Search PubMed⌕ Search

Biomedical subjects

C R West

Publications and source records attributed to C R West.

At least 91 records · Page 5Linked to original sources
PubMed1984

Fate of infants with transposition of the great arteries in relation to balloon atrial septostomy.

The palliation afforded by balloon atrial septostomy to 124 infants with transposition of the great arteries was assessed in terms of survival to 6 months of age without the need for further intervention. Prediction of success or failure in relation to palliation was significantly affected by the presence of associated ventricular septal defect, left ventricular outflow tract obstruction, or persistent ductus arteriosus and by the maximum volume of balloon used to perform the septostomy. There was a significant association between balloon volume and size of atrial defect found at subsequent surgery or necropsy.

Ductus Arteriosus, Patent↗
PubMed1983

1-beta-D-arabinofuranosylcytosine conjugates of corticosteroids as potential antitumor agents.

The antitumor activity and toxicity of two new 1-beta-D-arabinofuranosyl-cytosine (ara-C) conjugates of cortisol and corticosterone linked through a phosphodiester bond between the 5' and 21 positions of the respective moieties (cortisol- and corticosterone-p-ara-C) were investigated in L1210 lymphoid leukemia cells in mice. They are highly active against both i.p.- and i.c.-implanted ara-C-sensitive lymphoid leukemia in mice, exceeding the activity produced by the parent drug, ara-C. For example, corticosterone-p-ara-C exhibited the respective ILS values of 306% at 50 mg/kg/day X 9 and 294% at 75 mg/kg/day X 9 on survivals of i.p.- and i.c.-inoculated L1210 leukemic mice. The effectiveness of the conjugates seems to depend on schedules of the treatments. The 9-day continuous treatments showed a better therapeutic effectiveness than those with either a 5-day, a single or a widely spaced (q 4d., 1, 5, 9) treatment. However, they were found to be marginally effective against i.p.-implanted ara-C-resistant L1210 leukemia in mice. They were also inhibitory against proliferation of human leukemia-lymphoid cells in culture. Their superior antitumor activity and resistance to cytidine deaminase suggests that they serve as a prodrug form of ara-C or ara-CMP.

Animals↗
PubMed1983

Functional and chemical markers of PCNU activity.

A study was conducted to elucidate functional or chemical parameters that may be useful for in vivo toxicologic and pharmacokinetic analysis of PCNU. The growth-inhibitory and DNA-related parameters of this agent and its serum breakdown products in murine leukemia L1210 cells were carried out in direct comparison with BCNU. In human and dog sera, the T1/2 of intact PCNU (5-12 min) was similar to BCNU (5-16 min). However, much larger T1/2 values for PCNU (140 min) and BCNU (110 min) were determined for drug incubated in dog brain homogenates. Uptake of 14C-labeled PCNU in L1210 cells was rapid, and tenfold higher than in CCRF-CEM, a human leukemia cell line naturally resistant to BCNU and PCNU. BCNU was shown to induce DNA strand damage in L1210 and to inhibit radioactive thymidine incorporation into DNA and cross-link proteins with DNA in L1210. PCNU, by comparison, only weakly inhibited thymidine incorporation and did not induce DNA strand breakage or produce DNA-protein cross-links in L1210 at reasonable concentrations. The compounds are further differentiated in fetal calf serum by the breakdown products derived from initial concentrations of intact drug that are equipotent; those of BCNU inhibit L1210 growth whereas those of PCNU do not. PCNU, which is rapidly broken down into inactive metabolites, may have a selective therapeutic advantage if infused directly to the target site.

Animals↗
PubMed1983

Intraarterial 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and systemic chemotherapy for malignant gliomas: a follow-up study.

Twenty-five adults who harbored malignant gliomas received 72 courses of intraarterial 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) (100 mg/m2) and 67 courses of systemic vincristine (1.0 mg/m2) and procarbazine (100 mg/m2) as induction therapy (BVP) followed by 106 courses of systemic 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (methyl-CCNU) (130 mg/m2), vincristine, and procarbazine as maintenance therapy (MVP). With a 6-week interval between each treatment, the median and range for the number of courses of BVP were 3 and 1 to 4 and those for MVP were 3 and 0 to 14, respectively. Fifteen patients (60%) responded to both BVP and MVP, and 10 (40%) did not. The overall median survival time was 12.7 months (range, 1.8 to 48.5+ months). Two of 3 patients who had recurrent gliomas responded and survived for 37+ to 45+ months. Seven of 10 who had nonirradiated glioblastomas responded and survived for 9 to 22 months. Four who had nonirradiated anaplastic astrocytomas all responded and survived for 38+ to 48.5+ months. Two who also received radiotherapy (1 glioblastoma and 1 primitive neuroectodermal tumor) benefited and survived for 16.9 and 28.5+ months. All who did not respond favorably died within 8 months. During the infusion of BCNU, complications included transient orbital and head pain, periorbital and scleral erythema in all patients, and a focal seizure in 1 (4%). During the 6-month induction periods, leukopenia and thrombocytopenia occurred in 1 (4%), deep vein thrombosis occurred in 9 (36%), pulmonary emboli occurred in 8 (32%), upper respiratory infections occurred in 6 (24%), pneumonia occurred in 9 (36%), and herpes zoster occurred in 1 (4%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1982

Phospholipid-nucleoside conjugates. 3. Syntheses and preliminary biological evaluation of 1-beta-D-arabinofuranosylcytosine 5'-monophosphate-L-1,2-dipalmitin and selected 1-beta-D-arabinofuranosylcytosine 5-diphosphate-L-1,2-diacylglycerols.

Several new phospholipid-ara-C conjugates have been prepared and tested as prodrugs of the parent ara-C. The new derivative include ara-CMP-L-dipalmitin, ara-CDP-L-distearin, ara-CDP-L dimyristin, ara-CDP-L-diolein, and the radioactively labeled derivative ara-CDP-L-di[1-14C]palmitin. In addition, the unusually stable ara-CMP-L-dipalmitin-N-phosphoryldicyclohexylurea adduct was isolated as a crystalline solid (two diastereomers) in the reaction sequence to prepare ara-CMP-L-dipalmitin. The new prodrugs were solubilized by sonication methods and tested for their antiproliferative activity in vitro against mouse myeloma MPC-11 cells and against L1210 lymphoid leukemia. Such studies demonstrated that the antiproliferative activities of the prodrugs (as determined by ED50) were less that ara-C on a molar basis. In the mouse myeloma cell line some evidence was obtained that the antiproliferative activity was related to the chain length of the fatty acid side chains in the prodrugs. In in vivo studies against L1210 lymphoid leukemia in mice, the prodrugs were shown to be much more effective than ara-C, with the overall efficacy apparently being independent of the length of the fatty acid side chain. Some evidence was obtained in the vivo studies that the ara-CDP-L-dimyristin, which bears the shortest fatty acid side chain, was more toxic at the higher dosages than the longer chain length derivatives.

Animals↗
PubMed1982

Total anomalous pulmonary venous connection. Repair using deep hypothermia and circulatory arrest in 44 consecutive infants.

Forty-four consecutive infants aged from 3 days to 10 months underwent repair of total anomalous pulmonary venous connection using deep hypothermia with circulatory arrest. There were eight (18%) early hospital deaths. Using multivariate analysis no significant association could be shown between early mortality and age or weight at operation, preoperative pulmonary or systemic pressure, and preoperative condition for patients undergoing operation during the most recent five year period. Late pulmonary venous obstruction developed in four (11%) of the survivors and all of these patients died.

Female↗
PubMed1982

Transsphenoidal stereotaxic cryohypophysectomy for the management of pain in disseminated prostatic carcinoma.

Nineteen adult males with disseminated carcinoma of the prostate gland associated with intractable pain were subjected to a transsphenoidal stereotaxic cryohypophysectomy. Growth hormone (GH) assays following insulin-induced hypoglycemia were obtained once during the preoperative and twice during the postoperative period. In the postoperative assays, a 73% or greater suppression of GH levels correlated with significant clinical remission and extended survival. In all patients who had as much as 73% reduction in GH level, pain relief occurred within 4 days or less after surgery. This study shows that subtotal hypophysectomy may be adequate to achieve satisfactory clinical remission and pain control. GH assay is a useful index of the adequacy of hypophysectomy.

Adult↗
PubMed1982

Use of intrathecal and epidural morphine for pain relief in patients with malignant diseases: a preliminary report.

The results of a preliminary study involving the treatment of various malignant pain disorders by intrathecal (I.T.) or epidural (E) morphine sulfate (M.S.) injections in 18 patients are reported. Fourteen (78%) patients obtained satisfactory analgesic effects and 4 (22%) failed. The overall duration of pain relief was modest and ranged from 10 to 72 hours; the intrathecal route provided a slightly longer duration (median: 48 hours; range: 15-72 hours) of analgesia than that of the epidural route (median: 20 hours; range: 10-72 hours). Minor and transient complications occurred in 10 (55%) patients.

Adenocarcinoma↗
PubMed1982

The use of subcutaneous cerebrospinal fluid reservoirs for the prevention and treatment of meningeal relapse of acute lymphoblastic leukemia.

Subcutaneous cerebrospinal fluid reservoirs (Ommaya) were placed in 27 children and adolescents with acute lymphoblastic leukemia. Eleven of the reservoirs were used for administration of preventive central nervous system therapy and the remaining 16 reservoirs were used in the management of overt meningeal leukemia. Seven of the 11 patients treated prophylactically had recurrence of leukemia. The first site of recurrence was the central nervous system in three (42%) cases. Four of the 16 patients with reservoirs placed for the treatment of overt meningeal leukemia have not had recurrent disease. Of the 12 patients who relapsed, the site of first recurrence was the central nervous system in five cases. The incidence of major complications was 26%.

Adolescent↗
PubMed1982

Experience with transcutaneous electrical nerve stimulation for relief of intractable pain in cancer patients.

Sixty patients with intractable cancer pain were subjected to transcutaneous electrical stimulation for pain control. Evaluation, after two weeks of treatment, revealed: 17 (28.3%) excellent response, 22 (36.2%) fair and 21 (35.0%) no relief. Re-assessment after 3 months revealed 9 (15%) excellent responses, 11 (18.3%) fair and 40 (67%) failures. Extremity and trunk pains appeared to be most rewarding to patient pain, so far as pain relief is concerned. Perineal and pelvic pains were most difficult to control, only 5 of 12 (41%) cases obtained some short term relief. Pain location and sources correlated with treatment results.

Abdomen↗
PubMed1981

Phase II study--intra-arterial BCNU therapy for metastatic brain tumors.

Thirty-one patients with metastatic brain tumors (MBT) from lung cancer and ten patients with MBT from melanoma received BCNU, 100 mg/m2, every four weeks by intracarotid and/or vertebral artery infusion into each involved site. Twenty-five patients with lung cancer and all melanoma patients are currently evaluable. Twelve patients with lung cancer had complete and partial responses lasting from 1 to 14 months. Four of them with the histologic diagnosis of small cell carcinoma, one with large cell carcinoma and one with squamous cell carcinoma showed complete response. None of the patients with melanoma MBT experienced any response. All of the patients had periorbital erythralgia and/or occipital pain during the infusion. Four patients manifested mild focal seizures during the infusion or 6 to 24 hours after the treatment. Transient confusion with disorientation was observed in two patients 4 and 24 hours, respectively, after a BCNU infusion. Two patients developed reversible thrombocytopenia after the fifth course of the IA chemotherapy. Median survival of patients with MBT from lung carcinoma was 4 months, with two of them still alive at 10 and 14 months, respectively. Only one patients of the 25 with lung carcinoma died from MBT. Failure to control the primary disease resulted in the deaths of a vast majority of the patients.

Adenocarcinoma↗
PubMed1980

Nucleoside conjugates as potential antitumor agents. 3. Synthesis and antitumor activity of 1-(beta-D-arabinofuranosyl)cytosine conjugates of corticosteroids.

Six 5'-(steroid-21-phosphoryl)-1-(beta-D-arabinofuranosyl)cytosines have been prepared and evaluated against L1210 lymphoid leukemia in culture and in mice (C3D2F1/J). These include the ara-C conjugates of 11-deoxycorticosterone (5a), corticosterone (5b), cortexolone (5c), fludrocortisone (5d), 6 alpha-methylprednisolone (5e), and dexamethasone (5f). When the optimum dosage of ara-C [38 (mumol/kg)/day X 5] was given to mice bearing L1210, the ILS value found was 89%. A simple mixture of each steroid and ara-C gave ILS values that were on the whole significantly less than that of the parent nucleoside. However, of six conjugates, all but two (5d and 5f) were more active than ara-C at their optimal doses. Both corticosterone- (5b) and cortexolone-p-ara-C (5c) were especially effective at the respective optimal doses of 76.7 and 115 (mumol/kg)/day X 5. These gave ILS values of 200% each. All of the conjugates 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, 5'-nucleotidase, and acid phosphatase. However, they were shown to be resistant to hydrolysis by alkaline phosphatase.

Adrenal Cortex Hormones↗
PubMed1980

Ischemic cerebral edema in primates: effects of acetazolamide, phenytoin, sorbitol, dexamethasone, and methylprednisolone on brain water and electrolytes.

Brain edema was induced in primates (Macaca mulatta) after regional cerebral ischemia produced by selective embolization of the internal carotid artery bifurcation. Details of the alterations in the distribution of water and electrolytes in the brain during the evolution of ischemic cerebral edema have been described elsewhere. The effects of five theoretically useful pharmacological agents were studied. Acetazolamide failed to improve ischemic edema and, rather, increased mortality. Phenytoin definitely prevented both edema and infarction in only the cerebral cortex. Sorbitol was effective to induce dehydration of the affected cortex and the normal brain tissue, with obvious reduction of the brain bulk. High dose steroids showed an ability to modify edema in the cortex, putamen, and white matter. However, animals treated with methylprednisolone rather than dexamethasone showed a better neurological recovery and smaller infarcts.

Acetazolamide↗
PubMed1980

[Radioisotope ventriculography for functional evaluation of the Ommaya Reservoir (author's transl)].

Thirty nine patients with diagnosis of meningeal leukemia, meningeal lymphoma and leukemia having high risk of meningeal involvement were treated with intraventricular administration of chemotherapeutic drugs via Ommaya reservoir. In all of those patients, radioisotope ventriculography was always performed with ytterbium-169 diethyltriamine pentaacetic acid (169Yb-DTPA) at 1 week after placement of the Ommaya reservoir. In the patients who had normal cerebrospinal (CSF) flow, majority of the radioactivity injected moved to cisterna magna and basal cistern at 4 hours after injection and to subarachnoid space of the cortical surface at 24 hours. Two cases of ventricular catheter occlusion were diagnosed by this method. Two cases of catheter tip misplacement were suspected with computed tomography and confirmed with radioisotope ventriculography. One of the misplacement cases developed focal leukoencephalopathy possibly due to high concentration of methotrexate (MTX) in the brain adjacent to the ventricular cathter. Two cases showed delayed CSF circulation, and the doses of MTX were decreased to be half of the ordinary dose (12 mg/M2 once a week) during initial phase of the treatment. The dose was increased after successful treatment of meningeal dissemination and restoration of the normal CSF flow. Radioisotope ventriculography might be quite useful for detection of the flow of materials placed into Ommaya reservoir. Routine use of this procedure may be helpful to prevent reservoir- and drug-related complications.

Cerebral Ventricles↗