Lawrence R. Solomon

Pain Management in Adults With Sickle Cell Disease in a Medical Center Emergency Department

Guidelines for pain management in adult sickle cell patients with vaso-occlusive crises suggest prompt, frequent administration of parenteral opioids. Neither the ability to implement these guidelines in a busy urban emergency department nor opioid dose requirements in uncomplicated vaso-occlusive crisis have been previously documented. Thus, a retrospective review of vaso-occlusive crisis treated in an urban medical center emergency department in 2005 was performed to define opioid requirements and barriers to guideline implementation. Fifty-seven visits by 19 patients were evaluable. Opioid treatment was not initiated for more than 2 hours during 30% of visits; the interval between the first and second opioid doses exceeded 1 hour in 26% of visits and increased with subsequent doses; and total treatment time was less than 1 hour during 21% of visits (median, 2.2 hours). Opioid doses (as intravenous morphine equivalents) ranged from 4 to 26.7 mg (0.05-0.50 mg/kg) and exceeded 10 mg during 40 visits (70%) and in 10 patients (53%). Hospitalization occurred on 25 occasions with 48% of patients admitted after 3 or fewer opioid doses and 50% of patients admitted after less than 3 hours of treatment. Moreover, return emergency department visits occurred within 3 days after 9 of 32 home discharges (28%) with treatment times uniformly less than 3 hours during the preceding visit. It is concluded that: (1) opioid dose requirements vary widely, often exceeding guideline recommendations; and (2) treatment time and timely opioid administration are often compromised, resulting in delayed pain control and premature decisions on disposition with early return visits and possibly avoidable hospital admissions.

Advanced Age as a Risk Factor for Folate-Associated Functional Cobalamin Deficiency

To determine whether high serum folate levels contribute to metabolite changes in elderly subjects with normal cobalamin levels.

Depletion of cultured human fibroblasts of pyridoxal 5′-phospate: Effect on activities of aspartate aminotransferase, alanine aminotransferase, and cystathionine β-synthase

Abstract Human skin fibroblasts were grown in culture medium containing virtually no pyridoxal. Cells cultured under these conditions grew to confluence for several passages without morphologic signs of degeneration and without changes in activity of two control enzymes, hexokinase and lactate dehydrogenase. The pyridoxal 5′-phosphate content of these fibroblasts fell to about 3% of values obtained during growth in pyridoxal-supplemented medium. The effect of such depletion on the activities of three pyridoxal 5′-phosphate-dependent enzymes was assessed during four consecutive passages. Total activity of cystathionine β-synthase and of aspartate aminotransferase in cell extracts fell to a mean of 50% of control values whereas total activity of alanine aminotransferase remained unchanged. Saturation of these enzymes with cofactor differed as well. The ratio of holoenzyme activity to total enzyme activity fell to less than 15% or predepletion values for cystathionine β-synthase and to 60% for aspartate aminotransferase. In contrast, alanine aminotransferase remained completely saturated with cofactor. Maximal saturation of aspartate amino-transferase with pyridoxal 5′-phosphate was achieved when pyridoxal 5′-phosphate-depleted fibroblasts were grown in medium containing as little as 1 ng/ml of pyridoxal, but addition of 10 ng/ml of pyridoxal was required for maximal saturation of cystathionine β-synthase. Maximal intracellular content of pyridoxal 5′-phosphate was achieved only when 100 ng/ml of pyridoxal was added to the growth medium. Interestingly, the activity of pyridoxine kinase remained constant during all depletion and repletion experiments. We conclude that the ability to grow human fibroblasts under these conditions provides a system for the study of apoenzyme-coenzyme interactions both in intact cultured cells and in cell extracts.

Vitamin B12-responsive neuropathies: A case series

Objectives: Neuropathies often accompany vitamin B12 deficiency. Since many neuropathies are linked to oxidative stress and since B12 has both antioxidant and neurotrophic properties, B12 may also be effective treatment in non-deficient subjects. Thus, the characteristics and predictors of B12-responsive neuropathies and their relationship to disorders associated with increased oxidative stress (oxidant risks) were examined. Methods: Retrospective review of 78 subjects with neurological abnormalities treated with B12 and evaluated by the measurement of B12 and the B12-dependent metabolites, methylmalonic acid (MMA), and homocysteine. Results: Sixty-five subjects had neurological improvement (83%), including 35 with other known causes of neuropathy. Only two responders had B12-responsive macrocytosis. Pretherapy B12, MMA, and homocysteine values were normal in 72, 33 and 54% of responders, with all three normal in 23%. Moreover, B12 therapy did not significantly decrease elevated MMA and homocysteine levels in 20 and 37%, respectively, of responders tested but did decrease both metabolites in 75% of evaluable non-responders. At least one oxidant risk was present in 41 of the 46 responders with normal B12 levels (89%). Oral therapy was effective, but parenteral B12 improved responses in four subjects. Discussion: B12-responsive neuropathies are thus (1) common even when confounding disorders are present; (2) dissociated from the presence of hematological abnormalities; (3) dissociated from the presence of B12-responsive metabolical abnormalities; and (4) associated with the presence of oxidant risks when B12 levels are normal. Since no predictors of responses to B12 therapy were identified, empiric trials with parenteral B12 should be considered in appropriate subjects.

Thrombocytopenia due to low-dose colchicine therapy: A possible drug interaction with nivolumab and implications for supportive care

Hyperuricemia and gout often accompany hematologic and oncologic disorders. Colchicine, long used to manage gout, is rarely associated with hematologic toxicity. Infrequently, pancytopenia accompanied by gastrointestinal abnormalities may follow high dose or intravenous colchicine administration in subjects with underlying renal or hepatic dysfunction [1 – 3]. A case of thrombocytopenia during low-dose colchicine administration for gout prophylaxis is now described and a drug interaction with the investigational PD-1 pathway inhibitor, nivolumab is suggested [4].

Prospective controlled study of androgen effects on red cell oxygen transport and work capacity in chronic hemodialysis patients

Effects of androgens on red blood cell (RBC) oxygen transport, RBC metabolism and work capacity in chronic hemodialysis patients were evaluated in a prospective controlled study. Compared to control subjects, patients given nandrolone decanoate had a sustained fall in RBC ATP and a transient rise in RBC DPG but P50 values were unchanged. Despite increases in RBC mass of 16-44% on androgen therapy, exercise on the treadmill improved in only 1 patient and actually declined in 3 others. Thus, these preliminary observations suggest that androgens may not improve hemoglobin-oxygen transport and that androgen-induced increases in red cell mass may only balance increased tissue oxygen requirements produced by these anabolic hormones.

Vitamin B12 and Peripheral Nerve Function in Elderly Adults: “Functional” B12 Deficiency As a Confounding Variable

PDE data. Unfortunately, the finding of a “missingness” rate of 1% at Walmart, as reported by Stuart and Loh, is not reassuring, because “missingness” rates at other discount pharmacies can be substantially higher. We also received anecdotal reports from medical leader review of non-user lists that VA prescription fills account for some of the nonusers. We did not receive drug claims from the VA system. Moreover, as Stuart and Loh acknowledged, because “these (discount drug) plans have expanded considerably since 2007, it is entirely possible that utilization rates are higher now.” Therefore, we believe that the extent to which these programs are available in the local community may influence performance rates on the Part D star measures based on PDE data, which may result in significant variation in performance levels between Part D plan sponsors.