normal children during periods of free access to fluids and after oral hydration. In 13 patients with diabetes insipidus, Uosm-Posm coordinates were outside these regions in 50 of 64 pairs (one to ten per patient) during periods of free access to fluids. After three hours of fluid deprivation, the Uosm-Posm relationship was abnormal in 12 patients; the 13th was unable to void. For those with a normal Posm, and Uosm less than Posm, another pair of osmolality measurements after three hours of fluid restriction should determine the diagnosis.

Adolescent↗