Pulmonary manifestations of schistosomiasis

Bilharziosis or schistosomiasis is the third leading endemic parasitic disease in the world, following malaria and ambiasis. More than 300 million individuals are infested. Schistomosomes are blood flukes which live in the perivisceral veins. Clinical signs result from ova migrations. Transmitted by urine and feces, the parasite cycle requires intermediary host, usually fresh water snails. Bilharsiosis is endemic in tropical zones where it is a major public health problem closely correlated with the socio-economic conditions. Liver, intestinal or urinary complications, depending on the species, lead to underestimated morbidity and mortality. Pulmonary lesions are attributed to 3 species: S. haematobium, S. mansoni and S. japonicum. Although the lung is mandatory step in the parasite cycle, pulmonary manifestations are limited. They can be acute or chronic depending on the phase of the cycle, but are the most frequent extradigestive localization for S. mansoni. Morbidity due to chronic manifestations is particularly severe and should be prevented whenever possible.     

Orchidectomy and hormonal therapy of prostate cancer

The objective of this study is to document the use of hormonal therapies in treating prostate cancer in Ontario in the last decade. Drug utilization data were extracted from the Ontario Drug Benefit Program, while surgical orchidectomy rates were calculated from Hospital Medical Records Institute data. The provincial rate of orchidectomy showed a 55% relative increase from 1981 to 1991. There was a 6.4-fold variation in orchidectomy rates among counties in Ontario. As well, the expenditures on new hormonal therapies rose 38-fold between 1985 and 1990, and doubled between 1990 and 1992. There was no consistent relationship between use of orchidectomy and hormonal drug therapy at the county level. We conclude that both forms of hormonal therapy have increased in Ontario. The wide variation in surgical orchidectomy rates observed in Ontario suggests differences in practice styles and possible medical uncertainty. Guidelines for the hormonal therapy of prostate cancer may be a helpful step forward for practitioners and patients.     

The Older HIV-Positive Adult: A Critical Review of the Medical Literature

Older adults make up an ever-growing proportion of human immunodeficiency virus (HIV) cases in the United States, with approximately 25% of infections occurring in adults over the age of 50 years. Although there is a preliminary body of literature addressing the socioeconomic and prognostic issues of HIV infection in older adults, very little rigorous scientific research has looked at the significant clinical issues relevant to this growing population. Treatment of older adults is complicated by an increased prevalence of medical comorbidities, but little is known about the effects of complicated medication regimens in this group, as they are routinely excluded from clinical trials of newer HIV medications. The delay in diagnosis and treatment of HIV in older adults has led to poorer outcomes, including lower baseline CD4 counts, decreased time to acquired immune deficiency syndrome diagnosis, and increased mortality. Despite these facts, there is mounting evidence that timely diagnosis and treatment of HIV in older adults leads to improved outcomes, similar to younger patients. This review evaluates the literature focusing on HIV and older adults.     

Substrate for endothelial prostacyclin production in the presence of platelets exposed to collagen is derived from the platelets rather than the endothelium

Interactions between vascular endothelial cells and blood platelets have been investigated using a model microcirculation consisting of microcarrier beads colonized with human umbilical vein endothelial cells (HUVECs) and perfused with washed platelet suspensions. To simulate the effects of endothelial desquamation and exposure of subendothelium, fibrillar collagen in suspension was coinjected with the platelets. In this model, neither the passage of platelets alone nor collagen alone stimulated prostacyclin (PGI2) production by the HUVECs. Platelets activated by coinjection with collagen released thromboxane A2 (TXA2), and this was associated with the simultaneous production of PGI2 by the HUVECs. By means of double-isotope experiments with [3H]arachidonic acid (AA) incorporated into platelets and [14C]-AA into HUVECs, it was shown that all the PGI2 generated was derived from platelet AA and/or endoperoxides. This interpretation was strengthened by the finding that PGI2 production was not prevented by treatment of HUVECs with indomethacin followed by perfusion with collagen-stimulated platelets. AA metabolites in double-isotope label experiments were further characterized by reverse-phase chromatography, and it was shown that both cyclooxygenase and lipoxygenase products of the HUVECs were derived from platelet membrane lipid. Thrombin regularly produced transient PGI2 release, but showed rapid tachyphylaxis. Platelet-derived compounds including ADP, ATP, and platelet-activating factor (PAF) did not produce PGI2 release by HUVECs in this system. Thus, the transfer of AA and metabolites from collagen- stimulated platelets is likely to be the mechanism for PGI2 production in the context of minor degrees of endothelial desquamation.     

Adenosine regulates the Ca2+ sensitivity of mast cell mediator release.

Mast cells release histamine and other mediators of allergy in response to stimulation of their IgE receptors. This release is generally thought to be mediated by an elevation of cytosolic Ca2+. Recent evidence suggests that there might be factors that modulate the coupling between Ca2+ levels and mediator release. The present report identifies adenosine as one such modulator. Adenosine and several of its metabolically stable analogues were shown to enhance histamine release from rat peritoneal mast cells in response to stimuli such as concanavalin A. Metabolizing endogenous adenosine with adenosine deaminase dampened the response to stimuli, whereas trapping endogenous adenosine inside mast cells with nucleoside-transport inhibitors markedly enhanced stimulated histamine release. The metabolically stable adenosine analogue 5'-(N-ethylcarboxamido)adenosine (NECA) did not affect the initial steps in the sequence from IgE-receptor activation to mediator release, which are generation of inositol trisphosphate and increase of cytosolic Ca2+. However, NECA did enhance the release induced in ATP-permeabilized cells by exogenous Ca2+, but it had no effect on the release induced by phorbol esters. These data suggest that adenosine sensitizes mediator release by a mechanism regulating stimulus-secretion coupling at a step distal to receptor activation and second-messenger generation.     

Parental origin of mutation and the risk of breast cancer in a prospective study of women with a BRCA1 or BRCA2 mutation

The objective is to estimate the risk of breast cancer in women who carry a deleterious BRCA1 or BRCA2 mutation, according to parental origin of mutation. We conducted a cohort study of women with a BRCA1 mutation (n = 1523) or BRCA2 mutation (n = 369) who had not been diagnosed with breast or ovarian cancer. For each woman, the pedigree was reviewed and the origin of the mutation was assigned as probable paternal or maternal. The hazard ratio (HR) for developing breast cancer in the follow‐up period was estimated for women with a paternal mutation compared to a maternal mutation. The risk of breast cancer was modestly higher in women with a paternal BRCA1 mutation compared to women with a maternal BRCA1 mutation (HR = 1.46; 95% CI = 0.99–2.16) but the difference was not significant (p = 0.06). The parental mutation origin did not affect the risk in women with a BRCA2 mutation. Our results are consistent with the hypothesis that there is an increased risk of breast cancer among women with a paternally inherited BRCA1 mutation compared to a maternally inherited mutation. However, the data are not sufficiently compelling to justify different screening recommendations for the two subgroups.     

To tell or not to tell – what to do about p.C282Y heterozygotes identified by HFE screening

Hereditary hemochromatosis (HH) is a common preventable disorder of iron overload that can result in liver cirrhosis and reduced lifespan. Most HH is due to homozygosity for the HFE p.C282Y substitution. We conducted a study of screening for p.C282Y in high schools where p.C282Y heterozygotes (CY) individuals were informed of their genotype by letter. We studied whether these individuals understood the implications of their genotype, whether this resulted in anxiety or reduced health perception and whether cascade testing was higher in families of CY than wild‐type homozygous (CC) individuals. We found 586 of 5757 (1 in 10) screened individuals were CY. One month after receiving their result, 83% correctly answered that they have one copy of p.C282Y. There was no adverse change in anxiety or health perception from prior to screening to 1 month after receiving results. Significantly more family members of CY individuals than CC individuals were informed about HH and had testing for HH. In conclusion, we found that informing CY individuals of their genotype does not increase anxiety and the implications are generally well understood. This leads to cascade testing in a minority of families. CY individuals should be informed of their genetic status when identified by population screening.     

How to report the antinuclear antibodies (anti-cell antibodies) test on HEp-2 cells: guidelines from the ICAP initiative

Immunologic Research - Results of the anti-nuclear antibodies-indirect immunofluorescence assay (anti-cell antibodies test) on HEp-2 cell substrates should be communicated to clinicians in a...