Metastatic disease from untreated choroidal and ciliary body melanomas

We report the case histories of three patients with untreated malignant melanoma of the choroid or ciliary body. Metastatic disease which resulted in death was diagnosed four years in two patients and 13 years in one patient after the diagnosis of choroidal melanoma was suspected. The diagnosis of malignant melanoma was confirmed by histopathology in two of these patients.     

Islet function and insulin sensitivity in the non-diabetic offspring of conjugal type 2 diabetic patients

To determine whether the genetic predisposition towards Type 2 diabetes was associated with a defect in either islet-cell function or insulin action, 12 non-diabetic offspring each of whose parents both had Type 2 diabetes were studied, together with 12 control subjects matched for age, sex, and weight. Fasting plasma glucose was higher in the offspring (5.5 +/- 0.1 mmol l-1 (mean +/- SE)) than in the matched controls (5.1 +/- 0.1 mmol l-1) (p less than 0.05). Using an IVGTT insulin sensitivity was not significantly lower in the offspring compared with their controls (3.1 +/- 0.5 vs 3.8 +/- 1.0 min-1 mU-1 l 10(-4)). There was no significant difference in any of the measures of insulin secretion (first- and second-phase response to IV glucose, slope of glucose potentiation, and maximal glucose regulated insulin secretory capacity). Glucagon secretion measured before and after a stimulus of IV arginine at varying plasma glucose concentrations was virtually identical in the offspring and their controls. Among a total of 28 non-diabetic subjects of differing body-weights there was a significant inverse relationship between insulin sensitivity and insulin secretion. When adjusted for their generally lower insulin sensitivity, maximal insulin secretory capacity was reduced in the offspring (p = 0.038, one-tailed t-test). The results suggest that the genetic predisposition to Type 2 diabetes is not associated in young adults with any major pre-morbid impairment in insulin secretion or insulin action but the relationship between the two may be abnormal. Islet A-cell function appears to be normal.     

The role of platelet-activating factor in human fetal lung maturation

The presence of the potent bioactive glycerophospholipid 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine (platelet-activating factor) in a lamellar body-enriched fraction of amniotic fluid from women in labor has prompted the present investigation to examine the fetal lung as the possible tissue source of this platelet-activating factor. The metabolism of platelet-activating factor was assessed in an organ culture system in which human fetal lung tissue (12 to 16 weeks) was incubated for 6 to 7 days. During this period, the type II pneumonocytes differentiate and surfactant glycerophospholipid biosynthesis is greatly enhanced. The initial specific activity of the platelet-activating factor biosynthetic enzyme lyso-platelet-activating factor:acetyl-coenzyme A acetyltransferase is two to three times greater in microsomes prepared from fetal lung than in those from the fetal liver or kidney. The specific activity of acetyltransferase in lung tissue increased twofold after 6 days in organ culture. A similar increase in acetyltransferase activity was found in the lamellar body-enriched (18,000 X g) subcellular fraction of fetal lung. The activity of the major platelet-activating factor-inactivating enzyme platelet-activating factor acetylhydrolase did not change significantly in the lung explants during the incubation period. Associated with the enhanced platelet-activating factor biosynthetic activity in the fetal lung was an increase in the platelet-activating factor concentration, from 17 to 37 fmol/mg of protein between days 0 and 6 of culture. Corresponding increases of 3.3- and 3.8-fold in the concentrations of the platelet-activating factor lipid precursors lyso-platelet-activating factor and the 2-acyl congener were found after 6 days in culture. A reciprocal relationship was found between platelet-activating factor and glycogen content as the lung tissue matured in vitro; specifically, as the platelet-activating factor level increased, glycogen decreased from 340 to 77 micrograms/mg of protein. We suggest that platelet-activating factor may mediate the onset of glycogenolysis in fetal lung tissue similar to that in the isolated, perfused rat liver (Shukla SD, Buxton DB, Olson MS, Hanahan DJ. Acetylglyceryl ether phosphorylcholine. A potent activator of hepatic phosphoinositide metabolism and glycogenolysis. J Biol Chem 1983; 258:10212-4). The increased rate of glycogen degradation may serve as the carbon and energy source for the increased synthesis of glycerophospholipids required for surfactant production.(ABSTRACT TRUNCATED AT 400 WORDS)     

Development of a bullous pemphigoid after split-skin grafting.

An elderly female patient developed blisters localised to her split-skin donor and graft sites. Despite repeated swabs, bacteriology and virology returned negative; multiple antibiotic courses did not improve her condition, which generalised within weeks. Histology and immunofluorescence confirmed a clinical diagnosis of bullous pemphigoid and her condition resolved rapidly after treatment with prednisolone. Bullous pemphigoid can be precipitated or exacerbated by surgery and the diagnosis should be considered when patients present with persistent localised or generalised blisters, especially when microbiological investigations are negative.     

ATRIAL NATRIURETIC FACTOR IN CHRONIC RENAL FAILURE: STUDIES IN MAN AND THE RAT

1. Plasma concentration and atrial content of atrial natriuretic factor (ANF) were measured in rats with chronic renal failure induced by subtotal nephrectomy. 2. Plasma ANF was higher, and atrial ANF content lower in rats with renal failure when compared with sham-operated controls. 3. Plasma renin activity (PRA) and ANF were elevated at 1 week following subtotal nephrectomy. After 1 month plasma ANF had risen further, but PRA was suppressed to below control values. 4. Plasma ANF was also measured in six patients with chronic renal failure undergoing routine haemodialysis. 5. Elevated plasma ANF levels in patients with renal failure were lowered by haemodialysis, although extraction of ANF across the dialysis membrane was negligible. 6. Secretion of ANF is increased in chronic renal failure in man and the rat, possibly mediated by increased intravascular volume.     

Effect of cell wall skeleton and monophosphoryl lipid A adjuvant on the immunogenicity of a murine B16 melanoma vaccine

We examined the effect of a new adjuvant consisting of purified mycobacterial cell wall skeleton (CWS) and monophosphoryl lipid A (MPL) on the immunogenicity of a murine melanoma vaccine. C57BL/6 mice were immunized to partially purified B16 melanoma vaccine given alone or together with different dose levels of adjuvant, or with saline or adjuvant alone. Humoral response, delayed-type hypersensitivity (DTH), in vitro cytotoxicity, and tumor-protective immunity to melanoma were measured following three biweekly immunizations. The adjuvant potentiated the antibody response to some, but not all, melanoma antigens in a dose-dependent fashion. The adjuvant also potentiated cellular immunity as measured by in vitro cytotoxicity assays. No potentiation of tumor-protective immunity was detected. In comparison to Freund's complete adjuvant, cell wall skeleton plus monophosphoryl lipid A (CWS:MPL) induced fewer cutaneous toxic effects and stronger antibody and DTH responses but resulted in no greater in vitro cytotoxicity or tumor-protective immunity. Thus, the adjuvant had a selective and dose-dependent effect on humoral responses to vaccine immunization but did not potentiate a tumor-protective immunity to B16 melanoma.