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Biomedical subjects

W P Rogers

Publications and source records attributed to W P Rogers.

At least 19 recordsLinked to original sources
PubMed1998

A four-hour topotecan infusion achieves cytotoxic exposure throughout the neuraxis in the nonhuman primate model: implications for treatment of children with metastatic medulloblastoma.

The purpose of this study was to define the length of topotecan (TPT) i.v. infusion necessary to attain a cytotoxic exposure for medulloblastoma cells throughout the neuraxis. In vitro studies of human medulloblastoma cell lines (Daoy, SJ-Med3) were used to estimate the length and extent of TPT systemic exposure associated with inhibition of tumor cell growth or the exposure duration threshold (EDT). We evaluated TPT systemic and cerebrospinal fluid (CSF) disposition in six male rhesus monkeys (8-12 kg) that received TPT 2.0 mg/m2 i.v. as a 30-min or 4-h infusion. Plasma and CSF samples were assayed for TPT lactone by high-performance liquid chromatography, and the CSF exposures were compared with the estimated EDT. Results of the in vitro studies defined an EDT as a TPT lactone concentration of > 1 ng/ml for 8 h (IC99) daily for 5 days. The mean +/- SD for systemic clearance (CL(SYS)), penetration into fourth ventricle (%CSF(4th)), and penetration into lumbar space (%CSF(LUM)) were similar for the 30-min and the 4-h infusions. At a TPT lactone systemic exposure (AUC(PL)) of 56.7 +/- 19.9 ng/ml x h, time above 1 ng/ml in the fourth ventricle was 1.4-fold greater for a 4-h infusion compared with a 30-min infusion. At a TPT lactone AUC(PL) of 140 ng/ml x h, the 4-h infusion achieved the desired TPT exposure throughout the neuraxis (lateral and fourth ventricles and lumbar space), whereas the 30-min infusion failed to achieve it in the lumbar space. In conclusion, prolonging TPT i.v. infusion from 30-min to 4-h at a targeted AUC(PL) achieves the EDT throughout the neuraxis and represents an alternative method of TPT administration that will be tested prospectively in patients with high-risk medulloblastoma.

Animals↗
PubMed1996

Efficacy of various therapeutic regimens in eliminating Pasteurella pneumotropica from the mouse.

Pasteurella pneumotropica, a gram-negative opportunistic pathogen, can be isolated from the oropharynx, intestinal tract, and reproductive tract of clinically normal mice and has been associated with various clinical syndromes, including conjunctivitis, infections of the reproductive tract, otitis, and subcutaneous abscess formation. Enrofloxacin, a fluoroquinolone bactericidal antimicrobial, has been shown to be effective in eliminating P. multocida from rabbits. We sought to determine whether enrofloxacin would eliminate P. pneumotropica from mice known to be asymptomatically infected with the agent. Pasteurella pneumotropica-positive (culture and immunofluorescence assay) male (n = 55) and female (n = 55) C57BL/6N mice were randomly assigned to one of seven treatment groups or to a control group. These groups were designed to evaluate the efficacy of enrofloxacin administered orally via the drinking water or parenterally at three dosages (8.5, 25.5, and 85.0 mg/kg of body weight per day) over a 14-day treatment period. A tetracycline-treated group (60 mg/kg per day) and an untreated control group were included for comparisons. Repeated oropharyngeal swab and fecal specimens were obtained for culture through posttreatment day 30, and specimens from numerous enteric and reproductive organs collected during necropsy were used to evaluate group differences. Enrofloxacin eliminated evidence of P. pneumotropica from all sites when administered at 25.5 or 85 mg/kg but not at 8.5 mg/kg by either route for at least 30 days after treatment. Tetracycline-treated and control groups remained consistently culture-positive throughout the study. We concluded that the oral route may be a more practical method for treating large numbers of mice. Enrofloxacin may be a practical and inexpensive alternative to cesarian rederivation or embryo transfer for the elimination of P. pneumotropica in mice.

Administration, Oral↗
PubMed1987

The physiology of infection with nematodes: the role of intracellular pH in the development of the early parasitic stage.

1. H2CO3, the host's signal which induced (less than 25 min) the Ca2+-dependent development of the first parasitic stage of Haemonchus contortus, produced a diphasic change in the pHi (less than 30 min), measured with 5,5-dimethyl-2,4-oxazolidinedione, in the infective stage. The intensity of the diphasic change was related to the [H2CO3] and so to the efficiency of the stimulus for development. 2. MES and HEPES buffers induced a rapid rise in pHi of infective stages in step with pHo. Ortho-and pyrophosphate induced greater changes in pHi. Such buffers did not initiate development. 3. These and other results suggest that the stimulus for development, H2CO3, induced an energy-dependent Ca2+/H+ exchange mediated by mitochondria of the infective stage, which initiated development of the parasitic stage.

Ammonium Chloride↗
PubMed1987

The nature and action of host signals.

It is clear that excystations in vitro of the coccidia so far examined involves two steps, in the first of which CO2 is important, and the second, in which an external source of chymotrypsin and surface-active agents are required. However, the details of the mechanism of excystment are not clear. We do not know how the presence of CO2 changes the permeability of the oocyst wall. We do not know whether CO2 does anything to the sporozoite or sporocyst; the circumstance that mechanically-released sporocysts readily excyst under appropriate conditions without the necessity for high concentrations of, or perhaps any, CO2 suggests it does not. Circumstantial evidence suggests that the substrate in which chymotrypsin acts is the Stieda body, but whether the enzyme has other roles we do not know. Similarly, the role of bile is ill-defined, although it does seem that the induction of activity is important--but how is this brought about? The techniques available to excyst oocysts are, for many species, very efficient. If CO2 is, as it seems to be, a fundamental stimulus, then efficiency might be enhanced if more attention was given, not so much to increasing the time of exposure and amount of CO2 in the gas phase, but rather to the pH of the medium, which is rarely stated or apparently, controlled. The pH determines the proportion of the different carbonate species in solution, which may be of greater significance than the partial pressure of CO2 in the gas phase (see also Section V A). Although high numbers of excysted sporocysts can be obtained with a particular technique, this does not necessarily mean that all the signals supplied by the host are reproduced in vitro. Jackson (1962) found it necessary to wash oocysts in water or dilute buffers between the primary phase and the secondary phase, a step which implies a deficiency in the methods he used. Commonly, oocysts are exposed to a strong solution of L-cysteine. Does this reflect a general deficiency in the technique, or a counterpart of strongly reducing conditions in ruminant and non-ruminant alike? It seems that we have only a very general outline of excystment, and that we do not understand the details. Yet the problem seems to have been put aside; the most recent relevant reference we have found is dated 1983.

Acanthocephala↗
PubMed1982

Determination of oxidative deterioration of milk powder and reconstituted milk by measurement of chemiluminescence.

A scintillation counter was used to measure chemiluminescence (CL) from milk powder and reconstituted milk. Only a small amount of CL, just above the background level, was observed from powders, but reconstituted milks emitted easily measurable CL. CL from milk was stimulated by exposure to light and found to decline gradually but non-exponentially after the exposure ceased. CL was at a maximum immediately after the milk was reconstituted from milk powder. Without light exposure, CL then declined gradually but non-exponentially over several hours to reach a constant value related to the level of oxidation of the powder. When determined under standard conditions 60 min after reconstitution, CL of milk reconstituted from stored milk powders correlated well with peroxide values and oxidized flavour as assessed by a taste panel.

Animals↗