Disorders from perturbations of nuclear‐mitochondrial intergenomic cross‐talk

In the course of evolution, mitochondria lost their independence, and mitochondrial DNA (mtDNA) became the ‘slave’ of nuclear DNA, depending on numerous nucleus‐encoded factors for its integrity, replication and expression. Mutations in any of these factors may alter the cross‐talk between the two genomes and cause Mendelian disorders characterized by qualitative (multiple deletions) or quantitative (depletion) alterations of mtDNA, or by defective translation of mtDNA‐encoded respiratory chain components.     

Hypomagnesemia associated with chondrocalcinosis: A cross‐sectional study

Objective

To determine an association between magnesium (Mg) depletion and chondrocalcinosis, which has been reported but not investigated in a cross‐sectional study.

Methods

Prevalence of chondrocalcinosis was investigated in 144 individuals: 72 patients receiving home parenteral nutrition (HPN) compared with 72 age‐ and sex‐matched controls. Presence of chondrocalcinosis was assessed by knee radiographs. Blood serum and globular Mg levels and 24‐hour urinary Mg content were compared.

Results

Mean ± SD age for both patients and controls was 51 ± 17 years, and 51% in both groups were women. Mean duration of HPN was 6.4 years. Prevalence of chondrocalcinosis was markedly higher in patients receiving HPN than controls (16.6% versus 2.7%; P = 0.006, odds ratio [OR] 7.0, 95% confidence interval [95% CI] 1.45–66.1). Mean ± SD serum and globular Mg levels were significantly lower in patients than controls (serum: 0.75 ± 0.09 mmoles/liter versus 0.81 ± 0.08 mmoles/liter, P = 0.0006; globular Mg: 1.8 ± 0.31 mmoles/liter versus 2.0 ± 0.35 mmoles/liter, P = 0.0003). Twenty‐four‐hour urinary Mg level was lower in patients than controls (mean ± SD 3.85 ± 1.50 mmoles versus 5.37 ± 3.71 mmoles; P = 0.001). Prevalence of chondrocalcinosis was significantly higher in patients with a low serum Mg level (OR 13.5, 95% CI 2.76–127.3, P < 0.0001), with a similarly high but not significant occurrence of chondrocalcinosis in patients with a low globular Mg level (OR 4.09, 95% CI 0.603–20.26, P = 0.08) and in patients with a low 24‐hour urinary Mg level (OR 3.9, 95% CI 0.77–16.34, P = 0.05).

Conclusion

Long‐lasting Mg depletion is strongly associated with chondrocalcinosis.     

Randomized cross‐over trial comparing inpatient and outpatient administration of high‐dose cisplatin

Background/Aims: Treatment with high‐dose cisplatin (HDC) previously required inpatient (IP) admission with overnight hospitalization, but recently practice has shifted to outpatient (OP) therapy. We aimed to determine whether it is preferable to give HDC as an IP or OP using a two‐period cross‐over trial. Methods: Eligible patients were starting chemotherapy with ≥2 cycles of HDC (≥100 mg/dose) and were suitable for OP treatment. All patients received an IP cycle and OP cycle: the order was randomly allocated. Pre‐hydration, anti‐emetics and chemotherapy were identical for IP and OP. Post‐hydration varied by group (3 L normal saline (NS) for IP, 2 L NS for OP). The primary outcome was patient preference for IP versus OP treatment. Secondary outcomes included aspects of health‐related quality of life, adverse events (dose delays and reductions, elevated creatinine and unplanned readmissions) and resource use. Results: Fifty‐nine patients were randomized, 53 completed two cycles of HDC. Most patients preferred OP treatment (36 vs 13, P= 0.002). There were no significant differences in patients' ratings of nausea, vomiting, fatigue, anxiety, depression or overall quality of life. Adverse events were few and unrelated to IP versus OP treatment. Nursing time was longer for IP than OP (163 vs 104 min, P < 0.001). Conclusion: OP treatment was preferred by most patients, appeared safe and used less resources.     

Comparison of characteristics from White‐ and Black‐Americans with venous thromboembolism: A cross‐sectional study

When compared with Whites, Black‐Americans may have a 40% higher incidence venous thromboembolism (VTE) incidence. However, whether other VTE characteristics and risk factors vary by race is uncertain. To compare demographic and baseline characteristics among White‐ and Black‐Americans with VTE, we used data prospectively collected from consecutive consenting adults enrolled in seven Centers for Disease Control (CDC) Thrombosis and Hemostasis Centers from August 2003 to March 2009. These characteristics were compared among Whites (n = 2002) and Blacks (n = 395) with objectively diagnosed VTE, both overall, and by age and gender. When compared with Whites, Blacks had a significantly higher proportion with pulmonary embolism (PE), including idiopathic PE among Black women, and a significantly higher proportion of Blacks were women. Blacks had a significantly higher mean BMI and a significantly lower proportion with recent surgery, trauma or infection, family history of VTE, and documented thrombophilia (solely from reduced factor V Leiden and prothrombin G20210A prevalence). Conversely, Blacks had a significantly higher proportion with hypertension, diabetes mellitus, chronic renal disease and dialysis, HIV, and sickle cell disease. When compared with White women, Black women had a significantly lower proportion with recent oral contraceptive use or hormone therapy. We conclude that Whites and Blacks differ significantly regarding demographic and baseline characteristics that may be risk factors for VTE. The prevalence of transient VTE risk factors and idiopathic VTE among Blacks appears to be lower and higher, respectively, suggesting that heritability may be important in the etiology of VTE among Black‐Americans. Am. J. Hematol. 85:467–471, 2010 © 2010 Wiley‐Liss, Inc.