Previously, siblings of patients with idiopathic recurrent miscarriage (IRM) have been shown to have a higher risk of miscarriage. This study comprises two parts: (i) an epidemiological part, in which we introduce data on the frequency of miscarriage among 268 siblings of 244 patients with IRM and (ii) a genetic part presenting data from a genome-wide linkage study of 38 affected sibling pairs with IRM. All IRM patients (probands) had experienced three or more miscarriages and affected siblings two or more miscarriages. The sibling pairs were genotyped by the Affymetrix GeneChip 50K XbaI platform and non-parametric linkage analysis was performed via the software package Merlin. We find that siblings of IRM patients exhibit a higher frequency of miscarriage than population controls regardless of age at the time of pregnancy. We identify chromosomal regions with LOD scores between 2.5 and 3.0 in subgroups of affected sibling pairs. Maximum LOD scores were identified in four occurrences: for rs10514716 (3p14.2) when analyzing sister-pairs only; for rs10511668 (9p22.1) and rs341048 (11q13.4) when only analyzing families where the probands have had four or more miscarriages; and for rs10485275 (6q16.3) when analyzing one sibling pair from each family only. We identify no founder mutations. Concluding, our results imply that IRM patients and their siblings share factors which increase the risk of miscarriage. In this first genome-wide linkage study of affected sibling pairs with IRM, we identify regions on chromosomes 3, 6, 9 and 11 which warrant further investigation in order to elucidate their putative roles in the genesis of IRM.
The hypothesis that the damaging effect on the stomach mucosa of salicylic acid and its derivatives is ascribable to an uncoupling of oxidative phosphorylation has been investigated by testing of mitochondria isolated from the corpus gland area of mini-pig gastric mucosa. Mitochondria, influenced by salicylate or acetylsalicylate (0.7-5.6 mmol/l), demonstrated increased respiration rate, decreased respiratory control ratio, and decreased P/O ratio when tested in vitro. Uncoupling of oxidative phosphorylation occurred at a salicylate concentration between 3.5 and 5.6 mmol/l.
This study estimated the prevalence of serum antibodies against thrombocyte glycoproteins, at disease onset (54 patients) and later on during the course of the disease (71 patients), in sera from children with idiopathic thrombocytopenic purpura (ITP). Only a minority had serum antibodies at disease onset, with a significantly higher frequency in those who developed the acute form of the disease than in those who developed the chronic form. Serum antibodies may persist after spontaneous cure of acute disease. There was no switch from immunoglobulin M (IgM) to IgG antibodies over time.
Conclusion: The pathogenesis of the acute and chronic forms of ITP may be different.
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