PubMed HealthSearch

Biomedical subjects

R Goel

Publications and source records attributed to R Goel.

28 records · Page 2Linked to original sources

Selective intraperitoneal biochemical modulation of methotrexate by dipyridamole.

Dipyridamole increases the toxicity of methotrexate in a concentration-dependent manner. We hypothesized that concurrent intraperitoneal administration of both drugs would result in high peritoneal concentrations with much lower plasma concentrations, permitting a selective increase in the activity of methotrexate against intraperitoneal tumors without enhancing systemic toxicity. Initially, 2.16 mg/m2/d methotrexate and 12 mg/m2/d dipyridamole were delivered together as a constant intraperitoneal infusion for 48 hours. With escalation of chemotherapy, eventually 4.32 mg/m2/d methotrexate was administered for 168 hours. Forty-seven courses were administered to 18 patients. The mean peritoneal to plasma concentration ratios of methotrexate and non-protein bound dipyridamole were 71.6 +/- 34.8 and over 2,300, respectively. Chemical peritonitis was the dose-limiting toxicity. Three patients had some evidence of a response (two with decreasing tumor markers, and the third with a reduction in ascites). We conclude that the drug concentrations are in an appropriate range for selective intraperitoneal biochemical modulation of methotrexate, and that it is feasible to expose tumors confined to the peritoneal cavity to these drugs for long periods of time.

Adult

Novel approaches to intraperitoneal drug delivery.

The prolonged continuous intraperitoneal infusion of cytoarabin was studied in 28 courses. Only 9 courses were completed for the full period of 3 weeks. No cytoarabin was detected in the plasma of patients on any of these courses. The combination of intraperitoneal administration of methotrexate and dipyridamole did not show a synergistic interaction of these 2 substances. However, the addition of dipyridamole to etoposide showed a clear synergy between these 2 substances studied on a human ovarian carcinoma cell line.

Antineoplastic Agents

Peripheral carcinoid tumours of the lung: a clinicopathological study.

Peripheral carcinoid tumours (PCT) of the lung are a distinct entity. These tumours arise from subsegmental or distal bronchioles, are usually well circumscribed and encapsulated, and contain varying amounts of spindle cells. Their histogenesis is from the Kultchitsky or neurosecretory type of cells. Of 52 patients with carcinoid tumours of the lung, 11 (21.1%) had PCT. The mean age was 60.2 years, 9 out of 11 patients were females, and about two-thirds of tumours were in the left lung (8 out of 13). No patient developed carcinoid syndrome, but three patients had nonspecific respiratory symptoms. Bronchoscopy was not helpful in diagnosing any of these cases. Four patients required a wedge resection of the lung; the other six underwent lobectomy. One patient had tumours detected incidentally at autopsy. Mean tumour size was 2.39 cm (range 1.0-5.0 cm); four tumours were 3.0 cm or larger in diameter. Three cases (27.3%) had regional lymph node metastases, but no systemic metastasis was discovered. Apart from the patient who was discovered to have carcinoid tumours at autopsy, all others are alive and disease-free from 1 to 6 years after surgery.

Aged

The rabbit renotropic system.

Elevated levels of a specific renal growth factor, renotropin, have been associated with spontaneous hypertension. To examine this association more closely, we have undertaken the development of a better assay system to characterize and purify renotropin. Sera from rabbits prior to operation (control) and at a specified time after unilateral nephrectomy (uni) were examined for renotropic activity. Comparing the effects of uni to control sera in the same rabbit, significant stimulation of 3H-thymidine incorporation into the DNA of primary rabbit kidney cultures incubated in D-valine medium to eliminate fibroblast growth was noted: at 3 days postoperatively 73% (n = 13), at 7 days 103% (n = 39), at 10 days 130% (n = 31), at 21 days 101% (n = 24), at 42 days 89% (n = 13). All values were at least P less than 0.01. The stimulatory properties were dose-dependent but reached a plateau at high serum concentrations. Comparing CPM/mg protein in uni/control in different concentrations of sera 7 days postoperatively, uni versus control were 67/44 at 5% v/v, 139/72 at 10% v/v, 261/161 at 20% v/v, and 243/136 at 40% v/v. The renotropic effect of uni sera remained after dialysis in incubation medium and after sera were heated in boiling water for 5 minutes. Renal extracts obtained from growing kidneys 7 days postnephrectomy augmented renotropic activity. Atrial natriuretic factor, ouabain, PGF2 alpha, PGE1, and cAMP did not possess renotropic activity. We conclude that the primary rabbit kidney culture assay for renotropin is highly sensitive and will be an important tool to comprehend the role of renotropin in the pathogenesis of hypertension.

Animals

Isolation, purification and regeneration of protoplasts from Sporotrichum thermophile conidiospores.

Protoplasts of uniform size were prepared from mononucleated conidiospores of Sporotrichum thermophile. Conidia were preincubated in glucose yeast extract medium at 45 C for 4 h. The conidia were collected resuspended in buffer containing 0.6 M KCl (as stabilizer), and incubated with Novozyme SP249 and Cellulase CP at 37 C for 6 h. The protoplasts were separated from cell wall fragments and intact conidia by centrifugation over 50% sucrose. The purified protoplasts were regenerated in glucose yeast extract broth after 7 h of incubation at 45 C.

Cell Wall