Fludarabine: a new agent with major activity against chronic lymphocytic leukemia

Fludarabine was used to treat 68 patients with previously treated chronic lymphocytic leukemia (CLL). Nine (13%) patients achieved a complete remission and 30 (44%) a partial remission. The response rates for Rai stages 0 to 2, 3, and 4 were 64%, 58%, and 50% respectively. Seventeen (43%) of the 40 Rai stage 1 to 3 patients and four (19%) of the Rai stage 4 patients returned to Rai stage 0. Survival was strongly correlated with the final Rai stage achieved. The survival of the 11 partial responders with residual disease consisting only of residual bone-marrow nodules was similar to the complete responders (36+ months) and superior to the other partial response patients (16 months). The response to fludarabine was rapid, with 36 (92%) of the 39 responders having achieved at least a partial response following the first three courses. Complete responses occurred in the blood, liver, spleen, and lymph nodes in 48% to 69% of the patients. Eradication of all disease in the bone marrow occurred in only 13% of the cases. Neutropenia and thrombocytopenia occurred in 56% and 25% of evaluable courses. Major infections occurred in 9% of evaluable courses and fevers of unknown origin or minor infections in 12% of courses respectively. Myelosuppression and infection were more common in patients with initial Rai stages 3 and 4 and in nonresponding patients. Other toxicity was mild. No CNS toxicity was noted.     

眼部用药对老年人的全身影响

老年人使用眼药的情况是很普遍的,这些药物可能具有严重的全身影响,特别是在老年病人。这在医源性疾病的鉴别诊断中应予以考虑。文献报道的这个问题并非仅限于老龄人群,尽管大多数病人属于老年。眼药滴入球结膜囊中,除少量流出或吞下外,大部分均经由结膜毛细血管、鼻粘膜及咽部直接进入血液循环,其吸收量之大可足以产生副作用。由于老年人常常使用多种药物,因而与其他药物产生药物相互作用的可能性亦是存在的。现根据眼部用药的不良反应所涉及的主要     

Cutaneous Crohn''s disease mimicking Melkersson–Rosenthal syndrome: treatment with methotrexate

A woman with a 5-year history of unilateral orofacial granulomatosis required repeated evaluations (including sequential colonoscopies) to establish the diagnosis of cutaneous Crohn's disease, a condition that proved responsive to low doses of oral methotrexate administered weekly. To our knowledge this is the first report describing the use of methotrexate for treatment of orofacial granulomatosis caused by underlying Crohn's disease.     

Naevus lipomatosus cutaneous superficialis

A young male presenting with cutaneous papules and plaques in a segmental distribution in the pelvic girdle area is reported. The clinical features were suggestive of naevus lipomatosus cutaneous superficialis, but diagnostic biopsy is essential to demonstrate the typical histopathological features and exclude important differential diagnoses such as segmental neurofibromatosis.     

Antileukemic effect of recombinant tumor necrosis factor alpha in vitro and its modulation by alpha and gamma interferons

The effect of recombinant human tumor necrosis factor alpha (rTNF- alpha) on human myelogenous leukemia clonogenic cells growing either in semisolid media or in suspension cultures was studied and compared with the effect on normal granulocyte-macrophage progenitors (GM-CFC). Exposure of cells to a range of rTNF-alpha doses including pharmacologically achievable plasma concentrations revealed a large heterogeneity in the response of leukemic clonogenic growth to rTNF- alpha. Only one of 13 specimens was highly resistant to rTNF-alpha. Eight of ten leukemic samples were significantly more sensitive than were normal GM-CFC, particularly within the in vivo achievable dose range (1 x 10(0) to 1 x 10(2) ng/mL). No significantly increased inhibition of either normal or leukemic clonogenic growth could be achieved by increasing the rTNF-alpha concentration above 250 ng/mL. Proliferation of leukemic clonogenic cells (L-CFC) was studied in suspension cultures. In five cases the clonogenic cells were significantly inhibited by rTNF-alpha while in one case no inhibition was observed. The inhibition of L-CFC growth by rTNF-alpha was dose dependent between 1 x 10(0) and 1 x 10(2) ng/mL. In suspension cultures, the TNF effect on L-CFC was a function of time of exposure, particularly with low concentrations of TNF. A remarkably higher inhibition of L-CFC as compared with the total leukemic population was observed in suspension cultures. Stimulation of L-CFC growth by rTNF- alpha was not observed. Normal GM-CFC were inhibited by alpha and gamma interferons (INF-alpha, -gamma) in a dose-related manner, with higher sensitivity of colonies than clusters. The response of GM-CFC to combination of recombinant IFNs and TNF was influenced by the size of clones scored and the source of colony-stimulating activity. The response of L-CFC to recombinant IFN-alpha and/or -gamma was highly variable, and sensitivity to one of the lymphokines did not predict for sensitivity to another. The response of L-CFC to combinations of rTNF- alpha and either IFN-alpha or IFN-gamma was complex, varying from synergistic to additive and indifferent. In three of six specimens, IFN- gamma acted antagonistically with rTNF-alpha, a phenomenon not observed with IFN-alpha. These observations suggest that the action of rTNF- alpha in acute myelogenous leukemia could be exploited therapeutically and the dose-time-response relationship should be considered in designing treatment schedules.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effect of infants’ position on serum bilirubin level during conventional phototherapy

Aim: To compare the decrease in total serum bilirubin (TSB) concentration during conventional phototherapy in infants treated in supine position exclusively versus infants alternated between exposure in supine and prone position every third hour. Moreover, to survey current practice patterns in two Scandinavian countries as far as alternating exposure. Methods: A total of 112 infants with non‐haemolytic hyperbilirubinaemia, but otherwise healthy, and a gestational age ≥33 weeks were randomized to one of the treatment groups. All infants received phototherapy for 24 h. TSB was measured at start of phototherapy and after 12 and 24 h of treatment. Questionnaires about routines for position changes in infants during phototherapy were sent to all 41 neonatal departments in Denmark and Norway. Results: No statistically significant differences in the decrease in TSB were observed between the two treatment groups: at 12 h of therapy, TSB decreased 32% in both groups and at 24 h 49% and 50%, respectively. In two‐thirds of Danish and Norwegian departments, the infants were routinely turned during phototherapy, most often every third hours. Conclusion: The decrease in TSB was not significantly associated with positioning of the infant during conventional phototherapy. Alternating exposure is widely practiced in Scandinavia but is unnecessary.