Cholesterol lowering therapy inhibits the low-flow mediated vasoconstriction of the brachial artery in hypercholesterolaemic subjects

1 We tested whether lipid lowering treatment with HMG CoA reductase inhibitor modified the flow mediated large artery reactivity in primary pure hypercholesterolaemia.
2 Abnormalities in arterial reactivity have been described in the presence of high blood cholesterol, in particular an enhanced constriction of the brachial artery in response to acute induction of a low flow state.
3 Using pulsed-Doppler, we measured brachial artery diameter and flow velocity at rest and their changes induced by wrist occlusion before and after 3 months of double-blind treatment by pravastatin (40  mg orally) in 13 subjects and placebo in 15 others.
4 The significant decrease ( P <0.01) in diameter induced by wrist occlusion before (0.34±0.08  mm) placebo and pravastatin (0.39±0.10  mm) persisted after placebo (0.26±0.07  mm) but was abolished after pravastatin (0.07±0.05  mm). The absolute change in diameter induced by wrist occlusion was lower after than before pravastatin ( P <0.01) and lower after pravastin than after placebo ( P <0.05). Diameter during wrist occlusion was higher after pravastatin than after placebo (4.35±0.16 vs 3.89±0.09  mm); P <0.01).
5 These findings indicate that the lipid changes induced by pravastatin and/or some unknown but direct mechanism of the drug itself inhibit low-flow-mediated vasoconstriction associated with hypercholesterolaemia. Such effects may have important implications for the treatment of vasospasm often seen in the presence of high blood cholesterol.     

Preimplantation genetic diagnosis for hemophilia A using indirect linkage analysis and direct genotyping approaches

Summary. Background: Preimplantation genetic diagnosis (PGD) is an appealing option for couples at risk of having a child with hemophilia A (HA). Although many clinics offer PGD for HA by gender selection, an approach that detects the presence of the underlying F8 mutation has several advantages. Objectives: To develop and validate analysis protocols combining indirect and direct methods for identifying F8 mutations in single cells, and to apply these protocols clinically for PGD. Methods: A panel of microsatellite markers in linkage disequilibrium with F8 were validated for single‐cell multiplex polymerase chain reaction. For point mutations, a primer extension genotyping assay was included in the multiplex. Amplification efficiency was evaluated using buccal cells and blastomeres. Four clinical PGD analyses were performed, for two families. Results: Across all validation experiments and the clinical PGD cases, approximately 80% of cells were successfully genotyped. Following one of the PGD cycles, healthy twins were born to a woman who carries the F8 intron 22 inversion. The PGD analysis for the other family was complicated by possible germline mosaicism associated with a de novo F8 mutation, and no pregnancy was achieved. Conclusions: PGD for the F8 intron 22 inversion using microsatellite linkage analysis was validated by the birth of healthy twins to one of the couples. The other family’s situation highlighted the complexities associated with de novo mutations, and possible germline mosaicism. As many cases of HA result from de novo mutations, these factors must be considered when assessing the reproductive options for such families.     

The psychophysiology of crying

Two conflicting views have emerged as to why people cry when they are sad. One suggests that crying serves homeostasis by facilitating recovery; the other suggests that crying produces an aversive high-arousal state that motivates behavior aimed at ending the tears. To test hypotheses drawn from these views, we showed a short film known to elicit sadness to 150 women. During this film, 33 subjects spontaneously cried and 117 did not. Subjects who eried exhibited more expressive behavior and reported feeling more sadness and pain than did subjects who did not cry. Crying also was associated with increases in somatic and autonomic nervous system activity. The increases in autonomic activity could not be accounted for solely by the increases in somatic activity. Crying is thus associated with an aversive state, including negative emotion and a complex mixture of sympathetic, parasympathetic, and somatic activation, and we speculate about the functional implications of these findings.