Reversal of granulocyte adherence to nylon fibers using local anesthetic agents: possible application to filtration leukapheresis

The effects of the cationic anesthetic agents tetracaine and lidocaine on granulocyte function, morphology, and adherence to nylon fibers were studied in an attempt to improve current methods of granulocyte collection by filtration leukapheresis (FL). When dissolved in acid- citrate-dextrose (ACD) plasma, these drugs significantly increased granulocyte elution from the fibers in a dose-related fashion. Granulocytes exposed to tetracaine and lidocaine remained more than 95% viable, retained normal bactericidal capacity after the drugs were washed from the cells, and had preserved membrane integrity, as evidenced by the normal ultrastructural appearance of tetracaine- exposed cells and an absence of leakage of lysozyme or lactic dehydrogenase. Granulocytes eluted with the anesthetic agents were rounded in shape with a reduction in the number of filopodial cytoplasmic projections and a relative absence of cytoplasmic vacuolization when compared to granulocytes eluted with ACD plasma alone. Dose-related inhibition of phagocytosis and adherence, which was largely reversible after washing the granulocytes, was noted. Greater than 95% of the lidocaine could be removed from the eluate with a single centrifugation and resuspension, indicating that granulocytes prepared by FL with anesthetic-enhanced elution could be potentially transfusable.     

Fatal Hepatic Coma Complicating Oxymetholone Therapy in Multiple Myeloma

Fatal hepatic coma complicating oxymetholone therapy in multiple myeloma. G. P. Young, P. S. Bhathal, J. R. Sullivan, A. J. Wall, D. J. Fone and T. H. Hurley, Aust. N.Z. J. Med, 1977,7, pp. 47–51. Two patients with multiple myeloma died in acute liver failure. Both had been treated with the anabolic steroid oxymetholone and both subsequently developed severe cholestatic hepatitis. In one the histological lesion progressed despite cessation of oxymetholone therapy. Myeloma infiltration of the liver and peliosis hepatis were not seen. As a fatal outcome from cholestatic hepatitis due to oxymetholone is rare it is possible that an unknown potentiating factor is present in multiple myeloma that can lead to a fatal outcome. If oxymetholone therapy is to be used in such patients then close clinical and laboratory assessment of liver function should be carried out in an attempt to prevent this unusual and fatal complication.     

Modeling the progression of rheumatoid arthritis: a two-country model to estimate costs and consequences of rheumatoid arthritis

OBJECTIVE: Two simulation models were developed to analyze the cost-effectiveness of new treatments that affect the progression of rheumatoid arthritis (RA). METHODS: We used data from 2 cohorts of patients with early RA who had been followed up since disease onset (up to 15 years). In the Swedish study, 183 patients were followed up for a mean of 11.3 years. In the UK study, 916 patients were followed up for a mean of 7.8 years. Disease progression over 10 years was modeled as annual transitions between disease states, defined by Health Assessment Questionnaire (HAQ) scores. A regression model was used to estimate transition probabilities conditional on age, sex, and time since onset of disease, in order to allow simulation of different patient cohorts. Costs and utilities associated with different HAQ levels were based on data from the cohort studies and cross-sectional surveys. RESULTS: Costs increase and quality of life decreases as RA progresses. In Sweden, total annual costs range from 4,900 dollars to 33,000 dollars per patient, compared with 4,900 dollars to 14,600 dollars in the UK. Cumulative costs over 10 years for patients starting in disease state 1 (HAQ < 0.6) are 54,600 dollars in Sweden and 26,600 dollars in the UK. The cumulative numbers of quality-adjusted life-years (QALYs) are 5.5 and 5.6, respectively. Both costs and QALYs were discounted at 3%. CONCLUSION: The 2 models, which were based on different patient cohorts, reach a similar conclusion in terms of the effect of RA over 10 years. They appear to accurately capture disease progression and its effects and can therefore be useful in estimating the cost-effectiveness of new treatments in RA.     

Behavioral disturbances, not cognitive deterioration, are associated with altered food selection in seniors with Alzheimer's disease

OBJECTIVE: We previously reported alterations in circadian patterns of food intake that are associated with measures of functional and cognitive deterioration in seniors with probable Alzheimer's disease (AD). This study further explored disturbed eating patterns in AD, focusing on alterations in macronutrient (protein, carbohydrate, and fat) selection, and their association with measures of functional and behavioral losses. METHODS: Forty-nine days of food intake collections were conducted on 32 residents (26 females, 6 males; age = 88.4 +/- 4.1 years; body mass index = 24.1 +/- 4.0 kg/m(2)) with probable AD residing at a nursing home (a fully accredited geriatric teaching facility affiliated with the University of Toronto's Medical School). All residents ate their meals independently. The relationships between patterns of habitual food consumption and measures of cognitive function (Severe Impairment Battery), behavioral disturbances (Neuropsychiatric Inventory-Nursing Home Version) and behavioral function (London Psychogeriatric Rating Scale) were examined, cross-sectionally. RESULTS: Consistent with our previous studies, breakfast intakes were not predicted by any of the measures of behavioral, cognitive, or functional deterioration, although those residents with greater functional deterioration, especially disengagement, attained lower 24-hour energy intakes. The presence of "psychomotor disturbances," including irritability, agitation, and disinhibition, were strongly associated with shifts in eating patterns toward carbohydrate and away from protein, placing individuals with these conditions at increased risk for inadequate protein intakes. Between-individual differences in intake patterns could not be explained by the use of either anorexic or orexigenic medications. CONCLUSIONS: Behavioral, not cognitive, deterioration is associated with appetite modifications that increase risk of poor protein intake, perhaps indicating a common monoaminergic involvement.     

Estimating genome conservation between crop and model legume species

Legumes are simultaneously one of the largest families of crop plants and a cornerstone in the biological nitrogen cycle. We combined molecular and phylogenetic analyses to evaluate genome conservation both within and between the two major clades of crop legumes. Genetic mapping of orthologous genes identifies broad conservation of genome macrostructure, especially within the galegoid legumes, while also highlighting inferred chromosomal rearrangements that may underlie the variation in chromosome number between these species. As a complement to comparative genetic mapping, we compared sequenced regions of the model legume Medicago truncatula with those of the diploid Lotus japonicus and the polyploid Glycine max. High conservation was observed between the genomes of M. truncatula and L. japonicus, whereas lower levels of conservation were evident between M. truncatula and G. max. In all cases, conserved genome microstructure was punctuated by significant structural divergence, including frequent insertion/deletion of individual genes or groups of genes and lineage-specific expansion/contraction of gene families. These results suggest that comparative mapping may have considerable utility for basic and applied research in the legumes, although its predictive value is likely to be tempered by phylogenetic distance and genome duplication.     

Murrayafoline A Induces a G0/G1-Phase Arrest in Platelet-Derived Growth Factor-Stimulated Vascular Smooth Muscle Cells

The increased potential for vascular smooth muscle cell (VSMC) growth is a key abnormality in the development of atherosclerosis and post-angioplasty restenosis. Abnormally high activity of platelet-derived growth factor (PDGF) is believed to play a central role in the etiology of these pathophysiological situations. Here, we investigated the anti-proliferative effects and possible mechanism(s) of murrayafoline A, a carbazole alkaloid isolated from Glycosmis stenocarpa Guillamin (Rutaceae), on PDGF-BB-stimulated VSMCs. Murrayafoline A inhibited the PDGF-BB-stimulated proliferation of VSMCs in a concentration-dependent manner, as measured using a non-radioactive colorimetric WST-1 assay and direct cell counting. Furthermore, murrayafoline A suppressed the PDGF-BB-stimulated progression through G₀/G₁ to S phase of the cell cycle, as measured by [³H]-thymidine incorporation assay and cell cycle progression analysis. This anti-proliferative action of murrayafoline A, arresting cell cycle progression at G₀/G₁ phase in PDGF-BB-stimulated VSMCs, was mediated via down-regulation of the expression of cyclin D1, cyclin E, cyclin-dependent kinase (CDK)2, CDK4, and proliferating cell nuclear antigen (PCNA), and the phosphorylation of retinoblastoma protein (pRb). These results indicate that murrayafoline A may be useful in preventing the progression of vascular complications such as restenosis after percutaneous transluminal coronary angioplasty and atherosclerosis.     

Extremely Low Frequency Magnetic Field Modulates the Level of Neurotransmitters

This study was aimed to observe that extremely low frequency magnetic field (ELF-MF) may be relevant to changes of major neurotransmitters in rat brain. After the exposure to ELF-MF (60 Hz, 2.0 mT) for 2 or 5 days, we measured the levels of biogenic amines and their metabolites, amino acid neurotransmitters and nitric oxide (NO) in the cortex, striatum, thalamus, cerebellum and hippocampus. The exposure of ELF-MF for 2 or 5 days produced significant differences in norepinephrine and vanillyl mandelic acid in the striatum, thalamus, cerebellum and hippocampus. Significant increases in the levels of serotonin and 5-hydroxyindoleacetic acid were also observed in the striatum, thalamus or hippocampus. ELF-MF significantly increased the concentration of dopamine in the thalamus. ELF-MF tended to increase the levels of amino acid neurotransmitters such as glutamine, glycine and γ -aminobutyric acid in the striatum and thalamus, whereas it decreased the levels in the cortex, cerebellum and hippocampus. ELF-MF significantly increased NO concentration in the striatum, thalamus and hippocampus. The present study has demonstrated that exposure to ELF-MFs may evoke the changes in the levels of biogenic amines, amino acid and NO in the brain although the extent and property vary with the brain areas. However, the mechanisms remain further to be characterized.     

Acute esophageal necrosis after kidney transplantation: A case report

Rationale:Acute esophageal necrosis (AEN) is a rare syndrome with characteristic endoscopic and pathologic findings. It usually results from a combination of tissue hypoperfusion, impaired local defense barriers, and massive reflux of gastric contents. We report a case of AEN after a kidney transplant.Patient concerns:A 53-year-old man with hypertension and end-stage renal disease presented with abdominal pain and a single episode of hematemesis 14 days after kidney transplantation.Diagnosis:Upper endoscopy revealed circumferential black coloration in the mid to lower esophageal mucosa. Esophageal biopsy showed ulcer, and immunostains were negative for viral etiology.Interventions:Conservative management was done with total parenteral nutrition and proton pump inhibitor.Outcomes:The patient experienced no further episodes of hematemesis or abdominal pain and follow-up endoscopy showed remarkable changes from the black mucosa to a red friable mucosa with whitish exudates.Lessons:In the case, AEN occurred in the setting of normal blood pressure after major surgery despite the absence of preceding factors such as hypotension and infections. The possibility of AEN should be considered in patients with solid organ transplantation who present with abdominal pain, dysphagia, and hematemesis.