Recent changes in bacterial epidemiology and the emergence of fluoroquinolone-resistant Escherichia coli among patients with haematological malignancies: results of a prospective study on 823 patients at a single institution.

BACKGROUND: Regular monitoring of bacterial epidemiology allows evaluation of antibacterial strategies adopted. The aim of this study was to disclose evolving trends in the epidemiology of infections and emerging antibiotic resistance in unselected inpatients with haematological cancers. METHODS: Febrile/infectious episodes occurring in 823 patients consecutively admitted to a single institution during a 16 month period were analysed. Levofloxacin prophylaxis was used in patients with >7 days expected neutropenia. RESULTS: Fever developed in 364 patients (44.2%) and an infection was documented in 187 (22.7%), either clinically (6.1%) or microbiologically (16.6%). Levofloxacin prophylaxis, used in 39.4% of cases, caused a reduction in febrile episodes only among neutropenic patients and no difference in the frequency of documented infections. Among 164 pathogens isolated, gram-negative (49.4%) outweighed gram-positive bacteria (40.9%), Escherichia coli being most frequent (23.2%). Fluoroquinolone resistance and methicillin resistance were the most frequent types of antibiotic resistance, occurring in 56.1% of bacterial isolates and in 66.7% of staphylococci, respectively. Fluoroquinolone-resistant E. coli accounted for 20.1% of all isolates and for 86.8% of E. coli. Multivariate analysis of risk factors for fluoroquinolone resistance identified prophylaxis (P < 0.001) and neutropenia >7 days (P = 0.02) as independent. Methicillin resistance was independently associated with prophylaxis (P = 0.041) and central venous catheters (P = 0.036). Infections by fluoroquinolone-resistant strains did not show a worse outcome. CONCLUSIONS: A shift towards gram-negative bacteria has been occurring in recent years in the bacterial epidemiology of haematological patients. Fluoroquinolone resistance is emerging as a major type of antibacterial resistance, particularly among E. coli strains. Further investigation is needed to explore the consequences of such epidemiological changes.

Fatal hemophagocytic syndrome related to active human herpesvirus-8/Kaposi sarcoma-associated herpesvirus infection in human immunodeficiency virus-negative, non-transplant patients without related malignancies.

Hemophagocytic syndrome (HS) may occur as a consequence of herpes viral infections. Human herpesvirus 8 (HHV-8)/Kaposi sarcoma-associated herpesvirus has so far been recognized as a trigger of HS only in immunosuppressed subjects or in patients with Kaposi sarcoma and/or HHV-8-related lymphoproliferative diseases. We report two Italian human immunodeficiency virus (HIV)-negative elderly men who developed an HS with a rapidly fatal course, following treatment with corticosteroids for autoimmune hemolytic anemia. An overwhelming active infection with HHV-8 was unequivocally documented by molecular and immunohistochemical methods, in the absence of HHV-8-related tumors. The occurrence of HHV-8-associated HS, although rare, may be considered, even out of the HIV or the transplantation settings, at least in areas endemic for HHV-8 infection.

Prolonged treatment with imatinib mesylate in patients with advanced chronic myeloid leukemia causes a reduction of bcr/abl mRNA levels independent of cytogenetic response.

Bcr/abl mRNA levels were monitored in 13 patients with chronic myeloid leukemia receiving imatinib mesylate over a period of 78 weeks. During treatment median bcr/abl mRNA levels progressively declined from 77.2 normalized dose (nD) at baseline to 11.28 nD after 13 weeks ( P<0.05) and to 1.28 nD after 78 weeks ( P<0.05). After 13 weeks, bcr/abl mRNA levels were significantly lower in cytogenetic responders compared to nonresponders ( P<0.05), but subsequent decrease in the transcript levels caused the loss of any correlation to the cytogenetic status. These results suggest that bcr/abl mRNA levels may reflect cytogenetic response only during the early phases of imatinib therapy.

Streptozotocin-induced genotoxic effects in Chinese hamster cells: the resistant phenotype of V79 cells.

The genotoxic effects of the methylating agent streptozotocin (STZ) on Chinese hamster cells CHO-9 and V79 were evaluated. The induction of cell killing, chromosomal aberrations, sister-chromatid exchanges (SCEs) and mutations was analyzed. Comparisons were made with the the STZ aglyconic analogue N-methyl-N-nitrosourea (MNU). V79 cells were found to be more resistant than CHO-9 cells to STZ and MNU killing effects, as well as to the induction of chromosomal aberrations and SCEs; however, V79 and CHO-9 cells appeared to be equally sensitive to the induction of 6-thioguanine resistant mutants by STZ. These results suggest that an error-free mechanism that tolerates DNA methylation damage confers a resistant phenotype to V79 cells to the genotoxic effects of methylation damage.

Streptozotocin-induced chromosomal aberrations, SCEs and mutations in CHO-9 parental cells and in EM-C11 mutant cell line.

The genotoxic effects induced by the monofunctional nitrosourea derivative streptozotocin (STZ) were investigated in Chinese hamster ovary cells, parental (CHO-9) and its mutant hypersensitive to alkylating agents, designated EM-C11. The ability of this compound to induce chromosomal aberrations, cell killing, sister-chromatid exchanges (SCEs) and mutations was evaluated on these two cell lines. The mutant cells were found to be slightly more sensitive to the killing effects of STZ than the parental cell line. EM-C11 cells also showed higher levels of STZ-induced chromosomal aberrations than CHO-9 cells, but appeared to be equally sensitive to induction of SCEs. The frequencies of STZ-induced mutations, measured as resistant Na+/K(+)-ATPase and HPRT mutants, revealed a higher sensitivity of EM-C11 to the mutagenic effects of this compound.

Streptozotocin-induced toxicity in CHO-9 and V79 cells.

The cytotoxicity of streptozotocin (STZ) was investigated in Chinese hamster fibroblast lines (CHO-9 and V79) in comparison to two other alkylating agents, methylnitrosourea (MNU) and ethylnitrosourea (ENU), using cell survival as the endpoint. It was found that V79 cells were far more resistant to methylation induced by STZ and MNU than CHO-9 cells (20 and four times, respectively) but equally sensitive to the ethylating agent ENU. The extent of STZ-induced DNA methylation was estimated by analyzing the extent of O6-metG and N7-metG adducts in the DNA of treated cells through high-performance liquid chromatography (HPLC) with electrochemical detection. The number of adducts as well the efficiencies of their removal from the DNA were similar in both cell lines. The response of these cells to the presence of DNA damage was evaluated by analysis of STZ effects on DNA replication and cell cycle progression. Measurement of [3H]-thymidine incorporation showed a similar pattern of response at the level of inhibition of DNA synthesis in both cell lines. However, analysis of metaphase cells 36 hr after STZ exposure showed an accumulation of cells in the second cycle in the CHO-9 line, indicating induction of a cell cycle arrest. Only a slight effect was observed on cell cycle progression in V79 cells, indicating that the methylation resistance of these cells could be related to their ability to progress through the cell cycle despite the presence of DNA lesions.

[A free transfer of the pulp of the toe with an exteriorized flap. A compromise between microsurgery and traditional surgery]. / Transfert libre de pulpe d'orteil avec pédicule extériorisé. Un compromis entre la microchirurgie et la chirurgie traditionnelle.

Free toe pulp transfer represents the most sophisticated technique which corresponds functionally as close as possible to total restoration of the digital pulp. However, this operation presents technical disadvantages related to the very small calibre of the vessels when the vascular anastomosis is performed in the digit. When the artery and vein are anastomosed in the metacarpal region to achieve vessels with a larger calibre, the passage of the pedicle in the finger is difficult and requires complete opening of the digital canal, resulting in a finger which is often enlarged with limited mobility. The authors propose a technique which overcomes these two disadvantages.

Analysis of chimerism after bone marrow transplantation using specific oligonucleotide probes.

DNA hybridization with synthetic oligonucleotide probes was used to follow 18 leukemia patients who received bone marrow transplantation from HLA-identical siblings. Five oligomers complementary to the tandem repetitive sequences of different hypervariable regions of human DNA were designed to produce simple restriction fragment length polymorphism patterns. Each probe hybridized to one or two bands in Hinf I-digested genomic DNA. Combined use of these probes enabled us to distinguish all sibling pairs. DNA analysis early post-transplant (15 days) detected donor-specific fragments in 14 of 18 subjects; two patients had a combination of recipient and donor fragments. Later post-transplant, (102-15 days), one of these two showed only recipient-specific fragments, and the other donor-specific fragments. These data are in accord with other markers of engraftment including cytogenetics and red blood cell phenotyping.

Cerebral hemorrhage and thrombotic thrombocytopenic purpura during ticlopidine treatment: case report.

We report the second case of thrombotic thrombocytopenic purpura occurring during ticlopidine therapy. A cerebral hemorrhage was the first sign of the thrombocytopenia. Even if thrombocytopenia is a rare occurrence with ticlopidine therapy, we stress that platelets must be repeatedly monitored.

A phase II trial of ProMACE-CytaBOM in previously untreated non-Hodgkin's lymphoma of intermediate- or high-grade histology.

Between November 1985 and June 1989 the aggressive combination chemotherapy programme ProMACE-CytaBOM was used at a community-based hospital as primary treatment for non-Hodgkin's lymphoma (NHL) of intermediate or high-grade histology in Ann-Arbor stages IB-IV. The 53 patients entering the study represented 90 per cent of all consecutive eligible patients with NHL diagnosed during the time period considered. Their median age was 54 years and median observation time was 36 months. Of 50 patients evaluable for response, 35 (70 per cent) achieved complete remission (CR), seven (14 per cent) partial remission, and five (10 per cent) were refractory. Treatment was given on an outpatient basis. Actually delivered drug doses ranged from 88 per cent to 97 per cent of the theoretical doses. Life-threatening toxicity was experienced by four patients. Treatment was stopped in three cases (6 per cent) because of toxicity and there was one treatment-related death. Actuarial 2-year disease-free survival of patients in CR was 73 per cent. Overall actuarial 3-year survival and disease-free survival were 67 per cent and 51 per cent respectively. High LDH level was a significant adverse prognostic factor both for achievement of CR (P less than 0.005) and for survival (P less than 0.0002). Age was of no prognostic importance. We conclude that ProMACE-CytaBOM is an effective, easy to administer and well-tolerated regimen for patients with aggressive NHL.

Cystic nephroma in children. Report of a case.

A case of cystic nephroma is described in a 20-month-old female. The diagnosis of this rare renal pathologic lesion is essentially based on its pathologic features. The treatment consisted of nephrectomy followed by a brief course of chemotherapy. The literature is reviewed with regard to the pathologic features and treatment of this lesion, which has a favorable prognosis.

[Neuroblastoma metastatic to the skull. Radiologic aspects and therapeutic problems]. / Neuroblastoma metastatico al cranio. Aspetti radiologici e problemi terapeutici.

Clinical-radiological findings, treatment and prognosis of cranial involvement in 19 cases of neuroblastoma stage IV have been considered. The most frequent clinical features were periorbital ecchymosis and intracranial hypertension. The radiographic aspects, graduated according to the type of the lesion, showed a close correlation with clinical findings and sometimes preceded them. Computerized tomography, carried out in 12 cases, was more reliable than plain films in identifying the site and extent of cranial lesions and the presence of cerebral extensions, as occurred in 2 patients. The presence of cranial involvement at diagnosis was an unfavorable prognostic sign. The 19 children were treated in various ways so that firm conclusions cannot be drawn, but cranial radiotherapy in combination with chemotherapy appeared to be more efficacious than chemotherapy alone.