High levels of childhood rickets in rural North Yemen

Despite a warm sunny climate, rickets is extremely common in children living in an isolated mountainous area of North Yemen. In a small township the overall prevalence amongst children under five years attending for vaccination was 27%. The condition was most common at the end of the first year and had disappeared by the fifth year. Marasmus was commonly associated with rickets. Children from the rural villages outside the township had significantly lower rates of rickets. Several factors may contribute to the very high rates of rickets in rural Yemen. However, lack of exposure to sunlight as a consequence of particular cultural practices is likely to be the most important. The major social and behavioural factors which restrict the young child access to sunlight are outlined, and possible remedies discussed.     

Long-term protection of hematopoiesis against the cytotoxic effects of multiple doses of nitrosourea by retrovirus-mediated expression of human O6-alkylguanine-DNA-alkyltransferase

A human O6-alkylguanine-DNA-alkyltransferase (ATase) cDNA-containing retrovirus was used to infect murine long-term primary bone marrow cultures. High levels of ATase expression were obtained, and colony- forming cells of the granulocyte-macrophage lineage from the cultures transduced with the human ATase retrovirus were three times more resistant to the alkylating agent, N-methyl-N-nitrosourea (MNU), than control cultures. Furthermore, expression of the human ATase protected long-term hematopoiesis, measured as the output of progenitor cells to the nonadherent fraction of the culture, against the cytotoxic effects of repeated exposures to MNU. These results clearly show that a human ATase cDNA-containing retrovirus can be used to infect long-term primary bone marrow cultures and that this attenuates their sensitivity to nitrosoureas.     

SYNDROME OF INAPPROPRIATE ADH SECRETION AND DIPLOPIA: OAT CELL (SMALL CELL) RECTAL CARCINOMA METASTATIC TO THE CENTRAL NERVOUS SYSTEM

Extrapulmonary small cell carcinoma is being increasingly recognized as a distinct clinical entity. We report a patient with small cell carcinoma of the rectum metastatic to the brain, presenting with diplopia and inappropriate antidiuretic hormone syndrome.     

Regional aortic compliance studied by magnetic resonance imaging: the effects of age, training, and coronary artery disease.

Arterial compliance was measured in 70 healthy volunteers, 13 athletes, and 17 patients with coronary artery disease. Magnetic resonance images were acquired at end diastole and end systole through the ascending aorta, the aortic arch, and the descending thoracic aorta. Regional compliance was derived from the change in luminal area in a slice of known thickness and from the pulse pressure. Total arterial compliance was also measured from the left ventricular stroke volume and the pulse pressure. In the volunteers, mean (SD) regional compliance (microliters/mm Hg) was greatest in the ascending aorta (37 (18], lower in the arch (31 (15], and lowest in the descending aorta (18 (8], and it decreased with age. Compliance in the athletes was significantly higher than in their age matched controls (41 (16) versus 22 (11) microliters/mm Hg). In the patients with coronary artery disease it was significantly lower (12 (4) v 18 (10] than in age matched controls. Total arterial compliance also fell with age in those with coronary artery disease although there was more variation. The results suggest a possible role for compliance in the assessment of cardiovascular fitness and the detection of coronary artery disease.     

Adenosine versus regadenoson comparative evaluation in myocardial perfusion imaging: results of the ADVANCE phase 3 multicenter international trial.

BACKGROUND: Earlier phase 1 and 2 studies have shown that regadenoson has desirable features as a stress agent for myocardial perfusion imaging. METHODS AND RESULTS: This multicenter, double-blinded phase 3 trial involved 784 patients at 54 sites. Each patient underwent 2 sets of gated single photon emission computed tomography myocardial perfusion imaging studies: an initial qualifying study with adenosine and a subsequent randomized study with either regadenoson (2/3 of patients) or adenosine. Regadenoson was administered as a rapid bolus (<10 seconds) of 400 mug. The primary endpoint was to demonstrate noninferiority by showing that the difference in the strength of agreement in detecting reversible defects, based on blinded reading, between sequential adenosine-regadenoson images and adenosine-adenosine images, lay above a prespecified noninferiority margin. Other prospectively defined safety and tolerability comparisons and supporting analyses were also performed. The average agreement rate based on the median of 3 independent blinded readers was 0.63 +/- 0.03 for regadenoson-adenosine and 0.64 +/- 0.04 for adenosine-adenosine-a 1% absolute difference with the lower limit of the 95% confidence interval lying above the prespecified noninferiority margin. Side-by-side interpretation of regadenoson and adenosine images provided comparable results for detecting reversible defects. The peak increase in heart rate was greater with regadenoson than adenosine, but the blood pressure nadir was similar. A summed symptom score of flushing, chest pain, and dyspnea was less with regadenoson than adenosine (P = .013). CONCLUSIONS: This phase 3 trial shows that regadenoson provides diagnostic information comparable to a standard adenosine infusion. There were no serious drug-related side effects, and regadenoson was better tolerated than adenosine.     

Hemostatic plug formation in normal and von Willebrand pigs: the effect of the administration of cryoprecipitate and a monoclonal antibody to Willebrand factor

Hemostatic plug (HP) formation was investigated in the ear bleeding time incision in normal and von Willebrand pigs. HP volume was calculated by integrating the areas of serial sections. In normal pigs (n = 11), platelets immediately formed a layer on the surface of the cut channel. Platelet aggregates formed at the ends of transected vessels and gradually enlarged. Finally, all transected vessels were occluded by HP and bleeding stopped. In contrast, large HPs were formed in the incision in von Willebrand's disease (vWD) pigs (n = 4); these HPs did not cover the ends of the transected vessels, which continued to bleed, allowing the formation of large hemostatically ineffective platelet aggregates in the incision. Canals traversed these HPs, and bleeding from the open vessels may have continued through them. After infusion of cryoprecipitate into a vWD pig, the bleeding time shortened, and the morphological findings of the HPs were similar to those of normal pigs. In normal pigs (n = 3) infused with an anti- Willebrand factor monoclonal antibody, which prolonged the bleeding time, a large HP formed in the incision, similar to that observed in the vWD pig. The volume of the normal and vWD HPs increased with time. These in vivo findings suggest that Willebrand factor is involved in the localization of the HP to the damaged vessel and may also play a role in platelet-platelet interaction. A computerized morphometric technique was used for measuring the volume of the hemostatic plugs and the distance of sequential points on the perimeter of the HP from the center of selected bleeding vessels.