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Biomedical subjects

R Goel

Publications and source records attributed to R Goel.

At least 19 recordsLinked to original sources
PubMed1992

A nuclear magnetic resonance investigation of the upper airways in ferrets. II. Contrast-enhanced imaging to distinguish vascular from other nasal fluids.

Proton magnetic resonance imaging (MRI), used in conjunction with the intravascular contrast agent albumin-(Gd-DTPA), provides a means to distinguish vascular fluids from other nasal fluids in the upper airways. Ferrets were given an intravenous dose of albumin-(Gd-DTPA) followed by an intranasal challenge with either histamine (HS) or methacholine (MC). An observed increase in image intensity indicates that HS and MC both cause an accumulation of fluids in the nasal turbinate region. The MRI data are also influenced by the presence of blood, which contains the contrast agent, and a clear distinction can be made between vascular fluids and other nasal fluids (i.e., cellular and glandular secretions). The results show that HS causes an increase in vascular fluids in the nasal turbinates while MC does not. This methodology represents a new means to investigate airway pharmacology and the pathophysiology associated with various pharmacological agents, allergens, or viral infections.

Administration, Intranasal↗
PubMed1992

Pharmacokinetic study of intraperitoneal streptozotocin.

Streptozotocin, a nitrosourea, has limited antitumour activity. However, in concentrations and exposures higher than those achieved after intravenous dosing, streptozotocin has been reported to sensitize various cell lines in vitro to other nitrosoureas or alkylating agents. We hypothesized that the intraperitoneal administration of streptozotocin would achieve concentrations and exposures in the peritoneal cavity sufficient for this sensitization to take place. The pharmacokinetics of streptozotocin in the peritoneal cavity and in plasma were determined in patients who received 1 g of streptozotocin via the intraperitoneal route. Fifteen courses were administered to 12 patients. The mean total area under the concentration versus time curves (AUC) was 183 +/- 31 (SE) mM min in the peritoneal cavity (5 courses) and 5.3 +/- 1.1 (SE) mM min in plasma (6 courses). The mean peritoneal to plasma AUC ratio was 64 +/- 23 (5 courses). The mean peak streptozotocin concentrations in the peritoneal cavity (5 courses) and plasma (6 courses) were 1.9 +/- 0.4 mM and 0.03 +/- 0.01 mM, respectively. No significant toxicity was observed on any course. We conclude that intraperitoneal administration of streptozotocin is feasible, and that drug concentrations and exposures are in an appropriate range in the peritoneal cavity to cause sensitization to other nitrosoureas.

Adult↗
PubMed1991

A polyclonal antibody preparation with Michaelian catalytic properties.

1. 4-Nitrophenyl 4'-(3-aza-2-oxoheptyl)phenyl carbonate (I), an amide conjugate (XI) involving the carboxy group of 4-nitrophenyl 4'-carboxymethylphenyl phosphate and an amino group of keyhole-limpet haemocyanin, and a fluorescein derivative (XVII) were synthesized. 2. The conjugate (XI) was used as an immunogen with which to raise polyclonal antibodies in multigeneration cross-bred sheep; the fluorescent derivative (XVII) was used for the initial assessment of the antisera via binding assays monitored by fluorescence polarization; the carbonate ester (I) was used as a chromogenic substrate for the investigation of catalytic activity. 3. The IgG from the antiserum of sheep no. 270 was isolated by Na2SO4 precipitation and chromatography on Protein G-Sepharose. 4. This preparation of IgG catalysed the hydrolysis of the carbonate ester (I); the catalysis at pH 8.0 and 25 degrees C obeyed Michaelis-Menten kinetics with at least 25 turnovers, Km = 3.34 microM, and lower limits for kcat. of 0.029 s-1 and for kcat./Km of 8.77 x 10(3) M-1.S-1, on the unlikely assumption that the concentration of catalytic antibody is provided by twice the total IgG concentration (two sites per molecule); probable estimates of the fraction of the total IgG that is anti-haptenic IgG and of the fraction of this that is catalytically active suggest that the values of kcat./Km are actually very much larger than these lower limits. 5. The failure of the antibody preparation to catalyse the hydrolysis of the isomeric 2-nitrophenyl carbonate (II), which differs from compound (I) only in the position of the nitro substituent in the leaving group, compels the view that catalytic activity is due to antibody rather than contaminant enzyme; this conclusion is supported by (a) the failure of the following to discriminate effectively between the isomeric substrates (I) and (II): pig liver carboxylesterase, rabbit liver carboxylesterase (collectively EC 3.1.1.1), whole serum from a non-immunized sheep and whole serum from a sheep immunized with a derivative of 3-O-methylnoradrenaline and (b) the lack of catalytic activity in IgG preparations from sheep immunized with sulphoxide or sulphone analogues of immunogen (XI). 6. The various parameters used for the comparison of the kinetic characteristics of hydrolytic catalytic antibodies are discussed. 7. The characteristics of hydrolysis of compound (I) catalysed by the present polyclonal antibody preparation are shown to be substantially better in most respects than those of analogous reactions of two other carbonate esters catalysed by monoclonal antibodies.

Animals↗
PubMed1991

Experimental immune complex-mediated glomerulonephritis in the nonhuman primate.

This study was undertaken to develop a model of immune complex (IC)-mediated glomerulonephritis (GN) in the nonhuman primate that could be used in subsequent studies to examine critically the role of the erythrocyte complement receptor (E-CR) in the pathogenesis of IC-mediated disease. Cynomolgus monkeys were chosen for study because they constitutively express E-CR levels that are either less than, equal to, or greater than that seen in normal man. After immunization with bovine gamma globulin (BGG), the GN induction protocol was begun in 10 cynomolgus by initiating daily i.v. administration of BGG in amounts sufficient to achieve or exceed antigen/antibody equivalence (assessed by the quantitative precipitin assay) for precipitating antibody present in the plasma volume. We found that within eight weeks of daily BGG administration of all the cynomolgus developed IC-mediated GN, irrespective of the initial E-CR level of the animals. However, the high E-CR cynomolgus tended to receive the higher BGG doses because of higher initial antibody levels to BGG. When the total number of glomerular deposits (determined by morphometric studies) per total BGG dose for each animal was plotted against the initial CR/E of that animal, there was a tendency for the animals with higher CR/E levels to have a lower number of glomerular deposits/BGG dose (r = 0.62, P = 0.06). Also, the total number of glomerular deposits correlated with the severity of the GN. During the early weeks of the GN induction protocol, the IC that formed in vivo (assessed by infusion of 125I-BGG) bound in large amounts to the circulating erythrocytes of the cynomolgus with medium or high E-CR levels. However, when tested after the onset of heavy proteinuria, which occurred between weeks 5 and 8 of daily BGG administration, the IC that formed in the circulation bound only poorly to circulating erythrocytes. By this time the E-CR levels had declined to 43 +/- 9% of initial values (P less than 0.01). This study demonstrates that: 1) A workable model of IC-mediated GN has been developed in the nonhuman primate. 2) During the induction of GN, CR/E and the ability of the erythrocyte to bind IC in vivo are decreased significantly. This suggests that an intact E-CR system could play a role in the protection against IC-mediated disease. However, further study will be needed to test that hypothesis critically. The present model should be useful in such studies.

Animals↗
PubMed1991

A phase II trial of intraperitoneal cisplatin and etoposide as salvage treatment for minimal residual ovarian carcinoma.

We conducted a phase II study of intraperitoneal (IP) cisplatin (CDDP) and etoposide (VP-16) as salvage therapy in patients with ovarian cancer who had persistent disease or who had relapsed after primary systemic chemotherapy and had residual disease of less than 2 cm. Two hundred eleven courses of IP chemotherapy consisting of CDDP 200 mg/m2 and VP-16 350 mg/m2 were administered. All patients received intravenous (IV) thiosulfate protection. Treatment was given once every 4 weeks for a median of six cycles. Twenty-four of 37 assessable patients were clinically free of disease at the end of treatment (normal physical exam, computed tomographic [CT] scan, CA-125 and peritoneal cytology); one patient had a partial response. Ten of these 24 patients consented to reexploration at the end of treatment, and nine were in pathologic complete remission, while one patient had positive peritoneal washings as her only evidence of persistent disease. The median survival of the 37 patients was 26 months from the first day of IP treatment and 51 months from diagnosis. The major toxicity was myelosuppression, with median nadir WBC, granulocyte, and platelet counts of 2,400, 684, and 134,000/mm3, respectively. There was no cumulative renal damage, hypomagnesemia, or chemical peritonitis. We conclude that IP CDDP and VP-16 can produce pathologic complete remissions when used as a second-line regimen for patients with ovarian cancer who have received systemic cisplatin-based therapy and have less than 2 cm disease.

Adult↗
PubMed1990

The effect of corticosteroid administration on bleomycin lung toxicity.

Bleomycin is well recognized as an active antineoplastic agent in the treatment of germ cell tumors. Pulmonary toxicity is the most significant complication of bleomycin administration. In this report, an attempt is made to modify both the incidence and severity of this side effect. One hundred eleven patients with advanced germ cell tumors were treated with a combination chemotherapy program that included the administration of 30 units (U) of bleomycin as a continuous infusion daily for 3 days every 3 weeks rather than a weekly bolus injection of a total of 360 U (mean dose received, 307 U). Also, 31 patients received high-dose steroids, which have been shown to modify bleomycin-induced pulmonary toxicity, for the treatment of chemotherapy-induced emesis. Changes in carbon monoxide diffusion capacity (DLCO) prompting cessation of bleomycin therapy occurred in 15 cases (bleomycin was stopped in one case due to dyspnea and lung infiltrates, and one patient suffered fatal respiratory failure probably due to bleomycin lung toxicity). Thus, probable bleomycin pulmonary toxicity changed the clinical treatment in 15.3% of the cases. On long-term follow-up, only two patients have demonstrated a residual decrease in DLCO. The incidence of a greater than 25% decrease in DLCO was 34% and was not significantly altered by the administration of steroids (P = 0.96). It is possible, however, that the low incidence of clinically significant and fatal pulmonary toxicity, as experienced in this group of patients, may be related to the infusion of bleomycin. It also is possible that the reversibility of the decrease in DLCO in 95% of the patients may be related to the duration and schedule of bleomycin administration. As bleomycin continues to be an important drug in the treatment of advanced germ cell tumors, further studies are warranted to evaluate the role of the continuous infusion of bleomycin as opposed to bolus therapy.

Administration, Oral↗
PubMed1990

Production of cellulolytic enzymes by immobilized Sporotrichum thermophile.

Spores of Sporotrichum thermophile were immobilized in agar, polyacrylamide, and sodium alginate to generate in situ mycelium for production of cellulolytic enzymes. Immobilized mycelium was considerably less effective than free cells for cellulase productivity. Of the three gel types, agar beads proved to be the best carrier for the immobilized spores and subsequently generated mycelium. Results of repeated batch experiments suggested that the immobilized mycelia could be reused but at much reduced efficiency.

Acrylic Resins↗
PubMed1990

Comparison of the pharmacokinetics of ultrafilterable cisplatin species detectable by derivatization with diethyldithiocarbamate or atomic absorption spectroscopy.

The pharmacokinetics of the cisplatin (DDP) species detected by measurement of diethyldithiocarbamate (DDTC)-reactive species (DDTC-DDP) were compared to the pharmacokinetics of the species detected by measurement of total ultrafilterable platinum in patients receiving DDP alone or in combination with the nephroprotective agent sodium thiosulfate. The doses of DDP studied were 100 mg/m2 (11 courses given to eight patients) and 202.5 mg/m2 (five courses given to four patients) given as 2 h i.v. infusions, the latter with concurrent thiosulfate. When DDP was given alone (100 mg/m2) the two assays yielded the same area under the curve (AUC) values for DDTC-DDP and total ultrafilterable platinum during the first 4 h after the start of infusion; however, beyond 4 h post-infusion, the AUC for total ultrafilterable platinum was consistently greater than that for DDTC-DDP. When DDP was given with thiosulfate (202.5 mg/m2), the AUC for total ultrafilterable platinum was significantly greater than that of DDTC-DDP during the whole sampling period. The ratio of the AUC for total ultrafilterable platinum to DDTC-DDP, when DDP was given with thiosulfate, was barely significantly greater than that when DDP was given alone. These data indicate that during and immediately following a short infusion of DDP the major platinum-containing species present in plasma ultrafiltrate are still capable of reacting with nucleophilic sites on molecules such as DDTC; however, as the reactive species are eliminated, longer half-lived non-reactive ultrafilterable platinum species begin to predominate. They also indicate that although thiosulfate does neutralize a measurable amount of DDP in the plasma on the schedule employed, this degree of neutralization is not sufficient to explain the protection against DDP-induced nephrotoxicity produced by thiosulfate.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Excess sucrose and glucose ingestion acutely elevate blood pressure in spontaneously hypertensive rats.

Spontaneously hypertensive rats (SHR) were fed 6 different diets. The baseline diet (I) derived equal calories from sucrose, proteins, and fats. Three other diets (II, III, VI) derived the majority of calories from refined CHO, sucrose or glucose, with decreases in calories from proteins or fats. The last two diets (IV, V) were relatively low in sucrose with a higher percentage of the total calories from proteins and fats, respectively. From 3 to 15 weeks on the diets, the highest average BP was in rats consuming high concentrations of sucrose or glucose (II, III, VI). Urinary excretory rates of norepinephrine (NE) at 5, 10 and 15 weeks and epinephrine at 5 and 10 weeks were significantly elevated in rats ingesting diets high in refined CHO, and NE positively correlated with blood pressure (BP) at 5 and 10 weeks of the study. At the end of the study, serum insulin levels were not different, but plasma renin and serum glucagon levels were lower in SHR consuming the diets with high CHO concentrations. We conclude that equally elevated BP are seen with relatively high intakes of either sucrose or glucose, whether the balance of calories is derived from lessening fat or protein. This is secondary, at least in part, to alterations in NE metabolism.

Animals↗
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↗