Intermittent subclavian artery occlusion following clavicular fracture

Although fractures of the clavicle are common, complications are rare. A 41 year old painter developed two uncommon complications of clavicular fracture, mechanical intermittent subclavian artery occlusion and subclavian vein thrombosis. Both conditions were clearly identified on the clinical symptoms and signs and confirmed with dynamic angiography and computerised tomography. Operative intervention led to complete resolution of symptoms.     

Role of Plasma Vasopressin in Impaired Water Excretion of Glucocorticoid Deficiency

In the present study, the effect of selective glucocorticoid deficiency on renal water excretion was investigated in conscious, trained, adrenalectomized dogs. The animals were studied before and after a water load while on replacement therapy of desoxycorticosterone acetate, 5 mg/day, and dexamethasone, 0.8 mg/day (group I), and while off dexamethasone for 5-9 days (group II). Before the water load the weight, inulin space, cardiac output, blood pressure, glomerular filtration rate, renal blood flow, plasma osmolality, and plasma antidiuretic hormone measured by radioimmunoassay were similar in both groups I and II. However, after a 40 ml/kg water load a marked impairment in renal water excretion in the glucocorticoid deficient dogs became apparent. Maximal free water clearance was −0.046±0.16 vs. 6.51±0.72 ml/min (P < 0.001) and minimal urinary osmolality was 425±56 vs. 82±3.5 mosmol/kg H₂O (P < 0.001) in group II as compared to group I. Plasma antidiuretic hormone was maximally suppressed during the water load in group I to 0.34±0.08 pg/ml but remained elevated at 9.18±1.79 pg/ml (P < 0.005) in group II. This nonsuppressibility of plasma antidiuretic hormone during water loading in group II was associated with a significant tachycardia of 145±6 vs. 87±6 beats/min (P < 0.001) in group I and a significantly lower stroke volume of 27±0 vs. 59±0.5 ml/beat (P < 0.001). In conclusion, our results implicate a persistent secretion of antidiuretic hormone as an important factor in the impaired water excretion of glucocorticoid deficiency. A deleterious effect of glucocorticoid deficiency on cardiac function was observed and this hemodynamic alteration could be involved in initiating a nonosmolar, baroreceptor-mediated release of vasopressin.     

Comparison of the natriuretic response to atriopeptin III and loop diuretic in the isolated perfused rat kidney

1. Isolated rat kidneys were perfused at a constant perfusion pressure of 90 mmHg to study the natriuretic effects of atriopeptin III (AP-III) and to compare these effects with those of frusemide. AP-III (1 microgram) or frusemide (1 mg) were added to the perfusate (100 ml) after two 15 min control collection periods. 2. Compared with the control group, AP-III and frusemide increased urinary sodium excretion (UNa V, 5.6 +/- 1.1 and 4.6 +/- 0.6 vs control 1.8 +/- 0.3 mumol min-1 g-1, mean +/- SEM, P less than 0.01 and P less than 0.05, respectively), fractional sodium excretion (FENa, 4.8 +/- 1.1 and 6.7 +/- 0.8 vs control 2.0 +/- 0.2%, P less than 0.05 and P less than 0.001, respectively) and potassium excretion (UKV, 3.2 +/- 0.3 and 3.0 +/- 0.3 vs control 1.5 +/- 0.3 mumol min-1 g-1, both P less than 0.01). However, AP-III, but not frusemide, increased glomerular filtration rate (820 +/- 55 vs 590 +/- 24 microliter min-1 g-1, P less than 0.01) and urine flow rate (V 97.5 +/- 8.0 vs 44.1 +/- 5.2 microliter min-1 g-1, P less than 0.001). Calculated distal delivery of sodium (CNa +/- CH2O, 76.6 +/- 6.8 vs 30.7 +/- 3.8 microliter min-1 g-1, P less than 0.005) as well as fractional distal delivery of sodium [(CNa +/- CH2O)/CIn, 9.4 +/- 0.9 vs 5.1 +/- 0.6%, P less than 0.01] were increased by AP-III, but not frusemide.(ABSTRACT TRUNCATED AT 250 WORDS)     

Parasympathetic pathways, renin secretion and vasopressin release.

1. The interrelationship between parasympathetic neural tone, renin secretion and vasopressin release was examined by observing the effect of bilateral cervical vagotomy on renin secretion in intact and acutely hypophysectomized dogs undergoing a water diuresis. 2. In intact dogs bilateral cervical vagotomy decreased the mean renin secretion from 1245 to 682 units/min (P less than 0.01) as urinary osmolality increased from 95 to 414 mosmol/kg (P less than 0.001). In contrast, in acutely hypophysectomized dogs cervical vagotomy failed to alter renin secretion significantly (834 to 893 units/min) and urinary osmolality was also unchanged (78 to 71 mosmol/kg). 3. The results suggest that a diminution in vagal tone may significantly alter renin secretion by stimulating vasopressin release. Exogenous vasopressin was associated with changes in urinary osmolality and renin secretion which were qualitatively similar to those seen after servical vagotomy. 4. We suggest that there is a neurohumoral reflex mechanism by which a fall in parasympathetic tone increases the release of vasopressin, which, in turn, suppresses renin secretion. The results are also compatible with the hypothesis that vasopressin inhibits renin release by a direct effect on the juxtaglomerular cells.     

Mechanism of Effect of Thoracic Inferior Vena Cava Constriction on Renal Water Excretion

Persistent secretion of vasopressin and/ or diminished distal fluid delivery have been proposed to explain the impaired water excretion associated with low-output cardiac failure. In the present investigation cardiac output (CO) was diminished in anesthetized dogs undergoing a water diuresis by constriction of the thoracic inferior vena cava (TIVC). In intact animals (group I) acute TIVC constriction decreased CO from 3.5 to 2.2 liters/min (P < 0.005) as urinary osmolality (U(osm)) increased from 103 to 543 mosmols/ kg (P < 0.001) and free water clearance (C(H2o)) decreased from 2.1 to -0.6 ml/min (P < 0.001). This antidiuretic effect was disassociated from changes in renal arterial and venous pressures, glomerular filtration rate, solute excretion, and renal innervation. To examine the role of vasopressin in this antidiuresis, studies (group II) were performed in acutely hypophysectomized, steroid-replaced animals. In these animals TIVC constriction decreased CO to a similar degree from 3.4 to 2.1 liters/min (P < 0.001). However, the effects on U(osm) (87-104 mosmols/kg) and C(H2o) (2.1-1.6 ml/min) were significantly less than in intact dogs. In another group of hypophysectomized animals, (group III) renal arterial and venous pressures were not controlled, and the effect of TIVC constriction on U(osm) was not significant (65-79 mosmols/kg) although C(H2o) decreased from 3.3 to 1.9 ml/min (P < 0.001). In both the group II and III studies, there were linear correlations between the changes in C(H2o) and the urine flow. Studies were also performed in baroreceptor-denervated animals with intact hypothalamo-neurohypophyseal tracts, and acute TIVC constriction altered neither U(osm) nor C(H2o) when renal arterial pressure was controlled. These results therefore indicate that the effect of TIVC constriction on U(osm) is primarily vasopressin mediated while the effect on C(H2o) is mediated both by vasopressin release and diminished distal fluid delivery. A decrease in renal arterial pressure, or some consequence thereof, seems to be an important determinant of the latter effect.     

VEGF receptor inhibition slows the progression of polycystic kidney disease

Although the receptors for vascular endothelial growth factor (VEGF) exert their effects on vasculogenesis and angiogenesis through receptors located on endothelial cells, recent studies have shown that these receptors are also present on renal tubular epithelial cells. We investigated the role of VEGF on increased tubule cell proliferation in the Han:SPRD heterozygous (Cy/+) rat model of polycystic kidney disease. The levels of VEGF in the kidneys and the serum, and the expression of the two receptors on tubules were increased in Cy/+ rats. These rats were given ribozymes that specifically inhibited VEGFR1 and VEGFR2 mRNA expression. Tubule cell proliferation within the cysts was significantly decreased in the ribozyme-treated animals leading to decreased cystogenesis, blunted renal enlargement, and prevented the loss of renal function. Our studies show that inhibition of VEGF function may be an important therapeutic option to delay the progression of polycystic kidney disease.     

Vasopressin and aquaporin 2 in clinical disorders of water homeostasis

Impaired urinary dilution leading to water retention and hyponatremia may occur in patients with cardiac failure, cirrhosis, pregnancy, oxytocin administration, hypothyroidism, glucocorticoid, and mineralocorticoid deficiency. The mechanisms for these defects predominantly involve the nonosmotic stimulation of arginine vasopressin release with up-regulation of aquaporin 2 water channel expression and trafficking to the apical membrane of the principal cells of the collecting duct. These perturbations are reversed by V2 vasopressin receptor antagonists. In contrast, urinary concentration defects leading to polyuria are vasopressin resistant. They may involve several factors, such as impaired countercurrent concentration secondary to down-regulation of Na-K-2Cl cotransporter. Vasopressin-resistant down-regulation of aquaporin 2 expression has also been described as a factor in impaired urinary concentration.     

The sea within us: disorders of body water homeostasis

The use of a sensitive radioimmunoassay to measure plasma vasopressin led to the clarification of the role of vasopressin in most clinical hyponatremic states, an advance that had been impossible with the less sensitive bioassay for antidiuretic hormone. The cloning of the V2 vasopressin receptor on the basolateral membrane of the principal cells of the collecting duct demonstrated that the majority of congenital nephrogenic diabetes insipidus (NDI) was caused by mutations in this V2 receptor gene. The Nobel Prize discovery of the first membrane water channel by Agre and colleagues allowed for the molecular understanding of many disorders of water homeostasis, several of which are discussed in this review. Mutations of the vasopressin-regulated water channel on the principal cells of the collecting duct, namely aquaporin (AQP)2, account for a minority of cases of congenital NDI. Downregulation of AQP2 expression has subsequently proved important in an array of clinically significant causes of acquired NDI. Most important clinically, has been the discovery of several orally active, non-peptide V2 receptor antagonists, which have significant implications in the treatment of hyponatremic states. This review discusses the major advances that have increased our understanding of the mechanisms of renal water regulation in health and disease. The relationship between osmotic and non-osmotic regulation of antidiuretic hormone (arginine vasopressin) release is discussed.     

Electrical stimulation in the treatment of pelvic pain due to levator ani spasm

OBJECTIVE: To evaluate experience with intravaginal electrical stimulation for the relief of pain when used as adjunctive therapy in women with chronic pelvic pain and levator ani spasm. STUDY DESIGN: A retrospective cohort of consecutively treated patients from 1999 and 2000 was identified using billing records. Systematic chart review was completed using standardized data collection forms for all patients receiving electrical stimulation for pain from levator ani spasm. Data collected were objective for major variables and subjective for outcomes. Demographic data were reported as means and standard deviations. Stimulation characteristics were compared using ANOVA. Survival analysis was performed using life table methods. RESULTS: Medical records from 66 consecutive patients treated during an 18-month interval were reviewed. Demographic characteristics included mean age of 38.7 years, 13 years of education and parity of 2. Married women composed 75% of the study group, with 81% white, 10% Hispanic and 9% black. Of the 66 patients studied, 50 had follow-up documentation with an average duration of 14.5 weeks. Overall, 34 patients (52%) demonstrated improvement in pelvic pain following vaginal electrical stimulation. Using survival analysis, 51% of patients had persistent improvement 30 weeks after treatment. There were no differences in age, race, education or parity between patients reporting a sustained benefit of stimulation and those not reporting a benefit. CONCLUSION: Vaginal electrical stimulation may help a selected population of women with pelvic pain due to levator ani spasm.     

Interleukin-3 treatment of rhesus monkeys leads to increased production of histamine-releasing cells that express interleukin-3 receptors at high levels

To understand the hematopoietic and nonhematopoietic responses to interleukin-3 (IL-3), expression of cell-surface IL-3 receptors (IL-3R) was examined on bone marrow (BM) cells and peripheral blood (PB) cells of rhesus monkeys during the course of in vivo IL-3 treatment. Whereas IL-3R expression is low in untreated monkeys, IL-3 administration led to a gradual increase in both low- and high-affinity binding sites for IL-3. This increase reflected the total number of cells expressing IL- 3Rs, as detected by flow cytometry using biotinylated IL-3. Most of these IL-3R+ cells in both BM and PB could be characterized as basophilic granulocytes that contained high levels of histamine. In contrast to the effect on these differentiated cells, IL-3 administration did not significantly alter the low level IL-3R expression on immature, CD34+ cells. Further flow cytometric analysis using biotinylated growth factors showed that the IL-3R+ basophils also expressed receptors for granulocyte-macrophage colony-stimulating factor (GM-CSF), but not for IL-6 or Kit ligand. These findings indicated that the IL-3R+ cells included neither monocytes, which express GM-CSFRs and IL-6Rs abundantly, nor mast cells, which express c- kit. By combining flow cytometric and Scatchard data, it was calculated that the basophils contain as many as 1 to 2 x 10(3) high-affinity IL- 3Rs and 15 to 30 x 10(3) low-affinity sites. The finding that in vivo IL-3 treatment leads to the production of large numbers of cells that express high levels of IL-3R and are capable of producing histamine provides an explanation for the often severe allergic reactions that occur during prolonged IL-3 administration. It also indicates that IL- 3, in addition to its direct effects on hematopoietic cells, may also stimulate hematopoiesis through the release of secondary mediators such as histamine by IL-3-responsive mature cells.