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Biomedical subjects

J C Allen

Publications and source records attributed to J C Allen.

At least 217 records · Page 12Linked to original sources
PubMed1981

High-dose cyclophosphamide chemotherapy for recurrent CNS tumors in children.

A Phase Ii chemotherapy trial was conducted in 18 children with recurrent brain tumors, using high doses (80 mg/kg or greater) of intravenous cyclophosphamide cyclophosphamide. All eight patients with medulloblastomas responded; two patients with systemic metastases had complete responses and six others had partial responses. In seven patients with gliomas, there were one complete and four partial responses. In a third group, all three patients with intracranial germ-cell tumors had partial responses. The overall response rate was, therefore, 89% (16 of 18 patients), and the mean duration of response was 7 months (range 2 to 24 or more months). The hematological toxicity was considerable, with two deaths possibly related to chemotherapy: one patient, a recipient of unirradiated packed cells, died from a graft versus host reaction, and the other died from an intracranial hemorrhage during a thrombocytopenic episode. Four patients had prior chemotherapy, and 10 patients had prior neuraxis radiation therapy. These patients tolerated aggressive chemotherapy reasonably well. The results are sufficiently encouraging to justify a Phase III trial in patients with newly diagnosed disease.

Adolescent↗
PubMed1980

The reactivities of furocoumarin excited states with DNA in solution. A laser flash photolysis and fluorescence study.

The effect of DNA on both the fluorescence emission spectra and yields and lifetimes of the triplet stae of psoralen and 8-methoxypsoralen in aqueous solution has been determined. The changes in the fluorescence spectra are similar in nature for both of these furocoumarins and are attributed to binding of the drug to DNA. The yield of the 8-methoxypsoralen triplet state when bound to DNA was found to be similar, if not identical, to that measured in the absence of DNA. This contrasts sharply with data obtained for psoralen from which it is concluded that either the yield of bound psoralen triplet states is very low, if not zero, or that the lifetime of such species is less than 50 ns. The relevance of this data to the molecular basis of skin photosensitisation by furocoumarins is discussed.

Ficusin↗
PubMed1980

The determination of the heparin neutralising capacity of protamine using acridine orange fluorescence.

A new method to estimate the heparin neutralising capacity of protamine has been investigated. The technique has been applied to two commercial heparin preparations tested against the W.H.O. 1st International Reference preparation of protamine. The technique is based on the fluorescence of acridine orange dye and the selective binding of heparin with protamine. A titration procedure has been devised and the two variations of the assay are compared and evaluated. The titration is rapid, accurate and convenient.

Acridine Orange↗
PubMed1980

An investigation of calcium ion binding to heparins.

Using the line charge model of Manning and, where appropriate, a form of the empirical corrections to his limiting laws proposed by Wells, we have investigated the ion condensation phenomenon for four pure calcium heparin preparations and similar Ca-heparin/CaCl2 mixtures in aqueous solution. This has been expressed in terms of the single ion activity coefficient of the total calcium counter ion present. The results found for the single counter ion activity coefficient of pure Ca-heparin agree moderately well with the limiting law of Manning for a pure divalent counter ion polyanion salt in dilute solution. The results for Ca-heparin/CaCl2 mixtures when corrected for small ion-small ion interactions give a surprisingly good fit to the theoretical counter ion activity coefficient for a divalent counter ion/divalent cation simple electrolyte system, for values of X (X = the polyanion/co-ion ratio) up to 4, with slight deviations for values of X > 4. In the mixtures with the largest excess of polyelectrolyte, the single ion activity coefficients of the Ca2+ ion are in excess of the value predicted by Manning's theory. Ion exchange of sodium heparins to give the Ca-heparin samples used in the work did not appear to cause regular changes in the anticoagulant activity.

Blood Coagulation↗
PubMed1980

Amelioration of experimental bacterial meningitis by levamisole: evidence of a direct effect on the infecting bacteria.

The immune-modulating effects of levamisole were evaluated in vivo in rabbits with experimental meningitis due to Escherichia coli and in vitro in assays of ingestive and digestive functions of polymorphonuclear leukocytes. Intracisternal treatment of rabbits with 0.5 ml of levamisole (400 micrograms/ml) 48 and 24 hr before infection resulted in a longer survival time (mean, 49.3 hr) than either control (mean, 21.3 hr; P < 0.01) or intravenously treated animals (mean, 18.3 hr; P < 0.05). However, treatment of the organism by incubation in levamisole (100 micrograms/ml) resulted in survival times significantly longer than that of intracisternally treated animals (mean, 98.5 hr; P < 0.05). A reduction of 5 logs of viable bacteria 22 hr after infection was noted by previous therapy of either the animal or the bacteria. No antibiotic effect was demonstrated. In vitro studies revealed increased ingestion by polymorphonuclear leukocytes (P < 0.02) and digestion (P < 0.05) of bacteria incubated in levamisole. These results suggest that levamisole may alter the bacteria, enhance killing, and produce salutary in vivo effects.

Animals↗
PubMed1980

Comparison of cefamandole, cephalothin, ampicillin, and chloramphenicol in experimental Escherichia coli meningitis.

The activities of cefamandole, cephalothin, ampicillin, and chloramphenicol were compared in fulminant and temperate Escherichia coli meningitis in rabbits. Intensive dosing schedules were employed to achieve maximal therapeutic benefits with short-term treatment. In an 8-h schedule chloramphenicol was significantly more effective in sterilizing the cerebrospinal fluid and curing both fulminant and temperate infections than cefamandole or ampicillin. Cephalothin was without effect in fulminant meningitis. Cefamandole and ampicillin were equivalent in activity in this and longer (12- and 24-hr) treatment schedules. The therapeutic benefits of chloramphenicol were purchased via use of doses above those generally regarded as safe for human use. The mean serum, cerebrospinal fluid, and brain concentrations of chloramphenicol, cefamandole, and ampicillin were significantly greater in rabbits with fulminant meningitis than in those with temperate meningitis. The difference was of such magnitude as to support the need to monitor drug concentrations.

Ampicillin↗
PubMed1980

Central neurofibromatosis with bilateral acoustic neuroma: genetic, clinical and biochemical distinctions from peripheral neurofibromatosis.

Neurofibromatosis includes the common "peripheral" form and a recently documented "central" form. We describe the central form in 130 cases from 9 kindreds personally studied and 15 reported kindreds. Central neurofibromatosis with bilateral acoustic neuroma is an autosomal dominant disorder beginning about 20 years of age, accompanied by mild skin changes. In three kindreds with central neurofibromatosis, we measured nerve growth factor in serum by radioimmunoassay and radioreceptor assay. Only the antigenic activity of nerve growth factor was increased. In contrast, in peripheral neurofibromatosis, only the functional activity of nerve growth factor has been reported increased. Central and peripheral forms of neurofibromatosis are closely related but discrete diseases which appear to have separate alterations in nerve growth factor activity.

Adolescent↗
PubMed1980

Influence of a low chloride practical diet on acid-base balance and other factors of blood in young dairy calves.

Control (.5% chloride) or low-chloride (.038% chloride) practical diets and low-chloride (.00038% chloride) well water were fed to male Holstein calves for 7 wk. Substantial alterations in characteristics of blood associated with acid-base balance developed in those fed the low-chloride diet. Along with reduced potassium in plasma, concentrations of chloride in synovial fluid, saliva, and plasma also were reduced. Solids in plasma, blood pH, packed cell volume, carbon dioxide pressure (PCO2) in blood, and bicarbonate were increased. Most of the changes in plasma occurred within 1 wk with little change thereafter, indicating an adaptation by the calves to the low-chloride diet. The adaptation by the low-chloride calves was primarily due to a tremendous reduction in urinary chloride excretion. Change in blood factors was insufficient to cause severe alkalosis in calves. The low-chloride diet had no significant effect on sodium absorption, retention, or distribution in body fluids. Potassium in plasma and aqueous humor were reduced in calves fed the low-chloride diet, but potassium concentrations in other body fluid were not affected significantly.

Acid-Base Equilibrium↗
PubMed1980

Selenium binding and distribution in goat and cow milk..

Raw milk from goats and cows (bovine) was combined with sodium selenite (.5 muCi/10 ml milk) and incubated at 39 C to allow selenium binding to milk components. After incubation intervals between .5 and 24 h, samples were separated into cream, whey, and casein fractions by centrifugation and acid precipitation. When samples were incubated up to 6 h, the aqueous whey fraction contained the highest amounts of radioactivity, the casein substantially less, and the cream contained little senenium-75. Twenty-four hours of incubation at 39 C caused the samples to curdle, resulting in a major shift of radioactivity from the aqueous phase to the acid precipitable (casein) fraction. This shift occurred in all curdled samples irrespective of time or temperature of incubation. Acidifying milk samples with lactic acid in the presence of a bacterial inhibitor also increased selenium binding by the casein fraction. Samples of whey fractions were applied to a Sephadex gel filtration column for further separation. Most of the selenium-75 was recovered in low molecular weight fractions. Radioaactive selenium appeared to remain largely in the unbound ionic form when added to noncurdled goats' or cows' milk. Most of the selenite added to milk does not combine with proteins at normal pH but increasingly does so as pH falls below 6.0.

Animals↗
PubMed1980

Leukoencephalopathy following high-dose iv methotrexate chemotherapy with leucovorin rescue.

Seven patients with bone or soft tissue sarcomas but without metastatic CNS disease developed a chronic leukoencephalopathy after high-dose (8000-15,000 mg/m2) iv methotrexate (MTX) chemotherapy with leucovorin (LV) rescue. Approximately 12 MTX-LV treatments were administered over a 3-7 month period. None of the patients had cranial irradiation. The syndrome usually began several months after the initiation of chemotherapy with subtle personality changes followed by a progressive dementia, focal seizures, pseudobulbar palsy, spastic quadriparesis, and stupor. Computerized tomographic scans revealed diffuse white matter hypodensity in five patients and atropic changes in five patients. Serum MTX concentrations were elevated in four of six patients prior to several MTX-LV treatments, suggesting that MTX persisted in tissues for a long time. Abnormally high levels of MTX were detected in the cerebrospinal fluid of all four patients several days after an MTX-LV treatment, at a time when their encephalopathy was most severe. Pathologic brain material was obtained from three patients and revealed a spectrum of abnormalities. The syndrome observed in our patients clinically resembles the one described in children with acute lymphatic leukemia who received cranial irradiation and large cumulative amounts of low-dose (12-20 mg/m2) systemic MTX without LV.

Adolescent↗
PubMed1980

Mechanical and biochemical alterations of aorta induced by hydralazine hypotension.

Previous experiments from this laboratory indicated that the actomyosin content of aorta from spontaneously hypertensive (SHR) rats was greater than that from normotensive (WKY) rats. The purpose of the present experiments was to determine the effect of hydralazine-induced hypotension on actomyosin content and mechanical properties of aorta from SHR and WKY rats. Ten-week-old WKY and SHR rats were given to tap water or tap water containing 80 mg/l of hydralazine for 2 weeks and at the end of this time the actomyosin content (sodium dodecyl sulfate-polyacrylamide gel electrophoresis), the contractile responses to potassium chloride and phenylephrine and the passive stress-strain properties of the aorta were determined. Hydralazine-treated rats had a significantly lower systolic pressure after 1 week which remained lower for the remainder of the treatment period. Treated WKY and SHR rats exhibited a reduced actomyosin content relative to total protein content of cell number (based on DNA determination). Mechanically, aorta from treated animals showed no change in their passive elastic properties or in their sensitivity (ED50) to either agonist; however, the maximum contractile response to both agonists was significantly reduced. Normalization of force development to actomyosin content indicated: 1) that aorta from SHR rats develop less force for a given amount of actomyosin than WKY aorta; 2) a 2-week period of hydralazine hypotension results in a reduction in force development in both WKY and SHR aorta that can be accounted for by a reduction in cellular actomyosin content; and 3) this period of hydralazine hypotension does not return the contractile effectiveness of actomyosin from SHR aorta to that of actomyosin from WKY aorta.

Actomyosin↗