In vivo targets of recombinant human tumour necrosis factor-alpha: blood flow, oxygen consumption and growth of isotransplanted rat tumours

The impact of recombinant human tumour necrosis factor-alpha (1 microgram kg-1 to 1 mg kg-1; 6.6 x 10(6) U mg protein-1) on blood flow, oxygen consumption and growth of a moderately TNF-sensitive rat tumour (DS-carcinosarcoma) was studied. Tumour growth was stimulated at low TNF doses (1 and 10 micrograms kg-1) and significantly retarded at higher TNF dose levels (0.1 and 1 mg kg-1). Growth changes were concomitant with variations in oxygen consumption, lactate release and acidification of the metabolic micromilieu. Both single and repeated application of low TNF doses (1-10 micrograms kg-1 i.v.) increased tumour perfusion whereas single administration of high TNF dose levels (0.1-1 mg kg-1 i.v.) reduced tumour blood flow. After repeated application of high TNF doses tumours shrank to such small sizes that perfusion measurements could not be performed within the observation period of two weeks. It is concluded that TNF effects on solid tumours are at least partially mediated by changes in tumour perfusion. Thus, an altered tumour sensitivity towards other treatment modalities, e.g. irradiation, chemotherapy or hyperthermia, can be expected after TNF therapy. A beneficial TNF effect would critically depend on the dose level employed and on the sequence and timing of various combination regimes.     

Physiological properties of malignant tumours.

It is generally accepted that tumour microcirculation, blood flow, oxygen and nutrient supply, tissue pH distribution, and the bioenergetic status--factors which are usually closely linked and which define the so-called metabolic microenvironment--can markedly influence the therapeutic response of malignant tumours to conventional irradiation, chemotherapy, other non-surgical treatment modalities, and the cell proliferation activity within the tumours. Currently available information on the parameters defining the metabolic micromilieu in human tumours is presented in this paper. According to these data, significant variations in these relevant factors are likely to occur between different locations within a tumour, and between tumours of the same grading and clinical staging. Therefore, evaluation of the metabolic microenvironment in individual tumours before therapy and a corresponding 'fine-tuning' of treatment protocols for individual patients may result in an improved tumour response to treatment.     

Tripelennamine interactions with the psychotomimetic sigma agonist N-allylnormetazocine

The pharmacological effects of individual and combined intravenous doses of the antihistamine tripelennamine and the psychotomimetic sigma benzomorphan opioid derivative, N-allylnormetazocine (NANM), on nociceptive reflexes, autonomic parameters and behavior were assessed in the chronic spinal dog. NANM (1.65 mg/kg, IV) produced antinociception, mydriasis, tachycardia, hyperthermia and behavioral signs of canine delirium. Tripelennamine (1.25 mg/kg, IV) produced antinociception, mydriasis and tachycardia without affecting behavior. The combined effects of the two drugs were additive except for heart rate. However, tripelennamine did not antagonize any of the physiological effects or the signs of canine delirium produced by NANM. The findings are inconsistent with the hypothesis that tripelennamine antagonizes the psychotomimetic NANM-like effects of pentazocine to make pentazocine-tripelennamine combinations (T's and Blues) more desirable as a heroin substitute.     

Short-Ti inversion-recovery pulse sequence: analysis and initial experience in cancer imaging

Inversion recovery (IR), commonly considered a pulse sequence capable of producing T1-weighted images with excellent display of normal anatomy, is versatile: The null point and peak time provide a useful, succinct summary of the properties of IR and its capacity for producing both T1- and T2-weighted images. Shortening of the inversion time (TI) and creation of a short-TI inversion-recovery (STIR) pulse sequence increases sensitivity to malignancy and other abnormalities by making the effects of prolonged T1 and T2 on signal intensity additive and by nulling the signal from fat. The authors examined over 300 patients with various malignancies and compared STIR images with T1- and T2-weighted images obtained at 0.5 T. In 43 cases, signal-difference-to-noise ratios (SD/Ns) were calculated between tumor, fat, and muscle. In general, STIR images demonstrated tumor as a conspicuously high-intensity area in a background of muted, discernible anatomic detail. The good contrast achieved with STIR sequences between tumor and fat (SD/N = 18.1) and tumor and muscle (SD/N = 12.9) consolidated into a single image the information contained separately on T1- and T2-weighted images, which facilitates efficient detection and localization of malignancy.     

Solitary rectal ulcer syndrome: findings at barium enema study and defecography

Sixteen cases of histopathologically proved solitary rectal ulcer syndrome were encountered. Fifteen patients underwent barium enema study; in nine cases the findings--including rectal stricture, granularity of the mucosa, and thickened rectal folds-were nonspecific. In six cases the study was normal. All patients had a long history of defecation disorders, and defecography was performed in all. In seven cases, intussusception of the rectal wall was seen; in another case the intussusception was accompanied by a rectocele. One case showed rectal prolapse. In four cases, failed relaxation of the puborectalis occurred and prevented the passage of the bolus; in another case there was abnormal perineal descent. In two patients studies were normal. In patients with defecation disorders, the possibility of this syndrome should be considered. Defecography is the method of choice for establishing the diagnosis.