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Biomedical subjects

C R West

Publications and source records attributed to C R West.

At least 109 records · Page 6Linked to original sources

Chemotherapy of nonirradiated malignant gliomas. Phase II: study of the combination of methyl-CCNU, vincristine, and procarbazine.

Twenty-eight adult patients with nonirradiated malignant gliomas of the brain were administered a combination of methyl-CCNU (130 mg/m2, p.o., day 1), vincristine (2 mg/m2, i.v., day 1) and procarbazine (100 mg/m2, p.o., days 2 to 15) (MVP), scheduled to be given at successive 6 week intervals. Nineteen (67.9%) were not responsive to MVP and 9 (32.1%) were. Of 16 who had previous partial resection of their tumors, 8 (50%) responded to MVP and 8 (50%) did not. Of 12 who had previous biopsy, only 1 (8.3%) responded. Overall 1-year survival rate for the 28 patients was 28.6%. Major side effects of MVP were leukopenia, thrombocytopenia, pulmonary emboli, and thrombophlebitis, detected mainly during the first 20 to 24 weeks of treatment.

Adult↗

Intra-arterial BCNU therapy in the treatment of metastatic brain tumor from lung carcinoma: a preliminary report.

Nine patients with intracerebral metastasis from lung carcinoma were treated with intracarotid and intravertebral artery infusion of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). Four of these patients considered definite responders showed unequivocal clinical improvement and definite decreases in the size of tumors evaluated by neurologic examination, computerized tomographic (CT) scan and radionuclide brain scan (RBS). One patient's clinical condition stabilized with doubtful improvement of diagnostic tests (probable responder). The remaining four patients had further unfavorable progression of the clinical and scan findings and were clearly nonresponders. Complications were transient and included: local pain in the eye, orbit, and occipital-nuchal area during infusion in 7 patients, focal seizure in 3 patients, mild confusion with disorientation in 2 patients, and nausea in 2 patients. Our findings suggest that intra-arterial BCNU therapy may be effective and may be used as an adjuvant to surgery and/or radiotherapy for the treatment of metastatic brain tumor from lung carcinoma.

Adult↗

Nucleoside conjugates as potential antitumor agents. 2. Synthesis and biological activity of 1-(beta-D-arabinofuranosyl)cytosine conjugates of prednisolone and prednisone.

Two of the new anticancer drugs recently synthesized in our laboratory from conjugation of ara-C2 and several corticosteroids linked through a phosphodiester bond include prednisolone- (I) and prednisone-p-ara-C (II). They were demonstrated to be enzymatically hydrolyzed to the corresponding steroid and ara-CMP and the latter was further shown to be hydrolyzed to ara-C by phosphodiesterase I, snake venom, 5'-nucleotidase, and acid phosphatase. However, the conjugates were shown to be resistant to hydrolysis by alkaline phosphatase. The activity of conjugates I and II against L1210 lymphoid leukemia in female mice (C3D2F1/J) was significantly greater than that of ara-C alone or in combination with the steroid. In fact, when the optimum dosage of 75 (mumol/kg)/day x 5 was used, the administration of ara-C alone was followed by an increased life span (ILS) of 45%. This result is similar to that previously reported. With the same equimolar doses of mixtures of ara-C and either prednisolone or prednisone, the ILS values were 40 and 44%, respectively. However, when the conjugates were used, the ILS values were 89 and 100% respectively. These findings seem promising and have provided the bases for continued study of these new compounds.

Animals↗

Alterations in cortical oxygen tension during the development of ischemic cerebral edema in primates (Macaca mulatta).

With a closed head primate stroke model, acute cerebral ischemia limited to the middle cerebral artery (MCA) territory was produced by macrosphere embolization of the internal carotid artery bifurcation. Measurements of the oxygen tension (PO2) at the cerebral cortical surface were obtained by continuous on-line mass spectrometry. Percentage of dry weight and tissue sodium, potassium, and chloride concentrations from ischemic and nonischemic hemispheres were determined at various times. With this preparation, we registered the precise onset of cortical surface PO2 depletion, which showed an exponential downward trend (fast component from 0 to 5 minutes, t 1/2 = 0.8 minute, rate of change = 89% per minute; slow component from 5 to 240 minutes, t 1/2 = 285 minutes, rate of change = 0.3% per minute). After the onset of cerebral ischemia, there was an immediate fall of the cortical surface PO2 with reductions of more than 45% at 5 minutes before definite hemiparesis and electroencephalographic abnormalities were recognized. During the secondary phase from 5 to 240 minutes the cortical surface PO2 fell by only an additional 23% of the steady state. Even so, when cortical surface PO2 was maintained at this critically low level, the earliest cerebral cortical edema was evident 180 minutes after MCA occlusion. Thereafter, progressive accumulation of edema fluid in the cortex (90 to 170.8 microliters per g of tissue) and in the white matter (19 to 46.2 microliter per g of tissue) was detected by the end of 240 minutes of cerebral ischemia.

Animals↗

Effects of dexamethasone on tumor-induced brain edema and its distribution in the brain of monkeys.

A human choriocarcinoma was successfully adapted to grow in the brain of monkeys (Macaca mulatta), thus providing a model of tumor-induced brain edema. Four animals were given dexamethasone (3 mg/kg/day) during 3 to 5 days after the onset of clinical signs, and the other five received no treatment for the same period. Tissue water and electrolyte content of treated and untreated animals were compared in cortex and white matter at various distances from the edge of the tumor. In untreated animals, 67.9% and 23.6% swelling was detected in adjacent and remote white matter, respectively, but only 11.8% swelling was noted in adjacent cortex. In animals treated with dexamethasone these percentages of swelling were improved to 32.4% and 11.9% in the corresponding white matter, and to 4.9% in adjacent cortex. The electrolyte changes shown in edematous brain of control animals also demonstrated significant improvement in the dexamethasone-treated group. Tissue radioactivity of 3H-dexamethasone at 60 minutes after intravenous injection was high in the periphery of tumor, adjacent cortex, and white matter, but low in the center of tumor, remote cortex, and white matter. The sites with high concentrations of dexamethasone also showed significant improvement of brain edema after dexamethasone treatment, suggesting that dexamethasone may act directly at these loci.

Animals↗

Haematological correlates of phytohaemagglutinin-induced lymphocyte transformation in horses.

The purpose of these investigations was to assemble and compare data which might illustrate a functional relationship between phytohaemagglutinin-induced transformation of equine lymphocytes in vitro and the haematological profiles of the lymphocyte donors. Statistically significant correlation between transformation and a haematological parameter was taken as evidence that both may be part of a common regulatory system. There was no evidence that transformation in vitro was affected by artefactual variation in the cellular composition of the cultures. Transformational behaviour of lymphocytes in autologous plasma showed significant correlation with donors' total leucocyte, neutrophil and T cell count. Different batches of donor plasma varied in ability to support the transformation and this ability was found to correlate significantly with the total leucocyte, eosinophil, lymphocyte and T cell count of the original blood. It is concluded that previously reported variation in transformation ratios of normal equine lymphocytes is attributable to regulatory mechanisms affecting circulating blood as a whole and that helminth parasitism may be among the primary causal agents which modify the mechanism.

Animals↗

A study of the effect of environmental CO2 on experimental Wilm's tumor.

The effects of exposure of experimental murine Wilm's tumor to increased atmospheric concentrations of carbon dioxide were studied. Local tumor growth was not affected by concentrations of 76% and 55% of carbon dioxide applied for 10 and 30 minutes. There was no difference in survival of animals and weight of the tumor between the control and the experimental groups. Ten per cent of the animals treated with concentrations of 55% and 76% carbon dioxide developed metastases in contrast to 30% of metastatic growth detected in the control group. This observation, although without statistically significant difference, may lead toward further study of the carbon dioxide effect in different tumor models. Additional tumor models and different animals species will be studied.

Animals↗

The 'normal range' and precision of phytohaemagglutinin-induced equine lymphocyte transformation in vitro.

Data are presented on lymphocyte transformation by phytohaemagglutinin in 20 normal horses. The logarithms of transformation ratios were found to have an approximately normal distribution, giving (for the transformation ratios themselves) a geometric mean of 23.6, a range of 1.92 to 97.3, and an estimated 95 per cent tolerance interval of 1.1 to 488. Analysis of variance on the logarithms of the transformation ratios gave a coefficient of variation of 140 per cent of the transformation ratios themselves for the variation between horses; whereas the coefficient of variation between duplicate samples was only 20 per cent, that is, small compared to the variation between horses. In addition, wide fluctuations of response of individual horses over weekly periods of measurement (comparable with the variation between the horses themselves) suggest that a single set of measurements at one time cannot be taken as evidence of abnormality in a given horse.

Animals↗

A study of the effect of CO2 on experimental neuroblastoma.

The effects of high concentrations of CO2 on experimental murine neuroblastoma tumor were studied. Similar to the experience with the animal model of Wilms' tumor, the local growth of this neuroblastoma model was not affected by concentrations of 76% and 55% of CO2 applied for 10 and 30 minutes. The tumor bearing animals exposed to different CO2 concentrations tended to develop metastases more frequently than the control groups, although no change in survival was noted. Different animals and additional tumor models could be used by others to study the effects of different CO2 concentrations at different exposure times.

Animals↗

Spontaneous premature birth in twin pregnancy.

Factors associated with spontaneous premature birth were investigated in 459 consecutive twin deliveries at this hospital. Low maternal age, low parity, and zygosity were significantly related to the incidence of this complication. The number of previous abortions, sex combinations and related birth order, and mode of presentation of the first twin were not related to the incidence of spontaneous premature delivery. We conclude that apart from low maternal age and low parity there are no obvious factors that would permit early identification of twin pregnancies at risk from spontaneous premature birth.

Adolescent↗

Comparison of intravenous oxytocin and prostaglandin E2 for accelerating labour.

In a prospective study of 52 consecutive women who required acceleration of labour intravenous prostaglandin E2 (PGE2) was used as the oxytocic agent. These mothers were matched for age, parity, height, gestational age, initial cervical dilatation, and station and position of the fetal head with 52 women whose labours were accelerated with oxytocin; both drugs were equally effective. Acceleration to delivery intervals, second-stage durations, the number of assisted deliveries, and Apgar scores were similar regardless of the oxytocic used. Although PGE2 compares well with oxytocin, it offers no further advantages and is more expensive and less well tried than oxytocin.

Adolescent↗

Umbilical vein cortisol after spontaneous and induced labour and at elective Caesarean section.

Umbilical vein (UV) plasma cortisol levels were assayed at delivery after spontaneous labour, oxytocin-induced labour, prostaglandin E2-induced labour and after delivery by elective Caesarean section. Higher mean UV cortisol levels were observed after vaginal delivery than after delivery by elective Caesarean section. The highest mean UV cortisol level was observed in the PGE2 group which accords with the known ability of prostaglandins to increase steroid production. The significance of these findings is discussed.

Cesarean Section↗

Relation of umbilical vein cortisol to neonatal bilirubin concentrations.

Umbilical vein cortisol levels were assayed following spontaneous labour in 30 patients. Serum bilirubin was measured in the infants born at three days after delivery. No correlation was demonstrated between third day bilirubin concentration and the cord blood cortisol. The implications of this finding are discussed.

Bilirubin↗