Relationship between prorenin, IGF-I, IGF-binding proteins and retinopathy in diabetic patients.

Plasma prorenin and renin, serum insulin-like growth factor I (IGF-I) and IGF-binding protein (IGFBP-2 and IGFBP-3) concentrations were measured in 22 randomly selected male and female patients with insulin-dependent diabetes mellitus (IDDM) or non-IDDM (NIDDM). Plasma prorenin concentration was significantly elevated in patients with proliferative retinopathy (1869.5 +/- 785.0 mUL-1, mean +/- SEM) compared to patients with nonproliferative retinopathy (325.5 +/- 73.2 mUL-1, P < 0.003) and those without retinopathy (318.6 +/- 47.3 mUL-1, P < 0.007). Similarly, serum insulin-like growth factor-I (IGF-I) concentration in patients with proliferative retinopathy (126.3 +/- 21.5 micrograms L-1) was significantly higher than in patients with nonproliferative retinopathy (126.3 +/- 14.85 micrograms L-1, P < 0.004) and without retinopathy (135.2 +/- 37.26, P < 0.05). There was moderately strong positive correlation between plasma prorenin and serum IGF-I concentrations (r = 0.56, P < 0.01). Plasma prorenin concentration was uninfluenced by change in renal function (creatinine clearance, serum creatinine or BUN), but IGF-I levels were inversely related to creatinine clearance (r = 0.67, P < 0.002). There was no demonstrable relationship between IGF-binding proteins and prorenin or renin concentrations. In view of some overlap between plasma prorenin and serum IGF-I concentrations in diabetic patients with proliferative and nonproliferative retinopathy, measurement of both markers may be more useful in predicting the development of proliferative retinopathy in patients with diabetes mellitus than either measurement alone.

Relationship between serum estradiol concentration and IGF-I, IGF-II and IGF-binding proteins in patients with premature ovarian failure on short-term estradiol therapy.

OBJECTIVE: Insulin-like growth factors (IGFs) exert stimulatory effects on follicular growth and development, and early embryogenesis. In view of this, we studied the effect of short-term estradiol treatment, as used in preparing the uterus for embryo implantation, on the serum concentrations of IGFs and their binding proteins (IGFBP) in patients with premature ovarian failure (POF). PATIENTS AND METHODS: Twenty-four patients with POF, enrolled in an assisted reproduction program, were treated with increasing doses of estradiol up to 8 mg daily for 6 weeks. Blood was sampled for measurement of serum estradiol, IGF-I, IGF-II, and IGFBP 1, 2 and 3 at various times during estradiol treatment. RESULTS: There was no significant correlation between serum estradiol concentrations and the serum concentrations of IGF-I and IGF-II. As expected, IGF-I and IGF-II concentrations in serum correlated positively with the serum concentration of IGFBP-3, the major IGF-binding protein in serum. CONCLUSION: The results of this study suggest that estradiol therapy as used to prepare the uterus for implantation has no significant effect on serum IGF-I and IGF-II concentrations, and therefore probably does not influence, via an IGF-mediated mechanism, the success of implantation and early embryonic development.

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.

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.

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.

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.

A case of group B streptococcal pyomyositis.

The group B streptococcus is an opportunistic pathogen that causes a variety of serious infections including bacteremias, puerperal sepsis, and neonatal meningitis. Group B streptococcal infections of muscle are rare. We report here an unusual case of group B streptococcal pyomyositis. Pyomyositis arises predominantly from infections caused by Staphylococcus aureus and, occasionally, Streptococcus pyogenes. Because of the rarity of pyomyositis in temperate climates, the common lack of localizing signs or symptoms, and the frequently negative blood cultures, considerable delay often precedes the diagnosis of pyomyositis; in fact, the infection has been initially misdiagnosed as muscle hematoma, cellulitis, thrombophlebitis, osteomyelitis, or neoplasm. Diagnosis may be greatly aided by radiologic techniques that can demonstrate the sites of muscle enlargement and the presence of fluid collections. The response to antibiotics is usually rapid, but resolution of the infection may require aspiration of deeply situated muscle abscesses. This report describes a diabetic patient with an unusual presentation of pyomyositis that mimicked an acute abdomen.

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.

Propranolol toxicity presenting with early repolarization, ST segment elevation, and peaked T waves on the ECG.

A 58-year-old man presented stating that he had voluntarily ingested eight 80-mg propranolol tablets in approximately 24 hours. He was asymptomatic at the time of presentation. Subsequently, the patient developed only mild bradycardia. The ECG showed sinus bradycardia with striking early repolarization, ST segment elevation, and peaked T waves. These ECG abnormalities represent an unusual pattern for beta-adrenergic blocking agent toxicity.

Weight loss without dietary restriction: efficacy of different forms of aerobic exercise.

Since obese patients with orthopaedic disabilities are often advised to undertake swimming as a part of a weight loss program, the effect of swimming on body weight was systematically studied. Minimally to moderately obese, otherwise healthy young women seeking to lose weight through a program of exercise without dietary restrictions were randomly assigned to one of three groups in which only the type of daily exercise was different. The three types of exercise were brisk walking, riding a stationary cycle, and swimming laps in a pool. All women slowly but progressively increased the time spent in daily exercise to 60 minutes. After 6 months or slightly longer, the women assigned to walking lost 10% of initial weight, the women who cycled lost 12%, but the women who swam lost no weight. The thickness of the subcutaneous panniculus over the middle of the extensor surface of the upper arm was measured using a Lang skin-fold caliper (Graham Field Co, New York, NY) and showed equivalent substantial reductions in the walkers and cyclists, but no change in the swimmers. The results of this study show that both walking and cycling are effective methods of reducing body fat, but that swimming is not.

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.