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Biomedical subjects

G Thomas

Publications and source records attributed to G Thomas.

At least 739 records · Page 41Linked to original sources
PubMed1985

Calcium agonism, a new mechanism for positive inotropy. Hemodynamic effects and mode of action of BAY K 8644.

BAY K 8644 [methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethyl -phenyl)-pyridine-5-carboxylate] is a nifedipine-like 1,4-dihydropyridine (DHP). In contrast to the well-known calcium antagonistic DHPs, it has vasoconstricting and positive inotropic properties. In the pentobarbital-anesthetized dog, it increases blood pressure, peripheral resistance, and left ventricular (dP/dt)max dose-dependently from 3 to 100 micrograms/kg i.v. If the vagus is blocked, heart rate is unchanged. In the isolated isovolumic perfused guinea pig heart, BAY K 8644 has positive inotropic and coronary constricting actions from 10(-9) mole/liter. At 10 times higher concentrations, this compound also increases the heart rate up to 20%. BAY K 8644 has no effect on rabbit aortic strip at physiological K+ concentrations, but potentiates the K+ -induced contraction of the strip. In the partially depolarized aortic strip (18 mM K+), BAY K 8644 induces concentration-dependent contractions, which are competitively inhibited by the calcium-antagonistic DHP nifedipine. Chemically different calcium antagonists such as verapamil or diltiazem inhibit the BAY-K-8644-induced contractions noncompetitively. These results indicate that a specific DHP receptor exists, which binds nifedipine and BAY K 8644. In contrast to the calcium-antagonistic DHPs like nifedipine, BAY K 8644 increases the calcium influx into the cell.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1985

[The increase in the liberation rate of propyphenazone from preoral solid dosage forms].

The authors report on the influence of the granulation and tabletting applying macromolecular agents (polyvinylpolypyrrolidone Heweten 40, polyethylenglycol 6000, polyvinylpyrrolidone K25, polyvinylpyrrolidone K90 and potato starch) on the liberation rate of propyphenazone which exhibits by its hydrophobicity unfavourable dissolution parameters. A significant increase of the liberation rate of propyphenazone (re-crystallized from various media) has been realized by direct pressing of polyvinylpolypyrrolidone and Heweten 40 as well as by gelatine solution granulation, with which the last method exhibits the advantage of an increased accuracy of dosage and a decreased friability. The gelatine granulation of the drug itself as well as the starch granulate addition resulted in an increased dissolution rate. The addition of other agents (polyvinylpyrrolidone K25, K90 and polyethylenglycol 6000) as well as the pressing of a propyphenazone produced by re-crystallization of an aqueous tenside solution, which distinguishes by an extreme dissolution rate, were not at all suitable for the tabletting. The tablet disintegration caused by hydrophile disintegration media, is the condition granting the liberation of the hydrophobic drug. The wettability and thus the dissolution rate of the drug are increased by the liberation.

Antipyrine↗
PubMed1985

[Effect of tensides on the dissolution rate and crystal pattern of propylphenazone].

Propyphenazone has been recrystallized from different polarity solvents by means of various non-ionic tensides (Tween 20 and 80, Brij 35 and Myrj 51) and the ionic sodium lauryl sulphate. The tenside amount adsorbed by propyphenazone could be determined by measurements of the surface tension. Differences between the adsorption of the non-ionic tensides and the ionic product could be stated. Differences of the crystal areas can be eliminated by adding tensides to polar and apolar solvents. All the recrystallization products distinguish by a significant increase of the dissolution rate.

Antipyrine↗
PubMed1984

Results and toxicity of the treatment of anal canal carcinoma by radiation therapy or radiation therapy and chemotherapy.

The results of treating anal canal carcinoma by radical external beam radiation alone (RT) or by combined 5-fluorouracil, mitomycin C and radiation (FUMIR), were compared in nonrandomized groups of patients treated in a single center. In each treatment regimen, surgery was reserved for those patients with residual carcinoma. The uncorrected 5-year survival rate in each group was approximately 70%, but primary tumor control was achieved in 93% (28/30) with FUMIR compared to 60% (15/25) treated with RT. Acute hematologic and enterocolic toxicity with uninterrupted external beam radiation courses of 5000 cGy in 4 weeks plus chemotherapy led to the adoption of split-course treatment. Serious late toxicity requiring surgical intervention occurred in 3 of 25 following RT, and in 5 of 30 following FUMIR. Colostomies were needed as part of treatment for residual carcinoma or for the management of treatment-related toxicity in 11 of 25 treated by RT and have been required to date in 4 of 30 treated by FUMIR. The improvement in the primary tumor control rate and the reduction in the number of patients requiring colostomy when compared with the results of RT favor combined chemotherapy and radiation as the initial treatment for anal canal carcinoma.

Actuarial Analysis↗
PubMed1984

Adenocarcinoma of the rectum metastatic to the oral cavity. Two cases and a review of the literature.

Two cases of metastatic adenocarcinoma occurring in the oral cavity are presented. One patient experienced lip paresthesias and pain as the presenting complaint. The other patient developed a growth at the site of a recent tooth extraction, and had bony erosion of the adjacent maxilla. The literature on metastatic lesions to the oral cavity including mandible is reviewed. This problem has been described almost exclusively in the oral and dental surgery literature. The clinical symptoms and signs described here should suggest the possibility of metastatic tumor to the oral cavity, and may be the initial manifestation of malignant disease.

Adenocarcinoma, Mucinous↗
PubMed1984

Correlation of amniotic fluid optical density at 650 nm and lecithin/sphingomyelin ratios with phosphatidylglycerol.

In this study we have attempted to correlate amniotic fluid optical density measurements and lecithin/sphingomyelin (L/S) ratios with the presence of phosphatidylglycerol. An 85% correlation (126 of 148) of all three parameters was noted. When the assumption was made that phosphatidylglycerol is indicative of fetal pulmonary maturity, 93 of 94 fluid samples having an optical density at 650 nm greater than or equal to 0.15 had demonstrable phosphatidylglycerol for a 1% false positive rate. In 53 fluid samples having an optical density at 650 nm less than 0.15, phosphatidylglycerol was present in 11 and absent in 42, a 21% false negative rate. The same analyses with lecithin/sphingomyelin ratios showed a 5% false positive rate and a 31% false negative rate.

Amniotic Fluid↗
PubMed1984

An activated S6 kinase in extracts from serum- and epidermal growth factor-stimulated Swiss 3T3 cells.

Soluble extracts from serum- or epidermal growth factor-stimulated Swiss 3T3 cells show up to a 25-fold increase in their ability to phosphorylate 40 S ribosomal protein S6. The increased S6 phosphorylation is due to increased protein kinase activity in extracts of stimulated cells and not due to the inactivation of an S6 phosphatase. However, the presence of phosphatase inhibitors as well as EGTA is required during the preparation of cell extracts to obtain fully active S6 kinase(s). Epidermal growth factor has little effect at concentrations below 10(-10) M: activity increases sharply at 10(-9) M epidermal growth factor and reaches saturation at 10(-8) M (50-60% of the activity obtained by stimulating with 10% serum). Activation of the kinase activity in cell extracts is observed as early as 2 min after serum stimulation, reaches 50% between 10 and 15 min, and is maximal by 60 min of serum stimulation. Phosphorylation in vitro of ribosomal protein S6 with extracts from serum-stimulated cells followed by analysis of the tryptic phosphopeptides shows the presence of 9 of the 11 phosphopeptides induced by serum in vivo.

Animals↗
PubMed1984

[Congenital hypothyroidism with probable anomaly of thyroid receptiveness to thyrotropin. 2 cases].

Congenital hypothyroidism associated with unresponsiveness to thyrotropin (TSH) is a very rare condition. In the two cases reported the thyroid gland was not enlarged and endogenous THS secretion control was normal: the high TSH levels observed during hypothyroidism returned to normal after thyroid hormone replacement therapy and were normally responsive to TRH stimulation. Thyroid iodide clearance was investigated under various conditions of stimulation and inhibition. In hypothyroidism clearance was normal and TSH levels very high. During replacement therapy clearance seemed to be inversely correlated to levels of circulating thyroid hormones; it was almost nil in euthyroidism. Whatever the level of circulating hormones, clearance was not reactivated by exogenous TSH. In one patient in euthyroidism clearance, which was virtually zero, was unmodified after butyric AMPc stimulation, which suggests that the anomaly lies below the AMPc stage.

Adolescent↗
PubMed1984

Interstitial applications of laser irradiation in hematoporphyrin derivative-photosensitized Dunning R3327 prostate cancers.

Two prostate tumour models (Dunning R3327H and AT) were tested in rats to see if they were sensitive to hematoporphyrin-photoradiation therapy (HPD-PRT). The R3327H tumours were irradiated by implantation of a single fiber optic and the R3327 AT tumours were treated with implantation of four fiber optics simultaneously. Thermal measurements made at the tip of the fiber and up to 1 cm from the tip indicated temperature rises from 1.5 degree C to 20 degrees C at the tip and 0 degree to 8 degrees C distal to the tip, with power densities ranging from 100 mW to 500 mW. The R3327H tumour was controlled up to 8 weeks post-HPD-PRT, when the initial tumour size was 400-500 mm3. The R3327 AT tumours also respond to the HPD-PRT but a significant laser-induced thermal rise in the tumour is suspected.

Animals↗
PubMed1984

Inhibitory actions of enprofylline and aminophylline on extravasation of plasma proteins induced by various agents in the rat skin.

Increased plasma protein leakage induced by i.d. injections of histamine, 5-hydroxytryptamine, bradykinin, prostaglandin E2 and ionophore A23187 in the rat skin was inhibited non-specifically by enprofylline and aminophylline in a dose related manner. Depending on the agonist used, on a weight basis enprofylline was 2.9-6.6 times more potent than aminophylline when both were given i.p. and 1.4-2.2 times more active when administered orally. Inhibitory actions of enprofylline and aminophylline were unaffected by pretreatment of animals with phentolamine and propranolol, but reduced in adrenalectomized animals.

Aminophylline↗
PubMed1984

EGF, PGF2 alpha and insulin induce the phosphorylation of identical S6 peptides in swiss mouse 3T3 cells: effect of cAMP on early sites of phosphorylation.

Epidermal growth factor (10(-9)M), prostaglandin (8.5 X 10(-7)M), F2 alpha, and insulin (10(-9)M), each of which only leads to a partial phosphorylation of 40S ribosomal protein S6, generate the same first eight phosphopeptides induced by 10% serum, suggesting all three activate a common regulatory pathway for the phosphorylation of S6. Added together, they induce almost maximal S6 phosphorylation and a phosphopeptide pattern nearly equivalent to that of serum. Unlike the agents above, 8-Br-cAMP or PGE1 has no significant effect on protein synthesis, but does induce a small increase in S6 phosphorylation. Surprisingly, the three peptides that become phosphorylated are identical with insulin-induced phosphopeptides 10b, 11, and 9, based on either comigration, limited acid hydrolysis, or V8 protease digestion. Incubation of 40S subunits with cAMP-dependent protein kinase induces the phosphorylation of these same three phosphopeptides. The in vitro and in vivo studies described here raise the possibility that cAMP could, in part, be responsible for mediating the phosphorylation of S6 during the mitogenic response.

Animals↗
PubMed1984

The hormonal control of adenylate cyclase in rabbit myometrium: in vitro inhibition by adenosine and lack of effect of progesterone.

The mechanism by which progesterone modifies uterine smooth muscle cell contraction is still unknown. We investigated the biochemical basis of progesterone effects on myometrium of estradiol-primed rabbits. Progesterone did not affect adenylate cyclase basal activity and displayed no interaction with stimulators of myometrium adenylate cyclase (NaF, guanylyl nucleotides, beta-adrenoreceptor agonists, prostaglandins, forskolin) or with adenosine. On the other hand, adenosine inhibited myometrial adenylate cyclase, which correlates with its contracting properties in vivo; this inhibition is mediated through interaction at 'P sites'. We conclude that whilst adenosine inhibits myometrial adenylate cyclase by acting at 'P sites', progesterone does not interact directly with adenylate cyclase to regulate myometrial contractility.

Adenosine↗
PubMed1984

Concurrent radiation, mitomycin C and 5-fluorouracil in poor prognosis carcinoma of cervix: preliminary results of a phase I-II study.

Between July 1981 and June 1983, 27 patients with advanced primary squamous cell carcinoma (SCC) of cervix (FIGO Stages IIIB, IVA or extensive nodal involvement) and 8 with recurrent disease were treated using a pilot regimen of combination chemotherapy (CT): Mitomycin C (MIT), 5 Fluorouracil (5 FU), and radiation therapy (RT). CT and RT doses on this Phase I-II Study were escalated to the current regimen. A split course of RT was used, either pelvic RT alone (4560 Gy in 28 fractions) or the same pelvic RT plus para-aortic RT (3600 Gy in 24 fractions). CT was given: MIT 6 mg/M2 IV push day 1, and 5 FU 1.0 g/M2 (maximum daily 1.5 g) by continuous IV infusion days 1 through 4 of each half-course of RT. This was followed by one application of intrauterine 137Cs when possible. Three of the 8 patients with recurrence in the pelvis or para-aortic nodes had a complete response (CR) to CT-RT and are alive without disease at 19, 19 and 22 months after treatment, respectively. Twenty of the 27 (74%) primary patients had a CR. With a median duration of follow-up of 6 months 4/20 have relapsed, 1 in RT field, 2 at distant sites, and 1 in both. Pelvic disease remains controlled in 19/27 (70%) including one patient salvaged with surgery. The acute toxicity of this regimen was tolerable: 2/35 developed transient leukopenia with one febrile episode, 9/35 developed transient thrombocytopenia without bleeding. Symptomatic sigmoid strictures developed in two patients, one requiring surgical intervention. Sigmoid perforation occurred in one patient and contributed to death. Typically, near complete regression of tumor is noted on completion of the external RT, reproducing the dramatic responses that have been observed in SCC of the anal canal, esophagus and head and neck, with this CT-RT regimen. A Phase III Study is required to establish whether the enhanced response rates to CT-RT will result in increased pelvic control and cure rates compared to those after RT alone.

Antibiotics, Antineoplastic↗
PubMed1984

Endoscopic examination of the gastric remnant 31-39 years after subtotal gastrectomy for peptic ulcer.

In York between 1941 and 1949, 632 patients underwent Polya partial gastrectomy for peptic ulcer. Of 307 patients who were followed up in the York Gastric Clinic from 1971 to 1980, nine died of gastric cancer, three times the expected number. If gastrectomy was performed for gastric ulcer the risk of later development of carcinoma (7%) was significantly greater than that following operation for duodenal ulcer (1.6%) (p less than 0.001). No cancers were diagnosed in the 54 patients endoscoped. Atrophic gastritis was found in 98% of patients and intestinal metaplasia in 44%. Dysplasia was present in 35% but in no case was it severe. Although we have found that there is an increased risk of cancer developing in the gastric remnant we do not consider routine endoscopic follow up of all postgastrectomy patients to be a practical proposition.

Adult↗