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A novel single-nucleotide polymorphism (SNP), 829C--T in the 3'-untranslated region of the human dihydrofolate reductase (DHFR) gene transcript, was identified in the study population of 37 patients with childhood leukemias/lymphomas and 83 healthy Japanese children. Frequencies of the DHFR 829C/C, 829C/T, and 829T/T genotypes were 83.8, 10.8, and 5.4%, respectively, in the cases and 74.7, 19.3, and 6.0% in the controls, showing no significant difference in genotype frequencies between the cases and controls. When determined by real-time quantitative reverse transcription-PCR analysis, the highest expression of the DHFR transcript was demonstrated in the samples with a DHFR 829T/T polymorphism (P0.001). Direct association of the presence of the SNP with methotrexate-related adverse events in each patient was not demonstrated in this limited analysis. These data suggest that the novel DHFR 829 polymorphism is associated with a positive role in gene expression and provide evidence of a functional SNP in the 3' regulatory region of the gene.

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).

Microcapsules for internal radiation therapies containing the rare-earth metal elements Dy, Ho and Cu with a diameter of 5-10 microm were successfully obtained by an interfacial polymerization method and a successive sedimentation technique was employed to fractionate the microcapsules. A triisocyanate monomer and tricresylphosphate were used for a wall forming material and a core solvent for the metals, respectively. The amount of the metal elements loaded was measured using a high frequency plasma photoemission apparatus. The beta-ray radioactivity of 1 mg of microcapsules irradiated with a common neutron source is estimated as 370 microCi, which is satisfactorily strong for usual radiotherapy, when microcapsules containing Dy are used. Differential interference microscopy indicated narrow size distribution of the fractionated microcapulses.

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.

Transport of new quinolone antibacterial agents (quinolones) at the blood-brain barrier (BBB) was studied in vitro by using immortalized rat brain capillary endothelial cells RBEC1, and in vivo by using the brain perfusion method in rats and multidrug-resistant mdr1a/1b gene-deficient mice. The permeability coefficient of grepafloxacin measured by brain perfusion was increased by an excess of unlabeled grepafloxacin, suggesting a participation of a saturable BBB efflux system. Uptake coefficients of [(14)C]grepafloxacin, [(14)C]sparfloxacin, and [(14)C]levofloxacin by RBEC1 cells at the steady state were increased in the presence of the unlabeled quinolones. The steady-state uptake of [(14)C]grepafloxacin was increased in the presence of various quinolones. Brain distributions of [(14)C]grepafloxacin and [(14)C]sparfloxacin evaluated in terms of the brain-to-plasma free concentration ratio in mdr1a/1b gene-deficient mice were significantly higher than those in wild-type mice, demonstrating an involvement of P-glycoprotein as the efflux transporter. Anionic compounds, including 4, 4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) and genistein, increased the steady-state uptake of [(14)C]grepafloxacin by RBEC1 cells. Because [(14)C]grepafloxacin was transported by multidrug resistance-associated protein (MRP), in MRP1-overexpressing cells and because RBEC1 and primary cultured brain capillary endothelial cells expressed MRP1, this protein may be an additional efflux transporter for quinolones. Furthermore, the permeability coefficient of [(14)C]grepafloxacin across the BBB was increased by DIDS or in the absence of bicarbonate ions in the brain perfusion method. DIDS or bicarbonate ion did not affect MRP1 function. Accordingly, the brain distribution of quinolones is restricted by the action of multiple efflux transporters, including P-glycoprotein, MRP1, and an unknown anion exchange transporter.

Improved strains for the production of riboflavin (vitamin B2) were constructed through metabolic engineering using recombinant DNA techniques in Corynebacterium ammoniagenes. A C. ammoniagenes strain harboring a plasmid containing its riboflavin biosynthetic genes accumulated 17-fold as much riboflavin as the host strain. In order to increase the expression of the biosynthetic genes, we isolated DNA fragments that had promoter activities in C. ammoniagenes. When the DNA fragment (P54-6) showing the strongest promoter activity in minimum medium was introduced into the upstream region of the riboflavin biosynthetic genes, the accumulation of riboflavin was 3-fold elevated. In that strain, the activity of guanosine 5'-triphosphate (GTP) cyclohydrolase II, the first enzyme in riboflavin biosynthesis, was 2.4-fold elevated whereas that of riboflavin synthase, the last enzyme in the biosynthesis, was 44.1-fold elevated. Changing the sequence containing the putative ribosome-binding sequence of 3,4-dihydroxy-2-butanone 4-phosphate synthase/GTP cyclohydrolase II gene led to higher GTP cyclohydrolase II activity and strong enhancement of riboflavin production. Throughout the strain improvement, the activity of GTP cyclohydrolase II correlated with the productivity of riboflavin. In the highest producer strain, riboflavin was produced at the level of 15.3 g l(-1) for 72 h in a 5-l jar fermentor without any end product inhibition.

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.

We report a rare case of liposarcoma of the spermatic cord in the left scrotum and inguinal region. The patient was a 75 year old male, who visited our hospital with the complaint of painless left scrotal swelling and inguinal mass which had been noticed for 3 to 4 years. Ultrasonography and computed tomography (CT) showed a heterogenous mass in the left inguinal region and intrascrotum. We suspected a left testicular tumor and removed it by high inguinal orchiectomy. Histological examination revealed a well-differentiated liposarcoma of sclerosing type. Tumor local recurrence was not recognized at 8 months after operation. This is the 43rd case of liposarcoma of the spermatic cord in the Japanese literature.

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.

There are few epidemiological studies on traumatic brain injury (TBI), and those that allow broad comparative analyses of this problem are even more scarce, due to methodological obstacles. Usually, the studies address head injury (they include the cranial envelopments and content) but are reported as TBI, given the difficulty of mutual exclusion. It is also common for them to be centered at specific severity levels, only for hospitalized victims or according to the external cause, such as traffic accidents. With full respect to these limits, this study had as its objective the estimation of the TBI incidence in patients resident and in-hospital, in the hospital network in the city of São Paulo, Brazil, in 1997, as well as the estimation of TBI-caused mortality amongst external causes, at this same time and locale. Data for the study consisted of Ministério da Saúde data on hospital discharges, analyzed based on Autorizações de Internação Hospitalar (AIH) and obituary data on external causes, contained in the Programa de Aprimoramento das Informações de Mortalidade (PROAIM) data base. It was found that 29 717 patients were hospitalized due to lesions and poisoning; of these 3 635 (12%) had TBI; the hospitalization rate was 0.36/1000 pop.; and hospital mortality was 10%. The mortality coefficient due to external causes was 87.3/100 000 pop. Minimum TBI mortality rate is estimated at a minimum of 26.2 and a maximum of 39.3/100000 pop.

We reported the cases of thoracoscopic sympathectomy, that is, six cases of hyperhidrosis, three of post herpetic neuralgia, and four of reflex sympathetic dystrophy, including recurrent or incompletely resected or ineffective ones. Recently this procedure for hyperhidrosis had been performed frequently because of its effectiveness, less pain, early discharge and cosmetic aspect. For an ineffective case of hyperhidrosis abdominal respiration which emphasized the exhalation and using an upper abdomen decreased the sweating. The balance of autonomic nerve system, toward parasympathetic dominant, was thought to be improved by conscious respiration. The decrease of sweating right after the operation in a case of incomplete resection indicated that intraoperative maneuver could restrict the sympathetic nerve. This procedure for a pain control could be less effective than that for hyperhidrosis, so an adequate preoperative informed consent was thought to be necessary.

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 report on measurements of the incoherent elastic neutron-scattering intensity ${I}_{\mathrm{el}}(Q)$ of polyethylenes with degrees of crystallinity 0.46 and 0.96 in a wide Q (length of scattering vector) range from 0.4 to 6.2 ${\mathrm{\AA{}}}^{\mathrm{\ensuremath{-}}1}$ to observe the deviation from the Gaussian behavior. The non-Gaussian behavior was observed in both the amorphous and the crystalline phases. The non-Gaussian behavior in the theoretically well-known crystalline phase can be understood more or less quantitatively in terms of the anisotropy of the mean-square displacement. The result implies that at least a part of the non-Gaussian behavior of the amorphous phase is due to the same source, while another part may be due to the dynamical heterogeneity inherent to the amorphous phase.

Blast caused by Pyricularia grisea (telemorph Magnaporthe grisea) (Rossman et al., 1989) is the most destructive disease in Japan. Many rice cultivars with complete resistance have been developed to control the disease. However, the resistance in the cultivars has been broken down within several years after their release due to the increase in new races of rice bast fungus virulent to the resistance (Kiyosawa, 1974; Yamanaka and Yamaguchi, 1987). To prevent the breakdown of the resistance, the use of multilines proposed by Jensen (1952) and Borlaug (1959) was suggested, and reduction of blast development in mixtures of rice cultivars and near-isogenic lines with different complete resistance genes to blast has been reported (Koizumi, 1983; Shindo and Horino, 1989; Koizumi, 1994; Koizumi and Fuji, 1994; Koizumi et al., 1996; Nakajima et al., 1996a).

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.

A 31-year-old man admitted to our hospital complaining of right chest pain. Chest X-ray on admission revealed a collapsed lung and an air fluid line in the right thorax. A chest tube drainage was carried out, but hemorrhagic pleural fluid was drainaged. Forty minutes later, an anemia developed and chest X-ray showed increased massive right pleural collection. Therefore, emergent surgery was performed. An operation under thoracoscopic guidance was converted into thoracotomy because of massive blood clots and fresh bleeding. A bleeding originating from the branch of 1st intercostal artery and a bulla on upper lobes were noted. The artery was coagulated with electrocoutary and ligated using Endo-loop. This artery is not congenital abnormal one but collateral expanded one of which the elastic lamina is thickened. Spontaneous hemopneumothorax is life-threatening, emergent operation should be undergone.

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.

Chemotherapy regimens for high-risk (HR) groups for childhood acute lymphoblastic leukemia (ALL) are briefly reviewed in this study. For patients with B-precursor ALL, the HR category includes patients more than 10 years of age who have a WBC count at diagnosis of more than the 50,000/microliter that is becoming a global standard for HR classification. Since 1981, the Children's Cancer and Leukemia Study Group (CCLSG) has developed a series of protocols for HR-ALL. These include the H811, H851, H874, H/HH911 and more recent H/HH941 protocols. With the H874 protocol in particular, patient outcomes with new intensive regimens strengthened by early treatment with cyclophosphamide (CPM) plus cytosine arabinoside (Ara-C), and reinduction therapy with THP-adriamycin, vincristine, prednisone and L-asparaginase seem to be better than outcomes of patients with the previous protocols. An intermediate-dose of CPM plus Ara-C showed a significantly higher event-free survival (EFS) rate than a high-dose regimen with the same drugs. The EFS rates at 4 years based on the H941 and HH941 protocols were 72.8% and 62.8%, respectively. Although the various prognostic factors for acute myelogenous leukemia (AML) have been inconsistent, bone marrow chromosome abnormalities including monosomy 7 an 11q23 rearrangement have become indicators for a poor prognosis, whereas patients with t (15; 17), t (8; 21) and inv (16) have a decreased likelihood of relapse after achieving remission. The 11q23 abnormality is a very important prognostic factor for infant acute leukemia. Based on these findings renewal protocols for AML, including hematopoietic stem cell transplantation, have been conducted by our CCLSG and other study groups.

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.

The possible involvement of adenosine 5'-triphosphate (ATP) receptors in the function of the hippocampus and of pain transmission is discussed. Involvement of these receptors in the function of the hippocampus has been suggested by several reports. In the paper we presented the data that ATP inhibits the glutamate release in cultured hippocampal neurons. This and the report revealing that ATP protected against cell death by glutamate suggest that ATP may be playing a role in the protection of the hippocampus from over-stimulation. Microglia cells are activated by the stimulation of ATP and releases plasminogen which is well known to promote the development of mesencephalic dopaminergic neurons and enhance neurite outgrowth from explants of neocortical tissue. Therefore, ATP may have a role in repairing the damaged neuronal networks as well as protection.

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.

Multiple copies of a cis-acting DNA element, metal-responsive element (MRE) are required for heavy metal-induced transcriptional activation of mammalian metallothionein genes. To approach the regulatory mechanism mediated by these multiple elements, we studied the properties of seven MREs located upstream of the human metallothionein-IIA (hMT-IIA) gene in detail. Transfection assays of reporter gene constructs each containing one of these MREs as the promoter element revealed that only four MREs can mediate zinc response. With respect to the distribution of active MREs over the promoter region, the hMT-IIA gene is largely different from the mouse metallothionein-I gene, suggesting that MRE arrangement is not an important factor for metal regulation. Experiments using various model promoters showed that multiple MRE copies act highly synergistically, supporting the biological significance of the multiplicity. Only the four active MREs efficiently bound the purified transcription factor human MTF-1, and MRE mutants defective in binding this protein lost the ability to support zinc-induced reporter gene expression, strongly suggesting that the direct interaction between human MTF-1 and a set of the selected MREs plays the major role in heavy metal regulation. In protein/DNA binding reactions in vitro, the purified human MTF-1 was activated by zinc but not by other metallothionein-inducing heavy metals, supporting the idea that zinc is the direct modulator of human MTF-1.

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.

A 70-year-old man was given a diagnosis of sigmoidovesical fistula due to diverticulitis through the combination of examinations including cystoscopy, sigmoidoscopy, barium enema, urogram, computed tomography (CT), and magnetic resonance imaging (MRI). Among these, MRI was the most useful for the direct detection of the fistula in T1 weighted images and the confirmation of the lesion in T2 weighted images.

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.

We have measured Raman spectra of a diamond film prepared on the (111) surface of cubic boron nitride(c‐BN) by the dc plasma chemical vapor deposition method. The polarization property of the Raman line of diamond agrees well with that of LO phonon for the (111) surface of c‐BN. The agreement between the polarization property of Raman lines of diamond and c‐BN indicates a possibility of the heteroepitaxial growth of the diamond film on the (111) surface of c‐BN. It is found that the diamond layers on c‐BN are under tensile stress of 2.2×1011 dyn/cm2. The value of the corresponding tensile strain agrees well with the lattice mismatch calculated from the lattice constants of c‐BN and diamond, supporting the possibility of the heteroepitaxial growth of the diamond film. Raman spectroscopy is a powerful technique not only to estimate the stress in the diamond film but also to determine the crystallographic orientation.

We report here on the preliminary treatment findings of a CCLSG NHL 960 study that was initiated in March 1996. In this study, 37 patients with non-Hodgkin's lymphoma were assigned to 4 different treatment groups according to disease stage and histology: (1) localized disease; (2) advanced disease, lymphoblastic type; (3) advanced disease, large cell type; and (4) advanced disease, Burkitt type. The first three groups received the modified protocols of the NHL 890 study. Groups 1 and 3 received COPADM induction therapy (CPM, VCR, PRD, ADR, and MTX). After achieving remission, Group 1 received only maintenance therapy consisting of alternate administration of 7 drugs, while Group 3 received additional intensification therapy with combination chemotherapy consisting of MTX and Ara-C, followed by a maintenance phase involving the administration of 9 drugs. Group 2 received COPADL induction therapy (CPM, VCR, PRD, ADR, and LASP) and consolidation/intensification therapies followed by a maintenance phase. Group 4 received short-term intensive COPADM polychemotherapy. Twelve patients with localized with localized disease (stage I-II) and 25 patients with advanced disease (stage III-IV) were enrolled in this study. Except for 2 patients in the advanced disease stages who died earlier in the course of the study, all patients remained in remission.

We analyzed the mRNA expression of the FHIT gene by reverse transcription-PCR (RT-PCR) in 54 cases of acute lymphoblastic leukemia (ALL; 11 cases of T-cell ALL [T-ALL] and 43 cases of non-T-ALL) and 40 cases of acute myeloid leukemia (AML). In 46% of the ALL cases and 55% of the AML cases, FHIT expression was absent or markedly decreased. Only abnormal short bands were detected in 30% of the ALL cases and 5% of the AML cases. Eighteen of 19 abnormal transcripts had the same fusion of exons 2-7, and all lacked the starting codon in exon 5. No obvious normal-sized PCR products were detected in cases exhibiting abnormal transcripts. These findings suggest that the expression of functional FHIT protein was lost in the majority of ALL (76%) and AML (60%) cases. Differential quantitative PCR of exons 3-9 of the FHIT gene and RT-PCR of the PTPRG gene, which is centromeric to the FHIT gene, showed the presence of the target sequences. Fluorescence in situ hybridization analysis using probes covering exons 5 and 8 revealed no difference in the signal patterns between leukemia and normal cells, showing one or two signal doublets in more than 90% of nuclei, and indicated that gross segments of the FHIT gene were not homozygously deleted in these cases. A small number of transcripts with an aberrant fusion between exons 2 and 7 were detected by RT-PCR in the bone marrow cells from four healthy individuals. Granulocytes, lymphocytes, and monocytes in the bone marrow cells of a healthy individual contained transcripts with the same fusion. This unique fusion of exons 2 and 7 might be preferentially seen in either neoplastic or normal hematopoietic cells, regardless of their lineage. The finding that FHIT expression was abolished in the majority of leukemia cases might support the hypothesis that the FHIT gene acts as a tumor suppressor, at least in leukemia.

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.

This study is part of a project about ICU's characteristics in São Paulo city. This article describes the continuing education programs for nursing staff. 43 ICUs were analysed and the questionnaire answered by the ICU nurse coordinator was used to collect data. Results showed that 34 (79.1%) of the ICUs have initial program for training each nursing staff category and 18 (41.9%) had regular continuing education program focusing primarily on nursing procedures and routines and the update in pathologies. Continuing education programs are developed primarily by ICU's nurses. 50.2% of the nurses answered that they attended specialisation/extension courses too, in Medical Surgical Nursing or in other areas or in both areas. Due to this result and the development of the ICU's nurses as specialists, some suggestions are presented to improve the continuing education program in these Units.

The trauma severity assessment and basic life support maneuvers in prehospital setting can represent to the trauma victim the opportunity of survival until his/her can get assistance in the hospital.To study external cause victims assessed in the prehospital phase by the physiologic index named Trauma Score modificado (TSm).Retrospective analyses were made of 1414 victims attended by Sistema de Atendimento Móvel às Urgências (SAMU-RESGATE-SP) in the Municipality of São Paulo during 1991. Data were gathered from prehospital data recording sheets and necropsy records.Prehospital attendance was carried out in 81.31% until 40 minutes. Non-fatal victims (83.96%) had 12 and 11 TSm scores while 53.96% of the fatal victims had 0, 1 and 2 scores. External surface (30.25%) and head/neck (20.98%) were most injured areas and 63.63% fatal victims with Injury Severity Score (ISS)or = 16 died within first 24 hours. Comparing the fatal victims TSm and ISS scores verified that 81.20% victims with TSm score between 0 and 11 had major trauma (ISSor = 16).Strong trends were also found out in that fatal victims with low TSm scores showed relations to the high ISS scores.

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.

This is an analysis about critical care research production and publication as well as nursing research's profile in Brazil, focusing on the research producer, the research product and the product consumer.

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.

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.

1 The effect of adenosine 5'-triphosphate (ATP) on glutamatergic synaptic transmission in hippocampus was examined by an indicator of intracellular Ca2+ oscillations. These oscillations were postsynaptic responses by glutamate released from presynaptic sites. ATP completely inhibited the oscillations in a concentration-dependent manner. 2 The ATP-induced inhibition was mediated via P2-purinoceptors since ATP exhibited the inhibitory action even in the presence of P1-purinoceptor antagonists. Also non-hydrolysable ATP analogues and uridine 5'-triphosphate (UTP) inhibited the oscillation. 3 The rank order of agonist potency of ATP analogues for inhibition of the Ca2+ oscillation was as follows: 2-methyl-thio-adenosine 5'-triphosphateor = ATPadenosine 5'-O-(3-thiotriphosphate)UTPalpha, beta-methylene-adenosine 5'-triphosphate. These inhibitory effects were insensitive to suramin. Judging from this rank order of potency, the inhibitory P2-purinoceptor could be assigned to a subclass of GTP-binding protein coupled-type receptors. 4 The site of action of ATP was thought to be presynaptic since ATP did not affect the postsynaptic Ca2+ responses by glutamate. These results suggest the existence of a presynaptic inhibitory P2-receptor that inhibits glutamate release in the hippocampus.

This study is the first part in a series of the articles reporting results of a project conducted to analyse the structural resources of ICUs in São Paulo city. This article describes the characteristics of those Units, considering the quantity and geographic location, bed number, maintainer entity, type of assistance, type of client, as well the percentage of beds usage and length of stay. Forty three ICUs were analysed and a questionnaire answered by the ICU nurse coordinator was used to collect data. The results showed that the number of ICUs in the hospital varied from 1 to 4, being more frequently those with only one ICU (68.8%). 79.2% of the Units were in private hospitals, located in the central area of the city. ICU beds represented 8.0% of the total hospital beds and there was an average of 10 beds per Unit. There was a predominance of general ICUs (60.5%), destined only for adult patients (51.2%) and for clinical-surgical treatment (95.3%). The percentage of beds usage in majority of ICU was between 80 to 100% and the length of stay was 4,5 days.

A 3-year-old boy was referred because of a painless mass in the left scrotum. On palpation, the mass was discriminated from the testis, epididymis and spermatic cord and showed transillumination. A part of the mass was dark purple in color. Total surgical excision of the mass was performed. The lesion was multicystic (2-15 mm), adherent to the scrotal skin, and easily dissectable from the testicle. Pathological examination revealed lymphangioma as a major component and hemangioma as a minor part. He has been free of recurrent disease for 2 years. This is the 7th case of hemo-lymphangioma of the scrotum in the Japanese literature.