Silicon detector dark matter results from the final exposure of CDMS II.

We report results of a search for weakly interacting massive particles (WIMPS) with the silicon detectors of the CDMS II experiment. This blind analysis of 140.2 kg day of data taken between July 2007 and September 2008 revealed three WIMP-candidate events with a surface-event background estimate of 0.41(-0.08)(+0.20)(stat)(-0.24)(+0.28)(syst). Other known backgrounds from neutrons and 206Pb are limited to <0.13 and <0.08 events at the 90% confidence level, respectively. The exposure of this analysis is equivalent to 23.4 kg day for a recoil energy range of 7-100 keV for a WIMP of mass 10 GeV/c2. The probability that the known backgrounds would produce three or more events in the signal region is 5.4%. A profile likelihood ratio test of the three events that includes the measured recoil energies gives a 0.19% probability for the known-background-only hypothesis when tested against the alternative WIMP+background hypothesis. The highest likelihood occurs for a WIMP mass of 8.6 GeV/c2 and WIMP-nucleon cross section of 1.9×10(-41) cm2.

Drinking water and cancer mortality in Louisiana.

Multivariant regression analysis indicates a statistically significant relation between cancer mortality rates in Louisiana and drinking water obtained from the Missippi River. This is true for total cancer, cancer of the urinary organs, and cancer of the gastrointestinal tract.

The pathogenesis of post-obstructive diuresis. The role of circulating natriuretic and diuretic factors, including urea.

To investigate the pathogenesis of post-obstructive diuresis, a state of functional "anuria" during ureteral obstruction was created in awake rats by (a) bilateral obstruction (BO); (b) unilateral obstruction and contralateral nephrectomy (UO-Nx); or (c) unilateral obstruction and continuous i.v. reinfusion of urine from the intact contralateral kidney (UO-reinf). These groups were compared with unilaterally obstructed (UO) and sham-operated control (sham) rats. After release of obstruction of 24 h duration, mean urine flows (V) and sodium excretion rates (UNaV) were significantly elevated above those of sham rats in BO, UO-Nx, and UO-reinf animals, but slightly decreased in UO rats. Glomerular filtration rates were comparably depressed in UO, BO, UO-Nx, and UO-reinf rats. These results suggest that post-obstructive diuresis is due to one or more circulating diuretic factors that are normally excreted in the urine, and which, when retained )as in BO or UO-Nx rats) or returned to the circulation (as in UO-reinf rats), exert a diuretic affect. In additional experiments, UO rats infused with urea exhibited post-obstructive diuresis, if extracellular volume contraction was prevented. This result suggests that urea may be an important diuretic factor in post-obstructive diuresis, but does not exclude possible roles for other humoral factors. The intact kidney of UO-reinf rats displayed a massive unilateral diuresis and natriuresis, further suggesting the presence of potent diuretic factors in the urine. A marked increase in the fractional excretion of glomerular filtrate (V/GFR) by the intact kidney suggests that this diuresis may be attributable, in part, to impaired proximal reabsorption.

Obstructive nephropathy in the rat: possible roles for the renin-angiotensin system, prostaglandins, and thromboxanes in postobstructive renal function.

Relief of unilateral ureteral obstruction (UUO) of 24 h duration in rats is followed by severe renal vasoconstriction in the postobstructive kidney (POK). The present study examined possible roles of renal prostaglandins (PG) and thromboxanes (TX), as well as the renin-angiotensin system, in this vasoconstriction. Administration of the cyclooxygenase inhibitor indomethacin, which blocks both PG and TX production, failed to improve POK hemodynamics in UUO rats. To explore the possible role of the TX compounds, which include the potent vasoconstrictor thromboxane A2 (TXA2), UUO rats were infused with imidazole, an agent that blocks synthesis of TX, but not of PG. Imidiazole led to two- to threefold increases in the clearance of both inulin and rho-aminohippuric acid by the POK. This effect of imidazole was abolished by indomethacin, suggesting that the amelioration of POK vasoconstriction by imidazole was a result of inhibition of vasoconstrictor TX synthesis (e.g. TXA2), with PG vasodilators (e.g. PGE2 or PG12) still active. Urea, infused in a solution whose osmolality and volume were identical to the imidazole infusion, failed to improve hemodynamics in the POK, making it unlikely that nonspecific effects of volume expansion or osmotic diuresis mediated the beneficial effect of imidazole. Further studies examined the possible role of the renin-angiotensin systems in the vasoconstriction of the POK. UUO rats infused with the angiotensin II antagonist, Saralasin, exhibited no significant improvement in POK function, a finding that might be at least partly attributable to agonist/vasoconstrictor properties of Saralasin. In other experiments, treatment of UUO rats with the angiotensin-converting enzyme blocker SQ 14225 (Captopril), in order to inhibit angiotensin II formation, led to at least twofold increases in the clearance of both inulin and rho-aminohippuric acid in the POK. It is unlikely that Captopril exerted this beneficial effect by potentiating the vasodilator kinins, because the effect was not diminished by administration of either carboxypeptidase B (which destroys the kinins) or Trasylol (which blocks kinin synthesis). Thus, these results suggest that both angiotensin II, as well as metabolites of the PG-TX system, may be important determinants of postobstructive renal hemodynamics in the rat.

Bi-level positive airway pressure support system use in acute congestive heart failure: preliminary case series.

OBJECTIVE: To describe the use of a noninvasive bi-level positive airway pressure (PAP) support system for ED patients with acute congestive heart failure (CHF). METHODS: Retrospective case series analysis of ED patients presenting with acute CHF in imminent need of endotracheal intubation (ETI) managed with a bi-level PAP system. The bi-level PAP system was applied at the discretion of the treating emergency physician. Management of the bi-level PAP system, including setting of inspiratory PAP (IPAP) and expiratory PAP (EPAP), weaning, adjunct pharmacologic therapy, and failure of bi-level PAP support, was determined by the treating physician. RESULTS: Only two (9%) of 22 patient presentations necessitated ETI. The mean duration of bi-level PAP therapy was 7.9 hours. The mean maximum IPAP and EPAP settings were 10.8 and 5.8 cm H2O, respectively. Mean intensive care unit length of stay (LOS) was 2.4 days, with a median LOS of only 1 day. There were three deaths in the series; none were attributed to the bi-level PAP system. No technical difficulty with the bi-level PAP system was noted. CONCLUSION: Noninvasive pressure support ventilation with a bi-level PAP support system may avert ETI in acute CHF patients. This device can be effectively used by ED personnel.

Acute cardiogenic pulmonary edema. What's the latest in emergency treatment?

With the methods available today, most patients who arrive at the emergency department with acute cardiogenic pulmonary edema can be treated quickly and effectively. Modern pharmacologic therapy is based on directly counteracting the physiologic abnormalities that cause pulmonary edema. Agents that are useful in reducing LV preload and afterload and in managing hypotension are nitroglycerin, ACE inhibitors, vasodilators, vasopressors, and bipyrines. Noninvasive pressure support ventilation helps patients with pulmonary edema by decreasing the work of breathing, enhancing oxygen and carbon dioxide exchange, and increasing cardiac output. Use of BiPAP systems in emergency departments has averted endotracheal intubation in about 90% of patients with pulmonary edema who are experiencing acute respiratory failure.

Slowly dialyzable stimulators of renal protein synthesis in urine.

Previously, we demonstrated that continuous intravenous reinfusion of half the urine output (1/2UR) in rats for 1 wk led to increased renal mass. This suggested that reduced renal excretory function, or the retention of urinary factors, was capable of stimulating renal growth. The present study was designed to examine renal protein synthesis during the early phase of this growth and to better define the nature of the stimuli. Compared with matched sham-manipulated control rats, rats subjected to 24 h of 1/2UR displayed significant increases in both the incorporation of tritiated leucine into protein and in the cellular uptake of leucine by renal cortical tissue in vitro. In addition, total protein content of the kidneys, but not of the liver, was significantly increased after 24 h of 1/2UR. Dialysis of urine prior to its reinfusion did not diminish, but rather augmented, the incorporation of leucine into renal protein. These results suggest that renal protein synthesis can be stimulated by the retention of factors in the urine that are poorly dialyzable.

Ureteral catheter system for renal function studies in conscious rabbits.

To overcome the problem of obstruction of ureteral catheters with blood clots, a ureteral catheter was constructed which had a double lumen. Irrigation of blood from the catheter was accomplished by perfusion of heparinized saline through a small inner catheter. In renal function studies performed in 12 rabbits using this system, no instances of catheter obstruction occurred.

Urine-reinfusion natriuresis: evidence for potent natriuretic factors in rat urine.

In awake rats the entire urine output was continuously reinfused i.v. Urine-reinfusion (UR) consistently led to the appearance, within one to two hours, of massive, sustained natriuresis and diuresis, suggesting the existence of potent natriuretic factors in the urine. At the time of maximal natriuresis, mean sodium excretion rate and urine flow rate were 25 and 15 times their respective values in control rats. Ths "urine-reinfusion natriuresis" could be demonstrated despite treatment with desoxycorticosterone acetate, blockage of prostaglandin synthesis by indomethacin or meclofenamate, reduction of plasma urea by pretreatment with a protein-free diet, or heating the urine to 100 degrees C. The natriuresis was not prevented by the absence of vasopressin (in Brattleboro rats) and was augmented by vasopressin infusion. In the Brattleboro rats, a marked increase in (CH2O + CNa)/GFR with only a slight rise in CH2O/GFR during UR suggests inhibition of both proximal and distal tubular reabsorption. Renal blood flow and plasma flow increased markedly during UR with a lesser rise in GFR, consistent with post-glomerular vasodilatation. Thus, the phenomenon of urine-reinfusion natriuresis suggests the presence in rat urine of potent, heat stable natriuretic factors, whose action is largely independent of changes in mineralocorticoids, prostaglandins, urea, or vasopressin. Renal vasodilatation with decreased sodium reabsorption at both proximal and distal nephron sites, appears to play an important role in the natriuresis.

Uptake and intracellular distribution of ferritin in the rat distal convoluted tubule.

The purpose of this study was to determine the uptake and intracellular distribution of anionic ferritin (AF) and cationic ferritin (CF) in the distal convoluted tubule (DCT) of the rat kidney. Male Sprague-Dawley rats were prepared for micropuncture, and individual distal tubules were perfused with 5 or 10 mg/ml of AF or 0.1 or 0.5 mg/ml of CF in isotonic saline for either 30 sec or 3 min. The tubules were fixed by perfusion with 6.25% glutaraldehyde either immediately or at different time intervals after exposure to ferritin. Electron microscopy of tubules fixed immediately after perfusion showed no binding of AF to the apical cell membrane, and only traces of AF were observed in small apical structures. In contrast, CF was extensively bound to the apical cell membrane and located in apical vesicles and tubules, and in multivesicular bodies. Occasionally, CF was observed in Golgi vesicles and cisternae. Sixty min after perfusion with ferritin, traces of AF were present in multivesicular bodies and lysosome-like structures. Thirty and 60 min after perfusion, large concentrations of CF were located in multivesicular bodies and lysosome-like bodies. This study reveals that in the DCT, CF is bound to the apical cell membrane and taken up into the tubule cells, whereas only traces of AF are taken up, indicating that the charge of a protein molecule may determine whether or not the protein is reabsorbed by the DCT. The demonstration of CF in the Golgi complex is compatible with the existence of membrane recycling in cells of the DCT.

Renotrophic factors in urine.

Our previous observations of increased renal protein synthesis in rats subjected to the constant intravenous reinfusion of half their urine output has suggested that the circulatory retention of renotrophic factors in urine is capable of stimulating renal growth. In the present studies, using this same model of "half-urine-reinfusion," which is designed to produce a selective halving of renal excretory function, we have demonstrated significant increases in total DNA content and the incorporation of tritiated thymidine in renal DNA. In addition, a bioassay method was developed in which an assay rat, given an intravenous infusion of urine from another rat, exhibited increases in the incorporation of thymidine into renal DNA and the incorporation of radiolabelled choline into renal phospholipid. This renotrophic activity in the urine was only minimally decreased by heating to 100 degrees C for 30 min and was confined to ultrafiltration fractions retained on a membrane with a nominal 10,000-dalton solute rejection. Removal of one kidney from the rats from which the urine was obtained led to only a modest and transient reduction in the excretion of renotrophic activity, suggesting that the urinary renotrophic factors are of circulatory, not renal, origin. Isolated renal cortical fragments incubated with an ultrafiltration retentate of urine displayed a dose-dependent increase in choline incorporation into phospholipid, suggesting a direct action of the factors on kidney tissue. Finally, no evidence of stimulation of either DNA or phospholipid synthesis could be seen in hepatic tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Cellular mechanisms of prostaglandin action.

The human platelet and erythrocyte differ quite dramatically in relation to the arachidonic acid cascade. The platelet synthesizes its own characteristic products, while the erythrocyte lacks cyclo-oxygenase activity but possesses other metabolic enzymes. In these and other cell types the metabolites are potentially determined by the cascade enzymes, the availability of cofactors, the presence of specific activators and inhibitors, and the selective binding or transport of intermediates. Endogenously synthesized metabolites may have intracellular actions or may be released and exert their effects extracellularly. Study of the cellular mechanisms mediating these effects, like study of the fast-acting hormones, has focused primarily on the cyclic nucleotides and calcium. Considering the diverse activities of several metabolites in the platelet however, these mechanisms seem to need reevaluation or refining. The released cascade metabolites may also act as intercellular signals over a short range. The range depends on their chemical stability in the absence of protective carriers and their selective uptake and metabolism by surrounding cells. Additionally, the effects will reflect the selective interaction of responsive cells with the spectrum of metabolites released. Answering these questions of complex intercellular interactions requires the identification and classification of characteristic responses and the metabolic profile of individual cell types in each tissue. Consequently, this type of analysis may best be done with isolated cells, such as the platelet and erythrocyte.

Thromboxane, prostacyclin, and hemodynamic events in primate endotoxin shock.

Prostaglandins participate in the pathophysiology of septic shock; however, their exact role is unclear. In this study we investigated the possibility that thromboxane and prostacyclin, the most recently discovered prostaglandins, may be related to the pulmonary arterial hypertension (thromboxane) and systemic arterial hypotension (prostacyclin) during endotoxin shock in the baboon. There are no previously reported studies in the subhuman primate. In this study ten male baboons received an LD70 dose of E. coli endotoxin. Cardiac output, mean systemic arterial pressure, pulmonary arterial pressure, blood gases, WBC and platelet counts, and prostaglandins were determined at 0, 15, 60, 120, 180, and 240 minutes. Thromboxane and prostacyclin levels were significantly (P less than 0.05) increased after the endotoxin injection. Systemic arterial PGI values increased within 15 minutes, peaked at two hours, and was directly related to the fall in systemic arterial pressure (r = 0.93). In contrast, thromboxane values peaked at 15 minutes and directly related (r = 0.90) to the rise in pulmonary artery pressure. Thromboxane and prostacyclin are significantly increased in subhuman primate endotoxin shock. The temporal relationship of thromboxane and pulmonary arterial pressure suggests that thromboxane may mediate the effects of endotoxin on the pulmonary vasculature.