Effects of recombinant canine stem cell factor, a c-kit ligand, and recombinant granulocyte colony-stimulating factor on hematopoietic recovery after otherwise lethal total body irradiation

The effects of recombinant canine stem cell factor (rcSCF) on hematopoiesis were studied in normal dogs and in dogs given otherwise lethal total body irradiation (TBI) without marrow transplant. Results were compared with previous and concurrent data with recombinant granulocyte colony-stimulating factor (rG-CSF). Four normal dogs received 200 micrograms rcSCF per kilogram body weight daily either by continuous intravenous infusion for 28 days (n = 2) or by subcutaneous (SC) injection in two divided doses for 20 days (n = 2). All dogs showed at least a twofold increase in peripheral blood neutrophil counts starting approximately 7 days after the initiation of treatment. Hematocrit level and monocyte, lymphocyte, eosinophil, reticulocyte, and platelet counts were not elevated. Marrow sections after rcSCF treatment showed panhyperplasia. The only toxicity was facial edema during the first few days of rcSCF administration, presumably caused by mast cell stimulation. Ten dogs were given 400 cGy TBI at 10 cGy/min from two opposing 60Co sources. They were given no marrow infusion and received 200 micrograms/kg/d rcSCF SC in two divided doses for 21 days starting within 2 hours of TBI. Five of the 10 dogs showed complete and sustained hematopoietic recovery and survived as compared with 1 of 28 control dogs not receiving growth factor (P < .005). RcSCF treatment allowed for hematopoietic recovery in two of seven dogs administered 500 cGy of TBI but in none of five dogs given 600 cGy of TBI. Results with rcSCF are similar to those obtained with rG-CSF. The rate of neutrophil recovery in rcSCF-treated dogs after 400 cGy TBI was not different from that of rG-CSF-treated dogs (P = .65), but the rate of platelet recovery was faster (P = .06) in the rcSCF-treated animals. Combined treatment with rcSCF and rcG-CSF after 500 cGy TBI did not result in strongly improved survival as compared with results obtained with either factor alone.     

A COMPARISON OF TOPICAL MENTHOL TO ICE ON PAIN,EVOKED TETANIC AND VOLUNTARY FORCE DURING DELAYED ONSET MUSCLE SORENESS

Purpose/Background:

Pain can adversely affect muscle functioning by inhibiting muscle contractions. Delayed onset muscle soreness was used as a tool to ascertain whether a topical menthol-based analgesic or ice was more effective at reducing pain and permitting greater muscular voluntary and evoked force.

Methods:

Sixteen subjects were randomized to receive either a topical gel containing 3.5% menthol or topical application of ice to the non-dominant elbow flexors two days following the performance of an exercise designed to induce muscle soreness. Two days later, DOMS discomfort was treated with a menthol based analgesic or ice. Maximum voluntary contractions and evoked tetanic contractions of the non-dominant elbow flexors were measured at baseline prior to inducing muscle soreness (T1), two days following inducing DOMS after 20 (T2), 25 (T3) and 35 (T4) minutes of either menthol gel or ice therapy. Pain perception using a 10-point visual analog scale was also measured at these four data collection points. Treatment analysis included a 2 way repeated measures ANOVA (2 × 4).

Results:

Delayed onset muscle soreness decreased (p = 0.04) voluntary force 17.1% at T2 with no treatment effect. Tetanic force was 116.9% higher (p<0.05) with the topical analgesic than ice. Pain perception at T2 was significantly (p=0.02) less with the topical analgesic versus ice.

Conclusions:

Compared to ice, the topical menthol-based analgesic decreased perceived discomfort to a greater extent and permitted greater tetanic forces to be produced.

Level of Evidence:

Level 2b     

Prognostic importance of cytogenetic subgroups in de novo pediatric acute nonlymphocytic leukemia

Reports of close associations between recurring chromosomal abnormalities and the clinical behavior of acute nonlymphocytic leukemia (ANLL) have stimulated efforts to define this disease in cytogenetic terms. Here we report on the leukemic cell karyotypes of 155 children with ANLL who were treated from 1980 to 1987 in consecutive programs of chemotherapy at this institution. Of 121 cases with adequate banding, 20% were normal, 30% had miscellaneous clonal abnormalities, and 50% were classified into known cytogenetic subgroups: inv(16)/del(16q) (n = 15), t(8; 21) (n = 14), t(15;17) (n = 9), t(9;11) (n = 9), t(11;V)/del(11q) (n = 7) and -7/del(7q) (n = 6). The inv(16)/del(16q) cases showed a nearly equal distribution of myelocytic and monocytic French-American-British (FAB) subtypes; only four of these patients presented with M4Eo morphology. Despite a 100% remission induction rate, patients with inv(16)/del(16q)-positive ANLL fared no better overall than the entire group; only 40% of this subgroup were event-free survivors at 2 years from diagnosis (P = .23). Patients with inv(16)/del(16q) frequently had CNS involvement at diagnosis (eight of 15) or initially relapsed in this site (three of eight). Event-free survival (EFS) was clearly superior for young patients with FAB M5 leukemia and the t(9;11) (P = .041). These patients were clinically indistinguishable from others with the FAB disease subtype, yet their responses to etoposide-containing therapies were noteworthy. By contrast, children with structural abnormalities involving 11q23, other than t(9;11), were infants (median age, 6 months) with FAB M4 or M5 leukemia, hyperleukocytosis, and frequent coagulation abnormalities. Patients with such changes [t(11;V) or del(11q)] relapsed early during postremission therapy: none remained disease-free more than 16 months from diagnosis. Because of resistant leukemia, patients with monosomy 7/del(7q) had a poor remission induction rate (17%; P = .0015); patients with the t(15;17) were also poor responders to induction therapy (44%; P = 0.02) because of hemorrhagic deaths. These results identify several cytogenetic subtypes of pediatric ANLL that may represent unique disease processes for which more effective early cytoreduction [-7/del(7q), t(11;V)], better supportive care measures [t(15;17)], or more effective CNS prophylaxis [inv(16)/del(16q)] would be warranted.     

Clinicopathologic analysis of follicular lymphoma occurring in children

Follicular lymphoma is a rare lymphoid malignancy in pediatric patients and consequently remains poorly characterized, particularly with respect to its immunophenotype and molecular pathogenesis. A total of 23 pediatric patients with follicular lymphoma were identified, with a median age of 11 years and a male-to-female ratio of 2.3:1. Of the 19 patients for whom presenting clinical features were available, 15 patients had stage I, 1 had stage II, and 3 had stage III or IV disease. All tumors had a follicular architecture, and 74% of cases had grade 2 or 3 histologic features. All patients expressed CD20 and bcl-6, and 80% were positive for CD10. Bcl-2 expression was detected in only 5 of 16 cases. Consistent with this finding, bcl-2 gene rearrangements were detected in only 2 of 16 cases by polymerase chain reaction. These patients were treated primarily with cyclophosphamide, doxorubicin, vincristine, and prednisone-based chemotherapy; 4 patients also received involved-field irradiation. Of the 13 patients with available clinical follow-up, all but 2 achieved durable clinical remission. Importantly, all 4 patients with tumors diffusely positive for bcl-2 either presented with stage III/IV disease or had disease refractory to therapy, whereas patients with bcl-2-negative tumors uniformly had stage I disease, achieved complete remission, and experienced no relapses. These findings indicate that, in contrast to adult follicular lymphomas, dysregulated bcl-2 expression does not play a significant pathogenetic role in most pediatric follicular lymphomas. However, bcl-2 expression in pediatric follicular lymphoma identifies a subset of patients in whom disease is often disseminated at clinical presentation and is more refractory to combination chemotherapy.     

Unfavorable presenting clinical and laboratory features are associated with CALLA-negative non-T, non-B lymphoblastic leukemia in children

Twenty-four (5.7%) of 424 children with newly diagnosed acute lymphoblastic leukemia (ALL) were found to have blast cells that expressed HLA-DR antigens but not the common ALL antigen (CALLA), E-rosette receptors, T-cell antigens, or cytoplasmic or surface immunoglobulins. Each of the eight cases tested expressed the B-cell associated antigen B4, but not B1 or B2 antigen. Myeloid-associated antigens were not present in any of the 10 cases tested. By comparison with common (CALLA+ B-cell precursor) ALL, patients having this immunophenotype were more likely to be children less than 2 yr of age (p less than 0.001), to have higher initial leukocyte counts (p less than 0.001), and to have blast cells with a DNA index less than 1.16 (p = 0.05), a pseudodiploid karyotype (p = 0.01) and a chromosomal translocation (p = 0.003). The presence of any chromosomal translocation in these CALLA- ALL was related to measures of increased leukemic cell burden including higher leukocyte counts, larger liver and spleen sizes and higher serum lactic dehydrogenase levels. While the patients were entered into several treatment arms of two protocols, the CALLA- cases appeared to have lower remission rate (p = 0.06) and shorter event-free survival time (p = 0.05) than did those with common ALL. The association with clinical and laboratory features of known adverse prognostic significance provides some explanation for the poor treatment outcome of CALLA- ALL.     

Morphologic and cytochemical characteristics of childhood lymphoblastic leukemia

The majority of childhood acute leukemias can be classified as acute lymphoblastic leukemia and acute nonlymphocytic leukemia with light microscopy and cytochemical stains alone. However, myeloperoxidase-negative myeloblastic leukemias and megakaryoblastic leukemias, as well as some metastatic tumors, can mimic lymphoblastic leukemia when these cytologic examinations are used. Conversely, occasional cases of Sudan black B-positive ALL can be confused with myeloblastic leukemia. Thus, additional immunologic and sometimes further ultrastructural studies should complement the morphologic diagnosis of ALL. The significance of L1 and L2 subtypes of ALL is still controversial. Modern chemotherapy may have obscured any significance of this division. Future studies of lymphoblast morphology should center on biologic correlates of the L2 cytology. Little prognostic significance has been found for the morphologic variants of ALL, such as the granular and hand-mirror cell types. It is important not to confuse granular ALL with acute myeloblastic leukemia. Functional immunologic studies may help in delineating the cause of uropod formation in hand-mirror variant ALL.     

Steuerliche Einordnung der wirtschaftlichen Vorteile aus einer Vertragsarztzulassung

Der wirtschaftliche Vorteil einer Vertragsarztzulassung stellt kein gesondert zu bewertendes Wirtschaftsgut dar, sondern einen wertbildenden Faktor des Wirtschaftsguts “Praxiswert” im Rahmen des Gesamtkaufpreises zum Erwerb der Vertragsarztpraxis.