Fractionated total-body irradiation and high-dose etoposide as a preparatory regimen for bone marrow transplantation for 94 patients with chronic myelogenous leukemia in chronic phase

Ninety-four consecutive patients with chronic myelogenous leukemia in first clinical chronic phase, median age of 34.0 years (range, 6.8 to 52.4 years), with a histocompatible sibling donor, were treated with fractionated total body irradiation (1,320 cGy) and high-dose etoposide (60 mg/kg) followed by allogeneic bone marrow transplantation (BMT). The median time from diagnosis to BMT was 7.0 months (range, 2.3 to 72.0 months). Sixty patients were treated before BMT with hydroxyurea alone, four patients with busulfan alone, one patient with interferon alone, and the other 29 patients were treated with various combinations of these drugs. Cumulative probabilities of overall survival, event- free survival, and relapse at 5 years were 73%, 64%, and 14%, respectively. The median follow-up time for surviving patients was 38 months, ranging from 12 to 88 months. By stepwise Cox regression analysis, significant prognostic variables were age at transplant, acute graft-versus-host disease > or = grade II, cytomegalovirus- associated interstitial pneumonitis, and years from diagnosis to BMT.     

High-dose therapy and autologous bone marrow transplantation in patients with follicular lymphoma during first remission

We report the results of a study in previously untreated advanced stage patients with follicular lymphoma (FL) who underwent uniform induction chemotherapy with cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) followed by myeloablative therapy and anti-B-cell monoclonal antibody purged autologous bone marrow transplantation (ABMT). Eighty-three patients with previously untreated, low-grade FL were enrolled. After CHOP induction, only 36% achieved complete remission (CR) and 77 patients underwent ABMT. Before BM harvest, 70 patients had a known t(14;18), as determined by polymerase chain reaction (PCR), and all remained PCR positive in the BM at harvest. After ABMT, the disease-free survival (DFS) and overall survival are estimated to be 63% and 89% at 3 years, respectively, with a median follow-up of 45 months. Patients whose BM was PCR negative after purging experienced significantly longer freedom from recurrence (FFR) than those whose BM remained PCR positive (P = .0006). Continued PCR negativity in follow-up BM samples was also strongly predictive of continued CR. This study suggests that a subset of patients with advanced FL may experience prolonged clinical and molecular remissions following high-dose ablative therapy, although longer follow-up will be necessary to determine potential impact on overall survival.     

Assessment of stool colour in community management of prolonged jaundice in infancy

Jaundice persisting beyond the first 2 wk of life is often regarded as an indication for investigation to exclude cholestatic liver disease. Most babies with prolonged jaundice have breast milk-related jaundice, which is a benign condition. Cholestatic liver disease is usually accompanied by pale stools and yellow or orange urine. A community programme was established to ascertain the incidence of prolonged jaundice and determine whether abnormal stool and urine colour could be used to assist primary care staff in referral decisions. Data were collected on normal stool and urine colour and used to devise a colour chart and information sheet for parents. Babies with prolonged jaundice were identified and referred for investigation. In all, 3661 babies were recruited into the study, of which 127 were jaundiced at 28 d of age. Of these, 125 were breastfed. The incidence of jaundice in breastfed babies at 28 d was 9.2% (95% CI 7.8%-11.0%) Abnormal liver function tests (LFTs) were common, but no baby had abnormal stool or urine colour and none was found to have liver disease. Jaundiced breastfed babies who are well are unlikely to have serious disease. Elevated LFTs are compatible with a diagnosis of breast milk-related jaundice. Prolonged jaundice in bottle-fed babies, and persistent pallor of stools or yellow/orange urine, are rare and merit immediate referral. Parents and professionals can be advised to report pale stools without generating a large number of unnecessary referrals. Further work is needed to determine whether a colour chart reduces the mean age of referral and treatment of infants with cholestatic liver disease.     

Arterial and pseudoaneurysm ruptures complicating liver transplantation

Ruptures of the hepatic artery and hepatic pseudoaneurysms (PA) are rare but serious complications of hepatic transplantation. We conducted a retrospective study of 640 liver transplantations performed in our institution for a variety of pathologies. After surgery, seven major arterial bleeds occurred (0.9%). Of these seven cases, there were due to hepatic artery rupture (HAr) and four to PA rupture; all confirmed at either surgery (six cases) or autopsy (one case). Five of the seven patients died. In all cases the transplantation was difficult. All vascular injuries but one were caused by sepsis and occurred either after an undetermined cause septicemic syndrome (five cases) or graft dysfunction (one case). The last vascular injury was biliary drainage related. Six of the seven patients had imaging studies. Sonography (five cases) found a sub-hepatic hypoechoic collection in three cases but failed to do so in two. Duplex doppler (three cases) failed in all three cases to demonstrate a PA. Computed tomography (three cases) showed one PA, one perihilar sub-hepatic collection and failed in one. Conventional angiography (three cases) depicted a PA in all three cases. At the present time, our practice is to perform systematic angiography in patients with undetermined cause septicemic syndrome to research a PA. And if angiography is normal, to then puncture systematically any sub-hepatic collection to determine the bacteriological nature of this collection. Correspondence to: H. Caillet     

Lymphokine-induced phagocytosis in angiocentric immunoproliferative lesions (AIL) and malignant lymphoma arising in AIL

A factor that augmented the phagocytosis of IgG-coated ox red blood cells by the human monocyte/macrophage line U937 was identified in cell culture supernatants from two of two patients with angiocentric peripheral T cell lymphomas, three of three patients with angiocentric immunoproliferative lesions that were not frankly malignant, and one of two patients with T lymphoblastic malignancies. The factor was not present in supernatants derived from 14 nonangiocentric peripheral T cell lymphomas of other histologic types nor in ten cases of B cell lymphoma and two cases of Hodgkin's disease. A similar factor was present in the supernatants of concanavalin A (Con A)-stimulated normal peripheral blood mononuclear cells and in the supernatants of IL-2- dependent T cell lines derived from normal peripheral blood. The factor had an apparent mol wt of greater than 50,000 daltons, was heat labile (100 degrees C for two minutes), and stable at pH 2.0. Its stimulation of phagocytosis was independent of any increase in number of Fc receptors. Thus, this factor is probably not gamma-interferon. This factor may play a pathogenetic role in the hemophagocytic syndromes associated with certain T cell malignancies and immunodeficient states.     

敏定偶用于35岁以上妇女的疗效、安全性和周期控制

<正> 口服避孕药在投放市场之初,应用于各种年龄段的妇女。然而资料显示早期使用的高剂量口服避孕药会增加心肌梗塞的发病率;在1975年,美国食品药物管理局(FDA)不建议40岁以上的妇女服用避孕药,对30岁以上的吸烟妇女建议她们要么停止吸烟要么改换避孕方式。随着研究的进一步深入及低剂量口服避孕药的问市,已证实任何年龄的非吸烟     

Beta2 integrin/ICAM-1 adhesion molecule interactions in cutaneous inflammation and tumor promotion

The beta2 integrin (CD 18/CD 11 a, b, c) family of proteins mediate adherence of leukocytes to vascular endothelium and the associated ligand, intercellular adhesion molecule-1 (ICAM-1; CD 54), interacts with beta2 integrin proteins to allow transendothelial migration of leukocytes into sites of inflammation. The present study examines the function of these proteins in a murine model of acute cutaneous inflammation induced following topical application of 12-O- tetradecanoylphorbol-13-acetate (TPA) to the dorsal epidermis of SENCAR mice and in a model of skin multistage carcinogenesis. At 24 h following topical application of TPA to the dorsal epidermis of mice, dermal leukocytes expressed higher levels of beta2 integrin protein compared with the lower levels of beta2 integrin protein expression by peripheral blood leukocytes. ICAM-1 protein was localized to epidermal keratinocytes and vascular endothelium in TPA-treated skin and to proliferating papilloma cells. Intravenous (i.v.) injection of either 50 microg anti-beta2 integrin antibody alone or in combination with anti-ICAM-1 antibody significantly inhibited both TPA-stimulated neutrophil infiltration into the dermis (P < 0.001) and myeloperoxidase (MPO) activity (P < 0.03 anti-beta2 integrin antibody; P < 0.01 anti- beta2 integrin + ICAM-1 adhesion molecule antibodies), but had no effect on TPA-induced epidermal hyperplasia. In addition, injection of either anti-ICAM-1 adhesion molecule antibody alone (P < 0.004) or in combination with anti-beta2 integrin antibody (P < 0.001) significantly inhibited TPA-induced production of 7,8-dihydroxy-2'-deoxyguanosine (8- OHdG) immunoreactive proteins by epidermal keratinocytes. Beta2 integrin/ICAM-1 adhesion molecules work in concert to regulate migration, retention and functional activation of leukocytes within the dermis during TPA-induced skin inflammation and within stromal tissue of papillomas that form during multi-stage carcinogenesis. Agents that inhibit these receptor/ligand interactions may be useful in defining the roles of specific cell populations in cutaneous inflammation and multistage carcinogenesis and may also have potential as anti-promoting and anti-progression agents.      

The Kheda malaria project: the case for environmental control

The Kheda project experience has shown that bio-environmentalcontrol of malaria is feasible, cost effective and ecologicallysound. It clearly brings out the need to consider health issuesat the planning stage of all developments. Bio-environmentalcontrol of malaria is suggested as the first line of attackfor the control of mosquitoes, malaria and other mosquito-bornediseases. Insecticides may be reserved for short-term use. Thiswill enable judicious and selective use of insecticides in solelyepidemic situations. The growing problem of resistance to insecticidesin mosquitoes as well as environmental pollution, can then besolved on a long term basis.