The long-term course of factor VIII inhibitors in patients with congenital haemophilia A without immune tolerance induction

The development of alloantibodies that inhibit or neutralise the function of factor VIII is considered the most serious complication of the treatment of congenital haemophilia A. In order to describe their course without immune tolerance induction (ITI), we documented data on all performed inhibitor tests with dates as well as on clotting factor infusions of all consecutive patients who were treated in our centre between 1993 and 2006. Patients were tested every 7.1 months (95% confidence interval [CI], 6.6-7.8). A 'sustained negative inhibitor status' was defined as consistent non-positive inhibitor measurements for two years or longer. A total of 60/486 (12%) patients tested had a positive inhibitor titre in two or more occasions. Most of the patients (56%) with a maximum inhibitor titre of < 5 Bethesda unit (BU)/ml (named "low titre inhibitor") developed a sustained negative inhibitor status. Among patients with high (5-9.9 BU/ml) and very high (≥ 10 BU/ml) inhibitor titres, the proportions were 50% and 3%, respectively. Our findings suggest that ITI might not be needed for all patients with non-transient inhibitors, especially when their maximum inhibitor titre is below 10 BU/ml. Further studies in countries where ITI is not available are needed to examine predictors of the natural sustained negative inhibitor status.     

Xenograft Transplantation of Human Malignant Astrocytoma Cells Into Immunodeficient Rats: An Experimental Model of Glioblastoma

INTRODUCTION:

Astrocytic gliomas are the most common intracranial central nervous system neoplasias, accounting for about 60% of all primary central nervous system tumors. Despite advances in the treatment of gliomas, no effective therapeutic approach is yet available; hence, the search for a more realistic model to generate more effective therapies is essential.

OBJECTIVE:

To develop an experimental malignant astrocytoma model with the characteristics of the human tumor.

METHOD:

Primary cells from subcutaneous xenograft tumors produced with malignant astrocytoma U87MG cells were inoculated intracerebrally by stereotaxis into immunosuppressed (athymic) Rowett rats.

RESULTS:

All four injected animals developed non-infiltrative tumors, although other glioblastoma characteristics, such as necrosis, pseudopalisading cells and intense mitotic activity, were observed.

CONCLUSION:

A malignant astrocytoma intracerebral xenograft model with poorly invasive behavior was achieved in athymic Rowett rats. Tumor invasiveness in an experimental animal model may depend on a combination of several factors, including the cell line used to induce tumor formation, the rat strains and the status of the animal’s immune system.     

Maternal care and breastfeeding experience of women suffering intimate partner violence

OBJECTIVE: To describe maternal care and breastfeeding experience of women suffering intimate partner violence. METHODOGICAL PROCEDURES: A qualitative study was conducted in 11 women suffering intimate partner violence during pregnancy. Women aged 16-41 years were recruited in a hospital in the city of Rio de Janeiro between January and March 2005. Data were collected through in-depth interviews using a life history approach and complemented by a semi-structured guide. ANALYSIS OF THE RESULTS: Women expressed mixed feelings of loneliness and good moments regarding maternal care and breastfeeding experience. Most had early cessation of breastfeeding and the reasons reported included: the need to resume their working activities, lack of information on breastfeeding and the violence experienced by these women. CONCLUSIONS: The study shows a need to approach women as key actors of a nursing model, offering opportunities to listen to their concerns as well as to provide care to intimate partner violence victims and differentiated support.     

Raising children with mental disabilities: mothers' narratives

Technical advances in neonatology have increased the life expectancy of children with serious health problems. Many of these children experience developmental delay (mental disability) and require special care. The family must adapt to better provide for the child's needs. This study aimed to identify mothers' reactions and the obstacles they face to obtain what they consider the best treatment for their children. The study methodology was based on analysis of the mothers' narratives, drawing on medical anthropology and linguistics. The most typical plots in the narratives showed the impact of the diagnosis and the search for means to adapt to the child's care, as well as the difficulties encountered in the public health system to obtain what the mothers considered adequate care. The value ascribed to characters in the support network showed the importance of such support in these situations.     

Inhibition of angiotensin II receptor 1 limits tumor-associated angiogenesis and attenuates growth of murine melanoma

Purpose

We evaluated the involvement of angiotensin II (AngII)-dependent pathways in melanoma growth, through the pharmacological blockage of AT1 receptor by the anti-hypertensive drug losartan (LOS).

Results

We showed immunolabeling for both AngII and the AT1 receptor within the human melanoma microenvironment. Like human melanomas, we showed that murine melanomas also express the AT1 receptor. Growth of murine melanoma, both locally and at distant sites, was limited in mice treated with LOS. The reduction in tumor growth was accompanied by a twofold decrease in tumor-associated microvessel density and by a decrease in CD31 mRNA levels. While no differences were found in the VEGF expression levels in tumors from treated animals, reduction in the expression of the VEGFR1 (Flt-1) at the mRNA and protein levels was observed. We also showed downregulation of mRNA levels of both Flt-4 and its ligand, VEGF-C.

Conclusions

Together, these results show that blockage of AT1 receptor signaling may be a promising anti-tumor strategy, interfering with angiogenesis by decreasing the expression of angiogenic factor receptors.     

Factors of morbidity in hemispherectomies: surgical technique x pathology

OBJECTIVE: The objective of this paper is to evaluate factors of surgical morbidity from different techniques of hemispherectomy with emphasis on causative pathology. PATIENTS AND METHODS: Thirty patients underwent hemispherectomy in our institution from 1987 to 2003, two presented with Sturge-Weber Syndrome (SWS), sixteen with Rasmussen's Syndrome (RS), eight with established hemispheric lesions (EHL), and four with cortical development malformations (CDM). Six surgeons operated on three patients using anatomical hemispherectomies (AH), 11 patients using functional hemispherectomy (FH), and 16 patients employing hemispherotomy (HT). Surgical technique and causative pathology were studied independently as factors of morbidity in hemispherectomy. RESULTS: Overall mean surgical time was 11:50+/-3:20 h and increased proportionately in pathologies with larger hemispheres. Blood transfusion was particularly influenced by the approach adopted by our team of anesthesiologists, independently of technique or pathology. Pathology was the most important factor related to hydrocephalus as two out of four patients with CDM needed ventriculoperitoneal shunt whilst none with EHL or SWS. Four patients undergoing HT and one FH presented residual bridges connecting the hemispheres, three were reoperated and are seizure free. Two patients with CDM did not improve their seizures worthwhile with surgery and other two (one with RS and other with CDM) were waiting a second procedure due to incomplete inter-hemispheric disconnection. Five patients presented infection and one died after developing meningoencephalitis. CONCLUSION: Hemispherectomies are procedures where pathology and surgical technique interact narrowly. Therefore, in order to study surgical morbidity or outcome, both pathology and technique have to be analyzed independently.     

Adverse drug events in hospital: pilot study with trigger tool

OBJECTIVE

To estimate the frequency of and to characterize the adverse drug events at a terciary care hospital.

METHODS

A retrospective review was carried out of 128 medical records from a hospital in Rio de Janeiro in 2007, representing 2,092 patients. The instrument used was a list of triggers, such as antidotes, abnormal laboratory analysis results and sudden suspension of treatment, among others. A simple random sample of patients aged 15 and over was extracted. Oncologic and obstetric patients were excluded as were those hospitalized for less than 48 hours or in the emergency room. Social and demographic characteristics and those of the disease of patients who underwent adverse events were compared with those of patients who did not in order to test for differences between the groups.

RESULTS

Around 70.0% of the medical records assessed showed at least one trigger. Adverse drug events triggers had an overall positive predictive value of 14.4%. The incidence of adverse drug events was 26.6 per 100 patients and 15.6% patients suffered one or more event. The median length of stay for patients suffering an adverse drug event was 35.2 days as against 10.7 days for those who did not (p < 0.01). The pharmacological classes most commonly associated with an adverse drug event were related to the cardiovascular system, nervous system and alimentary tract and metabolism. The most common active substances associated with an adverse drug event were tramadol, dypirone, glibenclamide and furosemide. Over 80.0% of events provoked or contributed to temporary harm to the patient and required intervention and 6.0% may have contributed to the death of the patient. It was estimated that in the hospital, 131 events involving drowsiness or fainting 33 involving falls, and 33 episodes of hemorrhage related to adverse drug effects occur annually.

CONCLUSIONS

Almost one-sixth of in-patients (16,0%) suffered an adverse drug event. The instrument used may prove useful as a technique for monitoring and evaluating patient care results. Psycothropic therapy should be critically appraised given the frequency of associated events, such as excessive sedation, lethargy, and hypotension.     

Dominant form of arthrogryposis multiplex congenita with limited mouth opening: a clinical and imaging study

AIMS: Arthrogryposis multiplex congenita (AMC) is characterized by congenital contractures and joint deformities, but there are only a few reports of temporomandibular joint (TMJ) involvement. The objective of this investigation was to study the cause of limited mouth movement in this disease. MATERIALS AND METHODS: Four individuals from a family affected by AMC over 5 generations were examined clinically and by magnetic resonance imaging (MRI) and 3-dimensional computerized tomography (3D-CT). RESULTS: The CT scans of the 4 individuals showed hyperplasia of the coronoid process protruding into the infratemporal fossa in 2 of them and cranially to the zygomatic arch in the other 2; the hyperplasia was associated with mechanical limitation of the mouth opening. The MRI showed a disc displacement with reduction in 1 patient and a disc displacement without reduction in another; disc displacement could not be evaluated because of the limited mouth opening in the other 2. The condyle-disc complex of these last 2 individuals could only rotate. The MRI on T2-weighted images showed disc hyposignal in all cases but no alterations in the masticatory muscle tissue. The pedigree of the family suggests an autosomal dominant form of inheritance. CONCLUSIONS: The restriction of mouth opening in the 4 individuals affected by AMC was likely due to osseous dysplasia.