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Biomedical subjects

G S Gordon

Publications and source records attributed to G S Gordon.

31 records · Page 2Linked to original sources
PubMed1985

Nasal absorption of insulin: enhancement by hydrophobic bile salts.

We demonstrate that therapeutically useful amounts of insulin are absorbed by the nasal mucosa of human beings when administered as a nasal spray with the common bile salts. By employing a series of bile salts with subtle differences in the number, position, and orientation of their nuclear hydroxyl functions and alterations in side chain conjugation, we show that adjuvant potency for nasal insulin absorption correlates positively with increasing hydrophobicity of the bile salts' steroid nucleus. As inferred from studies employing various concentrations of unconjugated deoxycholate and a constant dose of insulin, insulin absorption begins at the aqueous critical micellar concentration of the bile salt and becomes maximal when micelle formation is well established. These and other data are consistent with the complementary hypotheses that bile salts act as absorption adjuvants by producing high juxtamembrane concentrations of insulin monomers via solubilization in mixed bile salt micelles and forming reverse micelles within nasal membranes, through which insulin monomers can diffuse through polar channels from the nares into the blood stream.

Administration, Intranasal↗
PubMed1983

Insulin administered intranasally as an insulin-bile salt aerosol. Effectiveness and reproducibility in normal and diabetic subjects.

Efficacy and reproducibility of insulin administered intranasally as an insulin-deoxycholate 1% (w/v) aerosol to normal and diabetic subjects were assessed by measurements of blood glucose and serum insulin levels. Following administration of 0.5 U insulin/kg with the unconjugated bile salt to fasting volunteers (N = 29), peak serum insulin levels of 103 +/- 49 microU/ml above baseline were observed at 10 min. Blood glucose concentration began to fall by 10 min, reaching 54 +/- 14% of control levels by 30 min, and returning to baseline by 60-80 min. Blood glucose response and peak serum insulin levels were reproducible when the same aerosol dose was repeatedly administered to the same subjects; however, intersubject variations were noted. By comparing serum insulin levels after i.v. and nasal routes of administration, nasal insulin absorption was approximately 10% as efficient as intravenous insulin. Dose response studies revealed that peak serum insulin concentrations were a linear function of the administered dose. In subjects with type I and type II diabetes mellitus, serum insulin levels increased in a manner similar to controls, and resulted in a prompt reduction of blood glucose concentration. However, in contrast to normal subjects, the duration of the glucose response was more prolonged, lasting as long as 5 h. Nasal administration of insulin as an aerosol with bile salts or bile salt analogs should be further evaluated as a possible nonparenteral approach to insulin therapy.

Absorption↗
PubMed1979

Effects of colchicine and vinblastine on in vitro gastric secretion.

The effects of colchicine and vinblastine on in vitro bullfrog gastric mucosal preparations were studied with respect to H+ and pepsinogen secretion. In the concentration range of 1--50 mM, an initial but transient colchicine-mediated stimulation of H+ secretion is followed by a dose-dependent inhibition. The transient stimulation of H+ secretion can be confirmed in resting preparations in the absence of added secretagogues. In the same concentration range, colchicine inhibits pepsinogen secretion to a greater degree than H+ secretion. Vinblastine (10(-5)--5 X 10(-4) M) was more effective than colchicine in inhibiting both H+ and pepsinogen secretion. The kinetics of inhibition of secretion by both colchicine and vinblastine were slow. Cytochalasin B had no effect on either secretion.

Animals↗
PubMed1966

Osteolytic sterol in human breast cancer.

Eleven of twelve human breast cancers contained a lipid which increased urinary (45)Ca and (40)Ca excretion of (45)Ca-labeled, parathyroidectomized rats receiving a low Ca diet. The lipid has mobility on thin-layer chromatography and gas-liquid chromatography close to, but not identical with, that of 7-dehydrocholesterol. Authentic 7-dehydrocholesterol has osteolytic activity similar to that of the extracted sterol. Fluorescence and Lieberman-Burchard reactions of the extracted sterol are similar to those of 7-dehydrocholesterol. The lipid was found by thin-layer chromatography in the extracts which had osteolytic activity. Neither the lipid nor osteolytic activity was found in extracts of tissue from two normal human breasts.

Animals↗
PubMedDate not supplied

Costs, effects and C/E-ratios alongside a clinical trial.

A general approach is discussed to assess the uncertainty surrounding the cost effectiveness ratio (C/E-ratio) estimated on the basis of data from a randomised clinical trial. The approach includes the calculation of a 95% probability ellipse and introduces the concept of a so called C/E-acceptability curve. This last curve defines for each predefined C/E-ratio the probability that the C/E-ratio found in the study is acceptable. The approach is illustrated by estimates of costs per life saved and costs per patient discharged alive on the basis of data from a phase II trial addressing the value of anakinra in treating sepsis syndrome.

Cost-Benefit Analysis↗
PubMedDate not supplied

Second-degree atrioventricular block: Mobitz type II.

Acute atrioventricular (AV) block occurs frequently in patients with myocardial infarction. Atrioventricular block is also a common manifestation of sclerodegenerative conduction system disease. Occasionally, heart block results from drug toxicity, hyperkalemia, cardiac valvular calcification, myocarditis, or infiltrative cardiomyopathy. Second-degree AV block is a form of "incomplete" heart block, in which some, but not all, atrial beats are blocked before reaching the ventricles. Mobitz type II second-degree block is an old term, which refers to periodic atrioventricular block with constant PR intervals in the conducted beats. The distinction between type II and type I block is descriptive; of greater importance to the clinician is the anatomic site of the block and the prognosis. In Mobitz type II block the site is almost always below the AV node; in Mobitz type I block the site is usually within the AV node. Type II AV block is more likely to progress to complete heart block and Stokes-Adams arrest. In most cases of second-degree heart block, including cases of 2:1 conduction, it is possible to determine the site of the AV block (intranodal or infranodal) using information about the age of the patient, the clinical setting, and the width of the QRS complex on the surface electrocardiogram. Second-degree atrioventricular block must be distinguished from other "causes of pauses." Nonconducted premature atrial contractions and atrial tachycardia with block are common conditions, which may mimic second-degree AV block.

Aged↗
PubMedDate not supplied

DNA segregation: putting chromosomes in their place.

Recent studies provide evidence that bacterial chromosomes are replicated by an enzyme factory, the replisome, located at a fixed position at the center of the cell; the fixed replisome could be a major factor in determining chromosome order in the cell, and may provide the force that drives chromosome segregation.

Bacteria↗
PubMedDate not supplied

Severe envenomation by the taipan (Oxyuranus scutellatus)

We describe cases of five patients with taipan envenomation which indicate that patients with paresis benefit from repeated doses of antivenom, even if given long after the bite, and that fresh frozen plasma should be given to correct coagulopathy that persists after reversal of neuromuscular blockade. We reiterate the importance of compression bandages.

Adult↗