Parenteral iron during hemodialysis.
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Biomedical subjects
Publications and source records attributed to J Evers.
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A 52-year-old man, who presented with Sézary syndrome with autoimmune hemolytic anemia (AIHA) and was successfully treated with corticosteroids is reported. Helper function assay determining immunoglobulin confirmed inducer capability of this clonal population. This patient brings to 4 the number of cases of T cell cutaneous lymphoma and AIHA now reported in the English literature, and is the first case of Sézary syndrome and AIHA thus far.
Cytogenetic analysis of a primary germ-cell tumor originating from the streak gonad of a 20-year-old phenotypic female with a 46,XY karyotype and mixed gonadal dysgenesis revealed a 48,XY, +7, +i(12p) chromosomal pattern. Germ-cell tumors originating from gonads of normal males are usually highly aneuploid. An isochromosome 12p as well as an overrepresentation of chromosome 7 material are among the specific changes most consistently observed. The present case shows that tumors of dysgenetic gonads, albeit being near-diploid, may exhibit similar chromosomal changes. This observation lends additional support to the hypothesis that these specific cytogenetic anomalies may play an important role in the pathogenesis of human germ-cell tumors.
This article describes concepts of drug treatment for patients with severe renal failure (creatinine clearance less than 10 ml/min), especially in intensive care. These subjects often develop multiorgan failure and require special considerations: 1. Not only should the maintenance dose of digoxin be reduced to 0.05-0.1 mg/day, but the loading or digitalizing dose should also be diminished to 0.4-0.6 mg. 2. Penicillins, cephalosporins, quinolones, and other antibiotics with a high therapeutic ratio can be given as recommended by the manufacturer or reference lists according to renal insufficiency. 3. For drugs with a low therapeutic index, such as aminoglycosides, vancomycin, flucytosine, some antiarrhythmic agents, cardiac glycosides, and theophylline, therapeutic drug monitoring is mandatory. 4. Steroids, insulin, atropine, catecholamines, anticoagulants, thrombolytic agents, antihypertensive drugs, and organic nitrates can be given according to their effect. However, nitroprusside should be discontinued after 2 days because its metabolites may be toxic. 5. The dose of H2-receptor antagonists used for the control of gastric acidity and the treatment of peptic ulcers should be reduced to 20-50% of the normal. The administration of aluminum, magnesium, and bismuth compounds should be avoided. 6. Loop diuretics (e.g., furosemide) can be effective at increased doses in patients with chronic renal failure and fluid overload, particularly when used in combination with a thiazide in refractory edema. Thiazides alone are useless, and potassium-sparing diuretics are contraindicated. 7. Colloid-containing solutions should be infused cautiously at a maximal rate of 2 x 500 ml/week only when the plasma volume is contracted.(ABSTRACT TRUNCATED AT 250 WORDS)
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We monitored the plasma levels of mexiletine in 20 dialysis patients with severe cardiac arrhythmias after repeated oral administration and the elimination by various dialysis procedures. The levels of mexiletine in plasma and dialysate were assayed by high-pressure liquid chromatography. After repeated administration of mexiletine 400-600 mg/day trough levels were in the range from 500-2,000 ng/ml. Treatment controlled by Holter monitoring was effective in 13/20 patients. Doses of 600 mg/day and more often were not tolerated by patients with dialysis after some weeks. There was no important removal of mexiletine from plasma during hemodialysis, hemofiltration, peritoneal dialysis, or plasmapheresis. In conclusion, we recommend a slightly reduced dosage of 400-600 mg mexiletine/day (usually 600-800 mg) for patients with end-stage renal insufficiency, irrespective of dialysis.
The pharmacokinetics of isosorbide dinitrate (ISDN) and its two active metabolites isosorbide-2-nitrate (IS-2-N) and isosorbide-5-nitrate (IS-5-N) were studied in 20 patients with normal and impaired renal function after repeated oral doses of standard 20 mg tablets ISDN t.i.d. Blood samples were taken in the steady-state on days 2 and 14, and the plasma concentrations were measured by electron capture capillary gas chromatography. We found a wide variation of pharmacokinetic parameters (AUCss0-8 and t1/2) of ISDN, IS-2-N, and IS-5-N in our patients. No correlation was detected between AUCss0-8 or t1/2 and the degree of renal insufficiency. No drug accumulation was observed after 14 days of administration.
We have studied the spontaneous and nerve-evoked synaptic currents during the initial period of nerve-muscle contact in Xenopus cell cultures. The precise timing of the contact was achieved by physically manipulating embryonic muscle cells into contact with co-cultured spinal neurons. Previous studies have shown that physical contact of the muscle membrane induces pulsatile release of acetylcholine (ACh) from the growth cone of these neurons, resulting in spontaneous synaptic currents (SSCs) in the muscle cell within seconds following the contact. In the present work, we first showed that these SSCs at the manipulated nerve-muscle contacts are similar to those observed at naturally occurring synapses. We then examined the possible cellular mechanisms responsible for the marked variation in SSC amplitude and showed that it most likely results from differences in either the amount of ACh contained in each release event or the extent of close membrane apposition near the release sites. During the first 20 min following the nerve-muscle contact, there was an increase in the frequency and mean amplitude of the SSCs. During a similar period, the evoked synaptic currents (ESCs), which were induced by suprathreshold electrical stimulation of the neuronal soma, also showed an increase in the mean amplitude and a reduction in the delay of onset following the stimulus. These postcontact changes in the efficacy of synaptic transmission may be related to an increase in the total area of close membrane apposition between the nerve and muscle cells. This was suggested by the finding that neurite-muscle adhesion increases over a similar postcontact period. The transition from low- to high-efficacy transmission during the early phase of contact may reflect the process of selective adhesion between the cells, and thus signify the formation of specific synapse. Analysis of the fluctuation in the ESC amplitude at the early nerve-muscle contact suggests that evoked release of ACh occurs as multiples of a quantal unit. However, this unit is apparently related to only a small subpopulation of SSCs of relatively high amplitudes.(ABSTRACT TRUNCATED AT 400 WORDS)
During early stages of postnatal development skeletal muscle fibres of mammals are contacted by several axons. The transition from poly- to mononeuronal innervation has been extensively studied on the rat soleus. The role of activity in this process has been acknowledged but the mechanisms leading to synapse remodelling are not understood. The participation of the muscle has to be taken into account; if muscles are paralysed by alpha-bungarotoxin, the elimination of terminals is arrested. Changes in Ca2+ also influence the rate of removal of terminals. Calcium seems to act through a calcium-activated neutral protease (CANP) present in nerve endings. If CANP is inhibited, elimination fails to take place. Thus Ca2+ enters the terminal and activates the CANP. Release of K+ ions from active muscle could link muscle activity and synapse elimination. Excess K+ was found to reduce nerve-muscle contacts, by depolarizing terminals and allowing Ca2+ entry. A greater increase of Ca2+ concentration in smaller terminals would be expected, because of their surface-to-volume ratio, and they are preferentially eliminated. Thus elimination depends on the unequal size of terminals at the endplate. Therefore the 'survivability' of individual nerve endings may already be determined at the time of synapse elimination.
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The pharmacokinetics of isosorbide-5-nitrate (IS-5-N) was studied in ten patients on haemodialysis (HD) after a single oral dose of 20 mg IS-5-N, and in six patients on continuous ambulatory peritoneal dialysis (CAPD) after repeated oral doses of 3 X 20 mg IS-5-N. There was significant removal of IS-5-N from blood during HD; Cmax decreased by about 20%, AUC(0-8 h) by 30% and t1/2 by about 20% from 4.3 to 3.4 h, and plasma clearance was increased by 81 ml/min. No important loss of IS-5-N was observed in patients on CAPD.
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The pharmacokinetics of the antianginal drug isosorbide-5-nitrate (IS-5-N) was studied in 20 patients with varying degrees of chronic renal failure after repeated oral doses of standard 20 mg tablets t.d.s. Blood samples were taken in the steady state on the 2nd and 28th days, and the plasma level was assayed by HPLC. There was no statistically significant difference in Cssmax, t1/2 and AUCss0-8 between the 2nd and 28th days, nor was a difference found between patients with mild and severe renal failure.
Dantrolene plasma concentrations and renal clearance calculations in a patient undergoing major surgery are reported. The family history was positive for malignant hyperthermia. Following oral pretreatment the plasma concentrations in this patient were not noticeably different from values obtained in a study in awake volunteers and which were thought to be effective. This is the first report of dantrolene measurements made during anaesthesia and in the post-operative period.
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