Primary therapy with ECF in combination with a GnRH analog in premenopausal women with hormone receptor-positive T2-T4 breast cancer

Patients with hormone receptor-positive tumors less often show a pathological complete response (pCR) than do those with hormone receptor-negative tumors. The addition of endocrine therapies may improve the clinical benefits of primary therapies in these patients. We investigated the efficacy of the epirubicin+cisplatin+fluorouracil (ECF) as continuous infusion) regimen in association with a gonadotropin-releasing hormone (GnRH) analog in 36 premenopausal women with T2-T4a-d N0-2 M0 ER and/or PgR-positive breast cancer. Median age was 39.5 years (range 26-53). Clinical response (complete or partial) was observed in 27 out of 36 patients (75% 95% CI 57.8-87.9%) and a pCR was observed in four patients (11%). Nine (25%) patients had stable disease and no progression was observed. Twenty-one patients (58%) were submitted for breast-conserving surgery and 15 had a radical mastectomy. No baseline clinical and biological characteristics significantly correlated with response. Thirty out of 31 patients evaluable for endocrine assessment had documented ovarian suppression, which occurred after a median of 28 days (range 20-43). We conclude that the combination of ECF and a GnRH analog is associated with a high response rate in the primary treatment of breast cancer. Further studies combining chemotherapy and endocrine agents are warranted in patients with hormone receptor-positive tumors.     

Chlamydia infection and lymphomas: association beyond ocular adnexal lymphomas highlighted by multiple detection methods

PURPOSE: Chlamydia psittaci (Cp) has been associated to ocular adnexal lymphomas (OAL) with variable geographic distribution. Herein, we used multiple Chlamydia detection tools to identify Cp elementary bodies-containing cell and to assess Cp prevalence in both nodal and extranodal lymphomas. EXPERIMENTAL DESIGN: TETR-PCR, immunohistochemistry, immunofluorescence, electron microscopy, and laser-capture microdissection were done in 35 OALs to define their effect in Chlamydia detection and, moreover, to identify the Cp cellular carrier. Cp prevalence was screened by TETR-PCR in 205 extraorbital lymphomas and 135 nonneoplastic controls. RESULTS: Twenty-six (74%) OALs were associated with Cp infection: immunohistochemistry, immunofluorescence, and laser-capture microdissection-assisted PCR showed that monocytes/macrophages were the Cp carriers; electron microscopy showed the presence of intact Cp elementary bodies into these cells. Immunohistochemistry and TETR-PCR showed a 70% concordance rate (P = 0.001). Cp DNA was equally prevalent in non-OAL, nodal, and extranodal lymphomas: among the latter, it was more common in diffuse large B-cell lymphomas of the skin (P = 0.03) and Waldeyer's ring. CONCLUSIONS: This multiparametric approach shows, for the first time, that monocytes/macrophages are the carriers of Cp, Cp seems preferentially associated with lymphomas arising in organs primarily exposed to antigens. The clinical implications of these findings deserve to be prospectively investigated.     

Plasma protein oxidation is associated with an increase of procoagulant markers causing an imbalance between pro- and anticoagulant pathways in healthy subjects

The aim of the present study was to investigate whether the overall oxidation state of plasma proteins is associated with changes of circulating pro- and anticoagulant markers in healthy subjects (n = 99, 49 males, 50 females, aged from 6 to 91 yrs.). The carbonyl content of plasma proteins was measured and validated as an ex vivo index of the overall protein oxidation state due to its correlation with the plasma level of o-tyrosine (r = 0.87, P <0.0001), which is a well known oxidized product of L-phenylalanine. Using a multivariate analysis the carbonyl content of plasma protein was positively associated with procoagulant markers such as prothrombin F1 + 2 (r = 0.28, P = 0.0019) and fibrinopeptide A, (FpA) (r = 0.278, P = 0.003), as well as with the soluble derivative of the endothelial protein thrombomodulin (TM) (r = 0.469, P <0.0001). The procoagulant marker of thrombin activity, FpA, was significantly and positively correlated with the anticoagulant product of thrombin, namely the Protein C activation peptide (PCP), only in the tertile with low protein carbonyl content. At higher tertiles this correlation was no longer observed, thus suggesting a detrimental effect of oxidative stress on the TM/Protein C anticoagulant pathway. In 15 subjects with high carbonyl content of plasma protein, treatment for 18 days with 600 mg/d of vitamin E did not substantially modify the protein carbonyl content, the anticoagulant markers APC/PCP, and all procoagulant markers except F1+2, whose value significantly decreased by 25%. In conclusion, the present study shows that a high plasma protein oxidation ex vivo is associated with an overall hemostatic imbalance, which favors procoagulant markers. Vitamin E treatment in vivo restores only in part the equilibrium between pro- and anticoagulant pathways. This may open the way to further studies aimed at elucidating the mechanisms by which the oxidative stress is linked to activation of the coagulation system in atherothrombotic disorders.     

Missense and splice site mutations in SPG4 suggest loss-of-function in dominant spastic paraplegia

We studied nine Italian families with a pure form of autosomal dominant spastic paraplegia (ADHSP) to assess the frequency of mutations in the SPG4 gene. We observed marked intrafamilial variability in both age-at-onset and clinical severity, ranging from severe congenital presentation to mild involvement after age 55 years to healthy carriers of the mutation after age 70. Four of nine probands harboured SPG4 mutations, We identified three new SPG4 mutations, all predicting a loss-of-function with apparently important consequences for spastin function. RT-PCR studies predict loss-of-function as a possible mechanism leading to spastin-related HSP. The current study expands the spectrum of allelic variants in SPG4, confirming their pathological significance in pure AD-HSP and suggesting implications for the presumed function of spastin. Received: 15 December 2000, Received in revised form: 29 May 2001, Accepted: 18 June 2001     

Citrobacter koseri in scalp folliculitis

Gram-negative folliculitis, an uncommon condition, is most often seen in older patients who have acne and who either have received prolonged courses of antibiotic therapy or have used antibacterial cleansers that selectively inhibit gram-positive organisms. Citrobacter infections are uncommon, and dermatologists seldom encounter them. In the past, these infections occurred in hospitals, particularly in neonatal intensive care units. Bacteremias also occur in elderly or immunocompromised patients. In this article, we present a case of Citrobacter koseri scalp folliculitis in an otherwise healthy patient.     

Impact of diet on the induction of infection with Giardia lamblia cysts in Sprague-Dawley rats

OBJECTIVE: To assess the effect of malnutrition on the development of giardiasis in Sprague-Dawley rats, using different inoculum sizes of Giardia lamblia cysts. MATERIAL AND METHODS: An experimental study was conducted between 1995 and 1999 at Centro de Investigación, Alimentación y Desarrollo (Center for Research, Food, and Development), in Hermosillo, Sonora, Mexico. The study population consisted of two groups of six to eight experimental units that were fed two different diets and inoculated five different concentrations of Giardia lamblia cysts. Data were collected on excretion of cysts, weight gain, food intake, bowel contents, and macro and microscopic lesions in the intestinal mucosa. Statistical analysis consisted of analysis of variance and residuals. RESULTS: Animals fed with a diet meeting nutritional requirements required an infecting inoculum of 60 cysts, while malnourished rats required only six cysts to develop mucosal lesions. CONCLUSIONS: Weight gain monitored during ten days was not a good indicator of Giardia lamblia infection. Infection depended on cyst inoculum size as well as on the nutritional status of the tested animals. The English version of this paper is available at: http://www.insp.mx/salud/index.html.     

Microcin E492, a channel-forming bacteriocin from Klebsiella pneumoniae, induces apoptosis in some human cell lines

The cytotoxic effect of microcin E492, a low-molecular-mass channel-forming bacteriocin (7,887 Da) produced by a strain of Klebsiella pneumoniae, was characterized in HeLa cells. At low (5 microg/ml) and intermediate (10 microg/ml) concentrations, microcin E492 induced biochemical and morphological changes typical of apoptosis, such as cell shrinkage, DNA fragmentation, extracellular exposure of phosphatidylserine, caspase activation, and loss of mitochondrial membrane potential. Treatment with zVAD-fmk, a general caspase inhibitor, completely blocked the cytotoxic effect of this bacteriocin. At higher microcin concentrations (>20 microg/ml) a necrotic phenotype was observed. Induction of apoptosis by microcin E492 was associated with the release of calcium from intracellular stores, probably after microcin-triggered ion channel formation. Microcin E492 also presented a cytotoxic effect on Jurkat and RJ2.25 cells, but had no effect on KG-1 cells nor on a primary culture of human tonsil endothelial cells, suggesting that there is a specific interaction of the bacteriocin with components of the target cell surface. This report describes a bacteriocin that has the capacity to induce apoptosis in human cell lines.     

Sentinel lymph node identification in breast cancer patients

PURPOSE: To evaluate the predictive value of sentinel lymph node biopsy versus axillary node dissection on lymph node status in patients with T1-T2 breast cancer. MATERIAL AND METHODS: Twenty-nine patients with T1 and 12 with T2 breast carcinoma and clinically N0 axillary lymph nodes, underwent lymphoscintigraphy following the administration of 99mTc-human albumin nanocolloids. The tracer was injected subdermally, over the tumor mass, in the 34 patients with palpable lesions and peritumorally (n=3) or intratumorally (n=4), under stereotactic or ultrasound guidance, in the 7 patients with non-palpable lesions. Anterior and lateral planar images were acquired 15 min after the injection of the tracer and repeated every 30 min up to 3 hr until identification of sentinel lymph node. At the end of the scintigraphic study, sentinel node skin projection was marked using a dermographic pen. Eighteen hours after lymphoscintigraphy, sentinel lymph node was identified and removed during surgery by hand-held gamma probe, then, the remaining axillary lymph nodes were dissected. All surgical specimens underwent histologic examination. Sentinel lymph nodes free of metastasis at histology, underwent additional examination with immunohistochemistry using monoclonal antibodies against cytokeratin and EMA to search for micrometastases. RESULTS: Sentinel lymph node was identified in the 34 patients injected subdermally and in the 3 patients injected peritumorally, while it remained undetected in the 4 patients injected intratumorally except for one case in which it was isolated by radioguided surgery but not scintigraphically. Sentinel nodes resulted free of metastases both at histology and immunohistochemistry in 32 cases and metastatic in 6. In the 32 patients with non-metastatic sentinel lymph nodes the other axillary nodes were also free of metastases. Among the 6 metastatic sentinel lymph nodes, in 3 cases they were the only metastatic nodes of the axilla while in the other 3 cases metastases were spread to other axillary nodes. CONCLUSIONS: In agreement with previous studies, our results showed that sentinel lymph node radioguided biopsy is a simple and reliable method for predicting axillary lymph nodes status and for avoiding axillary dissection in early breast cancer patients with sentinel node free of metastases.