Changes in Circulating Levels of 25-hydroxyvitamin D3 in Breast Cancer Patients Receiving Chemotherapy

Cancer treatments, toxicities and their effects on lifestyle, may impact levels of vitamin D. The aim of this study was to determine serum 25-hydroxyvitamin D3 (25(OH)D₃) levels before, directly after and 6 months after chemotherapy in breast cancer patients (n?=?95), and a comparison group of women (n?=?52) not diagnosed with cancer. Changes in 25(OH)D₃ levels over time were compared using linear mixed models adjusted for age and season of blood sampling. Before start of chemotherapy, 25(OH)D₃ levels were lower in patients (estimated marginal mean 55.8?nmol/L, 95% confidence interval (95%CI) 51.2–60.4) compared to the comparison group (67.2?nmol/L, 95%CI 61.1–73.3, P?=?0.003). Directly after chemotherapy, 25(OH)D₃ levels were slightly decreased (–5.1?nmol/L, 95%CI –10.7–0.5, P?=?0.082), but ended up higher 6 months after chemotherapy (10.9?nmol/L, 95%CI 5.5–16.4, P?<?0.001) compared to pre-chemotherapy values. In women without cancer, 25(OH)D₃ levels remained stable throughout the study. Use of dietary supplements did not explain recovery of 25(OH)D₃ levels after chemotherapy. We reported lower 25(OH)D₃ levels in breast cancer patients, which decreased during chemotherapy, but recovered to levels observed in women without cancer within 6 months after chemotherapy. Suboptimal 25(OH)D₃ levels in the majority of the participants highlight the relevance of monitoring in this vulnerable population.     

Hyposomatomedinemia in the nursing home patient

Plasma somatomedin C (SmC) concentration was compared in three groups of men: 58 healthy independent men aged 26 to 45 years; 28 independent men aged 52 to 87 years; and 50 male nursing home residents aged 51 to 95 years. Somatomedin C (mean +/- SE) was 0.73 +/- .04 U/mL, 0.41 +/- .03 U/mL, and 0.33 +/- .03 U/mL in these three groups, respectively (P less than .05 for the differences between all three groups). Somatomedin C less than 0.25 U/mL, a range consistent with severe growth hormone deficiency in children, occurred in 0% of the independent younger men, in 15% of the independent elderly, and in 37% of the nursing home men. Somatomedin C was inversely correlated with age in the independent elderly, but the excess of hyposomatomedinemia in the nursing home men was not explained by age.     

Hyponatremia in tube-fed elderly men

Previous reports have described 5-20% prevalence of hyponatremia in extended care facilities, due largely to drugs or inappropriate antidiuretic hormone secretion. In our 400 bed VA extended care facility, 15 men with organic brain syndrome (Alzheimer's, multi-infarct dementia, anoxic encephalopathy or alcoholism) currently receive Isocal via gastrostomy as the sole source of nutrition. We noted intermittent hyponatremia in about half of these patients, and conducted a chart review to investigate the cause. Mean age was 68 yr (range 46-92); tube feeding duration was 3 mo.-3 yr; 266 Na concentrations were obtained from the charts. Simultaneous with these Na analyses, one of three diets prevailed: (A) mixed foods (3-6 g Na/day) orally before gastrostomy; (B) Isocal supplemented with NaCl to give 2 g Na/day; (C) unsupplemented Isocal providing 1 g Na/day. (B) and (C) had been randomly varied by rotating physicians. Serum Na was directly related to Na intake. On (A), Na was within normal range (135-145 mEq/l) in all men. One patient was hyponatremic during diet (B). During (C), eight patients were hyponatremic. Na was less than 135 mEq/l in 40% of all samples during diet (C) and less than 130 mEq/l in 14%. Changing from diet (A) or (B) to diet (C) caused nearly equivalent declines in Na and Cl; K and HCO-3 were unaffected. No hyponatremic patient took drugs known to cause hyponatremia, or had congestive heart failure, hypoalbuminemia, lipemia or fasting hyperglycemia. At the end of the study, four hyponatremic men were changed from (C) to (B); serum Na became normal in all four patients, without edema or hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)     

Disulfiram generates a stable N,N-diethylcarbamoyl adduct on Cys-125 of rat hemoglobin beta-chains in vivo

Disulfiram (DSF) is a drug used in aversion therapy to treat alcoholics and acts by inhibiting mitochondrial low-K(m) aldehyde dehydrogenase. Investigations into the mechanisms for in vivo inactivation suggest that the DSF metabolite S-methyl-N, N-diethylthiocarbamate sulfoxide reacts irreversibly with an active site Cys. This work aimed to determine if DSF generates monothiocarbamate adducts on cysteine residues in vivo by examining hemoglobin. Sprague-Dawley rats were treated with DSF po for 2, 4, and 6 weeks. Rats have four different globin beta-chains, of which three (beta-1-3) contain two cysteine residues each. MALDI-TOF MS analysis of two new globin species from DSF-treated rats collected by HPLC revealed increments of 99 Da above the mass of the unmodified chains (beta-2 and beta-3). In a separate experiment, the globin mixture was digested for 2 h with Glu-C and reanalyzed by MALDI-TOF MS. Results showed a peptide at m/z 2716.3 having a mass 99 Da higher than a known Cys-containing peptide. Subsequently, the Glu-C digest was analyzed using Q-TOF tandem MS, enabling observation of the +4 charge state of the peptide with m/z 2716.3. This peptide was fragmented to produce y-sequence ions that located the modification to Cys-125 (present on both beta-2 and beta-3). Cys-125 is the most reactive of two cysteine residues on these beta-chains. To confirm the structure of the modification, globin was hydrolyzed with 6 N HCl at 110 degrees C for 18 h. The adduct survived these conditions so that S-(N,N-diethylcarbamoyl)cysteine was detected in the hydrolysates of treated rats on the basis of comparison with the tandem MS spectrum of a standard. These results extend the findings of others obtained using glutathione conjugates and demonstrate the ability of DSF to covalently modify Cys residues of proteins in a manner consistent with the production of S-methyl-N, N-diethylthiocarbamate sulfoxide, or sulfone, intermediates.     

Reducing under-five mortality through Hôpital Albert Schweitzer's integrated system in Haiti

BACKGROUND: The degree to which local health systems contribute to reductions in under-five mortality in severely impoverished settings has not been well documented. The current study compares the under-five mortality in the H?pital Albert Schweitzer (HAS) Primary Health Care Service Area with that for Haiti in general. HAS provides an integrated system of community-based primary health care services, hospital care and community development. METHODS: A sample of 10% of the women of reproductive age in the HAS service area was interviewed, and 2390 live births and 149 child deaths were documented for the period 1995-99. Under-five mortality rates were computed and compared with rates for Haiti. In addition, available data regarding inputs, processes and outputs for the HAS service area and for Haiti were assembled and compared. RESULTS: Under-five mortality was 58% less in the HAS service area, and mortality for children 12-59 months of age was 76% less. These results were achieved with an input of fewer physicians and hospital beds per capita than is available for Haiti nationwide, but with twice as many graduate nurses and auxiliary nurses per capita than are available nationwide, and with three cadres of health workers that do not exist nationwide: Physician Extenders, Health Agents and Community Health Volunteers. The population coverage of targeted child survival services was generally 1.5-2 times higher in the HAS service area than in rural Haiti. DISCUSSION: These findings support the conclusion that a well-developed system of primary health care, with outreach services to the household level, integrated with hospital referral care and community development programmes, can make a strong contribution to reducing infant and child mortality in severely impoverished settings.