Microbiologically documented infections in patients undergoing high-dose melphalan and autologous stem cell transplantation for the treatment of light chain amyloidosis.

BACKGROUND: Immunoglobulin light chain (AL) amyloidosis can be treated with high-dose melphalan and autologous stem cell transplantation (HDM/SCT). Risk factors for infections may include hyposplenism, hypogammaglobulinemia, treatment-related neutropenia, melphalan-induced mucositis, and nosocomial exposures. METHODS AND DESIGN: A review of 493 patients with AL amyloidosis undergoing treatment with HDM/SCT from August 1994 to August 2009 was performed. The objectives were to determine the rate and types of infections following HDM/SCT, to identify factors associated with microbiologically documented infections, and to assess the contribution of infections to all-cause treatment-related mortality (TRM; defined as deaths within 100 days of SCT). RESULTS: Microbiologically documented infections after HDM/SCT occurred in 24% (n = 119) of patients. TRM was 10% (n = 48) overall, and 21% (n = 25) in patients who had a documented infection. Thus, the relative risk of TRM in a patient with a documented infection was 3.42 (95% confidence interval [CI] 2.02-5.79). Infections were caused by gram-positive bacteria in 51%, anaerobic bacteria in 16%, gram-negative bacteria in 13%, and fungi in 9% of cases. Serum creatinine >2 mg/dL was associated with increased risk of post-SCT infection (38% vs. 21%, P = 0.0007) with an odds ratio of 2.27 (95% CI 1.40-3.68). No significant association for infection was found for age, gender, cardiac involvement, prior steroid therapy, dose of melphalan, multiorgan involvement, days to neutrophil engraftment, or dose of CD34 +  cells infused. CONCLUSION: Serum creatinine >2 mg/dL is a risk factor for infections in patients with AL amyloidosis undergoing HDM/SCT. The relative risk of TRM in a patient with a documented infection was increased >3-fold. A broad spectrum of infections, similar to that in other SCT patients, is seen in this population in the early post-SCT period.

Características do ejaculado de caprinos sob estresse calórico em câmara bioclimática / Sperm characteristics of bucks under heat stress in climatic chamber

Para verificar o efeito do estresse calórico (EC) na produção espermática de caprinos, oito machos das raças Saanen (n=4) e Pardo-Alpina (n=4) foram mantidos em câmara bioclimática, sob condições de termoneutralidade (13,0°C a 26,7°C) durante 30 dias e, após um período (60 dias) de descanso, submetidos ao EC (23,7°C a 34,0°C) por mais 30 dias. Para minimizar as variações sazonais na produção espermática, durante todo o período, o fotoperíodo foi controlado utilizando-se alternância de dias longos (16 horas de luz e 8 horas de escuro) e de dias curtos (8 horas de luz e 16 horas de escuro) a cada 30 dias. Avaliaram-se as temperaturas retal e testicular, o volume do ejaculado, a concentração espermática, as motilidades massal e individual progressiva (MIP), o vigor e a morfologia espermática. Houve aumento (P<0,05) da temperatura do testículo (31,0±1,1 vs. 32,8±0,9°C) e decréscimos (P<0,01) do volume (0,6±0,3 vs. 0,4±0,3ml), da concentração espermática (5,1±1,8 vs. 4,5±1,5 x10(9)), da motilidade massal (3,5±0,5 vs. 2,9±0,5), da MIP (67,4±14,3 vs. 53,3±13,1 por cento) e do vigor (3,5±0,6 vs.3,0±0,6) quando os animais foram submetidos ao EC. O EC não influenciou (P>0,05) o percentual total de células anormais e nem a temperatura retal. Os machos da raça Saanen apresentaram temperaturas do testículo e retal mais elevadas (P<0,01) e produziram maior volume (P<0,05) de ejaculado. O estresse calórico produzido em câmara bioclimática foi suficiente para afetar, negativamente, algumas características quanti-qualitativas do ejaculado de machos caprinos das raças Saanen e Pardo-Alpina.

To verify the effect of heat stress (HS) on caprine semen production eight male goats of Saanen (n=4) and Alpine Brown (n=4) breeds were kept in climate chamber under thermal neutral conditions (13.0°C to 26.7°C) for 30 days. After a resting period (60 days), the same bucks were submitted to heat stress (23.7°C to 34.0°C) for another 30 days. To neutralize the seasonal variations of sperm production throughout the period, the photoperiod was controlled every 30 days alterning long days (16 hours of light and 8 hours of darkness) and short days (8 hours of light and 16 hours of darkness). The following variables were evaluated: rectal and testicular temperatures, volume of ejaculate, sperm concentration, mass motility, individual progressive motility, vigor and sperm morphology. There was an elevation (P<0.01) of testicular temperature (31.0±1.1 vs. 32.8±0.9°C) and a decline of volume (0.6±0.3 vs. 0.4±0.3ml), sperm concentration (5.1±1.8 vs. 4.5±1.5x10(9)), mass motility (3.5±0.5 vs. 2.9±0.5), individual of progressive motility (67.4±14.3 vs. 53.3±13.1 percent) and vigor (3.5±0.6 vs.3.0±0.6) after HS treatment. There was no effect of HS (P>0.05) on percentage of morphologically normal spermatozoa and rectal temperature. The Saanen males showed higher testicular and rectal temperatures and produced more sperm volume than Alpine Brown males. The HS in climate chamber was sufficient to negatively affect some semen characteristics of Saanen and Alpine Brown male goats.

Adaptive effects of dietary ethanol in the pig: changes in plasma high-density lipoproteins and fecal steroid excretion and mutagenicity.

Six young mature male pigs were maintained on a high fat, low fiber "Western" type diet. Substitution of ethanol for sucrose raised plasma total cholesterol, an increase that was solely due to a rise in high-density lipoproteins. Plasma triacylglycerols and apo-B concentrations were unchanged and although apo-A1 rose with ethanol, this was not statistically significant. Ethanol did not alter total fecal steroids but both bile acids and the ratio of bile acids/neutral sterols were increased. In fecal extracts from these animals, mutagenic activity in the Ames bacterial test was also raised. The data are discussed in relation to the relationships between dietary ethanol and coronary heart disease and colorectal cancer.

Noise-induced hearing loss and stress-prone behavior.

Previous research found a relationship between stress-prone personality (pattern A) and noise-induced vasoconstriction in normal-hearing adult subjects. The present research sought evidence for a possible relationship between susceptibility to high-frequency noise-induced permanent threshold shift (NIPTS) found among industrial workers and the vasoconstrictive behavior of the same workers when they were exposed to high-intensity noise. It was hypothesized that pattern A workers would show more vasoconstriction in the presence of high-intensity noise, and hence more susceptibility to NIPTS, than pattern B (non-stress-prone) workers. The 35 male subjects tested were divided into two groups. Group 1 contained 16 subjects who showed significant vasoconstriction in noise; group I subjects were clearly pattern A types. Group II contained 19 subjects who did not show significant vasoconstriction in noise; Group II contained mostly pattern B but a few pattern A subjects. Unexpectedly, it was the group II subjects who showed the most susceptibility to NIPTS; the difference between the means of the two groups was statistically significant (p greater than or equal to 0.001). The explanation for this unexpected finding is obscure.

Mutagen production during pan-broiling compared with microwave irradiation of beef.

Segments of beef were cooked either by broiling on a hot plate or by irradiation at 2450 MHz in a microwave oven. Extracts of surface layers of the cooked meat were tested for mutagenic activity using Salmonella typhimurium TA98 and TA100 with and without S-9 liver microsomal preparation. The broiled beef extracts with S-9 activation exhibited marked frame-shift mutagenicity, which increased with cooking time. No such activity was detected with beef cooked by microwave irradiation, with exposures ranging from normal to 3 times the normal cooking period.

Induction of DNA repair by some selenium compounds.

Selenium compounds were found to induce DNA repair synthesis as a measure of DNA damage in both the isolated rat liver cell system and by Ames' Salmonella assay. In liver cells, DNA repair measured by uptake of [3H]thymidine was found to be greater with sodium selenite and selenate than with selenomethionine. In the bacterial culture system, selenomethionine inhibited the repair-deficient variant more than the selenite and selenate. These in vitro test systems have been used to indicate that selenium has a DNA-damaging potential.

The effect of molybdenum on the conversion of sulphate to sulphide and microbial-protein-sulphur in the rumen of sheep.

1. [35S]sulphate was used to measure the apparent turnover of sulphate, sulphide and microbial-protein-S in the rumen contents of four sheep that were intraruminally infused with 10 g sodium sulphate/d alone, or together with 126 mg sodium molybdate (50 mg molybdenum). 2. Infusion of molybdate increased the concentration of sulphate in rumen fluid from 2.2 to 7.2 mug S/ml and decreased the rate of reduction of sulphate to sulphide by 50%. Although the rate of sulphide production was slower, the concentration of sulphide in the rumen is suggested to explain these changes. 3. In animals that were not infused with molybdate, only one-third of the S (3.0 g/d) that passed through the sulphate pool in rumen fluid was converted to sulphide, decreasing to one-sixth when molybdate was infused. 4. The turnover of S amino acids in microbial protein was not significantly affected by molybdate. Only 52-57% of the S amino acid content of microbial protein was synthesized de novo by way of the sulphide pool.

Metabolic fate of cysteine and methionine in rumen digesta.

Estimates were obtained of the extent to which cysteine and methionine were incorporated into the protein of the microbes of rumen digesta without prior degradation and resynthesis. By using the amino acids labeled with both (35)S and (14)C, it was observed that a large proportion of the (35)S appeared in the sulfide pool and of the (14)C appeared in volatile fatty acids. By isolating the appropriate amino acid, obtaining the (14)C to (35)S ratio, and comparing this with the ratio in the added amino acid, the degree of direct incorporation was calculated. For cysteine it was estimated that at most 1% and for methionine, at most 11% of the amino acid in the free pool was incorporated unchanged into microbial protein. As a consequence of these findings, it is considered that the method for measuring microbial protein synthesis in rumen digesta based upon incorporation of (35)S from the free sulfide pool is not seriously affected by direct utilization of sulfur amino acids arising from dietary sources.

Method for measuring microbial growth in rumen content.

Radioactive sodium sulfide was used to label the sulfide pool of rumen contents in vitro. Microbial protein synthesis was calculated from the size and rate of dilution of label in the sulfide pool, and from the radioactivity incorporated into protein together with a conversion factor specifying the nitrogen-sulfur ratio determined for microbial protein. The microbial cell yield, calculated on the basis of the adenosine triphosphate (ATP) available from fermentation, was 13 to 14 g (dry weight) per mole of ATP, which is in good agreement with the values obtained for pure cultures of bacteria. Calculation of microbial protein yield per kilogram of ration agreed fairly well with previous estimates for similar rations.