Effect of the combination of anticoagulant and thromboxane synthetase inhibitor (Y-20811) or receptor blockade (S-1452) on preventing thrombotic cyclic coronary flow reduction in dogs with coronary stenosis. We examined the hypothesis that combined actions of anticoagulant (heparin) and Y-20811, thromboxane A2 synthetase inhibitor (TXSI), or S-1452, receptor blockade (TXRB), can provide better antithrombotic protection than TXSI or TXRB alone. In 20 of 33 dogs instrumented, placement of a critical stenosis at a focus of coronary vascular injury initiated a reproducible cyclic coronary flow reduction (CCFR). TXSI (1 mg/kg, IV) perfectly inhibited CCFR in 6 of 10 dogs (60%), and was associated with a significant decrease in 11-dehydro-TXB2 (85 +/- 8% of control; p < 0.05) and an increase in 6-keto-PGF1 alpha (155 +/- 38%; p < 0.05) in coronary sinus blood samples. In the remaining 4 dogs, additional administration of heparin (2000 IU) completely abolished CCFR. On the other hand, TXRB (1 mg/kg, IV) perfectly inhibited CCFR in 7 of 10 dogs (70%), and was accompanied by a significant increase in 6-keto-PGF1 alpha (214 +/- 65%; p < 0.05) and unchanged TXB2 level. In the remaining 3 dogs, additional administration of heparin (2000 IU) completely abolished CCFR. Thus, the combination of anticoagulant and TXSI or TXRB were more effective than TXSI or TXRB alone in abolishing thrombotic CCFR, suggesting that the combination might be effective for treating patients with impending myocardial infarction.


Are the various thrombolytic agents equally effective in the treatment of acute transmural myocardial infarction? While it is no longer possible to imagine the treatment of an acute transmural myocardial infarction without the use of thrombolytic agents, some discussion still exists as to the choice of the thrombolytic agent. Our study concerns a group of 160 patients with an acute transmural myocardial infarction, 60 of whom were treated with anistreplase, 52 with streptokinase and 48 with alteplase. Statistically, the administration of anistreplase was associated with a significantly higher frequency of ventricular arrhythmias in comparison to the other thrombolytic agents, whereas after subsequent coronary angiography, the anistreplase group revealed a significantly lower number of completely occluded coronary arteries. The data from this study demonstrate that anistreplase is a very valuable thrombolytic agent. It may even be more effective than streptokinase and alteplase in the treatment of acute myocardial infarction when the patency of the coronary arteries 1 month after the acute coronary event is considered the primary endpoint.


Early diagnosis of the site of infarction and the infarct-related coronary artery in patients with acute inferior myocardial infarction. We evaluated the relationship between the site of infarction and the infarct-related coronary arteries from electrocardiograms (ECGs) recorded early after the onset of chest pain in patients with an initial acute inferior myocardial infarction (IMI). The subjects were 80 patients (mean age 57 +/- 12 years) with IMI admitted within 6 hours from the onset of chest pain. This was prior to the thrombolytic era. We analyzed the ECGs on admission, at 24 hours and at 4 weeks. All patients underwent left ventriculography and coronary angiography at 4-6 weeks from the onset of the IMI. Left ventricular ejection fraction (EF) and regional area changes were measured. The infarct-related coronary artery was determined by the site of the asynergy. Patients were allocated into 2 groups according to the infarct-related artery, i.e. right (RCA, n = 52) and left circumflex (LCX, n = 28). Parameters measured were ST elevation, amplitude and width of R wave and R/S ratio in leads V1 and V2, and amplitude of U waves in leads V1 to V3. We defined the U wave as a prominent positive U wave (PPU) if it was > 0.5 mm (50 microV) in height. A significantly greater number of patients with PPU showed asynergy in posterolateral segments compared to those without PPU. The EF was significantly lower in patients with PPU than in those without (46 +/- 12% vs 54 +/- 13%, p < 0.05). Patients with PPUs eventually showed ECG evidence of posterior infarction (increased R wave duration and R/S ratio > or = 1 in lead V1 or V2) by 4 weeks compared to those without PPUs. Also a significantly greater number of patients with PPUs developed posterior infarction shown by left ventriculograms than those without PPUs. As to the infarct-related coronary arteries, a significantly greater number of patients with LCX disease showed concomitant posterior infarction than those with RCA disease. Also, a significantly greater number of LCX patients showed PPUs and ST elevations in leads V5 and V6 than those with RCA disease. The sensitivity of PPUs and ST elevations in leads V5 and V6 suggesting LCX disease was 60% and the specificity was 98% with a predictive accuracy of 87%. Therefore, we conclude that PPUs in leads V1-3 and ST elevations in leads V5 and V6 are specific markers for the diagnosis of LCX-related infarction in the setting of evolving IMI.


Interventional intra-arterial ultrasonography as an exclusive method of exploration to determine atherosclerotic lesions of the arterial wall at a preclinical stage. Intravascular ultrasonography of the peripheral arterial system was applied following coronarography in 56 patients with one or several critical stenoses of the coronary arteries. Even though the clinical vascular examination and the subsequent noninvasive examination of the peripheral arterial system of all these patients turned out to be completely normal, intra-arterial ultrasonography was able to reveal important atherosclerotic alterations in the wall of the abdominal aorta and of the iliac-femoral arterial system in 51 of these patients. Intra-arterial ultrasonography appears to be a very sensitive method of exploration, permitting atherosclerotic changes of the arterial wall to be detected at a very early preclinical stage, long before these deviations could have caused symptoms.


Plasma lipid profile in obese children and in children with hereditary predisposition to coronary heart disease. This study examined risk factors for coronary disease and plasma triglycerides, total cholesterol, HDL, LDL cholesterol (C), Apo A-1, and Apo B lipoprotein levels in obese children (n = 107) aged 9-12 years old and in children (n = 64) hereditarily predisposed to coronary heart disease (CHD). In the latter group, children's fathers had a history of MI before 50 years of age. A control group of 30 children was also studied, and the plasma lipid profile was investigated in 35 fathers with premature myocardial infarction. Seventy-five percent of the obese children and 60% of the children hereditarily predisposed to CHD had three or more coronary artery disease risk factors. Plasma HDL-C (p < 0.001), LDL-C (p < 0.001-p < 0.05, respectively), Apo A-1 (p < 0.001), and Apo B (p < 0.001) levels were different in both groups compared with controls.


Effects of pravastatin on cholesterol metabolism in Watanabe heritable hyperlipidemic rabbits. Pravastatin, a competitive inhibitor of hydroxymethylglutaryl CoA reductase (HMG CoA reductase) is a potent hypocholesterolemic agent in humans as well as experimental animals, including the Watanabe heritable hyperlipidemic (WHHL) rabbit, lacking low density lipoprotein (LDL) receptor activity. We studied the effect of pravastatin on several aspects of cholesterol metabolism in WHHL rabbits. Cholesterol synthesis was measured by intraperitoneal injection of radioacetate and determination of its incorporation into the nonsaponifiable lipid fraction of liver, plasma, adrenal glands and gonads. A single dose of pravastatin (25 mg/kg) caused statistically significant inhibition of hepatic cholesterol synthesis at 2, 6, 12, and 24 hours following oral administration. By 48 hours, the inhibitory effect of the drug was no longer demonstrable. The pattern of radioactivity in the plasma was similar to that in the liver. The drug had no statistically significant effect on cholesterol synthesis in adrenal glands and gonads, suggesting a selective effect on the liver. Cholesterol absorption was studied after simultaneous oral administration of [3H] cholesterol and [14C] beta-sitosterol. Pravastatin, 50 mg/kg for 10 days had no effect on fecal excretion of the radiolabelled steroids over 4 days. At 24 hours the plasma level of [14C] cholesterol was 1/3 that of control in pravastatin treated animals (p < 0.05) but did not undergo an accelerated decline over 6 days. The activity of acyl CoA: cholesterol acyltransferase (ACAT) in intestinal mucosa and the concentration of hepatic cholesterol were similar in animals treated over one year with pravastatin 50 mg/kg/day or with placebo. Our data do not allow us to make definitive conclusions about the effect of pravastatin on cholesterol absorption but are compatible with the hypothesis that the drug inhibits the hepatic synthesis as well as the assembly of cholesterol into lipoproteins.


Production of active and inactive renin by adrenal explant cultures and the existence of a prorenin activating enzyme in the adrenal gland. We previously demonstrated high levels of inactive renin (IR) in nephrectomized rat plasma which provided evidence for extra-renal sources of IR. However, the sources of IR were unknown. This study examined whether the adrenal gland is capable of producing active renin (AR) and IR, using explants of adrenal capsules (glomerulosa portions) from control and nephrectomized (Nepex) rats. Explants from both control and Nepex rats produced large quantities of IR and small quantities of AR. The productions of both IR and AR in Nepex rats were significantly greater than in control rats. High potassium culture medium markedly increased IR and slightly, but significantly, enhanced AR in both control and Nepex rats. On the other hand, sodium had little effect on either IR or AR. A renin-angiotensin system has been reported in the adrenal gland. Recently, a prorenin activating enzyme was demonstrated in the kidney and the aortic wall. The next study was performed to demonstrate the existence of a prorenin activating enzyme in the adrenal gland, using inactive renin from culture medium from Nepex rat explants as the substrate. A 26 KD component in adrenal zona glomerulosa tissues isolated by Sephacryl S-200 column chromatography, converted IR to AR in IR rich medium. The pH optimum for prorenin activation by the enzyme was 6.5. Inhibitor studies indicate that this enzyme is a serine protease. These data suggest that (1) the adrenal gland is an extra-renal source of inactive renin and (2) a prorenin activating enzyme exists in the adrenal gland.


Intramolecular oscillation of the phosphorylation domain of rat cardiac sarcoplasmic reticulum titrated with arachidonoyl phosphatidylcholine. Sarcoplasmic reticulum vesicles were prepared from rat myocardium. The intramolecular oscillation of the phosphorylation domain of Ca(2+)-ATPase in control vesicles and in vesicles titrated with diarachidonoyl phosphatidylcholine was studied with a nanosecond time-resolved fluorometer. The membrane viscosity of the lipid domain was decreased by the lipid titration. The phosphorylation domain was labeled with a fluorophore, anilinonaphthylmaleimide (ANM). The time course of anisotropy decay of ANM fluorescence reflects the localized oscillation in the protein structure. The half-decay time of the anisotropy was decreased by diarachidonoyl titration from 77 nsec in control vesicles to 66 nsec, suggesting an increase in the intramolecular oscillation. Concomitantly observed decreases in membrane viscosity and Ca(2+)-ATPase activity suggest that the decreased membrane viscosity destabilized the Ca(2+)-ATPase protein structure causing a reduction in Ca(2+)-ATPase activity.


Dilated cardiomyopathy with recurrent intraventricular thrombosis. Dilated cardiomyopathy with intraventricular thrombosis is a rare disease, most frequently encountered in adults. It rarely occurs in infants. We report here the case of a 2-year-old boy with intraventricular thrombosis due to dilated cardiomyopathy and emphasize the importance of prophylactic anticoagulant therapy in this case.


High output cardiac failure caused by multiple giant cutaneous hemangiomas. A 59-year-old Chinese woman had multiple giant cutaneous cavernous hemangiomas on her right upper limb which resulted in high output heart failure because they presented as a large peripheral arteriovenous (A-V) fistula. Selective right subclavian arteriography showed extremely hypertrophic arteries of the patient's right arm with a tremendous blood supply to the soft tissues; neither superselective embolization nor surgery seemed applicable to this patient. The patient's heart failure was not satisfactorily controlled by conservative treatment.


Recurrent atrial flutter in apical hypertrophic cardiomyopathy. Palpitations are a symptom often reported by patients with apical hypertrophic cardiomyopathy (HCM), yet the arrhythmias associated with this type of HCM have not been studied adequately. Herein, a case of persistently recurrent atrial flutter in a 63-year-old Greek man with apical HCM is presented. Synchronized direct-current shocks were used twice during his hospitalization in order to convert atrial flutter to sinus rhythm. No definite precipitating factor for the induction of atrial flutter was identified.


Possible intramural site of reentrant circuit in ventricular tachycardia of nonischemic cause. Pre and intraoperative mapping studies. A patient with a drug-refractory sustained ventricular tachycardia (VT) of nonischemic cause was mapped for the site of VT origin. The intraoperative mapping showed the earliest site of activation of VT on the epicardial surface at which the initial deflection of the local electrogram preceded the onset of the QRS complex of VT by 45 msec. The endocardial mapping could not indicate the site at which the electrogram was found prior to the onset of the QRS complex of VT. However, at the earliest site of the endocardial mapping, VT was entrained without change in the configuration of the QRS complex. After cessation of the rapid pacing, VT resumed at the intrinsic rate and the first post-paced return cycle was identical to each paced cycle length. The interval from the stimulus to the orthodromically captured local electrogram at the pacing site was identical to the cycle length of VT. Catheter ablation from the endocardial side and a cryoablative procedure from the epicardial side failed to eradicate the VT. These findings suggest an intramural site of VT origin and reentrant circuit of which the exit and the entrance face the epicardial and the endocardial surfaces, respectively.


[Thallium-201 myocardial perfusion imaging during adenosine-induced coronary vasodilation in patients with ischemic heart disease]. 201Tl myocardial perfusion imaging during adenosine infusion was performed in consecutive 55 patients with suspected coronary artery disease. Adenosine was infused intravenously at a rate of 0.14 mg/kg/min for 6 minutes and a dose of 111 MBq of 201Tl was administered in a separate vein at the end of third minute of infusion. Myocardial SPECT imaging was begun 5 minutes and 3 hours after the end of adenosine infusion. For evaluating the presence of perfusion defects, 2 short axis images at the basal and apical levels and a vertical long axis image at the mid left ventricle were used. The regions with decreased 201Tl uptake were assessed semi-quantitatively. Adenosine infusion caused a slight reduction in systolic blood pressure and an increase in heart rate. The rate pressure products increased slightly (9314 +/- 2377 vs. 10360 +/- 2148, p < 0.001). Chest pain (24%) and headache (13%) were the frequent side effects. The second-degree atrioventricular block was developed in 11 of 55 (20%) patients. All symptoms and hemodynamic changes were well tolerated and disappeared within 1 or 2 minutes after discontinuing adenosine infusion. The sensitivity and specificity for the detection of patients with coronary artery disease were 100% (31/31) and 88% (7/8), respectively. 201Tl myocardial imaging during adenosine infusion was considered to be safe and useful for evaluating the patients with ischemic heart disease.


[Assessment of cardiac function and left ventricular regional wall motion by 99mTc multigated cardiac blood-pool emission computed tomography]. Forty-three patients underwent the analysis of left and right ventricular (LV and RV) volumes, and LV regional wall motion by multigated cardiac blood pool single photon emission computed tomography (SPECT) with 99mTc. To calculate the cardiac volume correctly, the optimal cutoff level in relation to background level was first obtained by a phantom study. Left ventricular end-diastolic, end-systolic volume (EDV and ESV) and ejection fraction (EF) calculated thus with SPECT were correlated well with the data obtained with left ventriculography (LVG) and magnetic resonance imaging (MRI), especially using horizontal long axial image. RV stroke volume (SV) without shunt or valvular diseases was also correlated well with that of LV when it was calculated using horizontal long axial image. However, SV ratio (LVSV/RVSV) was not necessarily ideal numerical 1. In addition LV wall motion was evaluated by multicontour systolic display and phase analysis in SPECT and gated planar images. The results obtained with SPECT were better correlated with those of LVG than gated planar images. It is concluded that multigated cardiac blood pool SPECT is a clinically useful method for an evaluation of cardiac function and left ventricular regional wall motion.


[Pulmonary kinetics of 13N-ammonia in smoking subjects--a quantitative study using dynamic PET]. To evaluate the effect of smoking on nonrespiratory function in the lung, a dynamic PET with 13NH3 in the lung was performed in 18 normal volunteers without lung disease nor congestion (9 non-smokers, 4 exsmokers, 5 smokers). After intravenous bolus injection of 13NH3, twenty serial 5.5-second scans followed by six 30-second scans were performed. Regions of interests were assigned on the ventral, lateral and dorsal part of the right lung and time-activity curves were generated through 26 images. The activity curve demonstrated a biexponential clearance from the lung with fast and slow component. The retention fraction (RF), fractional size of the slow component, was calculated, and the half-times (t 1/2) of both components were also evaluated. A significant increase of RF and prolongation of t 1/2 of slow component were observed in smokers compared to non-smokers and exsmokers. However, no significant difference of RF nor t 1/2 of both components was observed between non-smokers and exsmokers. These results suggest that long term smoking may modify the pulmonary kinetics of 13NH3, but the change is reversible after cessation of smoking for one year or longer.


[Phase 2 clinical study of 99mTc-ECD--a multicenter study]. A phase 2 clinical study of a newly developed brain perfusion agent, 99mTc-ECD, was performed in 166 cases of cerebrovascular diseases and impairment of brain function to evaluate effectiveness, usefulness, optimum dose and optimum timing of imaging as a multi-center study involving 10 institutions in Japan. All cases were judged as no problems on safety and any side effects due to the administration of the compound were not observed. Out of 163 cases evaluated for the clinical usefulness, valuable information for clinical diagnosis was obtained in 160 cases (98.3%), and 154 cases (94.5%) were judged as "extremely useful" or "useful". Although SPECT imaging was possible from 5 min after injection, images obtained between 60 and 90 min after injection showed relatively better image quality in many cases. Regarding standard administration dose, 400 to 800 MBq were considered to be appropriate. 99mTc-ECD is considered to be a promising radiopharmaceutical as a brain perfusion agent.


[A case of meningioma with non-accumulation of 99mTc-ECD and increased accumulation of 99mTc-HMPAO in the tumor]. 99mTc-ECD SPECT and 99mTc-HMPAO SPECT with or without Matas test were performed in a 62-year-old woman with meningioma in the left anterior cranial fossa. After injection of 740 MBq 99mTc-ECD or HMPAO, 64 projection images were collected with a rotating Gamma camera. Matas test was carried out by compressing the left common carotid artery for about one minute immediately after RI injection. Although 99mTc-ECD SPECT showed non-accumulation in the tumor, 99mTc-HMPAO SPECT demonstrated increased accumulation in it. This area of increased accumulation disappeared on 99mTc-HMPAO SPECT with Matas test which causes decrease in blood flow of the tumor. These findings suggest 99mTc-ECD and 99mTc-HMPAO have a different mechanisms of accumulation in the meningioma.


[Clinical application of 18F-FDG-PET in patients with brain death]. In order to evaluate glucose metabolism in brain death, 18F-FDG-PET scans were performed in three patients with clinically highly suspected brain death. One case was caused by head trauma and other two cases were by subarachnoid hemorrhage. All of them were in deep coma without spontaneous breathing, whose intracranial pressure was remarkably elevated up to the level of mean arterial pressure. Nineteen frames of dynamic scan were started soon after intravenous injection of 18F-FDG for one minute per frame, followed by 10 minutes of static scan which started 40 minutes after the injection. Both in dynamic and static scan, no significant intracranial accumulation of 18F-FDG was seen in all of three cases. This finding can be interpreted as the evidence that there is no significant glucose utilization from blood in the brain. This is the first report of clinical application of 18F-FDG-PET to brain death. Our results support the clinical diagnosis of brain death and 18F-FDG-PET can be of value for the assessment of glucose metabolism in patients with suspected brain death.


[Clinical assessment of 99mTc-HMPAO scintigraphy in thoracic tumors]. 99mTc-hexamethylpropylene amineoxime (99mTc-HMPAO) scintigraphy was performed in 15 malignant tumors in 11 patients and a patient with bronchopneumonia. A high 99mTc-HMPAO affinity for the tumors was observed on SPECT, however, the mean tumor/contralateral normal lung ratios of 99mTc-HMPAO activity (1.26) was lower than that of 201Tl-chloride (2.29). 99mTc-HMPAO uptake was seen not only in the tumors but also in the bronchopneumonia, atelectasis, and irradiated lung (containing radiation fibrosis). Moreover, a diffuse uptake in the lung was seen in a patient received repeated chemotherapy. Therefore, it is emphasized that there is a non-specific 99mTc-HMPAO uptake in those various pulmonary conditions.


[Active tuberculosis in children who received INH chemoprophylaxis]. Twelve children who developed active tuberculosis even after receiving isoniazid (INH) chemoprophylaxis were seen at Tokyo Metropolitan Children's Hospital from 1982 through 1991. All cases received INH more than 9 mg/kg/day, except for one case in which the amount of INH administered at the referring hospital was unknown and Streptomycin was administered together with INH. The age of starting INH prophylaxis ranged from 2 months to 13 years, and the age at which clinical symptoms and/or laboratory evidences of active tuberculosis were first manifested ranged from 4 months to 18 years. Five patients developed active tuberculosis after the completion of chemoprophylaxis and patients during chemoprophylaxis, with the first presentation ranging from primary complex (seven), chronic pulmonary tuberculosis (two), tuberculous meningitis (two), and tuberculous pleuritis (one). None of the Mycobacterium tuberculosis resistant to INH was isolated. Reviewing these patients, eleven cases had at least one of the following factors: (1) age less than two years old (2) infectious sources expectorated more Mycobacterium tuberculosis (3) delay in starting INH. Above factors should be considered in initiating INH chemoprophylaxis and subsequent follow-up of the patients.


[Surgical treatment for tuberculous spondylitis; a case report]. A 64-year-old woman was admitted with the chief complaints of severe back pain. Chest X-ray film on admission showed an abnormal mass lesion in the right upper mediastinum. Chest tomography and chest CT films revealed destruction of thoracic vertebrae (Th 2 and 3) and paravertebral abscess. Chemotherapy containing RFP was started under diagnosis of active tuberculous spondylitis of thoracic vertebrae. Three months later, curative operation for spondylitis were performed. She underwent the resection of necrotic bone and the anterior spinal fusion using transplanted bone autograft. Her post-operative course was good and she discharged three months after curative operation. Tuberculous spondylitis is still important diseases at the differential diagnosis from metastatic vertebral tumors. This report describes a successful case of surgical treatment for tuberculous spondylitis of thoracic vertebrae.


[Counting efficacies of the CFU-enumerating method and microscopic counting method for mycobacteria located in cultured macrophages]. I compared counting efficacies of CFU-enumerating method for the number of mycobacteria (Mycobacterium intracellulare and M. fortuitum) locating in cultured macrophages with that of microscopic counting method. Zymosan A-induced macrophages from ddY mice were infected with either M. intracellulare or M. fortuitum by incubation in 10% FBS-RPMI 1640 medium containing the organisms for 1 hr, thereafter thoroughly washed to remove extracellular bacilli, and cultured for 3 to 5 days. At intervals, macrophages were thoroughly rinsed and subjected to either CFU-enumeration or microscopic counting, as follows. In the former method, macrophages were lysed with 0.2% Tween 80-distilled water by sonication using Handy Sonic and CFUs were counted on 7H11 agar plates. In the latter method, the number of acid-fast bacilli was counted by microscopy for macrophages after Ziehl-Toda's staining. The number of bacteria by the CFU-enumerating method was much greater than that by the microscopic counting method.


Effects of dietary protein restriction and oil type on the early progression of murine polycystic kidney disease. A paucity of research data exists on the potential for early dietary modification to directly retard cystic growth and proliferation in polycystic kidney disease (PKD). We have therefore examined the relative effects of dietary protein levels and oil type on the progression of disease in a murine model of PKD. In the first study, weanling DBA/2FG-pcy (pcy) mice were fed either a normal (NP), 25%, or low (LP), 6%, casein diet with 10% of either sunflower seed oil (SO) (containing n-6 fatty acids), or fish oil (FO) (containing n-3 fatty acids), in a 2 x 2 design. At the end of the dietary treatment, kidney weight relative to body weight was higher in mice on the NP diets. In addition, kidney phospholipid to kidney weight (mumol/g) was lower in pcy mice on NP diets, indicating that the increased kidney size was largely due to increased cyst development. Replacement of dietary SO with FO resulted in alterations in renal phospholipid fatty acid compositions: 18:2 n-6, 20:4 n-6, and 22:5 n-6 were lower, and 20:5 n-3, 22:5 n-3, and 22:6 n-3 were higher in FO-fed animals. No effect of dietary lipid type on disease progression was noted, however. In a second study, morphometric analysis revealed an 11% lower percentage cyst area and a 46% lower total cyst area (mm2) in kidney sections derived from mice on LP diets compared to NP diets. These results indicate that early dietary protein restriction in PKD prior to clinical manifestation of symptoms of the disease may have a significant impact on the pathogenesis of PKD.


Effect of loop diuretics on organic osmolytes and cell electrolytes in the renal outer medulla. Electron microprobe analysis on freeze-dried cryosections was used to determine the effect of the loop diuretics torasemide and furosemide on intracellular electrolyte concentrations in individual cells of the outer and inner stripe of the outer medulla and on cell rubidium uptake, the latter a measure of basolateral Na-K-ATPase activity. In addition, the organic osmolytes glycerophosphorylcholine (GPC), betaine, inositol and sorbitol in cortex, outer medulla and inner medulla were measured using HPLC. Both loop diuretics significantly reduced sodium and chloride concentrations and rubidium uptake in thick ascending limb cells, but did not affect sodium concentration or rubidium uptake in the proximal straight tubule (PST) cells or in the light or dark cells of the outer medullary collecting duct (OMCD). Chloride concentrations in these cells (that is, PST cells, OMCD light and dark cells) were lowered by loop diuretics, albeit less than in thick ascending limb cells. Administration of both loop diuretics for only 20 minutes was sufficient to significantly depress tissue concentrations of GPC, betaine, and myo-inositol in the outer medulla and of GPC, betaine and sorbitol at the papillary tip. These results indicate that loop diuretics, presumably by blocking apical sodium entry, decrease thick ascending limb cellular sodium concentration and, as a consequence, reduce Na-K-ATPase activity as assessed by cell rubidium uptake. Although this has been shown previously in in vitro preparations, the present study confirms this for the first time in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)


Failure of atrial natriuretic peptide to induce natriuresis in aortocaval fistula dogs. Creation of an aortocaval fistula (ACF) in dogs induces salt and water retention, activation of the renin-angiotensin and adrenergic nervous systems and renal papillary ischemia associated with high levels of circulating atrial natriuretic peptide (ANP). The effects of intrarenal ANP (1.2 micrograms/min) infusion on systemic and renal hemodynamics, renal excretory function, renal output of renin and norepinephrine (NE) and papillary plasma flow (PPF) were studied in both normal and ACF dogs. ANP did not alter systemic hemodynamics in either group, but led to a significant increase in renal blood flow (RBF), glomerular filtration rate (GFR), urine flow rate (V), sodium excretion (UNaV) and fractional excretion of sodium (FENa), and a significant decrease in renal vascular resistance (RVR) and urine osmolality (UOsm) in normal dogs. GFR, RBF, RVR, V, UNaV, FENa and UOsm remained unchanged, however, in ACF dogs. In ACF dogs, both renal renin and NE output were significantly greater during baseline and remained significantly greater following ANP infusion, associated with a significantly lower PPF compared with normal dogs. These data suggest that ACF dogs are resistant to the renal effects of ANP, which can neither mitigate the hormonal mediators of sodium retention nor reverse the papillary ischemia observed in this model.


Early glycosylation products induce glomerular hyperfiltration in normal rats. The effects of early glycosylation products (Amadori Products, AP) were investigated in male Munich-Wistar rats to establish whether AP play a role in the pathogenesis of glomerular hyperfiltration of early diabetic nephropathy. To mimic such a condition, normal rats were transfused with blood containing in vitro glycated serum (Group GLYC) to achieve plasma levels of Amadori products similar to those measured in rats with streptozotocin-induced diabetes. Rats transfused with normal blood were used as control (Group CON). Glomerular hemodynamics was evaluated in basal condition (B) and during acute hyperglycemia (HG). Blood transfusion did not alter basal hemodynamics. In Group CON, HG determined a rise of single nephron GFR (41.4 +/- 3.2 vs. 32.1 +/- 1.8 nl/min, P less than 0.005), secondary to the increase of afferent effective filtration pressure (EFPa, +19% vs. B, P less than 0.01). Rats of Group GLYC, in B, had values of SNGFR higher than those of Group CON B (46.8 +/- 3 nl/min, P less than 0.05, ANOVA). This increase was mediated by a significant reduction of glomerular afferent arteriole (Ra, -38% vs. Group CON B, P less than 0.05), a rise in hydrostatic gradient pressure in glomerular capillaries (delta P, +17%, P less than 0.05) and of EFPa (+31%, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


Microfilament disruption occurs very early in ischemic proximal tubule cell injury. Experimental ischemic acute renal failure results in disruption of proximal tubule apical membranes. Previous work utilizing immunofluorescence with an anti-actin antibody has demonstrated that the apical cytoskeleton of proximal tubule cells is disrupted during ischemic injury. In this study, using rhodamine-phalloidin which stains only filamentous actin, we demonstrate that graded durations of ischemia resulted in progressive disruption of proximal tubule apical microfilaments. Quantification using spectrofluorometry showed that 5, 15 and 50 minutes of ischemia resulted in 32.8 +/- 4%, 48.8 +/- 2.5%, and 58.4 +/- 2.6% decreases in apical F-actin relative to controls. Ischemia did not qualitatively affect either glomerular or distal tubule F-actin structure, though there were nonprogressive increases in glomerular fluorescence. In summary, rhodamine-phalloidin staining can be used to qualitatively and quantitatively assess proximal tubule microfilaments in vivo. We conclude that ischemia results in very early loss of proximal tubule apical microfilaments, with the majority of F-actin loss occurring within five minutes.


Thromboxane in the pathogenesis of glomerular injury in diabetes. The present study examined the role of thromboxane (TX) in the initiation and progression of glomerular injury in diabetic rats, as reflected by albuminuria and glomerular histology. Urinary thromboxane and albumin excretion (UTX and UAlb) were elevated by four months after induction of diabetes in the moderately hyperglycemic (200 to 400 mg/dl glucose) streptozotocin diabetic rat (SDR) compared to age-matched control rats. UTX and UAlb both increased progressively in SDR over the seven month period of study. Glomerular TX production, glomerular volume, fractional and absolute mesangial volume and glomerular basement membrane (GBM) width were also increased after seven months in SDR compared to control. Treatment of SDR with a thromboxane synthetase inhibitor (TXI) 4' (imidazol-l-yl) acetophenone (100 mg/kg/day) for seven months beginning at the time of induction of diabetes prevented the increases in UTX, UAlb, glomerular TX production, glomerular volume and mesangial volume and attenuated, but did not prevent, GBM thickening. When the same dose of the TXI was begun five months after induction of diabetes and continued for two months, UTX and ex vivo glomerular TX production were reduced by only 60% compared to untreated SDR and remained higher than corresponding values in control rats. Delayed treatment with the TXI alone did not alter UAlb compared to untreated SDR. By contrast, treatment of five month albuminuric SDR for only two months with the TXI plus the TX receptor antagonist (TXRA) Bay U3405 (5 mg/kg/day) prevented a further increase in UAlb, and reduced fractional albumin clearance and mesangial volume compared to values in untreated SDR. Combined treatment with the TXI and TXRA had no effect on GBM width or glomerular volume compared to values in untreated SDR. The results support roles for TX in the initiation of, and for TX and/or endoperoxides in the progression of glomerular injury in SDR.


Peritoneal defense in continuous ambulatory versus continuous cyclic peritoneal dialysis. Several centers have reported a lower rate of peritonitis among adult patients on continuous cyclic peritoneal dialysis (CCPD) as compared to those undergoing continuous ambulatory peritoneal dialysis (CAPD). Preliminary results of our ongoing prospective randomized study comparing CAPD-Y with CCPD also suggest a lower peritonitis incidence among CCPD-treated patients. To investigate whether the two dialysis regimens could result in differences in local host defense, we studied peritoneal macrophage (PMO) function and effluent opsonic activity in eight patients established on CAPD-Y matched with eight chronic CCPD patients. Since short and long dwell times are inherent to both dialysis modalities, and we previously found that dwell time has an impact on PMO function and effluent opsonic activity, patients were studied after both a short (4 hr) and a long (15 hr) dwell time. In both groups PMO phagocytic capacity increased significantly with dwell time (39 +/- 3.3% at 4 hr vs. 58 +/- 4.2% at 15 hr in CAPD patients, and 40 +/- 3.9 vs. 72 +/- 3.3% in CCPD patients; P less than 0.01), as did PMO peak chemiluminescence response (31 +/- 4.9 vs. 77 +/- 7.2 counts.min-1/10(4) cells in CAPD, and 22 +/- 3.9 vs. 109 +/- 21.2 counts.min-1/10(4) cells in CCPD; P less than 0.01) and effluent opsonic activity (41 +/- 7.6 vs. 73 +/- 5.8% in CAPD and 39 +/- 6.2 vs. 70 +/- 5.9% in CCPD; P less than 0.01). However, no significant difference was found in either variable between CAPD and CCPD patients when dwell times were equal.(ABSTRACT TRUNCATED AT 250 WORDS)


Interleukin-8 and polymorphoneutrophil leucocyte activation in hemolytic uremic syndrome of childhood. Polymorphoneutrophil leucocytes (PMNLs) are implicated in the pathogenesis of diarrhea-associated hemolytic uremic syndrome (D+ HUS). We investigated mechanisms of PMNL involvement by measuring tumor necrosis factor alpha (TNF alpha) and the novel cytokine, interleukin-8 (IL-8), a potent activator of neutrophils, together with alpha 1- antitrypsin-complexed elastase (alpha 1-AT-E) as a marker of neutrophil degranulation, and anti-neutrophil cytoplasmic antibodies (ANCA). IL-8 was not detected in the 17 normal children, but was significantly elevated in 20 of 25 D+ HUS children (P less than 0.005), and in three of nine children with non-diarrhea-associated (D-) HUS. Sequential data showed that IL-8 peaked transiently in the circulation, reaching a maximum just before a more protracted burst of alpha 1-AT-E. The IL-8 levels correlated significantly with circulating alpha 1-AT-E concentrations (r = 0.50, P less than 0.05). In D+ HUS IL-8 levels also correlated with the PMNL count (r = 0.63, P less than 0.005), and the highest values were seen in those children who died in the acute phase of the disease. TNF alpha was raised in only 1 of 16 D+ HUS children and in no patients were ANCA detected. The data suggest that PMNLs in HUS are recruited by IL-8, that this cytokine plays a key role in the PMNL activation which occurs, and that agents which suppress this recruitment and activation might play a therapeutic role in this disorder.


Renal handling of silicon in normals and patients with renal insufficiency. We have compared the renal handling of silicon in 16 patients with renal insufficiency to 14 normal individuals. Silicon, phosphate and creatinine were measured in plasma and urine samples. The renal insufficiency group showed significant increases in plasma silicon (1.28 +/- 0.19 vs. 0.17 +/- 0.03 mg/liter), creatinine (5.19 +/- 0.85 vs. 0.89 +/- 0.03 mg/dl) and phosphate (1.33 +2- 0.11 vs. 1.07 +/- 0.4 mmol/liter). Fractional phosphate excretion was increased in the renal insufficiency group (0.55 +/- 0.07 vs. 0.14 +/- 0.01). In contrast, the fractional excretion of ultrafiltrable silicon was not significantly different between groups (0.78 +/- 0.07 vs. 0.87 +/- 0.06). It is concluded that renal insufficiency does not alter the tubular handling of silicon and that regulatory control of silicon excretion is unlikely.


Predicting chronic renal insufficiency in idiopathic membranous glomerulonephritis. We developed an approach in quantifying the risk of developing chronic renal insufficiency (CRI) based on a cohort of 184 patients with idiopathic membranous glomerulonephritis (IMGN), prospectively followed by the Toronto Glomerulonephritis Registry between 1974 and 1988. After a mean follow-up period of 5.8 years, 26% of patients developed CRI (defined as persistent reduction of creatinine clearance (CCr) less than or equal to 60 ml/min/1.73 m2 for greater than or equal to 12 months). We found that when compared to the baseline probability of the unselected patients, the severity of proteinuria at kidney biopsy added only marginally to the prediction of CRI. We introduced a special test condition: persistent proteinuria (PP) (that is, duration of proteinuria, g/day, above different cut-off levels). We examined the positive predictive value (PPV) and sensitivity (SEN) of 15 arbitrarily chosen levels of PP (that is, proteinuria greater than or equal to 4, 6 or 8 g/day persisting for greater than or equal to 6, 9, 12, 18 or 24 months) to select levels with optimal predictive characteristics. We found that PP greater than or equal to 8 g/day for greater than or equal to six months was a simple and useful predictor of CRI with a PPV and SEN of 66%. To further improve our prediction, we tested the following parameters: age, sex, initial SCr and CCr, proteinuria, serum albumin, hypertension, rate of change of CCr over time, and therapy (steroids +/- immunosuppressive drugs) in a multivariate analysis. Proteinuria, initial CCr, and rate of change of CCr were most important in predicting CRI.(ABSTRACT TRUNCATED AT 250 WORDS)


Risk of peritonitis and technique failure by CAPD connection technique: a national study. Peritonitis has been a leading complication of long-term therapy with continuous ambulatory peritoneal dialysis (CAPD). This study was designed to evaluate the risk of peritonitis and technique failure according to the initial CAPD connection technique. Patients from all U.S. facilities starting CAPD therapy at home between January 1 and June 30, 1989 were followed for up to 21 months on the initial CAPD connection technique to change in technique or dialytic modality, to transplantation, death or loss to follow-up. Patients were grouped into standard connection techniques (SCT) (N = 1,133), Y-set (N = 1,067), standard UV set (N = 916) and O-set (N = 167). The time to first peritonitis episode was analyzed actuarially and by using the Cox proportional hazards model which adjusted for age, sex, race, cause of ESRD, CAPD program size and ESRD therapy prior to CAPD. Peritonitis occurred on average at 9.0 month intervals with SCT, 15.0 months with Y-set, 13.4 with standard UV and 9.4 with O-set. The relative risk (RR by Cox analysis) of first peritonitis compared to SCT was 0.60 (40% lower) for the Y-set (P less than 0.01), 0.75 for standard UV (P less than 0.01), and similar to SCT (RR = 0.96) for the O-set (NS), all else being equal. Analysis time to second (N = 1,271) peritonitis episode gave similar results as did analysis of time to CAPD technique failure. Significantly higher RR of peritonitis and technique failure was observed for younger and black patients. These findings suggest the utilization of connection techniques with superior results.


Effects of oxygen breathing and erythropoietin on hypoxic vasodilation in uremic anemia. Loss of hypoxic vasodilation has been proposed as a causative factor in the development of hypertension in dialysis patients treated with recombinant human erythropoietin (rHuEPO). Venous occlusion plethysmography was therefore performed on 22 dialysis patients (aged 23 to 71 years, dialysis duration 6 to 260 months, 8 males) before and after correction of anemia with rHuEPO, 50 U/kg 3x/week (Hb: 7.4 +/- 0.3 vs. 10.8 +2- 0.3 g/dl, P less than 0.0001). Hypertension (greater than 15 mm Hg rise in mean BP) occurred in 11 patients. The study was performed while breathing room air and repeated after breathing 60% O2 for 10 to 12 minutes. Before rHuEPO therapy, total blood O2 content increased from 10.01 +/- 0.39 to 10.32 +/- 0.29 ml O2/100 ml blood with breathing 60% O2 (P less than 0.01). After correction of anemia it was 14.65 +/- 0.40 ml O2/100 ml blood on room air (P less than 0.001). There was a significant decrease in forearm blood flow (7.9 +/- 0.5 vs. 6.5 +/- 0.6 ml/min/100 ml tissue, P less than 0.05) and increase in forearm vascular resistance (12.8 +/- 0.1 vs. 16.8 +/- 0.2 mm Hg/ml/min/100 ml tissue, P less than 0.05) with O2 breathing prior to rHuEPO therapy in the blood pressure responders, but no change in these parameters in the group in which blood pressure remained unchanged. When all patients were studied on room air, forearm vascular resistance rose significantly after correction of anemia (13.0 +/- 0.8 vs. 16.3 +/- 0.8 mm Hg/ml/min/100 ml tissue, P less than 0.05), compared with that prior to rHuEPO therapy.(ABSTRACT TRUNCATED AT 250 WORDS)


Methylprednisolone dosage effects on peripheral lymphocyte subpopulations and eicosanoid synthesis. Glucocorticoids have a major role in the treatment of glomerular diseases. Despite recent advances in understanding of their mechanism of action, very few studies have addressed the relative advantage of the wide range of different dose regimens employed in clinical practice. We studied the effects of methylprednisolone given intravenously for three consecutive days at the doses of 1 mg/kg (group 1, N = 7; group 2, N = 5), 5 mg/kg (group 3, N = 5) or 15 mg/kg (group 4, N = 6) on total blood peripheral leukocytes and on lymphocyte subsets in patients with glomerular diseases, and investigated whether such effects were a function of the drug concentration in the blood. Since glucocorticoids have an inhibitory effect on the formation of eicosanoids in different cells, we also investigated in the same patients the effect of 1 and 15 mg/kg methylprednisolone on systemic and renal eicosanoid synthesis. Results of pharmacokinetic study showed that the three different doses of methylprednisolone we used resulted in major differences in patient's exposure to the drug, and within the same dose there was a great individual variability. By contrast the three different doses of methylprednisolone induced a comparable drop in the absolute number of lymphocytes six hours after the first injection of methylprednisolone, while 24 hours later blood lymphocyte counts returned to the pre-injection values in all patients. Analysis of lymphocyte subsets showed a selective decrease in the number of circulating CD4+ and CD8+ cells six hours after methylprednisolone which was comparable in the four groups of patients studied. As for the effect of methylprednisolone on systemic and renal eicosanoid synthesis in patients with glomerular diseases, 1 and 15 mg/kg were equally unable to reduce thromboxane A2 (TxA2) and prostaglandin E2 (PGE2) release by circulating polimorphonuclear cells (PMNs). By contrast, methylprednisolone partially inhibited eicosanoid synthesis by PMNs in vitro. Consistent with the data on PMNs, urinary excretion of TxA2 and prostacyclin (PGI2) metabolites were unaltered by the different doses of methylprednisolone. By contrast urinary PGE2 was markedly and significantly reduced in patients given 15 but not 1 mg/kg. We conclude that 1 mg/kg methylprednisolone given to patients with glomerular diseases has the same effect on peripheral total blood leukocyte count and lymphocyte subsets than 5 and 15 mg/kg. The same is true for eicosanoid synthesis by PMNs. Renal synthesis of PGE2 is inhibited by 15 mg/kg but not by 1 mg/kg.(ABSTRACT TRUNCATED AT 400 WORDS)


Using USRDS generated mortality tables to compare local ESRD mortality rates to national rates. Mortality tables of the U.S. Renal Data System allow description of national mortality rates among prevalent dialysis patients in five-year age groups and four major categories of causes of ESRD for Black and White patients. Based on these tables derived from over 50,000 deaths in dialysis patients during 1987 to 1989 a methodology is described that allows comparison of local or regional mortality rates to national rates with determination of a standardized mortality ratio and statistical significance. Since this methodology adjusts for patient age, race and cause of ESRD, it can serve as a useful tool for dialysis research and local quality assurance.


Sodium-dependent phosphate transport in a rat kidney endosomal fraction. An endosome-enriched fraction was prepared from rat kidney cortex by a standard procedure employing centrifugation on a Percoll gradient. This fraction showed time-dependent accumulation of inorganic phosphate (Pi) which was stimulated two- to threefold during the initial phase by an inwardly directed Na+ gradient. Na+ gradient-dependent Pi accumulation decreased with increasing medium osmolality and Pi binding accounted for only 16% of the total accumulation at two minutes. Like the Pi transporter in the brush border membrane (BBM), the Na+ gradient-dependent Pi uptake (but not the Na(+)-independent component) by the endosomal fraction was stimulated by intravesicular Pi and by an outwardly directed proton gradient, and was inhibited by extravesicular arsenate. Unlike the Pi transporter in BBM, the endosomal Pi transporter was not changed by acidic pH under non-gradient conditions. Activation of the endosomal proton pump by extravesicular ATP, leading to acidification of the vesicle interior, was accompanied by stimulation of endosomal Na+ gradient-dependent Pi transport. Inhibition of the proton pump by deletion of chloride or addition of N-ethylmaleimide abolished the stimulation of Pi uptake by ATP. The data indicate that the Na(+)-dependent Pi transporter in renal endosomal fractions is an intrinsic endosomal component. It remains to be determined if the endosomal Pi transporter plays a role in regulation of renal Pi transport.


Reduced capillary density in the myocardium of uremic rats--a stereological study. Using stereological techniques capillaries, interstitium and myocardial fibers were analyzed in perfusion-fixed hearts of subtotally nephrectomized male Sprague-Dawley rats with uremia of 14 months duration (or their sham-operated controls). Uremic rats had higher systolic blood pressure (140 +/- 20.3 mm Hg vs. 119 +/- 6.61 mm Hg) and left ventricular weight/body weight ratio (3.37 +/- 0.09 mg/kg vs. 2.01 +/- 0.12 mg/kg) than controls, and had slight anemia (Hct 35.0 +/- 3.16% vs. 40.4 +/- 3.3%). Length density (Lv) of capillaries, that is, capillary length per unit myocardial volume, was significantly (P < 0.001) decreased in uremia (2485 +/- 264 mm/mm3 vs. 3329 +/- 194 mm/mm3) versus controls. In parallel, surface density and volume density of the capillary lumina were also reduced (7.95 +/- 1.69 cm3/cm3 vs. 11.4 +/- 1.8 cm3/cm3) in the uremic rats. We conclude that in experimental uremia, cardiac hypertrophy is not accompanied by a commensurate increase in capillaries.


Insulin-responsive glucose transporter expression in renal microvessels and glomeruli. The insulin-responsive glucose transporter (GLUT4) is expressed at high levels in fat and skeletal muscle, which account for the majority of insulin-stimulated glucose uptake. However, GLUT4 is also expressed at lower levels in kidney and several other tissues. We have used a variety of protein and mRNA detection techniques to determine the sites of renal GLUT4 expression. Indirect immunofluorescence experiments with two specific anti-peptide antisera detected GLUT4 in the smooth muscle cells of the rat renal microvasculature, in renal glomerulus, and in cultured glomerular mesangial and epithelial cells. PCR amplification of cDNA derived from microdissected renal glomeruli, microvessels and tubules corroborated this distribution of GLUT4, and Northern blotting demonstrated GLUT4 mRNA in cultured glomerular mesangial cells. Both the immunofluorescence and PCR data suggested that GLUT4 is most highly expressed in renal microvessels. Our results show that certain renal cells, such as renal microvascular smooth muscle cells, express the insulin-responsive glucose transporter and therefore may demonstrate altered glucose uptake and metabolism in diabetes mellitus.


IGF-I binding and IGF-I mRNA expression in the post-ischemic regenerating rat kidney. The localization of IGF-I peptide and IGF-I mRNA was investigated in the post-ischemic regenerating rat kidney using immunohistochemistry and non-radioactive in situ hybridization techniques. In addition, the distribution and relative quantity of IGF-I binding sites were studied by autoradiographic ligand-binding techniques. Two and three days after the injury, morphological signs of an intense regenerative activity was evident. By this time a substantial number of the regenerating cells were stained with a monoclonal antibody against the M1 subunit of ribonucleotide reductase, a proliferative marker used. Low proliferative tubular cells, replacing those that had been injured, were seen lining the tubular basement membrane. By seven days, the morphology in the cortex was quite normalized, while cells of the S3 segments in the outer medulla remained dedifferentiated. The regenerative cells expressed IGF-I peptide and IGF-I mRNA in a transient manner and this was found to correlate better to cell differentiation than cell division. In addition, non-tubular cells, predominantly macrophages, expressed both the IGF-I peptide and the mRNA. The IGF-I binding was significantly increased in the regenerative zone at all times studied and began to decline at day seven. The binding characteristics were found to be compatible with binding to the IGF-I receptor. Altogether, these findings provide circumstantial evidence that IGF-I is of trophic importance in the regeneration of renal tubular cells. The data are compatible with a local production and action of IGF-I, suggesting an autocrine and/or paracrine mode of action during the regenerative process.


Procoagulant effect of the OKT3 monoclonal antibody: involvement of tumor necrosis factor. We recently observed that the prophylactic administration of high doses of OKT3 monoclonal antibody (MoAb) in cadaveric renal transplantation favors the development of thromboses of the grafts' main vessels and of thrombotic microangiopathies. These clinical observations led us to perform sequential determinations of plasma levels of prothrombin fragment 1 and 2 (F 1 + 2) and fibrin degradation products (FDP) after the first injection of 5 or 10 mg OKT3 given as prophylaxis in kidney transplant recipients. The values observed have been compared with those of kidney transplant recipients not treated with OKT3. F 1 + 2 levels peaked four hours after the first injection of 5 mg OKT3 (mean +/- SEM: 4.82 +/- 0.73 vs. 1.75 +/- 0.37 nmol/liter in controls, P < 0.01), indicating activation of the common pathway of the coagulation cascade. FDP levels were already above baseline values at four hours and continued to increase until 24 hours (mean +/- SEM at 24 hr, 4729 +/- 879 vs. 1038 +/- 320 ng/ml in controls, P < 0.05), indicating a fibrinolytic process. The magnitude and the time course of the changes in F 1 + 2 and FDP plasma levels were similar whether the patients received 5 or 10 mg dose of OKT3. The levels of von Willebrand factor (VWF) antigen, a molecule released by activated or damaged endothelial cells, were also significantly increased after injection of OKT3 (mean +/- SEM at 24 hr, 3.67 +/- 0.18 vs. 2.17 +/- 0.11 U/ml in controls, P < 0.05). The procoagulant effects of OKT3 were further investigated in vitro on human umbilical vein endothelial cells (HUVEC).(ABSTRACT TRUNCATED AT 250 WORDS)


Hypoxia-mediated impaired differentiation by LLC-PK1 cells: evidence based on the protein kinase C profile. We recently reported that mild hypoxia in LLC-PK1 cells, grown in standard fashion under a still layer of overlying medium at 5% CO2/18% O2 environment, result in decreased oxidative metabolism and impaired differentiated functions in comparison to adequately oxygenated cultures maintained either under a higher oxygen (36% O2) environment or conditions of continuous rocking of the media fluid. In the present study, subcellular distribution of a regulatory enzyme protein kinase C (PKC) was examined between hypoxic still and normoxic rocked LLC-PK1 cells. Subconfluent cultures of hypoxic LLC-PK1 cells exhibited significantly lower and predominantly membrane-bound PKC activity in comparison to mostly cytosolic localization of this enzyme in normoxic rocked cells. One hour of exposure of adequately oxygenated-rocked LLC-PK1 cells with the phorbol ester TPA, a dedifferentiating agent that did not effect the cell ATP content, resulted in significant inhibition of dome formation and sodium-dependent glucose transport activity, a partial loss of pH-responsive ammoniagenesis, and almost complete translocation of protein kinase C activity from cytosol to the membrane pool; all of which resembles the behavior of hypoxic still cultured cells. In addition, acute re-oxygenation of hypoxic still cultures by rocking the media fluid for one hour resulted in an increase in cell ATP content to the cellular levels of ATP observed in normoxic rocked cells. However, all the parameters of differentiation were unaffected by re-oxygenation. These studies support the notion that hypoxia can act in some primary fashion, independent of its effects on energy metabolism, to impair cellular differentiation in LLC-PK1 cells. They also raise the possibility that activation of protein kinase C may act as an important mediator in this process.


Urodilatin, not nitroprusside, combined with dopamine reverses ischemic acute renal failure. The present study was undertaken to: (a) clarify the comparative renal potency of bolus injection of the natriuretic peptides urodilatin and ANF99-126 in the rat; (b) establish whether or not intravenous (i.v.) infusion of urodilatin (200 ng/min) combined with dopamine (UD) to maintain mean arterial pressure could improve GFR or renal histology in established experimental ischemic acute renal failure (ARF) induced by 30 minutes of bilateral renal artery clamping; (c) assess comparative efficacies of nitroprusside, an activator of soluble guanylate cyclase, combined with dopamine (ND) or control infusions of dopamine alone (DA), under equivalent conditions; and (d) determine effects of intra-renal arterial infusions of the stable cGMP analogue dibutyryl-cGMP immediately after renal artery clamping (RAC). After initial dose finding studies, i.v. infusion of UD 24 hours after 30 minutes of RAC improved GFR over five hours from 0.24 +/- 0.04 to 1.0 +/- 0.16 ml/min in association with a threefold rise in plasma cGMP and a 13-fold increase in urinary cGMP excretion. Plasma creatinine dropped by 41% from 230 +/- 16 to 135 +/- 18 microM/liter and was still reduced 24 hours later with values averaging 106 +/- 14 compared to 274 +/- 53 microM/liter in non-treated animals. During infusion, UV and FENa+ increased from 1.4 +/- 0.2 to 8.3 ml/min, and from 2.9 +/- 0.5 to maximum values of 15.8 +/- 2.4%. ND or DA alone were less effective, increasing GFR only to 14 and 20%, respectively, of normal values, but improvements were not sustained; in contrast to UD, ND did not alter plasma or urinary cGMP. In addition, DBcGMP was ineffective in improving GFR during early ARF. Histologically UD, but not ND, markedly reduced the incidence of granular casts, tubular desquamation and tubular necrosis in cortical areas and increased the incidence of medullary mitoses.


Glomerular hemodynamic alterations during acute hyperinsulinemia in normal and diabetic rats. Treatment of insulin dependent diabetes invariably requires exogenous insulin to control blood glucose. Insulin treatment, independent of other factors associated with insulin dependent diabetes, may induce changes that affect glomerular function. Due to exogenous delivery of insulin in insulin dependent diabetes entering systemic circulation prior to the portal vein, plasma levels of insulin are often in excess of that observed in non-diabetics. The specific effects of hyperinsulinemia on glomerular hemodynamics have not been previously examined. Micropuncture studies were performed in control (non-diabetic), untreated diabetic and insulin-treated diabetic rats 7 to 10 days after administration of 65 mg/kg body weight streptozotocin. After the first period micropuncture measurements were obtained, 5 U of regular insulin (Humulin-R) was infused i.v., and glucose clamped at euglycemic values (80 to 120 mg/dl). Blood glucose concentration in non-diabetic controls was 99 +/- 6 mg/dl. In control rats, insulin infusion and glucose clamp increased nephron filtration rate due to decreases in both afferent and efferent arteriolar resistance (afferent greater than efferent) resulting in increased plasma flow and increased glomerular hydrostatic pressure gradient. However, insulin infusion and glucose clamp produced the opposite effect in both untreated and insulin-treated diabetic rats with afferent arteriolar vasoconstriction resulting in decreases in plasma flow, glomerular hydrostatic pressure gradient and nephron filtration rate. Thromboxane A2 (TX) synthetase inhibition partially decreased the vasoconstrictive response due to acute insulin infusion in diabetic rats preventing the decrease in nephron filtration rate.(ABSTRACT TRUNCATED AT 250 WORDS)


Alport syndrome and diffuse leiomyomatosis: deletions in the 5' end of the COL4A5 collagen gene. Alport syndrome (AS) is an hereditary glomerulonephritis that is mainly inherited as a dominant X-linked trait. Structural abnormalities in the type IV collagen alpha 5 chain gene (COL4A5), which maps to Xq22, have recently been detected in several patients with AS. The association of AS with diffuse esophageal leiomyomatosis (DL) has been reported in 24 patients, most of them also suffering from congenital cataract. The mode of transmission and the location of the gene(s) involved in this association have not been elucidated. Southern blotting using cDNA probes spanning the whole COL4A5 and a 5' end COL4A5 genomic probe showed that three out of three patients with the DL-AS association had a deletion in the 5' part of the COL4A5 gene extending beyond its 5' end. This indicates that the same gene, COL4A5, is involved in classical AS and in DL-AS and that the transmission of DL-AS is X-linked dominant. These results also suggest that leiomyomatosis might be due to the alteration of a second gene involved in smooth muscle cell proliferation, which is located upstream of the COL4A5 gene, and that there might be a contiguous gene deletion syndrome, involving at least the genes coding for congenital cataract, DL and AS.


Low-dose intravenous calcitriol treatment of secondary hyperparathyroidism in hemodialysis patients. Italian Group for the Study of Intravenous Calcitriol. Intravenous calcitriol is known to directly suppress PTH secretion and release. We evaluated the effect of four months of treatment with low-dose intravenous calcitriol on PTH levels in 83 hemodialysis patients. The criteria for including patients in the study were a serum PTH levels at least four times the normal limit, a serum total calcium less than 10 mg/dl and good control of the serum phosphorus level. All patients underwent standard bicarbonate or acetate dialysis; dialysate calcium level was maintained at the usual 3.5 mEq/liter concentration. Initial calcitriol dose was 0.87 +/- 0.02 (SEM) micrograms (0.015 micrograms/kg body wt) thrice weekly at the end of dialysis, and it was reduced in case of hypercalcemia or elevated calcium-phosphate product. Seven out of 83 patients dropped out during treatment. Among the 76 patients who completed the study, 58 (76%) showed a highly significant decrease of intact PTH levels (average reduction 48%) and of alkaline phosphatase levels after four months of therapy. Total serum calcium increased slightly but significantly in the responder group but remained unchanged in the non-responders. No significant changes in ionized calcium levels could be detected, even in responders. Treatment was well tolerated by patients, but 60% of them had transient episodes of hyperphosphatemia. Mean serum phosphate was 4.95 mg/dl at the beginning of the study. It increased significantly after four months of treatment in patients who showed a decrease of PTH levels, although it remained within acceptable limits, below 5.5 mg/dl. Twenty-eight of 76 patients (37%) reduced the dose of calcitriol because their calcium-phosphate products exceeded 60.(ABSTRACT TRUNCATED AT 250 WORDS)


On the probability that kidneys are different in autosomal dominant polycystic disease. We hypothesized that highly variable cyst fluid sodium concentrations are a characteristic of every kidney in autosomal dominant polycystic kidney disease (ADPKD). We added our data on sodium concentrations in 124 fluids from ten ADPKD kidneys to data published by others of concentrations in 32 fluids from five kidneys. The values ranged from 3 to 207 mEq/liter; none fell between 59 and 74 mEq/liter. Fluids were designated as low (< 60 mEq/liter; 50 fluids) or high (> 60 mEq/liter; 106 fluids) sodium fluids. Transmission electron microscopy identified differences in the depths of apical tight junctions between cells from cyst walls of 12 of the low and 10 of the high sodium fluids from two kidneys (mean +/- SE depths of 2039 +/- 74 A vs. 386 +/- 18 A respectively; P < 0.0001). When fluids were grouped by kidney of origin, six of the 15 kidneys had only high sodium fluids. The probability that chance had led to the sampling of only high sodium fluids in these organs, given that 32% of all fluids were low sodium fluids, was calculated at < 0.00015. The possibility must be considered that all kidneys are not alike in ADPKD.


Influence of the level of hydration on the renal response to a protein meal. Recent studies have suggested that the renal effects of high protein intake could be mediated, at least in part, by vasopressin and/or an increase in the urinary concentrating activity. The present study investigated the influence of the level of hydration, and hence of the activity of the concentrating process, on the renal response to an acute oral protein load. Clearance studies were performed before (Control) and during three hours after a protein meal (1.5 g/kg body wt protein as cooked meat) in ten healthy volunteers. This study was performed twice at a two to three week interval under either constant low (LowH) or high (HighH) hydration. In spite of the marked difference in initial diuresis (3.1 +/- 0.3 in LowH vs. 13.9 +/- 0.7 ml/min in HighH) and urine osmolality (501 +/- 42 in LowH vs. 99 +/- 3 mOsm/kg H2O in HighH), a similar relative decrease in urine flow rate was observed following the meal in both conditions. TcH2O increased progressively by 70% in LowH whereas CH2O decreased by 40% in HighH. Plasma vasopressin showed a progressive increase with time in LowH (from 1.10 +/- 0.26 in control, to 1.98 +/- 0.35 pg/ml at the third hour after the PM, P < 0.05) but not in HighH (0.53 +/- 0.09 to 0.70 +/- 0.17 pg/ml). Glomerular filtration rate (inulin clearance) increased significantly on the second post-prandial hour under LowH but not under HighH. Excretions rates of Na, Cl, K, and urea increased after the meal, however, not to the same extent nor with the same time course in the two conditions. Significant positive correlations were observed between GFR and TcH2O, urine osmolality, or the ratio of urine-to-plasma urea concentrations in LowH. These results suggest that the protein-induced hyperfiltration is partially blunted by a high water intake, and hence is dependent, directly or indirectly, on the urine concentrating activity.


Ketodiet, physiological calcium intake and native vitamin D improve renal osteodystrophy. The effects of a very low-protein diet (VLPD) supplemented with amino acids and ketoanalogues (KA) and with 1 g of calcium carbonate and 1000 IU of vitamin D2, were studied in 17 patients with advanced renal failure (GFR < or = 20 ml/min) over a period of one year. The protein intake was 0.3 g protein/kg body wt/day. Daily phosphorus and calcium intake were respectively 1,500 mg and 300 mg. Sequential bone densitometry was performed and bone histomorphometry after double tetracycline labeling was evaluated, before and after one year of diet. Calcium and phosphate metabolism parameters were monitored every two months. In spite of a significant decrease of GFR, phosphorus, parathyroid hormone (1-84) and osteocalcin plasma levels decreased significantly, while low plasma bicarbonate normalized, and calcitriol and calcium levels remained respectively low and normal. Before the diet, histological study disclosed four cases of mixed osteopathy: osteomalacia associated with osteitis fibrosa (OM/OF), nine pure osteitis fibrosa (OF) and four with normal bone remodeling (NB). After one year of diet, the OM component of OM/OF disappeared, as evidenced by a normalization of the mineral apposition rate and osteoid thickness. In the patients presenting pure OF, a significant decrease in osteoblastic and osteoclastic surfaces, in the number of osteoclasts, and in the bone formation rate (BFR) were found. Vertebral mineral density measured by quantitative computerized tomodensitometry did not change significantly. In conclusion, this study not only confirms the beneficial effects of VLPD + KA + calcium on uremic hyperparathyroid bone disease in advanced renal failure assessed using static bone histomorphometry, but also shows a correction of histodynamic bone parameters.(ABSTRACT TRUNCATED AT 250 WORDS)


Renal function 17 to 23 years after chelation therapy for childhood plumbism. An elegant retrospective description of an epidemic of chronic renal failure occurring in patients with histories of untreated childhood lead poisoning in Queensland, Australia established beyond reasonable doubt the existence of lead nephropathy. However, a retrospective uncontrolled report from Boston in 1963 refuted the claim that there are serious renal consequences of untreated childhood lead poisoning. We conducted a controlled prospective, longitudinal study to examine the effects of childhood lead poisoning on renal function 17 to 23 years after chelation therapy. The present study reports the results of renal functional tests in a unique cohort of study subjects (N = 62) with significant lead poisoning (initial PbB > 100 micrograms/dl) diagnosed and treated between 1966 and 1972 and their age-matched control siblings (N = 19; initial PbB < 40 micrograms/dl). During the past nine years serial determinations of renal function on all study subjects and control siblings were obtained. Mean values of systolic and diastolic blood pressures, serum creatinine, serum beta 2-microglobulin, fractional excretion beta 2-microglobulin, urinary protein:creatinine ratio, serum phosphate, tubular reabsorption of phosphate, serum uric acid, and urinary specific gravity were similar in study subjects compared with sibling controls. The frequency of abnormal values for these tests was similar in the two groups. Multiple linear regression analyses failed to demonstrate a significant influence of the presence of plumbism or initial PbB on serum creatinine or systolic or diastolic blood pressure. A modest increase in serum creatinine values was observed over a nine year period in four of 62 study subjects (1.4, 1.4, 1.5, 1.6 mg/dl).(ABSTRACT TRUNCATED AT 250 WORDS)


Anaphylactoid reactions associated with reuse of hollow-fiber hemodialyzers and ACE inhibitors. From July 18 through November 27, 1989, 12 anaphylactoid reactions (ARs) occurred in 10 patients at a hemodialysis center in Virginia. One patient required hospitalization; no patients died. ARs occurred within minutes of initiating dialysis and were characterized by peripheral numbness and tingling, laryngeal edema or angioedema, facial or generalized sensation of warmth, and/or nausea or vomiting. All 12 ARs occurred with dialyzers that had been reprocessed with an automated reprocessing system. A cohort study, including all patients undergoing dialysis sessions on the six days when an AR occurred, showed that the patients who experienced ARs were significantly more likely than patients who did not to be treated with angiotensin-converting enzyme (ACE) inhibitors (7/10 vs. 3/33; relative risk = 7.9; 95% confidence interval = 2.5 to 25.2) and to have been exposed to reused dialyzers rather than to new dialyzers (12/70 sessions vs. 0/31; P = 0.016). In those sessions using a reused dialyzer, the mean number of dialyzer uses in case-sessions was significantly higher than for noncase-sessions (10.3 vs. 6.2; P = 0.016). After reuse of dialyzers was discontinued at the center, no further ARs occurred, despite the continued administration of ACE inhibitors. This is the first report of an outbreak of ARs associated exclusively with reused dialyzers. We hypothesize that interactions between a dialyzer that has been repeatedly reprocessed and reused, blood, and additional factors, such as ACE inhibitors, increased the risk of developing ARs.


Decreased low-density lipoprotein receptor function and mRNA levels in lymphocytes from uremic patients. The mechanisms by which renal failure causes hyperlipoproteinemia remain unclear. To investigate the potential role of the low-density lipoprotein (LDL) receptor in lipoprotein metabolism in uremia we measured LDL receptor function in peripheral blood mononuclear cells (PBMC) from uremic patients and control subjects using a functional assay in which proliferation of lectin-stimulated PBMC in the presence of lovastatin was dependent upon internalization of exogenous cholesterol via a functional LDL receptor. The amount of LDL required to reverse 50% of lovastatin-induced inhibition of proliferation in PBMC from uremic patients was significantly greater (3.6 +/- 1.8 micrograms/ml, N = 33, P < 0.05) than controls, (1.99 +/- 0.6 micrograms/ml, N = 37). Abnormal LDL receptor function in four uremic patients normalized following renal transplantation. To investigate the molecular basis for LDL receptor dysfunction, we directly quantitated LDL receptor messenger RNA (mRNA) in PBMC from uremic patients and control subjects using a ribonuclease protection assay. LDL receptor mRNA expression in uremic patients was 0.42 +/- 0.08 (N = 10), significantly lower (P < 0.015) than in normal subjects, 0.71 +/- 0.08 (N = 14). These data suggest that an acquired defect in LDL receptor function in PBMC from uremic patients exists which may be due to decreased LDL receptor expression. These abnormalities, if present in other tissues, could contribute to the aberrant lipoprotein metabolism which is a consistent feature of uremia.


Severe defect in clearing postprandial chylomicron remnants in dialysis patients. Lipid abnormalities have been suggested as a major cause of the accelerated atherosclerosis and the high incidence of coronary heart disease in chronic renal failure patients. In the present work the postprandial lipoprotein metabolism was studied in chronic dialysis patients with or without fasting hypertriglyceridemia using the vitamin A loading test. This method investigates specifically postprandial lipoprotein metabolism. The determination of vitamin A ester level retinyl palmitate (RP) differentiates the circulating plasma chylomicron and chylomicron remnant fractions from the endogenous VLDL and IDL. Subjects with normal renal function with or without fasting hypertriglyceridemia served as control groups. Dialysis patients have significantly higher level of chylomicron remnants for a more prolonged period of time than controls, irrespective of their fasting triglyceride levels. The area below retinyl palmitate chylomicron remnants curve was 26308 +/- 12422 micrograms/liter.hr in the normolipidemic dialysis patients, significantly higher than (6393 +/- 2098 micrograms/liter.hr; P < 0.0001) in the normolipidemic controls. The retinyl palmitate chylomicron remnants curve of the hypertriglyceridemic dialysis patients was 21021 +/- 4560 micrograms/liter.hr, which was higher than 12969 +/- 2215 micrograms/liter.hr (P < 0.0001) in the hypertriglyceridemic controls. Moreover, the hypertriglyceridemic dialysis patients had an additional defect in the lipolysis metabolic step, that is, accumulation of chylomicrons in circulation. These findings show a severe defect in postprandial lipoprotein metabolism in chronic renal failure patients. The prolonged exposure of the vascular wall to high chylomicron remnant concentrations might be an important pathogenetic factor in the accelerated atherosclerosis seen in chronic dialysis patients.


IgA nephropathy in patients with congenital C9 deficiency. The clinical, histologic, and immunopathological findings of three young Japanese males with congenital C9 deficiency and primary IgA nephropathy are reported. The C9 deficiency was discovered either through mass complement screening, or when low hemolytic activity for CH50 and normal C3 levels were detected in plasma. Hematuria and proteinuria were detected at the age of 8 or 9 years as a result of annual urinary screening tests for school children. Renal biopsy showed focal and segmental mesangial proliferation with small epithelial crescents in one patient, and mild, diffuse mesangial proliferation in two. IgA and C3 were deposited predominantly in the mesangial area, and staining for C9 was negative in these patients. Electron microscopy revealed electron dense deposits predominantly in mesangial and paramesangial zones. Immunohistochemical staining in renal biopsy tissues from two patients showed mesangial staining for C5, C8, and S-protein, but staining for C5b-9 neoantigen was completely negative. These results show that the formation of C5b-9 complex is not essential for the induction of human IgA nephropathy, and also for the proliferation of mesangial and even parietal epithelial cells.


Renal histology in polycystic kidney disease with incipient and advanced renal failure. Renal specimens were obtained at surgery or postmortem from patients with autosomal dominant polycystic kidney disease (ADPKD). Patients had either serum creatinine (SCr) below 350 mumol/liter (N = 12) or terminal renal failure (N = 50). Specimens were examined by two independent observers using a carefully validated score system. Mean glomerular diameters were similar in ADPKD patients with early renal failure (176 +/- 38 microns) and in victims of traffic accidents (177 +/- 23 microns), while they were significantly greater in diabetics with comparable renal function (205 +/- 16 microns). Glomerular diameters in ADPKD patients with terminal renal failure (191 +/- 45 microns) and with early renal failure were not significantly different. On average, 29% of glomeruli (17 to 62) were globally sclerosed in early renal failure, and 49% (19 to 93) in terminal renal failure. The proportion of glomeruli with segmental sclerosis was less than 4% in both groups. Marked vascular sclerosis, interstitial fibrosis, and tubular atrophy were present in early renal failure, and even more so in terminal renal failure. Interstitial infiltrates were scarce and consisted mainly of CD4 positive lymphocytes and CD68 positive macrophages. Immunestaining with monoclonal renin antibodies showed an increased juxtaglomerular index and expression of renin by arterioles adjacent to cysts, as well as by cyst wall epithelia. The data show more severe vascular and interstitial, but not glomerular, changes in ADPKD with advanced as compared to early renal failure.


[Surgical treatment of congenital aneurysm of the internal jugular vein in children]. In the pathogenesis of aneurysm of the internal jugular vein, the loss of its capacity function hampering blood outflow from the cranial cavity is of leading importance. Disorders in cerebral hemodynamics registered in rheoencephalography were revealed in all the patients examined. In 40% of them, the signs of venous encephalopathy were noted. Thus, presence of an aneurysm is an indication for operative intervention. The operation under the conditions of growing organism together with elimination of aneurysm is aimed at restoration of capacity function of the internal jugular vein and ensuring of its growth. Circular resection of aneurysm with end-to-end suturing of the vein and extravasal plasty with the use of polyurethane perforated tubular protector cut in a screw-shaped manner is an adequate operation.


[Use of ultraviolet irradiation of the blood after surgery in patients with tumors]. The results of ultra-violet irradiation of the blood in 207 patients after performance of thoracoabdominal operation for cancer of the esophagus and stomach were analysed. The method permits to reduce the incidence of postoperative complications, manifestations of endogenous intoxication, contributes to improvement in metabolic processes, and normalization of the state of the patients.


[Preclinical study of the general toxic effect of polyplatillen]. Toxic action of polyplatillen, a principally new platinum compound, was studied on laboratory animals and cell culture. When compared with cis-dichlorodiamminplatinum, the preparation is 10-fold less toxic in animals and 100-fold--in the cellular systems. Reversibility of damaging action of polyplatillen at "non-toxic" dosages conditions the perspectiveness of its further clinical trials.


[Radiologic diagnosis of Payr disease in children]. The experience with diagnosis of Payr disease in 119 children with the use of a roentgenologic method, in particular, irrigoscopy was summarized. Falling of the right colic flexure with formation of abrupt kinks of the transverse colon, and retention of contrast substance in the right portion of the large intestine are the main roentgenologic signs of the Payr disease.


[Ultrasound diagnosis of pyloric stenosis in young children]. The results of observation of 12 children ranging in age from 1 to 4 mos with tentative diagnosis of pyloric stenosis are presented. The study was performed by special method, using "Aloka" SSD-280 (Japan) ultrasound apparatus. The characteristic symptoms of the disease were revealed in 9 children, diagnosis of pyloric stenosis was confirmed by means of endoscopy, palpation, and intraoperatively. The use of US is practically harmless, and can completely substitute for a roentgenologic method in detecting the given congenital pathology.


[Current functional methods for investigating the rectoanal region in children]. Continuous rectoanal profilometry and electromanometry with the use of original three-channel "Electronika A-1" apparatus were performed in 40 children. The technique for performance of investigations is described, the scheme for deciphering of the results is given.


[Hemosorption with the use of porcine spleen in the treatment of purulent-septic diseases in children]. In 14 children with purulent septic diseases, the method of biohemosorption with the use of a porcine spleen was used. In 13 children, the treatment was effective. One child with bilateral uretherohydronephrosis, pyonephrosis, urosepsis, signs of aggravating polyorganic failure died. The data obtained are indicative of the expediency to use biohemosorption for treatment of children with purulent septic diseases.


[Diagnosis and therapy of tumors and tumor-like formations of the stomach and intestine in children]. The experience with diagnosis and treatment of 45 children at the age of from 2 mos to 15 yrs with tumours and tumour-like formations of the stomach and intestine was summarized. Most frequently (more than in 60% of cases), lymphosarcoma was revealed, cancer--in 4.4% of cases. The main causes of diagnostic errors--ignoring the data of history, wrong interpretation of the results of palpation of the abdomen, incomplete examination of a patient and absence of oncologic suspiciousness in a physician. Results of treatment of the patients with malignant masses depended on a stage of the disease.


[Comprehensive evaluation of long-term results of surgical treatment and principles of postoperative rehabilitation of children with anorectal atresia]. The examination and treatment of 22 children at the age of from 2 to 14 years after surgical correction of fistulous forms of atresia of the anus and rectum was carried out. In all the patients, besides of general clinical investigations, the special studies of the large intestine with the use of roentgenologic and functional methods were performed. A scale-table for assessment of a degree of anal incompetence have been developed, criteria for choice of rational tactics for rehabilitation of the patients established.


[Cysts and cyst-like formations of the abdominal cavity and retroperitoneal space in children]. The results of surgical treatment of 29 children with cysts, and 10--with cyst-like formations of the abdominal cavity and retroperitoneal space are described. In majority of the patients, a cyst at the terminal stage was revealed. In presence of complications, they were operated on with tentative diagnosis of acute appendicitis, or ileus. The operation consisted of cyst enucleation, its elimination with resection, or removal of the organ, creation of cystodigestive anastomosis. Postoperative lethality was 12.8%.


[Immunocorrective effect of hemosorption in the comprehensive therapy of malignant tumors in children]. In 25 children with malignant tumours of the retroperitoneal space and mediastinum, hemosorption was performed before and after operation in combination with chemotherapy with the aim of immunocorrection and detoxication of an organism. Under the influence of hemosorption, the general state of the patients improved, their immune status normalized permitting not to interrupt a course of chemotherapy.


[The use of diagnostic and therapeutic colonofibroscopy in children]. The results of investigation of the large intestine in 187 children were analysed. Of them, in 28 the terminal ileum was as well examined. In 38 patients with polyps and intestinal invagination, colonoscopy was performed in combination with endoscopy. Colonofibroscopy was used as a primary method of study to establish the causes of intestinal hemorrhage, colitis syndrome. The method has a high informative value, permits to extend the diagnostic and therapeutic possibilities in pediatric proctology.


[Stages of intestinal invagination in children]. The results of observation of 143 children with intestinal invagination are presented. In 105 patients, the disease was at the stage of compensation, in 27--subcompensation, in 10--decompensation. According to the data of clinical and laboratory investigations, the most pronounced changes in homeostasis were noted in children with intestinal invagination at the late stage. The measures aimed at stabilization of hemodynamics, improvement of microcirculation were carried out. In to the complex of treatment, the methods of extracorporeal detoxication of an organism and intestinal intubation going ahead of aggravation of toxemia were included.


[Prognostic value of blood indices in children with acute appendicitis]. The results of comparative analysis of blood formula, volume and cellular content of peritoneal effusion in children operated on for acute appendicitis are presented. In unfavourable course of the postoperative period, a significant decrease in content of neutrophil granulocytes in the peripheric blood and its increase in the peritoneal effusion as compared with the indices in the control group was noted.


[Diagnosis and treatment of intestinal obstruction in children in the inter-district pediatric surgery department]. Within 25 years, 302 children with different forms of acquired ileus were treated at the inter-district surgical department. Intestinal invagination was revealed in 221 patient. In the complex of diagnostic and therapeutic measures, intravenous administration of "chromosmon", through insufflation of the intestine were employed. Intestinal intubation was performed by means of a magnet-dependent tube of original construction. Lethality was 0.3%.


[Cryosurgical method of therapy for congenital vascular lesions in children]. The experience with the use of a cryosurgical method in the out-patient treatment of 3112 children of different age with congenital vascular formations was summarized. In the total structure of neoplasms, capillary hemangioma was predominant. The original apparatus was used with exposure of from 10 to 45 sec. The results of follow-up of the patients for 2 to 5 years are presented. A good cosmetic and functional result was noted in 96.2% of patients.


[Laparoscopy in the diagnosis of abdominal diseases in children]. The results of laparoscopy performed in 1988-1990 in 112 children with tumours and cysts of the abdominal cavity, with diseases of the liver and bile ducts are presented. Of them in 60%, the puncture biopsy was performed. Use of laparoscopy in 64.28% of the sufferers with closed abdominal trauma permitted to avoid performance of needless laparotomy. For suspected acute appendicitis, laparoscopy was performed in 80 patients: in 36 of them, no signs of the disease were revealed, in 14--other diseases were detected, in 30--diagnosis was confirmed. A high informative value of the given method in the diagnosis of abdominal diseases in children was noted.


[Study of large intestinal microflora in newborns with Hirschsprung disease]. In 35 newborns and children at the age under 4 mos with Hirschsprung's disease, colonic microflora was studied. Disbacteriosis at phase 1 was revealed in 1 (2.9%) child, at phase 2--in 7 (20%), at phase 3--in 27 (77.1%). In acute form of Hirschsprung's disease, in 68.5% of cases, disbacteriosis at phase 3 with the signs of enterocolitis causing acute ileus was revealed. Intestinal perforation against background of enterocolitis developed in 8 cases.


[Effect of intravascular laser therapy on the rheologic properties of blood in children with bilateral destructive pneumonia]. The effect of intravascular blood irradiation with helium-neon laser in 20 children with bilateral destructive pneumonia at a dose of 10-30 J/cm2 for a course of treatment on indices of hemostasis and rheologic blood properties was studied. Decrease in blood viscosity, hypocoagulative effect of intravascular laser therapy, normalization of clinico-roentgenologic data were revealed.


[Modified technique of the Ivanissevich operation for varicocele in children]. On the basis of the results of rheotesticulographic studies in 38 children with left-sided II-III degree varicocele, the impairment in hemodynamics in the testicle at the involved side was established. No suppression of androgen function of the organ was revealed. The expediency to perform in patients of pediatric and young age the Ivanissevich operation, the effectiveness of which is increased in use of intraoperative phlebotesticulography was noted. The effective method for varicocele treatment in children has been suggested. The testicular vein is ligated near the deep inguinal ring as well as at the level of the upper third, then it is excised between the ligatures together with the deviating branches. The method was used in treatment of 120 patients with II-III degree varicocele. No disease recurrence is noted during 1.5 years.


[Value of dacryocystography in diagnosis of lacrimal duct diseases]. The paper compares the preoperative localization of stenosis in the lacrimal passage after digital dacryocystography with the operative findings in 23 eyes of 22 patients in the years 1988 to 1991 at the Munich University Eye Hospital. In a very high percentage (95.6%) there is a positive correlation. The discussion shows the advantages of the method and includes a review of relevant literature.


[Change in the etiology and sequelae of severe eye injuries. A comparison of 197 personal patient admissions with other reports from the literature]. The spectrum of severe eye-injuries has clearly changed. We have analysed the documents of 197 patients treated in our clinic from 1988-1990. Of 119 (60.4%) contusions and 78 (39.6%) perforating injuries only 25.3% were occupational accidents. A more detailed analysis showed above all an increase of sport- and leisure-injuries and a considerable decrease of traffic-injuries (4.6%). Shocking is in contrast the percentage (10.7%) of severe injuries by brutality. More details concerning the consequences of injuries are presented and compared with older statistics. From this conclusions are drawn for better prophylaxis.


[Aesthesiometry of the cornea after refractive corneal surgery]. The corneal sensibility was examined with the aesthesiometer of Draeger in 41 patients after refractive corneal surgery, 31 patients after radial keratotomy, 5 after epikeratophakia, 5 after excimer laser ablation. It could be shown that after radial corneal incisions the sensibility remains normal. After epikeratophakia the corneal sensibility is asensible even 3 years after operation. The lenticle periphery shows an increase of sensibility after 6 months. Excimer patients with "haze" showed a significant hyposensibility in the centre. The central sensibility showed normal values after a normal corneal wound healing.


[Results of the bimedial muscle belt].

[Results of the bimedial muscle belt]. The effectivity of a retroequatorial muscle belt operation, modification of Cüppers' Fadenoperation, is demonstrated by its results in 206 patients with excess esotropia at near and variable angle esotropia. It is shown that this procedure can reduce excess esotropia at near by a significant amount and lessen the extent of variable angle esotropia without causing incomitance in horizontal eye motility. A belt, placed bimedially on both recti muscles, showed to be twice as effective on the deviation at near as on the angle at distance. Proposing a similar mode of action, the atraumatic fixation with the muscle belt can facilitate reoperations in comparison with the Fadenoperation. Damage to the muscle is limited to a minimum.


[Persistence and transient conjunctival pathogen colonization before planned intraocular interventions]. The risk of a postoperative endophthalmitis is influenced by the presence of a significant bacterial colonisation of the conjunctiva before intraocular surgery. Between February and August 1990 we performed conjunctival smears in 481 patients 1) on the eve of the operation and 2) just before planned intraocular surgery, to evaluate a persistent or transient microbial colonisation of the conjunctiva. 352 patients showed insignificant ("negative") and 129 patients a significant ("positive") bacterial growth in the first conjunctival smear. 96% of the patients (n = 336) had a negative result in both smears. 30% of the patients (n = 37) with a positive conjunctival smear showed a persisting bacterial colonisation, whereas 70% of the patients (n = 92) had a transient colonisation of the conjunctiva with a negative second smear. As a persisting microbial colonisation of the conjunctiva may be an important factor for the development of postoperative endophthalmitis, we recommend prophylactic conjunctival smears before surgery to diminish the risk of intraocular infections after surgery.


[Clinical and fluorescein angiography findings in patients with retinal vein occlusion. A unicenter study of 211 patients]. Between january 1986 and december 1989 we prospectively studied 211 patients with branch retinal vein occlusion (BRVO). Documented by fundus photography and fluorescein angiography clinical and angiographic findings were analysed. The age ranged from 28 to 83 with a mean of 63 years. 104 (48.8%) patients were male, 107 (51.2%) female. 51.1% right and 48.9% left eyes were affected. Mean visual acuity was 20/60. A non ischemic type of BRVO was found in 46.9% and an ischemic in 53.1% of the patients. The mean visual acuity in the non ischemic type was 20/50 and significantly better (p = 0.008) than in the ischemic type with a mean visual acuity of 20/60 (Mann-Whitney test). Preretinal neovascularisation was found in 14.7% and iris neovascularisation in 0.9%. One main branch was occluded in 82.9% and two main branches in 17.1%. The temporal superior quadrant was affected in 51.7%, the temporal inferior in 28%, the nasal inferior in 2.8% and the nasal superior in 0.5%. Hemisperical inferior BRVO were found in 8.1% and hemisperical superior in 5.7% of the patients. A BRVO in the fellow eye occurred in 8.5% and a CRVO in the other eye in 3.8%. Cystoid macular edema was present in 46.4%, a combination of cystoid and ischemic maculopathy in 23.7%, and ischemic maculopathy was found in 10%. Density of intraretinal hemorrhages was significantly (p = 0.046) and type of maculopathy highly significant (p < 0.0001) related to the ischemia type (Chi-square method).


[Cosmetic lower eyelid blepharoplasties]. Between April 1988 and December 1991 42 patients underwent a bilateral lower eyelid blepharoplasty. Depending on the etiology either a skin-muscle-flap or a skin-flap technique was used. When the lid was lax, it was shortened by a wedge-resection to prevent postoperative ectropion. The results were satisfactory with either technique.


[Extracapsular cataract extraction with phacoemulsification and pars plana vitrectomy with silicone oil tamponade in one session]. In phacic eyes the development of a cataract is induced by silicon oil. In this case the lens has to be removed in a second operation with or without intraocular lens implantation. In cataract surgery a new incision technique is used, which makes it easily possible to combine both operations in one session. A feature of the new incision technique is that a scleral tunnel is dissected before the anterior chamber is opened. The opening closes itself, if the intraocular pressure rises. The danger, that a rise in intraocular pressure during the vitrectomy makes an irisprolaps, for example during the substitution of perfluorcarbon by silicon oil, no longer exists. The operation technique and the postoperative course of three patients with intraocular lens implantation and pars-plana-vitrectomy using silicon oil is reported. By using the new incision technique in cataract surgery intraoperative complications during vitrectomy like an irisprolaps or penetration of silicon oil into the anterior chamber no longer exist. In selected cases one operation is saved for the patient.


[A new program for calculating intraocular lenses]. A principally new programme is described which overcomes the disadvantages of the usual calculation methods. It is based on the application of each surface of the optical system. The point for the anterior chamber lens is chosen in dependence on the anterior chamber depth; for the posterior chamber lens on the posterior surface of the eye lens. The programme is able to calculate 12 different cases. In each case calculations are made for intraocular lens power, aniseikonia and anisometropia. The calculations are made for possible emmetropia as well as for intended myopia or hypermetropia corresponding to the other eye. The programme can also be used to estimate the effect of mistakes made by measuring the single parameters, for instance: refraction, corneal curvature, eye length, anterior chamber depth. Compared to the SRK II-equation the results of the new programme are much more precise.