Microbial Typing by Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry: Do We Need Guidance for Data Interpretation?

The integration of matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) in clinical microbiology has revolutionized species identification of bacteria, yeasts, and molds. However, beyond straightforward identification, the method has also been suggested to have the potential for subspecies-level or even type-level epidemiological analyses. This minireview explores MALDI-TOF MS-based typing, which has already been performed on many clinically relevant species. We discuss the limits of the method''s resolution and we suggest interpretative criteria allowing valid comparison of strain-specific data. We conclude that guidelines for MALDI-TOF MS-based typing can be developed along the same lines as those used for the interpretation of data from pulsed-field gel electrophoresis (PFGE).     

Antisense oligodeoxynucleotide combination therapy of primary chronic myelogenous leukemia blast crisis in SCID mice

The proliferation of chronic myelogenous leukemia (CML) cells and the transformation of normal hematopoietic cells by BCR-ABL appear to require the expression of a functional MYC protein, suggesting an approach to treatment of Philadelphia leukemias based on simultaneous targeting of BCR-ABL and c-MYC. To test this hypothesis, CML-blast crisis (CML-BC) primary cells were treated in vitro with bcr-abl and c- myc antisense phosphorothioate oligodeoxynucleotides ([S]ODNs), individually or in combination. Compared with antisense ODNs targeting of individual oncogenes, downregulation of both BCR-ABL and c-MYC by specific antisense [S]ODNs resulted in a synergistic antiproliferative effect. Colony formation of normal bone marrow cells was not affected by either treatment. To assess the therapeutic potential of multiple oncogene downregulation, SCID mice injected with CML-BC primary cells were treated systematically with equal doses of bcr-abl or c-myc antisense [S]ODNs or with a combination of both antisense [S]ODNs. Compared with mice treated with individual compounds, the disease process was significantly retarded in the group treated with both [S]ODNs as revealed by flow cytometry, clonogenic assay, and RT-PCR analysis to detect leukemic cells in mouse tissue cell suspensions. These effects correlated with a markedly increased survival of leukemic mice treated with both antisense [S]ODNs. Leukemic cells harvested from antisense [S]ODN-treated mice were sensitive to the effects of antisense [S]ODNs in vitro, suggesting that the treatment can be successfully repeated. These data demonstrate the therapeutic potential of targeting multiple cooperating oncogenes.     

Navigating growth attenuation in children with profound disabilities. Children's interests, family decision-making, and community concerns

A twenty‐person working group convened to discuss the ethical and policy considerations of the controversial intervention called “growth attenuation,” and if possible to develop practical guidance for health professionals. A consensus proved elusive, but most of the members did reach a compromise.     

Health Care Cost Matters for Homeless People: An Example of Costing Mental Health and Addiction Services in Homeless Shelters in Canada

The cost of health care services and supports for mental health and addictions is important to know. In order to calculate it, one must know who is receiving what is being provided by whom at what price. Without tracking these types of data, it is difficult to know the cost of the activities being provided. The systematic collection and analysis of such data allows decision makers to become more aware of how money is being spent. Without this information, it is difficult to evaluate different models of care or determine relative responsibilities of different government players. As a case study, we describe the analysis and findings of a project to assess the costs of mental health and addiction services within homeless shelters in Toronto, Ontario, Canada.

Cryoablation and liver resection for noncolorectal liver metastases

BACKGROUND: Liver resection for noncolorectal liver metastases has merit for selected primary tumor types. The role of cryosurgical tumor ablation within this cohort of patients has not been evaluated. This is a single institutional review of treatment outcomes using cryosurgical ablation and conventional resection techniques for noncolorectal liver metastases. METHODS: The medical records of 42 patients undergoing 48 hepatic tumor ablative procedures from February 1991 through May 2001 at a single institution were retrospectively reviewed. Overall survival and local hepatic tumor recurrence-free survival were analyzed for different surgical procedures and primary tumor types. RESULTS: Overall survival rates at 1, 3, and 5 years are 82%, 55%, and 39%, respectively (median survival, 45 months). Local hepatic tumor recurrence-free survival rates for resection only (n = 25) and cryosurgery with or without resection (n = 23), at 3 years are 24% and 19%, respectively. The survival rates at 5 years are 40% and 37%, for resection only and cryosurgery with or without resection, respectively. CONCLUSION: Cryosurgical hepatic tumor ablation for metastatic noncolorectal primary tumors results in survival and local hepatic tumor recurrence rates similar to resection alone. The combination of cryosurgery and resection extends the cohort of patients with surgically treatable disease.     

Rapid field inversion gel electrophoresis in combination with an rRNA gene probe in the epidemiological evaluation of staphylococci.

A rapid field inversion gel electrophoresis (FIGE) protocol was combined with an rRNA gene probe in the analysis of staphylococci that were difficult to study epidemiologically by conventional means. The following groups of clinical isolates were examined: (i) predominantly antibiotic-susceptible Staphylococcus aureus strains containing no detectable plasmids and unresponsive to bacteriophage typing and (ii) methicillin-resistant Staphylococcus epidermidis strains carrying a single plasmid ca. 30 kilobases in size. The results indicated that strain interrelationships could be established on the basis of SmaI-generated chromosomal restriction fragment length polymorphisms (RFLPs) analyzed by FIGE. RFLP analysis of strains known to be unrelated established the importance of minor differences in DNA banding patterns as indicators of strain dissimilarities. Hybridization studies with an rRNA gene probe confirmed this conclusion. These results suggest that FIGE analysis of chromosomal RFLPs (especially in combination with molecular probes) is an important addition to the armamentarium of molecular epidemiology.     

Rapid method for epidemiological evaluation of gram-positive cocci by field inversion gel electrophoresis.

We report a rapid method for the isolation of intact chromosomal DNA from gram-positive cocci that is suitable for in situ restriction endonuclease digestion in agarose blocks. When combined with a rapid field inversion gel electrophoresis protocol, this approach allows the preparation and electrophoretic analysis of chromosomal restriction fragments produced by rare-cutting enzymes in a total time period of 2 days from start to finish. The utility of the method is demonstrated in the epidemiological evaluation of Staphylococcus epidermidis clusters from two hospitals as well as of additional representative staphylococci and enterococci.     

Psychiatric aftercare in a metropolitan setting

In the face of the trend toward brief hospitalization, rising re-admission rates and other indices of poor community adjustment, concern has developed about the adequacy of psychiatric aftercare services. The authors report on a comprehensive study of psychiatric aftercare in a large metropolitan area (population 2.5 million). The study followed prospectively a group of 747 patients, representative of a significant proportion of patients in the care system. The findings document inadequacies in hospital-based discharge planning, unbalanced use of aftercare services and poor patient outcomes six months and two years post-discharge. The study found heavy reliance on medical/therapeutic aftercare services with a relative neglect of housing, vocational/educational, financial and social/recreational services. Despite the large volume of medical/therapeutic service use, the patient group had a high readmission rate, high levels of symptomatology and poor social adjustment on follow-up. The authors suggest that community-based practitioners with specialized training in psychiatric rehabilitation would improve the system of aftercare.