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Recovery of overall and local lung function loss 18 months after irradiation for malignant lymphoma.

PURPOSE: To determine the local and overall pulmonary injury 3 to 18 months after irradiation and to investigate whether the changes in overall lung function can be predicted using the three-dimensional (3-D) dose distribution in combination with dose-effect relations for local injury; and to study the influence of chemotherapy on the injury. PATIENTS AND METHODS: Local perfusion (Q), ventilation (V), and tissue density were measured in 25 patients treated for malignant lymphoma, before, 3 to 4 months after, and 18 months after irradiation. Dose-effect relations for local injury, calculated using correlated single-photon emission computed tomographic (SPECT) and computed tomographic (CT) data, were combined with the 3-D dose distribution, to calculate the estimated mean local changes over the complete lung for each patient. The result was correlated with the actual changes in pulmonary function. RESULTS: A dose-dependent increase with injury was observed at 3 to 4 months after irradiation, which at 18 months had recovered by approximately 50% to 60%. The estimated mean relative reduction of local Q predicted the change in overall lung function within 10% of the actually observed values in 63% to 73% of patients. Chemotherapy given before radiotherapy enhanced radiation-induced reduction of local Q significantly, with dose-modifying factors of 1.22 and 1.37 at 3 to 4 months and 18 months, respectively. CONCLUSION: Partial recovery of radiation-induced reduction of local and overall lung function was observed at 18 months after irradiation. The overall functional outcome of most patients could be well predicted, based on the estimated mean local injury over the complete lung. Chemotherapy given before radiotherapy enhanced the radiation-induced reduction of local Q.

Adolescent↗

Loss of heterozygosity 1p36 and 19q13 is a prognostic factor for overall survival in patients with diffuse WHO grade 2 gliomas treated without chemotherapy.

PURPOSE: This study was conducted to elucidate the impact of loss of heterozygosity (LOH) for chromosomes 1p36 and 19q13 on the overall survival of patients with diffusely infiltrating WHO grade 2 gliomas treated without chemotherapy. PATIENTS AND METHODS: We assessed the LOH status of tumors from patients harboring WHO grade 2 gliomas diagnosed between 1991 and 2000. Patients were either followed after initial biopsy or treated by surgery and/or radiation therapy (RT). Overall survival, time to malignant transformation, and progression-free survival were last updated as of March 2005. RESULTS: Of a total of 79 patients, LOH 1p36 and LOH 19q13 could be assessed in 67 and 66 patients, respectively. The median follow-up after diagnosis was 6 years. Loss of either 1p or 19q, in particular codeletion(s) at both loci, was found to positively impact on both overall survival (log-rank P < .01), progression-free survival, and survival without malignant transformation (P < .05). Tumor volume (P < .0001), neurologic deficits at diagnosis (P < .01), involvement of more than one lobe (P < .01), and absence of an oligodendroglial component (P < .05) were also predictors of shorter overall survival. The extent of surgery was similar in patients with or without LOH 1p and/or 19q; RT was more frequently resorted to for patients without than for patients with LOH 1p/19q (30% v 60%). CONCLUSION: The presence of LOH on either 1p36 or 19q13, and in particular codeletion of both loci is a strong, nontreatment-related, prognostic factor for overall survival in patients with diffusely infiltrating WHO grade 2 gliomas.

Adult↗

Sensitivity of time allocation to an overall reinforcer rate feedback function in concurrent interval schedules.

Six pigeons were trained on concurrent variable-interval schedules in which feedback functions arranged that the overall reinforcer rate either (a) was independent of preference, (b) decreased with increasing absolute preference, or (c) increased with increasing absolute preference. In Experiment 1, the reinforcer rate in an interreinforcement interval was determined by the absolute time-allocation ratio in the previous interval. When arranged reinforcer ratios were varied, there was no evidence of control over preference by overall reinforcer rate. In Experiment 2, the feedback function arranged that reinforcer rates were an inverse function of absolute preference, and window durations were fixed times. In Phase 1, using schedules that provided a four-to-one reinforcer ratio, the window duration was decreased from 20 s to 5 s over four conditions. Then, in Phases 2 and 3, the arranged reinforcer ratios were varied. In Phase 2, the reinforcer rate in the current 5-s time window was determined by preference in the previous 5-s window, and in Phase 3, the window durations were 20 s. Again, there was no indication of control by obtained overall reinforcer rate. These data call into question theories that suggest that the process underlying matching is one of maximizing overall reinforcer rates, or that preference in concurrent aperiodic schedules is controlled to any extent by overall reinforcer rate. They also question the notion that concurrent-schedule preference is controlled by molecular maximizing.

Journal Article↗

How to teach a pigeon to maximize overall reinforcement rate.

In two experiments deviations from matching earned higher overall reinforcement rates than did matching. In Experiment 1 response proportions were calculated over a 360-response moving average, updated with each response. Response proportions that differed from the nominal reinforcement proportions, by a criterion that was gradually increased, were eligible for reinforcement. Response proportions that did not differ from matching were not eligible for reinforcement. When the deviation requirement was relatively small, the contingency proved to be effective. However, there was a limit as to how far response proportions could be pushed from matching. Consequently, when the deviation requirement was large, overall reinforcement rate decreased and pecking was eventually extinguished. In Experiment 2 a discriminative stimulus was added to the procedure. The houselight was correlated with the relationship between response proportions and the nominal (programmed) reinforcement proportions. When the difference between response and reinforcement proportions met the deviation requirement, the light was white and responses were eligible for reinforcement. When the difference between response and reinforcement proportions failed to exceed the deviation requirement, the light was blue and responses were not eligible for reinforcement. With the addition of the light, it proved to be possible to shape deviations from matching without any apparent limit. Thus, in Experiment 2 overall reinforcement rate predicted choice proportions and relative reinforcement rate did not. In contrast, in previous experiments on the relationship between matching and overall reinforcement maximization, relative reinforcement rate was usually the better predictor of responding. The results show that whether overall or relative reinforcement rate better predicts choice proportions may in part be determined by stimulus conditions.

Journal Article↗

Overall body fat and regional fat distribution in young women: quantification with MR imaging.

Overall body fat and its distribution in different regions are important predispositions to known aberrations in lipid and glucose metabolism. The accuracy of MR imaging in estimating overall body fatness and regional fat distribution at individual landmarks was determined by comparing it with well-accepted measures by deuterium-oxide (D2O) dilution and bioimpedance analysis. Fourteen normal young women (athletes and control subjects) were studied. A total of 308 axial, T1-weighted, spin-echo MR images over a specific region in the trunk (21-24 scans per subject) were obtained. Morphometric computer image analysis was performed to determine the subcutaneous, internal, and total fat volumes in each image. The data were analyzed in two ways: data from all slices were summed to assess overall body fatness, and six anatomic landmarks were chosen for regional comparisons. MR-determined estimates of overall body fatness strongly correlated with total body fat measures by D2O dilution in both total fat (r = .91) and subcutaneous fat (r = .92) determinations. Athletes in both the low- and high-intensity training phases had significantly lower values of MR-determined total body fatness than did control subjects. Parallel to total body fatness, athletes had significantly lower MR-determined ratios of total fat/total volume in four of six individual landmarks compared with control subjects. Our experience suggests that MR is an accurate method to quantify overall body fatness, when compared with D2O dilution and bioimpedance analysis. MR could also discriminate regional components of subcutaneous and internal body fat at individual landmarks.

Adipose Tissue↗

Overall management outcome of ruptured posterior fossa aneurysms.

A study of the overall management of ruptured posterior fossa aneurysms was conducted over a 1-year period (1993) in five neurosurgical centers in Sweden, serving a population of 6.93 million people. Forty-nine cases were identified and treated. One-third of the patients were in the seventh or eighth decade of life. Good overall management outcomes at 6 months were achieved in 30 cases (61%). The overall mortality rate was 27%. Patients with Hunt and Hess Grades I and II had a good overall recovery rate of 87%. On admission, 69% of the patients were assigned Hunt and Hess Grades III to V. The impact on patient outcomes of the intraoperative difficulties encountered, especially in the basilar tip area, is stressed. The authors found that delayed operation is not warranted in most cases. Frequent devastating rebleeding was observed among patients not offered early aneurysm clipping and the operative results were not at significant variance between the early and late surgical groups. Only 50% of the patients scheduled for delayed surgery ultimately made a good recovery, whereas 72% of patients scheduled for early operation did so. The data demonstrate that overall management results with posterior fossa aneurysms, comparable to achievements with supratentorial lesions, are within the reach of modern strategies, even in centers not specializing in these problems.

Adult↗

Clinical significance of P-glycoprotein expression and function for response to induction chemotherapy, relapse rate and overall survival in acute leukemia.

BACKGROUND AND OBJECTIVES: A multidrug-resistance (MDR) phenotype mediated by P-glycoprotein (P-gp) contributes to chemotherapy failure in acute leukemia. However, the exact prognostic significance of this resistance mechanism is still unclear, mostly due to methodologic problems in P-gp detection. We therefore investigated, whether P-gp expression levels or functional P-gp activity better predict response to induction chemotherapy, relapse rate and overall survival in acute leukemia. DESIGN AND METHODS: We examined cell samples of 121 adults with de novo acute myeloid leukemia (AML) and 102 children with newly diagnosed acute lymphoblastic leukemia (ALL) for P-gp expression and functional P-gp activity by flow cytometry. P-gp function was determined by the rhodamine 123 (rh123)-efflux test (AML n=121, ALL n=102) and P-gp expression levels using the P-gp specific monoclonal antibodies (moabs) MRK-16 (AML n=51, ALL n=31), 4.E3 (AML n=35, ALL n=32), or UIC-2 (AML n=68, ALL n=50). We correlated our findings with the immunophenotype, FAB morphology, cytogenetics and clinical data of the examined patients. RESULTS: P-gp expression levels as detected by MRK-16 and 4.E3 were very low and did not differ between AML and ALL as estimated using relative fluorescence intensity (RFI) values and D-values by Kolmogorow-Smirnov (KS) statistics. For moab UIC-2, P-gp expression levels were higher in AML than in ALL. Within AML, moab UIC-2 mainly reacted with myelomonocytic-differentiated leukemic cells of the FAB M4/5 subtypes. No correlation between P-gp expression levels as detected by MRK-16, 4.E3 or UIC-2 and the response to induction chemotherapy or relapse rate, both in AML and ALL, was observed. However, a prognostic impact of P-gp expression levels on overall survival in AML was seen for moab MRK-16. Moreover, within AML, P-gp function was higher in immature blast cells as defined by immunophenotype and FAB morphology and correlated with response to induction chemotherapy, relapse rate, overall survival as well as cytogenetic risk groups. In ALL, the overall functional P-gp activity was lower than in AML and did not correlate with immunophenotypical subgroups, response to induction chemotherapy, relapse rate or overall survival. INTERPRETATION AND CONCLUSIONS: Our data demonstrate a prognostic impact of P-gp in AML but not ALL and indicate that the functional rh123-efflux assay should be preferred for flow-cytometric P-gp evaluation in acute leukemia compared with P-gp expression analysis by monoclonal antibodies.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[Effect of overall alkali of Tongbiling on CD69 expression activated mouse T lymphocytes].

AIM: To investigate the effect of overall alkali of Tongbiling(TBL) on CD69 expression on activated mouse T lymphocytes and its possible mechanism. METHODS: Phorbol 12,13-dibutyrate(PDB) or concanavalin (ConA) were added successively into mouse lymphocytic culture with various concentration of overall alkali TBL. After 24 hours, CD69 expression rate on mouse T lymphocytes activated with PDB or ConA was analyzed by flow cytometry. RESULTS: Overall alkali TBL could significantly down-regulate CD69 expression in a dose-dependent manner. CONCLUSION: Overall alkali TBL can significantly inhibit CD69 expression on activated mouse T lymphocytes. This study provided an experimental basis for application of overall alkali TBL to treatment of rheumatoid arthritis.

Alkaloids↗

LEA-135 expression: its association with a lower risk of recurrence and increased overall survival of patients with lymph node-positive primary invasive breast cancer.

A retrospective study was undertaken to determine and compare the prognostic significance of LEA-135 protein expression by immunohistochemistry with other prognostic pathological parameters, with respect to recurrence and overall survival. This study was conducted in freshly-frozen tissue sections from a cohort of 367 patients having primary invasive breast cancer, with axillary lymph node metastasis. The association of LEA-135 expression was compared with estrogen and progesterone receptor status, segmentectomy or radical mastectomy and hormonal therapy or chemotherapy in terms of recurrence or disease-free survival. Pathologic parameters including tumor size, histological tumor type and histological grade, as well as age of patients at the time of initial diagnosis, and the treatments, together with a median follow-up of 8.8 years were contemplated for the study. Among these parameters, tumor size and histological grade were individually and significantly associated with an increased probability of recurrence (log rank p<0.001 in both cases) and short survival (log ranks p<0.001 and p=0.002, respectively), whereas age was only significantly associated with an increased probability of recurrence (log rank p=0.002) by univariate analysis. By multivariate analysis, both tumor size and histological grade remained statistically significant for recurrence (log rank p<0.001 and p=0.013, respectively) and overall survival (log ranks p<0.001 and p=0.016, respectively). Among the prognostic biomarkers, both ER and PR expression were associated with a decreased rate of recurrence (log ranks p<0.001 and p=0.008, respectively) and overall survival (log ranks p<0.001 and p=0.002, respectively) by univariate analysis. By multivariate analysis, only the ER expression remained significantly associated with a decreased recurrence and increased overall survival (log ranks p=0.023 and p=0.002, respectively). Patients with high (>50% positive cells) or moderate (5-50% positive cells) number of LEA-135-positive cells had a lower probability (46%) of recurrence at 10 years after surgery compared to 76% in LEA-135-negative patients (log rank p<0.001) by univariate analysis. Moreover, the probability of overall survival was higher in patients with high or moderate expression of LEA-135 (46% and 47%, respectively) compared to LEA-135-negative patients (24%) by univariate analysis (log rank p=0.009). By multivariate analysis, the association remained statistically significant for recurrence (log rank p<0.001) and survival (log rank p=0.002). However, there was no significant association between LEA-135 and any of the pathological parameters, age, hormone receptor status, the mode of surgery or the form of therapy (chemo- and/or hormonal) received by this cohort of patients. The results show that an improved prognosis was directly associated with the density of LEA-135-positive cancer cells, while loss of LEA-135 expression was associated with an aggressive phenotype of cancer cells during breast cancer progression. Thus, LEA-135 expression can be implicated as a significant and independent biomarker to identify and distinguish high- from low-risk patients with lymph node-positive invasive breast cancer for an aggressive treatment. Moreover, according to the present results, LEA-135 expression appears to be associated with the tumor cells that have retained certain normal biological characteristics, leading to their lack of aggressiveness and hence a better prognosis.

Age Factors↗

Ovarian cancer stage IIIC. Consequences of treatment level on overall and progression-free survival.

BACKGROUND: Maximum cytoreduction at primary surgery has been found to be one of the strongest prognostic factors for survival of ovarian cancer. The aim of the study was to investigate the influence of hospital level (primary vs secondary care centre), number and timing of surgery and chemotherapy on how radical the surgery was at primary treatment of epithelial ovarian cancer Stage IIIC. MATERIAL AND METHODS: A retrospective study based on record information from all patients with epithelial ovarian cancer Stage IIIC treated at the Norwegian Radium Hospital (NRH) 1985-2000, in total 776, subdivided into four groups: 1) Local primary surgery, no direct re-operation at NRH, no interval debulking; 2) local primary surgery, no direct re-operation, but interval debulking after 3-4 courses of chemotherapy at NRH; 3) local primary surgery, direct re-operation at NRH, no interval debulking; 4) primary surgery at NRH. Lymph node biopsies at re-operation in early stages and upgrading of stage where necessary were registered. RESULTS: Whether surgery was radical or not was an independent prognostic factor for overall and progression-free survival. The treatment group was an independent prognostic factor for overall, but not for progression-free survival. Group 3 had significantly the best overall and progression-free survival (p = 0.01 and 0.05). For macroscopically radical surgery both overall and progression-free survival were found significantly better for groups 3, 4 and 1 than for group 2. Most lymph node biopsies were performed during the last period and 28% were upgraded from Stage I and II to IIIC. More patients were referred for primary surgery at NRH during the last 5-year period during which overall survival and time to progression were significantly better. INTERPRETATION: Whether primary surgery is radical or not is a significant prognostic factor for survival and primary surgery is best performed by specialists in gynaecological oncology.

Adult↗

Amplification and overexpression of HER-2/neu (c-erbB2) in endometrial cancers: correlation with overall survival.

Few molecular genetic alterations have been identified in endometrial cancers that are associated with poor clinical outcome. Overexpression of HER-2/neu, transforming growth factor alpha, and p53 proteins have all been associated with poor prognosis in women with endometrial cancer. In this study, the level of HER-2/neu gene amplification and expression was characterized in 92 endometrial cancers. Fluorescence in situ hybridization (FISH) was used to characterize HER-2/neu gene copy number, and immunohistochemistry was used to characterize expression. Forty-seven of the 90 (52%) endometrial cancers were characterized as showing moderate or high immunostaining. HER-2/neu gene amplification was detected in 17 of 81 (21%) cases. Immunohistochemical staining and FISH results were both available for 80 cases. Fourteen of these cases showed both moderate or high immunostaining and gene amplification. Clinical follow-up information was available for 76 women in this study. Women whose endometrial cancer exhibited HER-2/neu gene amplification by FISH had a shorter overall survival than women whose endometrial cancer lacked amplification (P = 0.018). Likewise, tumors with moderate or high HER-2/neu immunostaining were associated with a lower cumulative overall survival than tumors with low immunostaining by log rank analysis (P < 0.0001). Multivariate analysis of survival rates revealed HER-2/neu overexpression to be an independent predictor of overall survival (P = 0.0163). Among those patients with HER-2/neu overexpression, adjuvant chemotherapy or radiation therapy was associated with an improved overall survival (P = 0.039). However, among those women whose tumor lacked overexpression, overall survival was not improved by adjuvant treatment.

Adult↗

Disease-free and overall survival after cryosurgical monotherapy for clinical stages B and C carcinoma of the prostate: a 20-year followup.

PURPOSE: We attempt to provide insight into the historical efficacy of cryosurgical monotherapy for prostate carcinoma through a single institution, retrospective, long-term followup. MATERIALS AND METHODS: From 1973 to 1977, 66 men underwent cryosurgical monotherapy for prostate carcinoma. Patient charts were reviewed to determine age, clinical stage, tumor grade, and progression-free, overall and cause specific survival status. RESULTS: Of 51 patients 47 to 81 years old (mean age 67.2) with clinically localized carcinoma 11 had clinical stage B and 40 had stage C disease. Tumor grade was well differentiated in 11 cases, moderately differentiated in 26, poorly differentiated in 11 and undetermined in 3. Recurrence was documented in 40 of the 51 men (78.4%) as local in 34 and unspecified in 6. Following recurrence all patients were treated with adjuvant therapy. All but 2 patients were followed until death with a mean followup of 93.7 months. Of the 51 men 24 (47.1%) died of disease and 17 (33.3%) died of an unspecified cause. Kaplan-Meier analysis demonstrated median overall progression-free survival of 34 months and median overall survival of 75 months. Median progression-free survival by grade was 34 months for well differentiated, 36 for moderately differentiated and 14 for poorly differentiated disease (p = 0.0288), and 57 for stage B and 30 for stage C disease (p = 0.0377). Median overall survival by grade was 114 months for well differentiated, 80 for moderately differentiated and 82 for poorly differentiated disease (p = 0.4437), and 60 months for stage B and 78.5 for stage C disease (p = 0.4915). CONCLUSIONS: As performed in this series cryosurgery was poorly effective for local control of prostatic carcinoma. Stage and grade correlated with the duration of tumor response but not with overall survival.

Aged↗

Volumetric changes following barrier regeneration procedures for the surgical management of grade II molar furcation defects in baboons: I. Overall defect fill.

A computer imaging technique has been advocated for measuring the volumetric fill in furcation defects. Histologic material for this investigation was obtained from an animal study using five adult baboons (Papio anubis). The photographed histology was converted into digitized electronic information, and a computer calculated the overall volume of defect fill for the treated and the untreated control sites. All volumetric measurements were expressed as a percentage of the original surgically created defect size, with 100% indicating complete healing of the defect. The results indicate that none of the defects achieved complete healing. Teeth that had received flap debridement had the most overall defect fill (79.50%). Teeth that received a biodegradable barrier (Epi-Guide) showed a mean overall defect fill of 74.98%, while sites treated with an exclusion barrier (Gore-Tex) showed 70.75% overall fill. The untreated control teeth showed a mean overall fill of 78.70%. A variety of statistical tests revealed no significant differences among teeth within the same animal and between treatments and controls. The following conclusions were drawn: (1) digital imaging technology is a useful research tool for determining the volume of defect fill in surgically created grade II molar periodontal furcation defects in the baboon model; and (2) no significant differences were found among the treatment modalities and the untreated control sites.

Animals↗

Salivary gland carcinoma: independent prognostic factors for locoregional control, distant metastases, and overall survival: results of the Dutch head and neck oncology cooperative group.

BACKGROUND: We analyzed the records of patients with malignant salivary gland tumors, as diagnosed in centers of the Dutch Head and Neck Oncology Cooperative Group, in search of independent prognostic factors for locoregional control, distant metastases, and overall survival. METHODS: In 565 patients, we analyzed general results and looked for the potential prognostic variables of age, sex, delay, clinical and pathologic T and N stage, site (332 parotid, 76 submandibular, 129 oral cavity, 28 pharynx/larynx), pain, facial weakness, clinical and pathologic skin involvement, histologic type (WHO 1972 classification), treatment, resection margins, spill, perineural and vascular invasion, number of neck nodes, and extranodal disease. The median follow-up period was 74 months; it was 99 months for patients who were alive on the last follow-up. RESULTS: The rates of local control, regional control, distant metastasis-free and overall survival after 10 years were, respectively, 78%, 87%, 67%, and 50%. In multivariable analysis, local control was predicted by clinical T-stage, bone invasion, site, resection margin, and treatment. Regional control depended on N stage, facial nerve paralysis, and treatment. The relative risk with surgery alone, compared to surgery plus postoperative radiotherapy, was 9.7 for local recurrence and 2.3 for regional recurrence. Distant metastases were independently correlated with T and N stage, sex, perineural invasion, histologic type, and clinical skin involvement. Overall survival depended on age, sex, T and pN stage, site, skin and bone invasion. CONCLUSIONS: Several prognostic factors for locoregional control, distant metastases, and overall survival were found. Postoperative radiotherapy was found to improve locoregional control.

Adenocarcinoma↗

A discrepancy between the instantaneous and the overall collection efficiency of the Fenwal CS3000 for peripheral blood stem cell apheresis.

The collection efficiency (CE) of the Fenwall CS3000 continuous flow blood cell separator in the apheresis of peripheral blood stem cells during haemopoietic recovery following myelosuppressive chemotherapy was analysed. Ninety-three apheresis were performed in 19 patients using procedure 3 on the Fenwal CS3000. The overall CE was calculated from the pre-apheresis cell counts and the stated blood volume processed. Instantaneous CE was calculated from cell counts in the inlet and return lines. The overall mononuclear cell and granulocyte-macrophage colony forming unit CE were 64.0% and 55.8%, respectively, significantly lower than the instantaneous CEs of 94.5% and 95.4%, respectively (P = 0.0001, t test, for both comparisons). Three factors unrelated to machine performance contributed to the lower overall CE despite a high instantaneous CE: (1) A fall in the patient's mononuclear cell counts during apheresis leading to an overestimation of the cells available for collection, (2) dilution of blood by anti-coagulant, and (3) the operational dead space of the Fenwal CS3000. The overall CE corrected for these 3 factors approximated the instantaneous CE closely. Thus there is little room for further enhancement of machine performance because the Fenwal CS3000 is already operating with a very high instantaneous CE. To achieve major improvement in the yield of peripheral blood stem cell harvests, more effective mobilization protocols and better timing of apheresis are required.

Antineoplastic Combined Chemotherapy Protocols↗

Evaluation of overall toxicity of high-dosage methotrexate regimens.

The occurrence of overall toxicity was analyzed for 43 patients with osteosarcoma who received 349 high-dosage courses of methotrexate (HD-MTX) with citrovorum factor (Leukovorin) "rescue" (CF). The dosages of HD-MTX ranged from 50 to 350 mg/kg. Overall toxicity was assessed on the basis of five manifestations of toxicity: stomatitis, dermatitis, myelosuppression, liver dysfunction, and kidney function abnormalities. The great majority (91.4%) of the infusions were well tolerated, but 8.6% were associated with moderate or severe toxicity. Stomatitis and serum glutamic-oxaloacetic transaminase (SGOT) changes were the most frequent postinfusion findings. Three patients died from causes related to MTX toxicity. Dose, age, sex, and number of prior infusions were investigated by logistic regression analysis for prognostic effect on frequency of moderate to severe overall toxicity. Age and number of prior infusions had significant (P less than 0.06) effects on overall toxicity. Patients older than 15 years with greater than 10 prior infusions constituted the "high risk" group with a risk of moderate to severe toxicity 6.3 times that of the younger patients with fewer than 10 infusions.

Adolescent↗

Dependency of overall fractionation effect of respiration on hemoglobin concentration within blood at rest.

In this study it was investigated in which way varying hemoglobin concentrations within blood influence overall fractionation effect of respiration, meaning a change in composition of isotopic oxygen molecules 16O2 and 16O18O within oxygen transported during entire respiration. Since overall fractionation effect of respiration is known to consist of different fractionating and non-fractionating processes, measuring it under condition of anemia could be useful in relating changes in isotopic compositions of oxygen to limitations of entire oxygen transport caused by one or more of these processes. Experiments were performed on 6 patients suffering from various degrees of anemia of a variety of etiologies and on 6 healthy humans. All test subjects breathed air at rest. Samples from inspiratory and expiratory gas were taken in order to analyse 16O18O/16O2 ratios with the aid of respiratory mass spectrometry. Values of overall fractionation effect decreased with respect to a drop in hemoglobin concentration from 17.6 to 6.6 g/100 ml in terms of a linear relationship (r = 0.79) provided that values of overall fractionation effect were normalized so as to exclude the influence of varying ventilatory conditions. It could be shown that at a value of hemoglobin content of 6.6 g/100 ml, 16O2 was transported in preference to 16O18O with a 0.57% higher rate compared to a value of 0.78% obtained at a hemoglobin concentration of 17.6 g/100 ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Anemia↗

Overall obesity and abdominal obesity and the risk of metabolic abnormalities.

BACKGROUND: Obesity is a risk factor for multiple chronic diseases. AIM: To determine the relationship between overall or abdominal obesity and various metabolic abnormalities. METHODS: The medical records of participants undergoing examination from January 2000 to December 2002 were analysed. Body mass index (BMI; kg/m2) for overall obesity and waist circumference (WC; cm) indicating abdominal obesity were measured. Four groups were studied: (1) BMI < 27kg/m2, WC: female < 80cm or male < 90cm; (2) BMI > or = 27kg/m2, WC: female < 80cm or male < 90cm; (3) BMI < 27kg/m2, WC: female > or = 80cm or male > or = 90cm; (4) BMI > or = 27kg/m2, WC: female > or = 80cm or male > or = 90cm. RESULTS: There were 1,342 (44%) females and 1,711 males aged 20-87 years. The prevalence of overall obesity was 20.4% and abdominal obesity was 48%. Obese subjects had more metabolic abnormalities than non-obese in terms of risk of hypertension, hyperglycaemia, hypercholesterolaemia, hypertriglyceridaemia, high level of LDL, low level of HDL, high ratio of TC/HDL, hyperuricaemia and fatty liver. CONCLUSIONS: As overall and abdominal obesity may predict clustering of metabolic abnormalities we suggest that BMI and WC are convenient methods for assessing metabolic abnormalities in primary healthcare settings.

Abdominal Fat↗