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Biomedical subjects

R Goel

Publications and source records attributed to R Goel.

At least 109 records · Page 6Linked to original sources
PubMed1990

A phase II trial of intraperitoneal cisplatin and etoposide for primary treatment of ovarian epithelial cancer.

We conducted a phase II trial of intraperitoneal (IP) cisplatin (DDP) and etoposide (VP-16) in stage III and IV newly diagnosed ovarian carcinoma patients with residual disease of any size. Twenty-three patients were entered, 19 had stage III and four stage IV disease. DDP 200 mg/m2 and VP-16 350 mg/m2 were given in 2 L saline IP via a Port-A-Cath (Pharmacia-Deltec, St Paul, MN). Sodium thiosulfate 4 g/m2 was given intravenously (IV) just before the start of IP instillation, and continued as a constant IV infusion of 2 g/m2/hr IV for a total of 6 hours. Treatment was given once every 4 weeks; six cycles of therapy were planned. Thirteen patients (56%) were in complete clinical remission at the end of treatment (normal physical exam, computed tomographic [CT] scan, CA-125, and peritoneal cytology). Seven of these 13 underwent a second-look laparotomy: three (13%) were in pathologic complete remission and four (17%) had microscopic disease only. Projected survival is 68% at 27 months, with 10 patients being alive and continuously free of disease. There was a very rapid fall in mean CA-125 to within normal limits at the end of the second course of treatment. The major toxicity was myelosuppression with median nadir WBC, granulocyte, and platelet counts of 2,600, 896, and 205,000/microL, respectively. There was no cumulative renal damage, anemia, hypomagnesemia, or chemical peritonitis. Neurotoxicity was similar to that observed with IV dosing. We conclude that therapy with the IP DDP/VP-16/IV thiosulfate regimen, in which all cytotoxic drugs are given only by the IP route, produces less anemia and renal damage than standard IV DDP-containing regimens, and that survival with this regimen appears to be at least as good as that produced by IV programs.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Effect of sodium thiosulfate on the pharmacokinetics and toxicity of cisplatin.

Concurrent administration of sodium thiosulfate (STS) can protect against the nephrotoxic effects of even very-high-dose cisplatin (CDDP) (i.e., 270 mg/m2 given intraperitoneally). The effect of STS on the pharmacology and toxicity of CDDP was investigated in patients receiving at each treatment 90 mg of CDDP/m2 intraperitoneally, with STS given concurrently on alternate cycles by the intravenous route. The patients received a total of 38 courses of therapy, 21 without STS and 17 with STS. STS reduced the total exposure to diethyldithiocarbamate-reactive CDDP for the peritoneal cavity and plasma by 36% and 25%, respectively. When given alone, CDDP caused a statistically significant acute reduction in creatinine clearance levels; this reduction was less evident when STS was given. We conclude that, whereas STS does reduce systemic exposure, the magnitude of this effect was not sufficient to account for the ability of STS to protect against high-dose CDDP.

Cisplatin↗
PubMed1989

Delayed erosion of intraperitoneal chemotherapy catheters into the bowel. Report of two cases.

Erosion of a silastic catheter into the small bowel occurred in two patients who previously had received multiple courses of uncomplicated intraperitoneal (IP) chemotherapy. Although bowel perforation is a recognized complication at the time of Tenckhoff catheter insertion, late erosion of the catheter into the bowel after its use for IP chemotherapy has not been previously reported. Catheter injection with radiographic contrast confirmed the diagnosis, evidence for which included nonspecific clinical findings of intraabdominal infection and pain during chemotherapy infusion.

Adult↗
PubMed1989

Pharmacologic basis for the use of dipyridamole to increase the selectivity of intraperitoneally delivered methotrexate.

Dipyridamole (DP) is an attractive agent with which to increase the selectivity of intraperitoneally delivered methotrexate (MTX). We demonstrated that DP synergistically increased the cytotoxicity of MTX to the human OV 2008 ovarian carcinoma cell line in vitro and that this synergy was highly concentration-dependent. DP did not alter MTX binding in plasma, and vice versa. We found that the two drugs were chemically compatible at concentrations of less than 400 microM, which was well above the concentration needed to make continuous i.p. infusion feasible. The ability of OV 2008 cells to accumulate uridine was used as a bioassay for the in vivo activity of DP. When this drug was infused i.p. at 12 mg/m2 per day, the steady-state peritoneal DP concentrations attained in patients were sufficient for maximal inhibition of uridine uptake, indicating concentrations high enough for synergism with MTX. We found no correlation between total peritoneal protein concentration and either free DP concentration or biologic activity. On the basis of these preclinical and pharmacologic measurements, we conclude that it should be possible to produce selective i.p. biochemical modulation of MTX with DP.

Ascitic Fluid↗
PubMed1989

Purtscher's retinopathy: an unusual association with a complicated malar fracture.

A case in which a malar fracture was associated with Purtscher's retinopathy with its accompanying impairment of vision is described. The literature concerning this uncommon condition is reviewed and its aetiology discussed. This case reinforces the importance of visual acuity testing and funduscopy following maxillofacial trauma, not only at presentation but throughout the patient's management.

Blindness↗
PubMed1989

Effect of cataract extraction on the pupil response to mydriatics.

Pupil diameters in the dark, in the light, and after mydriasis with tropicamide+ phenylephrine have been measured in 25 patients before and six months after cataract surgery. The aphakic pupil showed reduced mobility as evidenced by a smaller diameter in the and a larger one in the light. In patients who had intracapsular extraction or extracapsular extraction with intraocular lens implantation the pupils dilated less well than preoperatively. The difference in response to mydriatics is of practical importance in the assessment and treatment of peripheral retinal disorders in aphakic and pseudophakic eyes.

Aged↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1983

Astigmatism following retinal detachment surgery.

Eighty-three patients on whom successful retinal detachment had been performed were studied to note astigmatic changes following surgery. In the majority of cases the errors following such surgery are of no great clinical importance. However, in some situations a high degree of astigmatism may be produced. This study showed that these sequelae are particularly likely after radial buckling procedures, and surgeons favouring these techniques should be aware that astigmatic errors can be induced. The astigmatic errors may persist for several years after surgery.

Astigmatism↗
PubMed1982

Plasma copper in foetal malnutrition.

Plasma copper in the cord blood of 20 small for gestational age (SGA) term infants was studied. Twenty-five appropriate for gestational age (AGA) term infants were taken as control and another group of 20 preterm AGA infants for comparison. The plasma concentration of copper in term SGA infants was significantly lower than values obtained for the controls, while there was no significant difference from the levels observed in preterm infants. This lowering in the plasma copper levels was possible because of decreased liver synthesis of caeruloplasmin as a result of foetal malnutrition. There was a marked foeto-maternal difference in the plasma copper levels in all three groups which was due to much higher levels of non-diffusible caeruloplasmin in the mothers compared to the neonates.

Copper↗