Aqueous humor and serum IgE antibody in experimental ocular Onchocerca infection of guinea pigs

Infection of inbred Strain 2 guinea pigs by subcutaneous or intradermal injection of fresh or cryopreserved living Onchocerca lienalis microfilariae, followed by a challenge intracorneal infection of microfilariae, resulted in serum and aqueous IgE antibody and in significant corneal inflammation. Systemic or intraocular infections given separately were not sufficient to elicit IgE antibody or ocular inflammation. When intravenous transfer of pooled spleen cell suspensions from systemically infected donors to normal syngeneic recipients was substituted for the course of systemic infections, a subsequent intracorneal challenge of cell transfer recipients with microfilariae produced serum and aqueous IgE antibody. Administration of diethylcarbamazine citrate to infected animals following the intracorneal challenge resulted in increased serum IgE antibody and in increased corneal inflammation.     

The development of acquired immunity to tapeworms and progress towards active immunization, with special reference to Echinococcus spp

An assessment is made of the present state of knowledge on acquired immune responses developed by the intermediate and definitive hosts to tapeworm infections. From this evaluation, some gaps in knowledge and some of the problems associated with the development of practical immunization techniques are described. The principal conclusion reached is that absolute resistance to the larval stage can be acquired and resistance to a number of cestode species can be artificially induced in a number of hosts. Thus, research directed towards isolation and characterization of the functional antigens may lead to the development of vaccines for use in public health programmes, such as for the control of echinococcosis, as well as for improving the present status of meat hygiene in regions where cysticercosis, for example, exists.     

Does the Banff rejection activity index predict outcome in patients with early acute cellular rejection following liver transplantation?

The Banff schema incorporates a semiquantitative scoring system for grading of acute cellular rejection (ACR) of the liver allograft. The Banff rejection activity index (RAI) comprises 3 components scored from 0 to 3: venous endothelial inflammation (E); bile duct damage (B); and portal inflammation (P); the scores are combined to an overall score (the RAI). The purpose of this research was to determine the prognostic value of the Banff RAI score in predicting the response to increased immunosuppression and the long-term outcome of the graft. A retrospective study was done of patients undergoing primary liver transplantation between January 2000 and October 2004 with tacrolimus-based immunosuppression; 495 patients were included, 231 had histologically-confirmed ACR, 193 responded to 1 cycle of high-dose steroids. There was no correlation between the total RAI score and response to steroids, resistant rejection, development of chronic rejection, or graft survival. The E score was related to patient survival, a lower score being associated with a worse outcome (P = 0.048). In multivariable analysis, serum bilirubin, serum aspartate aminotransferase, and E score were significant predictors of death (P = 0.012). In univariable analysis, B score and bilirubin were significantly related to "resistant rejection" (P = 0.018 and 0.002, respectively), but only bilirubin was significant in multivariable analysis (logistic regression). In conclusion, although the Banff RAI score is a useful marker of the severity of rejection, neither the total RAI score nor any of the individual components correlated with response to steroids or graft survival.     

Selective targeting of angiogenic tumor vasculature by vascular endothelial-cadherin antibody inhibits tumor growth without affecting vascular permeability

Vascular endothelial-cadherin (VE-cadherin) is an endothelial cell-specific adhesion molecule that is localized exclusively at cell-cell contacts referred to as adherens junctions. VE-cadherin-mediated adhesion is crucial for proper assembly of vascular structures during angiogenesis as well as for maintenance of a normal vascular integrity. We have shown previously that a monoclonal antibody (BV13) to VE-cadherin not only inhibits the formation of vascular tubes during tumor angiogenesis but also disrupts adherens junctions of normal vasculature with a concomitant increase in vascular permeability. The goal of the current studies was to block VE-cadherin function during angiogenesis without disrupting existing junctions on normal endothelium. Using in vitro screening assays to test for functional blocking of adherens junction formation and in vivo assays to detect antibody effects on vascular permeability in normal tissues, we have identified a novel blocking antibody (E4G10) that inhibits VE-cadherin function during angiogenesis but does not disrupt existing adherens junctions on normal vasculature. E4G10 inhibited formation of vascular tubes in vivo in the Matrigel plug and corneal micropocket assays. E4G10 also inhibited tumor growth in three models of mouse and human tumors via an antiangiogenic mechanism. Examination of normal mouse and tumor tissues showed that E4G10 bound to endothelial cells in a subset of tumor vasculature but not to normal vasculature. Bromodeoxyuridine labeling experiments showed that E4G10 specifically targeted a subset of tumor endothelium that is undergoing active cell proliferation, which likely reflects the activated, angiogenic endothelium. These findings indicate that VE-cadherin can be selectively targeted during states of pathological angiogenesis, despite its ubiquitous distribution throughout the entire vasculature. Our data also suggest that antibody E4G10 recognizes VE-cadherin epitopes that are only accessible on endothelial cells forming new adherens junctions, such as in angiogenic tumor vasculature.     

Synergistic effects of F 11782, a novel dual inhibitor of topoisomerases I and II,in combination with other anticancer agents

PURPOSE: F 11782, or 2',3'-bis-pentafluorophenoxyacetyl-4',6'-ethylidine-beta- D-glucoside of 4'-phosphate-4'-dimethylepipodophyllotoxin 2 N-methyl glucamine salt, a novel dual catalytic inhibitor of topoisomerases I and II, characterized by marked antitumour activity in vivo in a series of experimental murine and human tumours, has been selected for further development. This preclinical study was undertaken to investigate its potential for inclusion in combination chemotherapy regimens. The in vitro cytotoxicity of F 11782 incubated simultaneously with the following drugs was investigated: aclarubicin, cisplatin, doxorubicin, etoposide, 5-fluorouracil, mitomycin C, paclitaxel, topotecan or vinorelbine. METHODS: The combinations were first evaluated in vitro against the GCT27 human testicular teratoma cell line and then against the A549 human non-small cell lung cancer cell line using median effect analysis. RESULTS: F 11782 in combination with cisplatin, mitomycin C, etoposide or doxorubicin showed synergistic cytotoxicity against both cell lines. Moreover, F 11782 combined with cisplatin or mitomycin C showed antitumour activity in vivo against P388 murine leukaemia grafted intravenously. Such synergy might have resulted from the identified nucleotide excision repair inhibitory activity of F 11782. CONCLUSIONS: F 11782 appears to be a promising candidate for combination chemotherapy, especially with DNA-damaging agents.     

PCB congeners and pesticides and female fecundity, New York State Angler Prospective Pregnancy Study

Consumption of PCB-contaminated sport fish from Lake Ontario has been reported to be associated with diminished female fecundity. To identify Polychlorinated biphenyl (PCB) congeners and other pesticides that might be associated with reduced fecundity, we followed 102 women aged 20-34 years attempting pregnancy who completed daily diaries for 12 at risk menstrual cycles. Fecundity referred to time-to-pregnancy (TTP) or the number of at risk menstrual cycles required for pregnancy. Blood specimens were obtained for 88 (86%) women and were analyzed using gas chromatography and electron capture for 66 PCB congeners and seven pesticides. Laboratory values were recovery, background and fat corrected prior to natural log transformation. Using stepwise discriminant analysis, congeners IUPAC #205 and #206 and hexaclorobenzene were significantly and positively associated with increasing TTP when women were categorized as becoming pregnant in the first or first three at risk menstrual cycles, respectively. Congeners #205 and #206 are reported to have (anti) estrogenic structural activity.     

Malignant eccrine acrospiroma with metastasis to the parotid

Malignant eccrine acrospiromas are rare. Clinically, they resemble other cutaneous lesions. A high index of suspicion must be maintained in cases of histologically benign eccrine acrospiromas for three reasons: (1) malignant transformation can occur, (2) the presence of both benign and malignant tissue can lead to a false-negative diagnosis if only the benign component is obtained in the biopsy specimen, and (3) benign-appearing tumors can recur locally or metastasize. The primary treatment is wide local excision with or without lymph node dissection. The efficacy of adjuvant chemotherapy and radiation therapy requires further investigation. We describe a case of malignant eccrine acrospiroma in an 80-year-old man, and we review the literature on this tumor, with emphasis on the differential diagnosis.     

Identity and role in parenting a child with cancer

In this paper we suggest that the needs and roles of parents of children with cancer have been inadequately conceptualized by traditional approaches to investigating the psychosocial aspects of chronic childhood illnesses such as cancer. Conducted mainly within discourses of psychopathology, traditional approaches have tended to characterize parents' experience of their child's illness in terms of 'maladjustment' and 'coping', but have done little to illuminate the processes involved in how parents live with their child's illness. In other areas, the research literature treats parents solely as proxy sources of their children's views, and the complexity of their roles as caregivers and individuals in their own right has been ignored. We attempt to re-characterize parenting a child with cancer, drawing attention to how the roles, identities and social obligations of parents position them in relation to the medical world, and highlight the emotional work carried out by parents, including protection of their own and their child's identity. Drawing on various bodies of empirical and theoretical work, including the developing field of childhood studies and the literature on informal carers, we suggest ways of rethinking our understanding of the experience of parenting a child with cancer. In doing so, we consider how the narratives of parents can inform the development of measures to assess the impact of the childhood cancer on the quality of parents' lives, and the role that social and organizational aspects of services can play in ameliorating some of the difficulties involved in parenting a child with cancer.     

Outcome 3 years after a road traffic accident

BACKGROUND: Road traffic accidents are known to have significant consequences for mental state and quality of life in the ensuing year that are largely unrelated to the nature of the injuries. Little is known of longer-term outcome in a representative population. METHODS: Questionnaires covering mental state and social adjustment were sent to 770 subjects who had previously participated in a prospective study of consecutive attenders at an emergency department following a road traffic accident and who had completed questionnaires at baseline, 3 months and 1 year. Outcomes were not predicted by measures related to injury type or severity but were predicted by baseline and later non-injury variables. RESULTS: Replies were received from 507 (66%) subjects. Although 76% of injuries were medically minor bruises and lacerations, 132 (26%) reported symptoms of psychiatric disorder and 104 (21 %) moderate or severe pain at 3 years. There was little evidence of improvement in prevalence between 1 and 3 years, with continuing physical symptoms, psychiatric disorder and reported consequences for everyday life. There was a significant reduction in the number of cases of post-traumatic stress disorder (PTSD) despite there being 21 late onset cases. Psychiatric outcomes and pain were unrelated to the severity of injury and were largely predicted by post-accident variables. CONCLUSIONS: Road traffic accidents have much greater consequences than would be expected from the largely minor nature of the physical injuries. There is a need for changes in medical care and in socio-legal procedures.