Evaluating Lead Bioavailability Data by Means of a Physiologically Based Lead Kinetic Model

A method of bioavailability estimation is presented in whicha physiologically based kinetic model of lead kinetics is fitsimultaneously to blood and bone lead concentrations after aperiod of exposure to dietary lead. Optimization of the simultaneousfit, varying only fractional absorption, gives the best estimateof fractional bioavailability for each treatment group. Theanalysis was applied to data from three separate studies inwhich rats were fed for 30 consecutive days purified diets containinglead added as lead acetate, mine waste-contaminated test soils,or mine waste itself. Fractional absorption decreased as leadintake increased, regardless of the source of the lead; butthe magnitude of this dose dependence was lead source-dependent.There were no differences in lead absorption by male and femalerats when lead intake was expressed per unit body weight. Fractionalabsorption varied from 4 to 5%, at low exposure rates (1–2mg lead/kg/day) when lead acetate was added to the diet, to0.24% at a high exposure rate (24 mg/kg/day) when a mine waste-contaminatedtest soil was added to the diet. Comparison of the results ofthis analysis with the results of a more conventional analysis,in which the bone and blood lead concentrations were separatelycompared with bone and blood lead concentrations in rats givendaily injections of lead acetate intravenously for 29 consecutivedays, demonstrated that the standard analysis failed to revealthe dose dependence of fractional absorption.     

RESOLUTION OF ACROMEGALY AFTER REMOVAL OF A BRONCHIAL CARCINOID SHOWN TO SECRETE GROWTH HORMONE RELEASING FACTOR

A 29 year old woman with an enlarged pituitary fossa and classical acromegaly, possibly present for ten years, had biochemical and partial somatic resolution of the disorder after removal of a bronchial carcinoid tumour. In addition, galactorrhea stopped, menstruation returned after two years, and amenorrhea and elevated prolactin levels fell towards normal.
Immunocytochemistry showed numerous growth hormone releasing factor (GRF) staining cells in the tumour. The tumour cells, when cultured, produced a supernatant selectivity stimulating human pituitary somatotrophic cell cultures to produce growth hormone (GH). The bronchial carcinoid did not secrete detectable GH, but extracts of it, and preoperative serum contained GRF immunoreactivity which coeluted with synthetic human pancreatic GRF.     

Seminal plasma biochemistry. IV: enzymes involved in the liquefaction of human seminal plasma

A significant positive correlation was found between the liquefaction time of human seminal coagula and bound sialic acid. There was also a similar relationship between bound sialic acid and the enzyme sialyl-transferase. This suggests that the degree of sialylation of the components of seminal coagulum are important in determining the liquefaction time of the coagulum. These results support previous findings. The coagulum is considered to be composed of glycoprotein-metal ion complexes, and the initial stage of liquefaction results from the reduction of these metal ions by L-ascorbic acid. The removal of hydrogen peroxide, generated by the oxidation of L-ascorbic acid, requires the presence of glutathione peroxidase and glutathione reductase. These enzymes have been identified in human seminal plasma and their possible physiological importance is discussed.     

A morphological and immunocytochemical study of a distinctive variant of ductal carcinoma in-situ of the breast

Because so-called 'carcinoid' tumour of the breast has proven to be a difficult entity to define, we studied in-situ carcinoma as there were reasons to believe that this might help clarify the complex problems involved. We studied a consecutive series of 30 cases of ductal carcinoma in-situ (DCIS) by light microscopy and silver impregnation methods and identified a relatively common endocrine variant of DCIS. This variant was studied by immunocytochemical and ultrastructural methods, using conventional DCIS as a control. Endocrine DCIS is identified by its organoid pattern, stromal 'inclusions', festooned structure and a distinctive type of polypoid invagination. It is argyrophilic and rich in neuron-specific enolase. Ultrastructurally it contains abundant dense core granules which are impregnated selectively by Grimelius' method. This tumour type frequently contains peptide hormones of the ACTH family. Three of seven cases contained cells reactive for ACTH and corticotropin-like intermediate lobe peptide CLIP or their precursor, pro-opiomelanocortin. A fourth tumour contained neurotensin, recently identified in a variety of endocrine tumours. Argyrophil invasive carcinomas are a much more heterogeneous group of tumours than argyrophil DCIS and only a minority have an endocrine structure comparable to that described here.     

A Study of Fifty-eight Patients with Renal Scarring Associated with Urinary Tract Infection

Fifty-eight patients, three male and 55 female, with radiologicallyapparent renal scarring together with urinary tract infectionhave been followed for periods from five to 13 years. Controlof urinary infection has been attempted by antibacterial treatmentand prophylaxis, and radiological appearances, renal functionand blood pressure have been monitored. Urinary infection waseliminated in 50 patients (86 per cent), all of whom becamesymptom-free. Evidence of new renal scarring was not seen, butthree patients showed contraction of kidney size and three developedradio-opaque renal calculi. Vesico-ureteric reflux was demonstratedin 20 patients; surgical re-implantation of ureters was carriedout in four patients and the indications for this operationare discussed. Of the 12 patients who had a raised serum creatinineat some time during the study only three showed progressivedecline in renal function; the serum creatinine returned tonormal in seven patients when infection was controlled. Hypertensionwas more common in patients with bilateral than in those withunilateral scarring, and all patients with evidence of impairedfunction at any time developed hypertension. We conclude thatmost patients with scarred kidneys and urinary infection canbe rendered symptom-free by control of infection, and that thereis some evidence that renal function can be preserved in thisway.