Picornaviruses in cerebrospinal fluid of children with meningitis in Luanda, Angola

Human enteroviruses are the most common cause of viral meningitis. Viral-bacterial interaction may affect the clinical course and outcome of bacterial meningitis. In Africa, viruses might be responsible for 14-25% of all meningitis cases. However, only few studies from Africa have reported detection of viruses in the cerebrospinal fluid (CSF) or mixed viral-bacterial infections of the central nervous system (CNS). The aim of the present study was to investigate the presence of picornaviruses in the CSF of children suffering from meningitis in Luanda, Angola. The study included 142 consecutive children enrolled in a prospective study of bacterial meningitis in Luanda between 2005 and 2006, from whom a CSF sample was available. CSF samples were obtained at hospital admission, stored in a deep-freeze, and transported to Finland for testing by real-time PCR for picornaviruses. Enteroviruses were detected in 4 (3%) of 142 children with presumed bacterial meningitis. A 5-month-old girl with rhinovirus and Haemophilus influenzae meningitis recovered uneventfully. An 8-year-old girl with human enterovirus and pneumococcal meningitis developed no sequelae. A 2-month-old girl with human enterovirus and malaria recovered quickly. A 7-month-old girl with human enterovirus was treated for presumed tuberculous meningitis and survived with severe sequelae. Mixed infections of the CNS with picornaviruses and bacteria are rare. Detection of an enterovirus does not affect the clinical picture and outcome of bacterial meningitis.     

Development of a new quantitative real-time HHV-6-PCR and monitoring of HHV-6 DNAaemia after liver transplantation

A quantitative HHV-6 PCR (qPCR) assay was developed and compared to an "in-house" qualitative PCR and to the commercial quantitative Argene CMV, HHV6, 7, 8 R-gene? test. Clinical specimens consisting of 127 whole blood and 57 cerebrospinal fluid (CSF) specimens were tested using the two qPCRs and the qualitative PCR in parallel. When the qualitative PCR was used as a "gold standard," the sensitivities of the qPCRs for the blood samples were 86% for the "in-house" qPCR and 76% for the Argene's test and the specificities were 96% and 92%, respectively. With CSF specimens the sensitivities were 92% and 80% and the specificities 98% and 82%, respectively. Furthermore, the two qPCRs were compared in the monitoring of liver transplant patients and retrospectively correlated to HHV-6 antigenaemia. In total, 223 blood specimens were tested. HHV-6 antigenaemia had been found in 21/36 (58%) patients and HHV-6 DNAaemia was demonstrated in 18/36 (50%). Viral loads by the "in-house" test varied from 280 to 19700 copies/ml (median 1200) and by Argene's test from 120 to 24070 copies/ml (median 458). The correlation of viral loads between the two qPCRs was good (R=0.94, p<0.01). The new in-house test was found to be reliable for the detection and quantitation of HHV-6 DNA in clinical specimens.     

Adjuvant glycerol and/or dexamethasone to improve the outcomes of childhood bacterial meningitis: a prospective, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Despite favorable meta-analyses, no study involving third-generation cephalosporins for the treatment of childhood bacterial meningitis has documented a benefit of adjuvant dexamethasone therapy if the outcomes are examined individually. METHODS: We conducted a prospective, randomized, double-blind trial comparing adjuvant dexamethasone or glycerol with placebo in children aged from 2 months through 16 years in Latin America. Ceftriaxone was administered to all children; children were randomized to also receive dexamethasone intravenously, glycerol orally, both agents, or neither agent. Primary end points were death, severe neurological sequelae, or deafness, with the first 2 end points forming a composite end point. A subgroup analysis for Haemophilus influenzae type b meningitis was undertaken. Intention-to-treat analysis was performed using binary logistic regression models. RESULTS: H. influenzae type b, pneumococci, and meningococci were the main agents found among 654 patients; dexamethasone was given to 166, dexamethasone and glycerol were given to 159, glycerol was given to 166, and placebo was given to 163. No adjuvant therapy significantly affected death or deafness. In contrast, glycerol and dexamethasone plus glycerol reduced severe neurological sequelae, compared with placebo; the odds ratios were 0.31 (95% confidence interval [95% CI], 0.13-0.76; P=.010) and 0.39 (95% CI, 0.17-0.93; P=.033), respectively. For neurological sequelae and death, the odds ratios were 0.44 (95% CI, 0.25-0.76; P=.003) and 0.55 (95% CI, 0.32-0.93; P=.027), respectively. Dexamethasone therapy prevented deafness in patients with H. influenzae type b meningitis only if patients were divided grossly into dexamethasone recipients and nonrecipients and if timing between dexamethasone and ceftriaxone administration was not taken into account (odds ratio, 0.27; 95% CI, 0.09-0.77; P=.014). CONCLUSION: Oral glycerol therapy prevents severe neurological sequelae in patients with childhood meningitis. Safety, availability, low cost, and oral administration also add to its usefulness, especially in resource-limited settings.     

Induction of cyclo-oxygenase-2 by acute liver allograft rejection and cytomegalovirus infection in the rat

Cytomegalovirus (CMV) infection has been shown to increase inflammation in rat liver allografts. In-vitro CMV has been shown to transactivate cyclo-oxygenase-2 (COX-2), while COX-2 plays a role in the CMV replication cycle. Our aim was to investigate the expression of COX-2 in liver allograft rejection and concomitant CMV infection. Expression of COX-2 was studied immunohistologically in rat liver allografts with or without rat CMV infection, in isografts, and in normal rat liver. There were small amounts of COX-2-positive mononuclear inflammatory cells in the normal liver and isografts. Acute rejection increased the amount of COX-2-expressing cells in the portal areas only, whereas concomitant CMV infection did this also in the sinusoid area. COX-2 may play a role in CMV infection in vivo as well. The possible role of COX-2 in the association between CMV infection and allograft rejection warrants further study.     

Platelet GPIbα, GPIV and vWF polymorphisms and fatal pre-hospital MI among middle-aged men

Background  The binding of platelet glycoprotein (GP) Ib-IX-V receptor complex to subendothelial collagen via von Willebrand factor is the initial step of the formation of platelet thrombi following atherosclerotic plaque rupture. Platelet GPIV binds to collagen and/or thrombospondin and further activates platelets. Genetic variation in these proteins could associate with platelet aggregability and the risk of myocardial infarction (MI). Methods and results  We studied the associations of polymorphisms of GPIbα, GPIV and von Willebrand factor with the extent of coronary atherosclerosis, coronary narrowing, and fatal MI in an autopsy series of 300 middle-aged, Caucasian Finnish men who had suffered sudden out-of-hospital death. 31% of men with MI under the age of 50 carried the GPIbα HPA-2 ThrThr/Kozak TT haplotype as opposed to 62% of control men (OR 0.27, 95% CI 0.08–0.93, P = 0.03). In addition, 7% of men with MI under the age of 50 carried the GPIV AA genotype versus 29% of control men (OR 0.16, 95% CI 0.03–0.98, P < 0.05). These associations were not due to any effects of these gene variants on the coronary atherosclerotic changes. The G/A polymorphism of the von Willebrand factor gene failed to show any association with MI or coronary atherosclerosis in this series of men. Conclusions  The combined ThrThr/TT haplotype of GPIbα as well as the AA genotype of GPIV seem to decrease the risk of fatal MI among men during early middle-age.     

Human herpesvirus 6 infection of the gastroduodenal mucosa.

BACKGROUND: Human herpesvirus 6 (HHV-6) infections are usually asymptomatic reactivations in adult liver transplant recipients, but they may also cause fever or graft dysfunction. HHV-6 infection can also present symptoms of gastroenteritis. In this study, we investigated the presence of HHV-6 in the gastroduodenal mucosa of liver transplant recipients and in immunocompetent patients undergoing gastroscopic examination because of dyspeptic symptoms. METHODS: HHV-6 and cytomegalovirus (CMV) examinations were performed on gastroduodenal biopsy specimens obtained during upper gastrointestinal endoscopic examinations from 90 liver transplant recipients and from 31 immunocompetent patients with upper gastrointestinal symptoms. In the gastroduodenal mucosa, HHV-6 and CMV was demonstrated by immunohistochemistry in frozen sections using monoclonal antibodies against HHV-6- and CMV-specific antigens. RESULTS: HHV-6-positive cells were found in biopsy specimens from 21 (23%) of the liver transplant recipients and 6 (19%) of the immunocompetent patients, CMV-positive cells were found in specimens from 55 (61%) of the transplant recipients and 7 (23%) of the immunocompetent patients, and 12 transplant recipients were found to have both HHV-6 and CMV infection. Fifteen transplant recipients with positive HHV-6 findings in the gastroduodenal mucosa also had HHV-6 antigenemia, whereas 30 patients with HHV-6 antigenemia did not have gastroduodenal involvement. Endoscopic findings in these patients included biliary complications in 10 patients and gastritis in 2 patients. Histopathological findings were nonspecific and included very mild inflammation. A total of 30 (94%) of the transplant recipients with biliary complications also had HHV-6 or CMV detected in the duodenal mucosa. CONCLUSIONS: HHV-6-positive cells and CMV-positive cells were frequently found in the gastroduodenal mucosa of liver transplant recipients and of immunocompetent patients undergoing gastroscopic examination because of dyspeptic symptoms.     

The persistence of behavioural symptoms and symptom groups in children: A study of the stability of parental reported symptoms

The investigation assessed psychiatric symptoms in children at two time points and the persistence of symptom groups over an interval of 4 years. We studied 1128 children by using parental questionnaires (Rutter Scale A2) in both studies (mean age of the children was 8.5 years in Study 1 and 12.5 years in Study 2). There was a tendency for the frequency of symptoms to decrease over the 4-year period. Most of the symptoms reported in Study 1 were also found in Study 2. Sex differences were similar in both studies. Four factors were constructed out of the items on Rutter Scale A2, reflecting externalizing, hyperactive, internalizing, and poorly socialized behaviours. Externalizing, hyperactive, and internalizing behaviours were moderately persistent in the sample studied. The stability of externalizing and internalizing behaviour was high among deviant children. Hyperactivity was not persistent among deviant boys but highly persistent among deviant girls. Poorly socialized behaviour was not persistent in the sample studied, but girls scoring high in this factor in Study 1 scored high on the externalizing factor in Study 2.     

Cytomegalovirus increases collagen synthesis in chronic rejection in the rat.

BACKGROUND: We have demonstrated previously that cytomegalovirus (CMV) infection enhances chronic renal allograft rejection in a rat model. Interstitial fibrosis, a characteristic finding for chronic rejection, was also more prominent in CMV-infected grafts. The effect of CMV on the development of fibrosis in this model was investigated here at the molecular level. The collagen/DNA ratio, gene expression of type I and III collagen mRNAs and the presence of myofibroblasts were examined. METHODS: Transplantations were performed under triple drug immunosuppression in a rat strain combination of DA(RT1(a)) and BN(RT1(n)). One group of animals was infected with rat CMV and the other was left uninfected. The grafts were harvested at different time points post-transplantation. Graft histology was evaluated according to the Banff criteria and quantified by the chronic allograft damage index (CADI). Total collagen was measured and DNA and RNA were extracted from the grafts. Type I and III collagen mRNAs were determined by slot blot and in situ hybridizations. Myofibroblasts were demonstrated by immunohistochemistry. RESULTS: The time-related increase of the collagen/DNA ratio in the CMV-infected grafts was higher than in the uninfected animals, correlating with the development of fibrosis at the histology. The expression of type I and III collagen mRNAs peaked shortly after transplantation, together with the presence of myofibroblasts, with significantly higher peaks in the CMV-infected grafts compared with the non-infected ones. CONCLUSIONS: CMV increases the expression of both type I and III collagens and the accumulation of myofibroblasts, and enhances total collagen synthesis in the development of interstitial fibrosis in chronic renal allograft rejection.     

Who benefits from clinical supervision and how? The association between clinical supervision and the work-related well-being of female hospital nurses

Aim and objectives. The aims of this study were (1) to identify which nurses benefitted most from clinical supervision and (2) to explore whether they were healthier and more satisfied with their work than their peers who did not attend clinical supervision. Background. To maintain quality nursing, there is currently a social call to improve the well-being of nurses at work. Restoring nurses' well-being is one of the main purposes of clinical supervision. However, research evidence on the effects of clinical supervision is scarce. Design. Survey. Methods. Questionnaires were distributed to female hospital nurses (n?=?304), about a half of whom (48·7%) had attended clinical supervision. Perceptions of work and health among the nurses who gave the best evaluations of clinical supervision (n?=?74) were compared with those of their peers who gave the worst evaluations (n?=?74) or who had not attended clinical supervision (n?=?156). Results. The nurses who received efficient clinical supervision reported more job and personal resources and were more motivated and committed to the organisation than their peers. However, professional inefficacy was the only burnout dimension on which they scored lower than other nurses. Conclusions. Clinical supervision can be conceptualised as an additional job resource associated with other job and personal resources, which mutually reinforce each other, promoting well-being at work. Efficient clinical supervision is probably both an antecedent as well as a consequence of well-being at work. Relevance to clinical practice. The results of this study advocate management planning to provide formal support for health care providers. Medical-surgical nurses are interested in clinical supervision. Reflecting on practice in clinical supervision generates new ideas about how to improve the quality of care and the psychosocial work environment. However, clinical supervision may be viewed as a preventive method rather than a treatment for burnout.