Relation of fine structure to prognosis for papillary adenocarcinoma of the lung.

Eight cases of papillary adenocarcinoma of the lung were investigated by light and electron microscopy. Prognoses for all but one patient were favorable. Two patients (husband and wife) who underwent tumor resection during the same year experienced no disease-related problems for more than seven years afterward. Microscopic study of the papillary adenocarcinomas revealed columnar, peg-shaped, mucus-secreting tumor cells lining the alveoli. The tumor tissue contained alveolar macrophages, with some multinucleated giant cells, interstitial lymphoid infiltrates, mildly thickened alveolar walls, and a few pneumoconiotic foci. These inflammatory stromal reactions in the tumor tissue might have been associated with the favorable prognoses. Nuclear inclusions were detected in some tumor cells in all cases. Ultrastructurally, the inclusions contained tubular, granular, crystalline, and electron-dense homogeneous structures in addition to unclassifiable nuclear bodies. The tubular structures were in close proximity to inner leaflets of the nuclear membranes. The papillary adenocarcinoma cells had features of totipotential bronchioloalveolar cells, differentiating toward type II pneumocytes, Clara cells, and ciliated epithelial cells.

Identification of asynergic but viable myocardium in patients with chronic coronary artery disease by gated blood pool scintigraphy during isosorbide dinitrate and low-dose dobutamine infusion: comparison with thallium-201 scintigraphy with reinjection.

To evaluate the ability of low-dose dobutamine and isosorbite dinitrate (ISDN) gated blood pool scintigraphy (GBPS) and thallium SPECT with reinjection to identify viability in asynergic myocardium, both procedures were performed in 38 consecutive patients with chronic coronary artery disease and left ventricular dysfunction. Twenty-two of the 38 patients with successful revascularization were analyzed. GBPS was performed at the baseline and during continuous infusion of low dose dobutamine (5 micrograms/kg/min) and ISDN (2 micrograms/kg/min). Cine mode GBPS wall motion was scored from normal (0) to dyskinesis (4) semiquantitatively. Forty-seven of 110 segments with severe asynergy at the baseline were analyzed. Viability determined by GBPS was defined as wall motion score improvement by more than 1 grade. Thallium viability was defined as the segment with redistribution or fill in with severe initial perfusion defect. GBPS was 76.7% sensitive and 70.6% specific for predicting post vascularization wall motion improvement (p < 0.005). Of 47 segments with severe asynergy, concordance of judgement was obtained in 40 segments (85.1%), and reversibility was correctly diagnosed in 34 of 40 patients (85.0%), but thallium with reinjection correctly identified tissue viability in 6 of 7 segments with discordance between 2 studies. These data suggest that most cases of reversible asynergy (hibernating myocardium) respond to ISDN and dobutamine, suggesting the possibility of predicting improvement by revascularization, although some underestimation of tissue viability remained to be resolved. Thallium with reinjection is superior to low-dose dobutamine + ISDN GBPS for the assessment of myocardial viability.

Assessment of area at risk and efficacy of treatment in patients with acute coronary syndrome using 99mTc tetrofosmin imaging in humans.

The determination of the myocardium at risk before intervention and the change in that region after intervention constitute a promising measurement tool for the assessment of acute therapy. A new 99mTc labeled myocardial blood flow tracer, 99mTc tetrofosmin, is expected to enable the evaluation of myocardium at risk because of the absence of redistribution. This preliminary study was performed in 9 patients with acute coronary syndrome (4 unstable angina and 5 acute myocardial infarction) to investigate whether recovery of perfusion by tetrofosmin imaging parallels mechanical improvement. Tetrofosmin imaging was performed acutely and 3-30 days later. Visual analysis of defect severity was assessed in both studies. Segments with improvement in perfusion were accompanied by significant wall motion recovery compared with normal and unimproved segments (delta WMI: normal segments 0.40 +/- 0.67, improved segments 1.79 +/- 0.68, unimproved segments -0.15 +/- 0.16, p < 0.01 for improved segments compared with other groups), suggesting the efficacy of this tracer for the assessment of the acute therapy. These data suggest that 99mTc tetrofosmin imaging is a useful method for the assessment of the myocardial area at risk and the efficacy of acute therapy in acute myocardial infarction and unstable angina.

[The diagnostic value of Tc-99m PYP, Tl-201 dual isotope SPECT to predict the viability of damaged myocardium in the acute phase of myocardial infarction--comparison with stress, delayed, and reinjected Tl-201 SPECT].

To assess the diagnostic value of Tc-99m PYP, Tl-201 dual isotope SPECT for the evaluation of myocardial viability, segmental comparison between dual isotope SPECT and exercise, delayed, and reinjected Tl study were performed with 18 AMI patients. Among 72 damaged myocardial segments, 48 segments (67%) were judged as viable by chronic phase Tl studies. The segments with severely reduced Tl uptake by dual SPECT showed significantly lower prevalence of viable myocardium than the segments with reduced and normal Tl uptake (p less than 0.001). The segments with PYP accumulation localized to the subendocardium represented the favorable outcome compared with the transmural accumulation (p less than 0.001). And overlap segments show better prognosis than the segments without overlap (p less than 0.05). Most importantly, we can get better predictive accuracy of myocardial scar by dual isotope SPECT than the judgement by Tl or PYP SPECT alone (83.3% vs 77.8%, 68.1%). Thus, we conclude that Tc-99m PYP, Tl-201 dual isotope SPECT is useful to assess the severity of myocardial damage in the acute phase of myocardial infarction.

[The prevalence and the clinical characteristics of silent myocardial ischemia detected by stress thallium scintigraphy].

The prevalence of silent myocardial ischemia was retrospectively assessed in a group of 100 consecutive patients with angiographically proved coronary artery disease, and diagnostic ECG, by symptom-limited exercise thallium-201 scintigraphy. Twenty-four patients had no evidence of ischemia despite adequate exercise level. So among 76 patients with exercise induced ischemia, only 33 patients (43%) stopped exercise due to anginal pain (symptomatic ischemia: Group 3). And 43 patients with asymptomatic ischemia composed of 23 patients (30%) with ECG change (Group 2B) and 20 patients (26%) without ECG change (Group 2A). Patients background including the history of old myocardial infarction and diabetes mellitus, were similar among Group 2A, 2B, and Group 3. And our major observation was that the extent and severity of quantified SPECT perfusion defects was nearly identical between 3 groups Thus in this study group, there was a rather high prevalence rate of silent ischemia (57%) by exercise thallium-201 criteria. Patients with silent ischemia, associated with positive and negative exercise ECG findings, and those with exercise angina had similar background and comparable amount of jeopardized myocardium.

[The value and limitation of resting 201Tl reinjection after stress-redistribution imaging for the assessment of myocardial viability: comparison with wall motion improvement by revascularization].

Clinical value and limitation of resting reinjection of small dose of thallium (37 MBq) for the assessment of myocardial viability were evaluated. The results were compared with the degree of wall motion improvement by revascularization to infarcted myocardium supplied by chronic total vessels in 12 patients with old myocardial infarction. Thallium uptake was visually scored and judged as normal, reversible defect (Group 1), new fill in after reinjection (Group 2A), and no fill in even after reinjection (Group 2B). Among 53 segments with initial perfusion abnormality, 21 segments reverted to almost normal, while 32 segments remained abnormal on redistribution images. New fill in after reinjection was observed in 11 segments of 32 segments showing persisting defect on stress and delayed image (37%). Wall motion score index of Group 2A improved significantly higher than Group 2B (p less than 0.01) and almost equal to Group 1, suggesting the utility of reinjection for the assessment of tissue viability which may be underestimated by conventional imaging. But significant wall motion improvement (greater than or equal to 0.6 mean SD/chords) was observed in 6 segments (29%) of 21 segments showing neither redistribution nor fill in after reinjection. These data indicate that small dose of thallium reinjection may enhance detection of viable but jeopardized myocardium, although some underestimation of viability remained to be resolved.

[Perfusion imaging with 99mTc PPN-1011 for the assessment of myocardial area at risk and the efficacy of PTCA/PTCR in myocardial infarction and unstable angina].

The determination of the myocardium at risk before intervention and the change in that region after intervention constitute a promising measurement tool for the assessment of acute therapy. We used 99mTc PPN-1011 in 4 patients with acute myocardial ischemia (2 patients with acute myocardial infarction, 2 unstable angina) and subsequent successful reperfusion. All 4 patients had perfusion defect on the pre-reperfusion image. Perfusion abnormality on post-reperfusion image was all improved significantly compared with pre-reperfusion image, suggesting the efficacy of acute treatment in acute myocardial ischemia. We conclude that 99mTc PPN-1011 scintigraphy is useful method for the assessment of myocardial area at risk and the efficacy of PTCA/PTCR in myocardial infarction and unstable angina.

[Effects of manidipine hydrochloride on renal function in renal parenchymal hypertensive patients].

The incidence of renal parenchymal hypertension is highest in patients with secondary hypertension. It is important to prevent the progression of renal dysfunction by appropriate treatment, especially by means of antihypertensive drugs. Calcium channel blockers are considered to have the advantage as antihypertensive drugs of maintaining the renal blood flow, even though the perfusion pressure may be decreased. However, these drugs can involve the risk of deteriorating the glomerular function due to hyperfiltration. To investigate whether calcium channel blockers can prevent the deterioration of renal function in renal parenchymal hypertensive patients, we administered manidipine hydrochloride (20 mg, once a day, 24 weeks) to 16 outpatients and evaluated its effects on blood pressure and renal function. The following results were obtained. (1) The systolic and diastolic pressure decreased from 2 and 4 weeks after administration, respectively. A stable antihypertensive effect appeared thereafter and no change was observed in the pulse rate. (2) The renal vascular resistance tended to decrease slightly. The glomerular filtration rate and renal blood flow did not change in spite of the decreased perfusion pressure. (3) No changes were seen in urinary protein, endocrine factors and cardiac function. (4) In some of the cases with decreased GFR (< 70ml/min), the drug could not prevent deterioration of the renal function and did not produce an antihypertensive effect.

[Lp(a) lipoprotein in patients on maintenance hemodialysis--a study from apo(a) isoform].

It has been suggested that lipid abnormalities may be involved in the development of cardiovascular disorders in patients on maintenance hemodialysis (HD). Hypertriglyceridemia commonly accompanies this condition and is associated with decreased concentrations of HDL-cholesterol. Recent clinical interest has been paid to the disturbances of Lp(a) and apo (a) isoform in relation to cardiovascular disorders. Although high concentrations of Lp(a) are associated with ischemic heart disease, we are unaware of the availability of such data concerning patients on maintenance hemodialysis. We therefore compared levels of Lp(a) and the frequency of occurrence of their isoforms in 310 patients (chronic glomerulonephritis, N = 221; diabetic nephropathy, N = 77; polycystic kidney disease, N = 12) on maintenance hemodialysis and in 212 normal subjects. The following results were obtained. (1) HD patients showed significantly elevated levels of Lp(a) compared to normal subjects. (2) Studies of apo (a) isoform showed that HD patients showed high frequency of S2 and low frequency of S4. (3) HD patients, especially long-term patients, showed high frequency of double band (S2/S3). (4) There were no significant differences in the levels of Lp(a) and in the frequency of apo(a) isoform among 3 different etiological studies.

[Clinical value of PMN elastase activity before reperfusion therapy in acute myocardial infarction: comparison with clinical characteristics, reperfusion events and myocardial damage].

Many recent studies demonstrate that neutrophils may be involved in the genesis and propagation of myocardial ischemia and reperfusion injury. Clinical value of PMN elastase activity before reperfusion which is released from activated polymorphonuclear leucocyte were evaluated in 30 patients with acute myocardial infarction. 19 patients with normal or moderately elevated PMN elastase activity (G1: less than 200 micrograms/l) revealed similar clinical characteristics before reperfusion therapy, compared to 11 patients with extremely high PMN elastase activity (Group 1: greater than or equal to 200 micrograms/l). But Group 1 represented fewer incidence of reperfusion events (Group 1 2/19, Group 2 7/11, p less than 0.01) such as arrhythmia, BP down, re-elevation of ST segments, and increased chest pain just after reperfusion, and higher incidence of salvaged myocardium in the risk area (Group 1 5/11, Group 2 4/19 p less than 0.1) evaluated by Tc-99m PYP, T1-201 dual SPECT, than Group 2. Wall motion analysis also showed that both global and regional wall motion were severely depressed in Group 2 compared with Group 1 (Group 1: Global EF 66.6 +/- 13.5, Extent 26.5 +/- 17.4, Severity 63.1 +/- 48.5, Group 2: Global EF 51.2 +/- 10.6, Extent 40.1 +/- 16.3, Severity 112.8 +/- 55.5, p less than 0.01 for Global EF, Extent, and p less than 0.05 for Severity). These data suggest that leucocyte activation before reperfusion may play important role in the genesis of reperfusion injury.

Ultrastructural comparison of hepatoblastoma and hepatocellular carcinoma.

The ultrastructural characteristics of fetal liver, two hepatoblastomas and two hepatocellular carcinomas were compared. Tumor cells of hepatoblastoma disclosed monotonous nuclei, poorly-developed cytoplasmic membrane system, abundant free ribosomes and prominent glycogen granules. Thos of hepatocellular carcinoma revealed comparatively pleomorphic nuclei, well-developed cytoplasmic membrane system, a few free ribosomes and numerous glycogen granules. Fetal liver showed monotonous nuclei, well-developed RER abundant free ribosomes and prominent glycogen granules. Young mesenchymal cells with well-developed RER and continuous basal lamina surrounding the epithelial cells were detected in both cases of hepatoblastoma but not in those of hepatocellular carcinoma. Tumor cells of hepatoblastoma in a case showed intramitochondrial crystalloids and thick bundles of fibrils in the cytoplasm.

Morphogenesis of pancreatoblastoma, infantile carcinoma of the pancreas: report of two cases.

Two cases of infantile carcinoma of the pancreas were diagnosed as pancreatoblastoma based on the morphogenesis of the tumors. These encapsulated tumors adhered to the head of the pancreas and to the descending portion of the duodenum. Histologic examination revealed an organoid structure made up of cords or nodules of squamoid cells with elongated nuclei arranged in a parallel fasciculating pattern (squamoid corpuscles), surrounding tubular structures of columnar epithelial cells and intermediate light cell masses with little differentiation. Electron microscopy revealed zymogen-like granules and well developed granular endoplasmic reticulum in the cytoplasm. There were no detectable islet cells in tumor tissue. Both of these tumors could be derived from the ventral pancreas and be isolated by the lack of communication with the duct of Wirsung. As the duct of Santorini was patent, extirpation of these organoid tumors would not influence secretion of pancreatic juice. Considering the favorable prognosis after extirpation of these tumors, they should be differentiated from the usual adenocarcinoma of the pancreas occurring in adults.

Effects of Ca++-antagonists on systemic capacitance vessels and venous return curves of dogs--a study with mean circulatory pressure.

We measured mean circulatory pressure (MCP) in anesthetized, open-chest dogs before and after intravenous administration of Ca++-antagonists to estimate the effects on systemic capacitance vessels and on venous return (VR) curves both with and without continuous intravenous infusion of norepinephrine (NE). Diltiazem (300 micrograms/kg) decreased total peripheral resistance (TPR) and MCP significantly. Nifedipine (5 micrograms/kg), nicardipine (30 micrograms/kg) and verapamil (200 micrograms/kg) decreased TPR significantly without any change in MCP in the absence of NE, but with the exception of verapamil, they decreased MCP in the presence of NE. This indicates that diltiazem relaxed the systemic capacitance vessels, and nifedipine and nicardipine significantly decreased the tone of the systemic capacitance vessels that had been previously elevated by NE, but this action was very slight with verapamil. These Ca++-antagonists rotated VR curves clockwise, decreased resistance to VR (RVR) and increased VR both in the presence and absence of NE. It was suggested that the decrease in the RVR would be at least partially responsible for the increase in the VR.

Coronary angioplasty using an over-the-wire balloon catheter through a new 6 French guiding catheter.

A new 6 French (F) guiding catheter with a large, teflon-coated internal lumen (4.2F) was developed, permitting use of the standard ultralow profile (less than 3F) over-the-wire system. This small coronary angioplasty system (6F-PTCA) was evaluated in 48 lesions in 45 of 137 patients (33%) who underwent coronary angioplasty between September 1990 and January 1991. The mean age was 64 years (range 49 to 82); 37 (82%) were male. The procedure was via the brachial artery in 28 patients (62%). The overall primary success rate was 96%. It was 100% via the brachial artery and 90% via the femoral artery. There were no major complications. The puncture compression time with the 6F-PTCA via the brachial artery and via the femoral and with 8F-PTCA via the femoral was 3.8, 9.6, and 16.9 hr, respectively (P less than 0.001), although the procedure time of the 6F-PTCA via brachial and via femoral and of the 8F-PTCA was not significantly different. The mean hospital stay was 3.1, 4.5, and 5.5 days, respectively (P less than 0.01). A small hematoma occurred in 2 patients (4.4%) after the 6F-PTCA and in 3 (3.3%) after 8F-PTCA, and a large hematoma (greater than 5 cm) was noted in 7 patients (7.6%) after 8F-PTCA. These results indicate that coronary angioplasty using the over-the-wire system through the new 6F guiding catheter is technically feasible. Moreover, this approach, especially when advanced via the brachial artery, could shorten the hemostasis time and facilitate early ambulation.