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Biomedical subjects

S Paul

Publications and source records attributed to S Paul.

At least 271 records · Page 15Linked to original sources
PubMed1986

Doxorubicin/vinblastine and doxorubicin/cyclophosphamide combination chemotherapy by continuous infusion.

Fifty-two patients received one of two doxorubicin (DOX)-based admixtures; DOX plus cyclophosphamide (CTX) or DOX plus vinblastine (VBL) administered as a continuous 24-hour infusion for protracted periods. Compatibility and stability of the two-drug admixture was established for a minimum of 7 days. Twenty patients on the DOX/CTX admixture were infused for a median of 20 days (range, 7-56 days). DOX/VLB was infused in 32 patients for a median of 18 days (range, 5-48 days). Dose limiting toxicity was leukopenia observed in 14/52 patients; 4/20 on DOX/CTX and 10/32 on DOX/VLB. Additional toxicities observed included stomatitis (15%) and subclavian vein thrombosis (23%). Tumor responses were observed in 11 patients, including 6/13 breast cancer; 2/2 hepatoma; 2/4 sarcoma and 1/1 ovarian cancer. Responses were relatively short-lived and no responses were noted in known anthracycline resistant tumors. Admixtures of chemotherapeutic agents represents a novel, but feasible, mechanism for delivery of multiple drugs with an infusion schedule and can be considered for Phase III comparative clinical trials.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Solubilization of active receptors for VIP from guinea pig lung.

The zwitterionic detergent 3-[(3-cholamidopropyl)dimethyl-ammonio]-1-propane sulfonate (CHAPS) was used to solubilize functional receptors for vasoactive intestinal peptide (VIP) from guinea pig lung. The binding of [125I]-VIP to the soluble receptors was time-dependent, reversible and saturable. Trypsin destroyed the activity of the receptors, indicating their proteinic nature. Dithiothreitol reduced the binding in a dose-dependent manner, suggesting the importance of disulfide bond(s) in receptor-binding activity. Binding of [125I]-VIP to the receptors was reversible and was competitively inhibited by unlabeled VIP, with 50% inhibition obtained at 305 nM VIP.

Animals↗
PubMed1986

Receptors for vasoactive intestinal peptide on isolated human sweat glands.

Human sweat gland function is predominantly under cholinergic control. Sweat secretion may also be regulated by Vasoactive Intestinal Peptide (VIP), which coexists with acetylcholine in nerves to sweat gland acini and ducts. We have examined the expression of VIP receptors on isolated human eccrine sweat glands. Two classes of specific binding sites for VIP were demonstrated: one with high affinity (Kd = 0.58-2.4 nM), and another with low affinity (Kd = 175-288 nM). The data suggest a physiological regulatory role for VIP in sweat gland function.

Eccrine Glands↗
PubMed1986

Vinblastine plus cisplatin in advanced non-small cell lung cancer: lack of advantage for vinblastine infusion schedule.

We have evaluated 31 patients with advanced non-small cell lung cancer treated by short-term 5-day vinblastine infusion combined with bolus cisplatin. Nine of 31 patients (29%) had partial and complete responses. Although five of nine (55%) of the responders were alive at greater than or equal to 1 year, three of the 31 patients experienced drug-related mortality. Our experience, as well as a review of previously reported trials in the literature, suggests that the infusion schedule of vinblastine offers no advantage over the bolus schedule.

Adenocarcinoma↗
PubMed1986

Protracted low-dose cisplatin infusion in advanced colorectal cancer.

Protracted, 24-hour, continuous-infusion cisplatin at a dose rate of 5 mg/m2/day was administered to 25 patients with advanced measurable colorectal cancer. All patients had previously received 5-FU administered on the same schedule. Sixteen patients received the infusion for greater than or equal to 14 days and were considered evaluable for response assessment. No patient achieved a response.

Ambulatory Care↗
PubMed1985

5-Fluorouracil and methotrexate administered simultaneously as a continuous infusion. A phase I study.

Infusion delivery systems have been evaluated for administration of many individual chemotherapeutic agents including 5-fluorouracil (5-FU) and methotrexate (MTX). This study combined the two drugs as an admixture, and in a Phase I trial design established a useful dose schedule for each of the component drugs. 5-FU at a fixed dose rate of 300 mg/M2/day was delivered with methotrexate (MTX) at four different dose rates (0.75, 1.0, 1.5, or 2.0 mg/M2/day, respectively). The drug solution was delivered via a subclavian venous access with a portable infusion pump in an ambulatory setting. Twenty-nine patients received a total of 38 courses of the two-drug infusion: 21 courses were delivered with the two agents admixed constantly throughout treatment (Schedule A) and 17 were administered the treatment with 5-FU delivered continuously and MTX added to the 5-FU for alternate 14-day cycles (Schedule B). For the former schedule, dose-rate-limiting toxicity was related to MTX and included stomatitis developing at days 8 to 14 (median, day 8) with the higher dose rates (1.5-2.0 mg/M2/day) and thrombocytopenia developing at days 11 to 56 (median, day 14) at the lowest dose rates (1.0 mg/M2/day). For Schedule B, dose-rate-limiting toxicity was similarly due to the MTX with thrombocytopenia and/or chemical hepatitis developing in six of seven courses of MTX at 1.0 mg/M2/day and in five of ten courses delivered at 0.75 mg/M2/day. On Schedule B the MTX-associated toxicities were reversed when the MTX administration was interrupted and in the face of continued 5-FU infusion. A reasonable dose rate and schedule for continuous infusion of 5-FU combined with MTX is: 5-FU 300 mg/M2/day X 28 days and MTX 0.75 mg/M2/day for days 1 to 14, with cycles administered consecutively each 28 days.

Adult↗
PubMed1985

Autoantibody to vasoactive intestinal peptide in human circulation.

In a radioassay for Vasoactive Intestinal Peptide (VIP)-binding, eight out of 33 plasma samples from healthy human subjects exhibited specific binding ranging from 2.6% to 46.7% of total [125 I]VIP. This binding was competitively displaced by unlabeled VIP. The structurally homologous peptides, Peptide Histidine Isoleucine (PHI) and secretin, were, respectively, 72-fold and 413-fold less potent than VIP in displacing bound [125 I]VIP, whereas the unrelated peptides, neurotensin, eledoisin, bombesin and metenkephalin, were without effect on the binding. The antibody nature of the VIP-binding factor was suggested by its precipitation with ammonium sulfate, attenuation after absorption with Staphylococcus aureus preparations, precipitation with antisera against human IgG and IgM, and coelution with standard IgG and IgM on anion-exchange and high-performance gel-filtration columns. Pepsin treatment of purified IgG fraction yielded a VIP-binding species with apparent molecular weight of 108 +/- 13 kDa that was precipitated by antiserum against the F(ab)2 fragment of the IgG molecule. These results demonstrate the existence in some human plasmas of an autoantibody that binds VIP.

Antibody Specificity↗
PubMed1985

[Intranasal TRH for the stimulation of hypophyseal and thyroid reserves. Preliminary report].

Intranasal, intravenous and oral TRH have been compared in 9 healthy volunteers. Intranasal administration of TRH leads to excellent stimulation of pituitary TSH secretion. Serum TSH levels are significantly higher than after intravenous TRH (p less than 0.005) and lower than after oral TRH (p less than 0.005). As with intravenous TRH, peak TSH response is reached at 20-30 minutes, but the stimulatory effect is prolonged and elevated TSH levels can be measured for up to 3 hours. Stimulation of T3 and free T4 at 3 hours is comparable in all three administration forms of TRH. The practical advantages of the intranasal route are that no intravenous injection is necessary, overnight fasting is not required and the duration of the test is short (30 minutes, in contrast to 3 hours in the oral test).

Administration, Intranasal↗
PubMed1985

Streptozotocin for metastatic malignant melanoma.

Streptozotocin was administered at a dose of 500 mg/m2/day by continuous infusion for 120 hours to 14 patients with advanced malignant melanoma. No responses were observed in this group of patients and the median survival for the entire group was 2 months. At the dose and schedule delivered, streptozotocin is inactive against malignant melanoma.

Adult↗
PubMed1985

Intranasal thyrotrophin releasing hormone is a potent stimulus for TSH release in man (comparison with intravenous and oral TRH).

Intranasally administered TRH was tested and compared to i.v. and oral TRH in respect to its efficacy of TSH stimulation and thereby the stimulation of thyroid reserve. TSH release after nasal application is as prompt as after the i.v. route, reaching a peak at 20 to 30 min. After that, however, compared to the i.v. administration its stimulatory effect is prolonged, lasting over 3 h. At the dose used in this study the peak TSH response after intranasal TRH administration was 14.7 +/- 1.6 mU/l compared to 8.4 +/- 1.4 and 23.1 +/- 4.4 mU/l after i.v. and oral administration respectively (P less than 0.005). Intranasal application of TRH is as potent as i.v. or oral TRH for the stimulation of thyroid reserve. At 3 h a marked increase of T3 and a smaller elevation of FT4 is observed (delta T3 = 48.4%, delta FT4 = 31.6%). The nasal peptide was well tolerated locally and systemic side effects were comparable to those of i.v. TRH. This form of application offers a practical advantage by avoiding intravenous injections. Its diagnostic potential in investigation of thyroid disease and its possible therapeutic application have yet to be elucidated.

Administration, Intranasal↗
PubMed1985

Vasoactive intestinal peptide as a possible transmitter of nonadrenergic, noncholinergic relaxation of pulmonary artery.

Electrical field stimulation of isolated guinea pig pulmonary artery induced a brief initial contraction followed by a more prolonged relaxation. alpha-Adrenergic blockade prevented the contraction and enhanced the relaxation. beta-Adrenergic and cholinergic muscarinic blockade partially reduced the relaxation, but 44.4% of the relaxation persisted after adrenergic and cholinergic blockade. The PA relaxation was associated with the release of immunoreactive VIP, both before and after this blockade. Tetrodotoxin abolished the nonadrenergic, noncholinergic relaxation and markedly reduced the release of VIP. This relaxation was similarly attenuated by a monoclonal antibody against VIP.

Acetylcholine↗
PubMed1985

[Effect of various factors on in vitro fertilization (IVF) and embryo transfer in the human in clomiphene/hMG/hCG stimulated cycles].

In the present study we tried to analyse data obtained on the occasion of an in vitro fertilization programme at the department of obstetrics and gynecology of the University of Kiel, to extract some of the important factors, because their positive or negative influence on the success of extracorporal insemination, embryo transfer and implantation has not been clearely defined till now and to value their concern. Between July 1982 and February 1983 105 sterile patients with ovulatory menstrual cycles have been treated by the technique of in vitro fertilization and embryo transfer, successively. Follicular growth was stimulated by 150 mg clomiphen daily from 3rd to 7th day and application of 225 IU hMG on 6th, 8th and 10th day. Finally ovulation was timed 36 hours before follicular puncture by 5000 IU hCG. In 24 per cent endogenous LH peak could be observed. In 86 per cent of the 80 patients exactly timed one oocyte was to be found minimally. In 68 per cent of these patients after all an embryo transfer was done (24 times one embryo, 13 times two, 9 times three and once four embryos). 89% of the embryos have been transfered as 4-or 8-cell stage, only 11 per cent as two cell stage. Transfer took place 48 to 50 hours following insemination. There was no correlation between the maturity classified morphologically of the oocytes and the diameter of their follicles. The speed of development of the embryos was not correlated with the size of their follicles. too. In 60-70 per cent of all cases, in which an embryo transfer was possible, husbands had normal spermiogram. The percentage of unfertilised oocytes following insemination using non-optimal sperma was increased in all types of cycles, additionally there was a reduction of the developing speed of resulting embryos. Doubtless two the four pregnancies resulted after insemination using sperma of less quality. The conjugation rate is said to be not correlated directly with the exactness of timing of the application of hCG with reference to follicular maturity, but in all pregnancies hCG was injected simultaneously with the peak of estradiol.

Chorionic Gonadotropin↗
PubMed1984

Electrophysiological and pharmacological actions of the convulsant benzodiazepine Ro 5-4864.

Ro 5-4864 (4'-chlorodiazepam) elicited convulsions in mice with a CD50 of 23.5 mg/kg (i.p.) and increased the firing rate of substantia nigra zona reticulata neurons in a dose dependent fashion (0.5-4 mg/kg i.v.). Diazepam and clonazepam, but not Ro 15-1788, were potent inhibitors of Ro 5-4864 induced convulsions. Ro 15-1788 was also ineffective in reversing Ro 5-4864 induced increases in cell firing of zone reticulata neurons. Muscimol potently inhibited the seizures and reversed increases in cell firing elicited by Ro 5-4864. Phenobarbital and pentobarbital inhibited Ro 5-4864 induced convulsions with moderate potencies, while phenytoin and carbamazepine were ineffective at doses of up to 100 mg/kg. These observations suggest that Ro 5-4864 does not elicit its pharmacologic actions through a direct action at a 'brain-type' benzodiazepine receptor. However, both the profile and potency of compounds effective in inhibiting the electrophysiological and pharmacological effects of Ro 5-4864 suggest that this compound may act by perturbation of a component of the GABA-benzodiazepine receptor chloride ionophore complex. These findings do not, however, rule out a direct involvement of the high affinity 'peripheral-type' benzodiazepine receptors found in brain.

Animals↗