Severe hypercalcemia caused by Milk‐Alkali syndrome requiring urgent hemodialysis – Tums by the ton

An increased frequency of the Milk‐Alkali syndrome in the last several years has been noticed related to increasing use of calcium carbonate as a phosphate binder in CKD patients, as an antacid or as calcium supplementation. We present a case of severe hypercalcemia secondary to Milk‐Alkali syndrome that precipitated acute renal failure requiring urgent hemodialysis. A 59-year‐old male with history of hypertension, diabetes mellitus, and acid reflux presented to the ER with confusion, lethargy, nausea, vomiting, and diarrhea. His family relayed a history of recent indigestion and relief with Tums. He was taking several tablets at short intervals to self‐treat the indigestion. At the time of presentation, patient was confused and noted to be dehydrated. Lab findings were significant for elevated BUN/Cr‐ 121 mg/dl/11.1 mg/dl (baseline Cr 1.1 mg/dl few months ago), bicarbonate 38 mg/dl, calcium 16.7 mg/dl, ionized Ca of 1.76 mmol/L, iPTH 10 pg/ml, PTHrP 0.7 pg/ml. Medical management with intravenous fluids and furosemide showed no improvement in renal failure, or calcium level. Patient was then started on hemodialysis with 2.0 mmol/L calcium in the dialysate the next day. There was gradual improvement in patient's mental status, calcium values, and renal failure over the ensuing 2 weeks.
Discussion and Conclusions:  The diagnosis of Milk‐Alkali syndrome is made on the basis of history. Metabolic abnormalities involved in this syndrome are hypercalcemia with low to normal PTH and Vit. D levels, renal failure, and metabolic alkalosis. Failed medical management required acute dialysis in this patient. Acute hemodialysis in such a case could be life saving. Due to increasing use of calcium carbonate for dyspepsia and osteoporosis, patients should be made aware of these severe, potentially life-threatening adverse effects.     

Evolutionary dynamics of genetic variation in Epstein-Barr virus isolates of diverse geographical origins: evidence for immune pressure-independent genetic drift

The question whether immune pressure exerted by cytotoxic T lymphocytes (CTLs) can influence the long-term evolution of genetically stable viruses such as Epstein-Barr virus (EBV) has generated considerable scientific interest, primarily due to its important implications for the overall biology of the virus. While arguing for a role of CTLs in the evolution of viruses, it is important to differentiate between genetic variation in virus and immune recognition of these variant virus by CTLs. To assess the role of genetic selection in the long-term evolution of EBV, we have analyzed a large panel of type 1 EBV isolates from African, Southeast Asian, Papua-New Guinean (PNG), and Australian Caucasian individuals. Seven different regions of the EBV genome, which include nine CTL epitopes restricted through a range of HLA class I alleles, were sequenced and compared. Although numerous nucleotide changes were identified within these isolates, comparison of synonymous and nonsynonymous substitutions in the CTL epitope indicated that the genetic variation was generated mostly independently of immune selection pressure. Surprisingly, an inverse correlation between genetic variation within certain CTL epitopes and the frequency distribution of HLA alleles that present the CTL epitopes was seen, suggesting that the evolutionary pressures on the CTL epitopes of the virus may be toward their conservation rather than their inactivation. Furthermore, molecular evolutionary genetic analysis of nucleotide sequences revealed that viral isolates from PNG are evolving as a lineage distinct from isolates from African, Southeast Asian, and Australian Caucasian individuals.     

Economics of herbaceous bioenergy crops for electricity generation: Implications for greenhouse gas mitigation

This paper examines the optimal land allocation for two perennial crops, switchgrass and miscanthus that can be co-fired with coal for electricity generation. Detailed spatial data at county level is used to determine the costs of producing and transporting biomass to power plants in Illinois over a 15-year period. A supply curve for bioenergy is generated at various levels of bioenergy subsidies and the implications of production for farm income and greenhouse gas (GHG) emissions are analyzed. GHG emissions are estimated using lifecycle analysis and include the soil carbon sequestered by perennial grasses and the carbon emissions displaced by these grasses due to both conversion of land from row crops and co-firing the grasses with coal. We find that the conversion of less than 2% of the cropland to bioenergy crops could produce 5.5% of the electricity generated by coal-fired power plants in Illinois and reduce carbon emissions by 11% over the 15-year period. However, the cost of energy from biomass in Illinois is more than twice as high as that of coal. Costly government subsidies for bioenergy or mandates in the form of Renewable Portfolio Standards would be needed to induce the production and use of bioenergy for electricity generation. Alternatively, a modest price for GHG emissions under a cap-and-trade policy could make bioenergy competitive with coal without imposing a fiscal burden on the government.     

Toward targets for initiation of chronic dialysis

OBJECTIVES: To better define the targets for initiation of chronic dialysis, we compared the relationship between the normalized protein equivalent of nitrogen appearance (nPNA, g/kg standard weight/day) and weekly urea clearance (Kt) normalized to total body water (V) in predialysis chronic renal failure (CRF) patients and in patients on continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis (HD). We also studied the relationships of other nutritional parameters to weekly Kt/Vurea in CRF patients. DESIGN: This cross-sectional study was a prospective observational design meant to study each patient once. SETTING: The University Hospital and Clinics and Harry S. Truman VA Medical Center, Columbia, Missouri. PATIENTS: Forty-five consecutive predialysis CRF patients were enrolled and the results compared with patients on CAPD and HD. RESULTS: In CRF, the nPNA calculated from urea appearance correlated with the weekly Kt/Vurea (r = 0.57, p < 0.0001) and, using exponential best-fit, nPNA = 1.217 x (1-e-0.769Kt/V). This exponential relationship was similar to that for CAPD and both were different from that in patients on HD. Likewise, nPNAs, calculated from Kjeldahl nitrogen output, and weekly Kt/Vurea were correlated (r = 0.37, p = 0.014) and, using exponential best-fit, nPNA = 1.102(1-e-0.867Kt/V), similar to the relationship in patients on CAPD. Evidence is presented that these relationships are not explained only by mathematical coupling. There was a significant correlation between the weekly Kt/Vurea and 24-hour urinary creatinine excretion. CONCLUSIONS: The findings suggest that in CRF, as in CAPD, a weekly Kt/Vurea less than 2.0 is likely to be associated with a nPNA less than 0.9 g/kg standard weight. In CRF patients, initiation of chronic dialysis should be considered if weekly renal Kt/Vurea falls below 2.0 and a nPNA greater than 0.8 is desired.     

Solution of mass transfer in step growth polymerization in films with bulk in equilibrium

We have analyzed step growth polymerization in a flat film with finite mass transfer resistance. We have shown rigorously that the molecular weight distribution (MWD) at equilibrium is given by the Flory distribution, and under reaction the form of the MWD does not change if the feed is either pure monomer or in equilibrium initially. Extensive computations have shown that it is possible to split the film into growing interfacial and shrinking bulk regions. It is possible to obtain similarity transformations of concentrations of condensation product, and polymer as time invariant profiles. Based on this finding, we have determined a solution for step growth polymerization with finite mass transfer in films. The results lie within 5% of the “exact” numerical computations, for all possible variations of parameters.     

Comparison of broth macrodilution, broth microdilution and E-test susceptibility tests of Cryptococcus neoformans for fluconazole

Forty Cryptococcus neoformans strains isolated from cerebral spinal fluid specimens collected from 39 patients were included in the study. The MICs for fluconacole were determined by YNB macrodilution test, microdilution tests using both RPMI1640 and YNB medium and E-tests on solidified RPMI1640 medium, Casitone and YNB agar. In comparison with the reference macrodilution method NCCLS M27-P both the microdilution as well as the E-test techniques can be used for fluconacole susceptibility testing of Cr. neoformans.     

Calpain activation is upstream of caspases in radiation-induced apoptosis

The molecular events involved in apoptosis induced by ionizing radiation remain unresolved. In this paper we show that the cleavage of fodrin to a 150 kDa fragment is an early proteolytic event in radiation-induced apoptosis in the Burkitts' Lymphoma cell line BL30A and requires 100 microM zVAD-fmk for inhibition. Caspases-1, -3, -6 and -7 were shown to cleave fodrin to the 150 kDa fragment in vitro and all were inhibited by 10 microM zVAD-fmk. We also show that the in vitro cleavage of fodrin by calpain is inhibited by 100 microM zVAD-fmk as was the calpain-mediated hydrolysis of casein. We demonstrate that calpain is activated within 15 min after radiation exposure, concomitant with the cleavage of fodrin to the 150 kDa fragment whereas caspase-3 is activated at 2 h correlating with the cleavage of fodrin to the 120 kDa fragment. These results support a role for calpain in the early phases of the radiation-induced apoptosis pathway, upstream of the caspases.