Ultrasonically guided breast-conserving surgery for palpable mammary tumours

Breast-conserving surgery for palpable mammary tumours is usually guided by palpation. It appears, however, that identifying tumour margins only by palpation can be problematic, resulting in less than optimal effectiveness of this type of operation. The use of ultrasonography is a simple and non-invasive way of facilitating real-time localisation of breast carcinoma during surgery so that a tumour can be excised with controlled precision. Ultrasound is used to localise the tumour prior to surgery; its location is subsequently marked on the skin. During tissue dissection, ultrasound can be used to inspect the location and depth of the tumour as well as determining whether the tumour's surrounding margins are sufficient, thereby preventing the unnecessary removal of healthy tissue. Ultrasound can be used again after the excision to verify that the tumour was indeed radically removed. The efficacy of ultrasonically guided surgery for palpable mammary tumours is currently being studied in a prospective, randomised, multicentre trial.     

Reconstitution of lymphocyte subpopulations after paediatric bone marrow transplantation

We prospectively studied the reconstitution of lymphocyte subpopulations in a group of 22 children, who survived disease-free at least 6 months after allogeneic BMT for a haematological malignancy. Absolute counts of total lymphocytes, B lymphocytes, T lymphocytes, and CD4+ helper T lymphocytes reached the 5th percentile (p5) of age-matched reference values within 6 months after BMT in 15, 17, 7 and 2 patients, respectively. In particular, CD4+ helper T lymphocyte reconstitution was very slow. Unexpectedly, CMV reactivation had a profound positive influence upon the number of CD4+ helper T lymphocytes in the children. In five patients, absolute B lymphocyte counts above the 95th percentile were reached from 6 months after BMT onwards, mimicking normal ontogeny. Unlike normal ontogeny, the percentages of helper T lymphocytes expressing the 'naive' CD45RA isoform were low and those expressing the 'memory' CD45RO isoform were high in the first 3 months after BMT, as described before. Thereafter, the CD45RA:CD45RO ratio slowly normalised. Also, CD7 expression was absent on up to 90% of T lymphocytes in the first months after BMT, and on a steadily decreasing percentage thereafter, as recently described in adults. However, the absolute counts of CD45RO+/CD4+ and CD7-/CD4+ helper T lymphocytes did not change significantly. So, we found no evidence of peripheral expansion of previously primed donor-derived 'memory' T lymphocytes during the follow-up period which spanned 1-18 months after BMT. The absolute counts of 'naive' CD45RA+ helper T lymphocytes did not show a faster increase after BMT than in adults, despite the presumed presence of a non-involuted thymus in children. Bone Marrow Transplantation (2000) 25, 267-275.     

Effect of 17 alpha-ethinylestradiol on the catabolism of high-density lipoprotein apolipoprotein A-I in the rat

The in vivo metabolism and tissue sites of catabolism of high-density lipoproteins (HDL), labelled specifically in the apolipoprotein (apo) A-I moiety, were studied in rats treated with 17 alpha-ethinylestradiol (EE) for 5 days. Apo A-I was labelled either with O-(4-diazo-3-[125I]iodobenzoyl)sucrose, a non-degradable labelling compound, or with 131ICl. It was found that EE treatment decreases the serum cholesterol concentration to 10 mg/dl and stimulates the serum decay of apo A-I labelled HDL. The latter effect could be attributed to an increased catabolism of apo A-I labelled HDL in the liver. The increased rates of the serum decay and tissue uptake of apo A-I labelled HDL in EE-treated rats were not affected by a bolus injection of unlabelled human low-density lipoprotein (LDL), administered at the time of the injection of the labelled HDL. When the serum cholesterol concentration was raised to physiological levels by a bolus injection of unlabelled rat HDL, both the serum decay and the tissue uptake of apo A-I labelled HDL were almost completely restored to conditions encountered in control animals. In vitro binding experiments showed that liver membranes obtained from EE-treated rats demonstrated a 6-fold increased specific binding of human 125I-LDL, but virtually unchanged specific binding of rat 125I-HDL, as compared with liver membranes obtained from control rats. It is concluded that rat HDL apo A-I catabolism is hardly mediated by the apo B/E receptor induced by EE treatment.     

Infections after stem cell transplantation in children: state of the art and recommendations

At the workshop on infections after stem cell transplantation (SCT) in children, the following topics were introduced by invited speakers and discussed with the audience: empirical antimicrobial therapy in the pre-engraftment period, early diagnosis of fungal and viral infections and possibilities to treat them and the possible role of G-CSF early post-SCT. Episodes of fever in the pre-engraftment period mostly are unexplained, and in about one quarter due to bacteremia, mostly by Gram-positive cocci. No single drug or combination of drugs used for antimicrobial therapy is superior, neither does it cover 100% of the pathogens. Close microbiological surveillance of the patients and knowledge of the local microbial epidemiology are requested for optimal therapy. Early fungal infections are reactivations of pre-SCT infections, late fungal infections mostly are associated with failure of engraftment or GvHD and its treatment. Except for suggestive ultrasound or CT-scan abnormalities, the possibilities for early diagnosis are limited c.q. not reliable. Fluconazol prophylaxis is recommended to prevent Candida albicans invasion. A number of new antifungal drugs are being tested in phase I and II studies. CMV, EBV and adenoviruses may reactivate after SCT, causing severe disease with a high mortality, especially in non-HLA-identical donor-recipient combinations. Frequent surveillance cultures for CMV and adenoviruses, pp65-CMV antigen detection in WBC and PCR techniques for CMV, EBV and adenoviruses all have their own contribution to the early diagnosis of dissemination of the viral infection. Therapeutical possibilities, except with respect to ganciclovir and foscarnet for CMV infection, are still limited. The effectiveness of cidofovir is under study. Adoptive therapy with virus-specific CTL's probably represents the new frontier. G-CSF administration early after SCT has a beneficial effect on PMN recovery, hospitalization time, use of antibiotics and total parenteral nutrition requirement in children undergoing allogeneic and autologous BMT. No benefit is observed in children undergoing peripheral blood SCT. The routine use of G-CSF in the latter group of patients is not justified.     

Human leukocyte antigens and susceptibility to tuberculosis: a meta-analysis of case-control studies.

OBJECTIVE: To evaluate the association between human leukocyte antigens (HLA) of the major histocompatibility complex (MHC) and thoracic tuberculosis (TB) in immunocompetent adults. DESIGN: We searched Medline, Pascal, Pascal Biomed and Francis databases (all years) with the terms 'tuberculosis' and 'HLA'. Case-control studies were included that reported frequencies for the full range of antigens analysed by serological methods in healthy controls and adult patients not treated with glucocorticoids or immunosuppressive drugs, human immunodeficiency virus status negative or not reported, no debilitating chronic disease, and with a diagnosis of thoracic TB based on microbiological or histological criteria. Two authors independently abstracted the data and resolved disagreements by consensus. RESULTS: We summarised 60 HLA antigens reported in at least four of 22 studies totalling 1988 patients and 2897 controls. A lower risk of thoracic TB was found in carriers of B13 (OR 0.64, 95% CI 0.50-0.81, P < 0.0001), DR3 (OR 0.72, 95% CI 0.59-0.89, P = 0.002), and DR7 antigens (OR 0.65, 95% CI 0.53-0.80, P < 0.0001). Carriers of DR8 were at higher risk for thoracic TB (OR 1.72, 95% CI 1.21-2.46, P = 0.003). For these antigens, we found no significant heterogeneity between samples or evidence of publication bias. The risk of thoracic TB tended to be higher in carriers of DR2 (OR 1.67, 95% CI 1.16-2.41, P = 0.006), but the results were not consistent between studies (P value for heterogeneity < 0.0001). CONCLUSION: Susceptibility to TB is modulated by class I and II HLA antigens. However, these results based on the serological determination of antigens require confirmation by DNA-based methods to precisely identify those alleles involved.     

Diurnal variation in vasopressin and oxytocin messenger RNAs in hypothalamic nuclei of the rat

Diurnal changes in the expression of the vasopressin (VP) and oxytocin (OT) genes in the supraoptic (SON), paraventricular (PVN) and suprachiasmatic nuclei (SCN) of the rat were investigated by dot-blot and in situ hybridization of the VP and OT mRNAs. A significant diurnal variation in VP mRNA level was measured in the SCN, with highest levels around 17.00 h and lowest levels around midnight. No variations in levels of VP mRNA and OT mRNA were detected in SON and PVN. The data indicate that the regulation of the VP gene in the SCN is independent of that in the magnocellular nuclei.     

Validation of a serum-free growth factor-replenished in vitro culture system for hematopoietic progenitor cells in healthy donors and recipients of an allogeneic bone marrow graft.

The in vitro colony formation of hematopoietic progenitor cells of bone marrow samples, taken before and early after allogeneic bone marrow transplantation (BMT), was investigated prospectively. In order to circumvent culture-related and sample-related variations, a serum-free recombinant growth factor-replenished culture system was developed using T cell- and monocyte-depleted bone marrow samples. Samples of healthy bone marrow donors were used to validate the technique. The standardized culturing technique gave reproducible results, with numbers of colonies above those in conventional conditioned-medium technique. Colony formation in vitro of myelomonocytic precursor cells was found decreased in graft recipients, also after addition of growth factors, in comparison with healthy donors. The growth-promoting effect of the combination of IL-3 + GM-CSF was superior to that of either growth factor alone or conditioned medium. No effect was observed of T lymphocytes and monocytes on in vitro colony formation after bone marrow transplantation, probably as a result of functional impairment of these cells at that period after transplantation.