Endothelium-denuded pulmonary resistance arteries from the fetal lamb: preparation and response to vasoactive agents.

A method was developed for preparing endothelium-denuded resistance arteries (mean internal diameter, 176 microns) from the term fetal lung to be used for tests in vitro. The endothelium was removed mechanically by passing a sandpaper-polished cat whisker through the lumen. Ultrastructurally, the preparation had a well-preserved internal elastic lamina which was facing the lumen without any endothelium superimposed. Its response to contractile agents (excess potassium, a thromboxane A2 analogue, endothelin-1) tended to be greater compared to the intact artery. Conversely, the relaxation to acetylcholine was abolished in the endothelium-denuded artery and, in its place, a modest contraction ensued. Sodium nitroprusside relaxation, unlike acetylcholine relaxation, was affected insignificantly by endothelium denudation. This preparation, in combination with the preparation of the intact resistance artery, is a useful, new tool for studying local factors responsible for pulmonary hemodynamic control in utero and through the transitional period at birth.

Intracranial malignant fibrous histiocytoma: characterization of GFAP-positive cells in the tumor.

A case of malignant fibrous histiocytoma (MFH) arising in the cerebellopontine angle of a 57-year-old woman was reported. The immunohistochemical and electron microscopic findings indicated distinct fibrohistiocytic nature and myofibroblastic differentiation of this peculiar tumor. Immunohistochemistry disclosed that the tumor cells expressed monocyte/macrophage markers including CD-68, MAC 387, and alpha-1-antichymotrypsin. In addition, the neoplasm contained scattered glial fibrillary acidic protein (GFAP)-positive cells which made small nests in some areas. These GFAP-positive cells had bundles of densely packed intermediate filaments and scanty organellae in the cytoplasm, as demonstrated by an immunostained-semithin and serial-ultrathin section method. By immunostaining of MIB-1 and GFAP, and silver nucleolar organizer region (AgNOR) impregnation on serial sections, the GFAP-positive cells were not labeled by MIB-1 and their AgNOR counts averaged 1.13/nucleus. Thus, these GFAP-positive cells seem to have lower proliferating activity than neoplastic astrocytes. It is concluded that they may be nonneoplastic astrocytic cells involved by MFH.

Changes in coagulation and fibrinolysis and effects of ticlopidine and cisternal drainage in the acute phase following aneurysm rupture.

In this study, changes in blood coagulation and fibrinolysis in the acute stage of subarachnoid hemorrhage (SAH) from ruptured intracranial aneurysms were investigated, and the effects of the platelet aggregation inhibitor ticlopidine and cisternal drainage were evaluated. All of the 53 patients underwent early surgery, and 27 patients received ticlopidine postoperatively. Cisternal drainage was implemented in 15 cases of severe SAH treated after late 1986. Of the hematologic factors studied, the activated partial thromboplastin time, fibrin and fibrinogen degradation products, fibrinogen, and platelet aggregation rate were found to be abnormal in the acute phase of SAH, and the "intravascular factor" scale obtained was also noted to be significantly (p less than 0.01) related to the outcome. Ticlopidine was consistently effective in reducing platelet aggregation but had little effect on other blood parameters. Cisternal drainage resulted in a significantly (p less than 0.01) lower incidence of symptomatic vasospasm and higher rate of good outcome. These results suggest that ticlopidine therapy plus cisternal drainage is highly beneficial in SAH, and that coagulation and fibrinolysis data are useful in determining the prognosis.

Hemodynamic evaluation and morphological changes of right ventricular out-flow tract and pulmonary valve after balloon pulmonary valvuloplasty.

Balloon pulmonary valvuloplasty (BPV) was attempted in 38 cases of congenital pulmonary valve stenosis. It was effective and was done without complication in 36 cases, however it was not effective in two cases of pulmonary valve dysplasia. The balloon used was 20-50% larger in diameter than the pulmonary valve annulus. In the seven cases in which the transvalvular pressure gradient was above 100 mmHg on cardiac catheterization, right ventriculography demonstrated that the functional obstruction of the right ventricular outflow tract increased immediately after BPV, however it subsequently improved at one year after the procedure. At between one and three months after BPV, two-dimensional echocardiography demonstrated that the morphological obstruction to the right ventricular outflow tract had diminished. In two cases, localized right ventricular septal hypertrophy with severe pulmonary valve stenosis was observed by two-dimensional echocardiography and right ventriculography, and persisted at one year. In all cases, two-dimensional echocardiography and angiography demonstrated doming pulmonary valves with valve stenosis, which was diminished by BPV. The pulmonary valve morphology was observed by two-dimensional echocardiography in three cases following BPV. In one case, partial relief of pulmonary valve obstruction was seen to be due to commissural splitting and in the other two, to tearing of cusp tissue. Inspection of the pulmonary valve at operation was made in one case who underwent elective surgery for repair of an atrial septal defect which was associated with pulmonary valve stenosis. It demonstrated partial relief of pulmonary valve stenosis by tearing of cusp tissue. In conclusion, BPV is as effective a treatment for congenital pulmonary valve stenosis as open valvulotomy. In our follow-up study, it has shown no apparent complications. The transient obstruction in the right ventricular outflow tract immediately after BPV improved within one month and improved further after three months and one year. However, in the more long-standing cases the localized right ventricular septal hypertrophy persisted and these cases will require, a long term follow-up.

[Pharmacokinetic and clinical studies of imipenem/cilastatin sodium in the pediatric field].

Pharmacokinetic and clinical studies of imipenem/cilastatin sodium (MK-0787/MK-0791), a newly developed combined antibiotic in a 1:1 ratio, were performed in the field of pediatrics. The MK-0787/MK-0791 was administered to 15 children. Ten and 20 mg/kg doses of MK-0787 were administered by a intravenous drip infusion for 30 minutes to 3 children each. In the remaining 9 cases, MK-0787 doses of 10, 20 and 30 mg/kg were administered to 3 children each by a 1 hour intravenous drip infusion. Levels of MK-0787 and MK-0791 in plasma, urine and urinary recovery rate of the drugs were also determined. In addition, MK-0787/MK-0791 was administered to a total of 29 children; 2 children with bronchitis, 16 with pneumonia, 4 with UTI, 2 with purulent lymphadenitis and 1 child each with tonsillitis, septicemia suspected disease, peritonitis, staphylococcal scalded skin syndrome and osteomyelitis/bacteremia. The average single dose was 15.3 mg/kg of MK-0787 and administrations were performed by 20-60 minutes intravenous drip infusion 3-4 times daily for an average period of 6 days. The clinical and bacteriological effects of this drug were evaluated in these cases and adverse reactions and unusual laboratory findings were also studied in a total of 33 cases including 4 other drop-out cases. Results of these studies were summarized as follows. In 6 children, 3 each who were given doses of 10 or 20 mg/kg, the mean peak plasma concentrations of the drugs were found at the end of the 30 minutes-infusion with values of 35.20 and 74.90 micrograms/ml for MK-0787 and 44.85 and 93.32 micrograms/ml for MK-0791 after the dose of 10 and 20 mg/kg, respectively. The peak plasma levels of MK-0791 were approximately 1.3 times higher than those of MK-0787 and higher peak levels were observed in the groups with larger doses of either drugs. In the 10 mg/kg group, the mean half-lives of MK-0787 and MK-0791 were 0.97 and 0.71 hour, respectively and those values were 0.89 and 0.63 hour, respectively in the 20 mg/kg group. In both group, MK-0787 tended to have longer half-lives than MK-0791. In 9 children, 3 each who were administered doses of 10, 20 and 30 mg/kg by a 1 hour intravenous drip infusion had the highest plasma levels for both MK-0787 and MK-0791 at the end of the infusion.(ABSTRACT TRUNCATED AT 400 WORDS)

[Actinomycotic granuloma of the optic chiasma: a case report].

A case of actinomycotic granuloma of the optic chiasma and the optic nerve is reported. A 53-year-old man was admitted to our hospital with headache and vomiting on September 25, 1989. General physical and neurological examination on admission revealed no remarkable findings. CT-scan demonstrated almost normal pictures. On the 17th hospital day, his temperature was 38 degrees C and white blood cell (WBC) count was 12000 cumm. And he presented right abducens palsy. MRI demonstrated no abnormal findings then. After antibiotic therapy of penicillin intravenously for 4 days, his temperature returned to normal and abducens palsy disappeared for two weeks. He was discharged 43 days after admission. But one year after discharge he developed progressive impairment of right visual acuity. He was admitted to our hospital again on January 19, 1991. His neurological examination revealed severe impairment of right visual acuity and bitemporal hemianopsia. WBC count was 5400 and CRP was negative and temperature was 36.2 degrees C. CT-scan and MRI demonstrated a suprasellar enhancing mass lesion. Serum prolactin was 38 ng/ml. A diagnosis of pituitary adenoma was considered and a right frontotemporal craniotomy was performed. At operation, abnormally swelled right optic nerve and chiasma were found and the swelled chiasma only was resected. Histological examination showed an abscess containing necrotic tissues and actinomycotic granules with radiating filaments. The patient was given penicillin intravenously for 37 days and orally for two months. At that time, MRI revealed no abnormal enhancing lesion, and his visual acuity improved gradually. Actinomycosis of the optic nerve and chiasma is very rare.(ABSTRACT TRUNCATED AT 250 WORDS)

[Studies of two cases of ruptured intracranial aneurysm with disseminated intravascular coagulation].

Two cases of ruptured intracranial aneurysm with severe DIC were reported. One case recovered due to early treatment. A 65-year-old man was admitted to our hospital in June, 1987 because he was suffering from sudden severe headache and nausea. On admission, CT-scan angiograms disclosed moderate subarachnoid hemorrhage (SAH) and probable ruptured anterior communicating aneurysm. However definitive diagnosis was not made at that time. On the 15th day after SAH, he had high fever and low blood arterial pressure. His laboratory findings were consistent with DIC, and therapy of FOY was then started with transfusion of fresh blood two days after. His laboratory findings and clinical status improved gradually and he underwent uneventful operation of the aneurysm on the 42nd day after SAH. Another case concerns a 71-year-old woman who was admitted to our hospital in June, 1988 because she had lost consciousness. On admission, CT-scan disclosed severe SAH and next day an operation was performed. On the 6th day after SAH, she showed clinical and laboratory evidence of severe DIC and died two days later. The association between DIC and ruptured intracranial aneurysms have been rarely mentioned in past reports. But the association might occur more frequently than we have supposed, and so more immediate and careful diagnosis and proper treatment for DIC should be given.

[A choroid plexus papilloma of the third ventricle in the neonatal period--a case report].

The incidence of choroid plexus papilloma is about 0.5% of all intracranial tumors, but choroid plexus papilloma in the third ventricle is rare. Fortuna reported 56 cases of choroid plexus papilloma of the third ventricle in 1979. Among them, the neoplasm of the third ventricle in the neonatal period was not found. This report is a case of choroid plexus papilloma of the third ventricle in the neonatal period. A 34 day-old female was admitted to our service with complaints of head enlargement, vomiting, and convulsive seizures on January 8, 1981. Enlarged head had been noticed by her family within the first two weeks. On admission, a marked congenital hydrocephalus was diagnosed by CT scan with symmetrical dilated ventricles and no abnormal high or low density area, and V-P shunt was performed on the next day. But several days later, she suffered from progressive abdominal distension, which was disclosed due to CSF overproduction by a choroid plexus papilloma. When the tumor was recognised by enhanced CT scan, her general condition was too poor to attempt a surgical procedure, and she died on March, 19, 1981. Histologically the neoplasm was a typical choroid plexus papilloma of the third ventricle. So far as we know, this case is the first one of the choroid plexus papilloma of the third ventricle in the neonatal period.

[Usefulness of open lung biopsy for corrective surgery on incomplete atrioventricular septal defect associated with severe pulmonary hypertension and right to left shunting].

In congenital heart defects, it is sometimes difficult to decide the operative indication in patients, who has severe pulmonary hypertension (PH) and right to left shunting, from clinical symptoms and cardiac catheterization. We here report a case of incomplete atrioventricular septal defect. The patient is 9 months old with the Down's syndrome. The cardiac catheterization showed severe PH and right to left shunting. Preoperative mean pulmonary artery pressure was 75 mmHg, pulmonary systemic pressure to systemic pressure ratio (PP/PS) was 1.17, pulmonary systemic flow to systemic flow ratio (QP/QS) was 0.79, pulmonary systemic resistance to systemic resistance ratio (RP/RS) was 1.54 and pulmonary vascular resistance (PVR) was 9.6 woodunits.m2. These data suggested that the irreversible pulmonary vascular disease was present. However the PVR decreased from 9.6 to 3.6 woodunits.m2 after inspiration of 100% oxygen. We therefore performed open lung biopsy for further evaluation of the pulmonary vascular bed. The pathological findings obtained at lung biopsy indicated that there was no irreversible pulmonary vascular disease. This case was diagnosed suitable for a corrective surgery. Total repair was performed and the subsequent clinical course was satisfactory. We thus suggest that the open lung biopsy is useful to decide the surgical indication when it is difficult to determine an operative indication from hemodynamic measurement alone.

Fetal echocardiography: new insight into fetal cardiology--a review.

Recent advance in echocardiography has permitted detailed imaging of the fetal heart, facilitating the prenatal diagnosis of congenital heart disease and the diagnosis and treatment of fetal arrhythmias. New advance in Doppler echocardiography has provided important information about the physiology of normal and abnormal fetal circulation. From 1980 to 1986, we performed echocardiography on 564 fetuses, including 254 normal and 310 high risk pregnants. Results are discussed in terms of the method and accuracy of the prenatal diagnosis of congenital heart disease, the recognition of and intrauterine treatment of fetal arrhythmias, the diagnosis of fetal heart failure, the assessment of fetal circulation by Doppler echocardiography, the management of the fetus with cardiac problems, and the ethical aspects of fetal cardiology.

Involvement of endothelin-1 in hypoxic pulmonary vasoconstriction in the lamb.

1. Using isolated pulmonary resistance vessels from mature fetal lamb and chronically instrumented lambs (8-17 days old), we have examined whether hypoxic pulmonary vasoconstriction is sustained by activation of a constrictor mechanism or suppression of a dilator mechanism. 2. Hypoxia contracted both arteries and veins in vitro, and the contraction was greater with the former. After removing the endothelium, arteries responded faster to hypoxia, but the magnitude of the response remained unchanged. 3. Hypoxic arteries, unlike normally oxygenated arteries, did not contract with either indomethacin (2.8 microM) or N omega-nitro-L-arginine methyl ester (L-NAME, 100 microM). The same vessels relaxed with sodium nitroprusside (SNP, 0.001-10 microM) but not with bradykinin (0.1-100 nM). 4. Endothelin-1 (ET-1, 0.01-10 nM) contracted isolated arteries and veins under normoxic and hypoxic conditions. In both vessels, the contraction was fast in onset and subsidence, and was inhibited by the ETA receptor antagonist BQ123 (1 microM). The ET-1 precursor, big ET-1 (100 nM), also contracted arteries and veins, but compared with ET-1 its action was slower in development. Big ET-1 contraction, unlike ET-1 contraction, was curtailed by the inhibitor of the ET-1-converting enzyme, phosphoramidon (50 microM). 5. ET-1 (0.1-10 nM) had no effect on isolated arteries precontracted with a thromboxane A2 (TXA2) analogue (ONO-11113) and treated with BQ123 (10 microM). Under the same conditions, ET-1 relaxed the veins. Accordingly, in the absence of BQ123 treatment, the selective ETB receptor agonist IRL-1620 (0.1-100 nM) relaxed the contracted veins but not the arteries. 6. BQ123 (10 microM) inhibited the constriction of isolated arteries and veins to hypoxia. Likewise, in the conscious lamb a bolus of BQ123 (0.4 mg kg-1, injected into the pulmonary artery) curtailed the rise in pulmonary vascular resistance (Rpa) brought about by alveolar hypoxia without changing significantly systemic vascular resistance (Rao). Under normoxia, Rpa was insignificantly affected by BQ123. 7. The results indicate that pulmonary resistance arteries are more susceptible to hypoxia than the veins, and that hypoxic vasoconstriction does not require an intact endothelium to occur. Hypoxic tone is ascribed primarily to intramural generation of ET-1, while removal of the tonic action of a relaxant may only have an accessory role in the response.

Effect of endothelium removal on prostaglandin and nitric oxide function in pulmonary resistance arteries in the lamb.

We have recently shown that isolated pulmonary resistance arteries of the fetal lamb have prostaglandin (PG) I2 based and nitric oxide (NO) based relaxing mechanisms, which are activated by oxygen (at neonatal levels) and bradykinin. The present study was carried out to ascertain whether these mechanisms remain operational after removal of the endothelium. Endothelium-denuded vessels pre-equilibrated at a neonatal Po2 were not affected by indomethacin (2.8 microM), while they contracted weakly to NG-nitro-L-arginine methyl ester (L-NAME, 100 microM). However, the latter response did not reach significance and resembled that of intact vessels at fetal Po2. Bradykinin (0.1-100 nM) dose dependently (from 1-3 nM upwards) relaxed endothelium-denuded arteries that had been precontracted with a thromboxane (TX) A2 analog (ONO-11113, 0.1 microM) or excess potassium (5 mM Ca2+ in K(+)-Krebs) at a neonatal Po2. The response was the same under the two conditions, but it was smaller than that of intact arteries. Bradykinin relaxation of ONO-11113-contracted arteries was completely or nearly completely inhibited by indomethacin and L-NAME. We conclude that endothelium-denuded, pulmonary resistance arteries maintain PG (conceivably PGI2) mediated and NO-mediated relaxing mechanisms. These extra-endothelial mechanisms are activated by bradykinin but not by oxygen.