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The toxicological evaluation of urinary human epidermal growth factor (u-hEGF) included mutagenicity, single and repeated dose general toxicity, and teratogenicity studies in various animal species. The mutagenic potential of u-hEGF was tested in vitro (Ames test, chromosome aberration in human lymphocytes, unscheduled DNA synthesis in HeLa cells) and in vivo (chromosome aberration in Chinese hamster bone marrow and micronucleus test in rat bone marrow). No mutagenic or clastogenic effects were found. The acute toxicity of u-hEGF was evaluated in mice and rats, using single subcutaneous (sc) or intravenous (iv) injection of 15 mg/kg. No toxic effects were observed. Four-week iv daily administration of u-hEGF at the doses of 0.3, 0.9, and 3 mg/kg in the SD rat followed by 2 wk of compound withdrawal induced pronounced and generally dose-related effects (i.e., epithelial hyperplasia) in a wide range of tissues and organs, at all doses. However, these effects were not apparently detrimental to the general health of the rats. The repeated sc administration of u-hEGF to cynomolgus monkeys for 4 wk at the same doses as used in the rat study resulted in lethality after about 7 days of treatment in the 2 higher dose groups or after 14 days at the lowest dose. The main clinical signs observed were gastrointestinal effects, respiratory distress, sedation, marked loss of body weight, and cutaneous desquamation. At histology, hyperplasia of most epithelia was seen in all groups. In addition, atrophy of the ovarian follicles and necrosis of the uterine endometrium were noted. Changes considered secondary to physical distress were atrophy of the hemopoietic and lymphatic system and hepatic steatosis. The embryofetal toxicity and teratogenicity of u-hEGF was tested, using the iv route in the SD rat and the iv and sc routes in the New Zealand White rabbit. In both species, the compound was administered at the doses of 0, 0.3, 0.9, and 3 mg/kg/day, from day 6 to 15 of pregnancy in rats and 6-18 in rabbits. In the rat, an increase in body weight was noted in the dams and fetuses at the 2 high doses. No embryotoxic or teratogenic effects were observed. In the rabbit studies, mortality and severe clinical signs involving various systems, with marked effects on the eyes, were observed at all doses tested during the first days of treatment by both routes. From the reproductive point of view, most of the surviving treated gravid females showed only resorptions.

The histological, immunohistochemical, and electron microscopic characteristics of a spontaneous case of atriocaval mesothelioma are described in a 102-wk-old male Sprague-Dawley rat. The immunohistochemical characteristics of the tumor are compared with those of a pericardial mesothelioma in a female Sprague-Dawley rat.

A new blood module for continuous renal replacement therapies has been utilized to perform CVVH in critically ill patients. The features of the new module named (HP300 and manifactured by Medica srl (Medolla, Modena) are the easy installation and transportability to the bedside, the simple and safe management and the continuous measurement of the pre and post filter pressure with automatic calculation of the end-to-end pressure drop inside the filter. The last feature permits to detect early malfunctions of the filter due to fibers clotting or due to the internal coating of the hollow fibers by plasma proteins. In both cases the efficiency of the treatment can be reduced because of a significant reduction of the ultrafiltration rates or a remarkable decay of the membrane permeability and solute sieving coefficients. In many cases this reduction is only detected when important effects on solute removal have already occurred. In our experience, the new module permitted the substitution of the filters when early malfunctions were detected and maximal treatment efficiency was therefore guaranteed over extended periods of time.

Conglomerates of food and mucus or phytobezoars composed of vegetable matter are sometimes found in the stomach in the general population. Reports of phytobezoars in uremic patients are, however, scarce. Here we describe 2 uremic patients in which esophagogastroduodenoscopy was performed due to dyspepsia associated with weight loss and in which stomach phytobezoars were discovered. Theoretically, uremic patients should be at risk for producing bezoars. In fact, these patients frequently present predisposing conditions such as autonomic neuropathy, diabetes mellitus and delayed gastric emptying. Gastric bezoars cause anorexia. Anorexia is a frequent symptom in dialysis patients and is associated with malnutrition. In these patients, malnutrition is strongly associated with mortality and is quite difficult to reverse. Similarly, phytobezoars cause chronic anorexia. We suggest that clinicians working in dialysis units should consider the possibility of a gastric bezoar when evaluating anorexic uremic patients.

While reports of venous calcifications are scarce, vascular calcifications frequently occur in the arteries of uraemic patients. Venous calcification of an aged arterious-venous (a-v) fistula in a young patient with a long-standing history of hyperparathyroidism was detected on a forearm X-ray. Risk factors for vascular calcifications are still under debate, but calcium-phosphate product appears to be involved in its pathogenesis. We suggest that a-v fistula of patients with hyperparathyroidism history should be monitored as calcifications could be a risk factor for access thrombosis.

Nephrolithiasis is a rare finding in kidney transplantation and anuria could be the only clinical sign. We report the case of a 52-year-old Caucasian male renal transplant recipient admitted due to acute renal failure (ARF) and anuria. He reported no symptoms and a palpable bulge in the right iliac fossa corresponding to the graft was present. Ultrasonography showed hydronephrosis of the graft. A double-J ureteral stent was inserted with resolution of ARF. ARF with anuria and the presence of a palpable non-tender, elastic mass over the graft could be the clinical picture of obstructive ARF in a transplanted kidney.

Evaluation of the Toxicity of Indomethacin in a 4-Week Study, by Oral Route, in the Marmoset (Callithrix jacchus). OBERTO, G., CONZ, A., GIACHETTI, C., AND GALLI, C. L. (1990). Fundam. Appl Toxicol. 15, 800–813. A subacute toxicity study of Indomethacin administered by oral route, was carried out in the marmoset (Callithrix jacchus). Groups of three males and three females received Indomethacin directly into the stomach by means of a catheter for a period of 4 weeks at the dose levels of 0, 2, 6, and 12 mg/kg body wt/day and then were euthanized for pathological evaluation. All marmosets given 12 mg/kg/day and one marmoset given 6 mg/kg/day died during the dosing period (within 20 days). At 12 mg/kg/day, Indomethacin induced severe gastrointestinal toxicity (hemorrhage, ulcers, and necrosis with peritonitis), while at the dosages of 6 and 2 mg/kg/day some moderate to slight dose-related functional and morphological renal alterations (increase of serum urea, reduction of serum albumin, increase of serum potassium and/or chloride, and subacute inflammation) were observed. The fact that in many respects these alterations are similar to those observed in man is a further demonstration of the validity of the marmoset as an experimental model.

Paired filtration dialysis (two-chamber haemodiafiltration) was evaluated as a short, highly efficient renal replacement therapy in 35 uraemic subjects belonging to three different dialysis centres. The study period was 1 year. Patients were divided into two groups according to their body-weight and drinking habits. The smaller patients underwent 150-min dialysis sessions three times weekly. The larger patients underwent 3-h treatments thrice weekly. The treatment was adequate in all patients according to the KT/V criteria of adequacy. The intradialytic symptomatology was remarkably low and the treatments were well tolerated in all patients. The study confirms the reliability of aired filtration dialysis as a short dialysis technique. In some patients 150 min may be insufficient to achieve an equate dialysis efficiency and 180 min may be required for the majority of the population.