Eight patients, of whom four had acute myeloid leukemia (AML) and four had chronic myeloid leukemia (CML) blast crisis, were treated with a combination of cytosine arabinoside (ARA-C: 1,600 mg/m2 in ...three patients, 1,200 mg/m2 in five patients), tetrahydrouridine (THU: 2,800 mg/m2 in two patients, 2,646 mg/m2 in one patient, 2,100 mg/m2 in five patients), and carboplatin (900 mg/m2 in four patients, 720 mg/m2 in one patient, 450 mg/m2 in three patients). As a result of this treatment, five of the eight patients became aplastic. Two of the four patients with CML blast crisis reverted to the chronic phase and two of the four patients with acute nonlymphocytic leukemia (ANLL) attained a remission (one partial remission and one complete remission). The major toxicities included myelosuppression, unacceptable hepatotoxicity, and diarrhea. Pharmacokinetics studies revealed that the addition of carboplatin did not significantly change the disposition of ARA-C. ARA-C levels were not significantly changed in comparison with those obtained in a prior study of ARA-C with THU (ARA-C plasma levels at 3 h, 2630 +/- 1170 ng/ml).
Several questions exist regarding CD5+ B cells. These include the ability of these cells, as compared to CD5- B cells, to undergo an Ig isotype class switch, the subclasses utilized, and the effects ...that switching may have on antigen binding. To address these issues, ten patients with chronic lymphocytic leukemia (CLL) whose CD5+ leukemic B cell clones produced IgG were studied. Monoclonal IgG was collected from PMA-stimulated CLL cells and from heterohybridomas constructed with these cells, and then analyzed for IgG subclass utilization, autoreactivity, and DNA idiotype expression. The monoclonal B cells from 80% of the CLL patients produced IgG1 and those from 20% produced IgG3. None produced IgG2. In contrast to the known autoreactivity of IgM-producing CD5+ CLL cells (> 50% autoreactive), none of these IgG antibodies reacted significantly with the autoantigens tested. However, three did react significantly with autoantigen after artificially increasing antibody valency by crosslinking. Whereas five of the IgG molecules expressed a cross reactive idiotypic (CRI) marker characteristic of non-mutated kappa anti-DNA antibodies, three expressed a CRI displayed primarily on mutated IgG anti-DNA antibodies. Thus, some CD5+ human B cells can undergo an isotype class switch that for these CLL cells is biased against IgG2 and in favor of the IgG1 and IgG3. In their native state the IgG molecules secreted by these isotype-switched CD5+ cells have diminished autoreactivity, as compared to IgM-producing CLL cells. Since some of the IgG antibodies could be made auto- and poly-reactive by increasing antigen-binding valency, while others expressed idiotypic markers of mutated antibodies, certain of these CD5+ B cells probably utilize non-mutated Ig V genes coding for polyreactive antibodies, whereas others may use genes that have undergone somatic mutation and that code for more restricted specificities. Therefore, both valency and VH gene mutation may account for the diminished autoreactivity of these CD5+ B cell-derived IgG antibodies.
The Prevention of Depression and Anxiety Seligman, Martin E. P; Schulman, Peter; DeRubeis, Robert J ...
Prevention & treatment,
12/1999, Letnik:
2, Številka:
1
Journal Article
Recenzirano
A brief and inexpensive cognitive-behavioral prevention program was given to university students at risk for depression.
At risk
was defined as being in the most pessimistic quarter of explanatory ...style. Two hundred thirty-one students were randomized into either an 8-week prevention workshop that met in groups of 10, once per week for 2 hr, or into an assessment-only control group. Participants were followed for 3 years and the authors report the preventive effects of the workshop on depression and anxiety. First, the workshop group had significantly fewer episodes of generalized anxiety disorder than the control group and showed a trend toward fewer major depressive episodes. The workshop group had significantly fewer moderate depressive episodes but no fewer severe depressive episodes. Second, the workshop group had significantly fewer depressive symptoms and anxiety symptoms than the control group, as measured by self-report but not by clinicians' ratings. Third, the workshop group had significantly greater improvements in explanatory style, hopelessness, and dysfunctional attitudes than the control group and these were significant mediators of depressive symptom prevention in the workshop group.
When 1-beta-D-arabinofuranosylcytosine (ara-C), 25 mg/m2, is infused over 3 h together with tetrahydrouridine (THU) at 10 to 350 mg/m2 to heavily pretreated patients with solid tumors, ...Michaelis-Menten type kinetic values are observed with leveling off of delta area under the curve, delta ara-C levels at 3 h, and delta total body clearance after 150 mg/m2 of THU. When the ara-C dose was increased to 50, 75, and 100 mg/m2 coinfusion of 250 or 350 mg/m2 of THU significantly increased plasma ara-C at peak and area under the curve. In contrast, total body clearance and volume of distribution decreased significantly. At 100 mg/m2 of ara-C coinfused with high doses of THU, i.e., at 350 mg/m2, the pharmacokinetics of plasma ara-C was changed from a biphasic decay of plasma ara-C at peaks (control) to a curve similar or identical to a monophasic curve, indicating that THU not only inhibits deamination but also changes the distribution of ara-C. This combination provides plasma ara-C levels (greater than or equal to 10 microM) comparable to high dose ara-C at 1 g/m2. Such plasma ara-C levels are considered to be sufficient for saturation of the kinases catalyzing the production of 1-beta-D-arabinofuranosylcytosine 5'-triphosphate. This reduced ara-C dose necessary to achieve saturation of kinases also reduces plasma 1-beta-D-arabinofuranosyluracil levels substantially. Toxicity of this combination was predominantly confined to bone marrow and gastrointestinal toxicity.
BACKGROUND:Ultrasound (US) is commonly used for the diagnosis of hemoperitoneum after blunt abdominal trauma, but the value of US as an aid for identification of operative lesions after penetrating ...trauma is not well documented. The purpose of this investigation was to determine the accuracy of US for the evaluation of penetrating torso trauma and to assess the impact of this information on patient management.
METHODS:We conducted a prospective cohort observational study of consecutive penetrating torso patients at a Level I trauma center.
RESULTS:During the 6-month trial period, 177 victims of penetrating torso trauma were assessed by our trauma teams. Ninety-two patients had stab wounds, 84 patients had gunshot wounds, and 1 patient had a puncture wound. All 28 patients with positive US examination had an exploratory laparotomy or thoracotomy (one patient had more than one procedure), resulting in 26 therapeutic operations. There were 149 negative US examinations, but in this group, 36 patients underwent laparotomy or thoracotomy, and 28 had therapeutic operations. The overall accuracy of the US examination was therefore 85%, the sensitivity was 48%, and the specificity was 98%. There were only three patients who had their initial management altered by a positive US examination.
CONCLUSION:The US examination lacks sensitivity to be used alone in determining operative intervention after gunshot or stab wounds. Rarely does US information contribute to the management of patients with penetrating abdominal injuries.
In patients with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, the concentrations of the cortisol precursor 17-alpha hydroxyprogesterone (17-OHP) and its metabolite delta ...4-androstenedione (delta 4 A) are increased. CAH was diagnosed in twins by measurement of 17-OHP and delta 4 A concentrations in amniotic fluid obtained by amniocentesis from both amniotic cavities at 17 weeks' gestation. Both prenatal karyotypes were 46,XX. Spontaneous labor and delivery of 2 nonviable fetuses with genital masculinization occurred at 26 weeks' gestation. It is concluded that delta 4 A measurement, like 17-OHP quantitation, is valuable in the prenatal diagnosis of CAH; that both methods appear useful in prediction of CAH in twin fetuses; and that abnormal adrenal-mediated masculinization in female CAH is well established before the end of the second trimester.
Sixteen patients with previously treated acute nonlymphocytic leukemia or chronic myelogenous leukemia in blast crisis were given one to three courses of esorubicin by continuous infusion over 48 h. ...Dosage levels extended from 35 to 85 mg/m2. Four patients showed partial responses of short duration. Nonhematological toxicity observed at dosages of 55 to 85 mg/m2 were mucositis, diarrhea, skin rash, transaminitis, nausea, vomiting, and cardiac dysfunction. One patient receiving 85 mg/m2 developed acute florid congestive heart failure within hours of administration of the drug. Pharmacokinetic analysis revealed large interpatient variation in plasma drug levels. At the end of infusion, plasma decay of esorubicin was rapid initially but slow thereafter, with a terminal half-life of 20 to 54 h. The metabolite 4'-deoxy-13-hydroxydoxorubicin reached significant plasma levels. Total body clearance, renal clearance, volume of distribution at steady state, and mean residence time show little variation during dose escalation for both esorubicin and 4'-deoxy-13-hydroxydoxorubicin. Urinary excretion of esorubicin and 4'-deoxy-13-hydroxydoxorubicin accounted for 10.5 and 1.5%, respectively, of the administered dose.
A pilot study was undertaken to assess the feasibility, toxicity, and efficacy of combined radiation therapy and chemotherapy in the adjuvant treatment of node-positive. Stage II patients with breast ...carcinoma who had undergone lumpectomy. Therapy consisted of three phases, starting with a six-week CMFVP (cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, prednisone) induction, followed by radiation therapy to the breast, and concluding with four cycles of VATH (vinblastine, Adriamycin, thiotepa, Halotesin). Twenty-seven patients were entered with an average age of 51.5 years (median 50 yrs) and a mean follow-up of 46.2 months. Twenty-three patients (85.2%) are alive and 19 (70.3%) disease free. There were no ipsilateral local recurrences. Cosmetic results were good to excellent in 26/27 patients. The doses of VATH were not compromised by the prior therapy. The regimen was found to be tolerable and is a reasonable approach in the adjuvant treatment of this particular patient population.
Vinzolidine (VZL) is a semisynthetic vinca alkaloid with broad antitumor activity in animal models of malignancy but had unpredictable toxic effects when given orally to humans. To minimize the toxic ...effects due to potential erratic gastrointestinal absorption, this drug was restudied in man as an intravenous preparation given as a rapid injection every two weeks. The maximum tolerated dose (MTD) on this schedule was 9.0 mg/m2 with unpredictable leukopenia (usually occurring 5-14 days post treatment but appearing erratically), constipation, paralytic ileus, and inappropriate ADH syndrome as major toxicities. Nonhematologic toxicities were dose-limiting. Repetitive dosing at two week intervals was associated with leukopenia at D 14-15 in some but not all patients treated above 5.0 mg/m2 precluding further treatment on schedule. In contrast, the oral MTD of this agent in our prior studies was 45 mg/m2 with no evidence of delayed leukopenia. Intrapatient variability of toxicity was small; interpatient variability of toxicity was substantial and did not correlate with prior therapy. Because of the presence of delayed hematologic toxicity on repetitive dosing schedules, intravenous VZL should be given on a dosing schedule longer than 14 days. No antitumor activity was seen in this study.
Two cases of acute megakaryoblastic leukemia are reported. The diagnoses were confirmed by clinical, morphologic, and cytochemical analysis. Karyotypic analysis demonstrated monosomy 5 in both ...patients, providing further evidence that acute megakaryoblastic leukemia is a subset of the acute nonlymphocytic leukemias and may be etiologically related to the myelodysplastic syndromes.
