Polymicrobial bacteremia in the late 1980s: predictors of outcome and review of the literature

Although polymicrobial bacteremia has been described in several previous series, there has been no recent study of patients using rigorous statistical analysis. Our objective was to characterize a present-day patient population with polymicrobial bacteremia and to define factors prognostic of survival. Polymicrobial bacteremia accounted for 6% of all positive blood cultures at a university hospital and a Veterans Administration hospital over a 2 1/2 year period in the late 1980s. The majority of these patients were elderly with significant underlying diseases, notably malignancies, and 56% of all episodes were nosocomially acquired. Enterobacteriaceae have remained the most common organisms, though the frequency of gram-positive cocci isolated has increased compared to older studies. Gastrointestinal, genitourinary, and skin and soft-tissue sources were the most common, although the incidence of infections due to central venous catheters appeared to be increasing. The source of 25% of bacteremia was not identified despite newer diagnostic techniques. By univariate analysis, mortality, which was 36% overall, correlated with thrombocytopenia, respiratory failure, disseminated intravascular coagulation, encephalopathy, severity of underlying disease, hemolysis, adult respiratory distress syndrome, use of steroids, renal insufficiency, institution, presence of central lines, and nosocomial acquisition. Using stepwise logistic regression analysis, mortality was predicted by respiratory failure, severity of underlying disease, and hemolysis. We conclude that polymicrobial bacteremia remains an important entity in the present-day hospitalized population, with an increasing frequency of gram-positive organisms and catheter sources, and a large proportion of undiagnosed etiologies.     

A Predictive Model to Identify Clostridium difficile Toxin in Hospitalized Patients with Diarrhea

Objectives : Although Clostridium difficile is a common pathogen in hospitalized patients with diarrhea, no study has attempted to develop a predictive model to estimate the likelihood of C. difficile positivity. Methods : We conducted a cross-sectional study at a single hospital of 271 patients with diarrhea for whom stool was tested for C. difficile toxin. The sample was randomly divided into a subset to derive the model (n = 180) and another to validate it (n = 91), and independent predictors of toxin positivity were identified using logistical regression analysis. Results : C. difficile toxin was present in 81 patients and absent in 19U. In the derivation set, a positive toxin was independently predicted (p < 0.0005) by readmission within 2 wk of prior hospitalization, by a white blood cell count ≥ 10,000/mm³, and by presence of fecal leukocytes. In the validation set, C. difficile toxin was present in 24, 29, and 77% of patients with 0, 1, and ≥2 risk factors, respectively. Conclusion : If validated prospectively and/or in other centers, the model could identify patients who should be considered for empirical management while awaiting results of toxin assays.     

Clinical features and outcome of T-cell acute lymphoblastic leukemia in childhood with respect to alterations at the TAL1 locus: a Pediatric Oncology Group study

Alteration of the TAL1 locus is the most common nonrandom genetic defect in childhood T-cell acute lymphoblastic leukemia (T-ALL). To determine if rearrangements of the TAL1 proto-oncogene confer a distinct leukemic phenotype, we studied leukemic peripheral blood or bone marrow samples from 182 children with newly diagnosed T-ALL enrolled on Pediatric Oncology Group treatment protocols. Forty-eight (26%) of the samples had a local rearrangement of the TAL1 locus. Demographic and clinical features were compared for patient subgroups with and without TAL1 rearrangements. The only clinical correlates that were significantly associated with TAL1 gene rearrangements were higher white blood cell count (P = .017) and higher hemoglobin (P = .007) at diagnosis. Immunophenotypically, samples with altered TAL1 were more likely to be CD2+ (P = .001) and lack CD10 (cALLa) expression (P = .007) than those without the rearrangement. There was a trend toward improved event-free survival (EFS) in patients with TAL1 rearrangements (4-year EFS was 44% +/- 7% for patients without the rearrangements v 59% +/- 11% for those with rearrangements), but the difference was not significant (P = .34). The role of TAL1 in leukemogenesis has yet to be clearly defined, and the prognostic significance of TAL1 gene rearrangements in T-ALL deserves further study.     

Minor histocompatibility antigens HA-1-, -2-, and -4-, and HY-specific cytotoxic T-cell clones inhibit human hematopoietic progenitor cell growth by a mechanism that is dependent on direct cell-cell contact

HLA-identical bone marrow transplantation (BMT) may be complicated by graft-versus-host disease or graft rejection. Both complications are thought to be initiated by recognition of minor histocompatibility (mH) antigens by HLA-restricted mH-antigen-specific T lymphocytes. Using HLA- A2-restricted mH antigens HA-1-, -2-, and -4-, and HY-specific cytotoxic T lymphocyte (CTL) clones, we studied the recognition by these CTL clones of interleukin-2 (IL-2)-stimulated T cells (IL-2 blasts), BM mononuclear cells (BMMNCs), and hematopoietic progenitor cells (HPCs). We showed that, when IL-2 blasts from the BM donors who were investigated were recognized by the HA-1-, -2-, and -4-, and HY- specific CTL clones, their BMMNCs and HPCs were recognized as well by these CTL clones, resulting in antigen-specific growth inhibition of erythrocyte burst-forming units (BFU-E), colony-forming units- granulocyte (CFU-G), and CFU-macrophage (CFU-M). the HA-2-specific CTL clone, however, inhibited BFU-E and CFU-G growth from four donors to a lesser extent than from two other donors. We further investigated whether inhibitory cytokines released into the culture medium by the antigen-specific stimulated CTLs or by stimulated BMMNCs were responsible for suppression of HPC growth or whether this effect was caused by direct cell-cell contact between CTLs and HPCs. HPC growth inhibition was only observed after preincubation of BMMNCs and CTLs together for 4 hours before plating the cells in semisolid HPC culture medium. When no cell-cell contact was permitted before plating, neither antigen-stimulated CTL nor antigen-nonstimulated CTLs provoked HPC growth inhibition. Culturing BMMNCs in the presence of supernatants harvested after incubation of BMMNCs and CTL clones together for 4 or 72 hours did also not result in HPC growth inhibition. Both suppression of HPC growth and lysis of IL-2 blasts and BMMNCs in the 51Cr-release assay appeared to be dependent on direct cell-cell contact between target cells and CTLs and were not caused by the release of inhibitory cytokines into the culture medium by antigen-specific stimulated CTLs or by stimulated BMMNCs. Our results show that mH-antigen-specific CTLs can inhibit HPC growth by a direct cytolytic effect and may therefore be responsible for BM graft rejection after HLA-identical BMT.     

The major histocompatibility complex region marked by HSP70-1 and HSP70- 2 variants is associated with clozapine-induced agranulocytosis in two different ethnic groups

Genes of the major histocompatibility complex (MHC) have been associated with susceptibility to drug-induced adverse reactions. We previously found that clozapine-induced agranulocytosis (CA) is associated with the HLA-DRB1*0402, DRB4*0101, DQB1*0302, DQA1*0301 haplotype in Ashkenazi Jewish patients and with the HLA-DRB1*1601, DRB5*02, DQB1*0502, DQA1*0102 haplotype in non-Jewish patients. In the present study, we tested the hypothesis that the variants of the heat- shock protein 70 (HSP-70) encoded by the HSP-70 loci located within the MHC region and known to be involved in apoptosis and regulation of cell proliferation could play an important role in molecular mechanisms of CA. First, we analyzed HSP70-2 polymorphism in risk-associated haplotypes from HLA homozygous cells and normal individuals and confirmed that the HSP70-2 9-kb variant was associated invariably with DR4 (HLA-DRB1*0402, DQB1*0302) and DR2 (HLA-DRB1*01601, DQB1*0502, DQA1*0102 and HLA-DRB1*1501, DQB1*0602) haplotypes, which were the haplotypes found increased in Jewish and non-Jewish patients with CA, respectively. The 9.0-kb variant was also found to be associated with HLA-B44, DRB1*0401 and HLA-B44, DRB1*07 haplotypes. Second, in patients with CA (12 Ashkenazi Jewish and 20 non-Jewish patients), HSP70-1 A and HSP70-2 9.0-kb variants were associated with the MHC haplotypes found by us to be markers of susceptibility to CA. The clozapine-treated control group had an excess number of HSP70-1 C and HSP70-2 8.5-kb variants, consistent with genetic resistance to CA associated with those variants. This finding supports our hypothesis that a dominant gene within the MHC region (marked by HSP70-1 and HSP70-2), but not necessarily HLA, is associated with CA in two different ethnic groups.     

Bone healing pattern in surgically created circumferential defects around submerged implants: an experimental study in dog

Objective: To describe the healing of marginal defects below or above 1 mm of dimension around submerged implants in a dog model. Material and methods: In 12 Labrador dogs, all mandibular premolars and first molars were extracted bilaterally. After 3 months of healing, full‐thickness flaps were elevated in the edentulous region of the right side of the mandible. Two recipient sites were prepared and the marginal 5 mm were widened to such an extent to obtain, after implant installation, a marginal gap of 0.5 mm at the mesial site (small defect) and of 1.25 mm at the distal site (large defect). Titanium healing caps were affixed to the implants and the flaps were sutured allowing a fully submerged healing. The experimental procedures were subsequently performed in the left side of the mandible. The timing of the experiments and sacrifices were planned in such a way to obtain biopsies representing the healing after 5, 10, 20 and 30 days. Ground sections were prepared and histomorphometrically analyzed. Results: The filling of the defect with newly formed bone was incomplete after 1 month of healing in all specimens. Bone formation occurred from the base and the lateral walls of the defects. A larger volume of new bone was formed in the large compared with the small defects. Most of the new bone at the large defect was formed between the 10‐ and the 20‐day period of healing. After 1 month of healing, the outline of the newly formed bone was, however, located at a similar distance from the implant surface (about 0.4 mm) at both defect types. Only minor newly formed bone in contact with the implant, starting from the base of the defects, was seen at the large defects (about 0.8 mm) while a larger amount was detected at the small defects (about 2.2 mm). Conclusion: Marginal defects around titanium implants appeared to regenerate in 20–30 days by means of a distance osteogenesis. The bone fill of the defects was, however, incomplete after 1 month. To cite this article:
Rossi F, Botticelli D, Pantani F, Pereira FP, Salata LA, Lang NP. Bone healing pattern in surgically created circumferential defects around submerged implants: an experimental study in dog.
Clin. Oral Impl. Res 23 , 2012; 41–48.
doi: 10.1111/j.1600‐0501.2011.02170.x