Platelet glutathione and thromboxane synthesis in diabetes.

The relationship of the reduced glutathione (GSH) content in unstimulated platelets and their capacity to synthesize thromboxane A2 (TXA2), measured by radioimmunoassay of TXB2, was investigated in diabetic and matched control subjects. The GSH content in platelets from diabetic subjects (6.52 +/- 0.73 microgram/10(9) platelets, mean +/- SD) was significantly (P less than 0.001) lower than in platelets from control subjects (10.10 +/- 1.58 microgram/10(9) platelets). When platelet-rich plasma (PRP) was stimulated with 1.65 mM arachidonic acid, significantly (P less than 0.001) more TXB2 was formed in PRP from diabetic subjects (344 +/- 87 ng/2.5 X 10(8) platelets) than in PRP from control subjects (132 +/- 35 ng/2.5 X 10(8) platelets). Furthermore, the plasma level of TXB2 was increased in diabetic subjects (522 +/- 117 pg/ml) in comparison with control subjects (187 +/- 63 pg/ml). An inverse correlation (r = 0.98) was observed between the GSH content in unstimulated platelets and their capacity to synthesize TXA2 when stimulated with 1.65 mM arachidonic acid. These data suggest that platelet GSH may have an important regulatory effect on platelet TXA2 synthesis and that increased TXA2 synthesis by platelets from diabetic subjects may be the result of low intracellular GSH levels.

Community screening for diabetes by blood glucose measurement. Results of a five-year experience.

The Diabetes Association of greater Cleveland screened 307,000 individuals in the metropolitan area for diabetes with a 75-gm. oral load of carbohydrate. Of these subjects 12,600 (4.1 per cent) had a two-capillary blood glucose level of greater than 139 mg. per cent and were defined as positive. Seventy per cent of the positives were retested, and 65 per cent of these again had two-hour levels greater than 139 mg. per cent. Seventy-one per cent of the original screening values were between 104 and 199 mg. per cent. The rate of positivity on retesting increased with the original screening bracket reaching 90 per cent at an original screening level of 240 mg. per cent or higher. The frequency of positive retests also increased with age irrespective of whether the original screening level was less than or greater than 200 mg. per cent. The implications of this large detection experience for conducting future mass surveys for diabetes are discussed.

Experience with low-dose insulin infusion in diabetic ketoacidosis and diabetic hyperosmolarity.

Forty patients with diabetic ketoacidosis and eight patients with the diabetic hyperosmolar state were treated with low-dose insulin infusion in four teaching hospitals in the Cleveland area. The clinical and biochemical responses observed support previous favorable reports on this treatment modality. Two elderly patients with the hyperosmolar syndrome died. The advantages of this form of treatment over intermittent insulin schedules are emphasized. Early potassium administration, unless otherwise contraindicated, is recommended. Rarely, increasing doses of insulin may be required if insulin resistance is encountered.

Autoimmune thyroiditis in manic-depressive patients treated with lithium.

To explore whether lithium-induced hypothyroidism is related to an exacerbation of underlying autoimmune processes such as thyroiditis, the authors comprehensively assessed thyroid function in 16 manic-depressive patients. Each of the three patients who showed detectable titers of thyroid microsomal antibodies before treatment manifested a marked increase in antibody titer from 4 to 12 months after lithium treatment was begun. Thus, lithium-induced thyroid dysfunction may not only involve direct effects on the thyroid itself but also involve exacerbation of an underlying indolent autoimmune thyroiditis, possibly by causing shifts in T lymphocyte subpopulations.

Lack of demonstrable tumor growth in progressive hyperprolactinemia.

Prolactin has been regarded as an excellent tumor marker for patients harboring prolactinomas, and a significant rise in the basal prolactin level is generally regarded as being commensurate with tumor growth. This report describes a case in which the basal serum prolactin level rose from 250 ng/ml to 1,528 ng/ml over a 10-year follow-up period in the absence of definitive therapy. Three sequential contrast-enhanced direct coronal computed tomographic scans obtained over a four-year period failed to demonstrate any evidence of growth of the 5 mm microprolactinoma. Progressive hyperprolactinemia may not be synonymous with tumor growth in patients with microprolactinomas.

Insulin-induced cardiac failure.

Self-limited edema is a well-recognized complication of insulin therapy. However, progression to overt cardiac failure has only recently been reported in one patient with pre-existing heart disease. This report describes the first case of insulin-induced cardiac failure in a patient without underlying heart disease. Current trends toward intensive insulin therapy for rapid near-normalization of blood glucose levels will increase the recognition of this entity. Careful follow-up of so-called "self-limited" insulin edema is encouraged, and the early institution of diuretic therapy is advocated in elderly patients to prevent the development of overt cardiac failure.

Measurement of serum C-peptide immunoreactivity by radioimmunoassay in insulin-dependent diabetics.

A radioimmunoassay for C-peptide utilizing synthetic C-peptide as an antigen and tyrosylated synthetic C-peptide for iodination was evaluated for its clinical use. Mean fasting C-peptide levels in 24 normal subjects was 2.6 +/- 0.8 ng/ml. During the oral glucose tolerance test, baseline C-peptide in five normal subjects was 1.5 +/- 0.8 ng/ml, and at 60 min was 5.6 +/- 1.6 ng/ml. For two insulin-dependent diabetic patients, diagnoses of factitious hypoglycemia were documented on the basis of simultaneous free insulin and C-peptide determinations. Sera from 24 insulin-dependent diabetics were analyzed for free and total immunoreactive C-peptide and insulin levels. For 20% of juvenile and 64% of maturity-onset diabetics, the presence of proinsulin-like material bound to insulin antibodies was demonstrated by measurement in unextracted serum. This accounted for 20% to 100% of total C-peptide immunoreactivity in these patients. Simple polyethylene glycol precipitation of immune complexes and the measurement of free immunoreactive C-peptide in the supernatant demonstrated subnormal levels (less than 0.5 ng/ml) in all juvenile diabetics and normal levels (1.8 +/- 1.3 ng/ml) in 70% of maturity-onset diabetics.

The relationship of thyroid-stimulating hormone (TSH), thyroxine (T4), and triiodothyronine (T3) in primary thyroid failure.

Thyroid-stimulating hormone (TSH), serum thyroxine (T4) and triiodothyronine (T3) in sera of 100 patients with primary thyroid failure were measured by radioimmunoassay. Effective thyroxine ratio (ETR) was also measured in 69 of these sera. TSH was elevated in all, with a mean of 76.7 +/- 55 micromicron/ml (range 11 to 140 micromicron/ml, and was used to confirm the diagnosis. Mean T4 and T3 levels in the group were 1.8 +/- 1.5 microgram/100 ml (range less than 0.2 to 7.0 microgram/100 u.) and 76.7 +/- 76 ng/100 ml (range less than 10 to 600 ng/100 ml), respectively. Mean ETR was 0.81 +/- 0.05. A moderate inverse relationship was observed between TSH and T4 (r = 0.73), in contrast to TSH and T3 and TSH and ETR, which showed comparatively poor relationships (r = 0.41 and 0.43). This observation, in addition to the finding that 17 patients had subnormal T4 but normal or elevated T3, suggests that normal T3 levels alone may not be sufficient to maintain euthyroidism. In contrast, there were only three clinically hypothyroid patients who had elevated TSH, normal T4, but subnormal T3 levels. This study indicates that T4 and T3 may function together to maintain euthyroidism, and that in addition to serum TSH, T4 determination has more diagnostic value than serum T3 or ETR in these patients.

Hyperparathyroidism after radioactive iodine therapy for Graves disease.

The association of external ionizing radiation to the head and neck and the subsequent development of hyperfunctioning parathyroid glands has been documented in recent years. This also has been demonstrated experimentally in animals. Despite the numbers of patients with Graves disease who have been treated with radioactive iodine, there are no reports in the literature of parathyroid surgery for hyperparathyroidism secondary to earlier treatment with radioactive iodine for Graves disease. This report describes the operative and pathologic findings in four patients with hyperparathyroidism. These patients had previously been treated with radioactive iodine for Graves disease. The pathologic findings at surgery included in three cases a single enlarged hyperplastic gland consistent with a parathyroid adenoma. One patient had hyperplasia of all four glands. The two largest glands and halves of the two remaining glands were removed. In a long-term follow-up of children and adolescents treated with radioactive iodine for Graves disease, Levy and Schumacher found calcium elevations in 10 of 159 patients. The increased incidence of hyperparathyroidism following radioactive iodine treatment for Graves disease in children and adolescents would seem several times higher than normal. Whether adults who have radioactive iodine treatment for Graves disease have a similar increase incidence is not known. Meanwhile it would seem reasonable to suggest that patients whose hyperthyroidism is treated with radioactive iodine should have their serum calcium levels determined at 5-year intervals.

[Effects of octreotide on serum and urine electrolytes in a patient with parathyroid carcinoma: clinical case]. / Efectos del octreotide sobre los electrolitos en suero y orina de un paciente con carcinoma de paratiroides: caso clínico.

Parathyroid carcinoma (PC) is a rare endocrine tumor whose management is difficult whenever surgery does not achieve complete en bloc resection or recurrence is detected. Medical options (mainly bisphosphonates) are scanty and often associated with toxic side-effects. We present a case report of a patient with recurrent PC after two surgical interventions who was treated with octreotide (SMS-201) taken into account the positive somatostatin staining of the specimen obtained during the last surgery. Short term effects (-2 weeks-) included a decrease in urinary calcium excretion paired with a simultaneous increase in urinary phosphorus excretion. Later on, continuous subcutaneous octreotide administration kept urinary calcium excretion at low levels and this effect was completely reversible/reinducible upon discontinuation/reintroduction of the drug. Neither iPTH nor total serum calcium were modified at short or long term basis. The lack of clear-cut therapeutic effects make this findings a pure clinical observation. Thus, octreotide cannot be recommended for the treatment of parathyroid carcinoma.

[Long-term results after Spitzy's umbilical hernia repair]. / Langzeitergebnisse der Nabelhernienreparation nach Spitzy.

A total of 140 patients presenting with umbilical hernia underwent Spitzy's operation and were included in a retrospective study to analyse the recurrence rate. The patients received a questionnaire and were invited for a physical examination including ultrasound. Participation included 108 patients (follow-up 77%). A total of seven patients (6.5%) developed postoperative wound infections. Prolonged postoperative impairment was mentioned by nine patients (8.3%). After a mean period of 16 days, the patients were able to continue their occupation, and after 27 days, they could manage their usual physical activity. The recurrence rate was 13.0%. The risk for a recurrence correlated with the relative bodyweight. In the group with a body-mass-index (BMI) of less than 30, the recurrence rate was 8.1 %, whereas 31.8% of the patients with a BMI of more than 30 developed a recurrent hernia. The size of the hernial orifice also had an influence on the postoperative result. In patients with a hernial gap smaller than 1 cm the recurrence rate was 6.3%, with hernia orifices from 1 to 2 cm the rate was 4.1%, from 2 to 3 cm 14.3%, from 3 to 4 cm 25.0% and in patients with hernial gaps greater than 4 cm the rate of recurrences was 54.5%. Considering these results,we recommend the use of alloplastic material for umbilical hernia repair for patients with a BMI greater than 30.0 and hernia orifice larger than 3 cm. The decision for use of a mesh in hernial gaps from 2 to 3 cm should depend on individual factors.