Hemodynamic effects of atrial natriuretic hormone

The atrial natriuretic hormone (ANH) alters cardiovascular function independent of changes in body fluid volume. Most investigators agree that ANH decreases mean arterial pressure (MAP). However, although some investigators have observed a decrease in total peripheral resistance in association with the decrease in MAP, a more frequent observation has been decreased cardiac output (CO). The mechanism whereby ANH decreases CO is unknown, but does not appear to be the result of direct myocardial depression, reductions in intravascular or cardiopulmonary volumes, or venodilation. Alterations in skeletal muscle and splanchnic blood flow have been reported by some but not all investigators. Although increases in renal blood flow have been reported, they are transitory and have not been consistently observed by all researchers. The cardiovascular effects of ANH appear to be influenced not only by the dose, but also by the cardiovascular control mechanisms that operate at the time of ANH administration. Non-renin-dependent hypertensive models exhibit a decrease in MAP associated with decreased CO, whereas in renin-dependent animals this hypotension is associated with a decrease in total peripheral resistance.     

Action of a microbial glycerophospholipid:cholesterol acyltransferase on plasma from normal and LCAT-deficient subjects

The action of a bacterial acyltransferase similar in overall reaction mechanism to the plasma enzyme lecithin:cholesterol acyltransferase (LCAT) has been studied using normal plasma and lipoproteins and plasma from LCAT-deficient patients. The microbial enzyme (GCAT) catalyzed acyl transfer using phosphatidylcholine and cholesterol in all of the lipoprotein fractions, presumably because it has no apolipoprotein cofactor. In addition, the enzyme was capable of hydrolyzing cholesteryl ester in lipoproteins but not in small unilamellar vesicles nor in micellar dispersions containing low amounts of Triton X-100. This suggests that cholesteryl ester is exposed on the surface of lipoprotein particles or that it may be transferred there quickly from the interior. Although considerable interconversion of radiolabeled cholesterol and cholesteryl ester could be demonstrated upon treatment of normal plasma or lipoproteins with the enzyme, there was little change in the actual amount of either steroid. This indicates that the rate of cholesteryl ester formation is very similar to the rate of hydrolysis. The relative proportions of cholesterol and cholesteryl ester in normal plasma are therefore near the equilibrium ratio for the reaction carried out by GCAT, or the ratio is controlled by the properties of the lipoproteins themselves. During reaction with the microbial acyltransferase, the ratio of cholesterol to cholesteryl ester in plasma from LCAT-deficient patients was reduced substantially, suggesting that the enzyme may have some practical applications.     

Isolation and characterization of plasma membrane-associated cortical granules from sea urchin eggs

Cortical granules, which are specialized secretory organelles found in ova of many organisms, have been isolated from the eggs of the sea urchins Arbacia punctulata and Strongylocentrtus pupuratus by a simple, rapid procedure. Electron micropscope examination of cortical granules prepared by this procedure reveals that they are tightly attached to large segments of the plasma membrane and its associated vitelline layer. Further evidence that he cortical granules were associated with these cell surface layers was obtained by (125)I-labeling techniques. The cortical granule preparations were found to be rich in proteoesterase, which was purified 32-fold over that detected in a crude homogenate. Similarly, the specific radioactivity of a (125)I-labeled, surface glycoprotein was increased 40-fold. These facts, coupled with electron microscope observations, indicate the isolation procedure yields a preparation in which both the cortical granules and the plasma membrane-vitelline layer are purified to the same extent. Gel electrophoresis of the membrane-associated cortical granule preparation reveals the presence of at least eight polypeptides. The major polypeptide, which is a glycotprotein of apparent mol wt of 100,000, contains most of the radioactivity introduced by (125)I-labeling of the intact eggs. Lysis of the cortical granules is observed under hypotonic conditions, or under isotonic conditions if Ca(2+) ion is present. When lysis is under isotonic conditions is induced by addition of Ca(2+) ion, the electron-dense contents of the granules remain insoluble. In contrast, hypotonic lysis results in release of the contents of the granule in a soluble form. However, in both cases the (125)I-labeled glycoprotein remains insoluble, presumably because it is a component of either the plasma membrane or the vitelline layer. All these findings indicate that, using this purified preparation, it should be possible to carry out in vitro studies to better define some of the initial, surface-related events observed in vivo upon fertilization.     

The effect of renal vasodilation and hypotonic volume expansion on water excretion in dogs after anesthesia and surgery

The possible effects of renal vasoconstriction from anesthesia and surgery on water excretion after hypotonic volume expansion (HVE) were studied in 18 well conditioned anesthetized dogs, with and without the infusion of phenoxybenzamine and acetylcholine into the renal artery of the cannulated kidney. In 6 dogs (Group 1 - Control) whose renal artery was infused with isosmotic saline, HVE resulted in a bilateral increase in GFR and UV (p < .05). ERPF, Cosm, C_H2O, U_NaV, U_KV, RBF, RVR and MAP did not change significantly. In 6 other dogs (Group 2), whose cannulated kidney was infused with phenoxybenzamine 50 μg/min before and during HVE, GFR increased on the infused side while CH₂O and UV increased bilaterally (p < .05). ERPF, Cosm, U_NaV, U_KV, RBF, RVR and MAP were not affected significantly. The addition of ADH, 2 mu/min into the phenoxybenzamine infusate, decreased ERPF, RBF and RVR bilaterally and CH₂O on the infused side (p < .05). It had no effect upon GFR, Cosm, U_NaV, U_KV and MAP. In another 6 dogs, (Group 3), whose cannulated renal artery was infused with acetylcholine (20 μg/min) before and during HVE, C_H2O, UV and RVR increased bilaterally (p < .05). ERPF and RBF decreased bilaterally (p < .05), whereas GFR, Cosm, U_NaV and MAP were unaffected. U_KV decreased on the infused side (p < .05). The addition of ADH (2 mu/min)_into the acetylcholine infusate, decreased C_H2O bilaterally and increased Cosm and U_KV on the control side (p < .05). It had no effect on ERPF, GFR, UV, U_NaV, RBF, RVR and MAP. These observations suggest that anesthesia and surgery produce renal vasoconstriction and this together with increased ADH release, interfere with water excretion by the kidney. Previous renal vasodilation prevents these influences of anesthesia and surgery.     

Necines of alkaloids in Heliotropium species from Mexico and the U.S.A.

The qualitative and quantitative compositions of necines in plants of 20 Heliotropium species collected in Mexico and the U.S.A. and one species from Spain are reported. Trachelanthamidine, supinidine and retronecine were found in all species after hydrolysis of their alkaloids; lindelofidine was detected in most species, whereas heliotridine only in four. Trachelanthamidine, lindelofidine, and supinidine were dominant in four, two and one species, respectively; retronecine was dominant in 15 species, whereas heliotridine only in one. The dominant necine in H. ternatum was either retronecine or lindelofidine depending on the collection locality. Qualitative as well as quantitative differences depending on the collection locality were found in H. curassavicum. Plants from Oaxaca, Mexico, contained lindelofidine and a pyrrolizidine-diol as major necines, trachelanthamidine as minor, and traces of retronecine. Plants originating from two other localities contained trachelanthamidine (dominant), retronecine, and supinidine. The necine patterns found in the examined species differ significantly from those previously reported for 21 species mainly collected in Asia, the Middle East and Australia.     

Role of the competitive microbial flora in the radiation-induced enhancement of ochratoxin production by Aspergillus alutaceus var. alutaceus NRRL 3174.

The radiation sensitivity and the toxigenic potential of conidiospores of the fungus Aspergillus alutaceus var. alutaceus were determined after irradiation with 60Co gamma rays and high-energy electrons. Over the pH range of 3.6 to 8.8, the doses required for a 1 log10 reduction in viability based on the exponential portion of the survival curve ranged from 0.21 to 0.22 kGy, with extrapolation numbers (extrapolation of the exponential portion of the survival curve to zero dose) of 1.01 to 1.33, for electron irradiation, and from 0.24 to 0.27 kGy, with extrapolation numbers of 2.26 to 5.13, for gamma irradiation. Nonsterile barley that was inoculated with conidia of the fungus and then irradiated with either electrons or gamma rays and incubated for prolonged periods at 28 degrees C and at a moisture content of 25% produced less ochratoxin A with increasing doses of radiation. Inoculation of barley following irradiation resulted in enhanced ochratoxin levels compared with unirradiated controls. In these experiments, inoculation with 10(2) spores per g produced greater radiation-induced enhancement than inoculation with 10(5) spores per g. There was no radiation-induced enhancement when the barley was surface sterilized by chemical means prior to irradiation. These results are consistent with the hypothesis that a reduction in the competing microbial flora by irradiation is responsible for the enhanced mycotoxin production observed when nonsterile barley is inoculated with the toxigenic fungus A. alutaceus var. alutaceus after irradiation.     

Programmatic Cost Evaluation of Nontargeted Opt-Out Rapid HIV Screening in the Emergency Department

Background

The Centers for Disease Control and Prevention recommends nontargeted opt-out HIV screening in healthcare settings. Cost effectiveness is critical when considering potential screening methods. Our goal was to compare programmatic costs of nontargeted opt-out rapid HIV screening with physician-directed diagnostic rapid HIV testing in an urban emergency department (ED) as part of the Denver ED HIV Opt-Out Trial.

Methods

This was a prospective cohort study nested in a larger quasi-experiment. Over 16 months, nontargeted rapid HIV screening (intervention) and diagnostic rapid HIV testing (control) were alternated in 4-month time blocks. During the intervention phase, patients were offered HIV testing using an opt-out approach during registration; during the control phase, physicians used a diagnostic approach to offer HIV testing to patients. Each method was fully integrated into ED operations. Direct program costs were determined using the perspective of the ED. Time-motion methodology was used to estimate personnel activity costs. Costs per patient newly-diagnosed with HIV infection by intervention phase, and incremental cost effectiveness ratios were calculated.

Results

During the intervention phase, 28,043 eligible patients were included, 6,933 (25%) completed testing, and 15 (0.2%, 95% CI: 0.1%–0.4%) were newly-diagnosed with HIV infection. During the control phase, 29,925 eligible patients were included, 243 (0.8%) completed testing, and 4 (1.7%, 95% CI: 0.4%–4.2%) were newly-diagnosed with HIV infection. Total annualized costs for nontargeted screening were $148,997, whereas total annualized costs for diagnostic HIV testing were $31,355. The average costs per HIV diagnosis were $9,932 and $7,839, respectively. Nontargeted HIV screening identified 11 more HIV infections at an incremental cost of $10,693 per additional infection.

Conclusions

Compared to diagnostic testing, nontargeted HIV screening was more costly but identified more HIV infections. More effective and less costly testing strategies may be required to improve the identification of patients with undiagnosed HIV infection in the ED.     

High Burden of Human Papillomavirus (HPV) Infection among Young Women in KwaZulu-Natal,South Africa

Objectives

HPV infection causes cervical cancer, yet information on prevalence and risk factors for HPV in Africa remain sparse. This study describes the prevalence of HPV genotypes and risk factors associated with HPV among young women ≤ 30 years of age in KwaZulu-Natal (KZN), South Africa.

Methods

Cervicovaginal lavage samples were tested for HPV genotypes in 224 women enrolled in a prospective cohort study. Clinical, behavioural and demographic data were collected. We measured prevalence of HPV genotypes and using logistic regression, examined for factors associated with HPV.

Results

Median age of participants was 21 years [interquartile range (IQR):18–23]. The overall prevalence of HPV was 76.3% (171/224) with multiple and single genotypes prevalent in 56.3% and 20.1% of women respectively. Proportion of women with high-risk genotypes (16, 18, 31, 33, 35, 39, 45, 51, 52, 56 and 58) was 54.5%. Women not living with their partner [adjusted odds ratio (aOR)] = 3.42 95% CI1.22–9.60; p = 0.019), was significantly associated with HPV infection and high-risk HPV genotype infection.

Conclusion

The high burden of HPV and associated risk behaviours highlight the need to intensify behavioural interventions to prevent HPV acquisition in young women. The large scale delivery of HPV vaccine should be prioritised to prevent HPV acquisition and reduce HPV-related morbidity.