Allogeneic stem cell transplantation improves the outcome of adults with t(1;19)/E2A-PBX1 and t(4;11)/MLL-AF4 positive B-cell acute lymphoblastic leukemia: results of the prospective multicenter LALA-94 study.

Adult patients with acute lymphoblastic leukemia (ALL) and t(1;19)/E2A-PBX1 or t(4;11)/MLL-AF4 have a poor outcome. We have evaluated the impact of an intensified post-remission therapy using a high-dose chemotherapy course followed by allogeneic or autologous SCT on the outcome of 58 patients with t(1;19)/E2A-PBX1 (E2A group, n=24) or t(4;11)/MLL-AF4 (MLL group, n=34) treated in the LALA-94 multicenter prospective study. Patients in the MLL group had higher WBC counts and more frequent DIC. CR rates achieved by MLL and E2A groups were similar to other B-cell ALL (87, 82 and 86% respectively). While in CR, patients with a donor were assigned to alloSCT (n=22), the remaining patients with were randomized between autoSCT (n=15) or chemotherapy (n=8). Five-year overall survival was 31 and 45% for E2A and MLL groups, respectively. In both groups, DFS was higher in the alloSCT arm as compared to autoSCT and chemotherapy arms. The results of this study show that chemotherapy intensification did not overcome the poor prognosis of adults with t(1;19)/E2A-PBX1. Allogeneic SCT should thus be offered in first CR to patients with t(1;19)/E2A-PBX1 or t(4;11)/MLL-AF4. New therapeutic approaches are needed for patients without donor.     

Perceptions and experiences of motherhood,health and the husband's role among Thai women in Australia

OBJECTIVE: to discuss the perceptions and experiences of motherhood among Thai immigrant women in Australia. DESIGN: ethnographic interviews and participant observation were used to elicit information. SETTING: Melbourne Metropolitan Area, Victoria, Australia. PARTICIPANTS: 30 Thai women who are now living in Australia. FINDINGS: becoming a mother meant different things to these women. Motherhood had both positive and negative aspects. Women believed that their health became worse as a result of becoming a mother. The contributing causes of their health status were multi-faceted, including their age, the demanding tasks of motherhood, the depletion of their strength and energy from childbirth, and in not following Thai traditional confinement practices. The findings in this paper support previous literature that motherhood has a profound effect on the life of many women. We, however, found that cultural beliefs and practices have an effect on women's perceptions and experience of motherhood. We also found that the 'presence' of the husband when a woman becomes a mother is important. The ethnicity of their husbands also played a significant role in their motherhood role and the ways in which they mothered their children. IMPLICATIONS FOR PRACTICE: understanding the social and cultural environment in which immigrant women try to be a mother is important if we are to provide culturally sensitive assistance and care to women who choose to become a mother in their new homeland.     

Lymphadenopathy due to Penicillium marneffei infection: diagnosis by fine needle aspiration cytology.

Penicillium marneffei is an opportunistic fungal infection that usually causes disseminated disease, mainly in immunocompromised individuals, especially those with HIV infection. Untreated cases are usually fatal. Diagnosis is traditionally made by biopsy and/or culture; successful diagnosis by fine needle aspiration (FNA) has only been reported once. We present eight cases of HIV-infected patients with lymphadenopathy caused by P. marneffei infection, in which the diagnosis was made by FNA. In all cases, intracellular and extracellular yeast forms were visualized, and the characteristic cross-septation of P. marneffei was highlighted by GMS staining. All diagnoses were confirmed by culture. Anti-fungal treatment for P. marneffei was initiated, resulting in marked clinical improvement. We conclude that a diagnosis of lymphadenopathy caused by P. marneffei can reliably be made by FNA. The diagnosis is more rapid than biopsy or culture, allowing rapid institution of therapy, particularly important in immunocompromised patients. In all our cases, not only were lymphoma and other causes of lymphadenopathy ruled out, but also the necessity for an open surgical biopsy was obviated. This can be especially beneficial to patients (e.g., three in our study) in which lymphadenopathy is confined to deep intra-abdominal nodes.     

Mathematical modeling and application of genetic algorithm to parameter estimation in signal transduction: trafficking and promiscuous coupling of G-protein coupled receptors

G-protein-coupled receptors (GPCRs) constitute a large and diverse family of proteins whose primary function is to transduce extracellular stimuli into intracellular signals. These receptors play a critical role in signal transduction, and are among the most important pharmacological drug targets. Upon binding of extracellular ligands, these receptor molecules couple to one or several subtypes of G-protein which reside at the intracellular side of the plasma membrane to trigger intracellular signaling events. The question of how GPCRs select and activate a single or multiple G-protein subtype(s) has been the topic of intense investigations. Evidence is also accumulating; however, that certain GPCRs can be internalized via lipid rafts and caveolae. In many cases, the mechanisms responsible for this still remain to be elucidated. In this work, we extend the mathematical model proposed by Chen et al. [Modelling of signalling via G-protein coupled receptors: pathway-dependent agonist potency and efficacy, Bull. Math. Biol. 65 (5) (2003) 933–958] to take into account internalization, recycling, degradation and synthesis of the receptors. In constructing the model, we assume that the receptors can exist in multiple conformational states allowing for a multiple effecter pathways. As data on kinetic reaction rates in the signalling processes measured in reliable in vivo and in vitro experiments is currently limited to a small number of known values. In this paper, we also apply a genetic algorithm (GA) to estimate the parameter values in our model.     

PREGNANCY AND TECHNOLOGY: THAI WOMEN'S PERCEPTIONS AND EXPERIENCE OF PRENATAL TESTING

In this paper we discuss the perceptions and experience of prenatal testing among 30 Thai women in Australia. Ethnographic interviews and participant observation were used to elicit information in the study. The results show that most Thai women have positive attitudes toward prenatal testing, particularly that of ultrasound scan. Women see prenatal testing as a means for reassurance about the health and well-being of their foetus, to detect the sex of their foetus, and to create excitement about life in their uterus. However, there are also women who have negative attitudes toward or are ambivalent about prenatal testing. Despite some doubts about prenatal testing, women fell that it offers some answers about the well-being of their foetus and hence in the end they accept it as part of their pregnancy. We also discuss explanations for the acceptance of prenatal testing among Thai women.     

Low-cost CD4 enumeration in HIV-infected patients in Thailand

In Thailand, over one million people have been infected with HIV since the beginning of the epidemic. This has created a great burden on the country's limited health care budget. Monitoring CD4+ T-lymphocytes is important to determine the success of any antiretroviral therapy as well as HIV vaccine trials. However, the high cost of CD4 counts makes monitoring of every HIV-infected patient impossible in Thailand. Therefore, the development of affordable strategies is necessary in order to allow more HIV infected persons to access CD4 testing to control the disease. The current standard methods for enumeration of CD4+ T-lymphocytes are performed on whole blood by flow cytometric immunophenotyping using the 6-tube 2-color and 3-tube 3-color panels recommended by the Centers for Diseases Control (CDC). In this study, percentage CD4+ T-lymphocyte values (from 142 HIV-seropositive patients and 26 anti-HIV negative adult blood donors) generated by the use of just 2 reagents (CD45/CD4) in a 1-tube 2-color panel employing side scatter/CD45 morphospectral gating were compared to those obtained by state of the art methods. We also compared the use of generic monoclonal antibody reagents with commercial reagents and found the results to be comparable with an overall correlation coefficient (r) of more than 0.95 for both CD4+ and CD8+ T-lymphocytes. Bland-Altman analysis of the mean CD4 values plotted against the difference in values between the generic reagents and the commercial reagents showed no bias. The 1-tube 2-color method using generic monoclonal antibody reagents potentially permits more affordable but reliable CD4 testing and therefore could increase access for more HIV-infected patients in resource-poor countries.     

Imaging features of unusual adrenal masses

The widespread use of cross-sectional imaging techniques has resulted in increased detection of adrenal masses. The imaging characteristics of common adrenal masses such as adenoma, phaeochromocytoma and metastasis are well established. In this pictorial essay, the imaging features of unusual adrenal masses including cyst, lymphoma, adrenal carcinoma, myelolipoma, haemangioma, smooth muscle tumour, haematoma, and infection (acute tuberculous adrenitis and histoplasmosis) are presented. Computed tomography permits a diagnosis of cyst, acute or subacute haematoma and myelolipoma. Although the imaging features of other lesions are non-specific, imaging has an important role in the detection of these unusual adrenal masses, and in aiding their diagnosis and management.