[Konno procedure for congenital aortic stenosis associated with complex left ventricular outflow tract obstruction].

Two successful cases of Konno procedure for congenital aortic stenosis and left ventricular outflow tract obstruction (LVOTO) were reported herein. A 3-year-old child previously underwent definitive repair of complete atrioventricular septal defect. Follow-up echocardiography revealed progression of valvular aortic stenosis and subaortic tunnel stenosis. Second patient was a 30-year-old male with congenital aortic stenosis, severe LVOTO and funnel chest. Both patients underwent Konno procedure, and their postoperative courses were uneventful. The Konno procedure is effective and stenotic lesion could be enlarged sufficiently even in complex LVOTO. Especially in the patient of advanced age, care should be taken to fragility of the left ventricular muscle and coronary malperfusion caused by the procedure itself.

Mechanism of methylmercury efflux from cultured astrocytes.

To study the mechanism of methylmercury (MeHg) efflux from the central nervous system cells, cultured astroglia obtained from neonatal rats were incubated with 10 microM MeHg-cysteine (CySH) for 30 min. After being washed four times, cells were incubated in Hg-free medium, and the release of MeHg from the cells was monitored. The amount of MeHg released in the medium approached a plateau level (ca. 31% of the loaded amount) at 4 hr. Treatment of the cells with a CySH precursor, 2-oxothiazolidine-4-carboxylic acid (OTC), resulted in a significant increase of cellular levels of CySH and glutathione (GSH). OTC also increased 1.5-fold the MeHg efflux from the loaded cells. Another GSH enhancer, GSH isopropyl ester, also stimulated MeHg export from the cells. Ion-exchange column chromatography using DEAE-Sephadex revealed that the MeHg metabolite thus released was exclusively MeHg-GSH conjugate, both with and without OTC. Since the MeHg efflux was suppressed significantly by the presence of probenecid, the efflux occurred via the probenecid-sensitive organic acid transport system. Even though the cellular GSH levels were depleted drastically by treatment with L-buthionine-(S,R)-sulfoximine (BSO), a considerable level (90% of the control) of Hg efflux was detected. Since neither GSH- nor CySH-MeHg was detected in the culture medium of the BSO-treated cells, GSH depletion may trigger some other secretion system(s) in the cells. These results suggest that conjugation with GSH is the major pathway for MeHg efflux in rat astroglia, and that elevation in the cellular GSH level would possibly be a logical therapy for MeHg poisoning, promoting the accelerated elimination of MeHg from the critical tissues.

Treatment of cerebrotendinous xanthomatosis: effects of chenodeoxycholic acid, pravastatin, and combined use.

Treatments by oral administration of chenodeoxycholic acid (CDCA) alone, 3-hydroxy-3-methylglutaryl (HMG) CoA reductase inhibitor (pravastatin) alone, and combination of the two drugs were attempted for 7 patients with cerebrotendinous xanthomatosis (CTX). CDCA treatment at a dose of 300 mg/day reduced serum cholestanol (67.3% reduction), lathosterol (50.8%), campesterol (61.7%) and sitosterol (12.7%). However, the sera of the patients changed to be "atherogenic"; total cholesterol, triglyceride and low-density lipoprotein (LDL)-cholesterol were increased, while high-density lipoprotein (HDL)-cholesterol was decreased. Contrarily, pravastatin at a dose of 10 mg/day improved the sera of the patients to be markedly "anti-atherogenic", but the reductions of cholestanol (30.4%), lathosterol (44.0%), campesterol (22.9%) and sitosterol (9.6%) were inadequate. Combined treatment with CDCA and pravastatin showed good overlapping of the effects of each drug alone. The sera of the patients were apparently more "anti-atherogenic" than those after CDCA treatment. Serum cholestanol concentration was still 2.7 times higher than in controls, but the serum lathosterol level was within the normal range, indicating that the enhancement of overall cholesterol synthesis in the patients was sufficiently suppressed. Plant sterol levels were also within the normal range. The combination of CDCA and pravastatin was a good treatment for CTX, based on the improvement of serum lipoprotein metabolism, the suppression of cholesterol synthesis, and reductions of cholestanol and plant sterol levels. In all of 7 patients, the progression of disease was arrested, but dramatic effects on clinical manifestations, xanthoma, and electrophysiological findings could not be found after the treatment of these drugs.

Muscular involvement in lysosomal acid lipase deficiency in rats.

We investigated the pathological and biochemical changes of skeletal muscle in rats with lysosomal acid lipase deficiency, which is an animal counterpart of human Wolman's disease. In the affected rats, the acid lipase activity for three different substrates, 4-methylumbelliferyl-oleate (18.9% of the normal control level), [14C]cholesteryl oleate (23.5%), and [14C]triolein (26.9%), was similarly decreased in the lysosomal fraction of skeletal muscle which was obtained by differential centrifugation. Histochemical studies showed that acid phosphatase activity was high in the endomysium and perimysium and in some muscle fibers. Some fibers showed vacuolar degeneration resembling "rimmed vacuoles". Ultrastructural studies demonstrated many membrane-bound lipid droplets in the muscle fibers, especially in the subsarcolemmal space, indicating that a low density lipoprotein (LDL) uptake pathway apparently existed in the muscle cells. However, such lipid accumulation was much greater in the interstitial cells and the endothelial cells. This distribution also suggests that LDL/cholesterol is supplied to muscle cells predominantly through endothelial cells.

Treatment of cerebrotendinous xanthomatosis with low-density lipoprotein (LDL)-apheresis.

We studied the effects of LDL-apheresis on the biochemical and clinical abnormalities of 5 patients with cerebrotendinous xanthomatosis (CTX). Levels of both cholestanol and cholesterol decreased to approximately 60% of those of pretreatment after one perfusion and gradually returned to their initial levels within 2 weeks. Improvement of clinical manifestations and regression of Achilles tendon xanthomas were detected after several perfusions, though dramatic changes could not be recognized. EEG abnormalities were improved immediately after LDL-apheresis in one patient. We conclude that LDL-apheresis may affect the serum cholestanol level and clinical manifestations in patients with CTX.

Cerebrotendinous xanthomatosis: clinical and biochemical evaluation of eight patients and review of the literature.

We present the clinical and laboratory findings of 8 patients with cerebrotendinous xanthomatosis. The clinical features consisted of a combination of bilateral Achilles tendon xanthomas, cataracts, low intelligence, pyramidal signs, cerebellar signs, convulsions, peripheral neuropathy, foot deformity, cardiovascular disease or atherosclerosis, EEG abnormality, and increased CSF protein. Increased cholesterol was present in the serum, CSF and red cell membrane of all 8 patients. The bile of one patient with late age onset of the disease showed an attenuated production of bile acids and bile alcohols. Three of the 7 had obstruction and/or marked narrowing of the coronary arteries. Data on 136 patients reported throughout the world are reviewed.

Atherogenic risk factors in cerebrotendinous xanthomatosis.

In a study of coronary artery disease in patients with cerebrotendinous xanthomatosis (CTX), we documented the presence or absence of atherogenic risk factors and performed detailed analyses of serum lipid and lipoprotein profiles. Four of the seven patients examined had coronary arterial narrowing and/or obstruction, but multiple atherogenic risk factors were not found in any of these patients. Total cholesterol (T.ch) levels and low density lipoprotein-cholesterol (LDL-ch) levels were lower, and high density lipoprotein2-cholesterol (HDL2-ch) levels were higher in CTX patients than in controls. Triglyceride and very low density lipoprotein (VLDL) levels were significantly lower in the former. Indices correlating with the risk of atherosclerosis, such as the atherogenic index, and the ratios of apolipoprotein B/apolipoprotein AI, HDL2-ch/LDL-ch, HDL2-ch/HDL3-ch, indicated that CTX serum was, in fact, 'anti-atherogenic'. However, coronary artery disease is frequently seen in patients with CTX. This discrepancy suggests the existence of a unique mechanism by which atherosclerosis is induced in patients with CTX. We discuss a mechanism of disturbed lipoprotein metabolism which might be responsible for the deposition of sterols in the tissues of patients with CTX.

Identification of (23S)-5 alpha-cholestane-3 alpha,7 alpha,12 alpha,23,25-pentol in urine of patients with cerebrotendinous xanthomatosis.

This paper describes the identification of a new bile alcohol possessing the 5 alpha-cholestane structure that was found in the urine of patients with cerebrotendinous xanthomatosis. The urine samples were extracted with reversed-phase resin, treated with beta-glucuronidase, and separated on silica gel and reversed-phase column chromatography. The new bile alcohol isolated was the second component of the urinary bile alcohols and was identified as (23S)-5 alpha-cholestane-3 alpha,7 alpha,12 alpha,23,25-pentol by means of gas-liquid chromatography/mass spectrometry and nuclear magnetic resonance spectroscopic studies.

Blood dolichols in a patient with abetalipoproteinaemia.

Dolichol and dolichyl derivatives have an important function as glycosyl carriers in the assembly of the N-asparaginyl-linked oligosaccharide core region of glycoproteins. Dolichols are synthesized through the cholesterol biosynthesis pathways in all mammalian organs and are present in all tissues, and are also associated with lipoproteins in the blood circulation. However, the origin and metabolic pathway of blood dolichols remain unknown. Abetalipoproteinaemia is a disorder of the secretion of very low-density lipoprotein (VLDL) from the liver and of chylomicrons from the intestine into the blood circulation. Therefore, examination of blood dolichols in this disorder may provide valuable information on their origin and metabolic pathway. Dolichols were exclusively associated with the high-density lipoprotein (HDL) fraction (80.7 +/- 6.3% of total dolichols) in control human blood. Serum from a patient also contained dolichols in the HDL fraction (82.8% of total dolichols). The total amount of dolichols was higher in the patient (207.0 ng/mL) than in the controls (106.2 +/- 22.7 ng/mL, n = 14). The compositions of dolichols were very similar to each other. These results indicated that, at least in the patient with abetalipoproteinaemia, the HDL-associated dolichols were possibly derived from the liver not through other lipoproteins but through dolichol transfer protein, or were possibly taken up and carried by HDL from peripheral tissues.

Successful surgical treatment of pulmonary artery sling and partial anomalous pulmonary venous drainage in an infant.

A 8 month old infant with pulmonary artery sling and partial anomalous pulmonary venous drainage was reported. The patient was seen initially with severe stridor. Diagnosis was made by barium swallow study, echocardiography, bronchoscopy, and pulmonary arteriography. The patient was operated on through a median sternotomy; the left pulmonary artery was dissected deep between the trachea and esophagus, and then reimplanted to the side of the main pulmonary artery. Systemic heparinization and microsurgical technique were used. Simultaneous intracardiac repair was carried out by means of extracorporeal circulation. The patient improved dramatically after operation. Postoperative pulmonary arteriogram revealed a wide patent left pulmonary artery, and postoperative perfusion lung scan confirmed improved perfusion of the left lung. It is concluded that pulmonary artery sling should be treated surgically as soon as diagnosed. From the surgical point of view, the left pulmonary artery should be anastomosed to the main pulmonary artery with micro-surgical technique to avoid late occlusion of the left pulmonary artery.

Spontaneous echo contrast in descending aorta correlates with low blood-flow velocity in carotid arteries and hemostatic abnormalities.

Spontaneous echo contrast in the descending aorta (DA-SEC) was examined as a possible risk factor for cerebral thromboembolism. In 19 patients (10 males, 9 females) in the chronic stage of cerebral infarction, abnormal findings by transesophageal echocardiography, flow dynamics of the common carotid artery (CCA), and hemostatic factors including blood coagulation and fibrinolysis were investigated. In nine patients, DA-SEC was detected, and SEC in left atrium (LA-SEC) was detected in nine patients. The DA-SEC positive group showed decreased blood-flow velocity (BFV) in bilateral CCA, high levels of thrombin-antithrombin III complex (TAT) and prothrombin fragment 1.2 (F1+2), a decrease in platelet count and a slight increase in D-dimer, which means an activated state of thrombin generation and resulting fibrinolysis, compared to the DA-SEC negative group. On the other hand, the LA-SEC positive group showed normal BFV in CCA and only a slight increase in D-dimer. We conclude that the condition producing DA-SEC is a stronger risk factor for cerebral infarction than that producing LA-SEC.

High cellular atypia in a pulmonary tumorlet. Report of a case with cytologic findings.

BACKGROUND: Pulmonary tumorlets are localized lesions of neuroendocrine cell proliferation, usually found in association with chronic pulmonary inflammation. Since they are mostly incidental histologic or radiologic discoveries, they have received little attention, and there have been no reports on their detailed cytology. We describe for the first time the cytologic features of a pulmonary tumorlet and discuss its differential diagnosis. CASE: An abnormal nodule in the right lung field was discovered on a regular checkup by chest roentgenogram in a 70-year-old, nonsmoking female. Intraoperative aspiration cytology demonstrated cohesive, spindle-shaped cells arranged in fascicles or singly. Since these cells showed nuclear atypia, such as hyperchromasia, a coarsely granular chromatin pattern and nuclear grooving, a nonepithelial malignant lesion was suspected and upper lobectomy performed. The final diagnosis was a pulmonary tumorlet on the basis of histologic examination of the resected material. CONCLUSION: This is the first cytologic report of a pulmonary tumorlet. In this case, differential diagnosis was made of a tumor consisting predominantly of spindle-shaped cells. Although cytologic findings included nuclear atypia, the lesion was not malignant.

Cytology of primary pulmonary meningioma. Report of the first multiple case.

BACKGROUND: Ectopic meningiomas arising in the lung are rare. We report here the first multiple primary case diagnosed by intraoperative imprint cytology. CASE: Asymptomatic pulmonary nodules, two in the left and three in the right lung, were found in a 61-year-old woman, and video-assisted thoracoscopic surgery was undertaken. Because the largest tumor was diagnosed as a meningioma by intraoperative imprint cytology using an excised biopsy specimen, further resection was not performed immediately. Histopathologically the tumor was characterized by whorled nests of cells accompanied by psammoma bodies intermingled with a fibrous pattern. The diagnosis was a transitional meningioma, positive for vimentin and epithelial membrane antigen and negative for keratin immunohistochemically. All the nodules were subsequently surgically resected and showed a similar cytohistologic appearance. Ultrastructurally the tumor cells demonstrated interdigitation of adjacent plasma membranes with numerous desmosomes and hemidesmosomes, typical of meningiomas. We failed to detect another primary tumor in the nervous system, and at this writing the patient was healthy three years after the operation. CONCLUSION: Because of the characteristic cytomorphologic features of primary pulmonary meningioma, the cytologic approach provides useful information for therapy.

[Hypothyroidism with increased serum levels of cholestanol and bile alcohol--analogous symptoms to cerebrotendinous xanthomatosis].

We reported a 53-year-old woman with hypothyroidism due to ectopic thyroid gland. She showed intellectual impairment, bilateral pyramidal tract sings, slight cerebellar signs, and degenerative changes of brain white matter on CT and MRI, which were similar to symptoms and signs in cerebrotendinous xanthomatosis (CTX). We found increases of serum cholestanol in the patient and additional 3 patients with hypothyroidism. Total bile alcohol was also increased in the serum of the patients. We speculate that hypothyroidism and CTX might have a similar pathophysiological background on the development of neurological complications and atherosclerosis.

[A case of rigid spine syndrome associated with severe respiratory failure].

Rigid spine syndrome (RSS) is clinically characterized by progressive limitation of flexion of the spine and contractures of other joints. We herein report a 27-year-old man with RSS, who underwent tracheotomy because of severe restrictive respiratory failure. He had limitation of neck flexion and proximal muscle weakness from early childhood and was diagnosed as having muscular dystrophy at 16 years old. He was suffered from dyspnea and his first tracheotomy was performed at 24 years old. Two years later, the second tracheotomy was done because his respiratory failure was aggravated. He had limitation of spine flexion, scoliosis, but no limited range of elbow and wrist joints movement except mild contracture of ankle joints. Serum CK level was elevated to 590 IU/L. Repeated ECG examinations showed negative T wave but no conduction block. In his family, his parents and brother had neither similar clinical symptoms nor heart block. Chest X-ray study showed elevated diaphragm and enlarged heart shadow (CTR = 65%). Percent VC and FEV1 in sitting position were 14.6% and 100%, respectively. Arterial blood gas analysis showed PaO2 of 34.2 mmHg and PaCO2 of 77.2 mmHg. The density of paraspinal muscle in CT scan was severely decreased. Needle EMG showed myogenic change. Muscle biopsy from left biceps brachii showed myopathic change with mild type 2 fiber grouping. After the second tracheotomy, he was on a respiratory during sleep but mostly off in the daytime. His clinical features are different from Emery-Dreifuss muscular dystrophy because he had no heart conduction block and no family history, but progressive respiratory failure.(ABSTRACT TRUNCATED AT 250 WORDS)

[Encephalopathy induced by fleroxacin in a patient with Machado-Joseph disease].

Convulsive seizure with unconciousness is an adverse effect of new quinolone antibiotics including fleroxacin. A block of GABA receptor in CNS has been reported as pathomechanism. A 48-year-old female patient with Machado-Joseph disease (MJD) had encephalopathy induced by fleroxacin. She revealed unconsciousness after the administration of fleroxacin (200mg/day) for three days. Electroencephrogram (EEG) showed diffuse slow waves. The administration was discontinued and her consciousness became clear after a day. The abnormal findings on EEG disappeared gradually. The concentrations of fleroxacin were within normal limits in serum and cerebrospinal fluid. The patient with MJD might have a tendency to develop encephalopathy by fleroxacin, because the GABA-ergic nervous system could be involved in MJD.

[Lewis-Sumner syndrome presenting unilateral quadriceps amyotrophy as an initial symptom].

We report a 55-year-old man with a chief complaint of wasting and weakness of the left quadriceps muscle. At age 54, he noticed difficulty in running and weakness in the left thigh, which gradually progressed. On the first admission to our hospital, based on the nerve conduction studies (NCS), the muscle biopsy findings showing neurologenic changes, and no abnormality of spinal MRI, we diagnosed as unilateral quadriceps amyotrophy, which resulted from an atypical form of spinal progressive muscular atrophy. One year later, he showed the bilateral hand weakness, conduction blocks on the right median and ulnar nerves by NCS, and the presence of serum anti-GM 1 antibody. From these findings, Lewis-Sumner syndrome was diagnosed. The therapy of high-dose intravenous immunoglobulin moderately improved his symptoms. The clinical symptoms of quadriceps amyotrophy is produced by various disorders including spinal progressive muscular atrophy, spinal extradural arachnoid cyst, rimmed vacuole myopathy, Becker dystrophy, limb-girdle dystrophy, and focal myositis. However, there have been no reports of a case of Lewis-Sumner syndrome. It is important to consider Lewis-Sumner syndrome in the differential diagnosis of quadriceps amyotrophy.

[Dopamine transporter SPECT in patients with Parkinson's disease].

The major neuropathological feature in Parkinson's disease (PD) is severe degeneration of the dopamine (DA) neurons in the substantia nigra. Dopamine transporter (DAT) is an important protein in the regulation of DA neurotransmission. It has been reported that PD patients show a loss of DAT in striatum. We report here the findings of single photon emission computed tomography (SPECT) of the DAT with 2 beta-carboxymethoxy-3 beta-(4[123I]iodophenyl)tropane ([123I] beta-CIT) to investigate striatal DAT in 10 patients with PD, one patient with vascular parkinsonism (VP), and one patient with dystonia syndrome. Patients were evaluated using the Webster rating scale. Specific/nondisplaceable striatal binding ratio (V3") was obtained in each case. In PD patients, the uptake of [123I] beta-CIT was reduced, especially in the tail of putamen compared with caudate nucleus. Even in the early stage of PD, the uptake of beta-CIT was reduced not only in the severely affected side, but also in the mildly disturbed side of the brain. Putamen caudate ratio was generally low in PD patients. In VP patient, the uptake was reduced, but putamen caudate ratio was not decreased. V3" values showed significant correlation with the severity of clinical symptoms such as self-care, facies, posture, gait, speech, and Hoehn-Yahr's stage. On the other hand, V3" values were not significantly correlated with the degree of tremor, seborrhea, and duration of the illness. In conclusion, we found that SPECT of the [123I] beta-CIT is a useful method for the diagnosis in the patients presenting parkinsonism, and for the clinico-physiological estimation of parkinsonian symptoms such as self-care, facies, posture, gait, and speech.

[Intraoperative coating of tumor surface using fibrin glue as a prophylaxis for cancer cell detachment].

With the aim of preventing cancer cells from becoming detached and spreading into the abdominal cavity by operative procedures during surgical resection of cancer infiltrating into gastrointestinal serosa, the exposed area of the serosa in mice was coated with fibrin glue, a biological tissue adhesive, prior to resection. We then determined whether the coating could reduce the detachment and spread of cancer cells during the surgical procedure, and thus be capable of inhibiting the occurrence of peritonitis carcinomatosa. In vitro experiments demonstrated that the fibrin glue uniformly and strongly coated the exposed area of cancer, and furthermore, that the presence of fibrin glue coating significantly reduced the number of cancer cells which became detached. As a result of using this glue, the number of deaths due to peritonitis carcinomatosa among assay mice was significantly decreased. It is therefore considered that coating the exposed area of cancer with fibrin glue inhibits cancer cells from being detached and spread during an operation, and thus can be an effective means of preventing the recurrence of peritonitis.

[Usefulness of local administration of methotrexate bound to activated carbon particles (MTX-CH)].

We developed a new dosage formulation, methotrexate bound to activated carbon particles (MTX-CH), and used it to reduce tumors via its long-acting effect at the administration sites. MTX-CH was injected locally into tumors on the back of BALB/c mice, 30 mg/mouse, as MTX and compared with mice treated with MTX aqueous solution, saline solution, activated carbon particles (CH-40) and non-treated mice. The MTX concentration at the administration sites was higher in the MTX-CH group than in the MTX aqueous solution group. A marked effect on the control of tumor growth by MTX-CH was noted after repeated administration (every 3 days, total 4 times) throughout the observation period. Although tumor size was not reduced, necrosis was microscopically observed around the site of MTX-CH administration. For the reasons mentioned above, MTX-CH is superior to MTX aqueous solution in terms of long-acting effect at the administration sites and the control of tumor growth.