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BACKGROUND AND PURPOSE: Angiogenesis is very important in clinical features of pituitary adenomas. We investigated the relationship between the blood flow of nonfunctioning pituitary macroadenomas measured by arterial spin-labeled perfusion imaging and the microvessel attenuation of the tissue. MATERIALS AND METHODS: Conventional MR imaging with contrast-enhanced T1WI and arterial spin-labeled perfusion imaging were performed before surgery in 11 consecutive patients with nonfunctioning pituitary macroadenomas. ROIs were drawn on the tumors, and the degrees of enhancement were calculated by dividing the signal intensity on the contrast-enhanced T1WI by that on the nonenhanced TIWI. As an index of tumor perfusion, a quantitative analysis was performed by using normalized tumor blood flow values calculated by dividing the mean value of the tumor region of interest by the mean region of interest values in the 2 cerebellar hemispheres. The relative microvessel attenuation was determined as the total microvessel wall area divided by the entire tissue area on CD-31-stained specimens. The degree of enhancement and the normalized tumor blood flow values were compared with relative microvessel attenuation. Additionally, intra- and postoperative tumor hemorrhages were visually graded. RESULTS: The degree of enhancement was not correlated with relative microvessel attenuation. Statistically significant correlations were observed between normalized tumor blood flow values and relative microvessel attenuation (P < .05). At surgery, 3 cases were visually determined to be hypervascular tumors, and 1 of these cases had symptomatic postoperative hemorrhage. A statistically significant difference in normalized tumor blood flow values was observed visually between the intraoperative hypovascular and hypervascular groups (P < .05). CONCLUSIONS: Arterial spin-labeled perfusion imaging reflects the vascular density of nonfunctioning pituitary macroadenomas, which may be useful in the preoperative prediction of intra- and postoperative tumor hemorrhage.

Although case-oriented evidence for an association of Epstein-Barr virus (EBV) with gastric carcinoma has been accumulating recently, the interaction(s) between EBV and gastric epithelial cells is/are largely unknown. In this study, we examined seven EBV-positive gastric carcinoma tissues for viral gene expression at the mRNA level, from which studies on the EBV oncogenicity in human epithelial cells will benefit. Reverse transcription-PCR analysis showed that all seven EBV-positive tumour tissues constitutively expressed EBV nuclear antigen (EBNA) 1 mRNA, but not EBNA2 mRNA. The EBNA transcription was initiated from one of three EBNA promoters, Qp: by contrast, both Cp and Wp were silent, thus resulting in the lack of EBNA2 mRNA. Latent membrane protein (LMP) 2A mRNA was detected in three of seven cases; however, neither LMP1 nor LMP2B mRNA was detected in any of the tumours tested. Transcripts from the BamHI-A region of the viral genome were detectable in all cases. BZLF1 mRNA and the product, an immediate-early gene for EBV replication, was not expressed in any of them, thereby suggesting that the tumour cells carried EBV genomes in a tightly latent form. These findings further extended our previous data regarding EBV latency in gastric carcinoma cells at the protein level, and have affirmed that the programme of viral gene expression in the tumour more closely resembles 'latency I' represented by Burkitt's lymphoma than 'latency II' represented by the majority of nasopharyngeal carcinomas. Images Figure 1 Figure 2 Figure 3 Figure 4

We identify possible differences in the cytokine/chemokine profiles in cerebrospinal fluid (CSF) from children with encephalopathy and febrile seizure. Interleukin (IL)-1beta, 2, 4, 5, 6, 7, 8, 10, 12, 13, 17, interferon-gamma, tumour necrosis factor-alpha, granulocyte colony-stimulating factor, granulocyte monocyte colony-stimulating factor, monocyte chemoattractant protein-1 and macrophage inflammatory protein-1beta were measured simultaneously in CSF supernatants from children with encephalopathy (n = 8), febrile seizure (n = 16) and fever without neurological complications (n = 8). IL-8 in CSF from children with encephalopathy was significantly elevated compared to that in CSF from children with febrile seizure and fever without neurological complications. IL-8 in CSF was also higher than serum IL-8, suggesting that increased IL-8 was generated from glia cells or astrocytes, not by leakage from serum. Increased IL-8 in CSF in encephalopathy may protect against severe brain damage.

We report 2 cases of resected CA19-9 producing adenocarcinoma of the lung. Immunohistochemical studies of the specimens in 2 cases showed positive staining for CA19-9 in most of tumor cells. The serum CA19-9 levels decreased after operations and effective chemotherapy in these cases. But the serum CA19-9 levels increased with regrowth of tumors or with no therapeutic gain by chemotherapy. The serum CA19-9 level was useful to evaluate the therapeutic effect of surgery and chemotherapy, and may be effective in detecting the recurrence of lung cancer.

Background: We report a 16 year-old girl with propylthiouracil (PTU)-induced antineutrophil cytoplasmic antibody (ANCA)-positive glomerulonephritis combined with Henoch-Schonlein purpura nephritis (HSPN) and antiphospholipid syndrome (APS). Case and methods: The patient had Graves' disease and had been treated with PTU for about 6 years. She complained of arthralgia, epigastralgia, purpura of the lower extremities, anemia, and abnormal urinalysis. Lupus anticoagulant was positive. Additionally, a high level of anti-myeloperoxidase (MPO) antibodies (IgG) and a low level of coagulation factor XIII were recognized. She had several complications including lung bleeding, lacuna infarctions of the right frontal and parietal brain lobes, and deep vein thrombosis of the left lower extremity. We studied tissue histology and carried out MPO-ANCA subtype analysis by immunofluorescence and flow cytometry and MPO-ANCA epitope analysis. Results: Histologically, purpura showed leukocytoclastic vasculitis with perivascular depositions of IgA and complement C3. Renal biopsy showed necrotizing glomerulonephritis with crescents and mesangial IgA deposits. Notably, IgG, IgM, and IgA ANCA were detected in the patient's serum by flow cytometry and immunofluorescence. We diagnosed an overlap syndrome of ANCA-positive vasculitis, HSPN, and APS. A change in the reactivity of MPO-ANCA from recognition of only the Hg epitope in the C-terminal region to recognition of multiple MPO epitopes was accompanied by a remission of symptoms. Conclusions: This report may provide a very rare description of an overlap syndrome of PTU-induced ANCA vasculitis, HSPN, and APS in which not only IgG ANCA but also IgA and IgM ANCA were found. Epitope analysis may be a useful marker for disease-monitoring of PTU-induced ANCA-positive vasculitis. This case may provide insight into the pathological mechanism underlying each of these diseases.

We encountered a 22-year-old man (case 1) and a 23-year-old woman (case 2), both unrelated and healthy. They were mosaic for the Rh blood group phenotype: one erythrocyte population was D-positive and the other was D-negative. Flow cytometric analysis of density profile of RhD antigen in their erythrocytes, and cytogenetic analysis including in situ hybridization using an RHD/RHCE-containing PAC clone, excluded a deletion of the RHD/RHCE gene complex, but suggested the presence of cells with uniparental disomy for chromosome 1 (UPD1). Microsatellite marker analysis was performed in both probands and their family members. In case 1, the analysis with markers spanning the chromosome 1 revealed both maternal and paternal alleles in his peripheral blood leukocytes (PBL), Epstein-Barr virus-transformed lymphoblastoid cells (EBL), and buccal mucosal cells. However, only paternal alleles were detected in all of 50 individual pieces of his hair or hair-roots and all of five monoclonal cell lines cloned from his established EBL. There was no direct evidence of heterozygous, biparental alleles in these two tissues. The presence of maternal isodisomy 1 was not absolutely ruled out in other tissues examined in case 1. Similar results were obtained in case 2, showing biparental, disomic patterns in her PBL and in 15 of 20 pieces of her hair roots, and showing monoallelic patterns in the remaining five pieces of hair roots. Analysis with markers for other autosomes confirmed their biparental inheritance. These findings indicated that both cases had at least two cell populations, one population having paternal UPD1 (isodisomy 1), and another heterozygous, biparental disomy 1. We emphasize that isodisomy for chromosome 1 is not infrequent and may cause unusual RhD phenotype, as seen in cases we described.

Brain-derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1) act on various neurons of the CNS as neurotrophic factors promoting neuronal differentiation and survival. We examined the survival-promoting effects of BDNF and IGF-1 on serum deprivation-induced death in cultured cerebral cortical neurons, and compared the intracellular signaling pathways stimulated by BDNF and IGF-1 in the neurons. We found that the survival-promoting effect of BDNF was much weaker than that of IGF-1 in serum deprivation-induced death of cultured cortical neurons. We found no differences in the levels of phosphatidylinositol 3-kinase (PtdIns3-K) activity or Akt (also called PKB) phosphorylation induced by BDNF and IGF-1 in the cultured cortical neurons, although many reports suggest that PtdIns3-K and Akt are involved in survival promotion. In addition, phosphorylation signals of mitogen-activated protein kinase (MAPK) and cAMP responsive element-binding protein (CREB), which have also been reported to be involved in survival promotion, were stimulated by BDNF much more potently than by IGF-1. These results show that there may be, as yet unidentified, intracellular signaling pathways other than the PtdIns3-K-Akt, MAPK and CREB signaling, to regulate survival promotion. These unidentified signaling pathways may be responsible for the distinct strengths of the survival-promoting effects of BDNF and IGF-1.

We report a case of a brainstem infarction and hemorrhage seen in a 21-year-old female with systemic lupus erythematosus (SLE) during treating retroperitoneal abscess. SLE has been treated with prednisolone and mizoribine for 4 years. The patient with right back and lower abdominal pain visited our hospital. Computed tomography (CT) revealed retroperitoneal abscess over surrounding right kidney, horizontal part of duodenum and in front of psoas muscle. Drainage was done with indwelled right single J catheter and penrose drain. Retroperitoneal abscess was much smaller, but, post drainage day 17, high fever, unconsciousness, down-blood pressure and down-beat nystagmus appeared suddenly. Brain CT scan revealed a brainstem wide infarction and hemorrhage spot. Pulse therapy with steroid was done, however unfortunately the patient was dead after 6 days.

We report the effects of direct hemoperfusion using polymyxin B-immobilized fiber (PMX treatment) on two patients with endotoxin shock from urosepsis. In both cases, urosepsis caused by pyelonephritis from a ureteral stone progressed to endotoxin shock and disseminating intravascular coagulation (DIC). Single J catheter was indwelt in the ureter for the purpose of drainage before PMX treatment. Drainage of the origin of infection, using effective antibiotics and PMX treatment improved shock state and DIC earlier than we expected.

Was examined the influence of depression in the occurrence and pain intensity. Patients presenting advanced cancer (n = 92) were evaluated. The patients were divided in 2 groups, with or without pain during the week preceding the interview. Pain and depression were evaluated. Pain was observed in 62.0% of the cases and lasted 10 months as an average. It was moderate in the majority of patients and severe in 1/5 of them. Depression was related with the presence and intensity of pain. Patients with pain presented higher depression scores than patients without pain (p0.05). Higher pain scores were also correlated with higher depressive scores (p0.05).

Traumatic brain injured (TBI) patients with different trauma severity were analyzed about their recollection concerning the period of hospitalization. The study was carried out in the Head Injury Outpatient Clinic at the Central Institute of the FMUSP Hospital including 45 conscious patients able to sustain an interview. Most patients were male, young adults with the major cause of trauma such as traffic accidents and falls. Most patients (86%) reported unconsciousness state of different time duration in their hospitalization period and were unable to remember anything related to that period. The predominant recollection reported by the patients who never had consciousness decreased after the trauma and that ones who had it but awoke during the hospitalization were: seeing, feeling, hearing, and reacting either to sounds and procedures.

To address the issue of salvageability in relapsed children with NHL who had all received the same frontline therapy, we retrospectively studied the treatment response and the outcome of 27 children who relapsed following the CCLSG-NHL890 protocol. The reinduction rates and 3-year survival rates (mean +/- SD) were as follows: lymphoblastic lymphoma (LB, n = 9), 44%17 +/- 14%; leukemia lymphoma syndrome (LLS, n = 8), 25%0%; large cell lymphoma (LC, n = 3) 100%67 +/- 27%; Burkitt's lymphoma (B, n = 7) 0%0%. Thus, the salvageability of LC lymphoma was good, but the outcome of Burkitt's lymphoma was very poor. CCLSG-NHL960 protocol for LB lymphomas and intensive multiagent regimens for LC lymphomas produced favorable response rates, but the effect of the high-dose Ara-C regimen for Burkitt's lymphoma was not determined. The initial stages of the disease seemed to be associated with the patient outcome: the outcome of the patients in stage IV was inferior to that of patients in stages II or III. Other clinical variables, such as relapse sites, relapse time and BM rescue did not affect the patients' outcome.

A prospective and longitudinal study about head injury victims was carried out in order to identify their return to productivity after 6 months and 1 year post-trauma and to analyze the relationship between their return to work and their educational level as well as to determine the relationship between their return to work and their type of job before the onset of the injury. Of the 72 patients who were students or employees pre-injury, or housewives at the time of injury, the majority (73.6%) had returned to productivity 6 months after onset of injury. Of the victims who had returned to productivity, 25.0% had changed their original occupations or reported significant problems when returning to productivity. Baseline return was achieved in 48.6% of the victims at 6 months. Return to productivity was higher at 1 year after injury than at 6 months. When the relationship between return to work and educational level and job type was analyzed, return to work was not related to educational level or job type.

The objective of this retrospective study is to characterize the nature and severity of injuries of hospitalized traffic accident victims using the "Abbreviated Injury Scale" (AIS). Two-hundred and twenty such patients in a trauma reference hospital in Sao Paulo, Brazil were assessed. One-hundred and eleven of them were pedestrians, eighty-three vehicular passengers and twenty-six motorcyclists. The most common injuries were of the limbs, pelvic girdle and head/neck. Injury severity in all these patients was AIS = 3. Two-thirds of the forty-five victims who died were pedestrians.

BACKGROUND: Second opinion behaviour is often observed among Japanese primary care patients. These patients secretly visit university-affiliated hospitals without informing their doctors. Research to elucidate the psychosocial determinants of this behaviour in the Japanese primary care setting is needed. AIM: To describe the sociodemographic characteristics of second opinion patients (SOPs), and to determine the factors related to this behaviour. METHOD: Patients from the general medicine clinic answered our original questionnaire and a 30-item General Health Questionnaire (GHQ-30). A random sample of patients was questioned using the Diagnostic Interview Schedule. SOPs were defined as those patients who had visited another medical facility with the same complaint, and 'doctor-shopping' patients (DSPs) were defined as those patients who had visited two or more medical facilities with the same complaint. RESULTS: There were 420 SOPs among 1033 patients (41.0%). The multivariate analysis showed that residence and GHQ-30 were the significant differences between the SOPs and the first-visit patients (FVP) (P < 0.0005 for both factors). Also, the SOPs were anxious and sought advice from anybody, unlike the FVPs. Compared with the DSPs, they had a short duration of illness and they did not feel a worsening of their symptoms (P = 0.0001 for duration of illness; P = 0.006 for condition of illness). CONCLUSION: Our results showed that the SOPs who lived far from the medical school hospital felt anxiety and went to a university-affiliated hospital on the advice of anybody. Determining the reasons for this behaviour will require empirical studies regarding the nature of the patient's anxiety for illness.

We experienced three cases of right hydronephrosis, which were later diagnosed to have been caused by gastric cancer (Borrmann type IV). The patients were 25-, 38-, and 50-year-old women who complained of right back pain. Ultrasound sonography revealed right hydronephrosis in all three cases. We conducted drip infusion pyelography, computed tomographic scan and retrograde pyelography, but there were no signs of urinary stones or tumors, except for the presence of right ureteral stenosis. Since the patients had upper abdominal discomfort, they underwent gastrofiberscopy, which revealed scirrhous gastric cancer. We suspected that the right ureteral stenosis was caused by metastasis of gastric cancer. After a double J catheter was indwelt at the right ureter, combination chemotherapy of methetrexate + 5-fluorouracil was conducted. The right hydronephrosis diminished and all three patients became catheter-free.

The purpose of this study was to discover the differences among victims who had traumatic brain injury due to traffic accidents.Medical record of the head injury patients were analyzed according to their classification as traffic accident victims (pedestrian, motorcyclist or passenger and other motor vehicle deriver or passenger), age, gender, admission type (admitted from scene of the injury or from another hospital), duration of hospitalization, type of head injury, types of lesions present in other body segments and mortality. Patient's injury severity was measured by Injury Severity Score and head injury severity was analyzed using the ranking on the Glasgow Coma Scale, recorded by neurosurgeons during their first neuro assessment. All head injured patients admitted to a trauma center in S. Paulo city over a four-month period from March through June 1993, were included in the study. The sample was of 156 victims, with subsets of 80 pedestrians, 26 occupants of motorcycles and 50 occupants of other motor vehicles.The results of this study showed that the mortality rate was higher in the pedestrian subset (25.0%) than among other victims and higher for motorcycle occupants (19.2%) than for motor vehicle victims (8.0%). Statistical differences between the subsets were established when the head injury severity variable was analyzed using the Glasgow Coma Scale. On the other hand, the differences between the three subsets was not statistically significant when the measurement used was the Injury Severity Score. Analyses of other variables showed important differences among subset distributions.

From July 1992 to May 1996, 16 patients with non-curative postoperative or recurrent colorectal carcinomas were treated with 5-fluorouracil (5-FU) plus leucovorin (LV) systemic chemotherapy. LV was given at a dose of 20 mg/m2/d immediately followed by 5-FU at 370 mg/m2/d. LV was given by rapid intravenous (i.v.) injection and 5-FU by rapid or drip i.v. for 5 consecutive days. Courses were repeated once every 4 weeks for two months and then once every 5 weeks. All patients took 3 or more courses. The toxicity was tolerable, but one patient needed hospitalization because of severe gastro-intestinal toxicity. We observed 3 PR cases, no CR and an overall response rate of 19%. The response duration was 6 to 8 months, averaging 7.3 months, and median survival was 12 months. It was possible to perform this chemotherapy on an outpatient basis, so we think this chemotherapy is superior to in-hospital chemotherapy considering the issue of quality of life. However, the response rate was low and its duration was short. We must investigate chemotherapy further with new and more powerful chemical modulations to increase the response rate and to prolong the response duration.

We reviewed the medical records and images of 39 women with palpable breast masses, including 18 cases with breast cancer and 21 cases with benign breast mass, to compare diagnostic accuracy and clinical agreement between ultrasonography and mammography in breast cancer detection. We showed that the operating characteristics of ultrasonography, including sensitivity, specificity and positive likelihood ratio, were superior to that of mammography. We also confirmed that the established malignant criteria for malignancy, including lobulated shape, irregular contour and non-uniform internal echo in ultrasonography, and stellate mass in mammography, were statistically significant in distinguishing breast cancer from benign breast lesion. Moreover, the interobserver agreement kappa of ultrasonography and mammography were 0.64 and 0.59, respectively. Ultrasonography was also superior to mammography in attaining clinical agreement between the different observers in breast cancer detection.

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.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).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.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.

The criteria proposed by Petersdorf has been in use internationally to define the fever of unknown origin (FUO) since 1961 and the research of FUO has progressed with this criteria. Mean-while, new diagnostic methods have been developed and illness behavior of febrile patients has changed considerablly. Accordingly, the definition by Petersdorf is becoming less matched to current clinical situation. Therefore, we have developed a new practical criteria of FUO; i.e., out-patients who are febrile more than 2 weeks, documented temperature higher than 37.5 degrees C at least on one occasion and undetermined diagnosis and in-patients who are febrile more than 1 week with documented temperature higher than 37.5 degrees C, and undetermined diagnosis. Between October 1, 1993, and October 31, 1996, we prospectively collected a series of febrile patients who fulfilled our new criteria. We identified 56 patients by our criteria (23 male and 33 female, age: 49.7 +/- 20.6. range 15 to 88). Of this 56 patients, 19 (32%) were found to have infections, 18 (31%) had collagen disorders, 5 (9%) had malignancy and 6 (10%) had died. Of 56 patients, 38 (68%) were in the newly added group. Of these 38 patients, 4 patients had subacute necrotizing lymphoadenitis, 4 cytomegalovirus infection, 3 polymyalgia rheumatica, 3 tuberculosis. Four patients (10%) died. With our criteria, febrile patients who previously had not been included were found to have as poor a prognosis as with the Petersdorf group.

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 (P0.05), and significantly shorter disease-free survival in patients with mutant FLT3 than in patients with wild-type FLT3 (P0.05). 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.

Among Haemophilus influenzae isolated from children with respiratory tract infections, the evolution of ampicillin resistance was investigated during 1996 and 1997 in Japan. beta-Lactamase production was assessed and minimum inhibitory concentrations (MICs) of eight antimicrobial agents were determined using a broth microdilution method in Mueller-Hinton-lysed horse blood medium. Of 74 H. influenzae, 11 strains (14.9%) produce beta-lactamase and were thus highly resistant to ampicillin (MIC of4.0 microgram/ ml). In addition, moderate resistance to ampicillin, defined as an MIC of==1.0 microgram/ml, was noted in 44.4% of all beta-lactamase-negative isolates. These beta-lactamase-negative ampicillin-resistant (BLNAR) organisms were resistant to other cephalosporins such as cefpodoxime and cefdinir, while beta-lactamase-producing strains were susceptible to them. Cefditoren, cefteram, and minocycline were active against all strains studied, whereas cefaclor and clarithromycin were inactive against all H. influenzae isolates in this study. Results indicate that BLNAR strains have emerged among children with respiratory tract infections in Japan.

To clarify the efficacy of modern intensive chemotherapy for ALL patients with unfavorable features, we compared the time to failure and initial clinical features of children who relapsed in the bone marrow or combined sites, as documented by early CCLSG studies (H811 and H851; 1981-1987) and later studies (H874 and H/HH911; 1987-1993) concerning high-risk ALL patients. In the later studies patients outcomes with new intensive regimens employing early intensification and reinduction therapy were apparently better than those of patients in the early studies with conventional regimens. When we compared the number of relapsed patients based on duration of first remission, we found that the improved outcomes for patients in the later studies were due to a decrease in the number who relapsed 7-36 months after the start of treatment (intermediate relapse), and that the percentage of those who relapsed within the first 6 months of therapy (early relapse) was higher. Patients with high initial WBC counts tended to relapse much earlier than those with low initial WBC counts. However, in the later studies, patients with high WBC counts often relapsed after the termination of therapy (late relapse). These results suggest that the intensive chemotherapy regimens used in the later studies can prevent the development of drug resistant leukemic clones, except in extremely high-risk patients likely to relapse within the first 6 months of therapy.

A point mutation of the N-ras gene is one of the known genetic alterations identified in patients with acute lymphoblastic leukemia (ALL), but its clinical importance is still controversial. Using polymerase chain reactions, we examined codons 12, 13 and 61 of this gene in 125 Japanese childhood ALL patients (64 common-ALL, 22 pre-B-ALL, 33 T-ALL, 2 B-ALL, 3 undifferentiated ALL, and 1 unclassified ALL) including 9 relapsed patients. An N-ras point mutation was observed in 14 (11%) patients (9 common-ALL, 3 T-ALL, and 2 undifferentiated ALL; 13 patients at diagnosis and 1 at relapse). The patients with undifferentiated ALL harbored an N-ras mutation at a significantly higher rate. However, no correlation was found between the presence of an N-ras mutation and sex, age, or white blood count. There was no significant difference in the event-free survival rate between 13 fresh patients with an N-ras mutation and 103 patients with a wild-type configuration. The N-ras mutation was present in about 10% of childhood ALL cases but it did not have a prognostic impact. The sequence analyses revealed that the majority of the patients (13/14) had an N-ras mutation of a G to A transition. This finding was consistent with previous reports on N-ras mutations in acute leukemias in which the incidence of a G to A mutation was significantly higher in ALL than in myeloid malignancies.

The influence of personal, cultural and affective factors and of the characteristics of the neoplastic diseases in the occurrence of pain and pain intensity in 92 patients presenting advanced cancer was evaluated. Pain usually moderate or severe during past week before the interview occurred in 62.0% of the patients. The duration of pain symptomatology lasted 10 months as an average. There was a higher proportion of patients with head and neck tumors in the group with pain than without pain. Cultural misconceptions about cancer pain control and the idea that doctors prescribe excessive amount of analgesics were correlated with higher intensities of pain (p0.05). Patients with pain presented higher depression scores than patient without pain (p0.05). Higher pain scores were correlated with higher depressive scores (p0.05).

We report here on treatment results of consecutive CCLSG NHL studies (NHL855, 1985-1989; NHL890, 1989-1996). The NHL855 protocol consisted of an induction phase of five drugs (VCR, PRD, CPM, DXR, and high-dose MTX) and a maintenance phase of 7 drugs. The probabilities of EFS at 7 years were 78% (SE, 10%) for the patients with localized disease, and 38% (SE, 7%) for those with advanced disease. In the NHL 890 protocol, the patients were assigned to two different treatment groups according to their histology and received different consolidation therapy; non-lymphoblastic subtype was treated almost identically to NHL855 while LASP and VP-16 were newly added for the lymphoblastic subtype. The 7-year EFS improved to 91% (SE, 6%) for localized disease, and 61% (SE, 6%) for advanced disease. A remarkable improvement was particularly evident for lymphoblastic type with mediastinal mass. Optional trial of high-dose sequential chemotherapy and peripheral blood progenitor cell auto grafting resulted in an unfavorable outcome. The 7-year EFS according to main histological subgroups were as follows: 84% (10%) for large cell type, 67% (11%) for Burkitt's-type, 58% (10%) for lymphoblastic type. Secondary cancer occurred in two of the 163 patients studied. Both patients were AML (M0/M4) and MLL rearrangement was detected in the M4 case.

This study was developed in order to compare the use of the ABBREVIATED INJURY SCALE (AIS) and the CONDENSED ABBREVIATED INJURY SCALE (CAIS) as basis to calculate INJURY SEVERITY SCORE (ISS) in head injured patients. The results showed that the ISS value was equivalent in the majority of the patients (58.51%) codified by both scales. Also no statistic differences between the scales were perceived when we compared the severity levels as severe, moderate and minor, 61.38% of the lesions scored by AIS/90 were scored by CAIS/85, too.

A 55-year-old woman was admitted with urinary frequency. She had undergone augmentation ileocystoplasty due to tuberculous bladder atrophy 37 years previously. Cystoscopy revealed a tumor on the posterior wall which had been augmented with the ileum. Partial cystectomy and bladder reconstruction using a segment of ileum and ascending colon were performed. Gross inspection showed a 15 x 10 mm, papillary tumor on the ileal mucosa near the vesico-ileal anastomosis. Histologically, moderately differentiated adenocarcinoma infiltrating into the muscle layer was surrounded by the normal ileal mucosa. She has been free of recurrence for 2 years postoperatively. This is the 8th case of adenocarcinoma following augmentation ileocystoplasty reported in the Japanese literature.

We investigated TEL/AML1 fusion mRNA in 108 children with acute lymphoblastic leukemia (ALL) (86 B-lineage ALL, 15 T-ALL, two mixed lineage ALL, and five other phenotypes) using reverse transcriptase-polymerase chain reaction (RT-PCR). TEL/AML1 transcripts were found in 14 patients (13%) including three relapsed patients, and were unexceptionally limited to B-lineage ALL patients. The incidence of TEL/AML1 transcripts among B-lineage ALL was 16% (14/86). The reciprocal AML1/TEL transcripts were detected in 12 (86%) of the 14 cases expressing a TEL/AML1 transcript. In three cases, the TEL gene was fused to exon 3 of the AML1 gene, and to exon 2 in the remaining cases. To evaluate the amount of TEL/AML1 molecules for the quantification of a minimal residual disease (MRD), a plasmid vector which contained either a long TEL/AML1 PCR product (464 bp) or a short one (425 bp) was used as a competitor. We amplified RNAs obtained from bone marrow (BM) at complete remission or from peripheral blood stem cell (PBSC) harvests in two representative cases. For one PBSC harvest showing a positive result, a competitive PCR was carried out to quantify the amount of MRD. A 1:4 dilution series of competitor vectors was constructed, and each vector was added to a PCR reaction which contain a constant amount of cDNA obtained from the PBSC harvest. An equivalent point was compared to that of corresponding samples at diagnosis. Using this method, MRD in the PBSC harvest was 3.9:10(3). Our results elucidated the incidence, lineage-specificity, and variant forms of TEL/AML1 fusion transcripts in childhood ALL. Since the percentage of other chromosomal translocations in childhood ALL is not more than 5%, TEL/AML1 transcript would be the most feasible clone-specific marker for these patients. In addition, our method could be a powerful tool for quantification of the TEL/AML1 transcript and for the detection of MRD.

The purpose of this study was the analysis of head injury severity based on physiologic and anatomic indexes, shown by hospitalized patients from the Intensive Care Unit. The study was characterized according to patients' age, gender, external cause and remaining time at the Intensive Care Unit, and it was verified that from the total of admitted patients the most of them were young adult males with a remaining time percentage of 6.28 days, Most frequent external cause was traffic motor vehicle accidents (65.72%). The study also considers the lesions and trauma severity according to the Abbreviated Injury Scale/ Injury Severity Score (AIS/ISS), reporting that the lesions were classified as severe lesions non-life threatening (AIS-3) and severe lesions life threatening (AIS-4). It was verified that the body region most affected was head and neck (57.65%). In relation to the trauma severity (ISS), most of the patients reached ISS 16. The study also presents the head injury severity by determining the consciousness level using the Glasgow Coma Scale (GCS); most of the patients showed severe head injury or GCS from 3 to 8. Analysis regarding a possible relation between the GCS and the AIS/ISS was performed to evaluate the head injury severity, considering the fact that the patient was victim of head injury or head injury and other body lesions. No meaning statistical element was observed regarding the relation between the GCS-1 and the AIS from the head region, except when analyzed by groups of severity, or GCS-1 3 to 8 and AIS-head 4 to 5; GCS-1 9 to 12 and AIS-head 2 to 3. Similarly, no meaning statistical relation between the GCS-1 and the ISS, isolated head injury or head injury and other body lesions and the ISS or the GCS. It is expected that this study may contribute with new data for the continuous assistance improvement of patients, with head injury severity either related to other lesions or not, offered both by the Nursing and Health teams.

We analyzed homozygous deletions and mutations of the CDKN2(p16(INK4A)/MTS1) gene, using polymerase chain reaction and Southern blot analysis, in 120 children with acute lymphoblastic leukemia (ALL). Homozygous deletion was found in 17 of 89 (19%) precursor B-ALL patients, in 11 of 24 (46%) T-ALL patients, and in 0 of 7 other phenotype ALL patients. After excluding 28 (23%) patients who showed a homozygous deletion of CDKN2, we found that three patients (3%) had mutation at exon 2 of CDKN2 using PCR-SSCP and sequencing strategy. One had a CGA to TGA nonsense mutation (Arg to stop) at codon 72, one had a 1-bp deletion at codon 117, and the third had a 2-bp deletion at codon 70, resulting in frameshifts in the two latter patients. All three of these patients were T phenotype ALL, and the incidence of mutation in the 24 T-ALL patients examined was 13%. In contrast, no mutation was detected in the remaining patients with precursor-B or other type ALL (0/96). Our results suggest that mutational inactivation of the CDKN2 gene may contribute to the leukemogenic growth, especially in some patients with T-ALL.

1. The facilitation by zinc (Zn2+) of neurotransmission and the mechanisms underlying it were electrophysiologically investigated in rat cultured hippocampal neurones using whole-cell voltage- and current-clamp techniques. 2. Under whole-cell voltage clamp with an intracellular solution containing CsCl as a major salt, inward postsynaptic currents were observed at -40 mV in a cell culture where a neuronal network had been formed. The postsynaptic currents appeared to be mediated by gamma-aminobutyric acid (GABA) because the inward currents were abolished when intracellular CsCl was replaced with caesium phosphate and they were blocked by bicuculline (10 microM), an antagonist to GABA-gated channels. The currents were, however, also blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 30 microM), an antagonist to non-NMDA glutamate-gated channels, suggesting a contribution of a glutamatergic mechanism to the generation of the currents. Zn2+ (10 and 100 microM) potentiated the postsynaptic currents. 3. In addition to the potentiation of the postsynaptic currents, Zn2+ shifted net membrane current at -60 mV in an outward direction. The current-voltage relationship obtained under various ionic conditions indicated that Zn2+ inhibits a current component which is mainly carried by extracellular Na+. 4. Under whole-cell current clamp, Zn2+ (10 microM) induced a small hyperpolarization (up to 20 mV), which was accompanied by potentiation of the postsynaptic potentials and spike potentials. Tests were carried out to examine whether changes in resting potential by different protocols mimic responses observed with Zn2+. Hyperpolarization induced by current injection through patch pipettes increased the amplitude of postsynaptic currents, but did not enhance the appearance of spike potentials. In contrast, when extracellular K+ concentration was decreased from 5 to 2.5 mM, cells were hyperpolarized and spike potentials of large amplitude appeared. 5. The results suggest that Zn2+ potentiates neurotransmission and inhibits a background cationic current mainly carried by extracellular Na+ under physiological conditions. The inhibition of the Na+ permeation may increase membrane excitability and thereby contribute to the potentiation of neurotransmission.

A prospective study for detecting minimal residual disease (MRD) was conducted on children with acute lymphoblastic leukemia (ALL). Thirty-nine patients (38 B-lineage ALL, one T-ALL) with TCR delta rearrangements could be followed for 21 to 44 months (mean 30.9 months) excluding four patients who died. One hundred and ninety four bone marrow (BM) samples and 13 peripheral blood stem cell (PBSC) grafts were available for detection of MRD. Initially 34 cases were treated prospectively according to the CCLSG risk-stratified protocols for ALL (ALL874 or ALL911), and five cases according to the other protocols. Conventional chemotherapy was replaced by autologous PBSC transplantation (PBSCT) in five patients, by allogenic BM transplantation (BMT) in one patient, or suspended in another patient. Twenty-nine of 32 children in whom conventional chemotherapy could be continued without interruption remain in complete remission (CR). In 24 of the 29 patients MRD became undetectable within 12 months of their diagnosis. In five cases, BM samples obtained during maintenance therapy exhibited residual leukemia cells, and yet none of them relapsed (mean follow-up period 28.6 months). Our results thus indicate that intensive maintenance therapy for patients with PCR-positive results during consolidation therapy may prevent subsequent relapse. Nine events of relapse were diagnosed in eight patients (five BM, two isolated central nervous system (CNS), one combined BM and CNS, one isolated skin relapse). An increase or a re-emergence of MRD was detected in BM samples obtained from patients prior to BM relapse, but one patient remained in CR despite reappearance of leukemic cells following a PCR-negative status. Monitoring of MRD failed to predict isolated CNS or skin relapse. PBSCT allows high-dose cytoreduction therapy for patients with refractory neoplasia. In our study, leukemic cells were identified in eight of 13 PBSC grafts harvested from five patients. Three of four children who received PBSC grafts containing leukemic cells relapsed within 6 months after PBSCT. Monitoring of MRD as part of quality control of PBSC grafts may ultimately contribute to improvements in PBSCT procedures.

Two pediatric leukemic patients with hepatosplenic candidiasis during multidrug antileukemic chemotherapy successfully underwent bone marrow transplantation (BMT) after aggressive antifungal chemotherapy employing fluconazole and amphotericin B with or without splenectomy. One patient received allogeneic marrow graft and the other received an autologous graft. One patient has been disease-free for more than 21 months after BMT without any recurrence of Candida infection. The other patient showed tentative reactivation of hepatic lesions just after BMT by CT scanning, but these lesions disappeared again by continuous administration of the antifungal agents. The second patient died of leukemia relapse without recurrence of fungal infection. Our cases indicate the possibility of successful BMT once a fungal infection is well controlled by antifungal chemotherapy and surgical resection.

The Children's Cancer and Leukemia Study Group (CCLSG) has conducted, since 1981, a series of protocols for treatment of acute lymphoblastic leukemia (ALL) in childhood. In a randomized control study of the 811 protocol (1981-1983) for standard-risk ALL, an intermittent cyclic regimen of an intermediate-dose of methotrexate (MTX) plus 6-mercaptopurine (6MP) showed significant superiority for maintenance chemotherapy as compared with conventional continuous administration of a low dose of the two drugs. The event-free survival (EFS) rate at 10 years was 65.4% for the intermittent cyclic regimen, while the EFS rate of continuous regimen was 36.1% (P0.01). The intermittent cyclic regimen may also be effective in preventing extramedullary relapses. In the 841 protocol (1984-1987), the three-drug induction therapy consisting of vincristine (VCR), prednisone (PDN) and L-asparaginase (L-ASP) improved the EFS rate (94.1% at 8 years) as compared with the two-drug therapy consisting of VCR and PDN (64.1%, P0.05). In the 874 protocol (1987-1990) two regimens with or without cranial irradiation for standard-risk patients were compared with respect to their ability to prevent central nervous system (CNS) leukemia and to improve overall outcome of ALL. The regimen with cranial irradiation showed a 79.9% EFS rate at 5 years, whereas the regimen without cranial irradiation demonstrated a 69.1% EFS rate (not significantly). Life-table analysis of serial CCLSG protocols for ALL in which the cyclic administration of intermediate-dose MTX plus 6MP has been standardized as maintenance therapy revealed that the outcome of allover ALL has gradually improved with increase of the EFS rate; 41.4% for the 811 protocol, 51.4% for the 841 protocol to 54.4% for the more recent 874 protocol.

A case of recurrent mediastinal goiter (oxyphilic cell carcinoma) in a 66-year-old female was reported. 19 years ago, the patient submitted to a right-hemithyroidectomy for the oxyphilic cell adenoma. Since two months, her dyspnea gradually aggravated. On admission, abnormal mass of right upper mediastinum was shown by chest X-ray. CT scan and MRI showed a 8 cm sized right upper mediastinal tumor with tracheal compression.

The goal of this study was to analyse the teaching-learning process of the pupil examination, in two aspects: the pupil diameter (DP), obtained by measurement and photomotor reflex (RFM), by subjective judgement. The sample was composed by 46 students of 4th semester in Nursing Undergraduate Course of University of São Paulo. The study was developed in two phases: the first was at nursing laboratory and the second, at clinical practice. The findings seemed to indicate that the learning was done because there was high level of agreement among students in their observation, development of an ability and a specific knowledge. The major difficulties was at clinical practice.

The authors report a case of poorly differentiated orbital rhabdomyosarcoma with intracranial extension in a 5-month-old female. The clinical and pathologic characteristics are discussed with reference to the differential diagnosis.

An analysis of the injury patterns presented by inpatients of a government teaching hospital, known as one of the emergency centers of S. Paulo city, Brazil, is given the majority of victims are young, male adults and most of them were later discharged from the hospital. In relation to the injuries the majority of the patients were classified as being of minor injury grade (ISS between 1 and 9) and the most frequent injuries were extremity and pelvic fractures, surface trauma, traumatic brain injury and extremity and pelvic dislocations. Besides extremity and pelvic fractures, the victims who died showed abdominal organ injury and traumatic brain injury and the ISS was over 20. Head injury patients who had a high Glasgow Coma Scale score had a low ISS and vice-versa.

Japanese mothers who had newly diagnosed diabetic children responded with shock, defensive retreat, and increased anxiety. During this process, the degree of their isolation was shown as trauma. Although many mothers had a strong reaction and suffered depression, loss of weight, pain, and feelings of exhaustion, they adapted to the diagnosis by the end of 1 year. Compared with an American study (HamburgInoff, 1983), some of the mothers' patterns of coping were similar to those used by mothers in the United States; others were related specifically to accepted Japanese cultural practices. They used several characteristic coping strategies: resignation, holding out, and believing in religion. Nurses need to be aware of the fact that mothers face a variety of psychological stress factors after their children are diagnosed as diabetic. They should be encouraged to feel and express a realistic hope.

The present study realized with 50 patients from an Intensive Care Unit, due to head injury and considering that the majority of them presented a score equal or below six (6) in the Glasgow Coma Scale, has shown that the utilization of invasive procedures is high. Regarding complications, there was predominance of fever, upper airway secretions, hematomas at the arterial puncture localization and diarrhea. Proportionally, the patients under a clinical treatment presented a lower number of invasive procedures and problems and the reverse occurred with those under surgery. The analysis of the association of the invasive procedures and problems compared to the level of consciousness has been affected.

Postinfarction left ventricular aneurysms are pathophysiologically divided into true, functional and false aneurysm. On 14 patients treated by aneurysmectomy, we studied the difference of pre- and post-operative cardiac function between true aneurysms (9 patients) and functional aneurysms (5 patients). The aneurysm area, which is expressed as the end-diastolic perimeter (akinetic or dyskinetic area/left ventricular silhouette), was 51.6 +/- 7.7% in the true aneurysms versus 35.7 +/- 6.0% in the functional aneurysms. Preoperatively, patients with a true aneurysm had a more severe clinical status than those with a functional aneurysm (Six of nine patients with a true aneurysm were in New York Heart Association functional class III or IV). Postoperatively, all patients except one with a true aneurysm and one with a functional aneurysm improved in clinical status. Nonaneurysmal EF, that is the function of the nonaneurysmal left ventricle, has a significant correlation to postoperative LVEF (r = 0.57, p less than 0.05). Nonaneurysmal EF was 54 +/- 4% in the true aneurysm group versus 51 +/- 16% in the functional aneurysm group. LVEF improved significantly (p less than 0.05) from 31 +/- 11% preoperatively to 55 +/- 10% postoperatively in the group of true aneurysm, but did not improved significantly from 43 +/- 12% to 50 +/- 9% in the functional aneurysm group. The postoperative akinetic area was 8.1 +/- 9.1% in the true aneurysm group versus 17.8 +/- 11.5% in the functional group. We conclude that larger and more adequate resection of aneurysms improves the cardiac function in the true aneurysm group more than in the functional aneurysm group.

The purpose of this study was to analyse the effects of sitting, supine and lateral positions on arterial oxygen tension (PaO2) and arterial carbon dioxide tension (PaCO2), in 22 adults patients, carier of some pulmonary bilateral disfunction, in recent post-operative cardiac surgery. The diagnosis of the pulmonary disfunction was done through radiographic torax evaluation. The patients stayed during 15 minutes in each position and after this, the arterial blood gases were measured. Based on Friedman test and Multiple Comparation test (a = 0.05), no significant changes in PaO2 and PaCO2 were noted.

A case, 23-year-old female of aortitis syndrome with left coronary ostial stenosis and aortic regurgitation was reported. The coronary angiography showed critical stenosis of the left coronary ostium with intact main stem and its branches. The aortogram revealed aortic regurgitation of grade III, and multiple obstructive or stenotic lesions on the left common carotid artery, the origin of the left renal artery, the inferior mesenteric artery and the abdominal aorta. After improvement of inflammatory findings by steroid therapy during 2 months, transaortic coronary endarterectomy and aortic valve replacement with 21 mm Björk-Shiley valve were performed successfully. Postoperative course was uneventful. Coronary angiography performed at the 57th day after the operation showed complete removal of the left coronary ostial stenosis, and aortography showed no evidence of perivalvular leakage of the aortic valve prosthesis. The indication of transaortic coronary endarterectomy and the technique used to avoid aortic valve detachment which may be caused by recurrence of aortitis were discussed in this paper.

alpha-Glucosidase activity was assayed in polymorphonuclear cells and lymphocytes from human peripheral blood with 4-methylumbelliferyl-alpha-D-glucopyranoside as substrate in the presence of sodium taurocholate. The pH vs. activity curve of the alpha-glucosidase indicated that differential estimation between acid and neutral alpha-glucosidases was difficult to perform with polymorphonuclear cells, but easily accessible with lymphocytes. The use of peripheral blood lymphocytes for the enzymatic diagnosis of Pompe's disease seemed to be more reliable than the use of whole leucocytes; this also the case with a classical Pompe's patient. The lymphocytes from the parents had normal or low normal activity of acid alpha-glucosidase in the freshly isolated state, but when cultured with phytohaemagglutinin for 72 h, the stimulated lymphocytes of both parents showed about half the enzyme activity of the cultured controls. It was deemed possible in all probability to identify the carrier state by assay of the enzyme activity in phytohaemagglutinin-stimulated lymphocytes.