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Biomedical subjects

J C Pickup

Publications and source records attributed to J C Pickup.

At least 109 records · Page 6Linked to original sources
PubMed1978

Continuous subcutaneous insulin infusion: an approach to achieving normoglycaemia.

A study was performed to examine the feasibility of achieving long periods of near-normoglycaemia in patients with diabetes mellitus by giving a continuous subcutaneous infusion of insulin solution from a miniature, battery-driven, syringe pump. Twelve insulin-dependent diabetics had their insulin pumped through a subcutaneously implanted, fine nylon cannula; the basal infusion rate was electronically stepped up eightfold before meals. The blood glucose profile of these patients was closely monitored during the 24 hours of the subcutaneous infusion and compared with the profile on a control day, when the patients were managed with their usual subcutaneous insulin. Diet and exercise were standardised on both days. In five out of 14 studies the subcutaneous insulin infusion significantly lowered the mean blood glucose concentration without producing hypoglycaemic symptoms; in another six patients the mean blood glucose concentration was maintained. As assessed by the M value the level of control was statistically improved in six out of 14 studies by the infusion method and maintained in six other patients. To assess the effects of blood glucose control on diabetic microvascular disease it will be necessary to achieve long-term normoglycaemia in selected diabetics. The results of this preliminary study suggest that a continuous subcutaneous insulin infusion may be a means of maining physiological glucose concentrations in diabetics. Though several problems remain--for example, in determining the rate of infusion--longer-term studies with the miniature infusion pumps are now needed.

Adult↗
PubMed1973

Subcellular organization of neurophysins, oxytocin, (8-lysine)-vasopressin and adenosine triphosphatase in porcine posterior pituitary lobes.

Posterior pituitary lobes from young pigs were fractionated by differential and sucrose-density-gradient centrifugation. The distributions of oxytocin and [8-lysine]-vasopressin were measured by bioassay and the distributions of neurophysin-I and -II by radioimmunoassays specific for each of these two proteins. Most of the hormone and neurophysin applied to the density gradient was localized in particles with the density expected of neurosecretory granules. However, the neurosecretory granules were separated into two bands (D and E). A close statistical correlation between the distributions of [8-lysine]-vasopressin and neurophysin-I, and of oxytocin and neurophysin-II on the gradients, suggested that in vivo porcine neurophysin-I binds [8-lysine]-vasopressin within one population of granules and porcine neurophysin-II binds oxytocin within another type of granule. However, there was no significant separation of oxytocin and vasopressin in fractions D and E. The molar ratios of hormones and neurophysins indicated that there was insufficient of either neurophysin to bind the [8-lysine]-vasopressin in the granule fractions or in the whole gland. Polyacrylamide-gel electrophoresis showed that only bands corresponding in mobility to porcine neurophysins-I, -II and -III were present in large amounts in the whole gland and in the granule fractions. The component with the mobility of neurophysin-III was, however, relatively enriched in whole young glands and granule fractions compared with adult gland extracts. It is suggested that the vasopressin that cannot be assigned to neurophysin-I may occur in (a) vesicles containing vasopressin but no neurophysin, (b) vesicles containing vasopressin and a protein that cannot be quantified by the radioimmunoassays used, such as porcine neurophysin-III, or (c) normal vasopressin-neurophysin granules which have accumulated extra vasopressin. Band E of the gradient was rich in adenosine triphosphatase activity, whereas band D possessed very little of this enzyme.

Adenosine Triphosphatases↗
PubMed1971

Protease and ribonuclease activities in bovine pituitary lobes.

1. Acid and alkaline protease activities in bovine anterior and posterior pituitary lobes were reinvestigated by measurement of u.v. and Folin-Ciocalteu colour values of trichloroacetic acid-soluble digestion products of denatured haemoglobin. 2. Both lobes of the pituitary gland contain a cathepsin with a pH optimum at 3.8. 3. When release of u.v.-absorbing material was used as the assay there was also an optimum at pH8.3-9.7, but this proved to be due to the release of nucleosides from an endogenous substrate. 4. The presence of a ;cyclizing' ribonuclease active at alkaline pH on endogenous RNA was confirmed by the inhibitory effects of phosphate, arsenate and bentonite. The activity was unaffected by heat, EDTA or metal ions. The enzyme also acted on exogenous RNA. 5. A purified preparation of neurosecretory granules from fresh bovine posterior pituitary lobes was free from alkaline ribonuclease activity. Most of the activity present in the tissue was recovered in the supernatant plus microsomal material. 6. The distribution of RNA did not follow that of the alkaline ribonuclease.

Animals↗
PubMedDate not supplied

Implantable glucose sensors: choosing the appropriate sensing strategy.

The special requirements for implantable glucose sensors which differ from laboratory analysers and in vitro probes include continuous operation without drift, compatibility with in vivo body conditions, electrical and toxicological safety and patient acceptability. We have studied the effect of oxygen tension, operating temperature and pH, and the stability of various potentially implantable amperometric glucose sensors so as to aid the choice of the technologies most suitable for in vivo application.

Biosensing Techniques↗
PubMedDate not supplied

Self-collection by diabetic patients of capillary blood for free insulin monitoring; reduction by diamide of haemolysis-induced insulin loss.

The need to precipitate bound insulin immediately after withdrawal of blood and the tendency to haemolysis, which reduces immunoassayable insulin, have prevented development of methods of self-collection of capillary blood for later free insulin measurement. We therefore investigated the use of the thiol-oxidizing agent, diamide, to prevent insulin loss with haemolysis and developed a self-collection procedure with capillary tubes pre-filled with diamide and polyethyleneglycol (PEG, for separation of free and bound insulin). Diamide (final concentration 5 mmol l-1) reduced serum insulin loss from 48 +/- 4 (+/- SE) to 11 +/- 4% (p less than 0.001) in maximally-haemolysed samples. The effect of diamide was concentration-dependent up to 5 mmol l-1. Diamide had no effect on the standard curve for radioimmunoassay of insulin. Levels of serum free insulin in self-collected capillary blood were significantly correlated with venous serum free insulin in 22 non-diabetic subjects (r = 0.92, p less than 0.001), 52 Type 1 diabetic patients (r = 0.86, p less than 0.001), and 18 Type 2 diabetic patients (r = 0.97, p less than 0.001). Mean capillary free insulin concentration was higher than in venous serum (22% in normal subjects, 64% in Type 1, and 23% in Type 2 diabetic patients). Storage at room temperature of capillary blood containing PEG/diamide for 72 h did not alter immunoassayable insulin concentrations.

Blood Specimen Collection↗
PubMedDate not supplied

Biosynthetic human insulin: effect in healthy men on plasma glucose and non-esterified fatty acids in comparison with highly purified pork insulin.

Biosynthetic human insulin (BHI) produced by recombinant DNA technology was administered subcutaneously and intravenously at two dose levels to two groups, each consisting of six normal men. Responses were compared with those for purified pork insulin (PPI) given by the same routes at the same dose levels to the same two groups. The glycemic response to the insulins was similar with a suggestion (seen both with intravenous and subcutaneous administration) that the glycemic depression with BHI was slightly greater at low dose and less at high dose. No significant difference between insulin types was found in the depression of non-esterified fatty acid (NEFA) concentrations, although significant differences between types with low-dose subcutaneous injection emerged during the later phases of the experiment. After termination of high-rate infusion with both insulins, NEFA concentrations rose more rapidly with some overshoot, suggesting that the rate and depth of blood glucose fall in these experiments might have triggered a brisker counterregulatory response. The small differences found between human and pork insulins, although in some cases significant, are unlikely to be of clinical importance.

Adult↗
PubMedDate not supplied

Plasma insulin and C-peptide after subcutaneous and intravenous administration of human insulin (recombinant DNA) and purified porcine insulin in healthy men.

We have compared the plasma profiles of C-peptide, human insulin (recombinant DNA), and purified porcine insulin of pancreatic origin (PPI) in six nondiabetic men after low-dose (4.8 U) or high-dose (9.6 U) subcutaneous injection and low-rate (1.0 U/h) or high-rate (1.7 U/h) intravenous infusion. There was no significant difference in plasma C-peptide or glucose levels when human insulin was compared with PPI at either dose level for subcutaneous injection or intravenous infusion. Thus, there was equal suppression of endogenous insulin by the two species of exogenous insulin. For low-dose subcutaneous injection there was no significant difference between plasma insulin levels of the two species at single time points or when areas were compared. For high-dose subcutaneous injection mean plasma insulin levels were higher after human insulin than after PPI (20-300 min); this serial difference reached conventional statistical significance at 50 min (P less than 0.05) and 90 min (P less than 0.01). For the area under plasma insulin profiles between 0 and 90 min after high-dose s.c. injection, human insulin was higher than PPI (P = 0.06). There was no significant difference between insulin concentrations after human insulin and PPI given by either low- or high-dose intravenous infusion, except that high-dose PPI values (55-110 min) were slightly but significantly higher after high-dose intravenous infusion. Further comparisons of the pharmacokinetics of human and other species of insulin are, therefore, justified in larger numbers of subjects and particularly in diabetic individuals.

Animals↗
PubMedDate not supplied

Preliminary evaluation of a skin conductance meter for detecting hypoglycemia in diabetic patients.

A portable device (the Diabalert), which measures the electrical conductivity of the skin surface and sounds an alarm at a preset conductivity, was evaluated as a possible detector of hypoglycemia-induced sweating in diabetic subjects. Insulin was infused intravenously into seven insulin-dependent diabetic subjects, and the course of the plasma glucose decline, hypoglycemic symptoms, and state of consciousness of the patients frequently monitored. In five patients sweating occurred with hypoglycemia, and the Diabalert alarm was activated at plasma glucose concentrations between 1.6 and 3.7 mmol/L. Three of these five diabetic patients were by then unaware of the alarm and would have failed to take corrective action to restore normoglycemia. Two further patients had virtually no symptoms despite marked biochemical hypoglycemia and the alarm was not triggered. Studies are needed in larger numbers of diabetic patients at home to fully assess the clinical usefulness of this device.

Adult↗
PubMedDate not supplied

Meeting the problems of first-generation insulin infusion pumps: clinical trial of a new miniature infuser.

We designed and constructed a new miniature, open-loop insulin infusion pump specifically to overcome the problems of many first generation insulin infusers. Special features are small size, adjustable volumetric basal infusion rate, rapid electronically mediated prandial insulin boosts, facility for doubling and halving the basal infusion rate and/or prandial delivery, and alarms for low battery state, motor over-run, stoppage, and control circuit malfunction. The infuser takes a specially designed syringe prefilled with short-acting insulin, sufficient in most diabetic patients for at least 7 days treatment with 100 U/ml insulin. To test clinical efficacy nine insulin-dependent diabetic patients received continuous subcutaneous insulin infusion (CSII) with the new infuser for periods up to 6 mo. Four patients previously CSII-treated with a first-generation pump and five who were new to CSII achieved and maintained the expected degree of near-normoglycemia. There were no pump breakdowns and a questionnaire completed by patients during the study confirmed ease and simplicity of operation and an appreciation of the advantages of the new pump compared with one widely used first-generation infuser.

Adult↗
PubMedDate not supplied

Continuous intravenous insulin infusion in the management of brittle diabetes: etiologic and therapeutic implications.

Continuous intravenous insulin infusion (CIVII) was used to treat five brittle insulin-dependent diabetic women (aged 16-29 yr) who had failed to achieve satisfactory glycemic control during intensified subcutaneous insulin treatment including continuous subcutaneous insulin infusion (CSII). Insulin was infused through an indwelling central venous catheter by a portable pump for 3-16 mo. During CIVII, only three subjects obtained satisfactory glycemic control and only for short periods. Generally, as with CSII, control was erratic and unpredictable and three subjects intermittently had high insulin requirements (200 U/day). By contrast, three stable insulin-dependent diabetic subjects achieved near-normoglycemia within 1-3 days of starting CIVII with daily insulin dosages of 30-90 U. The lives of all five brittle subjects continued to be disrupted by frequent hospital admissions during CIVII treatment. Deliberate interference with their own treatment (including tampering with pumps and central venous catheters) was thought to be a major contribution to instability in two of the brittle subjects. In the others, the ineffectiveness of CIVII suggests that brittleness was not due solely to defective subcutaneous insulin absorption, as had previously been suggested in other CSII-unresponsive brittle subjects. Although CIVII has reportedly been successful in managing brittle diabetes, the technique may not be useful in all brittle individuals, as illustrated by the poor glycemic responses of these subjects and the serious complications (including local infection, septicemia, and thrombosis) they suffered.

Adolescent↗
PubMedDate not supplied

Rarity of a marked "dawn phenomenon" in diabetic subjects treated by continuous subcutaneous insulin infusion.

We assessed the quality of overnight glycemic control and the frequency of the "dawn phenomenon" (nadir-0800 h glycemic increase) in 41 insulin-dependent diabetic patients treated by continuous subcutaneous insulin infusion (CSII). Mean plasma glucose levels were near-normal during the 24 h and, in particular, constant throughout the night. In a subset of six patients overnight plasma free insulin concentrations were also constant during CSII. The majority of profiles (88%) showed a glucose nadir from 2.0 to 5.9 mmol/L (most frequently at 0600 h) and had an 0800 h value from 2.0 to 6.9 mmol/L (92%). A large proportion (46%) of profiles showed a zero or negative nadir-0800 h glycemic increase. In 22 patients with three or more profiles recorded at the same basal insulin infusion rate, only one of 103 profiles had a fasting glycemic increase greater than an arbitrary value of 5.0 mmol/L (5.3), although many patients exhibited small dawn glycemic increases (e.g., 14 of 22 had a mean increase of from 0 to 2 mmol/L). In 12 subjects a 15% reduction in basal insulin infusion rate increased the mean +/- SEM dawn glycemic increase from 0.58 +/- 0.25 mmol/L to 2.7 +/- 0.76 mmol/L (P less than 0.025) as well as significantly increasing the nocturnal nadir and 0800 h plasma glucose concentrations. Thus, a marked dawn phenomenon is rare when a single but adequate basal infusion rate is used for CSII, and this questions the need in the majority of patients for preprogrammable pumps with nocturnal infusion rate changes.

Adult↗