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Biomedical subjects

R W Stevenson

Publications and source records attributed to R W Stevenson.

At least 73 records · Page 4Linked to original sources
PubMed1983

How to become comfortable talking about sex to your patients.

Dealing with patients' sex-related complaints is uncomfortable for many physicians. It can become more comfortable if the physician learns to apply his or her clinical knowledge of sexuality in combination with specific interpersonal interviewing skills. The level of comfort can be increased if the physician accepts his or her professional limitations in providing therapy and knows what other sources of care are available.

Counseling↗
PubMed1983

Further evidence for non-pancreatic insulin immunoreactivity in guinea pig brain.

The existence of large amounts of insulin in rat brain and of a porcine- or rat-like insulin in guinea pig brain have been disputed on the basis of differing results from standard (Method I) and hydrophobic adsorption techniques (Method II) for concentrating insulin from acid ethanol extracts. To try to resolve these differences, acid ethanol extracts of rat and guinea pig brains were divided into equal aliquots and concentrated for insulin radioimmunoassay (RIA) by both techniques. The RIA used guinea pig anti-porcine insulin serum, with 50% B0 for purified pancreatic porcine, rat and guinea pig insulin standards being 1.35, 2.38 and greater than 1,000 ng/ml, respectively. Oral glucose (4 g/kg) produced plasma glucose of 377 mg/dl in a guinea pig by 20 min but was not associated with any porcine- or rat-like immunoreactive insulin. Dilutions of guinea pig and rat brain extracts had parallel cross-reactivity with insulin standard curves. Insulin contents of rat brain (uncorrected for recovery) against porcine and rat insulin standards, respectively, were 1.33 and 1.93 ng/g (Method I) and 5.93 and 11.67 ng/g (Method II). Rat plasma was 0.85 and 1.42 ng/ml, respectively. Guinea pig contained 1.35 and 1.89 ng/g (uncorrected), respectively (Method I), and 2.99 and 5.62 ng/g, respectively (Method II). Guinea pig plasma was below the sensitivity of the RIA (less than 0.15 ng/ml). These results suggest that a porcine- or rat-like insulin may exist in guinea pig brain.

Animals↗
PubMed1983

Effect of intraportal and peripheral insulin on glucose turnover and recycling in diabetic dogs.

The effects of peripheral and portal intravenous infusions of insulin on hepatic glucose production and glucose recycling have been compared in conscious diabetic dogs. Glucose turnover (Ra) was estimated using a priming dose of [3-3H]glucose and [1-14C]-glucose followed by constant intravenous infusion. Glucose recycling was calculated from 3H-Ra - 14C-Ra. In eight normal dogs, mean 3H-Ra was 3.0 mg X kg-1 X min-1 and recycling 19%. When these dogs were made diabetic with alloxan and streptozotocin the 3H-Ra rose to 6.2 mg X kg-1 X min-1 (P less than 0.001) and recycling to 24% (P less than 0.05). Insulin infusion for 2.5 h at 0.006 U X kg-1 X h-1 intraportally decreased 3H-Ra to 4.0 mg X kg-1 X min-1 (P less than 0.01 compared with untreated diabetic), whereas peripheral infusion at this rate had no significant effect. Insulin infusion at 0.05 U X kg-1 X h-1 by the peripheral and portal circulations reduced 3H-Ra to the normal range: 3.1 and 2.8 mg X kg-1 X min-1, respectively. Glucose recycling was also normalized by portal insulin infusion (20%) but was significantly decreased by peripheral infusion (11%, P less than 0.01). Thus the liver responds to lower infusion rates of insulin by the intraportal route, and only this mode of administration normalizes both hepatic glucose output and glucose recycling.

Animals↗
PubMed1983

Metabolic responses to intraduodenal glucose loading in insulin-infused diabetic dogs.

The hormonal and metabolic responses to an intraduodenal glucose load (0.5 g/kg) were first determined in eight normal dogs before diabetes (alloxan/streptozotocin) was induced and then comparison made of the responses to the glucose load when normal plasma glucose profiles were recreated by preprogrammed infusion of insulin via the portal or peripheral circulations. Basal intraportal and peripheral insulin infusions at 0.021 +/- 0.001 and 0.022 +/- 0.000 U . kg-1 . h-1, respectively, for 16 h to fasting diabetic dogs normalized peripheral plasma levels of glucose (5.5 +/- 0.3 and 5.6 +/- 0.6 mmol/liter, respectively), immunoreactive insulin (IRI) (11.5 +/- 1.2 and 16.4 +/- 1.6 microU/ml), glucagon (65 +/- 7 and 62 +/- 5 pg/ml), lactate (0.63 +/- 0.04 and 0.54 +/- 0.03 mmol/liter), and alanine (0.236 +/- 0.037 and 0.191 +/- 0.008 mmol/liter). However, peripheral but not intraportal infusion of insulin depressed levels of glycerol, nonesterified fatty acids (NEFA), and 3-hydroxybutyrate (0.074 +/- 0.006 vs. 0.109 +/- 0.013, P less than 0.01; 0.67 +/- 0.04 vs. 0.84 +/- 0.09, P less than 0.05; and 0.018 +/- 0.004 vs. 0.059 +/- 0.015 mmol/liter, P less than 0.01, respectively). With the preprogrammed insulin infusions used to normalize plasma glucose profiles to the intraduodenal glucose load, all hormonal and metabolic responses were normalized during intraportal infusion (IRI, 72.5 +/- 4.2 microU/ml; glucagon, 66 +/- 10 pg/ml; lactate, 1.06 +/- 0.10 mmol/liter; alanine, 0.251 +/- 0.042 mmol/liter; glycerol, 0.043 +/- 0.013 mmol/liter; NEFA, 0.24 +/- 0.03 mmol/liter; and 3-hydroxybutyrate, 0.012 +/- 0.007 mmol/liter) but marked hyperinsulinemia (103.2 +/- 6.1 microU/ml) and depressed glycerol, NEFA, and 3-hydroxybutyrate responses at 2 h (0.056 +/- 0.005, 0.52 +/- 0.10, and 0.019 +/- 0.010 mmol/liter, respectively) resulted during peripheral infusion. Therefore, only the portal route of insulin infusion achieved complete metabolic normalization during glucose loading in diabetic dogs.

3-Hydroxybutyric Acid↗
PubMed1983

Effects of two treatment regimes with synthetic human parathyroid hormone fragment on bone formation and the tissue balance of trabecular bone in greyhounds.

The adult greyhound was found to be similar to adult man with respect to kinetic and histomorphometric indices of calcium metabolism. The relationship between trabecular bone tissue balance and the pattern of human PTH fragment 1-34 (hPTH 1-34) administration by daily injections or continuous sc infusions was investigated in this model and the results compared to those from a clinical trial of hPTH 1-34 in involutional osteoporosis (peptide administration by single daily injections). In the dogs, the daily injection regime elevated plasma levels of immunoreactive hPTH 1-34 for no more than 4 h/day. The greyhounds so treated showed significantly increased indices of bone formation (surface osteoid, plasma alkaline phosphatase activity, and skeletal accretion rate of calcium) and resorption (number of osteoclasts, resorption surfaces). Iliac trabecular bone volume increased significantly, as it did in the patients. The infusions did not significantly increase the trabecular bone volume or the 47Ca accretion rate, two parameters which increased in parallel in dogs and patients treated successfully by daily injections. The osteoclastic surfaces, however, were clearly increased by continuous infusions, while the increases in the osteoblastic surfaces were less statistically significant. Since hPTH 1-34 may inhibit osteogenesis in Friedenstein chambers, it is possible that the increased osteoblastic activity induced by the daily injection regime in trabecular bone is dependent on the noncontinuous nature of the PTH stimulus.

Animals↗
PubMed1983

Changes in plasma calcium and in radiocalcium kinetics after termination of 5-week infusions of synthetic parathyroid peptide in dogs.

Nine dogs were infused at constant rates with the synthetic parathyroid peptide hPTH 1-34 (initially sc) to produce consistent hypercalcaemia. Over the final week, the infusions were iv. Radioisotopic tracers were injected iv 30 days (5 dogs) and 2 days (9 dogs) before the infusions were suddenly terminated. In 5 dogs, complete urine collections were obtained via a bladder catheter over 8 h beginning 2 h before stopping the infusions. Cessation of treatment caused small rises in the urinary Ca: creatinine ratio. Plasma calcium levels fell by a mean of 0.44 mmol/l, of which total urine calcium excretion only accounted for 55%. Immediately after the PTH infusions were stopped, consistent but transient increases were seen in the ratio of 'new' 47Ca to 'old' 45Ca label, suggesting inflow of 40Ca of high 47Ca specific activity from a fairly rapidly exchangeable bone pool. These data confirm and extend previous evidence that the immediate response of the calcium equilibrium between bone and bloodstream to rapid changes in plasma PTH concentrations in the supra-physiological range is paradoxical relative to the classical later response.

Animals↗
PubMed1983

Effects of parathyroid hormone and the synthetic 1-34 amino-terminal fragment in rats and dogs.

Since the structural requirements for all known biological activities of parathyroid hormone (PTH(1-84)) are virtually satisfied by the amino-terminal 34 amino acid fragment, PTH(1-34), we investigated whether this fragment could elaborate the overall actions of the intact hormone in the whole animal by comparing the effects of equimolar infusions of each peptide to dogs and rats. Infusion of bovine PTH(1-84) (bPTH(1-84)) at 17 pmol/kg per h for 20 h to three dogs or at 100 and 200 pmol/kg per h to groups of six rats for 5 days produced greater hypercalcaemia (3.02 +/- 0.03, 2.52 +/- 0.07 and 3.24 +/- 0.11 mmol/l respectively) than equimolar infusions of human PTH(1-34) (hPTH(1-34)) (2.61 +/- 0.03, 2.46 +/- 0.05 and 2.71 +/- 0.09 mmol/l respectively). A significant calcium rise was not observed in dogs until after 4 h of PTH infusion. No rise in plasma calcium was apparent in rats, however, until the third day of PTH infusion. Only in parathyroidectomized rats was there a rise in plasma calcium within 24 h of starting an infusion of PTH. The hypercalciuria and plasma phosphate responses in dogs during equimolar infusions of hPTH(1-34) and bPTH(1-84) were not significantly different. However, by day 5 of infusion in rats greater hypercalciuria was produced by bPTH(1-84). Although infusion of hPTH(1-34) and bPTH(1-84) caused rises in urinary cyclic AMP excretion (measured only in the dog) of immediate onset and equal magnitude, bPTH(1-84) tended to produce greater phosphaturia than hPTH(1-34) in both species. If the assumption is correct that the half-lives of hPTH(1-34) and bPTH(1-84) in the circulation are similar and provided that hPTH does not inherently have less biological activity than bPTH, then during equimolar infusions of these peptides into dogs and rats, the greater responses observed with bPTH(1-84) suggest that intact PTH may have a direct action of its own in vivo before being metabolized into smaller biologically active fragments. In additional experiments using parathyroidectomized rats, the infusion rate of bPTH(1-84) required to restore normocalcaemia was 26 pmol/kg per h. Although near-normal calcaemia and intestinal calcium absorption could still be maintained when the infusion rate was increased to 39 pmol/kg per h, hypercalciuria and phosphaturia became apparent.

Animals↗
PubMed1982

Electrophysiological evidence of adaptation to colored filters.

Subjects wore blue filters (Kodak Wratten 45) in front of their normal spectacle correction for a period of 4.5 hr. Visual evoked potential (VEP's) were measured (monocularly) before, in white light and through the blue filters at the start and finish of wearing the filters. Predictably, from the chromatic interval, the subjects initially showed some degree of myopia, confirmed by more negative lens power required to give maximum VEP response. However, after 4.5 hr of wear of the filters, VEP's were measured again and it was found that the maximum VEP response was obtained in each case with less negative lens power, indicating adaptation of the visual system toward emmetropia. The role of accommodation in this adaptive process is discussed.

Accommodation, Ocular↗
PubMed1982

In vitro studies on an antagonist of parathyroid hormone [Nle-8, Nle-18, Tyr-34]bPTH-(3-34)amide.

1 The actions of parathyroid hormone (PTH) are antagonized in vitro by the peptide [Nle-8, Nle-18, Tyr-34]-bPTH-(3-34)amide, an analogue of PTH. In this paper, the actions of the inhibitory peptide were investigated in vivo. 2 Native parathyroid hormone (bPTH-(1-84)), administered i.v. (0.17-1.51 nmol in volume of 0.3 ml) to 7 day old chicks produced hypercalcaemia but administration of the analogue in doses up to 173 nmol was ineffective in this respect. 3 The analogue failed to antagonize the hypercalcaemia produced by bPTH-(1-34) when injected, in 10 fold molar excess, 2 min before or simultaneously with bPTH-(1-34). 4 Normocalcaemia was restored in parathyroidectomized rats by intravenous infusion of bPTH-(1-84) at 32 pmol kg-1 h-1. Addition of the analogue to the infusion fluid in a 200 fold molar excess did not affect the concentrations of calcium and phosphate in the plasma, cyclic adenosine 3',5'-monophosphate (cyclic AMP) in the urine or phosphate clearance but produced a significant (P less than 0.05) rise in urinary calcium clearance. 5 The results suggest that the peptide [Nle-8, Nle-18, Tyr-34]-bPTH-(3-34)amide does not antagonize the actions of PTH in vivo and demonstrate an important dichotomy between in vitro and in vivo biological properties of the PTH analogue.

Animals↗
PubMed1982

Activation and clearance of a hormonogen, triglycyl-oxytocin, in the conscious dog.

Triglycyl-oxytocin (TGOT) and oxytocin (OT) were administered iv and sc to conscious dogs and the plasma concentrations of these peptides determined simultaneously by RIA and bioassay. Constant iv infusions (1 h) at 23 pmol/kg/min produced plateau levels of 1.1 and 1.6 pmol/ml plasma for OT and TGOT respectively. Whilst the distribution space was similar for each peptide. TGOT persisted longer in the circulation (t1/2, for TGOT 6.6 min; for OT 4.2 min). Bioactive values for OT followed RIA values whether this peptide was given iv or sc. Although very little bioactivity was generated by iv infusions of TGOT, considerable amounts of bioactive OT were found in plasma after injection of TGOT subcutaneously. The hormonogen proved relatively resistant to oxytocinase, an enzyme that destroys OT rapidly. Our results indicate that TGOT is converted to OT in vivo and that its action as a hormonogen is more pronounced after sc than iv administration.

Animals↗
PubMed1982

Prolonged hypoglycemic effect in diabetic dogs due to subcutaneous administration of insulin in liposomes.

The biologic action of insulin entrapped in liposomes (phospholipid vesicles) has been investigated following subcutaneous injection to dogs made diabetic with a combination of alloxan and streptozotocin. The fats of the liposomally entrapped material was determined by injecting rats subcutaneously with either 125I-insulin or the labeled polysaccharide 14C-inulin, incorporated in liposomes labeled with 3H-cholesterol. Injection of liposome insulin (0.75 U/kg) to five diabetic dogs resulted in a mean (+/- SEM) blood glucose fall from 16.4 +/- 0.8 to 2.9 +/- 0.4 mmol/L. The glucose level had still not returned to baseline after 24 h and, correspondingly, immunoreactive insulin (IRI) could still be detected in frozen and thawed plasma 24 h after injection. In contrast, the hypoglycemic effect of the same dose of free insulin with or without empty liposomes virtually ended within 8 h and IRI levels returned to baseline by 3 h after injection. In experiments on rats with liposomally entrapped 125I-insulin or 14C-inulin the proportion of the injected dose of tracer recoverable by excision of the injection site remained constant after about 1 h and 70% of the dose was still fixed in subcutaneous tissue for at least 5 h thereafter. When the plasma collected 3 h after subcutaneous injection of labeled liposomes containing 125I-insulin was passed through a column of Sepharose 6B, 50-75% of the 125I-activity was found in the fractions associated with intact liposomes. One possibility for the persistence of the hypoglycemic effect and of measurable IRI following injection of liposome insulin could be the presence of intact liposomes in the circulation for many hours after adsorption had ceased.

Animals↗
PubMed1980

Matched glucose responses to insulin administered subcutaneously and intravenously. Evidence for subcutaneous inactivation of insulin.

A new technique of programmed intravenous insulin infusion at a series of decreasing rates has been used to imitate the magnitude and time course of biological responses obtained by the subcutaneous route. Groups of normal rats prepared with indwelling venous cannulae were injected subcutaneously with soluble porcine insulin, 0.4 U/kg. The pattern of the resulting hypoglycaemic response was subsequently matched by a 2-hour intravenous insulin infusion at rates decreasing stepwise from 0.3 to 0.05 U kg-1h-1. The total amount of insulin infused intravenously was only 50% of that required subcutaneously. In addition, subcutaneous or intravenous infusions of insulin at 0.05 U kg-1h-1 were given to two groups of rats from the same batch. When both infusions were continued until plateau responses were reached, a significantly greater lowering of plasma glucose was caused by the intravenous route. These results suggest that when insulin is given subcutaneously significant inactivation of the insulin occurs at or near the injection site.

Animals↗
PubMed1980

An homologous and sensitive radioimmunoassay for the synthetic amino-terminal (1-34) fragment of human parathyroid hormone: application to the clearance of this peptide administered in vivo.

The synthetic 1-34 amino-terminal fragment of human parathyroid hormone (hPTH 1-34) is undergoing multicentre clinical trials to assess its long term therapeutic potential in the treatment of osteoporosis. An homologous radioimmunoassay (reagents prepared from the synthetic hPTH 1-34 peptide) has been developed to monitor the pharmacokinetics of hPTH 1-34 in man and in a dog model. The assay is rugged, sensitive (detection limit 1.75 x 10(-11) moles/litre) and precise (coefficient of variation 6%). Three different ampouled preparations of the native intact hPTH 1-84, of different degrees of purity (approximately 3%-90% pure) gave complete log dose response curves parallel to that of the ampouled synthetic hPTH 1-34 peptide, and were equipotent on a molar basis. Native intact bovine PTH 1-84 showed an incomplete non-parallel displacement curve; there was no recognition of synthetic hPTH 44-68 and 53-84 peptides. Preliminary application of the assay to the determination of the plasma disappearance of hPTH 1-34 in man and dog gave half-times (t1/2) of 3-8 minutes for a first exponential component and 12-18 minutes for the second; in the dog, metabolic clearance rate was calculated to be 9ml/kg/minute and the distribution space 160ml/kg.

Amino Acids↗