Aims: To investigate a population of individuals with 22q11 deletion syndrome for hypocalcaemia. Methods: A detailed clinical history enquiring into symptoms of hypocalcaemia and blood sampling to assess for hypocalcaemia and hypoparathyroidism, of patients outside the neonatal period known to have the 22q11 microdeletion from fluorescent in situ hybridisation studies was taken. Results: Sixty one individuals were identified, of whom 23 were untraceable and one was unable to give informed consent. Biochemical investigations were performed on 27 subjects. Ten subjects had review of notes only. Four subjects had previously identified hypoparathyroidism. A new case of hypoparathyroidism was identified. Three subjects had borderline hypocalcaemia. Discussion: In this population of patients with 22q11 deletion syndrome, 13% of the total or 30% of those biochemically assessed had evidence of reduced serum calcium concentrations. It is likely that 13-30% of patients with 22q11 deletion syndrome have possible hypoparathyroidism outside the neonatal period. Reported symptoms of hypocalcaemia did not correlate with biochemical evidence of persisting hypocalcaemia. We have shown that previously undiagnosed asymptomatic hypoparathyroidism occurs in patients with 22q11 deletion syndrome and conclude that screening of this population should be considered.

In adult non-replicating tissues such as heart, demand for dNTPs (deoxynucleoside triphosphates) is low but essential for mitochondrial DNA replication and nuclear DNA repair. dNTPs may be synthesized from salvage of deoxyribonucleosides or by reduction of ribonucleotides. We have hypothesized that the cardiac mitochondrial toxicity of the nucleoside analogue AZT (3'-azido-3'-deoxythymidine; known as zidovudine) is caused by inhibition of thymidine kinase 2 of the salvage pathway and subsequent TTP pool depletion. The extent to which this hypothesis has merit depends on how much the heart relies on thymidine phosphorylation for maintenance of the TTP pool. In the present study, we used isotopic tracing to demonstrate that both TTP and dCTP are solely synthesized by phosphorylation of thymidine and deoxycytidine respectively, with no evidence for synthesis from other precursors. We have also shown that UTP and CTP are synthesized by phosphorylation of uridine and cytidine respectively, with no detectable role for the de novo pyrimidine synthesis pathway. Lastly, we have demonstrated that AZT decreased the TTP pool by 50% in 30 min of perfusion, while having no effect on other dNTPs. In summary, the present study demonstrated that adult rat heart has a limited mechanism for dCTP and TTP synthesis and thus these pools may be more sensitive than replicating cells to drugs such as AZT that affect the salvage pathway.

Holstein calves were managed from less than 1 wk of age as in the special-fed veal industry but subjected to three dietary regimens (n = 10/group): low dietary iron (LI = approximately 5 mg iron/kg dry milk replacer) throughout 16 wk; 2) high then low dietary iron (H-LI = 140 mg/kg through d 18, then approximately 5 mg/kg through wk 16; a typical industrial scheme) or 3) high dietary iron (HI = approximately 105 mg/kg throughout the study). Several physiologic, behavioral and health indicators of welfare were monitored at various times. From wk 7 on, blood hemoglobin concentration was higher in HI calves than in LI, whereas that in H-LI calves was intermediate. Blood red cell count was higher in HI calves than in LI from wk 11 to 16, and was higher in HI than in H-LI from wk 14 to 16. Ratio of blood segmented neutrophils to lymphocytes (an indicator of stress) did not differ due to dietary regimen. Between wk 2 and 16, lying time increased from 69.5 to 76.6% of total time. Oral behaviors (e.g., licking and gnawing) occupied less than 15% of total time. Dietary regimen did not affect time spent either lying or engaging in oral behaviors. Calves in all dietary-regimen and slaughter-age groups experienced high frequencies of pneumonia, digestive-tract maladies and trichobezoars, but neither disease nor medical-treatment frequency was related to dietary regimen. Live, hot-dressed carcass and liver weights of the five calves/group slaughtered at 16 wk were not affected by dietary regimens, but carcass grade was highest for LI calves and lowest for HI.(ABSTRACT TRUNCATED AT 250 WORDS)

The percentage of cocaine adulterated with levamisole is steadily increasing in the United States. In susceptible persons, this combination of drugs leads to a clinical syndrome that can include leukopenia and cutaneous manifestations. Many patients also demonstrate positive autoimmune markers. Biopsies of skin lesions often reveal a thrombotic pattern, leukocytoclastic vasculitis, or both. We report 2 cases of this clinical phenomenon, one of which was severe enough to require skin grafting. It is important for clinicians be aware of this emerging public health threat. (J Am Board Fam Med 2012;25:531-535.)