The future of employee benefit-related public policy.

The past decade has seen frantic legislative activity in the employee benefits area, Ms. Rappaport observes. Several long term issues will continue to affect benefits, she predicts.

Transhepatic absorption and biliary excretion of insulin.

The application of insulin to the liver in rats is followed by an increase of the insulin concentration in the bile. The pathway of insulin from the liver surface to the bile may include a secretory process by the hepatic cells, or it may bypass the hepatic cells, using direct anatomical pathways from blood and lymph to bile. The concentration of insulin in arterial and venous blood, in lymph, and in bile was measured following application of insulin to the liver surface and following peritoneal or intravenous administration. The results confirm that insulin is absorbed from the surface of the liver, but the glucose modulating effect was less effective than after intravenous administration. The insulin concentration in bile was increased after insulin administration by all routes, with the highest and most prolonged increases found after intraperitoneal administration. The results suggest that following transhepatic and intravenous administration, insulin reaches the bile without passing through the liver cells.

The future of employer-sponsored retiree medical plans.

Complex issues cloud the economic security of people who are covered by employer-sponsored retiree medical plans. The future stability of these plans is especially confusing. In their paper, the authors carefully analyze the current structure of retiree medical plans, including the effect of certain laws. Their clarifications are objective and concise. Of particular timeliness and practicality--particularly for public policy markers--is the authors' four-point strategy to help stabilize the future.

Studies on transhepatic insulin absorption.

The intraperitoneal administration of insulin has been recommended because it was found to effectively control the plasma glucose level. Several authors have suggested that intraperitoneal insulin administration may be more "physiological" and therefore preferable because the insulin is absorbed into the portal venous system without, however, identifying the exact pathways. The possibility that insulin is absorbed through the surface of the liver was investigated in rats. The results show that insulin is absorbed rapidly by this route, but the effect on glucose modulation is similar to that of insulin given by other routes. In contrast, the effect on glucose modulation was delayed following insulin administration into the lower peritoneal cavity with exclusion of the liver.

The effect of mouse hepatitis virus infection on the microcirculation of the liver.

Mouse hepatitis virus type 3 infection results in strain-dependent liver disease. The effects of mouse hepatitis virus type 3 on the microcirculation of the liver in both fully susceptible (Balb/cJ) and fully resistant (A/J) mice were studied. In Balb/cJ mice, 6 to 12 hr following infection, abnormalities in liver blood flow were observed which consisted of granular blood flow in both terminal hepatic and terminal portal venules. In addition, sinusoidal microthrombi were present predominantly in periportal areas. By 24 to 48 hr, liver cell edema and small focal lesions were prominent. At 48 hr, thrombi and hepatocellular necrosis were widespread, and blood was shunted from damaged areas into patent sinusoids. In sharp contrast to these abnormal findings, normal streamlined blood flow was present in the resistant A/J animals at all time points following infection. Since large amounts of virus were demonstrated by immunofluorescene in and by recovery and growth from livers of both resistant and susceptible strains, the presence of the virus per se cannot explain the abnormalities observed.

The scarring of the liver acini (Cirrhosis). Tridimensional and microcirculatory considerations.

Cirrhosis is defined as the scarring of the liver acini in zone 3, zone 1 or in both; the resulting nodules are scarred and modified remnants of acini of various orders. The division of the nodules into "micronodules" and "macronodules" is difficult to justify as their two dimensional appearance changes at different planes of section. Early scar formation precedes changes in the microcirculatory dynamics. Sprouting of vascular branches, especially of arterioles, takes the leading role in the development of mature scars, i.e. of fibro-vascular membranes. The fibrous repair is at the same time the road builder for collateral flow. The pathophysiology of the collateral circulation is the basic determinant in the formation of the cirrhotic patterns. The three microcirculatory phases in the cirrhotic process are due to a changeover of the intrahepatic circulatory path from the normal trichotomy of the preterminal vascular branches to convoluted collateral channels. The three phases of the cirrhotic process are: The Triadal Nodule. It receives blood from the TPV and THA and from the perinodular plexus. The nodular parenchyma may already be segregated from the ThV, a situation that leads to portal hypertension. The Para-triadal Nodule. It is a conglomerate of nodules that often are not completely separated from each other; they are derived from neighbouring acini of various orders which receive blood from large triads contained in the perinodular scar. The blood arrives into the sinusoids primarily via the perinodular plexus. Some sinusoids may receive additional blood through sclerosing remnants of terminal afferent branches and through irregular vascular twigs which, along with septa, enter the nodules at various sites. The A-triadal Nodule. It is completely separated from neighbouring nodules by thick scars, its parenchyma totally segregated from afferent and efferent vascular branches. The nodules receive blood only from a dense perinodular plexus of wide capillaries.

Hepatic blood flow: morphologic aspects and physiologic regulation.

The study of the morphology of the hepatic circulation has given evidence that the liver consists of a large vascular delta formed by the confluence of the portal and arterial streams. Their arms, which subdivide the delta into lobar areas, start to run parallel and close to each other when they are still visible to the naked eye. Dwindled down to microscopic size, they become the scaffold of the parenchymal cell masses nestling between the microvessels. The arterioles, as they merge with the sinusoidal and portal channels, assume the role of organizing the microcirculation into units. These units are the vascular core of the structural and functional liver acini. It has now been demonstrated beyond doubt that a PO2 gradient exists in the hepatic vessels and tissues, decreasing from the site of the arteriolar rivulets joining the venous stream toward the site of their common egress via the terminal hepatic venules. The gradient permits the subdivision of the microscopic vascular units into three microcirculatory zones, each of them creating an appropriate microenvironment for specific enzymic and metabolic activity. The microcirculatory shifts in arterial flow from tide to ebb will cause change in the activity of the zones. These are essentially dynamic subdivisions of the metabolic activity in the large liver swamp. Here also start the tiny rivulets forming a green river, the bile stream, that runs in the opposite direction to the portal and hepatic arterial flow. It is to be expected that the quantity and quality of bile carrying important products back to the gastrointestinal area for digestion and absorption of fat are influenced by the tides in portal and arterial flow. All in all, it is evident that vascular morphology is the visual aspect of the dynamic blood flow, thus permitting us to perceive its functional orderliness, and to study the circulatory physiology in the hepatic delta. Means of measurement of hepatic blood flow have been reviewed and its methodological problems have been discussed. It was found that the term "estimated" hepatic blood flow is still justified. Also the relationship between hepatic blood flow and metabolism is not yet clear-cut. The role of the arterial and portal components of the hepatic circulation has been analyzed. There is a reciprocal relationship between arterial and portal volume flow; it is effectuated by the state of constriction or dilation of the mesenteric and hepatic arterioles, both under myogenic control. Portal blood delivers directly to the hepatocyte all water-soluble substances absorbed from the intestines or produced in the intestinal walls. The hepatic artery maintains an appropriate PO2 gradient between the acinar zones and flow of blood against increased tissue resistance; it assures a steady clearance of blood-borne substances, e.g., hormones and endogenous products. Regulation of arterial flow is less neural than neurohumoral; metabolites and bile salts exert additional effects on blood flow...

Effects of arterial or portal ischemia on survival and metabolism of partially and totally depancreatized dogs.

The role of arterial blood flow in hepatic metabolic functions was compared to that of portal flow in two groups of totally depancreatized dogs. Survival times and glucose and nitrogen excretion were significantly greater in dogs with ligation of the hepatic artery than in dogs with an Eck fistula. The dogs with ligated hepatic arteries also showed a significantly slower rise in plasma ketones. The course of diabetes was compared in three additional groups of partially depancreatized dogs consisting of a) dogs with ligated hepatic arteries, b) dogs with Eck fistulas, and c) controls. Hepatic arterial ischemia: 1) increased survival, without insulin treatment (a--650, b--167, c--124 days) 2) did not decrease tracer-determined rate of glucose production 3) led to a greater urinary excretion of glucose, ketone bodies and nitrogen than portal ischemia. Partially depancreatized dogs with either arterial or portal hepatic ischemia maintained a high rate of glucose disappearance on acute deprivation of endogenous insulin (clamping of vessels of their pancreatic remnant) due probably to decreased insulin degradation by the ischemic liver. The dogs died in coma after losing all fat depots. There was severe fatty change in the livers of dogs with hepatic artery ligation, slight in those with Eck fistulas and no fat in the livers of controls.