Multifocal tuberculosis revealed by multiple cutaneous gummas in the immunocompetent

Cutaneous tuberculosis is rare. Its occurrence in multifocal tuberculosis (MT) is uncommon and happens frequently in the context of immunosuppression. We report the case of MT with multiple cutaneous gummas and bone and lung involvement that occurred in an apparently immunocompetent patient.     

Differential effects of bexarotene on intrinsic and extrinsic pathways in TRAIL-induced apoptosis in two myeloid leukemia cell lines

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces programmed cell death (apoptosis) preferentially in tumor cells. However, not all cancer cells are sensitive to TRAIL. We determined whether ligation of the retinoid receptor, RXR, would sensitize cells to TRAIL-mediated apoptosis. The leukemic cell lines KG1a (apoptosis-resistant) and ML-1 (apoptosis-sensitive) were treated with the RXR-specific retinoid bexarotene, TRAIL, or both, and apoptosis was determined. In KG1a cells, bexarotene downregulated FLIP(Long) and activated caspase-8, thereby allowing for TRAIL-triggered apoptosis. Overexpression of FLIP(Long) in ML-1 cells abrogated apoptosis. In unmodified ML-1 cells bexarotene enhanced programmed cell death via truncation of Bid and release of cytochrome C. Blockade of caspase-8 prevented enhancement in both cell lines; blockade of caspase-9 had a significant effect only in ML-1 cells. Thus, the effect of bexarotene on TRAIL-mediated programmed cell death involved proximal events of the extrinsic pathway; however, downstream signals involved the intrinsic pathway in ML-1 but not in KG1a cells. These studies add further information to the regulation of programmed cell death in leukemic cells that have to be considered when designing therapeutic strategies.     

Étude clinicopathologique des carcinomes lobulaires du sein dans le Centre tunisien : à propos de 74 cas

Objective

To analyze the epidemiological characteristics and clinicopathologic features of breast lobular carcinomas in the Central Region of Tunisia.

Patients and methods

A retrospective study was carried out on all breast lobular carcinomas cases diagnosed in the Department of pathology, CHU Farhat Hached Sousse (Tunisia) from 1990 to 2005. The demographic, clinical, histological and treatment were analyzed. The probability of survival or recurrence was calculated using the Kaplan-Meier method. Prognostic factors were studied using the log-rank test.

Results

The mean age was 51 years old and half of the patients were postmenopausal. The average clinical tumor size at diagnosis was 49.9 mm. Seventy five percent of the patients were seen at an advanced stage of the disease (stages T3 an T4). The histological diagnosis was based in all cases on preoperative biopsies. It was in most cases the classical form (94.6%), a low histological grade (64.8%) and hormone receptor positive (65.5%). Surgical treatment was performed in 74.3% cases. Overall survival and disease-free survival at 5 years were respectively 94 and 70.9%. No local recurrence was observed after conservative treatment. Metastasis to lymph node, the clinical stage, the histological grade and non-expression of hormone receptors were significant factors influencing disease-free survival.

Conclusion

Our results were compared with data from literature and show that lobular carcinoma is rare, its diagnosis is often difficult and late, surgical treatment and its prognosis do not currently appear to differ from ductal carcinomas.     

La maladie de Trevor: à propos de deux nouvelles observations

Trevor’s disease is a rare skeletal developmental disorder affecting the epiphysis in children. It usually affects a lower limb and involves one or more than one epiphysis. We report two new cases of Trevor’s disease of knee and ankle in 8 and 14 years old boys respectively. The treatment was surgical excision. We discuss the modalities of recognition and the treatment of this rare disease.     

Cyclosporin and methotrexate therapy induces remission in type 1 diabetes mellitus

Cyclosporin and methotrexate administration induces remission of type 1 diabetes mellitus. Administration of high-dose cyclosporin (cyclo) has been demonstrated to induce remission of type 1 diabetes mellitus (T1D). Its usefulness was limited by its toxicity. Since methotrexate (mtx) and cyclo synergistically inhibit autoimmune processes, we postulated that low doses of cyclo and mtx could safely induce remission of T1D. In a pilot study, insulin dose requirements and glycemic control were compared in 10 new onset T1D control children with seven children who were administered cyclo at 7.5 mg/kg/day for 6 weeks and then 4 mg/kg/day in addition to mtx 5 mg/kg/wk for 1 year. After 6 weeks, cyclo doses were adjusted to maintain blood cyclo levels 110–220 ng/ml. All children were treated with two daily injections of insulin. Clinical and biochemical toxicity of drug therapy was assessed. There were only very minor adverse effects and no drug induced biochemical test abnormalities. Mean HbA1c levels were similar in the experimental and control groups at baseline and at 3, 6, and 9 months but was lower in the cyclo + mtx group at 12 months. Daily insulin requirements of the groups were similar at baseline but lower in the cyclo + mtx group at 3, 6, 9, and 12 months. Although no control subjects became non-insulin requiring, four of seven cyclo + mtx-treated subjects were entirely off insulin therapy for 2.5, 4.5, 8, and 12 months. Low-dose cyclo and mtx treatment of subjects with new onset T1D can safely induce remission of disease and decrease the amount of required insulin.     

High-level gentamicin-resistant Enterococcus faecium strains isolated from bone marrow transplant patients: accumulation of antibiotic resistance genes, large plasmids and clonal strain dissemination

Twenty-six high-level gentamicin-resistant (HLGR) Enterococcus faecium strains colonising neutropenic bone marrow transplant patients were studied. Polymerase chain reaction analysis showed that high-level gentamicin resistance was mediated by the aac(6′)-Ia-aph(2″)-Ie gene; the aph(2″)-Id gene responsible for gentamicin resistance was also detected in 16 strains. Multiple antibiotic resistance was related to the presence of aph(3′)-IIIa, ant(6)-Ia, erm(B), erm (A) and tet(M) genes. Strains clustered into 18 groups according to their plasmid content as well as 16 pulsed-field gel electrophoresis (PFGE) patterns. Although the majority of PFGE patterns were single isolates, three microclones were identified. Hybridisation showed that in the majority of the strains the aac(6′)-aph(2″) gene resided on a large plasmid of ca. 96 kb detected only on PFGE gels. Based on these findings, colonisation by HLGR E. faecium strains was a result of either possibly related plasmid spread or strain dissemination.     

Enterococcus faecium isolated from bone marrow transplant patients in Tunisia: high prevalence of antimicrobial resistance and low pathogenic power

Objectives

Investigation of the occurrence and antibiotic susceptibility of Enterococcus faecium isolates, collected during four years from neutropenic patients at the Tunisian bone marrow transplantation centre.

Materials and methods

E. faecium strains were identified by conventional methods and by the Api20 Strep (Bio-Mérieux, France). Antibiotic susceptibility was determined by the disk diffusion method on Mueller-Hinton agar and interpreted as recommended by CA-SFM. MICs of ampicillin, vancomycin, and teicoplanin were determined by E-test method.

Results

Two hundred and thirty five E. faecium isolates were recovered from stool cultures or rectal swabs (229), throat (three), urine (two), and pus of wound (one). None was responsible for bacteraemia. Ampicillin resistance, without production of β-lactamase, was observed in 43.8% of isolates. All the isolates were susceptible to glycopeptides. High rates of resistance were observed: high-level resistance (HLR) to gentamicin (33.6%), HLR to kanamycin (55.7%), HLR to streptomycin (47.6%), erythromycin (86.4%), ciprofloxacin (78.7%), rifampicin (85%), and tetracycline (43%). Strains with HLR to gentamicin were significantly more resistant to ampicillin and streptomycin. Multiple drug resistance was observed in most isolates.

Conclusion

These findings demonstrated the low pathogenic power of E. faecium in our patients, and the high frequencies of resistance to ampicillin and aminoglycosides. In the absence of glycopeptide-resistance, vancomycin remains an alternative treatment against multidrug resistant strains.     

Detection of ica genes and slime production in a collection of Staphylococcus epidermidis strains from catheter-related infections in neutropenic patients

Slime production, principal virulence factor of Staphylococcus epidermidis associated with catheter-related infections is mediated by icaADBC operon wich expression is subject to phase variation. Reversible transposition of IS256 element into this operon is one of the most important mechanisms of biofilm phenotypic variation. Our study compared 28 S. epidermidis strains from catheter-related infection to 28 strains from nasal carriage concerning slime production on Congo red agar plate and ica genes and IS256 presence by PCR. ica operon was present among all slime-producing strains, and was absent among slime-negative strains. Only 79% of ica-positive strains were slime producers and no insertion of IS256 element was detected inside ica genes. A significative difference was found between catheter-related infections strains and commensal ones in terms of oxacillin (67,8 versus 35,7%) and ofloxacin resistance (75 versus 35,7%), slime production (64,2 versus 28,5%), phase variability (46,4 versus 7,1%) and ica genes presence (82,1 versus 35,7%). Our study demonstrates the role of ica genes, of phenotypic variability of slime production and antibiotic multiresistance as virulence factors of S. epidermidis associated with catheter-related infections; it confirms also the complexity and the diversity of regulation mechanisms implicated in biofilm formation.     

Immune activation and regulatory T cells in <Emphasis Type="Italic">Mycobacterium tuberculosis</Emphasis> infected lymph nodes

Background

Lymph node tuberculosis (LNTB) is the most frequent extrapulmonary form of tuberculosis (TB). Studies of human tuberculosis at sites of disease are limited. LNTB provides a unique opportunity to compare local in situ and peripheral blood immune response in active Mycobacterium tuberculosis (Mtb) disease. The present study analysed T regulatory cells (Treg) frequency and activation along with CD4+ T cell function in lymph nodes from LNTB patients.

Results

Lymph node mononuclear cells (LNMC) were compared to autologous peripheral blood mononuclear cells (PBMC). LNMC were enriched for CD4+ T cells with a late differentiated effector memory phenotype. No differences were noted in the frequency and mutifunctional profile of memory CD4+ T cells specific for Mtb. The proportion of activated CD4+ and Tregs in LNMC was increased compared to PBMC. The correlation between Tregs and activated CD4+ T cells was stronger in LNMC than PBMC. Tregs in LNMC showed a strong positive correlation with Th1 cytokine production (IL2, IFNγ and TNFα) as well as MIP-1α after Mtb antigen stimulation. A subset of Tregs in LNMC co-expressed HLA-DR and CD38, markers of activation.

Conclusion

Further research will determine the functional relationship between Treg and activated CD4+ T cells at lymph node sites of Mtb infection.