Effects of resuscitation with human albumin 5%, hydroxyethyl starch 130/0.4 6%, or crystalloid on kidney damage in an ovine model of septic shock.

BACKGROUND: Colloid solutions have been associated with kidney dysfunction in septic animals and humans. The present study investigated the influence of resuscitation with human albumin (HA) 5%, hydroxyethyl starch (HES) 130/0.4 6%, and balanced crystalloids on ultrastructural kidney damage, kidney function, and survival in a model of ovine septic shock. METHODS: After induction of peritoneal septic shock, animals were randomised to one of the following groups: (1) HA 5%, (2) HES 130/0.4 6%, (3) balanced crystalloid, and (4) control (each n=10). Causal therapy included re-laparotomy, peritoneal lavage, and antimicrobial therapy. Sequential kidney biopsies were obtained for the assessment of the electron microscopic tubular injury (EMTI) score. RESULTS: Serum creatinine and urea were highest in the control group, and there were no differences between the intervention groups. Cumulative diuresis was significantly higher in the HA group [1.0 ml kg-1 h-1 (0.6; 1.2)] compared with control [0.7 ml kg-1 h-1 (0.6; 0.9), P<0.05]. Creatinine clearance was highest in the HA and crystalloid groups. Ultrastructural kidney damage was highest in the control group [EMTI score 7.8 (6.7; 9.0)] without differences between intervention groups. Survival was 100% in the colloid groups vs 90% (crystalloid) and 60% (control, all P<0.05). CONCLUSION: In an ovine model of septic shock, kidney function and cumulative diuresis were preserved in the 5% albumin and crystalloid resuscitation groups, whereas HES 130/0.4 6% resulted in diminished creatinine clearance. Differences in kidney function between resuscitation fluids could not be explained by differences in ultrastructural kidney damage. CLINICAL TRIAL REGISTRATION: 84-02.04.2011.A300.

Ventilation rates in recently constructed U.S. school classrooms.

Low ventilation rates (VRs) in schools have been associated with absenteeism, poorer academic performance, and teacher dissatisfaction. We measured VRs in 37 recently constructed or renovated and mechanically ventilated U.S. schools, including LEED and EnergyStar-certified buildings, using CO2 and the steady-state, build-up, decay, and transient mass balance methods. The transient mass balance method better matched conditions (specifically, changes in occupancy) and minimized biases seen in the other methods. During the school day, air change rates (ACRs) averaged 2.0±1.3 hour-1 , and only 22% of classrooms met recommended minimum ventilation rates. HVAC systems were shut off at the school day close, and ACRs dropped to 0.21±0.19 hour-1 . VRs did not differ by building type, although cost-cutting and comfort measures resulted in low VRs and potentially impaired IAQ. VRs were lower in schools that used unit ventilators or radiant heating, in smaller schools and in larger classrooms. The steady-state, build-up, and decay methods had significant limitations and biases, showing the need to confirm that these methods are appropriate. Findings highlight the need to increase VRs and to ensure that energy saving and comfort measures do not compromise ventilation and IAQ.

Acyclovir and transmission of HIV-1 from persons infected with HIV-1 and HSV-2.

BACKGROUND: Most persons who are infected with human immunodeficiency virus type 1 (HIV-1) are also infected with herpes simplex virus type 2 (HSV-2), which is frequently reactivated and is associated with increased plasma and genital levels of HIV-1. Therapy to suppress HSV-2 reduces the frequency of reactivation of HSV-2 as well as HIV-1 levels, suggesting that suppression of HSV-2 may reduce the risk of transmission of HIV-1. METHODS: We conducted a randomized, placebo-controlled trial of suppressive therapy for HSV-2 (acyclovir at a dose of 400 mg orally twice daily) in couples in which only one of the partners was seropositive for HIV-1 (CD4 count, > or = 250 cells per cubic millimeter) and that partner was also infected with HSV-2 and was not taking antiretroviral therapy at the time of enrollment. The primary end point was transmission of HIV-1 to the partner who was not initially infected with HIV-1; linkage of transmissions was assessed by means of genetic sequencing of viruses. RESULTS: A total of 3408 couples were enrolled at 14 sites in Africa. Of the partners who were infected with HIV-1, 68% were women, and the baseline median CD4 count was 462 cells per cubic millimeter. Of 132 HIV-1 seroconversions that occurred after randomization (an incidence of 2.7 per 100 person-years), 84 were linked within couples by viral sequencing: 41 in the acyclovir group and 43 in the placebo group (hazard ratio with acyclovir, 0.92, 95% confidence interval [CI], 0.60 to 1.41; P=0.69). Suppression with acyclovir reduced the mean plasma concentration of HIV-1 by 0.25 log(10) copies per milliliter (95% CI, 0.22 to 0.29; P<0.001) and the occurrence of HSV-2-positive genital ulcers by 73% (risk ratio, 0.27; 95% CI, 0.20 to 0.36; P<0.001). A total of 92% of the partners infected with HIV-1 and 84% of the partners not infected with HIV-1 remained in the study for 24 months. The level of adherence to the dispensed study drug was 96%. No serious adverse events related to acyclovir were observed. CONCLUSIONS: Daily acyclovir therapy did not reduce the risk of transmission of HIV-1, despite a reduction in plasma HIV-1 RNA of 0.25 log(10) copies per milliliter and a 73% reduction in the occurrence of genital ulcers due to HSV-2. (ClinicalTrials.gov number, NCT00194519.)

Herpes zoster incidence in a multicenter cohort of solid organ transplant recipients.

BACKGROUND: Immunosuppressed patients are at increased risk for herpes zoster (HZ), but incidence in solid organ transplant (SOT) recipients has varied in multiple studies. To assess incidence of HZ, we examined patients who underwent SOT and received follow-up care within the large multicenter US Department of Veteran's Affairs healthcare system. METHODS: Incident cases of HZ were determined using ICD-9 coding from administrative databases. A multivariable Cox proportional hazards model, adjusted for a priori risk factors, was used to assess demographic factors associated with development of HZ. RESULTS: Among the 1077 eligible SOT recipients, the cohort-specific incidence rate of HZ was 22.2 per 1000 patient-years (95% confidence interval [CI], 18.1-27.4). African Americans (37.6 per 1000 [95% CI, 25.0-56.6]) and heart transplants recipients (40.0 per 1000 [95% CI, 23.2-68.9]) had the highest incidence of HZ. Patients transplanted between 2005 and 2007 had the lowest incidence (15.3 per 1000 [95% CI, 8.2-28.3]). In a multivariable model, African Americans (hazard ratio [HR] 1.88; 95% CI: 1.12, 3.17) and older transplant recipients (HR 1.13; 95% CI: 1.01, 1.27 [per 5-year increment]) had increased relative hazards of HZ. CONCLUSIONS: These data demonstrate that HZ is a common infectious complication following SOT. Future studies focused on HZ prevention are needed in this high-risk population.

Use of the designation "shedder" in mucosal detection of herpes simplex virus DNA involving repeated sampling.

OBJECTIVES: We evaluated two methods to describe detection of herpes simplex virus (HSV) from the genital mucosa. METHODS: We assessed genital swabs from HSV-2 seropositive people participating in longitudinal studies of HSV DNA detection at the University of Washington Virology Research Clinic. We determined the length of observation period necessary to ensure some HSV detection for most individuals. We compared two measures to assess differences in shedding according to HIV status, the shedding rate ratio, defined as the proportion of total samples with detectable HSV in HIV-1 seropositive versus HIV-1 seronegative participant, and the ratio of "shedders", defined as the proportion of people with any shedding over the interval in HIV-1 seropositive versus HIV-1 seronegative people. RESULTS: While only 17% (51/308) of HSV-2 seropositive people shed on their first day on study, 77% (238/308) had some genital shedding over 30 days (any HSV DNA detected on genital swabs). Shedding rate ratios (SRR) for HIV-seropositive versus HIV-seronegative people varied from SRR = 1.42 using 10 samples to SRR = 1.35 using 50 samples. The ratio of "shedders" (RS) approached 1 as the observation period increased (RS = 1.13 using 10 samples to RS = 1.01 using 50 samples). In a hypothetical case, the ratio of "shedders" was shown to exceed 1 when shedding rates were equal. CONCLUSIONS: Most HSV-2 seropositive people shed HSV from the genital mucosa. Dichotomisation of people into "shedders" and "non-shedders" or "high" and "low" shedders yields inferences that depend upon sampling interval length. Overall shedding rates provide consistent measures regardless of the number of swabs collected.

The use of antiviral drugs in the prevention and treatment of Kaposi sarcoma, multicentric Castleman disease and primary effusion lymphoma.

Kaposi sarcoma-associated herpesvirus [KSHV, also known as human herpesvirus 8 (HHV-8)] is the most recently identified member of the human herpesvirus family. Kaposi sarcoma (KS), primary effusion lymphoma, and multicentric Castleman disease are all associated with KSHV infection. Although the incidence of KS has declined dramatically in areas with access to highly active antiretroviral therapy, it remains the most common AIDS-associated malignancy in the developed world and is one of the most common cancers in developing nations. Current treatment options for KSHV-associated disease are ineffective, unavailable, or toxic to many affected persons. A growing body of basic science, preclinical, and observational data suggests that antiviral medications may play an important role in the prevention and treatment of KSHV-associated disease.

Frequent genital herpes simplex virus 2 shedding in immunocompetent women. Effect of acyclovir treatment.

Reactivation of herpes simplex virus type 2 (HSV-2) occurs intermittently as perceived clinically and by viral culture. We performed a series of studies to evaluate the frequency and pattern of HSV-2 reactivation using both viral isolation and HSV PCR assay. Daily samples of genital secretions were obtained from 27 HSV-2 seropositive women; a subset of subjects obtained samples while receiving oral acyclovir 400 mg PO twice a day. HSV DNA was detected in genital swab specimens on 28% of 1,410 d compared with 8.1% of days by viral isolation. 11 of 20 women had HSV DNA detected on > 20% of days, 4 on > 50%, and 2 on > 75% of days; in contrast, none of the women shed on > 21% of days by viral isolation. The daily administration of oral acyclovir promptly reduced the frequency of HSV DNA detection by a median of 80%. Within 3-4 d of discontinuing daily acyclovir, HSV DNA again appeared in the genital area. HSV-2 shedding in the genital mucosa occurs much more frequently than previously appreciated. This frequent reactivation likely plays a role in the epidemic spread of genital herpes worldwide.

The burden of constipation on quality of life: results of a multinational survey.

BACKGROUND: The impact of constipation on quality of life (QoL) may vary in different cultural or national settings. AIM: We studied QoL in a multinational survey to compare different social and demographic groups with and without constipation (defined according to Rome III criteria) and to detect country-specific differences among the groups studied. METHODS: Health-related QoL (HRQoL) was assessed with the Short Form 36 (SF-36) questionnaire in 2870 subjects in France, Germany, Italy, UK, South Korea, Brazil and USA. Results Respondents were mainly middle-aged, married or living together and part- or full-time employed. General health status, measured by the SF-36 questionnaire, was significantly worse in the constipated vs. non-constipated populations. RESULTS: were comparable in all countries. QoL scores correlated negatively with age. Constipated women reported more impaired HRQoL than constipated men. Brazilians were most affected by constipation as to their social functioning (35.8 constipated vs. 51.3 non-constipated) and general health perception (29.4 constipated vs. 54.4 non-constipated). CONCLUSIONS: There are significant differences in HRQoL between constipated and non-constipated individuals and a significant, negative correlation between the number of symptoms and complaints and SF-36 scores. The study detected a correlation of constipation with QoL and the influence of social and demographic factors on HRQoL in constipated people.

HIV prevalence, previous HIV testing, and condom use with clients and regular partners among Senegalese commercial sex workers.

OBJECTIVES: To assess HIV prevalence and risk factors for HIV infection, to investigate condom use among registered female commercial sex workers (CSWs) in Senegal, West Africa, and to examine the association between previous HIV testing, knowledge of HIV serostatus and condom use with both regular sex partners and clients within this population. METHODS: A cross-sectional study was conducted at three sexually transmitted disease clinics among 1052 Senegalese registered CSWs between 2000 and 2004. Inperson interviews soliciting information concerning demographic characteristics, medical history, sexual behaviour with clients and regular partners, and previous HIV testing history were performed. Blood samples were collected for determination of HIV-1 and/or HIV-2 serostatus. Multivariable, Poisson and log-binomial models were used to calculate prevalence ratios. RESULTS: The overall HIV prevalence was 19.8%. Over 95% of CSWs reported always using a condom with clients, but only 18% reported always using a condom with their regular partners. A history of previous HIV testing was not associated with condom use with clients (adjusted prevalence ratio (APR) = 0.98, 95% confidence intervals, CI: 0.90 to 1.06). However, prior HIV testing was associated with decreased condom use with their regular partners (APR = 0.44, 95% CI: 0.28 to 0.69), especially in women who tested HIV negative (APR = 0.17, 95% CI: 0.08 to 0.36). CONCLUSIONS: CSWs in Senegal have a high HIV prevalence; therefore preventing HIV transmission from this population to the general population is important. Condom use with regular partners is low among registered CSWs in Senegal, and a prior HIV negative test is associated with even less condom use with regular partners. Intervention efforts to increase condom use with regular sexual partners are needed.

Chronic constipation: advances in management.

Only a relatively small percentage of clinically constipated patients seek medical attention and most can be managed satisfactorily with conservative measures. This review mainly addresses those patients who have refractory or difficult-to-manage functional constipation who are referred to gastrointestinal specialists. Areas of review include insights into pathophysiology, the utility of diagnostic testing and the author's opinions concerning available pharmacologic agents, the role of behavioural therapies and the indications for surgical interventions in this heterogeneous group of patients.

Enrichment of herpes simplex virus type 2 (HSV-2) reactive mucosal T cells in the human female genital tract.

Local mucosal cellular immunity is critical in providing protection from HSV-2. To characterize and quantify HSV-2-reactive mucosal T cells, lymphocytes were isolated from endocervical cytobrush and biopsy specimens from 17 HSV-2-infected women and examined ex vivo for the expression of markers associated with maturation and tissue residency and for functional T-cell responses to HSV-2. Compared with their circulating counterparts, cervix-derived CD4+ and CD8+ T cells were predominantly effector memory T cells (CCR7-/CD45RA-) and the majority expressed CD69, a marker of tissue residency. Co-expression of CD103, another marker of tissue residency, was highest on cervix-derived CD8+ T cells. Functional HSV-2 reactive CD4+ and CD8+ T-cell responses were detected in cervical samples and a median of 17% co-expressed CD103. HSV-2-reactive CD4+ T cells co-expressed IL-2 and were significantly enriched in the cervix compared with blood. This first direct ex vivo documentation of local enrichment of HSV-2-reactive T cells in the human female genital mucosa is consistent with the presence of antigen-specific tissue-resident memory T cells. Ex vivo analysis of these T cells may uncover tissue-specific mechanisms of local control of HSV-2 to assist the development of vaccine strategies that target protective T cells to sites of HSV-2 infection.

Suppressed murine mammary tumor virus (MuMTV) expression in RIII female mice treated neonatally with goat antiserum to MuMTV.

Passive immunization of newborn inbred RIII (R3) mice with the globulin fraction of goat antiserum to murine mammary tumor virus (MuMTV) successfully suppressed MuMTV expression in the milk of some of the treated mice throughout nine successive lactations. No mammary tumors developed in the MuMTV-suppressed mice during the first 9 months, whereas all untreated R3 female breeders expressed MuMTV in the milk of the third lactation, and all developed tumors before 9 months of age (mode and median: 189 days).

[Favourable results with surgical treatment in 43 children with hypoplastic left-heart syndrome or similar disorders, 1999-2005]. / Gunstige resultaten van chirurgische behandeling van 43 kinderen met het hypoplastisch linkerhartsyndroom of een equivalente afwijking, 1999/'05.

OBJECTIVE: To describe the results of surgical treatment of hypoplastic left-heart syndrome (HLHS) and HLHS-like disorders in the Amsterdam-Leiden Centre for Congenital Heart Disease, the Netherlands. DESIGN: Retrospective, descriptive. METHOD: Data were collected on 43 neonates with HLHS or similar disorders who underwent surgical treatment between December 1999 and December 2005. HLHS was present in 37 patients and 6 had disorders similar to HLHS (unbalanced atrioventricular septal defect, truncus arteriosus with hypoplastic left ventricle, double inlet left ventricle). Surgery was performed in 3 steps: Norwood operation shortly after birth (n = 43), bidirectional cavopulmonary anastomosis a few months later (n = 30) and total cavopulmonary connection at the age of 2-3 years (n = 10). During the Norwood operation, the first 21 patients received a modified Blalock shunt (between the right brachiocephalic artery and pulmonary artery), whereas the following 22 patients received a Sano shunt (between the right ventricle and pulmonary artery). RESULTS: Of the 43 patients, 11 died: 7 within 30 days of the first operation, 2 between the first and second operation, and 2 between the second and third operation. Actuarial survival for the entire group is 74% (32/43). The mortality rate was lower with the Sano shunt (9%; 2/22) than with the modified Blalock shunt (43%; 9/21). Catheter interventions were necessary in 10 patients: 6 had balloon dilatation of the distal aortic arch and 4 had balloon dilatation/stent placement for narrowed pulmonary arteries. With a median follow-up of 22 months (range: 1-75), 2 patients had marked neurological side effects. All 32 surviving patients were in good clinical condition.

Colonic transit and anorectal manometry in chronic idiopathic constipation.

Twenty-one patients with refractory idiopathic constipation underwent studies of segmental colonic transit of radiopaque markers and anorectal manometry to determine the utility of these tests in planning therapy and in predicting subsequent clinical outcome. Colonic transit studies defined three groups: normal transit (n = 6), colonic inertia (n = 8), and distal slowing (n = 7). Normal transit was universally associated with evidence of psychosocial disturbances. During follow-ups ranging from 23.2 to 26.7 months, six of eight patients with colonic inertia failed to improve compared with only one of seven with distal slowing. Anorectal manometry was useful in excluding abnormalities of anorectal function. Segmental colonic transit of radiopaque markers is a simple and useful test in the evaluation of refractory idiopathic constipation and appears to have both prognostic and therapeutic utility in selected cases.

Clinical and epidemiologic features of infection with Mycobacterium genavense. Swiss HIV Cohort Study.

OBJECTIVES: To characterize clinical and epidemiologic features of infections with Mycobacterium genavense. DESIGN: Case series and case-control studies. Patients with M genavense were compared with two control groups: CD4 controls were matched on the basis of CD4 counts, and Mycobacterium avium-intracellulare complex controls had disseminated infection with M avium-intracellulare complex. RESULTS: Fifty-four patients with disseminated infections caused by M genavense were found, from Europe (37), North America (15), and Australia (two). All were infected with human immunodeficiency virus. The median CD4 count was 0.016 x 10(9)/L (16/mm3) (range, 0.001 to 0.082 x 10(9)/L). Eighty-seven percent had fever and weight loss, 44% had diarrhea, 43% had splenomegaly, 39% had hepatomegaly, and 72% had anemia. In Swiss university hospitals, M genavense was responsible for 12.8% of nontuberculous disseminated mycobacterial infections in patients with human immunodeficiency virus from 1990 to 1992. The median survival was 190 days after the first isolation of M genavense. Among the patients who had been treated with at least two antimycobacterial drugs for 1 month or more, median survival was 263 days (95% confidence interval, 144 to 382 days), compared with 81 days (95% confidence interval, 73 to 89 days) for those not treated (P = .0009). Survival in patients with M genavense was similar to the survival of M avium-intracellulare complex controls. However, patients with similar CD4 counts (CD4 controls) survived longer (median, 342 days; 95% confidence interval, 269 to 415 days; P < .0003). CONCLUSIONS: Infection with M genavense may be responsible for more than 10% of disseminated nontuberculous mycobacterial infections in patients with human immunodeficiency virus infection. Its clinical presentation and response to treatment are similar to those of infection with M avium-intracellulare complex.

Persistence of mucosal T-cell responses to herpes simplex virus type 2 in the female genital tract.

Relatively little is known about the human T-cell response to herpes simplex virus type 2 (HSV-2) in the female genital tract, a major site of heterosexual HSV-2 acquisition, transmission, and reactivation. In order to understand the role of local mucosal immunity in HSV-2 infection, T-cell lines were expanded from serial cervical cytobrush samples from 30 HSV-2-infected women and examined for reactivity to HSV-2. Approximately 3% of the CD3+ T cells isolated from the cervix were HSV-2 specific and of these, a median of 91.3% were CD4+, whereas a median of 3.9% were CD8+. HSV-2-specific CD4+ T cells expanded from the cervix were not only more frequent than CD8+ T cells but also exhibited greater breadth in terms of antigenic reactivity. T cells directed at the same HSV-2 protein were often detected in serial cervical cytobrush samples and in blood. Thus, broad and persistent mucosal T-cell responses to HSV-2 were detected in the female genital tract of HSV-2+ women suggesting that these cells are resident at the site of HSV-2 infection. Understanding the role of these T cells at this biologically relevant site will be central to the elucidation of adaptive immune mechanisms involved in controlling HSV-2 disease.

The sink action of cerebrospinal fluid volume flow. Effect on brain water content.

Effects of changes in serum osmolarity on volume flow of fluid into the cerebral ventricles of cats were measured by ventriculocisternal perfusion with mock cerebrospinal fluid (CSF), mock CSF containing acetazolamide, or a 30 mOsm/liter sucrose solution. Serum osmolarity was altered by intravenous infusion of a sucrose solution ranging between 10 and 650 mOsm/liter changing volume flow. For all perfusion fluids, regression lines relating volume flow to infused solution osmolarity were parallel. After infusion of a 10 mOsm/liter solution, brain water content increased. One hour after infusion, volume flow returned to normal, although serum was still hypotonic. Gray matter water content was still elevated; white matter returned to normal. The results suggest that the source of increased volume flow is the brain, and that the CSF acts as a sink, limiting excess water accumulation during water intoxication.

Kaolin-induced hydrocephalus impairs CSF secretion by the choroid plexus.

CSF volume flow and sodium (Na+)-influx rates in normal and kaolin-induced hydrocephalic cats were measured during ventricular perfusion with anisotonic sucrose solutions. When ventricular fluid osmolality was 120 mOsm, CSF volume flow ceased for both groups of cats. As ventricular fluid osmolality was increased, the CSF volume flow rate of normal cats increased to 70 microliter per minute, and in hydrocephalic cats to 40 microliter per minute. In normal cats, for ventricular fluid osmolality between 50 and 350 mOsm, Na+-influx was constant and thought to occur by diffusion; while for higher osmolalities, Na+-influx increased. In hydrocephalic cats, Na+-influx increased over the entire range of ventricular osmolality but was less than in normal cats. Acetazolamide decreased the CSF volume flow in normal cats by 40 percent, but was ineffective in hydrocephalic cats. These results suggest that CSF secretion by the choroid plexus of cats with kaolin-induced hydrocephalus is impaired.

On the movement of fluid through the brain of hydrocephalic cats.

The effects of changes in serum osmolality on the volume flow of fluid into the cerebral ventricles and on brain water content was examined in cats with kaolin-induced hydrocephalus. Slopes of the regression lines relating volume flow and serum osmolality for both normal and hydrocephalic cats are the same. The constant difference in flow rates between the two lines, 7 mul per minute, is probably due to impaired choroid plexuow rates between the two lines, 7 mul per minute, is probably due to impaired choroid plexus function of the hydrocephalic cats. The osmotic pressure gradient that causes the flow of fluid is therefore probably between blood and brain. Under these conditions changes in brain water content of hydrocephalic cats were smaller than in normals and can be related to the edema present in this disorder. Despite the inflammatory response to kaolin, the blood-brain barrier remains intact. From the calculated filtration coefficient, it can be inferred that the flow of water from serum through brain and into cerebrospinal fluid is limited by the resistance of fluid flow through the brain.