Thermodynamic method of B/A analysis of liposome suspensions: prediction via single relaxation theory.

The enhanced ultrasonic nonlinear B/A measurements (via thermodynamic method) from liposome systems first reported by Zhang and coworkers are analyzed through relaxation theory. The enhanced ultrasonic absorption and sound velocity dispersion due to lipid structural relaxation are theoretically shown to accurately predict the enhanced B/A findings reported by Zhang and coworkers.


The effect of body heating and cooling on the ankle and toe systolic pressures in arterial disease.

Although changes in body temperature alter limb blood flow, little information exists on the effect of body heating and cooling on systolic pressures in limbs with arterial disease. Ten patients with stable claudication were studied. Mean ankle systolic pressure index during body cooling (0.79 +/- 0.04) exceeded (p less than 0.01) both the value during routine test (0.69 +/- 0.03) and during heating (0.65 +/- 0.04). The individual, paired difference in ankle systolic pressure index between cooling and heating exceeded 0.15 in seven limbs and between cooling and routine test in five. Mean toe systolic pressure index during heating, but not during cooling, was lower than during routine test (p less than 0.01). There was no significant difference in the mean toe systolic pressure index between heating and cooling. However, compared with heating, toe systolic pressure index increased with cooling in 12 limbs and decreased in eight, including three with loss of measurable pressure. The paired difference in toe systolic pressure index between cooling and heating exceeded 0.15 in 10 limbs and between cooling and routine test in eight; whereas between heating and routine test the paired difference was within 0.15 in all but three limbs. The results indicate that changes in body temperature have significant effects on distal pressures in arterial disease. Preliminary warming in routine tests should improve reproducibility.


Photoplethysmography: a valuable noninvasive tool in the assessment of venous dysfunction?

We have investigated the photoplethysmography findings in 152 patients admitted to the Middlesex Hospital Vascular Laboratory with suspected lower limb venous disease, and we compared the results obtained with patient grouping using clinical criteria and the presence of reflux on color duplex scanning. All photoplethysmography traces were normalized with use of computer software to enable direct comparison between the traces. The parameters investigated were the 95% and 50% refilling times and the initial gradient of the refilling curve. Receiver operating characteristic curves were constructed to determine which parameter was the most useful predictor of disease and to identify which value within each observation gave the greatest sensitivity and specificity. We found a large overlap between interquartile values for all three parameters, with limbs grouped both clinically and by duplex scanning, making differentiation between normal and abnormal limbs difficult on the basis of photoplethysmography traces alone. We found that a 95% refilling time of less than 15 seconds indicated venous dysfunction with the greatest sensitivity and specificity and suggest that this value is most useful. Photoplethysmography readings are reproducible, noninvasive, and correlate well with the presence of clinical disease, and photoplethysmography remains useful in the assessment of venous dysfunction.


Silent myocardial ischemia monitoring predicts late as well as perioperative cardiac events in patients undergoing vascular surgery.

In a previous study we have shown that perioperative monitoring for silent myocardial ischemia can noninvasively identify those patients undergoing peripheral vascular surgery who are at significantly increased risk for perioperative myocardial infarction. In the present study a group of 385 patients undergoing peripheral vascular surgery was studied long-term as well as short-term to determine whether perioperative monitoring for silent ischemia can identify those patients who are at significantly increased risk of late cardiac death or late cardiac complications as well as those patients at increased risk of perioperative myocardial infarction. All patients were monitored before, during, and after operation and were divided into two groups on the basis of results of monitoring: patients whose total duration of silent ischemia as a percentage of the total duration of perioperative monitoring was 1% or greater (group I, n = 120) and those for whom this value was less than 1% (group II, n = 265). Among patients in group I 13.3% (16 of 120) suffered a perioperative myocardial infarction in contrast to only 1.1% (3 of 265) patients in group II (p less than 0.001). Multivariate logistic regression analysis of preoperative and perioperative characteristics showed that the presence of a total perioperative percent time ischemic 1% or greater and age were the only significant predictors of perioperative myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)


Elastin content, cross-links, and mRNA in normal and aneurysmal human aorta.

Although elastin depletion is thought to be an etiologic factor in abdominal aortic aneurysm, little is known about its transcription and posttranslational modification in normal and diseased human aorta. Our objectives were to quantify total elastin and elastin cross-links (desmosine/isodesmosine [DID]) and to determine if elastin mRNA was detectable in the disease-prone infrarenal aorta from patients with abdominal aortic aneurysm and a comparative group with no aneurysmal diseases. After preliminary extraction and thermolysin digestion, content of DID and the elastin tetrapeptide, valine-alanine-proline-glycine (VAPG), were determined by high-performance liquid chromatography. Tissue mRNA was studied by Northern blot analysis. Mean values (+/- SE) were compared by Student's t test. The proportion of insoluble elastin was markedly decreased in abdominal aortic aneurysm tissue (1.3% +/- 0.04% vs 12% +/- -2.8%; p less than 0.001). There was no difference in the small percentage of elastin solubilized during extraction in abdominal aortic aneurysm (5.3% +/- 1%) and no aneurysmal disease (6.0% +/- 1.2%; p = 0.71) tissues. The DID concentration of insoluble elastin was not different for abdominal aortic aneurysm and no aneurysmal disease tissue (0.18% +/- 0.07 vs 0.18 +/- 0.05 nm DID/nm VAPG; p = 0.97). On the basis of VAPG content, only 26% +/- 4% of the sodium hydroxide insoluble residue from abdominal aortic aneurysm was elastin; the predominate protein(s) was high in polar amino acids. Elastin mRNA was detectable in all tissues.(ABSTRACT TRUNCATED AT 250 WORDS)


Epidemiology of carotid endarterectomies among Medicare beneficiaries.

Extensive debates exist in the literature on the indications, effectiveness, and risks of carotid endarterectomy. However, no investigations analyze the procedure's epidemiology. Medicare paid for essentially all carotid endarterectomies on patients over 65 years old, more than two thirds of all such surgery. Accordingly, we identified all 1985 to 1989 Medicare bills for ICD-9-CM code 38.12. This report found an average annual decrease of 6.4% in the frequency of carotid endarterectomies. Higher proportions and incidence rates occurred among 65- to 79-year-old people, men, and whites. Larger, urban, and nonprofit hospitals performed the procedure more often. The number of hospitals performing this procedure has increased over time. Mortality rates within 30 days decreased from 3.0% of procedures in 1985 to 2.5% in 1989. Higher than average death rates occurred among older, male, and black patients, and in low volume hospitals. Clinical trials undertaken in large, urban, teaching, high-volume institutions reported only 1% deaths. The institutions actually performing carotid endarterectomies differ from the clinical trials in their demography and perioperative mortality rates. This difference in community practice may limit the applicability of the clinical trials.


Long-term results of infrainguinal revascularization with polytetrafluoroethylene: a ten-year experience.

Two hundred fifty-eight patients underwent 322 infrainguinal revascularizations with use of polytetrafluoroethylene (PTFE) between 1978 and 1988. The indication was limb salvage in 190 (59%) reconstructions. Two hundred nineteen (68%) were above-knee, and 75 (23%) were below-knee femoropopliteal bypasses. Twenty-eight (8.6%) were femoral-infrapopliteal bypasses, all done for limb salvage. Follow-up ranged from 24 to 144 months (mean, 66 months). The perioperative mortality rate (1 to 30 days) was 3.4% (9 patients), with no significant difference according to indication (2.9% vs 3.7%). Actuarial primary patency at 8 years for the entire series of femoropopliteal bypasses was 53% (above knee 53%; below knee 39%; p less than 0.05), and improved with additional procedures for a secondary patency of 72%. Femoropopliteal bypasses done for severe claudication had an 8-year actuarial primary patency of 63%, compared with 38% for limb salvage (p less than 0.02). Actuarial limb salvage in the latter group at 8 years was 66%. Femoral-infrapopliteal reconstructions with PTFE had a significantly lower primary patency at 3 years (22%, with a 37% limb salvage). Sixty-four percent of the failures for all reconstructions (N = 111) occurred within 12 months, with remarkable stabilization of patency curves beyond that interval. This experience represents the largest reported series of PTFE reconstruction with longest follow-up to date and may serve as a basis for comparison of other conduits. These results suggest an important role for PTFE in femoropopliteal revascularization and a limited role of this prosthetic conduit in femoral-infrapopliteal arterial reconstructions.


A comparative analysis of transcutaneous oximetry (tcPO2) during oxygen inhalation and leg dependency in severe peripheral arterial occlusive disease.

Transcutaneous oximetry (tcPO2) performed during either oxygen inhalation or leg dependency was intra-individually compared in 64 patients suffering from a peripheral arterial occlusive disease, with and without critical limb ischemia. Among the 81 extremities investigated, 29 had a moderate peripheral arterial occlusive disease (6 in stage I, 23 in stage II) and 52 were initially affected by rest pain or ulceration (stage III/IV). Thirty-seven legs out of the latter improved under conservative treatment. In the remaining 15 limbs, vascular surgery or an amputation became necessary. The tcPO2 was measured at the forefoot with the patient in supine and sitting positions while breathing room air and in the supine position while inhaling 100% oxygen. In limbs with a tcPO2 below 15 mm Hg of patients in the supine position breathing room air, leg dependency generally provoked larger tcPO2 increases than oxygen inhalation. This difference between oxygen inhalation while supine and room air breathing leg dependency tcPO2 values exhibited an approximately linear correlation with the resting tcPO2. Responses of tcPO2 to leg dependency and oxygen inhalation seemed to reflect different mechanisms, that is, microvascular flow redistribution and supine perfusion reserve, respectively. The best discrimination of critical limb ischemia was observed for the tcPO2 of patients breathing room air while in the supine position, which was not surpassed by either the oxygen inhalation or the leg dependency test. Satisfactory results were achieved by combining limits for, first, supine (10 mm Hg) and sitting (45 mm Hg) tcPO2, as well as, second, ankle arterial pressure (60 mm Hg) and supine tcPO2 (10 mm Hg).


Prevention of smooth muscle cell phenotypic modulation in vein grafts: a histomorphometric study.

This is a prospective study of the relationship between graft preparation technique and the subsequent morphologic fate of vein grafts. Paired vein grafts (optimal vs injury prepared) were placed in a canine model and removed over time. Vein grafts intentionally injured by warm saline storage demonstrated endothelial and smooth muscle cell damage. In the acute postimplantation period, platelet adhesion and white cell infiltration of the graft were present. By 7 days, the endothelium had "healed", but the underlying smooth muscle cells had modulated and were of the transitional or synthetic phenotype. This persisted at 30 days, but by 60 days the graft wall had remodeled to a contractile smooth muscle cell phenotype. Changes in the extracellular matrix were greatest at 30 days corresponding to changes in the smooth muscle cell phenotype. None of these injurious responses were noted in optimally prepared, papaverine treated vein grafts. The combined intima and media (lumen to adventitial edge) was measured at baseline and at graft excision with use of digitized graphic techniques. The intimal/medial thickness of injured vein graft walls was always greater than that of pair-matched optimally treated vein grafts (p less than 0.01 analysis of variance). Optimal preparation of vein grafts is effective in minimizing endothelial and smooth muscle cell injury at the time of arterial reconstruction. This preservation of endothelial and smooth muscle cell integrity prevents subsequent morphologic changes associated with the "arterialization response".


Effect of prostaglandin I2 analogue TRK-100 on the suppression of intimal fibrous proliferation.

This study investigated the effect of prostaglandin I2 analogue (TRK-100) on the healing of arterial anastomoses. The infrarenal abdominal aorta was divided and reanastomosed immediately in rabbits. A control group of rabbits were fed commercial rabbit food (ORC 4); a cholesterol group of rabbits were fed a diet with 1% cholesterol added to ORC 4; and a TRK group of rabbits received the same diet as the cholesterol group, but TRK-100 was given subcutaneously at a dose of 0.3 mg (TRK-I group) or 1.0 mg (TRK-II group) every other day. After 3 months a blood sample was taken for biochemical analysis, and the abdominal aorta was harvested for histologic examination. The serum lipid and thromboxane B2 concentrations and the thromboxane B2/6-keto prostaglandin F1 alpha ratio in the TRK groups were significantly lower than in the cholesterol group. The proliferative connective tissue did not cover the anastomotic suture line in either the control or the TRK groups. However, the suture line was covered completely by connective tissue in the cholesterol group. Intimal thickness in the cholesterol group was greater than in either the control or the TRK-II group (p less than 0.01 and p less than 0.05, respectively). These data suggest that TRK-100 may suppress intimal fibrous proliferation at anastomotic suture lines by a mechanism affecting the thromboxane B2/6-keto prostaglandin F1 alpha ratio.


Intraoperative arteriography and carotid surgery.

To minimize morbidity in carotid surgery we have adopted the practice of routine operative arteriography. In our total experience of 692 carotid artery reconstructions done since 1979 no arteriography was used for the first 157 procedures. The combined morbidity and mortality rate in this group was 4.5% (4 strokes and 3 deaths as a result of stroke). After 157 carotid operations we used intraoperative arteriography on all cases, and the neurologic morbidity and mortality rate for this part of the series was 1.3% (6 strokes and 1 fatal cerebral hemorrhage). One death was due to myocardial infarction. The difference in ischemic neurologic sequellae between these two groups was statistically significant by chi-square analysis (p less than 0.01). Although the difference in these two cohorts could be related to the "learning curve" effect, it is unlikely that this is the only reason for the difference. Intraoperative arteriography has demonstrated unsuspected stenoses, occlusions, flaps, and kinks. There was also a statistically significant difference (p less than 0.01) in the number of reoperations for recurrent stenosis: 3.8% in the first group and 0.8% in the second group. No complications were thought to be directly associated with the arteriogram. Since the development of better digital imaging systems for the operating suite, this technique is much more easily used than when it was first described.


The ischemic window: a method for the objective quantitation of the training effect in exercise therapy for intermittent claudication.

Twenty-two patients with intermittent claudication were prospectively enrolled in a 12-week program of supervised, graded treadmill exercise therapy. Severity and distribution of arterial occlusive disease were ascertained by noninvasive determination of segmental lower extremity blood pressures and waveforms. No attempt was made to modify risk factors for atherosclerotic occlusive disease. The exercise-induced reduction of the ankle pressure and its recovery were recorded over time, and the area under this curve, the "ischemic window," represents the severity of the ischemic deficit. Absolute systolic ankle pressure, ankle-brachial index, maximum walking time, claudication pain time, and the ischemic window were measured before and after exercise training in all subjects. Maximum walking time and claudication pain time increased 659% and 846%, respectively, among the 19 patients completing the 12-week program (p = 0.001; p = 0.0002). These patients underwent a mean reduction of 58.7% in the ischemic window after a standardized workload (p less than 0.05), and this correlated with the degree of symptomatic improvement. Absolute ankle pressure and ankle-brachial index were unchanged after exercise training. This study confirms the utility of supervised exercise therapy in the treatment of intermittent claudication. The ischemic window is a useful method for quantifying the ischemic deficit produced by exercise and provides a reproducible means of documenting functional improvement in patients undergoing exercise training.


A prospective randomized evaluator-blinded trial of two potential wound healing agents for the treatment of venous stasis ulcers.

Chronic wounds such as venous stasis ulcers have become a socioeconomic problem. Even with successful initial management, the recurrence rate approaches 70%. With the advent of new wound healing agents, nonoperative attempts to heal these wounds appear indicated. This study reports a prospective randomized evaluator-blinded trial comparing two potential wound healing agents to an inert vehicle placebo. Eighty-six evaluable patients completed the trial. Silver sulfadiazine 1% in a cream proved to statistically reduce the ulcer size compared with a biologically active tripeptide copper complex 0.4% cream formulation or the placebo. There was no difference between the latter two treatments. Silver sulfadiazine has been shown to allow keratinocyte replication and to have antiinflammatory properties. In this trial its antibacterial action was not used since all ulcers had comparable bacterial levels (less than or equal to 10(5)/gm of tissue) before treatment. These results suggest that the silver sulfadiazine cream used in this study may facilitate healing in wounds healing largely by the process of epithelialization.


Transjugular intrahepatic portosystemic shunts: preliminary results in 25 patients.

A retrospective study of transjugular intrahepatic shunts performed between June 1990 and June 1991 is reported. Twelve patients were actively bleeding at the time of the procedure; 12 other patients had had one to five bleeding episodes within the previous 2 weeks, and one patient had massive ascites from Budd-Chiari syndrome. Most patients had severe liver disease: 21 Child's class C, three Child's class B, and one Child's class A. Transjugular intrahepatic shunting was technically successful in all cases. Portal vein pressures were reduced on average from 36 +/- 7 cm H2O to 22 +/- 6 cm H2O. Variceal bleeding ceased after transjugular intrahepatic shunting in all patients who were actively bleeding. Five patients died (30-day mortality, 20%), and eight patients subsequently underwent elective liver transplantation. The transjugular intrahepatic shunts in the 12 other patients have remained patent an average of 5.5 months. Shunt occlusion occurred in three patients at 21, 24, and 102 days, respectively. All three occlusions were successfully reopened with percutaneous techniques, yielding a primary shunt patency of 88% and secondary shunt patency of 100%. Complications included new onset encephalopathy in one patient, which cleared with medical therapy and transient renal failure in one patient. These preliminary data suggest that transjugular intrahepatic shunting is a safe and effective therapy for the short-term treatment of patients with variceal hemorrhage, particularly in patients with severe liver disease awaiting transplantation. The long-term benefit of transjugular intrahepatic shunting awaits further follow-up.


Acute aortic occlusion as a result of extrinsic compression from peritoneal encapsulation.

Acute aortic occlusion frequently occurs with catastrophic visceral, spinal, or lower extremity ischemia and is most often caused by embolic or thrombotic events in older individuals with known cardiovascular disorders. This case describes the rapid development of the clinical signs of acute aortic occlusion in a young and completely healthy individual. Aortic occlusion was produced by extrinsic compression of the juxtarenal aorta from a closed-loop small intestinal obstruction contained within a peritoneal encapsulation, an extremely rare intraabdominal developmental anomaly.


Perforation of a vein valve leaflet: a mechanism for incomplete valve incision during in situ bypass.

The modified Mills retrograde valvulotome has been our preferred instrument for valve incision for in situ saphenous vein bypass. In one case during completion angioscopy the valvulotome was identified to have perforated a posterior valve leaflet and left the leaflet intact. This intact leaflet was identified and incised under direct vision. Valve leaflet perforation by the valvulotome tip is proposed as one possible mechanism for incomplete valve lysis.


Septic emboli from a radial artery catheter with local manifestations of subacute bacterial endocarditis.

Septic emboli, giving rise to physical signs similar to those of subacute bacterial endocarditis, are extremely rare complications of radial artery catheterization. A case is reported with splinter hemorrhages and Janeway lesions, resulting from an infected radial artery catheter. Five other cases with these signs are collected from among 21 patients with localized septic complications described in the literature. The duration of radial artery catheterization was 4 days or longer in all cases, and Staphylococcus aureus was the offending agent in all. We conclude that arterial lines should be removed as early as possible, and in any case they should be pulled out at the earliest sign of a local complication. In the presence of signs of local infection, antistaphylococcal treatment should be given until results of cultures are available.


Clinical significance of late potentials in patients after intracardiac operation for congenital heart disease.

The aim of this study was to evaluate the late potentials (LPs) in postoperative patients with congenital heart disease (CHD) and to study the association with the clinical characteristics in the postoperative patients with LPs. Signal averaged electrocardiogram (SA-ECG) was recorded in 119 postoperative patients aged 4 to 23 years and compared with those in age matched 49 healthy volunteers with and without right bundle branch block. Based on control data, criterias of LP were defined and altered in the presence of bundle branch block. Abnormal SA-ECGs were not detected in the patients with non-cyanotic CHD. However, abnormal and borderline SA-ECGs were recognized in 5 (12%) of 42 patients after intracardiac operation for tetralogy of Fallot and 3 (30%) of 9 patients after Rastelli's operation. The patients with abnormal and borderline SA-ECGs were significantly older at the time of operation, and had more frequent ventricular arrhythmias (7/8: 3/111, p less than 0.01) and depression of the ST-T segment on ECG (7/8: 11/111, p less than 0.01), compared with the normal SA-ECG group. Abnormal SA-ECGs including those of borderline patients were 50% sensitive and 96% specific for documented ventricular arrhythmias. However, there was no association between abnormalities of SA-ECGs and cardiomegaly on chest X-ray or left ventricular ejection fraction on echocardiogram. These results indicate that prolonged exposure to hypoxia may be the main cause of the primary role in the development of LPs. And late surgical intervention may result in histological background for the development of LPs.


Sequential appearance of fibronectin, collagen and elastin during fatty streak initiation and maturation in hypercholesterolemic fat-fed rabbits.

To elucidate whether tissue fibronectin increases in the early stages of atherogenesis induced by hypercholesterolemia without mechanical trauma, we investigated sequential changes in the distribution of tissue fibronectin during fatty streak initiation and maturation in the aortas of hypercholesterolemic fat-fed rabbits. The presence of fibronectin was examined on immunoperoxidase stained tissue specimens with the aid of a microscope-photometric technique. Twenty male albino rabbits were used. Cholesterol supplemented chow (1%) was given for 4 weeks (n = 6), 8 (n = 5) or 14 weeks (n = 5). A membrane-like layer positive for fibronectin was observed along the endothelium in the normal aorta. After 4 weeks of the cholesterol-feeding, fatty streaks were initiated in the intima, where fibronectin was more densely accumulated than the normal intima. After 8 weeks of the cholesterol-feeding, fatty streaks were expanding, associated with the dense staining for fibronectin. After 14 weeks, fibronectin was still concentrated in the endothelial layer and also in the superficial areas of the thickened intima, but decreased in the deep areas of the thickened intima where collagen and elastin appeared as bundles. The photometric data of fibronectin supported these visual observations. Thus, fibronectin appeared early and disappeared later in the intima during the process of fatty streak initiation and maturation. These findings suggest that in hypercholesterolemia without mechanical endothelial injury, fibronectin may play an important role in an early process of atherogenesis.


Augmented contractile response to endothelin and blunted endothelium-dependent relaxation in post-ischemic reperfused coronary arteries.

To elucidate the pathogenesis of the post-ischemic vascular injury in reperfused coronary arteries, the left anterior descending coronary artery (LAD) was occluded for 30 min or 60 min in 26 dogs. After 120 min of reperfusion, vascular strips were prepared from LAD and the left circumflex coronary artery (LCX) as control, and suspended in organ chambers containing Krebs-Henseleit solution and vascular reactivity was evaluated pharmacologically. In a separate experiment, LCX-strips from 12 dogs were subjected ex vivo to blood cell-free simulated ischemia by the substitution of perfusate to hypoxic, low pH and high K+ for 60 min and the following 60 min of reoxygenation. Vascular responses to various agents were compared prior to and after simulated ischemia. Vascular injury was also investigated histologically with electron microscopy. As the results; significantly blunted endothelium-dependent relaxations to acetylcholine (10(-6) M) and Ca-ionophore (A-23187: 10(-6) M) in LAD-strips compared to LCX were noticed (43.7 +/- 4.8 vs 61.6 +/- 7.3%, 22.7 +/- 5.2 vs 47.9 +/- 8.4% in % relaxation, respectively). Augmented contractile response selective to endothelin was also observed in reperfused vessels (LAD) compared to control vessels (10(-9) M: 105.4 +/- 19.5 vs 42.4 +/- 12.3% of 20 mM-KCl induced contraction, p less than 0.01). Electron microscopy revealed partial detachment and blebbing of endothelial cells in reperfused coronary arteries. Similar changes were also observed in the simulated ischemia and reoxygenation study, but the augmented response to endothelin was seen only when polymorphonuclear leukocytes (PMN) activated with phorbol myristate acetate were added. Our results suggest that endothelial injury does not essentially depend on PMN, but PMN promote augmented response to endothelin. These changes indicate that enhanced spasmogeneity is present in reperfused arteries, which may contribute to post-infarction angina and prolonged myocardial dysfunction after reperfusion.


Acute myocardial infarction in a young adult as possible sequela of Kawasaki disease--a case report of successful intracoronary thrombolytic therapy and histological study of an aneurysm.

Emergency coronary angiography in a 28-year-old male suffering an acute anteroseptal myocardial infarction revealed complete obstruction of the left anterior descending artery in association with multiple aneurysms of the 3 major coronary arteries. Successful intracoronary thrombolytic treatment with urokinase infusion directly into the infarct-related artery was performed 2 h after the onset. Follow-up left ventriculogram showed preservation of left ventricular wall motion. Fifty days after the infarction, he underwent aorto-coronary bypass surgery. Histological examination of the biopsy specimen obtained from the aneurysm of the distal portion of the right coronary artery revealed that the 3-layer architecture of the arterial wall had been completely lost. The wall was replaced by fibrotic tissue, with slight mononuclear cell infiltration around the small vessels, but no acute inflammatory reaction or atheromatous change was seen. In spite of the presence of the coronary risk factors of hypertension and hyperlipidemia, angiography revealed no evidence of atherosclerosis of systemic arteries. It is suggested that the coronary aneurysms in this case are possible sequelae of Kawasaki disease in childhood.


An orange-shaped aortic root aneurysm in aortitis syndrome with severe aortic regurgitation.

A 57-year-old man, who had undergone aorto-coronary bypass surgery 4 years before when the shape of the ascending aorta had been normal, had a unique orange-shaped aortic root aneurysm associated with severe aortic regurgitation and congestive heart failure. Replacement of the aneurysm and the aortic valve was successfully carried out, and histopathological examination revealed that the aneurysm was caused by aortitis syndrome.


Myocardial energetics and cardiac function of preserved rat heart.

We studied mitochondrial function in relation to ATP production and its relationship with myocardial oxygen consumption (VO2) and total mechanical energy using isolated rat hearts after 8, 12, and 24 h of hypothermic preservation. In isovolumic contraction, ventricular contractility and total mechanical energy were respectively assessed by the end-systolic elastance (Ees) and pressure-volume area (PVA). Ees significantly decreased after hypothermic ischemia, although the difference was not significant between 8 and 12 h. In contrast, VO2 measured at each left ventricular volume increased after hypothermic ischemia. PVA and VO2 were found to stay in linear correlation after prolonged hypothermic ischemia, although VO2 at null PVA and VO2 to PVA ratios significantly increased after hypothermic ischemia, especially after 12-h ischemia. Mitochondrial oxidative phosphorylation significantly decreased after hypothermic ischemia for longer than 12 h. These results indicate that mitochondrial oxidative phosphorylation was impaired due to long time hypothermic ischemia especially after 12-h ischemia. We conclude that energy uncoupling between VO2 and PVA in hypothermically preserved heart is attributable to disturbed mitochondrial oxidative phosphorylation and that 8 h is a critical point for efficient conversion of energy from VO2 into PVA in rat heart.


Left ventricular contractility and energetic cost in disease models--an approach from the pressure-volume diagram.

Left ventricular contractility and the energetic cost of contraction were assessed in various disease models in experimental animals utilizing frameworks of Emax (left ventricular contractility index) and pressure-volume area (PVA, a measure of total left ventricular mechanical energy expenditure) derived from the pressure-volume (P-V) diagram. Under various contractile conditions, PVA linearly correlates with myocardial oxygen consumption per beat (VO2) in a load-independent manner. The reciprocal of the slope of the linear VO2-PVA relation indicates "contractile efficiency" (the energy transduction efficiency from oxygen to total mechanical energy). It was similar between dog and rabbit hearts (about 40%) and was not significantly affected by enhanced contractility with calcium, epinephrine, or cardiac cooling, or by depressed contractility with propranolol, decreased coronary perfusion pressure, or stunned myocardium. However, in thyrotoxic rabbit hearts contractile efficiency was significantly depressed compared to normal hearts. On the other hand, the VO2 intercept of the VO2-PVA relation (PVA-independent VO2), which reflects VO2 for non-mechanical activities such as excitation-contraction coupling and basal metabolism, positively correlates with Emax. Therefore, the ratio of an increase in PVA-independent VO2 to an increase in Emax indicates "oxygen cost of contractility". Oxygen cost of contractility was higher in stunned myocardium than in normal hearts, suggesting that the energy cost of calcium handling is elevated in stunned myocardium. Thus, using the frameworks of Emax and PVA, we can interconnect cardiac mechanics and energetics. Further, using the concepts of contractile efficiency and oxygen cost of contractility, we can approach the pathogenesis of variously altered contractile conditions.


Ventricular-load optimization in patients with heart failure.

The effects of unloading or inotropic agent in 22 patients with dilated cardiomyopathy were assessed in terms of optimal coupling between the ventricle and arterial system. In 13 patients (group A), lower body negative pressure (LBNP) was applied to reduce preload and nitroprusside was used to decrease afterload. In 9 patients (group B), dobutamine was used to enhance inotropic state. In all patients, the direct arterial pressure was simultaneously recorded with left ventricular echocardiogram as the pressure was elevated by phenylephrine. The left ventricular contractile properties were defined by the slope (Ees) of the end-systolic pressure-volume relation. The arterial system properties were expressed by the slope (Ea) of the end-systolic pressure-stroke volume relation. When the Ea/Ees ratio ranged from 0.5 to 1.0, both external work and mechanical efficiency are nearly maximized. In group A, baseline ventricular-load coupling was characterized by an increase in the Ea/Ees ratio (1.96 +/- 1.08) where the heart could maximize neither external work nor mechanical efficiency. Ea/Ees significantly fell to 1.45 +/- 0.77 with nitroprusside, while increasing to 2.37 +/- 1.17 during LBNP. In group B, Ea/Ees was decreased from 1.43 +/- to 0.82 +/- 0.47 with dobutamine. It is concluded that reduction in afterload rather than preload, or augmentation of contractility could restore optimal ventricular-load coupling in patients with severe cardiac dysfunction.


Assessment of left ventricular function using a conductance catheter in the human heart.

To validate the usefulness of the conductance catheter in the clinical setting, we first studied the accuracy of human left ventricular (LV) volume measured by conductance catheter in comparison with LV volume measured by biplane angiography in 19 patients with heart disease. Secondly, we made a comparison of end-systolic pressure volume relation (ESPVR) and preload recruitable stroke work (PRSW) relation in 60 patients with heart disease. Thirdly, we studied the myocardial oxygen consumption (VO2)-pressure volume area (PVA) relation to assess contractile efficiency in 22 patients with heart disease. There was a good correlation between the corrected conductance volume (Vcc) and the angiographic volume (V angio) (Vcc = 0.94 Vangio + 5.4, r = 0.94, P less than 0.001). Two relations, ESPVR and PRSW, were well described by straight lines with high correlation coefficients. However, PRSW was a more linear contractile index than ESPVR. The reciprocal of the slope of the VO2-PVA relation was approximately 40% in the control contractile state. We conclude that the conductance catheter accurately measures LV volumes and facilitates the assessment of ESPVR, PRSW and contractile efficiency in human LV.


Ventricular contractility evaluated by mechanical perturbation of the myocardium--experimental and clinical approach adopting small amplitude vibration input.

Small amplitude mechanical vibration has been reported to depress the function of the isolated left ventricle in an amplitude dependent manner. We examined, 1) contractility and preload dependency of the magnitude of functional depression (VID) by applying 50 Hz, 2 mm amplitude vibration to the epicardium of the canine left ventricle and 2) whether VID is present in the failing human ventricle. The magnitude of VID was independent of preload in the physiological range of LV volume showing peak LV pressure greater than 75 mmHg, and VID was correlated with Emax at each inotropic state. In the in-situ condition, VID appeared only in the failing condition with a sensitive increase at a mild level of heart failure. In a study during routine cardiac catheterization (n = 27), the presence of VID has been demonstrated in the human ventricle (n = 18). The magnitude of VID was correlated with ejection fraction (EF) as, VID in peak LV pressure (mmHg) = 80.6 - 110 x EF, r = 0.84, p less than 0.01 in patients with EF less than or equal to 0.7 (n = 14). Therefore, we concluded that VID could be a clinical tool for evaluation of mild heart failure.


Contributors of characteristic mitral flow velocity pattern in congestive heart failure--from clinical observations back to experimental validations.

Mitral flow velocity pattern in patients with left ventricular (LV) diastolic dysfunction usually includes decreased peak early diastolic filling velocity (E), slowed deceleration of the early diastolic filling wave and increased peak filling velocity at atrial contraction (A). However, the abnormal mitral flow velocity pattern can be normalized in the presence of concomitant congestive heart failure. In such cases E can be equal to or even higher than normal, its deceleration is normal or faster than normal value, and A can be normal or lower than normal value. Clinical observations in patients with severe heart failure showed that the mitral flow velocity pattern changes with vasodilating therapy, reflecting the changes in the left atrial (LA) to LV pressure difference rather than those in the absolute LA pressure or LV pressure alone. This was validated in the canine study in which levels of LV dysfunction were made by the injection of microspheres into the left coronary artery to study the interrelation among the mitral flow velocity pattern and LA and LV pressures. In this experiment, the changes in the mitral flow velocity pattern could not be explained by the changes in LA or LV pressure alone but was better explained by the changes in the LA to LV pressure difference. Not only LA-LV crossover pressure but also LA compliance seem to be important as determinants of LA pressure level in diastole. In addition to LV relaxation rate, incompleteness of relaxation, elastic recoil and LV passive elastic properties, extracardiac constraint is also considered to be an important determinant of the level of the LV diastolic pressure and hence of the mitral flow velocity pattern at least in the presence of congestive heart failure. Thus, mitral flow velocity pattern is determined by the interaction of LA and LV pressures, both of which are affected by chamber properties as well as loading conditions.


Dynamic determinants of left ventricular early diastolic filling in old myocardial infarction.

The determinants of left ventricular early diastolic filling were assessed in 15 patients with old myocardial infarction. The left atrial pressure (LAP) and left ventricular pressure (LVP) were simultaneously measured by a Millar's multisensor micromanometer with the pusled Doppler mitral inflow velocity at baseline and during angiotensin infusion (20 ng/kg/min). Cardiac output was measured by a thermodilution method. LV peak systolic pressure and end-diastolic pressure were significantly (p less than 0.001) increased during angiotensin infusion from 137 +/- 19 to 170 +/- 21 mmHg and from 13.3 +/- 5.9 to 20.4 +/- 6.2 mmHg, respectively. Cardiac index was significantly decreased during angiotensin infusion. Heart rate, diastolic time, and peak positive dP/dt were unchanged. Although the LA-LV peak pressure gradient[(LAP-LVP) max] was unchanged (from 2.8 +/- 1.0 to 3.0 +/- 1.4 mmHg), the pressure gradient interval (the interval between the first and second points of transmitral pressure crossover) was significantly (p less than 0.001) decreased from 154 +/- 38 to 117 +/- 26 msec during angiotensin infusion. Peak early diastolic mitral inflow velocity (peak E) and the time-velocity integral of E wave (Ei) were significantly decreased during angiotensin infusion from 51 +/- 10 to 45 +/- 11 cm/sec (p less than 0.002) and from 7.47 +/- 1.96 to 5.70 +/- 1.66 cm (p less than 0.001), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


Prediction of surgical result of valve replacement for chronic isolated mitral regurgitation--the significance of preoperative estimation of postoperative left ventricular afterload.

Left ventricular (LV) afterload increases after mitral valve replacement, thus it would be useful to estimate postoperative LV afterload before surgery. We tested the usefulness of an index, wall stress, obtained from preoperative end-diastolic LV dimensions and diastolic blood pressure which would represent LV afterload after surgery. The data were compared with surgical mortality and morbidity. The wall stress ranged from 98 to 220 kdynes/cm2 and was 202 or higher in 3 patients who died. Five patients had wall stress above 200 kdynes/cm2. Among these, intra-aortic balloon pumping (IABP) was used in 4, and 3 died. Prolonged catecholamine support for greater than 10 days was given to all of the 4 patients, including two who died 14 and 23 days after surgery. Among 38 patients who had wall stress less than 200 kdynes/cm2, none died, IABP was performed in 3 patients, and prolonged catecholamine infusion was required in 5 patients. The incidence of mortality and morbidity were significantly higher in the high stress than in the low stress group (Chi-square analysis). Left ventricular end-diastolic index was larger in the high stress than in the low stress group (p less than 0.05). The mass/end-diastolic volume ratio was smaller in the high stress group than in the low stress group (P less than 0.05). In conclusion, this new index, predictive wall stress, is useful in selecting patients who would have high mortality and morbidity.


[Adrenal catecholamine releases during hypotension with continuous administration of calcium entry blockers and nitroglycerin].

We investigated the effect of nicardipine and diltiazem on adrenal catecholamine releases, and compared it with the effect of nitroglycerin in dogs. A 35% reduction in mean arterial pressure was achieved and maintained for 45 minutes. The dogs were observed until 60 minutes after the discontinuation of drug infusions. Adrenal catecholamine releases increased during hypotension with continuous administration of nicardipine, diltiazem and nitroglycerin, but they showed no significant differences between each drug. There was no more increase in adrenal catecholamine releases in spite of additional nicardipine administration. These results suggest that Ca2+ antagonist such as nicardipine directly inhibits the catecholamine releases from the adrenal glands.


[Differences of regional blood flow after stellate ganglion block with local anesthetic and that after stellate ganglion resection using ultrasonic Doppler flowmeter].

Ten mongrel dogs were divided into two groups; stellate ganglion block (SGB, n = 5) group and stellate ganglion resection (SGR, n = 5) group. Anesthesia was induced with pentobarbital 25 mg.kg-1. The animals were mechanically ventilated to maintain a constant PaCO2 (35-40 mmHg). Left common carotid arterial flow (CCAF), left external carotid arterial flow (ECAF), left vertebral arterial flow (VAF) and left brachial arterial flow (BAF) were measured using an ultrasonic transit time flowmeter. Internal carotid arterial flow (ICAF) was calculated by subtracting ECAF from CCAF. After thoracotomy, the first SGB with 0.5% mepivacaine 1.5 ml or SGR was performed. Ninety minutes after the first SGB, the second SGB was performed. The data were taken for 180 minutes after the first SGB or SGR. In SGB, CCAF and BAF increased significantly for the duration of action of local anesthetic. But VAF and ICAF increased significantly for a short time after the block. In SGR, CCAF, BAF and ICAF increased significantly during the experiment. But VAF showed a transitory increase immediately after the resection. The authors conclude that sympathetic ganglion block with local anesthetic should be performed repeatedly when increase of blood flow in blood vessels with strong autoregulation from the brain is anticipated.


[Anesthesia and postoperative stroke in patients with previous cerebrovascular disease].

A retrospective study was performed to determine the incidence of perioperative stroke in patients with previous history of cerebrovascular disease (CVD). One hundred and seventy eight out of 20048 patients who underwent anesthesia and surgery during the period of 1985 to 1989 had history of prior CVD. Of them, 137 patients were managed with general anesthesia and 41 with regional anesthesia. Factors analyzed were interval between the prior CVD and the operation, intraoperative hemodynamic changes, perioperative changes in the hematocrit and urinary output, and postoperative neurological complications. Postoperative neurological complications occurred in 31 of the patients given general anesthesia (delayed awakening in 26, dementia syndrome in 6 and deterioration of paralysis in 1), whereas only one patient developed dementia syndrome postoperatively in those given regional anesthesia. None of the patients developed a postoperative stroke. There was no direct relationship between the factors analyzed and the incidence of postoperative neurological complications. Further studies are needed to identify more precisely factors contributing to the occurrence of cerebrovascular complication in a high risk patients.


[The effect of epidural analgesia on respiratory muscles].

The effect of epidural analgesia on respiratory functions and muscular power was studied in patients. The subjects had no abnormality of cardiopulmonary system, and were classified into two groups; the adult group whose ages were 21 to 59, and the aged group, 60 to 72. Either 1% or 2% mepivacaine for epidural anesthesia was used to obtain the analgesic level up to Th4 and Th7 in adult group, and Th4 in aged group. The analgesic level was assessed by the pin-prick method. Vital capacity, forced vital capacity, forced expiratory volume 1 second, peak expiratory flow rate, maximal mid-expiratory flow rato, maximal inspiratory pressure and maximal expiratory pressure decreased significantly after epidural anesthesia in all patients whose analgesic levels were up to Th4. In all patients, the change of maximal expiratory pressure was larger than that of maximal inspiratory pressure after epidural analgesia. The patients whose analgesic levels were up to Th7 by 1% mepivacaine in adult group, showed a significant increase of maximal inspiratory pressure. It is concluded that epidural anesthesia diminishes respiratory functions and respiratory muscular power associated with a higher level of analgesia.


[Effects of prostaglandin E1 and epidural block on circulatory, hepatic and renal functions during anesthesia for major upper abdominal surgeries].

The effects of low dose (0.02 microgram.kg-1.min-1) prostaglandin E1 (PGE1), epidural block (EP) or combination of PGE1 and EP (PGE1 + EP) under general anesthesia on circulatory, hepatic and renal functions were studied in 31 patients undergoing major upper abdominal surgeries without hepatic or renal dysfunction preoperatively. Mean arterial pressure decreased by 10% in PGE1 and EP groups, while 20% in PGE1 + EP group. Cardiac output decreased significantly in EP group, increased in PGE1 group and was unaltered in PGE1 + EP group during anesthesia and the operation. The arterial ketone body ratio as a hepatic function test increased following the administration of PGE1 or epidural block. Urine output, osmotic clearance and free water clearance were higher in PGE1 + EP group during the operation. These results suggest that the combination of low dose PGE1 and epidural block maintain cardiac output and organ blood flow during anesthesia and surgery in spite of a greater decrease in arterial blood pressure.


[Comparison of continuous epidural fentanyl and morphine for postoperative pain management after upper abdominal surgery].

Fentanyl and morphine were administered epidurally to the patients after upper abdominal surgery for postoperative pain management. One hundred and ninety patients were divided into 3 groups; F group: bolus and continuous administration of fentanyl, M group: bolus and continuous administration of morphine, FM group: bolus of fentanyl and morphine and continuous administration of morphine. Pain scores of 1, 2, 3, 4, 8, 12 hours after administration and of the next morning were examined and side effects were recorded. Pain scores at 1 and 2 hours in F and FM group were significantly lower than those in M group. There were no significant differences in the scores among 3 groups from 3 hours to the next morning. The incidence of itching in F group was significantly less than in other groups. Respiratory depression (less than respiratory rate 8.min-1) occurred in 2 cases in M and FM group, but no case in F group. FM group had no advantage compared with F group. We conclude that continuous epidural infusion of fentanyl is more useful than morphine for postoperative pain management after upper abdominal surgery.


[Amnesic effect of oral midazolam as premedication in children].

We evaluated the sedative and amnesic effects of oral midazolam as premedication in children. Sixteen children, aged 4-12 yr, undergoing elective minor surgery were divided into 2 groups. One group received midazolam 0.5 mg.kg-1 with atropine 0.03 mg.kg-1 orally. The other control group received only atropine 0.03 mg.kg-1. There was no significant difference in the sedative scale at induction between the 2 groups. Doll-recall was used to assess the amnesic effects. In the midazolam group, 75% of the children forgot dolls they had seen on entering the operating room. Midazolam produced significant anterograde amnesia but no retrograde amnesia. This result suggests that children who received midazolam as premedication forget unpleasant memories at induction and their postoperative emotional responses are least influenced by their memories. We conclude that oral midazolam 0.5 mg.kg-1 is an effective preanesthetic medication in children.


[Epidural midazolam with bupivacaine--optimal dose for postoperative pain relief].

Optimal dose of epidural midazolam with bupivacaine for postoperative pain relief was investigated. Forty seven patients for upper abdominal surgery were divided into 5 groups. Each group had either 0.25% bupivacaine 6 ml (control group), 0.25% bupivacaine 6 ml + midazolam 0.025 mg.kg-1 (0.025 group), 0.05 mg.kg-1 (0.05 group), 0.075 mg.kg-1 (0.075 group), or 0.1 mg.kg-1 (0.1 group) administered epidurally for complaint of first postoperative pain. Blood pressure (BP), heart rate (HR), respiratory rate (RR) and sedation score (SS) were monitored for 120 minutes, and the time interval for next analgesics (TNA) was checked. In each group, BP fell down 10 minutes after injection, HR was unchanged, and RR (except for 0.1 group) decreased, compared with the preinjection level. There was no difference between control group and others in BP, HR and RR. But 3 cases in 0.075 group and 4 cases in 0.1 group needed chin lift with a pillow under the shoulder for slight airway obstruction. The most optimal SS was obtained in 0.05 group. TNA was significantly longer in 0.025 and 0.05 groups than in the control group. It was concluded that the optimal dose of epidural midazolam with 0.25% bupivacaine 6 ml was 0.05 mg.kg-1 for postoperative pain relief after an upper abdominal surgery.


[Effects of hypothermia with cardiopulmonary bypass on posterior tibial nerve somatosensory evoked potentials in man].

Somatosensory evoked potential after posterior tibial nerve stimulation (PTN-SEP), as well as nasopharyngeal, bladder and plantar temperature were recorded in ten patients during cardiac surgery with hypothermic cardiopulmonary bypass. There was a best negative correlation between latencies (P27, P40 and the interpeak latency between P40 and P27 (P40-P27)) and nasopharyngeal temperature, but no correlation was found between latencies and plantar temperature during cooling and rewarming (27-37 degrees C) with cardiopulmonary bypass. No correlation was found between changes in amplitude and temperature. The slope of linear regression line of latencies versus nasopharyngeal temperature was -1.05 msec.degrees C-1 for P27 (r = -0.93), -1.47 msec.degrees C-1 for P40 (r = -0.95) and -0.43 msec.degrees C-1 for P40-P27 (r = -0.78). This study suggests that nasopharyngeal temperature measurement is required to aid the interpretation of PTN-SEP changes during hypothermia.


[The influence of infusion volume on hemodynamics during experimental laparotomy].

The influence of infusion volume on hemodynamics was studied in adult mongrel dogs undergoing laparotomy. Study 1: Total blood volume (TBV) was measured in 5 dogs undergoing laparotomy without fluid administration for 180 min. TBV before surgery was 71.2 +/- 10.7 ml.kg-1 and remarkably decreased to 59.9 +/- 11.5 ml.kg-1, at a rate of 3.8 ml.kg-1.h-1. Study 2: 21 dogs were divided into 3 groups. Group C had restricted fluids during the study. Group I had infusion of lactated Ringer's solution (LR) at a rate of 10 ml.kg-1.min-1 and Group II at a rate of 20 ml.kg-1.min-1 for 180 min. In group C, mAP and HR were unchanged but CVP, cardiac output, renal blood flow (RBF) and skin blood flow decreased after laparotomy. On the other hand, CVP and RBF were maintained until 180 min in Group I. In Group II, though the hemodynamic parameters were well maintained and urine output was maximal, Ht, Na, concentration and especially plasma colloid osmotic pressure (Pcop) decreased. These results suggest that administration of LR at a rate of 20 ml.kg-1.min-1 is rational to prevent the decrease of TBV and to maintain the peripheral circulation during the surgical procedure, but it may decrease Pcop.


[The effects of 20% saline solution on the circulatory dynamics during the hemorrhagic shock state].

This experiment was performed to study the effects of administration of 20% saline solution 1.5 ml.kg-1 on the circulatory dynamics during the hemorrhagic shock state. Administration of 20% saline solution 1.5 ml.kg-1 during the hemorrhagic shock produced twofold increase of the mean arterial blood pressure for one hour, 2.5 fold increase of the cardiac output, increasing tendency in the mean pulmonary arterial pressure, central venous pressure, and the heart rate, accompanied by decrease in total peripheral resistance and the pulmonary blood vessel resistance. There were no improvements in acidosis and hematocrit. These data suggest that the circulatory improvements after the administration of 20% saline solution depend on an increase in cardiac output as the result of improvements in both pre- and after-load, but not of plasma volume expansion. The results also suggest that the administration of 20% saline solution 1.5 ml.kg-1 is useful for an emergency case with acute circulatory insufficiency or for emergency resuscitation.


[Perioperative renal functions in patients with chronic renal disease].

Renal function was studied in patients with compensated renal failure and in those with slight renal disorder during and after operations focusing on several aggravating factors. After perioperative episodes of hypovolemia, bleeding and shock, the levels of urine beta 2 microglobulin and FENa were elevated, showing the abnormal renal tubule functions. Elevation of NAG and the decrease of Ccr were observed, showing the organic damage on the renal tubular cell and the influence on GFR. These aggravating factors should be eliminated to prevent the irreversible renal changes.


[Thrombelastography as a bedside monitor of coagulation and fibrinolysis during surgery--a report of three cases].

Three patients with abnormal hemostasis during surgery were reported. They were monitored by thrombelastography (TEG). The first case was a 48 year old male who underwent extravivo hepatectomy. TEG showed hypo-coagulability during anhepatic phase. After reperfusion to the liver, the coagulability determined by TEG returned to a normal pattern. The second patient was a 32 year old female who underwent laparotomy to stop bleeding for cervico-vaginal laceration after delivery. The patient had been in severe hemorrhagic shock, and massive blood transfusion and fluid administration were performed. TEG showed remarkable hypocoagulability probably due to blood dilution and consumption coagulopathy. When TEG returned to a normal pattern after administration of fresh frozen plasma and fresh whole blood, the abnormal bleeding stopped. The third patient was a 48 year old male who underwent resection of metastatic brain tumor. He had hepatocellular carcinoma and liver cirrhosis. During surgery, abnormal bleeding was seen at surgical field, when TEG revealed remarkable hyper-fibrinolysis. After antifibrinolytic therapy coupled with replacement therapy, TEG returned to a normal pattern and the abnormal bleeding ceased. We conclude that TEG is a useful bed side monitor for the diagnosis of coagulopathy and hyper-fibrinolysis during surgery.


[Perioperative management for type A acute aortic dissection].

Twenty nine cases of type A acute aortic dissection were subjected to a retrospective study concerning perioperative management. Two keys pointed out for the management were as follow; (1) An optimal control of blood pressure is the most important measure to avoid advance of aortic dissection or rupture of dissecting aneurysm. Both pericardiac tamponade and aortic valve insufficiency should be taken care of from their onset, since they are often complicated after aortic dissections and their onset is fatal. (2) Separated brain perfusion and profound hypothermia with total circulatory arrest might involve a high risk of inducing postoperative brain damage and mortality, especially for old patients.


[A disposable tracheal spray device for patients in whom it is difficult to indwell a urinary catheter].

A disposable tracheal spray device was utilized for 20 patients in whom it was difficult to indwell a urinary catheter in the past 4 years. Among them, 18 patients were successfully inserted with a Foley catheter after sufficient lubrication of whole urinary tract with lidocaine using this device. In one patient for gastrectomy, it was not possible to insert because of obstruction of the urinary tract at the prostate. Another patient showed abnormal urinary tract with normal urination. There were no major complications by this manipulation. It was concluded that this application could provide useful informations about the urinary tract in the patients with difficulty for insertion of the urinary catheter, and it provides sufficient lubrication for the indwelling.


[Anesthetic management of a neonate with esophageal atresia with double tracheoesophageal fistulae].

We reported the anesthetic management of a 1-day-old female neonate (2,110 gm) with esophageal atresia combined with double tracheoesophageal fistulae, which is classified as Gross type D. Though Gross type C was suspected preoperatively, the proximal fistula was found coincidentally during the preparation of the upper pouch. Because, for one thing, the origin of the proximal fistula was close to the end of the upper pouch (1cm), and for another, the distance between the both fistulae was short (1cm). As for the proximal fistula, it was 2 mm in diameter, and it was easily sealed with the side of the endotracheal tube. No other respiratory managements were needed except frequent suctionings of copious intratracheal secretions. On the other hand, the distal fistula, 10 mm in diameter, caused hypercapnea due to hypoventilation before gastrostomy. It was so big that it is easily intubated. This type of tracheoesophageal fistula is extraordinarily rare and its proximal fistula is difficult to find before, during, and even after operation. The missing of the proximal fistula often provokes severe respiratory infections and furthermore, sepsis postoperatively. It is concluded that in all the cases of tracheoesophageal fistula, the existence of the proximal fistula should be considered without fail and managed accordingly. To diagnose correctly, the use of preoperative bronchofiberscopy is also recommended.


[Anesthesia for cesarean section in a patient with Ebstein's anomaly].

A 30-year-old woman with Ebstein's anomaly was scheduled for Cesarean section at 38 week gestation because of latent fetal distress. After arterial and central venous catheters were inserted, general anesthesia was started. Anesthesia was induced smoothly and rapidly through intravenous route. Following induction, her hemodynamics was stable until post-operative period. The baby weighed 1564g and had an Apgar score of 8 at 1 minute. A patient with Ebstein's anomaly during pregnancy and anesthesia has potential for a variety of hemodynamic disturbances. This case illustrates the importance of careful attention to the preoperative findings and the perioperative hemodynamic parameters.


[The anesthetic management for adrenalectomy of a patient with Cushing's syndrome in pregnancy].

The anesthetic management for left adrenalectomy of a pregnant patient with Cushing's syndrome caused by adrenal adenoma during pregnancy was reported. At 21 week gestation, anesthesia was induced with modified NLA and maintained with nitrous oxide-enflurane-oxygen combined with continuous lumbar epidural anesthesia. Postoperatively, she was delivered a normal, 1990 g infant at 37 week gestation. The present case is believed to be the first reported case of general anesthesia in detail for adrenalectomy in a patient with Cushing's syndrome during pregnancy. The anesthetic management including choice of anesthetics, anesthetic method, intraoperative monitoring, influence of catecholamine, and fetal as well as maternal complication was reviewed from literatures.


[The factors that influence intraoperative blood loss during total hip replacement].

Fifty cases of total hip replacement performed by one surgeon were reviewed to compare the effects of epidural and general anesthesia. The blood pressure in patients under epidural anesthesia was significantly lower (P less than 0.001; t-test). There was a highly significant correlation between the operation time and the intraoperative blood loss (P less than 0.005, r = 0.67). A significant correlation was noted between the blood pressure and the minute loss of blood (P less than 0.01, r = 0.43). It is concluded that epidural anesthesia is to be recommended rather than general anesthesia in patients undergoing total hip replacement.


[Use of diltiazem in the anesthetic management of epinephrine predominant pheochromocytoma].

This report describes a case of epinephrine predominant pheochromocytoma successfully managed intraoperatively with an infusion of diltiazem. A 50-yr-old woman with a 10-yr history of diabetes mellitus was admitted to the hospital because of thirst and general fatigue. A cystic left adrenal tumor was found on computed tomographic scan. Although resting plasma catecholamine levels were normal, plasma norepinephrine and epinephrine levels obtained from the left adrenal vein were 1.6 ng.ml-1 (normal, 0.04-0.35) and 6.2 ng.ml-1 (normal, less than 0.12), respectively. Diltiazem was administered i. v. at a rate of 3 micrograms.kg-1.min-1 before induction of anesthesia. Anesthesia was induced with enflurane 2-3% and nitrous oxide in oxygen, followed by tracheal intubation facilitated with vecuronium. Anesthesia was maintained with enflurane 1-3% and nitrous oxide in oxygen. Paralysis was maintained with vecuronium. Hypertension during the manipulation of the tumor was controlled by increasing the inspired concentration of enflurane or by increasing the infusion rate of diltiazem to 5 micrograms.kg-1.min-1. There was no tachyarrhythmia. The infusion of diltiazem was continued until the draining vein from the tumor had been ligated. Hypotension, after removal of the tumor, was treated by the rapid infusion of fluid. Plasma norepinephrine and epinephrine levels during tumor manipulation were 1.18 ng.ml-1 and 6.57 ng.ml-1, respectively.


[Acute pulmonary edema in five patients undergoing sevoflurane anesthesia].

Four adults and a child undergoing surgery with sevoflurane anesthesia developed acute pulmonary edema immediately after anesthesia. Prior to development of pulmonary edema all patients exhibited severe arterial hypertension and tachycardia. Their episodes of circulatory changes were, we believed, caused by the local injection of epinephrine for hemostasis in 2 patients (9 y.o. child, 45 y.o. man) and the intrusion of painful surgical stimuli in one patient (67 y.o. man). Circulatory changes in these three patients were treated by increasing the inspired sevoflurane concentration. We, however, speculate that the increase in inspired sevoflurane decreased the cardiac output and that the resulting increase in pulmonary wedge and capillary pressures was caused by an abrupt increase of arterial blood pressure, followed by a rapid increase in afterload due to cardiac suppression from the high concentration of sevoflurane. In 2 patients (74 y.o. man, 61 y.o. woman) arterial hypertension occurred during endotracheal extubation after sevoflurane anesthesia. Because of fast uptake and elimination of sevoflurane due to a low blood/gas partition coefficient, a fast awakening in the latter 2 patients, may be responsible for the abrupt increase in arterial blood pressure. In conclusion, it should be noted that pulmonary edema may be involved when severe circulatory changes occur in a patient undergoing sevoflurane anesthesia.


[Coronary artery spasm during coronary artery bypass surgery].

We report two cases of coronary artery spasm during coronary artery bypass surgery. As one of the complications during cardiac surgeries, coronary vasoconstriction occurs mainly after coming off cardiopulmonary bypass. The factors responsible for the spasm include high endogenous catecholamine levels due to inadequate anesthesia and hypothermia, exogenous catecholamines for circulatory support, various chemical mediators and combination of these factors. Coronary artery spasm was suspected strongly because of sudden ischemic change in electrocardiography and simultaneous aggravation of circulatory parameters, which improved immediately after direct injection of coronary vasodilators into vein graft. This method, popular in coronary angiography and catheterization, is effective for release of coronary-artery spasm observed particularly after cardiopulmonary bypass. Then mechanical circulatory assist is readily available to treat possible systemic side effect of the vasodilators.


[Synergistic action of cefodizime with other antimicrobial agents on clinically isolated microorganisms. II. Synergistic action with sisomicin].

Cefodizime (CDZM) possesses a broad antimicrobial spectrum and a relatively long half life in the blood. In addition, it shows excellent therapeutic efficacies in the treatment of infections in leukopenic animal models, hence it is expected that CDZM may have good efficacies against various infections in immunocompromised hosts. In the meantime, sisomicin (SISO) not only has strong antibacterial activities against Gram-negative rods (GNR), but has relatively low nephrotoxicity and ototoxicity. Thus, we examined antibacterial effectiveness of the combination of CDZM and SISO against clinical isolates in vitro. 1. Antibacterial effects of CDZM+SISO combination were examined using SISO susceptible strains of Escherichia coli, Citrobacter freundii, Klebsiella pneumoniae, Enterobacter cloacae, Serratia marcescens, Proteus vulgaris, Morganella morganii and Pseudomonas aeruginosa. Observations that the combination of the 2 drugs showed FIC indices between less than 0.5-less than 1.0 against most of these strains at SISO concentrations of 1 MIC or sub MIC levels strongly suggested the presence of a synergistic action between the 2 drugs against SISO susceptible strains of GNR. 2. Of the strains tested, 10% of C. freundii, 6.7% of E. cloacae, 63.3% of S. marcescens, 23.3% of P. vulgaris and 18.0% of P. aeruginosa were found to be resistant to SISO, and little synergistic effect of the 2 drugs was observed against these strains. 3. As the synergistic effect of the 2 drugs against GNR was observed against SISO susceptible strains including those which were resistant to CDZM, but not against those strains which were resistant to SISO, it seems reasonable to conclude that the appearance of the synergistic effect between the 2 drugs depends on the activity of SISO.


[Pharmacokinetic studies on oral antibiotics in pediatrics. V. A pharmacokinetic study on cefdinir in pediatrics].

A pharmacokinetic study was performed on cefdinir (CFDN, FK482) 5% fine granules for pediatric use, and pharmacokinetic parameters were calculated. 1. Twenty school children were administered orally a dose level of 3 mg/kg of CFDN fine granules either at 30 minutes before meal (14 children) or 30 minutes after meal (6 children). Plasma concentrations and urinary recovery rates of CFDN were measured. Tmax, Cmax, T 1/2 and urinary recovery rate (0-8 hours) following the administration before meal were 2.00 +/- 0.00 hours, 1.14 +/- 0.11 micrograms/ml, 1.63 +/- 0.14 hours and 23.68 +/- 2.92%, respectively, Tmax, Cmax, T1/2 and urinary recovery rate following the administration after meal were 3.67 +/- 0.33 hours, 0.71 +/- 0.06 micrograms/ml, 2.18 +/- 0.16 hours and 21.76 +/- 2.36%, respectively. Earlier Tmax and higher Cmax were observed when the drug was administered before meal than when administered after meal. There was no statistically significant difference between the 2 groups in urinary recovery rates. However, statistically significant difference was found between the 2 groups when the cross-over technique was used in 6 school children. Nineteen younger children (before meal) and 6 younger children (after meal) were administered with the drug in the same way, and several parameters were measured. Tmax, Cmax, T1/2 and urinary recovery rate following the administration before meal were 2.11 +/- 0.11 hours, 0.98 +/- 0.14 micrograms/ml, 1.71 +/- 0.23 hours and 23.60 +/- 1.72%, respectively, Tmax, Cmax, T1/2 and urinary recovery rate following the administration after meal were 3.33 +/- 0.42 hours, 0.47 +/- 0.14 micrograms/ml, 2.35 +/- 0.27 hours and 12.24 +/- 2.02%, respectively. Earlier Tmax, higher Cmax and higher urinary recovery rate were observed when the drug was administered before meal than when administered after meal. Seven infants (before meal) and 8 infants (after meal) were administered with the drug in the same way, and several parameters were measured. Tmax, Cmax, and T1/2 following the administration before meal were 4.00 +/- 0.62 hours, 0.61 +/- 0.13 micrograms/ml and 3.14 +/- 0.62 hours, respectively, Tmax, Cmax and T 1/2 following the administration after meal were 3.75 +/- 0.25 hours, 0.79 +/- 0.13 micrograms/ml and 2.44 +/- 0.42 hours, respectively. These was no statistically significant difference between the 2 groups. 2. Twenty one school children were administered orally with CFDN fine granules at 30 minutes before meal ata dose level of either 3 mg/kg (14 children) or 6 mg/kg (7 children). Plasma concentrations and urinary recovery rate of CFDN were measured.(ABSTRACT TRUNCATED AT 400 WORDS)


[The influence of cefdinir on the intestinal bacterial flora].

The influence of cefdinir (CFDN), a new oral cephalosporin, on the intestinal bacterial flora was studied in tetra-contaminated mice and in pediatric patients. CFDN in fine granules was administered at a dose of 10 mg/kg once a day for 5 consecutive days to mice contaminated with 4 different species of organism: Escherichia coli, Enterococcus faecalis, Bacteroides fragilis and Bifidobacterium breve. No remarkable changes were observed in the fecal viable cell counts except that decreases in E. coli counts were observed on the day 3 to 5 after starting administration. The subjects in pediatric study were 7 children with infections, 3 boys and 4 girls, with their ages from 6 months to 12 years 7 months. Their body weights ranged from 5.5 to 29.2 kg. CFDN fine granules was administered at each dose of 3.0 mg/kg to 3.7 mg/kg, 3 times a day for 4 to 14 days. During the administration of CFDN, some variations were observed in the pattern of changes in the fecal bacterial flora between subjects. Although Enterobacteriaceae and total counts of anaerobes were markedly decreased in 2 cases, total counts of aerobes were unchanged in the 2 cases, whereas main aerobes and anaerobes except enterococci hardly varied in the other cases. There was no case in which glucose non-fermenting Gram-negative rods and fungi became predominant species continually. Although Clostridium difficile and C. difficile D-1 antigens were detected in 1 and 4 cases, respectively, no relationship was found between the number of C. difficile and the characteristics of the feces. With regard to the drug sensitivities of bacteria isolated from feces before and after administration of CFDN, higher levels of resistance were found in some bacteria such as Enterococcus and Bacteroides during or after administration than before administration. CFDN was detected in fecal samples from 2 cases during administration with concentrations ranging between 0.99-254 micrograms/g. High value of CFDN was found in a case with low beta-lactamase activity in feces, in which marked decrease of Enterobacteriaceae and total counts of anaerobes was observed. The above results suggest that CFDN is considered to be a drug with relatively small influence on the intestinal bacterial flora. But as high concentrations of drugs were detected in feces under some circumstances, our attention will be required. Particular care is also required for the occurrence of diarrhea and microbial replacement during continuous, long-term administration of the drug.


[Bacteriological, pharmacokinetic and clinical studies of 5% and 10% granules of cefdinir in the pediatric field].

Bacteriological, pharmacokinetic and clinical studies on cefdinir (CFDN, FK482), a new oral cephalosporin, 5% and 10% granules, were performed in the field of pediatrics. The results are summarized below. 1. Antibacterial activities Antibacterial activities of CFDN against Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, Haemophilus influenzae, Branhamella catarrhalis, Escherichia coli and Klebsiella pneumoniae were studied in comparison with those of cefaclor (CCL), cefixime (CFIX) and amoxicillin (AMPC). MIC80's of CFDN against S. aureus, S. pneumoniae, S. pyogenes, H. influenzae, B. catarrhalis, K. pneumoniae and E. coli were 0.78, 0.20, less than or equal to 0.025, 0.39, 0.10, 0.20 and 0.10 micrograms/ml, respectively. These results show that CFDN has high antibacterial activities against these organisms. MIC80's of CFDN against Gram-positive bacteria were similar to those of AMPC, and was lower than those of CCL and CFIX. As for antibacterial activities against Gram-negative bacteria (GNB), the MIC80 of CFIX against H. influenzae was 0.05 micrograms/ml, which was slightly lower than that of CFDN. THe MIC80's of CFDN against other GNB were similar to those of CFIX. 2. Absorption and excretion Blood concentrations and urinary excretion rates of CFDN 5% and 10% granules and 100 mg capsule were determined. The data on CFDN 10% granules were similar to those on CFDN 5% granules. At a dose of 3 mg/kg, peak blood concentrations (Cmax's) of CFDN ranged from 0.20 to 2.12 micrograms/ml with 5% granules and from 0.50 to 1.15 micrograms/ml with 10% granules at 2 to 3 hours after dosing. At a dose of 6 mg/kg, peak concentrations were 0.66-2.06 micrograms/ml and 0.70-1.52 micrograms/ml with 5% granules and with 10% granules, respectively. At 8 hours after dosing, blood concentrations were 0.04-0.54 micrograms/ml at 3 mg/kg and 0.06-0.27 micrograms/ml at 6 mg/kg. Blood half-lives were 1.33-4.36 hours at 3 mg/kg and 1.14-3.27 hours at 6 mg/kg. AUC's were 1.7-11.0 micrograms.hr/ml with 3 mg/kg and 2.4-8.7 micrograms.hr/ml with 6 mg/kg. With administration of single 100 mg capsule, Cmax's, blood concentrations after 8 hours, T1/2's and AUC's were 0.79-1.88 micrograms/ml, 0.20 micrograms/ml, 1.54-2.72 hours, and 5.2 micrograms.hr/ml, respectively. Urinary recovery rates in the first 8 hours ranged from 6.85 to 39.2% with 3 mg/kg and 6.08-25.5% with 6 mg/kg.(ABSTRACT TRUNCATED AT 400 WORDS)


[Pharmacokinetics and clinical effects of cefdinir 10% fine granules in pediatrics].

Cefdinir (CFDN), a newly developed oral cephalosporin in a 10% fine granular form, was administered to 8 children and concentrations of the drug in plasma and urine and urinary recovery rates of the drug were determined. The subjects were divided into 2 groups of 4 children each; one group received 3 mg/kg of CFDN at 1 hour before meal (in the fasting state), and the other, at 30 minutes after meal. To study clinical and bacteriological effects of this drug, a mean dose of 4.8 mg/kg t.i.d. was administered for 8 days on the average to 9 children with various infections; tonsillitis (3 cases), acute bronchitis (1), pneumonia (1), acute purulent otitis media (1), urinary tract infection (2), and impetigo (1). MICs were determined for 6 drugs including CFDN, cefaclor, cefixime (CFIX), methicillin, cloxacillin, amoxicillin (AMPC) against 4 strains freshly isolated from children receiving CFDN. An inoculum size of 10(6) cfu/ml was used in the MIC-determinations. Adverse reactions and abnormal laboratory findings attributable to this drug were also examined in these children. The results obtained are summarized as follows. 1. Mean plasma peak levels of CFDN were observed at 2 hours after administration in the before-meal group and 4 or 5 hours after administration in the after-meal group mean peak values of 0.88 and 0.50 micrograms/ml, respectively. Mean half-lives were 1.61 hours in the before-meal group and 2.54 hours in the after-meal group, and mean AUCs were 4.24 in the former and 3.59 micrograms.hr/ml in the latter. 2. Mean urinary peak concentrations of CFDN were observed during 2-4 hours after dosing in the before-meal group and during 6-8 hours in the after-meal group with values of 93.3 and 44.8 micrograms/ml, respectively, in cases for which plasma concentrations of drugs were determined. Mean urinary recovery rates during the first 8 hours after administration in the before- and after-meal groups were 16.6 and 13.4%, respectively. 3. Good clinical effects were obtained with an efficacy rate of 100% in 9 patients with 6 diseases due to bacterial infections. 4. Good bacteriological effects were also obtained against 2 strains of Streptococcus pyogenes, 2 strains of Escherichia coli and 1 strain of Haemophilus influenzae with an eradication rate of 100%. In 3 cases of these and another case (normal flora), strains present before the study were replaced by other strains.(ABSTRACT TRUNCATED AT 400 WORDS)


[Microwave therapy for diseases of the genitourinary organs].

Microwave energy had become a valuable component in the electromagnetic spectrum. Because of its unique energy source, the microwave radiation can penetrate several centimeters into biologic tissue. The energy is absorbed and converted into heat within the tissue. Clinical applications of microwave irradiation fall into two categories; thermotherapy and hyperthermia. Microwave therapy has generated great interest in the field of urology because of its safety, efficiency, and its simplicity as a surgical tool. This review analyses the fundamentals of the science of microwave energy as a therapy and presents an in-depth discussion of its theoretical principles, unique characteristics, appropriateness of application, and its potentiality as a long-term modality for the treatment of urologically-related diseases.


[The limits of recovery in hydronephrosis. An experimental pathological study].

The object of this experimental study is to elucidate the limits of recovery in hydronephrosis. Hydronephrosis in the rabbit kidney was made by left ureteric ligation for 1, 2, 3 and 4 weeks, followed by relief of obstruction with uretero-ureteric anastomosis. Two and 4 weeks after relief, histopathological examination was performed. In proportion to the obstructive period, both proximal tubule and thin portion of Henle's loop showed atrophy of epithelial cells, multi-laminar thickening of basement membranes, and splitting between epithelium and basement membranes. The interstitium showed edema and subsequent fibrosis. These damages were thought to be due to severe ischemia, which such tubules did not recover and even showed more advanced damages after relief. On the other hand, thick portion of Henle's loop, distal tubule and collecting duct showed advanced compression atrophy and dilated lumen, while no severe ischemic damage was demonstrated. Therefore, after relief, they showed recovery, and, even in the case of no recovery, they showed no advanced damages. In hydronephrosis, severe ischemic damages brought about a loss of the ability of recovery.


[Growth inhibitory effect of a new anticancer antibiotics, kazusamycin A, on human transitional cancer cell lines in vitro].

Kazusamycin A (KZMA) is a new anticancer antibiotic, which has been proven to have strong anticancer effect and several characteristic features different from currently available anticancer antibiotics. However, there has as yet been no report which had concerned itself with the effect of KZMA on urological cancer. This study was undertaken to determine the inhibitory effects of KZMA on transitional cancer cells in vitro, the augmentation of the inhibitory effect by combining thermal treatment and the effect of KZMA upon DNA distribution. Human transitional cancer cells, KU-1, and T-24 were used as targets. Fifty % inhibitory concentration of KZMA was determined after these cells were exposed to graded concentrations of KZMA for 2 to 48 hours, and to the concentration of KZMA for 2 hours at the temperature of 42 degrees C. Viable cells were counted by dye exclusion assay (DEA) and by tetrazolium-based colorimetric assay (MTT-assay) exposure. KZMA inhibited the growth of the three transitional cancer cells strongly and this inhibitory effect appeared to be depend upon the exposure time and the concentration of KZMA. IC50s after 2-hour exposure at the temperature of 42 degrees C was shown to be decreased to 23 to 87% of that at the temperature of 37 degrees, indicating an augmentation of the inhibitory effect of KZMA by combining thermal treatment. MGH-U1 was the most sensitive to the combination of KZMA and hyperthermia. The cell cycle analysis showed that KZMA had G2-arresting and M-retarding effects, which were different compared with currently available anticancer antibiotics.(ABSTRACT TRUNCATED AT 250 WORDS)


[Histopathological study of metallothionein in bladder cancer and renal cell carcinoma].

Metallothionein (MT) is a low molecular-metal binding protein with multiple biological functions. Recently, MT has been implicated as a factor involved in resistance to anticancer drugs, which presumably inactivates anticancer drugs, including cisplatin, and doxorubicin. In this report, we investigated the relationship of MT expression with the clinical features in bladder cancer and renal cell carcinoma. In 35 cases of bladder cancer, 10 cases of renal cell carcinoma and 3 cases of normal mucosa of bladder, the expression of MT was immunohistologically examined by avidinebiotin-peroxidase (ABC) staining of paraffin-embedded tissue specimens with anti-MT antibody. Intense MT expression was noted in all cases of normal mucosa of bladder. MT was detected in 10 of 35 cases of bladder cancer, with the incidence of MT expression being significantly higher increases with lower pathological tumor grade. MT was detected in 8 of 10 cases of renal cell carcinoma, and all of the their normal renal tubules showed more intense staining. A number of hypotheses can be proposed from these observations. First, our observation of decreased MT expression in poorly differentiated carcinomas, which are the more proliferating tumors, this suggests correlation of MT expression with proliferative status of cancer. Second, the higher incidence of MT expression in renal cell carcinoma than in bladder cancer may suggest that it is a factor responsible for the lower efficacy of chemo-therapy in renal cell carcinoma than in bladder cancer.


[Immunological study of induction of metallothionein in bladder cancers].

Metallothionein (MT) in tumor cell has been indicated as one of the factors involved in the mechanism of resistance to anticancer drugs. The relationship between expression of MT and chemotherapy with anticancer drugs was studied with bladder cancer culture cell lines and tissue samples from clinical cases. In drug-resistance cell lines, MT expression was studied by immunohistological staining of the avidin -biotin peroxidase complex (ABC) method, and by the radioimmunoassay (RIA) method, using an anti-MT antibody. As for tissue samples from clinical cases, 114 paraffin embedded samples of 29 cases before and after chemotherapy were subjected to immunohistological staining of MT. Human-bladder cancer cell lines with resistance to anticancer drugs (C1-7/CDDP, T-24/ADM) showed increased of expression of MT compared to each parental cell lines (C1-7, T-24), suggesting relationship of resistance to anticancer drugs and MT expression. In the clinical cases, those with continuous administration such as intra-vesicle chemotherapy or oral administration chemotherapy showed greater incidence of positive staining of MT expression in comparison with cases with fewer administrations, such as intra-arterial infusion therapy or intravenous administration chemotherapy. These results demonstrated that repetitive and continuous administration of anticancer drugs cause increase of MT in bladder cancer cell, which may be a possible mechanism of acquired resistance to anticancer drugs.


[Recurrence following surgery for primary renal pelvic and ureter cancer--clinicopathologic analysis of distant metastasis].

A retrospective analysis of 59 patients with renal pelvic and ureter cancer (56 transitional cell carcinomas, 2 squamous cell carcinomas, and 1 adenocarcinoma), which were treated surgically, was performed in relation to postoperative recurrence, particularly distant metastasis. Of the 59 cases, postoperative recurrences developed as distant metastasis in 9 cases (15.3%), as bladder cancer in 19 cases (32.2%) and as contralateral renal pelvic and ureter cancer (bilateral metachronous cancer) in 3 cases (5.1%). Three of the 9 cases with the development of distant metastasis were squamous cell carcinoma or adenocarcinoma, and the others transitional cell carcinoma. All the metastases occurred within 2 years. In cases with transitional cell carcinoma, nonpapillary tumor, grade 3, high stage (pT3 and pT4), positive vascular invasion and IFN beta or gamma had a significant influence on the rate of distant metastasis. On the other hand, location, diversity and previous or coexistent bladder cancer did not seem to be related to the frequency of the development of distant metastasis. Thus, tumor aggressiveness was the only predictive valuable of the development of distant metastasis after surgery for renal pelvic and ureter cancer.


[An approach to stoma-less continent urinary diversion by uretero-ileoceco-proctostomy (ileocecorectal bladder)].

The current practice of continent urinary diversion still places the patients under the restraint of the stoma and intermittent catheterization. To overcome these problems, we developed a new technique of urinary diversion of which continent is controlled by the anal sphincter. The isolated ileocecal segment is intussuscepted and interposed between the ureters and the rectum. The conjoined ureters are anastomosed to the stump of the ileal limb, and the antimesenteric portion of the cecal limb is joined to the anterior wall of the rectum. The surgical procedure is simpler than that of the continent reservoirs currently employed. The intussuscepted ileocecal segment prevents fecal reflux to the upper urinary tract and may also inhibit carcinogenesis at the uretero-intestinal junction. Additionally, the rectal capacity is augmented by the side to side anastomosis between the cecal limb and the rectum. Our preliminary experience in 10 cases were satisfactory with respect to voiding function, antireflux mechanism of the intussuscepted ileocecal segment and quality of life. The results will justify further trials with this stomaless continent urinary diversion for those in whom the urethra cannot be used.


[Results in treatment of urinary incontinence in the elderly].

The diagnosis and treatment of urinary incontinence in the elderly out-clinic patients were reviewed. Sixty-three patients (24 males and 39 females) over 60 years old, who consulted our clinic complaining urinary incontinence, were subjected to the present study. The patients' ages ranged from 60 to 91, with the mean age of 72.9 years old. The types of the incontinence were urge in 44 cases (69.8%), stress in 10 (15.9%), outflow in 5 (7.9%) and mixture of urge and stress in 4 (6.4%). Urge incontinence resulted from unstable bladder in 63.6% and from neurogenic bladder (overactive detrusor) in 36.4%. Cerebrovascular diseases were the most common cause of the neurogenic bladder. Fifty-four patients (85.7%) were out-patients and 9 (14.3%) were hospitalized for other diseases. Thirteen patients (20.6%) with dementia were included. Diagnosis was made on the basis of a detailed questionnaire, physical examination and voiding chart, and confirmed by urodynamic study. Treatment was positively made by means of drug therapy, operation, clean intermittent catheterization and/or behavior training. As results, incontinence disappeared in 52.4% (frequency of incontinence/day: 5.0 +/- 2.6 times/day to 0), was fairly improved in 30.2% (5.1 +/- 2.3 to 1.2 +/- 0.8), was slightly improved in 7.9% (3.4 +/- 1.4 to 2.4 +/- 1.4) and unchanged in 9.5% (8.2 +/- 2.3 to 8.3 +/- 2.2). Severe neurogenic bladder (overactive), dementia and physical disability were proposed to be important factors responsible for treatment failure. Aggressive therapy should be tried to treat the urinary incontinence in the elderly, since favourable results can be expected in most of the cases.


[A case of urinary retention due to tuberculous pyometra].

A rare case of urinary retention due to tuberculous pyometra is presented. A 70-year-old woman visited our hospital complaining of dysuria and pollakisuria on January 26, 1990. In spite of medication of cholinergic agents, urinary retention developed on April 6, 1990. Cystoscopy revealed elevation of the urethra and bladder neck. Physical examinations disclosed a child-head-sized tumor in the lower abdomen, which persisted following catheterization. Excretory urogram showed a large retrovesical mass. Chain urethrocystogram revealed anterior dislocation of the bladder neck and the proximal portion of the urethra. CT scan and MRI demonstrated a fluid-filled pelvic mass, which positioned above the vagina and compressed the urinary bladder anteriorly. Total hysterectomy was performed on August 6, 1990. Pathological diagnosis was tuberculous endometritis. Urinary symptoms disappeared immediately after the operation. Postoperative chain urethrocystography revealed complete cure of the dislocation of the bladder neck and urethra. We collected 34 cases of urinary retention due to gynecological disease in Japan, and 110 cases in English literature. Among the frequent diseases were retroverted gravid uterus, prolapse uteri, uterine leiomyomas, ovarian cyst, imperforated hymen and vaginal atresia. The mechanisms of urinary retention in gynecological disease are discussed. No case of urinary retention due to tuberculous pyometra was found in the literature.


[The effectiveness of anal submucosal injection of methotrexate for relapsed prostatic cancer--a case report].

The case is a 77-year-old man who was first examined in August 1980 (at age 67). Prostatic biopsy revealed a poorly-differentiated adenocarcinoma, and clinically, diagnosis was made as stage B. Castration and DES administration were carried out. Subsequent chemotherapy with BLM, MMC, and 5-FU led to CR. A periodical check-up in September 1985 detected a pelvic lymph node metastasis, which was, however, completely remitted by radiotherapy and chemotherapy. In April 1990, local relapse was noted in the left lobe of the prostate. Biopsy revealed a poorly-differentiated adenocarcinoma. Three courses of intravenous administration of CDDP, THP, and VP-16 caused no change. From August 1990 on, anal submucosal injection of MTX was started. 20 mg of MTX administration once a week, for consecutive 5 weeks, followed by 4-week interruption on ambulatory basis formed one course. The tumor was distinctly reduced following one course, disappeared (MRI) following two courses and showed only a few viable cells (biopsy) following four courses. We consider that the present method is a hopeful new therapeutic approach.


[A new vaccination schedule].

In July 1991 a new vaccination strategy has been recommended. Two alterations are involved; the general recommendation of the pertussis immunization and a second MMR vaccination. Comments are given on BCG-, pertussis-, MMR- and HIB-vaccinations. The continued existence or the new foundation respectively of medical advisory boards on immunization problems in all states of the Federal Republic of Germany are strongly recommended.


[Current therapy of febrile convulsions].

The author gives a review on clinical features and therapeutic aspects of febrile seizures. The treatment with different anticonvulsants is described. Differentiation between simple and complicated febrile convulsions seem to be useful for therapeutic management.


[Kinetics of vaccine antibodies to tetanus toxoid, diphtheria toxoid, measles virus, poliomyelitis virus and pneumococci after allogenic and autologous bone marrow transplantation and booster immunization. 1: The kinetics of vaccine antibodies to tetanus toxoid after allogenic and autologous bone marrow transplantation].

Today BMT belongs to the established methods of treatment in haematology and oncology. Because of the constant increase of healthy long-term survivors after BMT the problem of immunological reconstitution and eventual possible late effects gets more and more importance. One problem, which til now has been few attention paid to, is that of the protection by vaccination after BMT. We report on the kinetics of the tetanus-antitoxin in 20 patients after allogeneic or autologous BMT and demonstrate the influence of a graft-versus-host disease and its therapy on the antibody kinetics. In the group of allogeneic transplanted children without a GvHD the tetanus-antitoxin titers felt below their detection range after a time of about 8 months whereas in the group with GvHD this effect already occurred after nearly 4 months. The autologous transplanted patients have a positive antibody level til the time of 20 months after BMT. As a consequence of the lost protection by vaccination after BMT follows the necessity of revaccinations respectively of boostering after immunological reconstitution.


[Fatal course of B-streptococcal infection in early infancy].

We report on a fatal case of "late onset" -sepsis by B-streptococcus in a seven weeks olk suckling. B-Streptococcus is considered to be a typical strain of early stage neonatal sepsis that is connected with foudroyant progress and high letality. As in our case the outcome is decisively determined by early diagnosis and timely beginning therapy for the strain can still be controlled effectively. Misjodging early symptoms of the infection may lead to fateful progression even after the neonatal period.


[Cold agglutinin syndrome after rubella infection].

Cold agglutinins are antibodies against erytrocyte membrane antigens, and are produced primarily or secondarily. We report on the case of a 5 year old girl who developed cold agglutinin disease 3 days after an attack of German measles. Following exposure to cold, appeared blue-red cutaneous manifestations of the fingers, hands cheeks and nose. The clinical manifestations cleared up without any specific therapy. The occurrence of cold agglutinins after German measles is rare. The case report is discussed within the context of reports in the literature.