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Biomedical subjects

G Gwinup

Publications and source records attributed to G Gwinup.

At least 19 recordsLinked to original sources

Effective portal insulin delivery with enzyme-protected capsules in pancreatectomized pigs.

1. Plasma concentrations of insulin, C-peptide, glucagon and glucose were measured in surgically pancreatectomized pigs given insulin into the colon directly and in enteric peptidase-resistant (methacrylic acid copolymer-encapsulated) form. 2. Following introduction of insulin-containing capsules, plasma insulin concentration rose from 2.7 +/- 0.1 microU/ml to 110.9 +/- 51.9 microU/ml in the portal vein, and from 2.6 +/- 0.1 microU/ml to 26.9 +/- 7.3 microU/ml in the systemic circulation. Corresponding portal and systemic values after direct (non-encapsulated) insulin instillation were 28.2 +/- 15.9 microU/ml to 44.8 +/- 13.0 microU/ml and 7.5 +/- 2.6 microU/ml to 15.2 +/- 2.5 microU/ml respectively. Insulin concentrations peaked at 75 min in the group as a whole and between 60-90 min in individual animals. Absorption was most pronounced in pigs given aprotinin (a trypsin inhibitor) with insulin. 3. Plasma portal vein glucose concentrations fell from 76.2 +/- 8.9 mg/dl to 31.1 +/- 3.2 mg/dl 150 min after encapsulated insulin administration. Corresponding systemic glucose levels were 84.5 +/- 11.0 mg/dl and 37.0 +/- 1.4 mg/dl. 4. Colonic administration of insulin in methacrylic acid coated capsules results in peak portal and systemic insulin levels 60-90 min after administration. Co-administration of aprotinin enhances the fraction of insulin absorbed.

Animals

Immobilization osteoporosis in paraplegia.

The pathophysiology of osteoporosis as it relates to immobilization or disuse osteoporosis in paraplegics is briefly reviewed. The physiology of bone formation and resorption is discussed, and the influence of piezoelectric forces on bone integrity and the consequences of the loss of this effect in paraplegics is addressed. When bone is stressed, negative charges accumulate on the side from which the stress is applied and positive charges accumulate on the opposite side. Presumably the collagenous component of bone plays the major role in the generation of electrical potentials. Another mechanism important in the generation of electrical potentials is created by liquid planes streaming past solid planes. Diminished forces acting on bone, as in paraplegia, are translated into changes in the activity of bone remodeling units which can be assessed by histomorphic and histoenzymatic techniques. Other biochemical and endocrine consequences of immobilization involve increased serum calcium, decreased serum parathyroid hormone (PTH), and decreased dihydroxy-vitamin D synthesis. Urinary hydroxyproline and calcium excretion are increased, as is stool calcium. The bone loss that follows immobilization may produce an increased susceptibility to fractures involving long bones more than the spinal column, and is due more to decreased bone formation than to accelerated bone resorption. The treatment of immobilization osteoporosis primarily involves early remobilization, but other treatments, including the use of electrical fields and the administration of bisphosphonates, calcitonin, and a growth hormone are being actively investigated.

Bone and Bones

Nelson's syndrome.

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Adrenocorticotropic Hormone

Insulin and C-peptide levels following oral administration of insulin in intestinal-enzyme protected capsules.

1. Crystalline beef insulin was administered orally in capsules composed of a methacrylic acid copolymer which prevented breakdown of the insulin by enteric and pancreatic peptidases. 2. In studies performed in 3 individuals blood was sampled before oral ingestion of the insulin (40 144 units), and at 15 or 30 min intervals thereafter for 5.5 hr for measurement of immunoreactive insulin and C-peptide concentrations. 3. Following the administration of oral insulin, plasma immunoreactive insulin concentrations became elevated 4-5 hr after ingestion. 4. The rise in plasma insulin concentrations was associated with a corresponding fall in the concentration of C-peptide. 5. The data suggest that this preparation of oral insulin can produce significant enteric absorption of the peptide, and that further investigation of agents that facilitate insulin absorption from the gut might render the use of methacrylic acid copolymer coated capsules a physiologically sound and a commercially feasible method of oral insulin administration.

Administration, Oral

Hypothesis: insulin is responsible for the vascular complications of diabetes.

It is proposed that the systemic hyperinsulinemia and hepatic portal hypoinsulinemia that occurs with conventional injectable preparations of insulin currently used in the treatment of patients with diabetes mellitus is largely responsible for the morbidity associated with this disease. Epidemiological evidence and animal experimentation strongly support systemic hyperinsulinemia as a major factor in genesis of atherosclerosis in diabetic patients. In addition, in vitro studies demonstrate a direct effect of insulin on endothelial cell and arterial smooth muscle proliferation. On the other hand, inadequate hepatic delivery of insulin is associated with overproduction of renal vasoregulatory factors leading to glomerular hyperfiltration and ultimately to glomerulosclerosis and its clinical endpoint--end-stage renal disease. In the absence of widespread success of pancreatic and islet-cell transplantation as a means to deliver insulin physiologically into the hepatic portal circulation, methods must be devised and perfected to accomplish such delivery using approaches such as orally administering insulin in intestinal-enzyme protected capsules. Until such methods of delivery are available for safe and widespread use, one should abandon the illusory goal of rigid glucose control in favor of methods that reduce insulin requirement. Along these lines, dietary restriction and aerobic exercise should be the major life style changes advised for diabetic patients. Reduction of glomerular hyperfiltration in diabetic patients can be promoted with the use of low protein diets and/or angiotensin converting enzyme inhibitors.

Animals

Oral insulin.

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Administration, Oral

The thyroid.

The integument contains many components whose function is influenced by thyroid hormone. Thus, an increase or decrease in hormone levels results in a variety of cutaneous, hair, and nail changes. These changes are important to recognize, as they may aid in the early diagnosis of thyroid disorders. Other cutaneous disorders are more prevalent in patients with thyroid disease, and their recognition may likewise be helpful. Finally, several syndrome complexes occur with which thyroid disorders are regularly associated.

Hair Diseases

Acute suppurative thyroiditis.

A 25 year old woman suddenly developed pain in a neck mass which had been present for 10 years. Aspiration of a large cyst revealed by ultrasonography produced blood stained fluid from which E. coli was subsequently grown. Acute suppurative thyroiditis is the least common inflammation of the gland, and E. coli infection has been reported only once before in the past decade. A technetium scan is helpful in distinguishing acute from subacute thyroiditis.

Acute Disease

A TSH secreting pituitary tumour causing hyperthyroidism: presentation of a case and review of the literature.

A 45 year old male with a 12 year history of mild hyperthyroidism and a pituitary tumour is presented. He had both clinical and laboratory evidence of hyperthyroidism and his serum TSH was persistently and markedly elevated. A TRH test resulted in no further rise in serum TSH. No evidence of pituitary or peripheral endocrine deficiencies existed and prolactin levels were normal. Craniotomy was performed and a pituitary adenoma was removed. On light microscopy, it was mostly composed of chromophobes. However, occasional granulated cells were observed, and on electron microscopy, most of the cells contained fine granules, which suggested possible thyrotroph origin of the tumour. One week post-operatively the patient's serum TSH returned to normal. Again, TRH produced no response in TSH. The patient became hypothyroid by clinical and laboratory findings and is currently on thyroid replacement therapy. The previously reported TSH secreting tumours associated with hyperthyroidism are reviewed.

Adenoma, Chromophobe

Thyroid function studies in the nephrotic syndrome.

Total serum and urinary thyroxine (T4), triiodothyronine (T3), and thyroxine-binding globulin (TBG) as well as serum free T4, thyroid-stimulating hormone (TSH), and T3 resin uptake (T3RU) were measured in seven patients with the nephrotic syndrome. The nephrotic syndrome was defined by proteinuria exceeding 3 g/24 h. All patients were clinically euthyroid. Most values for total serum T4, free T4, T3, T3RU, TBG, and TSH were within normal limits. However, the mean serum T3 and TBG values were significantly lower in patients compared with the control group. The values (mean +/- 2 SD) for urinary T4 were 24.3 +/- 20.3 in the patient group and 1.5 +/- 0.7 microgram/24 h in the control group. Urinary T3 values for patients and the control group were 2100 +/- 856 and 848 +/- 253 ng/24 h respectively. Urinary TBG was 2.1 +/- 1.8 mg/24 h in the patients and undetectable in the control group. There was no correlation between daily urinary T3 and T4 and urinary TBG. There was a weak correlation between daily urinary protein excretion and urinary T4 (r = 0.5).

Adult

Prospective randomized comparison of propylthiouracil.

Forty-nine patients with Graves' disease were randomly divided into two groups. One group received propylthiouracil, 150 mg every eight hours, and the other group received propylthiouracil, 450 mg as a single daily dose. All patients' conditions were evaluated clinically anc chemically at two-week intervals. The response to the divided dosage schedule was prompt and predictable, and by ten weeks all but one patient had achieved remission. The group that received the single daily dose regimen responded less favorably, and at ten weeks ten patients had failed to achieve remission (P less than .001). However, when these patients' regimens were switched to the every-eight-hour schedule, all but one patient became euthyroid in an additional four weeks.

Drug Evaluation