Calligraphy and causation : two obstetric management cases

Child born with gross hydrocephalus - cerebral palsy - questions surrounding obstetrician's notes - ultrasound not ordered - illegible handwriting - importance of legible, accurate and detailed medical records - causation - child born with congenital varicella syndrome (CVS) - chicken pox - forseeability of risk.

Sharing of clinical data in a maternity setting: How do paper hand-held records and electronic health records compare for completeness?

Background Historically, the paper hand-held record (PHR) has been used for sharing information between hospital clinicians, general practitioners and pregnant women in a maternity shared-care environment. Recently in alignment with a National e-health agenda, an electronic health record (EHR) was introduced at an Australian tertiary maternity service to replace the PHR for collection and transfer of data. The aim of this study was to examine and compare the completeness of clinical data collected in a PHR and an EHR. Methods We undertook a comparative cohort design study to determine differences in completeness between data collected from maternity records in two phases. Phase 1 data were collected from the PHR and Phase 2 data from the EHR. Records were compared for completeness of best practice variables collected The primary outcome was the presence of best practice variables and the secondary outcomes were the differences in individual variables between the records. Results Ninety-four percent of paper medical charts were available in Phase 1 and 100% of records from an obstetric database in Phase 2. No PHR or EHR had a complete dataset of best practice variables. The variables with significant improvement in completeness of data documented in the EHR, compared with the PHR, were urine culture, glucose tolerance test, nuchal screening, morphology scans, folic acid advice, tobacco smoking, illicit drug assessment and domestic violence assessment (p = 0.001). Additionally the documentation of immunisations (pertussis, hepatitis B, varicella, fluvax) were markedly improved in the EHR (p = 0.001). The variables of blood pressure, proteinuria, blood group, antibody, rubella and syphilis status, showed no significant differences in completeness of recording. Conclusion This is the first paper to report on the comparison of clinical data collected on a PHR and EHR in a maternity shared-care setting. The use of an EHR demonstrated significant improvements to the collection of best practice variables. Additionally, the data in an EHR were more available to relevant clinical staff with the appropriate log-in and more easily retrieved than from the PHR. This study contributes to an under-researched area of determining data quality collected in patient records.

Microarrays in the Diagnosis of Human Herpesvirus infections

Currently, there are nine known human herpesviruses and these viruses appear to have been a very common companion of humans throughout the millenia. Of human herpesviruses, herpes simplex viruses 1 and 2 (HSV-1, HSV-2), causative agents of herpes labialis and genital herpes, and varicella-zoster virus (VZV), causative agent of chicken pox, are also common causes of central nervous system (CNS) infections. In addition, human cytomegalovirus (CMV), Epstein-Barr virus (EBV) and human herpesviruses 6A, 6B, and 7 (HHV-6A, HHV-6B, HHV-7), all members of the herpesvirus family, can also be associated with encephalitis and meningitis. Accurate diagnostics and fast treatment are essential for patient recovery in CNS infections and therefore sensitive and effective diagnostic methods are needed. The aim of this thesis was to develop new potential detection methods for diagnosing of human herpesvirus infections, especially in immunocompetent patients, using the microarray technique. Therefore, methods based on microarrays were developed for simultaneous detection of HSV-1, HSV-2, VZV, CMV, EBV, HHV-6A, HHV-6B, and HHV-7 nucleic acids, and for HSV-1, HSV-2, VZV, and CMV antibodies from various clinical samples. The microarray methods developed showed potential for efficiently and accurately detecting human herpesvirus DNAs, especially in CNS infections, and for simultaneous detection of DNAs or antibodies for multiple different human herpesviruses from clinical samples. In fact, the microarray method revealed several previously unrecognized co-infections. The microarray methods developed were sensitive and provided rapid detection of human herpesvirus DNA, and therefore the method could be applied to routine diagnostics. The microarrays might also be considered as an economical tool for diagnosing human herpesvirus infections.

Peripheral facial palsy : Grading, Etiology, and Melkersson-Rosenthal Syndrome

The objective of this study was to assess the utility of two subjective facial grading systems, to evaluate the etiologic role of human herpesviruses in peripheral facial palsy (FP), and to explore characteristics of Melkersson-Rosenthal syndrome (MRS). Intrarater repeatability and interrater agreement were assessed for Sunnybrook (SFGS) and House-Brackmann facial grading systems (H-B FGS). Eight video-recorded FP patients were graded in two sittings by 26 doctors. Repeatability for SFGS was from good to excellent and agreement between doctors from moderate to excellent by intraclass correlation coefficient and coefficient of repeatability. For H-B FGS, repeatability was from fair to good and agreement from poor to fair by agreement percentage and kappa coefficients. Because SFGS was at least as good in repeatability as H-B FGS and showed more reliable results in agreement between doctors, we encourage the use of SFGS over H-B FGS. Etiologic role of human herpesviruses in peripheral FP was studied by searching DNA of herpes simplex virus (HSV) -1 and -2, varicella-zoster virus (VZV), human herpesvirus (HHV) -6A, -6B, and -7, Epstein-Barr virus (EBV), and cytomegalovirus (CMV) by PCR/microarray methods in cerebrospinal fluid (CSF) of 33 peripheral FP patients and 36 controls. Three patients and five controls had HHV-6 or -7 DNA in CSF. No DNA of HSV-1 or -2, VZV, EBV, or CMV was found. Detecting HHV-7 and dual HHV-6A and -6B DNA in CSF of FP patients is intriguing, but does not allow etiologic conclusions as such. These DNA findings in association with FP and the other diseases that they accompanied require further exploration. MRS is classically defined as a triad of recurrent labial or oro-facial edema, recurrent peripheral FP, and plicated tongue. All three signs are present in the minority of patients. Edema-dominated forms are more common in the literature, while MRS with FP has received little attention. The etiology and true incidence of MRS are unknown. Characteristics of MRS were evaluated at the Departments of Otorhinolaryngology and Dermatology focusing on patients with FP. There were 35 MRS patients, 20 with FP and they were mailed a questionnaire (17 answered) and were clinically examined (14 patients). At the Department of Otorhinolaryngology, every MRS patient had FP and half had the triad form of MRS. Two patients, whose tissue biopsies were taken during an acute edema episode, revealed nonnecrotizing granulomatous findings typical for MRS, the other without persisting edema and with symptoms for less than a year. A peripheral blood DNA was searched for gene mutations leading to UNC-93B protein deficiency predisposing to HSV-1 infections; no gene mutations were found. Edema in most MRS FP patients did not dominate the clinical picture, and no progression of the disease was observed, contrary to existing knowledge. At the Department of Dermatology, two patients had triad MRS and 15 had monosymptomatic granulomatous cheilitis with frequent or persistent edema and typical MRS tissue histology. The clinical picture of MRS varied according to the department where the patient was treated. More studies from otorhinolaryngology departments and on patients with FP would clarify the actual incidence and clinical picture of the syndrome.

Maladies infectieuses [Infectious diseases]

In 2008, several publications have highlighted the role of climate change and globalization on the epidemiology of infectious diseases. Studies have shown the extension towards Europe of diseases such as Crimea-Congo fever (Kosovo, Turkey and Bulgaria), leismaniosis (Cyprus) and chikungunya virus infection (Italy). The article also contains comments on Plasmodium knowlesi, a newly identified cause of severe malaria in humans, as well as an update on human transmission of the H5NI avian influenza virus. It also mentions new data on Bell's palsy as well as two vaccines (varicella-zoster and pneumococcus), and provides a list of recent guidelines for the treatment of common infectious diseases.

Étude de l’immunité antivaricelleuse chez l’enfant transplanté au moyen de moelle osseuse ou de sang de cordon ombilical

L’infection primaire au VZV et la réactivation du VZV latent sont fréquemment observées à la suite d’une GMO ou d’une GSCO, ce qui cause de sérieuses complications chez le patient. Pour prévenir ces infections, une prophylaxie antivirale est administrée systématiquement chez tous les greffés de MO ou de SCO, alors qu’il n’existe aucun consensus sur la durée optimale d’une telle prophylaxie. Pour résoudre ce problème, notre objectif est de développer et valider une méthode ELISpot-VZV-IFN- qui permettra de suivre la reconstitution de l’immunité à médiation cellulaire anti-VZV chez les receveurs de GMO ou de GSCO et ainsi déterminer le moment opportun pour réduire ou interrompe la prophylaxie chez les receveurs de greffes de CSH. Dans un premier temps, des valeurs-seuil de la réponse à médiation cellulaire anti-VZV chez la population pédiatrique saine ont dû être générées. À la lumière de nos résultats, un enfant avec un résultat ELISpot-VZV-IFN- > 190.0 SFU/106 PBMC devrait être protégé contre une possible infection à VZV. Pour valider cette étude, une étude prospective de la reconstitution immunitaire anti-VZV a été effectuée chez 9 enfants greffés de MO ou de SCO. Nos résultats préliminaires ont montré qu’il n’y avait eu aucune reconstitution significative de l’immunité à médiation cellulaire anti-VZV dans les 18 premiers mois post-transplantation chez 8 de ces 9 enfants. Les résultats de ces expériences vont fournir d’importantes informations quant à la reconstitution de l’immunité anti-VZV à la suite d’une GMO ou d’une GSCO et pourraient permettre l’amélioration des soins apportés aux receveurs de GMO ou de GSCO.

Approximation de la distribution a posteriori d'un modèle Gamma-Poisson hiérarchique à effets mixtes

La méthode que nous présentons pour modéliser des données dites de "comptage" ou données de Poisson est basée sur la procédure nommée Modélisation multi-niveau et interactive de la régression de Poisson (PRIMM) développée par Christiansen et Morris (1997). Dans la méthode PRIMM, la régression de Poisson ne comprend que des effets fixes tandis que notre modèle intègre en plus des effets aléatoires. De même que Christiansen et Morris (1997), le modèle étudié consiste à faire de l'inférence basée sur des approximations analytiques des distributions a posteriori des paramètres, évitant ainsi d'utiliser des méthodes computationnelles comme les méthodes de Monte Carlo par chaînes de Markov (MCMC). Les approximations sont basées sur la méthode de Laplace et la théorie asymptotique liée à l'approximation normale pour les lois a posteriori. L'estimation des paramètres de la régression de Poisson est faite par la maximisation de leur densité a posteriori via l'algorithme de Newton-Raphson. Cette étude détermine également les deux premiers moments a posteriori des paramètres de la loi de Poisson dont la distribution a posteriori de chacun d'eux est approximativement une loi gamma. Des applications sur deux exemples de données ont permis de vérifier que ce modèle peut être considéré dans une certaine mesure comme une généralisation de la méthode PRIMM. En effet, le modèle s'applique aussi bien aux données de Poisson non stratifiées qu'aux données stratifiées; et dans ce dernier cas, il comporte non seulement des effets fixes mais aussi des effets aléatoires liés aux strates. Enfin, le modèle est appliqué aux données relatives à plusieurs types d'effets indésirables observés chez les participants d'un essai clinique impliquant un vaccin quadrivalent contre la rougeole, les oreillons, la rub\'eole et la varicelle. La régression de Poisson comprend l'effet fixe correspondant à la variable traitement/contrôle, ainsi que des effets aléatoires liés aux systèmes biologiques du corps humain auxquels sont attribués les effets indésirables considérés.

Effect of viral load on the outcome of herpes zoster

Varicella-zoster virus (VZV) is a member of the Herpesviridae family, primary infection with which causes varicella, more commonly known as chicken pox. Characteristic of members of the alphaherpesvirus subfamily, VZV is neurotropic and establishes latency in sensory neurons. Reactivation of VZV causes herpes zoster, also known as shingles. The most frequent complication following zoster is chronic and often debilitating pain called postherpetic neuralgia (PHN), which can last for months after the disappearance of a rash. During episodes of acute zoster, VZV viremia occurs in some, but not all, patients; however, the effect of the viral load on the disease outcome is not known. Here we describe the development of a highly specific, sensitive, and reproducible real-time PCR assay to investigate the factors that may contribute to the presence and levels of baseline viremia in patients with zoster and to determine the relationship between viremia and the development and persistence of PHN. VZV DNA was detected in the peripheral blood mononuclear cells (PBMCs) of 78% of patients with acute zoster and in 9% of healthy asymptomatic blood donors. The presence of VZV in the PBMCs of patients with acute zoster was independently associated with age and being on antivirals but not with gender, immune status, extent of rash, the age of the rash at the time of blood sampling, having a history of prodromal pain, or the extent of acute pain. Prodromal pain was significantly associated with higher baseline viral loads. Viral load levels were not associated with the development or persistence of PHN at 6, 12, or 26 weeks.

Humoral immunity following chickenpox is influenced by geography and ethnicity

Objectives To investigate the contribution of ethnicity and geographical location to varicella-zoster virus (VZV) serostatus and antibody concentrations. Methods The presence and concentrations of antibodies to VZV were measured in 639 Bangladeshi women born in Bangladesh (BBB), 94 Bangladeshi women born in the UK (BUK) and 262 White women born in the UK (WUK). The results were anaylsed in relation to demographic and social data. Results BBB women were significantly less likely to be VZV seropositive at all ages than both BUK and WUK women. However, the odds of a Bangladeshi-born woman being seropositive increased by 1.04 for each year under the age of 15 spent in the UK. In contrast, antibody concentrations were significantly lower in ethnic Bangladeshi women, irrespective of country of birth. White, but not Bangladeshi women, showed evidence of antibody boosting over time despite the latter having more exposure to children. Conclusion Geographical location during childhood is the major influence on age of primary infection with VZV while the level of antibody is related to ethnicity. Since the risk of re-infection with VZV following both natural infection and vaccination is increased as antibody concentrations fall, these results have implications for VZV vaccination programmes particularly in non-White populations.

Unilateral Facial Paralysis Caused by Ramsay Hunt Syndrome

The Ramsay Hunt syndrome is a rare disease caused by an infection of the geniculate ganglion by the varicella-zoster virus. The main clinical features of the syndrome are as follows: Bell palsy unilateral or bilateral, vesicular eruptions on the ears, ear pain, dizziness, preauricular swelling, tingling, tearing, loss of taste sensation, and nystagmus. We describe a 23-year-old white woman, who presented with facial paralysis on the left side of the face, pain, fever, ear pain, and swelling in the neck and auricular region on the left side. She received appropriate treatment with acyclovir, vitamin B complex, and CMP nucleus. After 30 days after presentation, the patient did not show any signs or symptoms of the syndrome. At follow-up at 1 year, she showed no relapse of the syndrome.

Immunohistochemical approach to the pathogenesis of clinical cases of bovine Herpesvirus type 5 infections

Meningoencephalitis by Herpesvirus type 5 (BoHV-5) in cattle has some features that are similar to those of herpetic encephalitis in humans and other animal species. Human Herpesvirus 3 (commonly known as Varicella-zoster virus 1), herpes simplex viruses (HSV), and equid Herpesvirus 1 (EHV-1) induce an intense inflammatory, vascular and cellular response. In spite of the many reports describing the histological lesions associated with natural and experimental infections, the immunopathological mechanisms for the development of neurological disorder have not been established. A total of twenty calf brains were selected from the Veterinary School, University of São Paulo State, Araçatuba, Brazil, after confirmation of BoHV-5 infection by virus isolation as well as by a molecular approach. The first part of the study characterized the microscopic lesions associated with the brain areas in the central nervous system (CNS) that tested positive in a viral US9 gene hybridization assay. The frontal cortex (Fc), parietal cortex (Pc), thalamus (T) and mesencephalon (M) were studied. Secondly, distinct pathogenesis mechanisms that take place in acute cases were investigated by an immunohistochemistry assay. This study found the frontal cortex to be the main region where intense oxidative stress phenomena (AOP-1) and synaptic protein expression (SNAP-25) were closely related to inflammatory cuffs, satellitosis and gliosis, which represent the most frequently observed neurological lesions. Moreover, MMP-9 expression was shown to be localized in the leptomeninges, in the parenchyma and around mononuclear infiltrates (p < 0.0001). These data open a new perspective in understanding the role of the AOP-1, MMP-9 and SNAP-25 proteins in mediating BoHV-5 pathogenesis and the strategies of host-virus interaction in order to invade the CNS.

Opportunistic and Other Infections in HIV-Infected Children in Latin America Compared to a Similar Cohort in the United States

Opportunistic and other infections have declined since the introduction of highly active antiretroviral therapy (HAART) in developed countries but few studies have addressed the impact of HAART in HIV-infected children from developing countries. This study examines the prevalence and incidence of opportunistic and other infections in Latin America during the HAART era. Vertically HIV-infected children enrolled in a cohort study between 2002 and 2007 were followed for the occurrence of 29 targeted infections. Cross-sectional and longitudinal analyses were performed to calculate the prevalence of infections before enrollment and the incidence rates of opportunistic and other infections after enrollment. Comparisons were made with data from a U. S. cohort (PACTG 219C). Of the 731 vertically HIV-infected children 568 (78%) had at least one opportunistic or other infection prior to enrollment. The most prevalent infections were bacterial pneumonia, oral candidiasis, varicella, tuberculosis, herpes zoster, and Pneumocystis jiroveci pneumonia. After enrollment, the overall incidence was 23.5 per 100 person-years; the most common infections (per 100 person-years) were bacterial pneumonia (7.8), varicella (3.0), dermatophyte infections (2.9), herpes simplex (2.5), and herpes zoster (1.8). All of these incidence rates were higher than those reported in PACTG 219C. The types and relative distribution of infections among HIV-infected children in Latin America in this study are similar to those seen in the United States but the incidence rates are higher. Further research is necessary to determine the reasons for these higher rates.

Meningoencefalite concomitante a herpes zoster oftálmico em escolar previamente hígido

INTRODUÇÃO O vírus Varicella-Zoster é o agente da varicela, doença auto-limitada comum da faixa etária pediátrica. Cerca de 20% dos casos evoluem com herpes zoster em algum momento da vida, devido a reativação do vírus dos gânglios nervosos ou reexposição. O envolvimento do ramo oftálmico do nervo trigêmio, defido como zoster oftálmico, tem como complicação mais descrita a nevralgia pós-herpética, podendo evoluir com outras alterações locais agudas e tardias. Meningoencefalites concomitante a herpes zoster são pouco descritas na literatura. DESCRIÇÃO DO CASO Paciente de 9 anos, com antecedente de varicela com 1 ano de idade, com queixa de vômitos e cefaléia há dois dias, associada a queda do estado gerale hiporexia. Referiu aparecimento de lesões vesico-bolhosas dolorosas em região periorbitária esquerda há 1 dia e evoluiu com agitação psicomotora e confusão mental. No exame físico de entrada apresentava-se sonolento, com lesões vesico-bolhosas em dermátomo do ramo oftálmico do nervo trigêmio, sem sinais de irritação meníngea ou déficits motores, sem alterações visuais ou oculares. Realizada tomografia de crânio e eletroencefalograma sem alterações. Coletado líquor que revelou líquido límpido e incolor, com aumento de celularidade às custas de linfócitos, glicorraquia normal, bacterioscopia negativa e culturas negativas. Feita hipótese diagnóstica inicial de herpes zoster oftálmico complicado com meningoencefalite e introduzido aciclovir. Paciente evoluiu bem, com melhora do estado geral, remissão dos sintomas neurológicos e melhora das lesões de pele. Evidenciado PCR positivo para o vírus varicela-zoster (VVZ) no líquor. DISCUSSÃO Encontramos poucas descrições na literatura de herpes zoster oftálmico associado à alterações neurológicas. A presença da PCR positiva no liquor foi fundamental para o diagnóstico. CONCLUSÃO O VVZ pode reativar na forma de herper zoster oftálmico e acometer o sistema nervoso central. Apesar de evento raro em crianças, especialmente nas imunocompetentes, a presença da PCR positiva liquor confirmou a meningoencefalite.

Mechanismus der Apoptose, Gentoxizität und DNA-Reparatur in Herpesvirus-Thymidinkinase-exprimierenden Säugerzellen nach Behandlung mit Antiherpes-Virustatika vom Typ der Nukleosidanaloga

Um Cytotoxizität und Gentoxizität nukleosidischer Antiherpes-Virustatika zu untersuchen, wurden stabile CHO-Klone etabliert, die Thymidinkinase (TK) des Herpes simplex-Virus Typ 1 (HSV-TK) oder des Varicella zoster-Virus (VZV-TK) exprimieren. In HSV-TK-exprimierenden Zellen wurde das Purinanalogon Ganciclovir (GCV) effizient in die genomische DNA eingebaut, worauf in den nächsten Replikationsrunden DNA-Strangbrüche und Aberrationen entstehen und Apoptose ausgelöst wird. GCV-induzierte Apoptose wird hauptsächlich über den mitochondrialen Weg vermittelt, wobei das anti-apoptotische Protein Bcl-2 im Mittelpunkt steht. Nach GCV-Behandlung konnte eine Caspase-9-vermittelte post-translationale Spaltung von Bcl-2 nachgewiesen werden. Das 23 kDa-großes Bcl-2-Fragment wirkt im Gegensatz zum intakten Bcl-2-Protein pro-apoptotisch und verstärkt die Cytochrom C-Freisetzung und damit die Aktivierung der Caspase-9, die Bcl-2 spaltet, was zu einem positiven 'Amplifikationsloop' des mitochondrialen apoptotischen Weges führt. In weiteren Experimenten wurde gezeigt, daß in die DNA inkorporiertes GCV durch Basenexzisionsreparatur repariert wird, wobei die DNA-Polymerase ß eine entscheidende Rolle spielt. Diese Reparatur führte zu einer signifikanten Reduktion der Apoptose und Klastogenität und damit zur Resistenzsteigerung gegenüber GCV. In VZV-TK-exprimierenden Zellen wurde gezeigt, daß Brivudin (BVDU), gleichermaßen Apoptose und Nekrose induzierte. Für die BVDU-induzierte Cytotoxizität konnte die Hemmung der Thymidylatsynthetase als Ursache identifiziert werden. Im Gegensatz zur GCV-induzierten Apoptose war für die BVDU-induzierte Apoptose der Rezeptor (Fas/CD95/APO-1)-vermittelte Weg von vorrangiger Bedeutung.

Forme atipiche di malattia mani-piedi-bocca: La nostra esperienza

Introduzione: La malattia mani-piedi-bocca è una patologia infettiva tipica della prima infanzia causata dagli enterovirus, in particolare i sierotipi Coxsackievirus A16 ed Enterovirus 71. A partire dal 2008, ne è stata descritta un’epidemia da Coxsackievirus A6, in genere accompagnata da febbre elevata e che si distingue per lo sviluppo di piccole vescicole che progrediscono a lesioni vescicolo-bollose e a bolle vere e proprie. Inoltre, nei pazienti affetti da dermatite atopica, le lesioni tendono a localizzarsi sulle aree eczematose. Abbiamo quindi svolto uno studio osservazionale prospettico per descrivere le caratteristiche cliniche delle forme atipiche di malattia mani-piedi-bocca. Metodi: Sono stati arruolati i pazienti affetti da una forma atipica di malattia mani-piedi-bocca giunti consecutivamente presso l’Ambulatorio di Dermatologia Pediatrica del Policlinico S.Orsola-Malpighi di Bologna tra gennaio 2012 e febbraio 2014. Abbiamo valutato distribuzione, tipologia ed estensione delle lesioni. In un gruppo di pazienti è stata inoltre eseguita l’identificazione virale sul fluido vescicolare. Risultati: Abbiamo arruolato 47 pazienti (68% maschi) con un’età mediana di 22 mesi. Sono stati individuati 3 aspetti clinici principali: 1) forma acrale (distribuzione delle lesioni prevalentemente acrale), nel 62% dei soggetti; 2) eczema coxsackium (lesioni localizzate su aree eczematose), nel 23% dei soggetti; 3) forma diffusa (estensione delle lesioni al tronco), nel 15% dei soggetti. Inoltre, nell’80% circa dei pazienti si riscontravano macule purpuriche acrali, circa la metà dei pazienti aveva lesioni con aspetto purpurico e il 72% un interessamento dei glutei. In 9 su 11 soggetti genotipizzati è stato isolato il Coxsackievirus A6. Conclusioni: Questo studio ha permesso di descrivere tre fenotipi di malattia mani-piedi-bocca atipica, che deve essere correttamente identificata al fine di non porre diagnosi errate quali varicella, eczema herpeticum, vasculiti, impetigine, e di potere così procedere ad una gestione appropriata della patologia.