HIV/AIDS selective infectivity–report of two peculiar cases

We report two peculiar cases that were observed in two communities of Anambra State, South East Nigeria. The first case was a woman of 44 with a history of blood transfusion from a donor of questionable HIV status. A pint of blood was transfused in a private Hospital on the 15 th January, 2000. She has had no form of antiviral therapy until 22nd April, 2008 when she came to the hospital for routine medical check up. Her HIV result came out confirmed positive while that of her husband came out negative. She has had active sexual life with her husband in the previous eight years as they have had some difficulties in getting their desired extra two children having earlier gotten a boy and a girl. The second case involves a family of six. A couple with four children of ages about 6 months, 2 years, 3 years and 5 years. The youngest, a female presented with fever and multiple lymphadenopathy. She tested HIV positive and so was her mother and her second sibling. But her father and two other siblings remained negative at post three and six months intervals from their very first test date with us. These reported cases appear to go contrary to earlier formed opinion on HIV transmission. We support the opinion on a naturally, occurring substance, APOBEC3G which possibly confers permanent immunity against the HIV virus. We recommend clinical trials of the characterized APOBEC3G as a vaccine for non HIV infected persons of all ages and to people living with as a therapeutic drug.     

IL-10 has a protective role in experimental autoimmune uveoretinitis

The role of IL-10 in the regulation of ocular autoimmune disease was studied in experimental autoimmune uveoretinitis (EAU) elicited in mice by immunization with the retinal antigen interphotoreceptor retinoid binding protein. IL-10-deficient mice were susceptible to EAU, indicating that pathogenesis can occur without presence of IL-10. Treatment of normal mice with IL-10 for 5 days after uveitogenic immunization ameliorated subsequent EAU scores, and down-regulated antigen-specific production of tumor necrosis factor-alpha and IFN- gamma. A concomitant treatment with IL-4 further reduced disease, and resulted in emergence of antigen-specific IL-4 and IL-10 production, as well as in enhancement of the IgG1 antibody isotype. IL-4 by itself was not protective. Only IL-10, but not IL-4, was able to inhibit the function of differentiated uveitogenic T cells in culture. Expression of mRNA for Th1 and Th2 cytokines in the eye during the course of EAU showed that while a Th1 pattern predominated early, IL-10 mRNA expression coincided with down-regulation of the Th1 response and resolution of EAU. Systemic neutralization of IL-10 during the expression phase of EAU resulted in elevated disease scores. Our results suggest that endogenous IL-10 limits expression of EAU and may play a role in the natural resolution of disease. The data further suggest that exogenous IL-10 may be useful in therapeutic control of autoimmune uveitis. While IL-10 by itself is sufficient to suppress Th1 effector development and function, a concomitant administration of IL-4 is required to shift the autoimmune response towards a non-pathogenic Th2 pathway.      

De novo 16p13.11 microdeletion identified by high-resolution array CGH in a fetus with increased nuchal translucency

Objective  We investigated the application of high-resolution microarray-based comparative genomic hybridisation (array CGH) on a fetus showing increased nuchal translucency (NT).
Design  Case study.
Setting  Tertiary referral obstetrics unit.
Sample  Pregnant woman attended the antenatal clinic.
Methods  Conventional karyotyping and genetic test was carried out for the alpha-globin gene. High-resolution array CGH using the high-density 244K Agilent microarray was performed on fetal blood sample by cordocentesis to investigate the possibility of any genomic imbalance.
Main outcome measures  Detection of chromosomal abnormality.
Results  Karyotyping analysis showed 46,XY. Molecular genetic diagnosis confirms the fetus has Hb-H constant spring disease but cannot explain the increased NT to 3.2 mm. Array CGH analysis discovered a 1.32-Mb microdeletion on chromosome 16p13.11. Deletion at 16p13.11 has been implicated to predispose to autism and/or mental retardation. Baby was delivered at 40 weeks of gestation, and follow up was carried out at 3 months of age without sign of mental retardation/developmental delay.
Conclusions  This case study demonstrated that array CGH can accurately calibrate the size and identify de novo interstitial chromosome imbalances. However, the presence of chromosome copy variants with unknown clinical significance currently limits its wider scale application in prenatal diagnosis and needs further investigations.     

How much now to tell? Patients' attitudes to an information sheet prior to angiography and angioplasty

A prospectively controlled pilot study of 100 patients undergoing an invasive radiological procedure was undertaken to test patients' acceptance of risk disclosure and whether this increases anxiety and rate of procedure cancellation. Two sheets with differing amounts of information on adverse outcome were randomly allocated and patients provided a graded response to statements following the procedure. Eighty-one completed questionnaires were received (brief sheet n= 40; long sheet n= 41). There were 19 non-compliers with main causes either due to lack of interest or problems such as language difficulties, visual impairment and dementia. There were no significant differences between the two groups with respect to subjective anxiety caused by the information or risk of procedure cancellation. This preliminary work has shown that information sheets are well accepted and provide a simple, standardized format for risk disclosure.     

The use of drugs for the inhibition of prostaglandin or leukotriene synthesis from arachidonic acid is theoretically hazardous

It would appear that it has become almost common practice to regard arachidonic acid (AA) as the sole precursor of eicosanoids. The fact that both dihomogamma-linolenic acid (DGLA) and eicosapentaenoic acid (EPA) give rise to distinct families of eicosanoids is commonly almost completely ignored. Elevated tissue levels of AA eicosanoids have been found in and have been implicated in the etiology of a number of diseases. Drugs which selectively block AA mobilization or its eicosanoid metabolism have therefore been developed for therapeutic use in these conditions. The fact that such drugs will also simultaneously block the eicosanoid metabolism from DGLA as well as from EPA is also commonly ignored. It is suggested that the profoundly adverse side-effects displayed by some of these drugs, resulting in some instances in their withdrawal from use, could be the direct result of their concomitant action of interfering with the eicosanoid metabolism of DGLA and EPA. It is further suggested that, before the interactions between the eicosanoids derived from AA and those derived from DGLA and EPA are understood, the use of drugs for the manipulation of AA eicosanoid metabolism in isolation, could be hazardous. This implies that all such drugs currently in use are to be regarded as experimental and provisionally toxic in terms of their effects on the whole system of eicosanoid metabolism. Thus even drugs which have been passed by the FDA and similar Drug Control Councils require total re-evaluation especially in view of the fact that the non-steroidal anti-inflammatory drugs are often prescribed for chronic conditions which require therapy for several years.(ABSTRACT TRUNCATED AT 250 WORDS)     

Primitive neuroectodermal tumours of the cerebrum

Summary Eighteen cases of cerebral tumour composed partly or totally of primitive embryonal cells are reported. These lesions comprise 2.8% of all primary cerebral hemisphere tumours in the histopathology files of The Royal Marsden Hospital between 1971 and 1980 inclusive. Most exhibited some degree of differentiation towards neuronal or glial elements and, as more than one type of differentiation was often present in the same lesion, we agree with others that the term primitive neuroectodermal tumour (PNET) is more appropriate to describe these lesions than terms based on histogenesis. The extent of the primitive component varied, but usually accounted for more than 80% of the tumour. Although the tumours bear some similarities to posterior fossa medulloblastomas, they exhibit important differences in histology, immunohistology, natural history and response to treatment. Nearly all PNETs examined expressed some glial fibrillary acidic (GFAP) both in primitive areas and zones of astrocytic differentiation. GFAP staining may thus be of value in distinguishing PNETs from undifferentiated non-neurogenic tumours. Of 14 patients referred for radiotherapy, the survival rate at 3 years was 29% (\414) and 5 years 25% (\312). Patients with tumours in which at least 90% of the tissue was undifferentiated exhibited an extremely poor prognosis with none of 9 patients still alive at 3 years in contrast to 3 of 5 patients (60%) with tumours showing less than 90% undifferentiation. Radical tumour removal, where feasible, followed by irradiation of the whole cerebrospinal axis is recommended. Adjuvant chemotherapy with such agents as CCNU and Vincristine may be of value: the 3 long term survivors in the present series (7–11 years), including one who presented disseminated intracranial disease, received such adjuvant treatment.