Catheterization of the portal vein via the umbilical vein was performed under local anesthesia in twelve nondiabetic subjects prior to exploratory laporatomy for a variety of conditions. Immunoreactive insulin (IRI) in simultaneously obtained portal and peripheral vein plasma was determined before, during, and after a two-minute glucose infusion (25 gm.). Two phases of insulin secretion were apparent from portal vein IRI concentrations. A rapid secretory phase beginning one minute after start of the infusion and lasting three to four minutes was followed by a slower secretory phase beginning approximately ten minutes after start of the glucose infusion. The absolute amount of "big" insulin (proinsulin-like material) in the portal vein was similar during the first phase and the early part of the second phase of insulin secretion. A significant positive correlation between portal vein and peripheral vein IRI responses to glucose was noted. DIA-BETES 79:302-06, May, 1970. Peripheral vein insulin concentrations have been widely used as an index of pancreatic insulin secretion. Insulin concentrations in peripheral veins may not accurately reflect pancreatic secretion, however, since insulin is secreted into the portal system and must traverse the hepatic bed before reaching the periphery. In order to study the relationship between portal vein and peripheral vein insulin concentrations, a relatively simple method of obtaining blood samples from the portal vein via the collapsed umbilical vein was utilized so that simultaneously obtained portal and peripheral vein immunoreactive insulin (IRI) could be compared before and after glucose administration. In addition to the quantitative aspects, qualitative properties of insulin released into the portal system were studied by determining "big" and "little" insulin. Although the

We describe the surgical excision of submacular scar in end-stage age-related macular degeneration and transplantation of autologous and homologous retinal pigment epithelial (RPE) cells. The technique involves the preparation of a large retinal flap encompassing the macula and the arcades, removal of the submacular scar, and replacement of the RPE cells, using either an autologous pedido graft or homologous RPE cells and Bruch's membrane. Fourteen months following the procedure, visual acuity in a patient with a pedicle graft had improved from counts fingers to 20/400 and the patient fixated over the transplanted RPE cells. After 10 months, a homologous graft in a second patient had become encapsulated with a fine subretinal membrane without neovascular tissue; visual acuity had not improved. No intraoperative or postoperative complications resulting from the surgery occurred in either patient.

We describe the development of several hybridization assay formats involving acridinium-ester-labeled DNA probes. The simplest of these is a homogeneous assay procedure that requires only three steps to complete, including a 5-s detection step. Using this format, we have detected target sequences in the 10(-16) to 10(-17) mol range; when rRNA is the target, this translates to 3000 to 300 bacterial organisms. The entire assay can be carried out in less than 30 min. This is the first homogeneous DNA probe assay to be of practical use in the clinical laboratory, and it represents a major simplification of hybridization formats. We also demonstrate the use of this homogeneous assay format to discriminate single-base differences between two closely related target sequences and to detect DNA as well as RNA target molecules. By combining homogeneous hybrid discrimination with solid-phase separation, we have been able to decrease background readings from unhybridized probe to only a few parts per million. This enhances assay sensitivity about 10-fold, to a range of 10(-17) to 10(-18) mol of target. We are in the process of further improving the performance of these assays.

The primary role of iodine deficiency in goitrogenesis and the prevention and treatment of endemic goiter by iodine supplementation is firmly established. Unfortunately, implementation of iodine prophylaxis programs has met with considerable technical and socioeconomic difficulties. Besides, lack of knowledge concerning some of the other causative factors of endemic goiter has prevented development of appropriate measures for its complete eradication in those areas where goiter persists in spite of prolonged and adequate iodine supplementation. At present, no less than 5% of the world's population have goiters and associated disorders, resulting in a public health and socioeconomic problem of major proportions. Seventy-five percent of people with goiter live in less developed countries where iodine deficiency is prevalent. Goiter prevalence rates of more than 50% and the highest frequency of severe cases of iodine deficiency disorders, namely, cretinism, congenital hypothyroidism, and various degrees of impairment of growth and mental development are found in endemic areas with extreme iodine deficiency. Goiters are usually multinodular and of very large size, producing, on occasion, signs of compression that require surgery. Recurrence rates are as high as 25-30% and second surgery accounts for 16% of all thyroidectomies. Unfortunately, most of these goiters occur in areas with highly restricted medical and surgical facilities. Twenty-five percent of people with goiters live in more developed countries where goiter continues to occur in certain areas despite iodine prophylaxis. Iodine-sufficient goiters are associated with autoimmune thyroiditis, hypothyroidism, hyperthyroidism, and thyroid carcinoma. Goiter is of considerable surgical significance in iodine-sufficient endemic areas and, to a lesser degree, in nonendemic areas where it is called "sporadic" goiter. Recurrence rates of iodine-sufficient goiter are 10-19% following thyroidectomy. Since most of these goiters grow by mechanisms other than increased thyrotropin (TSH) stimulation, treatment with suppressive doses of L-thyroxine is inefficient and, because of possible complications, not recommended. Although Graves' hyperthyroidism is not directly related to endemic goiter, it does relate adversely with ingestion or administration of iodine. At present, Graves' disease is treated with 131I or antithyroid drugs in more than 90% of the cases. The incidence rates of papillary, follicular, and anaplastic thyroid carcinomas appear to be related to endemic goiter and iodine supplementation, with surgery being required in essentially all of these cases.

Catheterization of the portal vein via the umbilical vein was performed under local anesthesia in eight nondiabetic subjects before exploratory laparotomy for a variety of conditions. Levels of immunoreactive glucagon (IRG) and immunoreactive insulin (IRI) were determined in simultaneously obtained portal and peripheral vein plasma before, during and after a fifteen minute arginine infusion (30 gm.) in five subjects. The mean portal vein to peripheral vein glucagon ratio in the postabsorptive state was 1.7 ± 0.5. A biphasic portal vein IRG response to arginine was observed, with the initial glucagon peak occurring within one minute of the beginning of the infusion. Peripheral IRG concentrations did not reflect the biphasic response. The portal vein IRI response to arginine was also mildly biphasic, and the first phase occurred before a detectable increase in blood glucose. The portal vein IRG peak either preceded or coincided temporally with the portal vein IRI peak. In three nondiabetic subjects, portal vein IRG decreased rapidly to its nadir within two minutes after a two minute glucose infusion (25 gm.) was started.