Validity of pulmonary cine arteriography for the diagnosis of pulmonary embolism.

The aim of this study was to assess the interobserver variations in diagnosis of pulmonary embolism (PE) with cine technique and to compare the diagnostic accuracy of pulmonary arteriograms to final-outcome diagnosis. One hundred and seventy patients with clinical suspicion of acute PE were examined with ECG, laboratory tests, chest X-ray, pulmonary scintigraphy and selective pulmonary cine arteriography. The follow-up time was 6 months. Fifty-one arteriograms were interpreted as positive for PE. Two pulmonary emboli were missed when compared with the diagnosis as stated by the final-outcome committee. No arteriograms were considered as not of diagnostic quality. Mean interobserver agreement in lobar vessels was 100%, in segmental vessels 93% and in subsegmental vessels 63%. The mean interobserver agreement was 89%. Pulmonary cine arteriography produces high diagnostic accuracy and few inconclusive results in patients with suspected PE.

Endothelial cells expressing an inflammatory phenotype are lysed by superantigen-targeted cytotoxic T cells.

The objective of this study was to investigate whether the superantigen staphylococcal enterotoxin A (SEA), which binds to HLA class II and T-cell receptor Vbeta chains, can direct cytotoxic T cells to lyse cytokine-stimulated endothelial cells (EC). In addition, we wanted to determine whether SEA-primed cytotoxic T cells could be targeted to EC surface molecules as a means of a novel cancer immunotherapy. Human umbilical vein EC (HUVEC), dermal microvascular EC (HMVEC), or the EC line EA.hy926 stimulated with gamma interferon (IFN-gamma) or tumor necrosis factor alpha (TNF-alpha) displayed upregulated HLA class II and adhesion molecule (CD54 and CD106) expression, respectively. SEA-primed T cells induced a strong cytotoxicity against IFN-gamma- and TNF-alpha-activated EA.hy926 which had been preincubated with SEA. Blocking of CD54 completely abrogated the T-cell attack. SEA-D227A, which has a mutated class II binding site, did not promote any cytotoxicity. A strong lysis was observed when a fusion protein consisting of protein A and SEA-D227A was added together with T cells to TNF-alpha-induced EA.hy926 and HUVEC precoated with monoclonal antibodies (MAb) directed against HLA class I, CD54, or CD106 molecules. Finally, an scFv antibody fragment reactive with an unknown EC antigen was fused with SEA-D227A. Both EA.hy926 and HMVEC were efficiently lysed by scFv-SEA-D227A-triggered cytotoxic T cells. Taken together, superantigen-activated T-cell-dependent EC killing was induced when EC expressed an inflammatory phenotype. Moreover, specific MAb targeting of the superantigen to surface antigens induced EC lysis. Our data suggest that directed T-cell-mediated lysis of unwanted proliferating EC, such as those in the tumor microvasculature, can be clinically useful.

The urokinase inhibitor p-aminobenzamidine inhibits growth of a human prostate tumor in SCID mice.

Malignant cells possess a high degree of proteolytic activity in which the plasminogen activator system plays an important role. An increased expression of urokinase type plasminogen activator (uPA) is of significance for degradation of the extracellular tumor matrix, facilitating invasiveness and growth. Inhibition of the active site of uPA makes it possible to evaluate the significance of uPA in tumor growth. We report here experiments on a uPA-producing human prostate xenograft (DU 145) using a competitive inhibitor of uPA, p-aminobenzamidine. In vitro experiments with DU 145 cells showed that p-aminobenzamidine caused a dose-dependent inhibition of uPA activity. DU 145 cells were inoculated s.c. in SCID mice and, once tumors were established, treatment with p-aminobenzamidine added to drinking water was started and lasted for 23 days. Mice receiving 250 mg/kg/day of p-aminobenzamidine showed a clear decrease in tumor-growth rate compared to the non-treated mice, resulting in 64% lower final tumor weight. In addition, uPA-antigen levels in the membrane fractions of DU 145 tumors from p-aminobenzamidine-treated mice were found to be decreased by 59%. We also show that p-aminobenzamidine has an anti-proliferative effect in cell culture at low cell number, correlating with a dose-dependent decrease in uPA production. In conclusion, we show that a low-molecular-weight uPA-inhibitor, p-aminobenzamidine, has a growth-inhibitory effect on a solid uPA-producing tumor.

Significance of mechanoreceptors in the subglottal mucosa for subglottal pressure control in singers.

According to Wyke and Kirchner (Wyke B, Kirchner J. Neurology of the larynx. In: Hinchcliffe R, Harrison D, eds. Scientific foundation of otolaryngology. London: William Heinemann Medical Books, 1976:546-66) mechanoreceptors in the subglottal mucosa play a significant role in the control of laryngeal muscle activity in response to changes of subglottal pressure during phonation. In singers this pressure is adapted not only to phonatory loudness but also to fundamental frequency. By spraying Xylocaine solution with a needle inserted into the trachea through the anterior gap between the cricoid and thyroid cartilages, the subglottal mucosa was anesthetized in three singers. The effects on subglottal pressure and fundamental frequency of this anesthesia were examined. The pressure effects varied between the subjects, whereas the fundamental frequency accuracy was adversely affected in all three subjects. The implications of these findings are discussed.

Differential expression of uPA in an aggressive (DU 145) and a nonaggressive (1013L) human prostate cancer xenograft.

Prostate cancer has a slow growing noninvasive phase, but, in general, is invasive on diagnosis. An initial step in the invasion of surrounding normal tissue is the activity of proteolytic enzymes such as components of the plasminogen activator system (PA). In cell culture, the primary human prostate cancer cell line 1013L expressed no urokinase type-PA (uPA), while DU 145, a cell line derived from a metastatic lesion, expressed high levels of uPA. The DU 145 cells grew easily as xenografts but the establishment of 1013L in the SCID mice was possible only with the aid of a gelatin sponge (Spongostan). The latency period was 42-64 days, followed by a slow growth phase before a fast growth phase occurred. This fast growth phase was characterized by rapid degeneration of tumor tissue, while high proliferation occurred around the blood vessels. On serial transplantation of tumor material, the growth pattern was similar. Furthermore, the 1013L tumor was encapsulated by connective tissue and no invasiveness could be detected. We found that 1013L tumor homogenates had hardly detectable levels of uPA, i.e., 300-fold lower than we found in the invasive prostate xenograft DU 145. In addition, no expression of uPA was found in the plasma of 1013L tumor-bearing mice whilst uPA antigen was detected in the plasma of DU 145 tumor-bearing mice. In conclusion, the 1013L cell line, which exhibits a nonaggressive pattern, could be a good model for studying progression of prostate cancer to a more aggressive phenotype in vivo and in vitro.

Estramustine depolymerizes microtubules by binding to tubulin.

To investigate the mechanism of action of the antineoplastic drug estramustine, we compared its effects on human prostate cancer cells with those of vinblastine. At their respective concentrations that result in 50% inhibition of clonogenic growth, both drugs caused an accumulation of cells blocked at mitosis and similar dose- and time-dependent depolymerization of interphase microtubules. Also, colcemid-resistant and colcemid-hypersensitive Chinese hamster ovary cells with tubulin mutations were collaterally cross-resistant or -sensitive to estramustine. Thus, the cytotoxicity of estramustine is due to its microtubule depolymerization properties. This could be caused by interaction with tubulin and/or with microtubule-associated proteins (MAPs). Previous investigations have shown that high concentrations of estramustine phosphate can inhibit microtubule polymerization in vitro by binding to MAPs. However, estramustine phosphate is the clinical prodrug to estramustine, the intracellular active compound. In this study, we investigated the effects of estramustine on the binding of MAPs to taxol-stabilized microtubules in vivo. In contrast to previous reports, no effect of estramustine on the binding of MAPs to microtubules was found. Furthermore, we found that polymerization of purified tubulin could be inhibited by estramustine in vitro. Taken together, these results demonstrate that estramustine causes depolymerization of microtubules by direct interaction with tubulin.

Pulmonary involvement in nephropathia epidemica as demonstrated by computed tomography.

In a prospective study 19 adult patients with nephropathia epidemica were examined in the acute phase of disease with computed tomography (CT) of the lungs and conventional chest radiography. Infiltrates and/or pleural effusions were seen in ten of 19 patients. In two of the patients, abnormalities were disclosed only by CT. Patients with pathologic radiography findings had a more pronounced inflammatory response, as measured by C-reactive protein and leukocyte count, than did those with normal radiography findings. It is concluded that radiological evidence of pulmonary involvement is a common finding early in the course of nephropathia epidemica. The possibility that the lung may be a site of viral replication merits further investigation.

Comparison of iopromide versus iohexol in aortobifemoral arteriography. A Swedish multi-center study of 446 patients.

A double-blind randomized, clinical trial was conducted in 9 hospitals comparing the use of non-ionic contrast media (CM) iopromide 300 (Ultravist) and iohexol 300 (Omnipaque) during peripheral arteriography in a total of 446 patients. After premedication with morphine-scopolamine each patient was given two consecutive injections of 50 ml CM at a rate of 12 ml/s above the aortic bifurcation. Both CM were well tolerated. There were no differences between the two substances as far as general tolerance, pulse rate, blood pressure, sensation of heat or pain after CM injection were concerned.

Contrast media and pain in patients with acute ureteral stone obstruction. A comparative study with iohexol and metrizoate.

A randomized study was conducted in 43 patients who were in pain due to acute ureteral obstruction. Emergency urography was performed in all patients, using either a low osmolar non-ionic (iohexol) or a high osmolar ionic (metrizoate) contrast medium. Increase of pain following injection of contrast media was found in 56 percent of all patients. Increase of pain occurred with both contrast media without any difference between the degree of pain nor the number of patients who experienced an increase of pain. Delayed excretion was considered the only reliable indicator of the degree of obstruction in the present study. Nineteen (68%) of the 28 patients with a delayed excretion greater than 10 min experienced increased pain while the incidence of pain increase was significantly lower (33%) in patients without that sign of ureteral obstruction (p less than 0.05). The increase of pain was not associated with a simultaneous increase of the mean arterial blood pressure.

Nephrotoxicity of contrast media in patients with diabetes mellitus. A comparative urographic and angiographic study with iohexol and metrizoate.

A double-blind urographic and angiographic study was done with the ionic contrast medium meglumine metrizoate and the non-ionic iohexol in 90 patients with diabetes mellitus. Twenty patients were insulin dependent, and 70 non-insulin dependent diabetics. Diabetic patients with decreased as well as normal renal function prior to the examination sustained a reversible and small increase in the plasma creatinine level postexamination. The small increase caused by meglumine metrizoate was significantly higher than the increase caused by iohexol. There was also a significantly higher increase in plasma creatinine among the patients with diabetic nephropathy compared with those without nephropathy.

Identification by C-banding of two human prostate tumour cell lines, 1013L and DU 145.

Two human prostate carcinoma cell lines are easily distinguished by C-banding. DU 145 has one metacentric chromosome with a large centromeric band, 1 metacentric and 2 acrocentric chromosomes with interstitial C-bands. The Y chromosome was present in 48% and 42% of the cells at passages 83 and 106, respectively, whereas in 1013L only one metacentric chromosome contained distinct extra C bands--one at the centromere and one interstitially. The Y chromosome was present in 72% of the cells at passage 15 and in 20% at passage 22, but by passage 44 it had disappeared. Karyotype analysis using G-banding revealed that DU 145 had retained several of its original markers, and demonstrated multiple marker chromosomes in 1013L.

Effects of metrizoate and iohexol on the liver at visceral angiography.

Hepatic angiography was performed in a double-blind two-group study in 60 patients using iohexol 350 mg I/ml and metrizoate 350 mg I/ml. A slight increase in serum values of hepatic enzymes was found when metrizoate was used, particularly in patients with impaired liver function. Iohexol gave considerably less pain and sensation of heat than did metrizoate. A non-expected significant increase of creatine kinase was recorded when iohexol was used. The reason for this is not yet known.

C-banding of two Walker 256 rat carcinoma cell lines sensitive and resistant to bifunctional mustards.

Walker 256 rat carcinosarcoma cell lines sensitive (WS) or resistant (WR) to bifunctional nitrogen mustards have modal chromosome numbers of 60 and 55 respectively. Karyotype analysis revealed that these cell lines have retained the major marker chromosomes present in the original in vivo Walker tumours. One new marker chromosome, a metacentric, was found in the WR cell line. C-banding revealed that in the WS cell line the secondary constriction of the marker chromosome was stained, whereas no staining was found on this chromosome in the WR cell line. Three autosomes containing very prominent non-centromeric C-bands were present in WS but not in the WR cell line which has 2 other chromosomes with minor C-bands. As non-centromeric C-bands do not occur in the normal rat karyotype, these are easily identifiable specific tumour markers for these two cell lines.

Cardio-pulmonary elimination of 5-fluorouracil after bolus injection in the hepatic artery.

Theoretically, administration of 5-fluorouracil (5-FU) into the hepatic artery should improve the clinical response rate by high tumor cell extraction of the drug. However, previous studies in animals and man have also found a major extrahepatic elimination route for 5-FU. In the present study of 7 patients with primary and secondary liver cancer, we have found indications that a considerable elimination of 5-FU takes place in the cardio-pulmonary circuit. Thus, the mean AUC in the hepatic vein was 7185 mumol X min X l-1 and 3792 in a peripheral vein.

Relationships between coronary artery obstruction, asynergy, presence of collaterals and the ejection fraction of the left ventricle in patients with coronary heart disease.

Cardioangiographic scores of coronary artery obstructions and corresponding myocardial involvement (MCOS), presence of collaterals (CollS), and asynergy of the left ventricular wall (LVMS) as well as the left ventricular ejection fraction (EF) were examined in 67 patients with coronary heart disease. A covariation was found between LVMS, EF, ECG changes, and a history indicating a previous myocardial infarction (MI). In a multiple regression analysis the EF covariated with LVMS but not with MCOS and CollS. LVMS indicated a previous MI with at least the same sensitivity and specificity as EF. MCOS and CollS give additional information. Collaterals as well as a high MCOS in relation to the LVMS indicate obstruction of coronary arteries which subserve 'non-fibrotic' myocardium. A patient with a high MCOS and CollS and a low LVMS should be expected to gain most functional improvement from coronary bypass surgery. The scores MCOS, CollS and LVMS are comparatively easy to determine and give a more diversified picture of the state of the myocardium than the EF alone.

Decreased removal of triglycerides from the blood--a mechanism for the hypertriglyceridemia in male patients with coronary artery disease.

We determined serum apolipoprotein A I and A II concentrations and triglyceride and cholesterol concentrations in serum lipoprotein density classes in 28 male patients with severe ischaemic heart disease (IHD) and with angiographically verified coronary artery disease (CAD) and in age-matched controls. Both triglyceride and cholesterol concentrations in very low density lipoproteins and in low density lipoproteins were higher in IHD-patients than in the controls. The triglyceride but not the cholesterol concentration in serum was higher in IHD-patients than in the controls. The cholesterol in high density lipoproteins and the serum apolipoprotein A I concentration were lower in IHD-patients than in the controls. At least in part the higher triglyceride concentration in very low density lipoproteins could be attributed to a decreased removal of triglycerides from the blood since the fractional removal rate of an i.v. injected artificial triglyceride emulsion (Intralipid) was slower in IHD-patients than in the controls.

Proteinuria following nephroangiography. IX. Chemical and morphological analysis in dogs.

Following unilateral selective nephroangiography with diatrizoate, changes in urinary concentrations of prealbumin, albumin, IgG and alpha 2-macroglobulin were analysed in 8 dogs. All reacted with increased proteinuria. The median increase of urinary albumin concentration was 1,300 times (range 27-3 500). The proteinuria was caused mainly by increased glomerular permeability exhibiting some molecular size selectivity in filtration of the proteins measured. Light and electron microscopy did not reveal any glomerular on tubular abnormalities which could be attributed to effects of the angiography. It is suggested that the increased glomerular permeability to proteins might be an effect of disturbance of the electrical hindrance in the glomerular capillary wall.