Analytical and numerical modelling of Newtonian and non-Newtonian liquid in a rotational cross-flow MBR.

Fouling is the main bottleneck of the widespread use of MBR systems. One way to decrease and/or control fouling is by process hydrodynamics. This can be achieved by the increase of liquid cross-flow velocity. In rotational cross-flow MBR systems, this is attained by the spinning of, for example, impellers. Validation of the CFD (computational fluid dynamics) model was made against laser Doppler anemometry (LDA) tangential velocity measurements (error less than 8%) using water as a fluid. The shear stress over the membrane surface was inferred from the CFD simulations for water. However, activated sludge (AS) is a non-Newtonian liquid, for which the CFD model was modified incorporating the non-Newtonian behaviour of AS. Shear stress and area-weighted average shear stress relationships were made giving error less that 8% compared with the CFD results. An empirical relationship for the area-weighted average shear stress was developed for water and AS as a function of the angular velocity and the total suspended solids concentration. These relationships can be linked to the energy consumption of this type of systems.

Use of serum amyloid A and other acute phase reactants to monitor the inflammatory response after castration in horses: a field study.

REASONS FOR PERFORMING THE STUDY: Early recognition of excessive inflammation and infectious complications after surgery, leading to early institution of therapy, reduces post operative discomfort and facilitates recovery. Because serum amyloid A (SAA) is a highly sensitive marker of inflammation, measurements of SAA and other acute phase reactants in the equine surgical patient may be valuable in assisting clinical assessment of post operative inflammation. OBJECTIVES: To investigate changes in inflammatory markers after castration and to correlate levels of acute phase reactants with clinical severity of inflammation after castration. METHODS: Leucocyte numbers and blood levels of iron, SAA and fibrinogen were determined before castration and on Days 3 and 8 post operatively in 2 groups of horses; Group 1 (n = 11) had mild post operative inflammation and an uncomplicated recovery and Group 2 (n = 7) had local clinical signs of moderate to severe inflammation. RESULTS: Both groups had elevated serum SAA levels at Day 3 post operatively. In Group 1 concentrations had returned to preoperative levels by Day 8, whereas in Group 2 concentrations remained elevated. Plasma fibrinogen concentrations in serum increased to equal levels in both groups and stayed elevated throughout the study period. Serum iron concentrations of Group 1 did not change in response to castration, whereas concentrations in Group 2 decreased below preoperative levels on Day 8. Leucocyte numbers remained unchanged during the post operative period in both groups. CONCLUSIONS: Serum SAA and iron profiles reflected the course of inflammation and their levels correlated with the clinical severity of inflammation. In contrast, fever and changes in leucocyte numbers, which are usually considered to be hallmarks of inflammation and infection, were not useful for monitoring post operative recovery. POTENTIAL RELEVANCE: Measurements of SAA and iron may improve post operative monitoring. As sustained inflammation may indicate that the surgical wound has become infected, SAA and iron measurements may facilitate early recognition and hence early treatment of infection.

Elimination of mange mites Sarcoptes scabiei var. suis from two naturally infested Danish sow herds using a single injection regime with doramectin.

Attempts to eliminate Sarcoptes scabiei var. suis were made in 2 naturally infested sow herds, by intramuscular (i.m.) injection of doramectin (Dectomax, Pfizer, New York, USA). A single injection strategy was used. In one of the herds, the environment was treated with an acaricide following dry cleaning of floors, walls and equipment. In the second herd, no environmental treatment was performed. Results were measured by skin lesion scoring, ear scrapings to show Sarcoptes scabiei var. suis, and calculating rubbing index throughout the observation period of 20 months following treatment. Skin lesion scores decreased and stayed low following treatment for the entire observation period. Live Sarcoptes scabiei var. suis mites were isolated prior to treatment from both herds, but not following treatment. Rubbing index decreased following treatment, but was occasionally at or above 0.4. The results of these studies indicate that elimination of Sarcoptes scabiei var. suis from 2 naturally infested herds was successful, using doramectin in a single injection strategy. Precautions must be taken to ensure adequate dosing of every pig, and to avoid reinfestation due to poor biosecurity.

Allelic loss detected on chromosomes 8, 10, and 17 by fluorescence in situ hybridization using single-copy P1 probes on isolated nuclei from paraffin-embedded prostate tumors.

We have implemented a reliable new technique for preparing isolated prostate cancer nuclei from paraffin-embedded tissue sections followed by analysis with single-copy fluorescence in situ hybridization (FISH). Our initial validation is described by comparison of our data with fresh prostate tumor tissue and loss of heterozygosity (LOH) studies. We also describe evaluation of 36 previously unstudied prostate cancer patients. Fifteen archival samples were selected from patients who underwent radical prostatectomy in which direct FISH and LOH data were available. Isolated nuclei were prepared and allelic loss was detected on 17q using a single-copy DNA (P1 phage) probe by FISH. A high (80%) concordance was found when comparing isolated nuclei data with 17q results from fresh preparations and LOH studies. We also examined loss at sites on 8p, 10q, and 17q in samples from 36 patients for whom clinical information was available. Loss was found at any of the three loci in 32/36 (89%) of the specimens with specific loss in 53% of the cases at the 8p locus, 33% at the 10q locus, and 61% at the 17q locus. Studies indicate that, as well as providing potential clinical information, isolated nuclei preparations are as reliable as fresh tissue for single-copy FISH studies.

Prevention of chronic radiation enteropathy by dietary glutamine.

BACKGROUND: Nearly 50% of all cancer patients receive therapeutic radiation during the course of their disease. The risk of late complications is the main dose-limiting factor in the delivery of radiation therapy. The small intestine, the major site of chronic radiation enteropathy, is also the principal organ of glutamine consumption. We therefore hypothesized that the provision of supplemental glutamine may have a protective effect on the development of chronic radiation enteropathy. METHODS: This study evaluated the effects of supplemental oral glutamine on the development of chronic radiation (XRT) enteropathy. After scrotalization of a loop of small intestine, rats were randomized to receive 1 g/kg/day glutamine (GLN) or glycine (GLY) by gavage. After 2 days of prefeeding, rats were randomized to 1 of 4 groups: GLN + XRT (n = 10), GLY + XRT (n = 10), GLN only (n = 10), GLY only (n = 10). Twenty Gy was delivered to the scrotalized bowel in the GLN + XRT and GLY + XRT groups via a collimated beam. Gavage was continued for 10 days. Animals were then pair-fed chow. Rats were killed at 2 months postirradiation. Chronic radiation injury was assessed microscopically. RESULTS: Injury scores in GLN + XRT were similar to those of unirradiated bowel and significantly different from GLY + XRT (1.89 +/- 0.48 in XRT + GLN vs. 6.42 +/- 1.55 in the XRT + GLY, p < 0.01). Elevated Injury Scores in the XRT + GLY group correlated with gross thickening and fibrosis, a 10-fold decrease in gut GLN extraction (1.40 +/- 4.3% in GLY + XRT vs. 16.0 +/- 5.1% in GLN + XRT, p < 0.05), and a 30% decrease in glutathione content (2.46 +/- 0.19 and GLY + XRT vs. 3.17 +/- 0.17 GLN + XRT, p < 0.05). CONCLUSIONS: Provision of GLN during abdominal/pelvic XRT may prevent XRT injury and decrease the long-term complications of radiation enteropathy.

Effect of supplemental dietary glutamine on methotrexate concentrations in tumors.

This study evaluated the effects of supplemental dietary glutamine (GLN) on methotrexate sodium concentrations in tumors and serum of sarcoma-bearing rats following the initiation of methotrexate. After randomization to a GLN diet (+GLN) or GLN-free diet (-GLN), tumor-bearing rats received 20 mg/kg of methotrexate sodium by intraperitoneal injection. The provision of supplemental GLN in the diet increased methotrexate concentrations in tumor tissues at 24 and 48 hours (38.0 +/- 0.20 nmol/g for the +GLN group vs 28.8 +/- 0.10 nmol/g for the -GLN group and 35.6 +/- 0.18 nmol/g for the +GLN group vs 32.5 +/- 0.16 nmol/g for the -GLN group, respectively). Arterial methotrexate levels were elevated only at 48 hours (0.147 +/- 0.007 microns/L for the +GLN group vs 0.120 +/- 0.006 microns/L for the -GLN group). Tumor morphometrics were not different between the groups but significantly greater tumor volume loss was seen even at 24 hours (-2.41 +/- 1.3 cm3 for the +GLN group vs -0.016 +/- 0.9 cm3 for the -GLN group). Tumor glutaminase activity was suppressed in both groups at 48 hours, but more so in the +GLN group (0.94 +/- 0.13 mumol/g per hour for the +GLN group vs 1.47 +/- 0.22 mumol/g per hour for the -GLN group). This study suggests that GLN may have therapeutic as well as nutritional benefit in oncology patients.

Role of tumor necrosis factor in oxygen toxicity.

mRNA from lungs of mice exposed to high-dose oxygen (greater than 95%) for 3 days demonstrated increased expression of the genes for tumor necrosis factor (TNF), interleukin-1, and interleukin-6 compared with mRNA from lungs of mice exposed to room air. Daily treatment of mice exposed to high-dose oxygen with an antibody to TNF improved survival compared with mice receiving a similar dose of control immunoglobulin G. Pretreatment of mice with repetitive sublethal intraperitoneal doses of recombinant human TNF for 3 days or a single intravenous dose followed by exposure to high-dose oxygen afforded a significant survival advantage compared with high-dose oxygen-exposed mice pretreated with vehicle or interleukin-1. The repetitive intraperitoneal TNF pretreatment reduced the development of interstitial pneumonitis, pulmonary edema, and lung weight gain associated with oxygen toxicity and enhanced expression of the gene for the free radical protective enzyme manganous superoxide dismutase in lung tissue, a gene that is augmented as mice are exposed to high-dose oxygen. Furthermore a single intravenous dose of TNF 24 h after oxygen exposure was still protective. The results suggest that the toxicity of oxygen therapy can be partially ameliorated by either treatment with anti-TNF antibody or pretreatment and early treatment with TNF. These findings are consistent with the hypothesis that oxygen exposure induces TNF, which causes part of the toxicity of high-dose oxygen, and that pretreatment or early treatment with TNF induces the gene for an enzyme that recently has been shown to be very effective in protecting mice from the toxicity of oxygen.

Biomonitoring of genotoxic exposure among stainless steel welders.

A biosurvey in the Danish metal industry measured the genotoxic exposure from stainless steel welding. The study comprised measurements of chromosomal aberrations (CA), sister-chromatid exchanges (SCE), unscheduled DNA synthesis (UDS) in peripheral lymphocytes and serum immunoglobulin G. Environmental monitoring of welding fumes and selected metal oxides, biomonitoring of chromium and nickel in serum and urine and mutagenic activity in urine, and evaluation of semen quality were also done. Manual metal arc (MMA) welding and tungsten inert gas (TIG) welding were the dominant welding processes. A higher frequency of chromosomal aberrations, classified as translocations, double minutes, exchanges and rings, was observed in stainless steel welders than in non-welders. SCE was lower in welders working with both MMA and TIG welding than in reference persons. N-Acetoxy-N-acetylaminofluorene (NA-AAF)-induced UDS was lower in 23 never-smoking welders than in 19 unexposed never-smokers. Smoking was a confounding factor resulting in significantly higher CA, SCE, NA-AAF binding to DNA and mutagenic activity in urine. Age was also a confounder: CA, SCE, NA-AAF binding to DNA and UDS increased significantly with age. No significant correlation between SCE and CA or between CA and UDS was found. UDS decreased significantly with increasing lymphocyte count and a higher lymphocyte count was seen in MMA welders than in reference persons and in smokers than in non-smokers. Differences in the composition among lymphocytes in exposed persons compared with non-exposed are suggested. MMA welding gave the highest exposure to chromium, an increased number of chromosomal aberrations and a decrease in SCE when compared with TIG welding. Consequently improvements in the occupational practice of stainless steel welding with MMA is recommended.

Hormonal regulation of inflammatory cell cytokine transcript and bioactivity production in response to endotoxin.

Tumor necrosis factor (TNF), interleukin 1 (IL-1) and interleukin 6 (IL-6) are central mediators of the inflammatory response. We investigated the modulation of these cytokines by hormones in vitro. Murine adherent peritoneal exudate cells (PEC) were exposed to various concentrations of hormones followed by lipopolysaccharide (LPS, 10 micrograms/ml). TNF, IL-1 and IL-6 production were assessed by bioassays, enzyme-linked immunosorbent assays (ELISA) or Western blot, and specific RNA transcripts by Northern blot. Hydrocortisone in concentrations as low as 10 ng/ml had dramatic inhibitory effects on supernatant levels of TNF and IL-1 and on TNF, IL-1 and IL-6 transcript number. Supernatant levels of IL-6 were only slightly diminished by hydrocortisone. Adrenocorticotrophic hormone (ACTH) and insulin increased supernatant levels of TNF bioactivity in response to LPS, while each decreased available TNF-alpha gene transcripts. Thus TNF protein production was affected at a post-transcriptional level. ACTH and insulin increased supernatant levels of IL-6 produced in response to LPS without altering available transcripts. Corticotrophin-releasing factor (CRF), epinephrine and glucagon had no effect on supernatant levels of cytokine. Thus, physiological and pharmacological concentrations of hydrocortisone had dramatic inhibitory effects on the supernatant levels of TNF and IL-1, and on the number of available TNF, IL-1 and IL-6 transcripts in PEC exposed to LPS, but had minimal effects on supernatant levels of IL-6 bioactivity. This hydrocortisone action may be a specific negative feedback system for IL-1 and TNF, with relative sparing of IL-6.

Genotoxicity of acrylic bone cements.

The genotoxicity of conventional polymethylmethacrylate (PMMA) and a new formulation of bone cement: methylmethacrylate/n-decylmethacrylate/isobornylmethacrylate (MMA/DMA/IBMA) were tested by micronucleus test and reverse mutation assays of Salmonella typhimurium (Ames test). In extracts from cement pellets (37 degrees, 72 hr) with water and water/ethanol the concentration of MMA was reduced by 13-19 times with the new formulation and the concentrations of accelerators were reduced by 4-5 times. New chemical constituents (DMA, IBMA, dihydroxy-propyl-p-toluidine) were found in negligible concentrations. In the micronucleus test all three cement brands were found non-mutagenic and in the Ames test scattered increased revertant ratios were found without differences between the three brands. The new formulation does not possess any increased risk of genotoxicity.

Single-dose tumor necrosis factor protection against endotoxin-induced shock and tissue injury in rats.

Tumor necrosis factor (TNF), a macrophage product released in response to endotoxin and other stimuli, has been shown to be a central mediator of endotoxin or septic shock. However, its highly conserved and wide-ranging physiological effects suggest that it may also be an essential cytokine in the host defense against acute bacterial infection or sepsis. A single nontoxic dose of human recombinant TNF administered intravenously 24 h prior to a lethal infusion of Escherichia coli lipopolysaccharide (LPS) completely prevented acute LPS-induced hypotension, ameliorated tissue injury in the lungs and liver, and improved survival in male Fisher 344 rats. The protective effects of TNF were dose dependent and required a 24-h pretreatment interval. After the infusion of LPS, animals in both groups (TNF-treated animals and saline-pretreated controls) initially appeared acutely ill and had a similar severe metabolic acidosis, indicating that TNF did not inactivate or prevent the toxic effects of LPS. Twelve hours after the administration of TNF, the gene for manganous superoxide dismutase, a mitochondrial enzyme which scavenges toxic reactive oxygen species and is induced during conditions which generate a free radical stress, was expressed in liver tissue, suggesting that the induction of manganous superoxide dismutase may be an important in vivo protective mechanism against cellular injury during lethal endotoxemia.

Pentoxifylline suppression of tumor necrosis factor gene transcription.

Pentoxifylline decreases lung injury after intravenous endotoxin; the mechanism is unknown. Tumor necrosis factor-alpha (TNF) is secreted by macrophages in response to endotoxin and mediates some of the toxicity of endotoxin. This study investigates the effects of pentoxifylline on endotoxin-stimulated TNF production in vitro and in vivo. Pentoxifylline concentrations of 100 and 1000 micrograms/ml inhibited TNF production by murine adherent peritoneal exudate cells incubated with endotoxin 1 microgram/ml. Similarly, pentoxifylline at 100 and 1000 micrograms/ml decreased the number of available TNF messenger RNA transcripts in peritoneal exudate cells assessed by Northern blot. Pentoxifylline had no effect on TNF mRNA stability, but appeared to act by inhibiting the rate of TNF mRNA production (transcription). In murine in vivo experiments at each dose of endotoxin administered from 0.01 to 30 mg/kg, pentoxifylline treatment significantly reduced serum TNF levels, suggesting a favorable shift of the endotoxin dose-response curve. Expression of murine TNF gene in the livers of these animals showed fewer TNF transcripts in the pentoxifylline-treated animals compared to controls. Pentoxifylline inhibited endotoxin-induced TNF production both in vivo and in vitro and exerted this control by inhibiting endotoxin-induced transcription of the TNF gene. This study suggests that pentoxifylline may ameliorate endotoxic shock by decreasing macrophage TNF production.

Treatment with recombinant human tumor necrosis factor-alpha protects rats against the lethality, hypotension, and hypothermia of gram-negative sepsis.

Tumor necrosis factor (TNF) is a peptide secreted by macrophages in response to endotoxin that can produce many of the changes seen in septic shock. After cecal ligation and puncture (CLP) rats gradually develop tachycardia, hypotension, tachypnea, and hypothermia. At 5 h post-CLP, rats have a peak in serum levels of endotoxin and 60% of rats have blood cultures that grow Gram-negative rods (Escherichia coli and Klebsiella pneumonia). At 20 h post-CLP all rats develop positive blood cultures. Serum levels of TNF are not reproducibly measurable in rats following CLP. Rats undergoing CLP have a 50-80% mortality with deaths usually occurring 24-72 h postinjury. Repetitive (twice daily x 6 d) i.p. injection of sublethal doses of recombinant human TNF-alpha (100 micrograms/kg) to rats undergoing CLP 1 d after the treatment period resulted in a significant reduction in mortality compared to control rats previously unexposed to rTNF (P less than 0.03). Animals treated with rTNF had no hypotension or hypothermia after CLP and regained normal food intake faster than control rats. 12 h after CLP the gene expression for manganous superoxide dismutase (MnSOD), an inducible mitochondrial metalloenzyme responsible for cellular resistance to injury from toxic reactive oxygen species, was higher in livers of rats treated with rTNF suggesting that the TNF treatment augmented expression of this protective enzyme. Unlike MnSOD, expression of the gene for copper-zinc SOD was not affected by CLP or rTNF treatment. The results suggest that prior treatment with recombinant TNF can ameliorate the lethality, hypotension, hypothermia, and anorexia of Gram-negative sepsis in rats and that the mechanism may be related to enhanced hepatic expression of the gene for MnSOD. Repeated administration of recombinant TNF may be a strategy to minimize mortality and morbidity of Gram-negative sepsis.

A report of familial carotid body tumors and multiple extra-adrenal pheochromocytomas.

A case of familial carotid body tumors and multiple extra-adrenal pheochromocytomas is reported. The carotid body tumors, resected previously, were bilateral and associated with 4 intra-abdominal extra-adrenal pheochromocytomas. Magnetic resonance imaging was far superior to computerized tomography and 131iodine-metaiodobenzylguanidine in visualizing the intra-abdominal lesions, and may soon become the imaging technique of choice in the evaluation of patients with suspected pheochromocytoma.

Recurrent or metastatic disease in select patients with adrenocortical carcinoma. Aggressive resection vs chemotherapy.

In a retrospective, nonrandomized comparison of patients with first recurrence of adrenocortical cancer, 18 patients were treated with chemotherapy (primarily mitotane) and 15 patients were treated with surgical resection plus similar chemotherapy. Surgical resection of recurrent adrenocortical cancer was often extensive, with morbidity in 20% of patients and no mortality. Mitotane therapy was ineffective at controlling tumor growth. Median survival from the time of diagnosis for all patients was only 23 months and no patient was cured. Disease-free interval greater than 12 months was associated with prolonged survival, but it only occurred in six patients (18%), with a similar frequency in both treatment groups. Surgical resection of recurrent disease was associated with prolonged survival from the time of first recurrence. The potential benefit of this resection was evident in the 5 patients (33%) who were able to live greater than 5 years from the time of first recurrence with improvement in symptoms and signs of hypercortisolism. Although no patient with recurrent adrenal cancer could be cured, resection of recurrent disease was associated with a slight prolongation of survival and good palliation of Cushing's syndrome.

Parotid salivary flow rates in two patients during immediate denture treatment.

Parotid salivary flow rates in response to chewing or citric acid stimulation were studied in two patients who had their last maxillary teeth extracted and immediately replaced with complete dentures. The patients were monitored 6 months from the last week before extraction. Parotid salivary flow rate in response to chewing was increased after insertion of the denture. For one of the patients a particularly high output from the parotid gland was found 2 weeks after treatment. Throughout the experiment, parotid salivary flow was higher on the chewing side than on the contralateral side. At the end of the experimental period the dentures were relined. Salivary flow measured immediately after relining was lower than prior to this procedure. An increased salivary response was also observed during citric acid stimulation after transition from the dentate to the denture wearing state. This increase was more marked if the patients had their dentures in situ when the gustatory provocations were performed. It is concluded that parotid salivation increases during masticatory and gustatory stimulation in patients subjected to total extraction and immediate complete denture treatment, and that the presence of a complete denture per se appears to act as an additional mechanical stimulus in the salivary reflexes.

Effect of high hematocrit and high blood flow rates on transmembrane pressure and ultrafiltration rate in hemodialysis.

Removal of prescribed ultrafiltration volumes in hemodialysis requires knowledge of both the ultrafiltration coefficient of the dialyzer and the average transmembrane pressure (TMP) in the dialyzer. While it has been a fairly common practice to assume that the TMP is constant along the length of the dialyzer, it actually decreases linearly from a maximum value at the blood inlet to a minimum value at the blood outlet. In the past, ignoring the difference between arterial and venous TMPs when calculating the dialysate pressure setting did not result in significant errors in ultrafiltration volume. However, with the introduction of erythropoietin therapy and the trend toward high-efficiency dialysis, increases in hematocrit and blood flow rate have led to axial variations in TMP which, if ignored, can lead to inaccurate fluid removal. The goals of this paper are to provide an understanding of how high hematocrits and high blood flow rates affect TMP and ultrafiltration rate, and to provide simple guidelines for ensuring accurate fluid removal. Sample calculations are given on the last page for easy reference.

Lactic acidosis increases tumor necrosis factor secretion and transcription in vitro.

Lactic acid has been shown to affect numerous biologic processes. We investigated the role of lactic acidosis as a signal for the production of TNF by macrophages in vitro. Male F344 rats were administered thioglycolate media intraperitoneally. Macrophages were recovered 7 days later, cultured for 24 hr in complete media (CM), or CM with L-lactic acid (5, 10, or 15 mM), or with endotoxin (LPS) (10 micrograms/ml). TNF levels were measured in the supernatants. Female C57BL/6 mice were similarly treated, and macrophages were harvested and cultured in CM or CM containing lactic acid (15 mM), or LPS (10 micrograms/ml). RNA was extracted after 24 hr, separated by electrophoresis, and transferred to nitrocellulose. Human 32P-cDNA TNF and actin probes were used to determine relative TNF gene expression. Gel densitometry was used to calculate the TNF expression index (EI) in lactic acid and LPS treated cells as described. pH levels of the supernatant indicated that increasing concentrations of lactic acid caused increasing acidosis. Trypan blue exclusion demonstrated that lactic acidosis did not reduce cell viability. LPS significantly increased secretion of TNF relative to control (P less than 0.001). Each concentration of lactic acid significantly increased TNF secretion (P less than 0.05), but not in a dose-dependent manner. TNF gene transcription was elevated in macrophages cultured with lactic acid and LPS relative to control (EI = 1.13 and 1.18, respectively). This suggests that lactic acid concentration can regulate TNF secretion at the level of transcription, and is consistent with the hypothesis that local levels of lactic acid (lactic acidosis) may be a regulator of cytokine secretion.