Accuracy of portable infusers under hyperbaric oxygenation conditions.

Three types of portable infusers with different infusion mechanisms were evaluated with regard to their accuracy during a hyperbaric oxygenation protocoL The power driving the pump is provided by either a balloon, a spring or a vacuum mechanism. Performance during hyperbaric oxygenation (HBO) varied between the devices, probably due to the difference in driving mechanism. Flow delivery by the vacuum type infuser is substantially affected by HBO. Doubling the ambient pressure approximately doubled flow delivery from the vacuum type device. We suggest that other devices are more suitable for use in this clinical situation. We conclude that it is desirable to check the performance of any infuser intended for use during hyperbaric oxygenation and to be mindful of potential differences among such devices.

Solitary neurofibroma of the nasal cavity: resection with endoscopic surgery.

We present a case of neurofibroma of the nasal cavity treated by endoscopic surgery. A 71-year-old female had complained of left-sided nasal obstruction for the past four years. Anterior rhinoscopy, computed tomography (CT) and magnetic resonance imaging (MRI) revealed a tumour involving the left nasal cavity. Histological and immunohistochemical examination showed the tumour to be a neurofibroma. The tumour was resected with endoscopic surgery. Neurofibroma arising in the area of the nose and paranasal sinuses is rare. We discuss the clinical and pathological characters of neurofibroma arising in the nasal cavity.

Decreased perfusion of the bilateral thalami in patients with chronic pain detected by Tc-99m-ECD SPECT with statistical parametric mapping.

The purpose of this study was to examine whether the Tc-99m-ECD SPECT can detect any difference between the brain perfusion in patients with chronic pain and normal controls by means of the Statistical Parametric Mapping (SPM96). The subjects were twelve patients with chronic pain (CP group) and twelve normal controls (NC group). After informed consent was obtained, 720 MBq of Tc-99m-ECD was intravenously injected as a bolus. The SPECT data were acquired once for 20 mins from 5 mins after i.v. injection of Tc-99m-ECD, with a triple-head rotating gamma camera. The SPECT data were transformed into a standard stereotactic space, and group comparisons between CP and NC groups were performed on a voxel-by-voxel basis. The subset of voxels exceeding a threshold of p < 0.001 in omnibus comparisons and remaining significant after correction for multiple comparison (p < 0.05) was displayed as a volume image rendered in three orthogonal projections. There was a significant decrease in perfusion in the bilateral thalami in the CP group, suggesting that perfusion in the thalamus generally decreases in patients with chronic pain. Tc-99m-ECD SPECT with SPM96 may be useful for studies of the mechanisms of chronic pain.

Identification of human chromosome 22 transcribed sequences with ORF expressed sequence tags.

Transcribed sequences in the human genome can be identified with confidence only by alignment with sequences derived from cDNAs synthesized from naturally occurring mRNAs. We constructed a set of 250,000 cDNAs that represent partial expressed gene sequences and that are biased toward the central coding regions of the resulting transcripts. They are termed ORF expressed sequence tags (ORESTES). The 250,000 ORESTES were assembled into 81,429 contigs. Of these, 1, 181 (1.45%) were found to match sequences in chromosome 22 with at least one ORESTES contig for 162 (65.6%) of the 247 known genes, for 67 (44.6%) of the 150 related genes, and for 45 of the 148 (30.4%) EST-predicted genes on this chromosome. Using a set of stringent criteria to validate our sequences, we identified a further 219 previously unannotated transcribed sequences on chromosome 22. Of these, 171 were in fact also defined by EST or full length cDNA sequences available in GenBank but not utilized in the initial annotation of the first human chromosome sequence. Thus despite representing less than 15% of all expressed human sequences in the public databases at the time of the present analysis, ORESTES sequences defined 48 transcribed sequences on chromosome 22 not defined by other sequences. All of the transcribed sequences defined by ORESTES coincided with DNA regions predicted as encoding exons by genscan. (http://genes.mit.edu/GENSCAN.html).

[Myocardial ischemia during cesarean section in a patient with placental abruption].

A 27-year-old woman (38 week pregnant) was admitted to an obstetric hospital with an acute severe abdominal pain. At that time, the fetal heart sound was not audible. The diagnosis of placental abruption was made and she underwent an emergency cesarean section (C/S) under general anesthesia. She had anemia which became worse in the first few hours after C/S, requiring blood transfusion. ST depression was also present in the ECG during this period. Subsequently, we found an increase in myocin light chain, but not in troponin-T. On the 2nd postoperative day, pulmonary edema appeared and DIC was suspected. We treated her with nitrates, diuretics, protease inhibitors and oxygen by mask. She was discharged on 14th postoperative day with no other complications. Cardiac echogram showed no abnormalities, but a borderline change was seen in her exercise ECG. Depression of the ST segment has been reported in C/S patients, but this does not indicate myocardial ischemia (MI) nor treatment is necessary in most cases. In our case, the diagnosis was not conclusive, but in view of the risks associated with MI, patients with placental abruption should be managed strictly as if they have MI.

Improvement in CNS protective treatment in non-high-risk childhood acute lymphoblastic leukemia: report from the Japanese Children's Cancer and Leukemia Study Group.

BACKGROUND: Prevention of central nervous system (CNS) leukemia by early introduction of therapy to this sanctuary site is an essential component of modern treatment strategy for acute lymphoblastic leukemia (ALL). However, the optimal form of preventive CNS therapy remains debatable. PROCEDURE: To address this issue, we evaluated the efficacy of CNS preventive therapy for 572 children with ALL who achieved complete remission in the Children's Cancer and Leukemia Study Group (CCLSG) ALL874 (1987-1990) and ALL911 (1991-1993) studies. They received risk-directed therapy based on age and leukocyte count. In the ALL 874 study, the non-high-risk (low-risk [LR] + intermediate risk [IR]) patients were randomly assigned to the conventional cranial irradiation (CRT) regimen (L874A and I874A) and the high-dose methotrexate (HDMTX) regimen without CRT (L874B and I874B). The former patients received 18-Gy CRT plus 3 doses of intrathecal (i.t.) MTX and the latter patients received 3 courses of HDMTX at 2 g/m2 plus 13 doses of ITMTX (L874B) or 4 courses of HDMTX at 4.5 g/m2 plus 1 dose of ITMTX (I874B). RESULTS: The 7-year probabilities (+/- SE) of CNS relapse-free survival were 97.3% +/- 2.6% (L874A, n = 41) vs. 90.3% +/- 5.3% (L874B, n = 39) (P = 0.25) in the LR patients, and 100% (I874A, n = 55) vs. 78.5% +/- 6.5% (I874B, n = 54) (P = 0.002) in the IR patients. The corresponding disease-free survival (DFS) rates were 79.4% +/- 6.5% vs. 74.4% +/- 7.3% (P = 0.62) in the LR group and 63.3% +/- 6.8% vs. 58.3% +/- 7.2% (P = 0.66) in the IR group. Thus, the HDMTX regimen could not provide better protection of CNS relapse as compared with the CRT regimen, although their overall efficacy was not significantly different. In the ALL 911 study, intensive systemic chemotherapy with extended i,t, injections of MTX plus cytarabine achieved a high CNS relapse-free survival (98% +/- 1.9% at 7 years) and a favorable DFS (85.5% +/- 5% at 7 years) in the IR patients. The patients in the high-risk (HR) group in both ALL874 and ALL911 studies received the 18-Gy or 24-Gy CRT with intensive systemic chemotherapy. Their 7-year probabilities of CNS relapse-free survival ranged from 88% to 95%, among which the T-ALL patients had a risk of CNS leukemia, which was 3-4 times higher compared with B-precursor ALL patients. CONCLUSIONS: These results indicate that long-term intrathecal CNS prophylaxis as well as appropriate systemic therapy for the non-high-risk patients can provide protection against CNS relapse equivalent to that provided by cranial irradiation.

Internal tandem duplication of the FLT3 gene and clinical evaluation in childhood acute myeloid leukemia. The Children's Cancer and Leukemia Study Group, Japan.

We analyzed tandem duplication in the juxtamembrane (JM) domain of the FLT3 (FMS-like tyrosine kinase 3/FLK2, CD135) gene in 94 children with acute myeloid leukemia (AML) and evaluated its correlation with clinical features. Longer polymerase chain reaction (PCR) products were observed in five patients; 1/3 of M0, 119 of M1, 1/39 of M2, 1/9 of M3 and 1/12 of M5. The sequence analyses of abnormal PCR products showed that all the abnormal products were derived from tandem duplications involving the JM domain and that all the lengthened sequences were in-frame as we previously reported. Statistical analyses revealed a significantly lower incidence of the tandem duplication in childhood AML patients than in adult patients (P < 0.05), and significantly shorter disease-free survival in patients with mutant FLT3 than in patients with wild-type FLT3 (P < 0.05). Our results suggest that the tandem duplication in the JM domain of the FLT3 gene is not a frequent phenomenon but might be a factor of poor prognosis in childhood patients with AML.

[Pulmonary edema due to acute airway obstruction immediately after tracheal extubation].

A 33-year-old male was scheduled for tonsillectomy and pharyngoplasty due to sleep apnea syndrome. The intubation was uneventful following induction with thiamylal and vecuronium. Anesthesia was maintained with O2-N2O-sevoflurane. No complications were observed during the 90 min operation. After the termination of the anesthesia, a hyperadrenergic state was observed: arterial pressure and heart rate rose to 230/135 mmHg and 135 bpm, respectively. Immediately after extubation, he developed dyspnea with tracheal tag and stridor, and became cyanotic despite the use of a simple oxygen mask and assisted ventilation. Laryngospasm was suspected. The patient was reintubated and suctioned; pink, frothy sputum was not obtained. Arterial blood gases 5 minutes after reintubation revealed a pH of 7.24, Pao2 86 mmHg (FIo2 1.0), and Paco2 54 mmHg. Chest X-ray 30 minutes after reintubation revealed bilateral diffuse alveolar infiltration. The diagnosis was interstitial pulmonary edema. The patient was ventilated mechanically by applying a positive end-expiratory pressure of 5cm H2O, and furosemide and dopamine were administered intravenously. The patient was extubated the next day, and discharged from hospital ten days later. We considered that the lung edema was induced by the severe negative pressure generated by inspirating against a closed upper airway, as well as by the hyperadrenergic state and severe hypoxemia observed during and after extubation.

[Clonal analysis by fluorescence in situ hybridization in a patient with de nove acute myeloid leukemia with myelodysplasia].

A 12-year-old girl presenting leukocytosis, anemia and thrombocytopenia was diagnosed as de nove acute myeloid leukemia (AML, M2) with concurrent myelodysplastic features in myeloid and erythroid cells. Her karyotype was defined as 47, XX, +8[20]. Though she was treated successfully with multi-drug chemotherapy, she relapsed after 2 years of remission. A bone marrow transplantation from HLA matched her brother was performed to induce hematological remission which persisted for one year. She again relapsed with AML with myelodysplasia, and an abnormal complex karyotype was newly detected. She eventually died without further chemotherapy. We performed FISH on the patient's stained bone marrow smears using DNA probes for chromosome 8 and Y to analyze the clonality. The results showed that the most of blasts and bone marrow cells except lymphoid cells were of trisomy 8 at onset, while in the 1st remission, trisomy 8 clone was slightly detected only in monocytes. At 1st and 2nd relapse, trisomy 8 clone was detected again in most of myeloid cells. Thus, in this case, it was considered that underlying stem cell disorder with trisomy 8 during the entire disease course contributed to leukemogenesis.

[Myelogenous leukemia in children. ANLL9205 study by Children's Cancer and Leukemia Study Group (CCLSG)].

Treatment results were evaluated in 45 children with acute myeloblastic leukemia (AML) treated on the ANLL-9205 protocol of the Children's Cancer Leukemia Study Group (CCLSG, Japan). In this protocol, terarubicin (THP-ADR), vincristine and continuous infusion of cytosine arabinoside (Ara C) were applied for remission induction therapy (AVC), and VP16+ high dose Ara C were used sequentially for 32 or 48 weeks. Eleven patients received stem cell transplantation. Thirty-eight out of the 43 eligible patients (88.4%) achieved complete remission, and the overall 3-year event-free survival (EFS) was 55.6% (S.E.,10%). This favorable response was attributed mainly to the high induction rate of patients with the M5, M7 FAB subtypes and higher WBC counts (> or = 10 x 10(9)/L). There was no difference in the 3-year EFS of these patients who discontinued treatment between 32 weeks and 48 weeks. Serious toxicities were not observed in this study. These findings suggest that the ANLL-9205 protocol is an effective and safe treatment regimen for childhood AML. When comparing the treatment period of 32 or 48 weeks, the difference was not statistically significant.

Overview of clinical studies of childhood acute lymphoblastic leukemia for more than ten years by the Japanese Children's Cancer and Leukemia Study Group.

Since 1981, the Children's Cancer and Leukemia Study Group (CCLSG) has developed a series of protocols for treatment of acute lymphoblastic leukemia (ALL) in childhood. In the first randomized controlled study of the 811 protocol (1981-1983) a comparison of conventional daily 6-mercaptopurine and methotrexate with a pulsed regimen of the two drugs was performed. The superiority of the pulsed regimen was shown. In the next 841 protocol (1984-1987) a comparison of two drugs and three drugs during induction therapy was conducted. The three-drug regimen resulted in a significantly higher event-free survival (EFS) rate. In the 874 protocol (1987-1990) two regimens with or without cranial irradiation were randomly compared, and there was no significant difference between the two regimens for the standard-risk group. To further improve the EFS rate a risk group-directed protocol 911 was conducted starting in January 1991. Life-table analysis of serial CCLSG protocols revealed that the outcome of overall ALL has gradually improved with an increase of the EFS rate; 41.4% +/- 3.6% at 14 years for the 811 protocol, 51.3% +/- 3.5% at 11 years for the 841 protocol, 56.7% +/- 3.1% at 8 years for the 874 protocol, and 78.2% +/- 3.1% at 4 years for the more recent 911 protocol.

[Treatment results of intermittent and cyclic regimen with ATRA and chemotherapy in childhood acute promyelocytic leukemia. Children's Cancer and Leukemia Study Group].

An intermittent and cyclic regimen with All-Trans Retinoic Acid (ATRA) and intensive chemotherapy was conducted due to pharmacokinetic studies on ATRA for acute promyelocytic leukemia (APL) in children. We have treated 17 children with APL using ATRA for remission induction followed by an intermittent schedule of ATRA plus intensive chemotherapy (APL-ATRA protocol). There were 10 males and 7 females. The median age was 9.0 years old. The median baseline white blood cell count was 12.1 x 10(3)/microliter, hemoglobin 7.8 g/dl, platelet 4.5 x 10(4) microliters at diagnosis. Sixteen patients showed t(15; 17) translocation. RT-PCR analysis was available in 15 patients and showed PML/RAR alpha rearrangement in all patients. Overall, 13 or 17 newly diagnosed patients (88%) achieved complete remission and EFS was 67%. Compared to the control (same chemotherapy without ATRA regimen), remission induction and EFS were significantly increased. The toxicity of ATRA consisted of retinoic acid syndrome in 1 and pseudotumor cerebli in another. Other toxicities included headache, chelitis, gastrointestinal trouble and bone pain. These results suggest that intermittent and cyclic regimen with ATRA and intensive chemotherapy (APL-ATRA protocol) is highly effective for APL patients.

[Anesthetic management of a patient with congenital cystic adenomatoid malformation].

Congenital cystic adenomatoid malformation (CCAM) is a rare disease that is diagnosed by severe respiratory dysfunction from birth. A 5-day-old-boy with CCAM underwent removal of a large cyst which was present at lower lobe of right lung. Anesthesia was induced slowly and maintained with oxygen and sevoflurane. Severe airway obstruction occurred transiently by the secretion from the lung cyst. Thereafter, the surgery was completed safely and his postoperative course was uneventful. Perioperative anesthetic management of the patient with CCAM is also discussed.

[Clinical characteristics and treatment results of acute promyelocytic leukemia in children (Children's Cancer and Leukemia Study Group)].

The clinical characteristics and treatment outcome in 40 children with acute promyelocytic leukemia (APL) treated at institutions participating in the Children's Cancer and Leukemia Study Group (CCLSG) were studied retrospectively. The median age at diagnosis was 8 years old. Bleeding diathesis was the predominant presenting symptom (90%), associated with laboratory findings of disseminated intravascular coagulation. Hepatomegaly, splenomegaly and lymphadenopathy were observed in 35%, 10%, and 15% of the cases, respectively. The median WBC count was 4.25 x 10(9)/l. Anemia (hemoglobin < 8 g/dl) and thrombocytopenia (< 30 x 10(9)/l) were present in more than half of the patients. Cytogenetic studies demonstrated the characteristic 15; 17 translocation in about 90% of the patients analyzed. Induction therapy consisted of cytosine arabinoside and an anthracycline, with or without other agents. Twenty-nine patients (73%) achieved complete remission (CR) while early fatal hemorrhage was the predominant cause of induction failure. The survival rates continued to decrease (28% at 3 years, 24% at 5 years, and 7.9% at 10 years) due to late marrow relapses. Anthracycline cardiotoxicity was fatal in three patients in remission. These clinical features of childhood APL should be taken into account in the development of new protocols.

[A infant case of rhabdomyosarcoma arising from the left iliac region with complete remission for 2 years after combination therapy].

A case of rhabdomyosarcoma in a 14-year-female is reported herein. The patient developed left inguinal pain and tumor. She was initially seen by her local medical doctor, who biopsied her left inguinal tumor with a pathological report of malignancy. She was referred to the Ryukyu University Hospital in July, 1990. CT and MRI demonstrated a large tumor 10 cm in diameter arising from the left iliac region. The tumor was extirpated and the pathological report indicated rhabdomyosarcoma (alveolar type). The patient was treated with VAC chemotherapy and local irradiation. Her course has been uneventful for the past 2 years without any clinical manifestation of recurrence since surgery.

Accumulation of large neutral amino acids in the brain of sparse-fur mice at hyperammonemic state.

Sparse-fur mice which are deficient in ornithine transcarbamylase, the second-step enzyme in the urea cycle, were examined for hyperammonemia and its relationship with encephalopathy. We compared amino acid concentrations in the serum and brain of spf mice with those of control mice. Unlike hepatic encephalopathy we could not find marked amino acid changes in the serum of spf mice besides low levels of citrulline and arginine. But in the brain of spf mice, glutamine was increased strikingly during hyperammonemia, and a concomitant accumulation of large neutral amino acids such as tyrosine, phenylalanine, methionine, and histidine was observed. The accumulation of these large neutral amino acids in the brain was not influenced by 24-hr fasting which caused increases in branched chain amino acids in the serum. From these results, we conclude that the accumulation of the large neutral amino acid in the brain of hyperammonemic state is caused by uptake of ammonia in the brain and the subsequent accumulation of glutamine, but is not influenced by a decreased ratio of branched chain amino acids to aromatic amino acids in the serum.

Transient hyperammonemia during aging in ornithine transcarbamylase-deficient, sparse-fur mice.

Ornithine transcarbamylase [EC 2.1.3.3] (OTC) deficient, sparse-fur (spf) mice are considered to be a good model of human OTC deficiencies. We measured the blood ammonia concentration in spf mice. It was not always at a high level. It was high only during weaning, then gradually decreased and finally fell to a normal level. A similar phenomenon was observed in the change of hepatic ammonia concentration. Excretion of urinary orotate in spf mice was 15-20 times higher than in control mice just after weaning. It also gradually decreased during aging, but remained at a high level compared with adult control mice. OTC activity at pH 7.7 in the liver of spf mice increased significantly between the weaning period and 30-40 days old, when blood ammonia was falling to a normal level.

Effect of Fluosol-DA on the blood coagulation/fibrinolytic system and the renin-angiotensin system in man.

Either F-DA, Ringer's lactate or HES was given to three groups of six patients each who were undergoing elective gynecologic surgery, and their effects on the blood coagulation/fibrinolytic systems, and the renin-angiotensin systems were evaluated. Platelet counts were found to increase markedly using the Coulter Counter method, but no change was observed when the Rees-Ecker method was used. Platelet aggregation was inhibited and AT-III concentrations were decreased by administration of F-DA. There were no significant changes in PT or a-PTT as a result of F-DA administration. Similarly, there were no significant changes in the concentrations of fbg, FDP, a2-PI, P-FN and renin, angiotensin I, II and angiotensin converting enzyme following F-DA administration. Based upon these findings, it is suggested that a clinical dosage of 20 to 30 ml/kg of F-DA can be safely administered to patients with normal platelet and RES function.