Systemic methotrexate toxicity. A pharmacological study of its occurrence after intrathecal administration in a patient with renal failure

Methotrexate pharmacokinetic studies, performed on a patient with renal impairment who had toxic effects following 20 mg/sq m of intrathecally administered methotrexate, demonstrated prolonged serum concentrations of the drug, which accounted for the condition. After the return of normal renal function, pharmacokinetic studies were repeated following the same dose and route of administration of methotrexate. On this occasion there was a rapid clearance of serum methotrexate below toxic levels.     

Studies on vesicourethral reflexes. II. Urethral sphincteric responses to spinal cord stimulation

A bipartite bladder model was developed with and without complete muscular separation in order to isolate and analyze separately sphincteric and detrusor responses. Spinal cord stimulation of the sacral micturition center evoked responses in the detrusor compartment as well as in the urethral sphincteric compartment. The micturition center was easily definable in the spinal cord at a variable point lying in the segment L51/2 to L6 vertebral levels. It was not possible to isolate a separate detrusor center from a sphincteric center. They did overlap-with the sphincteric center extending both above and below the detrusor center. Parameters of stimulation were tested and it was noted that 1 to 3 v, frequency of 10 to 15 cps, and duration of 1 msec gave the optimal responses. Complte muscular separation did not alter sphincteric response to spinal cord stimulation. Nerve-mediated impulses resulted in rise in detrusor pressure and a simultaneous rise in urethral pressure that interfered with proper voiding and hindered bladder emptying. This problem remains to be solved before central spinal cord stimulation for the purpose of controlled bladder evacuation becomes fully effective.     

Leptomeningeal mycosis fungoides

Central nervous system involvement with mycosis fungoides complicated the clinical course of a patient at a time when his skin was clinically free of disease following systemic chemotherapy. A leptomeningeal syndrome of blurred vision and papilledema, and confusion progressing to coma, was associated with elevated spinal fluid pressure and abnormal spinal fluid cells morphologically similar to those seen in the Sezary syndrome. The symptoms were dramatically reversed by intrathecal methotrexate, brain irradiation, and steroids. Mycosis fungoides recurred in the skin, in the spinal fluid, and in both eyes. Despite continued systemic and intrathecal chemotherapy, the patient died from mycosis fungoides. This is the second patient reported with meningeal mycosis fungoides.     

Voiding pressure as it relates to outlet and/or sphincteric resistance

Electrically quantitated and controlled detrusor contraction can produce either minimal or excessive rise in intravesical pressure depending upon openness or occlusion of the bladder outlet. Higher rise in intravesical pressure thus does not imply stronger detrusor contraction but should be viewed as a reflection of the outflow resistance mechanism. Possible damaging hydrodynamic effect of sudden partial or complete functional occlusion of the bladder outlet by intermittent or sustained voluntary sphincter activity is illustrated.     

Corn grain-processing method interacts with calcium salts of palm fatty acids supplementation on milk production and energy balance of early-lactation cows grazing tropical pasture

The objective of our study was to investigate the associative effects of feeding Ca salts of palm fatty acids (FA) and corn grain-processing method on production, nutrient digestibility, energy balance, and carryover effects of early-lactation dairy cows grazing a tropical pasture. Treatment diets were offered from 3 to 16 wk postpartum (treatment period), in which all cows grazed elephant grass (Pennisetum purpureum L. Cameroon) and treatments were added to a concentrate supplement. Treatments were flint corn grain-processing method either as fine ground (FGC) or steam-flaked (SFC) associated with Ca salts of palm FA supplementation either not supplemented or supplemented (CSPO). From 17 to 40 wk postpartum (carryover period) all cows received a common diet fed as total mixed ration. During the treatment period, a tendency for an interaction between CSPO and corn grain-processing method were observed for milk yield, milk fat yield, and energy-corrected milk (ECM), as CSPO caused them to increased to a greater extent in the FGC diet compared with the SFC diet. Furthermore, a tendency for an interaction between CSPO and corn grain-processing method was observed for body weight change, because CSPO increased body weight loss in the FGC diet but not in the SFC diet. The CSPO increased milk yield, milk fat yield, 3.5% fat-corrected milk, ECM, and cumulative milk yield compared with not supplemented. Also, CSPO increased energy intake, milk energy output, and energy partitioning toward milk, whereas reduced energy was allocated to body reserves. The SFC increased milk yield, ECM, milk protein yield, milk casein yield, and cumulative milk yield, and decreased milk urea N compared with FGC. The SFC compared with FGC also increased body condition score and body weight change, and increased energy partitioning toward body reserves. During the carryover period, an interaction between CSPO and corn grain-processing method was observed for milk yield, which occurred because CSPO maintained higher milk yield in the FGC diet but not in the SFC diet. Therefore, in the carryover period, the additive effect between SFC and CSPO that occurred in the treatment period was not maintained throughout the carryover period. However, CSPO increased yields of milk fat, protein, casein as well as fat-corrected milk and ECM. In conclusion, corn grain-processing method interacts with CSPO supplementation on production responses and carryover effects of grazing cows. When CSPO was fed in the FGC diet, milk production increased to a greater extent than when fed in the SFC diet, but also caused greater mobilization of reserves at early lactation. This suggests an interaction between fat supplementation and corn grain-processing method on energy partitioning of dairy cows. Also, both supplementation with CSPO and SFC were effective strategies to increase energy intake and yields of milk and milk solids. The carryover effect on milk production was greater for CSPO supplementation than corn grain-processing method, whereas feeding SFC diets had lower mobilization of reserves and less body weight and body condition score variation throughout lactation.     

Detection and analysis of triterpenic compounds in apple extracts

A new technique for the rapid detection and analysis of triterpenic compounds in apple extracts using HPLC was developed and validated. The main advantage of this technique is the short duration of the analysis – this makes this technique superior to others currently applied for the routine HPLC analysis of triterpenic compounds. The developed, optimized, and validated technique was used for the evaluation of triterpenic compounds in samples of different cultivars of apples, their peels, and flesh. In total, four triterpenic compounds were isolated and identified. Ursolic acid was the dominant compound in all the tested apple samples. The highest amounts of triterpenic compounds were detected in the peels of the ‘Lodel’ apple cultivar, and thus apples of this cultivar may be potentially useful for the isolation of individual compounds and the production of functional food and dietary supplements.     

Involvement of yeast YOL151W/GRE2 in ergosterol metabolism

The Saccharomyces cerevisiae gene YOL151W/GRE2 is widely used as a model gene in studies on yeast regulatory responses to osmotic and oxidative stress. Nevertheless, information concerning the physiological role of this enzyme, a distant homologue of mammalian 3-beta-hydroxysteroid dehydrogenases, is scarce. Combining quantitative phenotypic profiling and protein expression analysis studies, we here report the involvement of yeast Gre2p in ergosterol metabolism. Growth was significantly and exclusively reduced in gre2Delta strains subjected to environmental stress straining the cell membrane. Furthermore, whereas no compensatory mechanisms were activated due to loss of Gre2p during growth in favourable conditions (synthetic defined media, no stress), a striking and highly specific induction of the ergosterol biosynthesis pathway, represented by the enzymes Erg10p, Erg19p and Erg6p, was observed in gre2Delta during growth in a stress condition in which lack of Gre2p significantly affects growth. Involvement of Gre2p in ergosterol metabolism was confirmed by application of an array of selective inhibitors of lipid biosynthesis, as gre2Delta displayed vastly impaired tolerance exclusively to agents targeting the ergosterol biosynthesis. The approach outlined here, combining broad-spectrum phenotypic profiling, expression analysis during conditions reducing the growth of the mutant and functional confirmation by application of highly selective inhibitors, may prove a valuable tool in gene functional analysis.     

Evaluation of <Emphasis Type=Italic>flaA</Emphasis> Short Variable Region Sequencing,Multilocus Sequence Typing,and Fourier Transform Infrared Spectroscopy for Discrimination between <Emphasis Type=Italic>Campylobacter jejuni</Emphasis> Strains

Discriminatory and robust typing methods are needed to improve the understanding of the dynamics of food-borne Campylobacter infections and epidemiology in primary animal production. To evaluate the strain discriminatory potential of typing methods, flaA short variable region (SVR) sequencing and Fourier transform infrared (FTIR) spectroscopy were applied on a collection of 102 epidemiologically related and unrelated Campylobacter jejuni strains. Previous application of FTIR spectroscopy for subtyping of Campylobacter has been limited. A subset of isolates, initially discriminated by flaA SVR sequencing, were further subjected to multilocus sequence typing (MLST). It was found that flaA SVR sequencing had a slightly higher discriminatory power than FTIR spectroscopy, based on the Simpson diversity index. The clustering of strains indicated that FTIR spectroscopy is indeed a suitable method for discrimination of Campylobacter. The isolates were assigned to six clusters based on flaA SVR sequences and nine clusters based on the FTIR spectroscopy profiles. Furthermore, the cluster analysis of flaA SVR sequences, MLST, and FTIR spectroscopy profiles showed a high degree of congruence, assigning the isolates to similar cluster structures. In conclusion, FTIR spectroscopy can be applied for subtyping of Campylobacter, and the high discriminatory potential of both flaA SVR sequencing and FTIR spectroscopy render them suitable screening methods for large numbers of strains.     

Similarities between lime and limestone in wet—dry scrubbing

Lime is utilized as a sorbent in most commercial wet—dry scrubbing processes for SO₂ control, while limestone is not considered to be sufficiently reactive for such a purpose. Faced with the fact that limestone is potentially the least expensive sorbent for SO₂ control, a study was conducted to uncover ways to increase the reactivity of this sorbent in order to use it in wet—dry scrubbing applications. The study was focused on a comparison of the reactivity of lime and limestone during the dry reaction period. The conditions which have a major impact on the reactivity include the sorption capacity of water vapour, the BET surface area, the relative humidity and the sorbent utilization. The experiments revealed several similarities between the two sorbents, which led to a number of ways to obtain increased limestone acitivity.