The kinetics and distribution of methotrexate in intraventricular and intrathecal cerebrospinal-fluid spaces were studied in patients with meningeal leukemia and meningeal carcinomatosis after drug administration by intravenous infusion, indwelling intraventricular subcutaneous reservoir (Ommaya), or standard lumbar puncture. Negligible ventricular concentrations followed a single intravenous dose. During an intravenous infusion (500 mg per square meter for 24 hours) the ventricular cerebrospinal-fluid concentration rose to 6 times 10-minus 7 M. Methotrexate administered by Ommaya reservoir, at a dose of 6.25 mg per square meter, rapidly distributed in the subarachnoid space; the peak ventricular concentration of 2 times 10-minus 4 M declined exponentially over 48 hours. Lumbar cerebrospinal-fluid concentration reached a maximum of 5 times 10-minus 5 M four hours after injection and then fell exponentially. Administration by lumbar puncture occasionally produced epidural and subdural leakage; even with successful lumbar puncture, ventricular methotrexate concentration varied considerably from patient to patient despite similar doses. Administration by Ommaya reservoir more reliably produced adequate cerebrospinal fluid distribution than administration by lumbar puncture.
We studied 85 cancer patients with lumbosacral plexopathy and documented pelvic tumor by CT or biopsy. Three clinical syndromes were delineated: lower (L4-S1), 51%; upper (L1-L4), 31%; and pan-plexopathy (L1-S3), 18%. Seventy percent of patients had the insidious onset of pelvic or radicular leg pain, followed weeks to months later by sensory symptoms and weakness. The quintet of leg pain, weakness, edema, rectal mass, and hydronephrosis suggests plexopathy due to cancer. CT showed pelvic tumor in 96%. On myelography, epidural extension, usually below the conus medullaris, was seen in 45%. With treatment, only 28% of patients had objective responses on CT and 17% on examination.
Fourteen trials were conducted to evaluate the effects of feeding monensin at 33 ppm alone, tylosin at 11 ppm alone and the two feed additives in combination on the average daily gain, average daily feed intake, feed:gain ratio and the incidence of liver abscesses in feedlot cattle. Monensin reduced feed intake and improved feed efficiency (P less than .05), and had no effect on average daily gain. Tylosin improved average daily gain (P less than .05) and had no effect on daily feed intake. The effect of tylosin on feed efficiency approached significance. The interaction of monensin and tylosin was nonsignificant for daily gain, daily feed intake and feed:gain ratio. Monensin had no effect on liver abscess incidence, while tylosin reduced abscess incidence from 27 to 9%.
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