Abnormally sustained aldosterone secretion during salt loading in patients with various forms of benign hypertension; relation to plasma renin activity

Among 25 patients with benign, essential hypertension, and an equal number with other benign forms of hypertension, without serious cardiac, renal, or cerebrovascular impairment, 41 cases failed to reduce aldosterone excretion rates into the normal range (less than 5 mug/day) on a daily intake of 300 mEq of sodium. The hypertensive patients excreted slightly less than the normal fraction of labeled aldosterone as acid-hydrolyzable conjugate. Secretion rates were significantly higher in the hypertensive patients than in normotensive controls taking the high-sodium intake.On a 10 mEq sodium intake, the increase in excretion and secretion rates of aldosterone in the hypertensive patients could be correlated with plasma renin activity (PRA). The patients with the least increase in PRA had subnormal increase in aldosterone secretion and excretion, while unusually large rises in aldosterone secretion accompanied high PRA, especially in the cases with increased plasma angiotensinogen induced by oral contraceptives.The persistence of inappropriately high aldosterone secretion in most hypertensive patients during sodium loading could be related to a higher PRA than that found in normotensive controls under comparable conditions. In other hypertensives, whose PRA was unresponsive to sodium depletion, there was no significant correlation between PRA and aldosterone output, and no known stimulus to aldosterone production was detected. Five obvious cases of hyperaldosteronism were found among the 16 low-renin patients. The cause of the nonsuppressible aldosterone production in the other low-renin cases remains to be determined.     

Hepatitis C and hospital outcomes in patients admitted with alcohol-related problems

BACKGROUND/AIMS: Alcohol is known to act synergistically with chronic hepatitis C virus (HCV) infection to cause liver disease; however, their combined effect on outcomes in acutely hospitalized patients is less clear. We examined the impact of HCV infection on hospital mortality and length of stay among hospitalized patients with alcohol abuse problems. METHODS: We retrospectively identified 6354 admissions to an urban, public hospital between July 1996 and January 2002 with discharge diagnoses related to alcohol dependence or abuse. Hepatitis C diagnosis and other information were extracted from a clinical database and tested for associations with death and length of hospital stay using multivariable regression techniques. RESULTS: The prevalence of diagnosed HCV infection in this sample of patients with alcohol abuse was 15%. Patients with HCV were about twice as likely to die during hospital admission (4.4 vs. 2.4%; P-value < 0.01), and there appeared to be a trend toward increased mortality even after adjustment for demographics, medical service, homelessness and comorbidities (fully adjusted OR 1.41; 95% CI: 0.97-2.04). Length of stay was significantly longer for patients with HCV (19% longer; 95% CI: 12-27% after adjustment) than those without. CONCLUSIONS: Patients admitted to the hospital with alcohol-related diagnoses have longer hospital stays and are more likely to die in hospital if they have a diagnosis of HCV.     

Adenovirus pneumonia in infants and factors for developing bronchiolitis obliterans: a 5-year follow-up

To describe clinical, pulmonary function, and chest tomography profiles in a 5-year follow-up of infants with adenovirus pneumonia and determine the factors that potentially contributed to the development of bronchiolitis obliterans (BO). We prospectively assessed 45 hospitalized infants with adenovirus pneumonia with additional follow-up for 5 years. At the end of the study, pulmonary function by impulse oscillometry technique (IOS) and chest tomography were performed in the 38 surviving patients (mean 5.7 years of age). We divided the population between those who developed chest tomography evidence of BO and those who did not. Most of the children developed adenovirus infection before 2 years of age. During the 5 years of follow-up, almost half (47.4%) developed BO. Children who developed BO had significantly more respiratory compromise (intensive care admission, need for mechanical ventilation and for oxygen therapy, and systemic corticosteroid and beta agonist use) during their adenovirus pneumonia episode than those who did not develop BO. Only 33.3% of children with BO had normal impedance compared with 85% in the no BO group. Children who developed BO had significantly higher levels of Zrs, R5, X5 and predicted Zrs, R5, and X5 and frequency. However, there were no differences in the beta 2 agonist response between the children with and without BO (94% vs. 80%, respectively). This study represents the spectra of adenovirus pneumonia ranging from relatively mild to severe and fatal cases. Children with severe pulmonary compromise are usually more prone to develop BO.     

Weekly luteal-phase dosing with enteric-coated fluoxetine 90 mg in premenstrual dysphoric disorder: a randomized, double-blind, placebo-controlled clinical trial

BACKGROUND: Because the symptoms of premenstrual dysphoric disorder (PMDD) are limited to the luteal phase of the menstrual cycle, the potential benefit of luteal-phase dosing has been hypothesized. OBJECTIVE: This multicenter, randomized, double-blind, placebo-controlled, parallel-group trial evaluated the efficacy and tolerability of enteric-coated fluoxetine 90 mg given once or twice during the luteal phase for the treatment of PMDD. METHODS: Study drug was given 14 and 7 days before expected menses during the luteal phase of 3 menstrual cycles. After a screening period and single-blind placebo lead-in period, eligible women were randomized to I of 3 treatment groups: enteric-coated fluoxetine 90 mg on both days (LPWDx2); placebo 14 days before menses and enteric-coated fluoxetine 90 mg 7 days before menses (LPWDx1); or placebo on both days (PLC). The primary efficacy measure was change from baseline in mean luteal-phase scores on the Daily Record of Severity of Problems (DRSP). Secondary efficacy measures included scores on the Rating Scale for Premenstrual Tension Syndrome, Clinician-Rated (PMTS-C); the Clinical Global Impression (CGI)-Severity scale; and the Patient Global Impression (PGI)-Improvement scale. Quality of life was assessed using the Sheehan Disability Scale. RESULTS: Two hundred fifty-seven women were randomized to treatment. At the end of the study, the LPWDx2 group had statistically significant improvements in DRSP total, DRSP mood subtotal, DRSP social functioning subtotal, PMTS-C, CGI-Severity, PGI-Improvement, and Sheehan Disability Scale work and family life scores compared with LPWDx1 and PLC (each measure, P < 0.05). There was also a statistically significant improvement in the score on the social life section of the Sheehan Disability Scale with LPWDx2 compared with PLC (P = 0.037). Across all treatment groups, 5 patients discontinued due to nonserious adverse events. Rates of discontinuation for any reason did not differ between the 3 treatment groups. CONCLUSION: The findings of this study support the efficacy and tolerability of enteric-coated fluoxetine 90 mg given twice during the luteal phase of the menstrual cycle for the treatment of PMDD.     

Optimal Disinfection Times for Needleless Intravenous Connectors

BackgroundElimination of catheter-related bloodstream infections is a major focus in health care. According to the Centers for Disease Control and Prevention and the Infusion Nurses Society, the optimal time for needleless connector disinfection has not yet been empirically established.MethodsUsing experimental design and established lab procedure, a 0.5 MacFarland suspension was used to inoculate 172 needleless connectors with bacteria (Staphylococcus aureus, Staphylococcus epidermidis, and Pseudomonas aeruginosa) and allowed to dry for 18 hours. Five groups of connectors (n = 27 per group) were disinfected using 70% isopropyl alcohol with friction for 5, 8, 10, 12, and 15 seconds, and flushed with 0.5 mL nonbacteriostatic sterile normal saline onto sheep-blood agar plates for incubation at 35°C for 48 hours. Bacterial growth (1 colony) was noted on 2 negative controls; therefore, a second sample (n = 172) was tested as above using additional precautions of masking, gloving, and gowning. A third group of connectors was tested using a 0.5 MacFarland suspension containing yeast (Candida albicans).ResultsGroup 1 showed significant (χ²₄ = 37.93; P = .00) and strong (Cramér's V = 0.53; P = .00) associations between scrub time and growth status. Although not statistically significant, Groups 2 and 3 demonstrated clinically significant associations between these factors.ConclusionsAlthough additional research is warranted, our study showed that disinfection times of 5 and 8 seconds were inadequate for reducing bacterial transfer. However, disinfection times of 10, 12, and 15 seconds resulted in comparable, decreased rates of bacterial migration.     

Human leukocyte antigen-DQ8 transgenic mice: a model to examine the toxicity of aerosolized staphylococcal enterotoxin B

Staphylococcal enterotoxins (SEs) belong to a large group of bacterial exotoxins that cause severe immunopathologies, especially when delivered as an aerosol. SEs elicit the release of lethal amounts of cytokines by binding to major histocompatibility complex (MHC) class II and cross-linking susceptible T-cell receptors. Efforts to develop effective therapeutic strategies to protect against SEs delivered as an aerosol have been hampered by the lack of small animal models that consistently emulate human responses to these toxins. Here, we report that human leukocyte antigen-DQ8 (HLA-DQ8) transgenic (Tg) mice, but not littermate controls, succumbed to lethal shock induced by SEB aerosols without potentiation. Substantial amounts of perivascular edema and inflammatory infiltrates were noted in the lungs of Tg mice, similar to the pathology observed in nonhuman primates exposed by aerosol to SEB. Furthermore, the observed pathologies and lethal shock correlated with an upsurge in proinflammatory cytokine mRNA gene expression in the lungs and spleens, as well as with marked increases in the levels of proinflammatory circulating cytokines in the Tg mice. Unlike the case for littermate controls, telemetric evaluation showed significant hypothermia in Tg mice exposed to lethal doses of SEB. Taken together, these results show that this murine model will allow for the examination of therapeutics and vaccines developed specifically against SEB aerosol exposure and possibly other bacterial superantigens in the context of human MHC class II receptors.     

Progressive lung disease and surfactant dysfunction with a deletion in surfactant protein C gene

Mutations in the surfactant protein (SP)-C gene are responsible for familial and sporadic interstitial lung disease (ILD). The consequences of such mutations on pulmonary surfactant composition and function are poorly understood. To determine the effects of a mutation in the SP-C gene on surfactant, we obtained lung tissue at the time of transplantation from a 14-mo-old infant with progressive ILD. An in-frame 9-bp deletion spanning codons 91-93 in Exon 3 of the SP-C gene was present on one allele; neither parent carried this deletion. SP-C mRNA was present in normal size and amount. By immunofluorescence, proSP-C was aggregated within alveolar Type II cells in a compartment separate from SP-B. In airway surfactant, there was little or no mature SP-B or SP-C; SP-A content was increased. Minimum surface tension was increased (20 mN/m, normal < 5 mN/m). Type II cells contained normal and disorganized appearing lamellar bodies by electron microscopy. This spontaneous deletion on one allele of the SP-C gene was associated with sporadic ILD and abnormalities in surfactant composition and function. We propose that a dominant negative effect on surfactant protein metabolism and function results from aggregation of misfolded proSP-C and subsequent cell injury and inflammation.     

Antibacterial role for natural killer cells in host defense to Bacillus anthracis

Natural killer (NK) cells have innate antibacterial activity that could be targeted for clinical interventions for infectious disease caused by naturally occurring or weaponized bacterial pathogens. To determine a potential role for NK cells in immunity to Bacillus anthracis, we utilized primary human and murine NK cells, in vitro assays, and in vivo NK cell depletion in a murine model of inhalational anthrax. Our results demonstrate potent antibacterial activity by human NK cells against B. anthracis bacilli within infected autologous monocytes. Surprisingly, NK cells also mediate moderate antibacterial effects on extracellular vegetative bacilli but do not have activity against extracellular or intracellular spores. The immunosuppressive anthrax lethal toxin impairs NK gamma interferon (IFN-γ) expression, but neither lethal nor edema toxin significantly alters the viability or cytotoxic effector function of NK cells. Compared to human NK cells, murine NK cells have a similar, though less potent, activity against intracellular and extracellular B. anthracis. The in vivo depletion of murine NK cells does not alter animal survival following intranasal infection with B. anthracis spores in our studies but significantly increases the bacterial load in the blood of infected animals. Our studies demonstrate that NK cells participate in the innate immune response against B. anthracis and suggest that immune modulation to augment NK cell function in early stages of anthrax should be further explored in animal models as a clinical intervention strategy.     

Dietary sodium effects on heart rate variability in salt sensitivity of blood pressure

High dietary sodium intake is a risk factor for hypertension, and heart rate variability (HRV) is decreased in hypertension. Effects of dietary sodium intake on HRV of normotensive persons have not, however, been investigated to date. The present study examined effects of low and high sodium diets on blood pressure, heart rate, and HRV in 36 healthy, normotensive women, ages 40-70. Each was placed on a low sodium diet for 6 days followed by a high sodium diet for 6 days. The high salt diet increased mean systolic blood pressure, decreased heart rate, and increased high frequency HRV (HF). Cardiac vagal tone, estimated at baseline from heart period and a time domain estimate of respiratory sinus arrhythmia, was higher in salt-sensitive than salt-insensitive subjects. The finding of increased vagal tone in normotensive persons on high salt intake indicates that dietary sodium status should be considered in behavioral studies of HRV.