Breakthrough Hormographiella aspergillata infections arising in neutropenic patients treated empirically with caspofungin

Hormographiella aspergillata, a filamentous basidiomycete, has rarely been involved in human infections. We describe 2 febrile neutropenic patients who developed a severe pulmonary infection due to H. aspergillata while receiving empirical caspofungin therapy for presumed fungal pneumonia. After introduction of liposomal amphotericin B, one patient, who had neutrophil recovery, presented a favorable outcome, while the other, who remained neutropenic throughout the course of infection, died. Resistant fungi, including basidiomycetes, may emerge during empirical treatment with caspofungin in febrile neutropenic patients. A rapid switch to any other potent antifungal should be rapidly considered in case of failure of caspofungin in this setting.     

Perception of pain in the minimally conscious state with PET activation: an observational study

BACKGROUND: Patients in a minimally conscious state (MCS) show restricted self or environment awareness but are unable to communicate consistently and reliably. Therefore, better understanding of cerebral noxious processing in these patients is of clinical, therapeutic, and ethical relevance. METHODS: We studied brain activation induced by bilateral electrical stimulation of the median nerve in five patients in MCS (aged 18-74 years) compared with 15 controls (19-64 years) and 15 patients (19-75 years) in a persistent vegetative state (PVS) with (15)O-radiolabelled water PET. By way of psychophysiological interaction analysis, we also investigated the functional connectivity of the primary somatosensory cortex (S1) in patients and controls. Patients in MCS were scanned 57 (SD 33) days after admission, and patients in PVS 36 (9) days after admission. Stimulation intensities were 8.6 (SD 6.7) mA in patients in MCS, 7.4 (5.9) mA in controls, and 14.2 (8.7) mA in patients in PVS. Significant results were thresholded at p values of less than 0.05 and corrected for multiple comparisons. FINDINGS: In patients in MCS and in controls, noxious stimulation activated the thalamus, S1, and the secondary somatosensory or insular, frontoparietal, and anterior cingulate cortices (known as the pain matrix). No area was less activated in the patients in MCS than in the controls. All areas of the cortical pain matrix showed greater activation in patients in MCS than in those in PVS. Finally, in contrast with patients in PVS, those in MCS had preserved functional connectivity between S1 and a widespread cortical network that includes the frontoparietal associative cortices. INTERPRETATION: Cerebral correlates of pain processing are found in a similar network in controls and patients in MCS but are much more widespread than in patients in PVS. These findings might be objective evidence of a potential pain perception capacity in patients in MCS, which supports the idea that these patients need analgesic treatment.     

BAGE hypomethylation, a new epigenetic biomarker for colon cancer detection.

Early detection of colorectal cancer is a decisive step in the successful and complete cure of the disease. Epigenetic markers, in particular, those based on aberrant DNA methylation, can be used to diagnose cancer. B melanoma antigens (BAGE) are a family of genes and truncated genes located in the heterochromatic regions of several human chromosomes. Our previous work showed that BAGE loci (i.e., genes and truncated genes) were hypermethylated in normal tissues and hypomethylated in 98% of human cancers. In the present study, we analyzed DNA methylation of the BAGE loci in 54 colon cancers and in neighboring histopathologic normal tissue samples. Using a combined bisulfite restriction assay, we showed that BAGE loci were hypomethylated in 81% of carcinoma samples. Colon cancer could be diagnosed with 94% specificity, 83% sensitivity, and 89% accuracy. No correlation was found between DNA methylation of BAGE loci and age, gender of patients, nor with the tumor stage or site. Based on the hypothesis that during neoplastic transformation, hypomethylation occurs in juxtacentromeric CpG islands, we suggest that other genes located in the heterochromatic compartment should be tested. These new markers enrich the list of currently studied epigenetic alterations in colon cancer and could be associated with hypermethylation markers to develop reliable diagnostic tests.     

Two novel cases of cerebral haemorrhages at the neonatal period associated with inherited factor VII deficiency, one of them revealing a new nonsense mutation (Ser52Stop).

Factor VII (FVII) is a plasma glycoprotein that plays a key role in the initiation of blood coagulation cascade. Inherited FVII deficiency is a rare autosomal recessive disorder with a wide heterogeneous clinical pattern. The severe form may be associated with intracranial haemorrhages occurring closely to birth with a high mortality rate. In the present article, we report two novel cases of neonatal intracerebral bleeding associated with FVII activity levels below 1% of normal. FVII genotyping investigations revealed particular genotypes including the deleterious Cys135Arg mutation and a novel Ser52Stop nonsense mutation at the homozygous state. Both mutations, through different mechanisms, are expected to be inconsistent with the production of functional FVII. These putative mechanisms are discussed through a review of the literature on phenotypic and genotypic characteristics of cerebral haemorrhages in severe inherited FVII deficiency.     

alpha-Linolenic acid content of adipose breast tissue: a host determinant of the risk of early metastasis in breast cancer.

The association between the levels of various fatty acids in adipose breast tissue and the emergence of visceral metastases was prospectively studied in a cohort of 121 patients with an initially localised breast cancer. Adipose breast tissue was obtained at the time of initial surgery, and its fatty acid content analysed by capillary gas chromatography. A low level of alpha-linolenic acid (18:3n-3) in adipose breast tissue was associated with positive axillary lymph node status and with the presence of vascular invasion, but not with tumour size or mitotic index. After an average 31 months of follow-up, 21 patients developed metastases. Large tumour size, high mitotic index, presence of vascular invasion and low level of 18:3n-3 were single factors significantly associated with an increased risk of metastasis. A Cox proportional hazard regression model was used to identify prognostic factors. Low 18:3n-3 level and large tumour size were the two factors predictive of metastases. These results suggest that host alpha-linolenic acid has a specific role in the metastatic process in vivo. Further understanding of the biology of this essential fatty acid of the n-3 series is needed in breast carcinoma.     

MRSA Harboring mecA Variant Gene mecC, France

We describe human cases and clustered animal cases of mecA(LGA251)-positive methicillin-resistant Staphylococcus aureus in France. Our report confirms that this new variant has a large distribution in Europe. It may represent a public health threat because phenotypic and genotypic tests seem unable to detect this new resistance mechanism.     

A three-base deletion removing a leucine residue in a leucine-rich repeat of platelet glycoprotein Ibα associated with a variant of Bernard-Soulier syndrome (Nancy I)

Summary. Leucine-rich repeats are conserved structural motifs present in the four components of the human platelet glycoprotein Ib/IX/V complex receptor for the adhesive protein von Willebrand factor. The absence or abnormality of this complex is responsible for Bernard-Soulier disease, an autosomal recessive bleeding disorder. We report a deletion of leucine 179, located in a highly conserved position of the seventh leucine-rich repeat of GPIbα, found in a variant form of Bernard-Soulier disease (Bernard-Soulier Nancy I). Three affected siblings of a family were characterized by absence of ristocetin-induced platelet agglutination, although ADP aggregation was normal. Flow cytometry studies showed detectable amounts of all four members of the GPIb/IX/V complex on the surface of the patients' platelets. Western blotting revealed normal levels of GPIX, decreased levels of GPIbβ and GPV, and <1% of GPIbα. RT-PCR studies showed the presence of mRNA coding for GPIbα. GPIbβ, GPIX and GPV. Sequencing showed a three-base deletion which results in the absence of a leucine residue, highly conserved across the seven leucine-rich repeats of GPIbα and also within the other members of the leucine-rich glycoprotein family. The absence of the leucine 179 in a patient's GPIbα is believed to cause a conformational change in the protein which would account for the lack of binding of most of the MoAbs tested and would be responsible for the absence of von Willebrand factor binding. These results point to the leucine-rich region of GPIbα as being required for the correct exposure of the von Willebrand binding site as well as for the correct assembly and stability of the GPIb IX V complex on the platelet surface.     

Biological effects of a dipeptide methyl ester on Echinococcus multilocularis metacestodes in vivo

The biological effects of Phe-Phe-OMe (1) were evaluated in gerbils against the causative agent of alveolar echinococcosis, Echinococcus multilocularis. Morphological damage to the parasite was examined by transmission electron microscopy. Administration of (1) led to a considerable alteration of the laminated layer. Although a histoenzymatic study showed a decrease in alkaline phosphatase activity in the parasite, a precise mode of action for (1) cannot be proposed.     

Carcinoma of the cervical stump. Retrospective analysis of 43 cases

Seven to eight percent of cervix carcinomas are carcinomas of the cervical stump. The prognosis for these tumors has sometimes been considered more unfavourable than that for carcinomas on intact uterus. From 1976 to 1986 we treated 43 patients with carcinoma of the cervical stump. The mean age was 63.6 years. Staging system used was FIGO classification modified according to the criteria of Institut Gustave Roussy in Villejuif. There were 12 stage IB, 12 early stage II, 5 late stage II and 14 stage III. Twenty-four centropelvic tumors (IB and early stage II) were treated with radiotherapy and surgery, 2 with surgery alone and one with radiotherapy alone. Late stage II and stage III tumors were treated with radiotherapy alone (+ hysterectomy for two patients). Local control rate was 83% for centropelvic tumors and 53% for late stage II and stage III. Seven patients developed distant metastases. Uncorrected 5-year actuarial survival rate was 78% for centro-pelvic tumors and 46% for late stage II and stage III. Three patients developed severe complications (grade 3). Prognostic factors were: stage, nodal status and pathological status of the cervix after radiotherapy. For the same stage the results were similar to those observed for carcinomas on intact uterus treated at our institution during the same time period.     

Cellulitis Revealing a Cryptococcosis-Related Immune Reconstitution Inflammatory Syndrome in a Renal Allograft Recipient

Immune reconstitution inflammatory syndrome (IRIS) has rarely been described in the course of disseminated cryptococcosis in solid organ transplant recipients. We report here the case of a renal transplant recipient who developed severe cellulitis in the context of Cryptococcus neoformans-associated IRIS while undergoing reduction of his immunosuppressive therapy. IRIS appeared concomitantly with a dramatic increase of blood CD4+ T cells (94-460/mm(3)) and required the administration of a short-term steroid therapy to resolve.