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Background Talactoferrin alfa is an oral dendritic cell (DC)-mediated immunotherapy (DCMI). We tested whether talactoferrin was superior to placebo in advanced non-small-cell lung cancer (NSCLC). Patients and methods An FORTIS-M trial was an international, multicenter, randomized, double-blind comparison of talactoferrin (1.5g p.o. BID) versus placebo BID, in patients with stage IIIB/IV NSCLC whose disease had failed two or more prior regimens. Treatment was administered for a maximum of five 14-week cycles. The primary efficacy end point was overall survival (OS); secondary end points included 6- and 12-month survival, progression-free survival (PFS), and disease control rate (DCR). Results Seven hundred and forty-two patients were randomly assigned (2:1) to talactoferrin (497) or placebo (245). The median OS in the intent-to-treat (ITT) population was 7.66 months in the placebo arm and 7.49 months in the talactoferrin arm [hazard ratio (HR), 1.04; 95% CI, 0.873–1.24; P = 0.6602]. The 6-month survival rates were 59.9% (95% CI, 53.4% to 65.8%) and 55.7% (95% CI, 51.1% to 59.9%), respectively. The 12-month survival rates were 32.2% (95% CI, 26.3% to 38.2%) and 30.9% (95% CI, 26.8% to 35%), respectively. The median PFS rates were 1.64 months and 1.68 months, respectively (HR, 0.99; 95% CI, 0.835–1.16; P = 0.8073). The DCRs were 38.4 and 37.6%, respectively [stratified odds ratio (OR), 0.96; 95% CI, 0.698–1.33; P = 0.8336]. The safety profiles were comparable between arms. Conclusions There was no improvement in efficacy with talactoferrin alfa in patients with advanced NSCLC whose disease had failed two or more previous regimens.

The synthesis of some of the products of cycloxygenase and lipoxygenase metabolism of arachidonic acid (AA) in mononuclear cells (MNCs) in vitro was studied with [3H]AA in five healthy subjects and five patients with liver cirrhosis (LC). FGA, ionophor Ca A23187 and levamisole were investigated. The eicosanoid synthesis by non-stimulated MNCs of the patients was normal. Mitogens augmented the outcome of PGs, TXB2 and HETE and increased the outcome of LTB4 in comparison with the control group. In liver pathology prostanoid and LT synthesis differed. In patients, but not in healthy subjects, prednisone suppressed eicosanoid production stimulated by FGA and reduced LTB4 and HETE outcome in MNCs treated by ionophor. The role of LTB4 hyperproduction in the pathogenesis of LC and the possibility of prednisone-induced suppression of synthesis of lipoxygenase metabolites in MNCs are discussed.

The authors analyze possible heat-transfer agents for heat pipes operating within the structural members of a gas-turbine motor. The authors have examined silicone liquids, for which they present thermophysical properties and the results of heat-pipe tests.

The correlation of collagen metabolism to liver contents of cyclic AMP and GMP as well as blood level of hormones was investigated in 105 patients with chronic hepatitis and liver cirrhosis. In patients with active hepatitis and cirrhosis showing the highest intensity of collagen metabolism there appeared elevated levels of cyclic AMP, somatotropic hormone and insulin against low levels of hydrocortisone and thyroxin. The relations between characteristics of plasma protein-bound oxyproline (PBOP), circadian oxyprolinuria and regulatory mechanisms under study suggest a competitive control of hepatic connective tissue metabolism maintained by hormones via cyclase systems. In high levels of blood PBOP and low ones of hydrocortisone, glucocorticoids unlike D-penicillamine promoted inhibition of liver collagen synthesis.

The authors studied acid and nonparietal secretion and the level of the blood flow in the gastric mucosa combined with the determination in it of the concentrations of prostaglandins (PGE and PGF2 alpha) and cyclic nucleotides (cAMP and cGMP) in 39 patients with primary (mostly medio-gastric) gastric ulcers, in 22 patients with secondary gastric lesions (with relation to duodenal ulcer) and in 58 patients with peptic ulcer. 30 healthy persons were investigated for control. More active acid secretion of the stomach was shown in the patients with secondary ulcers (as compared to the patients with primary ulcers) with similar indices of bicarbonate and fucose. The deficit of PGE in gastric mucosa was observed in ulcers of different sites with its lowest values in secondary gastric ulcers. In the patients with primary and secondary gastric ulcers the level of mucosal PGF2 alpha was decreased, in duodenal ulcer it was normal. A higher rate of the gastric blood flow was observed in the patients with duodenal and secondary gastric ulcers, and a normal one-in primary gastric ulcers. Normal gastrinemia was noted in ulcers of different sites. The development of secondary gastric ulcers in patients with duodenal ulcers appeared to result from insufficiency of prostaglandin biosynthesis in the gastric mucosa.

A study was made of the dopamine (DA) level in the gastric and duodenal mucosa, blood and urine of 54 patients with duodenal ulcer and 19 healthy persons. An increase in the DA level in the duodenal mucosa, blood and urine during exacerbation of disease was noted. The DA level in the gastric mucosa was normal. Reverse correlation between the DA content in the gastric mucosa and blood, on the one hand, and criteria of acid production, on the other hand, was established. An increase in the activity of chromaffin cells was interpreted as a compensatory reaction ensuring the reduction of catecholamine metabolism, a decrease in gastric secretion, a rise of the rates of reparative regeneration in the duodenal mucosa.

A study was made of the indices of lipid peroxidation (LPO)--conjugated dienes (CD) and diene ketones (D), cyclic nucleotides (CN)--cAMP and cGMP, prostaglandins (PG) E and F2 alpha in biopsy tissue of the liver in 55 patients with chronic hepatitis (CH) and liver cirrhosis (LC). LPO was determined by spectrophotometry, CH and LC--by a radioimmunoassay. In patients with CPH and CAH the indices of LPO and cGMP were normal, cAMP, PG and PGE/PGF2 alpha were raised. In a severe fast progressive liver lesion disorder of coordination activity of the cell membranous systems was characterized by a high LPO activity, a decrease in cAMP and relative deficit of liver PG.

Patients with chronic recurrent pancreatitis were examined for the blood content of insulin, glucagon, somatostatin (SS), somatotropin (STH), cAMP and cGMP. The blood content of insulin, glucagon and STH was normal, that of SS and cAMP elevated, and that of cGMP lowered. In severe pancreatitis, the endocrine part of the pancreas was activated. The relationship was established between the level of amylasemia and the activity of islet cells and the blood content of cGMP. The compensatory importance of hypersecretion of SS and glucagon for pancreatitis exacerbation is demonstrated. The role of cyclic nucleotides in the pancreatic activity is discussed.

The structure of the portal vein was studied in 210 preparations of the liver. The structure of the main trunk of the portal vein and its lobe branches was estimated orienting by the typical shape and the main variations of the structure. Two variants of the structure of the right and left portal veins (after the type of a "pine branch" and the variant of the "minimum length" of the lobe vein) were common for both veins. The structure of the "snail" type was found only in the left portal vein of the "whisk" type -- only in the right one. The sources of the segment blood supply changed depending on the structure of the main trunk and lobe veins. They can be supplied by terminal or lateral branches of the lobe veins, vascular branches of the main trunk of the portal vein and of the vessels of neighbouring segments. Estimation of the angioarchitectonics of the liver operated on should be approached individually in each case. It is expedient to take into account the above typical shape and the main variants of the intrahepatic portion of the portal vein.

Mucous membrane ultrastructure was studied after extracorporeal perfusion of the small intestine under auto- (12 experiments), allo- (10 experiments) and xenotransplantations (4 experiments). In all mucosal structures the lesions are demonstrated to depend on nonspecific factors on the one hand, and on genetically foreigh tissue, on the other hand. In every experimental group, the earliest changes occur in microcirculatory bed. Disorders in vessel and blood flow tone lymphotasis and interstitial edema result in disturbances of capillary-epithelial interrelations and metabolic processes. Destructive changes are followed by tissue neutrophilosis, activation of macrophages and plasmocytic cells, degranulation of eosinophil, enterochromaffin and mast cells, profound mucin excretion. Unlike autoperfusion, alloperfusion is characterized by massive neutrophillic degranulation and more severe lesions of mucosal structures. At allotransplantation, neutrophil cell reaction (nonspecific by its nature) is supposed to be the earliest and primary in the course of establishing transplantation immunity. At xenotransplantation, intestinal destruction, developing and rapidly progressing, is connected with the influence of natural antibodies.

The determination of mean time of transport of an agent in radionuclide phlebography is technically a simple and highly effective method of diagnosis of diseases of the lower limb veins that can be effectively used in all hospitals, fitted out with gamma-cameras with a computerized system.

The authors gave morphometric assessment of the mucous membrane of the stomach (MMS), investigated the proliferative activity of its cells and the levels of cyclic nucleotides (cAMP and cGMP) in 60 patients with different types of chronic gastritis. A parallel study was made of the blood levels of cortisol, thyroxine, insulin, STH, and gastrin. 10 healthy persons were investigated for control. A decrease in MMS thickness, redistribution of the sizable lobes of the glandular epithelium and stroma in favor of the latter were shown in atrophic (but not superficial) gastritis. In patients with atrophic gastritis the proliferative activity of MMS cells was significantly raised, the blood levels of cortisol and gastrin were elevated, the level of thyroxine was lowered, and insulin and STH levels were normal. Marked MMS atrophy was accompanied by cAMP and cGMP insufficiency. The relationships between the morphofunctional status and the proliferative activity of MMS cells, on the one hand, and the activity of the hormonal-cyclase systems, on the other hand, were followed. The mechanisms of pathological regeneration of MMS cell elements was specified, and its importance in the morphogenesis of atrophic gastritis was confirmed.

Lipid peroxidation and the activity of the antioxidant system were studied in the mucous membrane of the stomach of 60 patients with peptic ulcer. Maximum activation of lipid peroxidation was at the ulcer edges and in the surrounding mucosa. In the same regions the following changes were noted: an increase in the activity of superoxide dismutase, depression of activity of glutathione peroxidase and glutathione reductase, a decrease in the amount of reduced glutathione and accumulation of oxidated glutathione. Activation of lipid peroxidation and disruption of activity of the antioxidant system in the mucous membrane of the stomach were considered to be important pathogenetic factors leading to a chronic and recurrent course of peptic ulcer.