Seasonality and zoonotic foodborne pathogens in Canada: relationships between climate and Campylobacter, E. coli and Salmonella in meat products.

Infections due to Campylobacter, Escherichia coli and Salmonella pose a significant health burden in Canada, resulting in major costs to the health care system and economic impacts due to lost productivity resulting from illness. Recent literature suggests that climate may play a role in the prevalence of these pathogens along the food chain. This study used integrated surveillance data to examine associations between weather variables, serving as a proxy for climate, in agricultural areas and Campylobacter, generic E. coli and Salmonella contamination on samples of beef, poultry and swine meat products in Canada. Various temperature metrics (average, maximum and variability) were correlated with Campylobacter prevalence along the food chain. The prevalence of E. coli and Salmonella was correlated with both precipitation and temperatures metrics; however, analysis for E. coli was limited to beef and swine meats at retail settings, because prevalence in other combinations approached 100%, which obviated further analysis. Campylobacter contamination in poultry and swine at abattoir and retail settings demonstrated a seasonal trend, with increased prevalence generally from June or July through November, compared to the baseline month of December. Based on these analyses, Campylobacter is the most likely foodborne bacteria studied whose occurrence in meat products is affected by climatic changes in Canada. An exploratory analysis of data at the provincial scale, using Ontario as an example, revealed similar directional relationships between climate and bacterial prevalence.

Liver transplant for metastatic pancreatoblastoma: 7-year event-free survival after chemotherapy, pancreatectomy, complete hepatectomy, and liver transplant.

Pancreatoblastoma is a rare malignant tumor in children. Surgical resection of the tumor is necessary for cure; however, due to its aggressive nature, it is often unresectable at presentation due to tumor size, local invasion, and/or metastasis. Because it is a rare tumor, there is currently no standard treatment regimen. We report a case of a 4-year-old boy who presented with metastatic pancreatoblastoma with multiple large metastases involving all four sectors of the liver. We began treatment with chemotherapy (cisplatin, 5FU, vincristine, and doxorubicin), which significantly reduced the tumor burden in both the pancreas and liver. We then performed a staged subtotal pancreatectomy, complete hepatectomy, and living donor left lateral segment liver transplant. This was followed by postoperative adjuvant chemotherapy. Our patient is alive and healthy and has now been tumor-free for 7 years with no tumor relapse.

Non-operative treatment versus percutaneous drainage of pancreatic pseudocysts in children.

PURPOSE: The objective of this study was to characterize the clinical course and outcomes of children with pancreatic pseudocysts that were initially treated non-operatively or with percutaneous drainage. METHODS: A retrospective review of children with pancreatic pseudocysts over a 12-year period was completed. Categorical variables were compared using Fischer's exact method and the Student's t test was used to compare continuous variables. Analysis was done using logistic and linear regression models. RESULTS: Thirty-six children met the criteria for pancreatic pseudocyst and 33 children were treated either non-operatively or with percutaneous drainage. Of the 22 children managed non-operatively, 17 required no additional intervention (77 %) and five required surgery. Operative procedures were: Frey procedure (3), distal pancreatectomy (1), and cystgastrostomy (1). Eight of the 11 children treated with initial percutaneous drainage required no additional treatment (72 %). The other three children underwent distal pancreatectomy. Success of non-operative management or percutaneous drainage was not dependent on size or complexity of the pseudocyst Logistic regression did not identify any patient demographic (gender, age, and weight), etiologic (trauma, non-traumatic pancreatitis) or pseudocyst characteristic (size, septations) that predicted failure of non-operative therapy. CONCLUSIONS: In children, pancreatic pseudocysts can frequently be managed without surgery regardless of size or complexity of the pseudocyst. When an intervention is needed, percutaneous drainage can be performed successfully, avoiding the need for major surgical intervention in the majority of patients.

ARF mediates recruitment of PtdIns-4-OH kinase-beta and stimulates synthesis of PtdIns(4,5)P2 on the Golgi complex.

The small GTPase ADP-ribosylation factor (ARF) regulates the structure and function of the Golgi complex through mechanisms that are understood only in part, and which include an ability to control the assembly of coat complexes and phospholipase D (PLD). Here we describe a new property of ARF, the ability to recruit phosphatidylinositol-4-OH kinase-beta and a still unidentified phosphatidylinositol-4-phosphate-5-OH kinase to the Golgi complex, resulting in a potent stimulation of synthesis of phosphatidylinositol-4-phosphate and phosphatidylinositol-4,5-bisphosphate; this ability is independent of its activities on coat proteins and PLD. Phosphatidylinositol-4-OH kinase-beta is required for the structural integrity of the Golgi complex: transfection of a dominant-negative mutant of the kinase markedly alters the organization of the organelle.

Fibre architecture and song activation rates of syringeal muscles are not lateralized in the European starling.

The songbird vocal organ, the syrinx, is composed of two sound generators, which are independently controlled by sets of two extrinsic and four intrinsic muscles. These muscles rank among the fastest vertebrate muscles, but the molecular and morphological foundations of this rapid physiological performance are unknown. Here we show that the four intrinsic muscles in the syrinx of male European starlings (Sturnus vulgaris) are composed of fast oxidative and superfast fibres. Dorsal and ventral tracheobronchialis muscles contain slightly more superfast fibres relative to the number of fast oxidative fibres than dorsal and ventral syringealis muscles. This morphological difference is not reflected in the highest, burst-like activation rate of the two muscle groups during song as assessed with electromyographic recordings. No difference in fibre type ratio was found between the corresponding muscles of the left and right sound generators. Airflow and electromyographic measurements during song indicate that maximal activation rate and speed of airflow regulation do not differ between the two sound sources. Whereas the potential for high-speed muscular control exists on both sides, the two sound generators are used differentially for modulation of acoustic parameters. These results show that large numbers of superfast fibre types are present in intrinsic syringeal muscles of a songbird, providing further confirmation of rapid contraction kinetics. However, syringeal muscles are composed of two fibre types which raises questions about the neuromuscular control of this heterogeneous muscle architecture.

Desulfurization of coal.

Coal combustion is the largest single source of sulfur oxide pollution. Treatment of some major representative U.S. coals with aqueous ferric solution removes 40 to 75 percent of the sulfur content through near quantitative oxidation of the pyritic sulfur contained in the coal matrix. Elemental sulfur and iron sulfate are recovered as products of the reaction. Engineering assessment indicates that the system, when fully developed, offers high potential for the economic abatement of sulfur oxide pollution.

A DNA segment encoding two genes very tightly linked to Huntington's disease.

The discovery of D4S10, an anonymous DNA marker genetically linked to Huntington's disease (HD), introduced the capacity for limited presymptomatic diagnosis in this late-onset neurodegenerative disorder and raised the hope of cloning and characterizing the defect based on its chromosomal location. Progress on both fronts has been limited by the absence of additional DNA markers closer to the HD gene. An anonymous DNA locus, D4S43, has now been found that shows extremely tight linkage to HD. Like the disease gene, D4S43 is located in the most distal region of the chromosome 4 short arm, flanked by D4S10 and the telomere. In three extended HD kindreds, D4S43 displays no recombination with HD, placing it within 0 to 1.5 centimorgans of the genetic defect. Expansion of the D4S43 region to include 108 kilobases of cloned DNA has allowed identification of eight restriction fragment length polymorphisms and at least two independent coding segments. In the absence of crossovers, these genes must be considered candidates for the site of the HD defect, although the D4S43 restriction fragment length polymorphisms do not display linkage disequilibrium with the disease gene.

Evaluation of the effect of signalment and owner-reported impairment level on accelerometer-measured changes in activity in osteoarthritic dogs receiving a non-steroidal anti-inflammatory.

In veterinary medicine, evaluation of osteoarthritis (OA) treatment efficacy remains challenging. Measurement of activity, utilizing accelerometers, provides a surrogate measure of pain through measuring effects on activity, and the objective data collected can be used to assess the efficacy of treatments. However, little is known about how dog characteristics impact the accelerometry-measured response to treatment. The objectives of this study were to evaluate the effect of signalment and initial impairment level on accelerometer-measured changes in activity in osteoarthritic dogs after receiving a non-steroidal anti-inflammatory (NSAID). Fifty-seven client-owned dogs with OA-associated pain and mobility impairment were administered meloxicam for 2 weeks, following a 2-week baseline, and spontaneous activity was measured using an Actical accelerometer unit. Signalment factors and disease variables were recorded (age, sex, weight, impairment level, forelimb or hindlimb pain). Initial degree of impairment had a significant effect on changes in weekly (P=0.009), weekday (P=0.044) activity following NSAID treatment. Greater initial impairment was associated with larger positive changes in activity. Degree of impairment should be taken into consideration during the development of a clinical trial. Appropriate selection of candidates based on initial degree of impairment may permit a greater treatment effect, therefore increasing the power of the study.

TATA-binding protein and associated factors in polymerase II and polymerase III transcription.

Transcription by RNA polymerase I (pol I), pol II, and pol III requires the TATA-binding protein (TBP). This protein functions in association with distinct TBP-associated factors (TAFs) which may specify the nature of the polymerase selected for initiation at a promoter site. In the pol III transcription system, the TBP-TAF complex is a component of the TFIIIB factor. This factor has been resolved into a TBP-TAF complex and another component, both of which are required for reconstitution of transcription by pol III. Neither the TBP-TAF complexes B-TFIID and D-TFIID, which were previously characterized as active for pol II transcription, nor TBP alone can complement pol III transcription reactions that are dependent upon the TBP-TAF subcomponent of TFIIIB. Surprisingly, the TBP-TAF subcomponent of TFIIIB is active in reconstitution of pol II transcription.

Identification of the factor responsible for autogenous bleaching of glycollate oxidase.

Autogenous bleaching of glycollate oxidase (glycollate:oxygen oxidore-ductase, EC 1.1.3.1) is characterized by a loss of absorption due to enzyme-bound FMN and the presence of a lag in the catalytic assay. The extent of bleaching varies with different preparations. The following evidence indicates that bleaching is due to the presence of sulfite in the enzyme preparation which forms a reversible complex (EFMN + Y = EFMN . Y, Y = sulfite) with enzyme-bound FMN. Both EFMN . Y and authentic enzyme-sulfite complex exhibit similar spectral and catalytic properties. At pH 7.0 both complexes are decomposed by agents (2,6-dichlorophenolindophenol, H2O2) which cause sulfite oxidation. In the absence of such agents the complexes are extremely stable at pH 7.0 even during extensive dialysis. A pronounced decrease in complex stability is observed at pH 9.0 and 25 degrees C. Both sulfite and Y are readily removed by dialysis under these conditions. At lower temperatures both complexes exhibit an increase in stability at pH 9.0. Reversible association-dissociation is observed with EFMN . Y and EFMN . SO3 at pH 9.0, when the temperature is varied between 25 and 0 degrees C. The supernatant obtained after heat denaturation of EFMN . Y causes bleaching when mixed with EFMN, indicating that Y is present in the heat extract. A stable Bunte salt is formed by reacting sulfite with 4,4'-dithiodipyridine. Reaction of the latter with the heat extract yields a product with spectral and chromatographic properties identical to the authentic Bunte salt, indicating that the heat extract contains sulfite.

Safety of autotransplants with high-dose melphalan in renal failure: a pharmacokinetic and toxicity study.

Melphalan (MEL) is probably the most effective chemotherapeutic agent in multiple myeloma (MM) with a clear dose-response effect. It can be escalated without excessive toxicity to 200 mg/m2, a myeloablative dose requiring hematopoietic stem cell support. Patients with marked renal insufficiency, not an infrequent finding in MM, have either received reduced doses or have been excluded from therapy with high-dose MEL. A prospective study was performed to evaluate the relationship between MEL pharmacokinetics and renal function in 20 patients with MM. Six patients had severe renal insufficiency (creatinine clearance, <40 ml/min), including five on chronic hemodialysis. Three patients with severe renal impairment first received a low test dose of MEL (16 mg/m2) for pharmacokinetic studies. All patients received 200 mg/m2 MEL divided into two equal doses of 100 mg/m2 i.v. on 2 consecutive days, followed by the administration of peripheral blood stem cells. MEL pharmacokinetics, performed after the first dose of 100 mg/m2, was not adversely affected by impaired renal function. The median half-life (t1/2), area under the concentration curve, and clearance of MEL were 1.1 h, 5.5 mg h/liter, and 27.5 liter/h, respectively, in patients with a creatinine clearance of <40 ml/min compared to 1.9, 7.9, and 23.6 for the others. Renal insufficiency also had no apparent negative impact on the quality of peripheral blood stem cell collections and did not adversely affect posttransplant engraftment, transfusion requirements, incidence of severe mucositis, or overall survival. However, it was associated with longer durations of fever (P = 0. 0005) and hospitalization (P = 0.004). No transplant-related deaths were observed. Plasma t1/2 and area under the concentration curve differed by a factor of 10 and MEL clearance by a factor of 5 between patients with the lowest and highest values. These large variations in MEL elimination could not be explained by patient or disease characteristics. We conclude that renal failure does not require dose reduction of MEL in autologous transplant. Due to marked interindividual variation in MEL elimination, pharmacokinetically guided dosing as well as cellular pharmacology studies may be helpful in achieving a more uniform antitumor effect.

Magnetic Nanoparticles with High Specific Absorption Rate at Low Alternating Magnetic Field.

This paper describes the synthesis and properties of a new type of magnetic nanoparticle (MNP) for use in the hyperthermia treatment of tumors. These particles consist of 2-4 nm crystals of gamma-Fe2O3 gathered in 20-40 nm aggregates with a coating of carboxymethyl-dextran, producing a zetasize of 110-120 nm. Despite their very low saturation magnetization (1.5-6.5 emu/g), the specific absorption rate (SAR) of the nanoparticles is 22-200 W/g at applied alternating magnetic field (AMF) with strengths of 100-500 Oe at a frequency of 160 kHz.

Monotherapy with cyclosporine for chronic immunosuppression in pediatric liver transplant recipients.

Children who survive liver transplantation (LT) suffer the adverse effects of life-long immunosuppression. In an attempt to minimize these effects, we have instituted a program of tapering immunosuppression, resulting in chronic monotherapy for children after LT. Seventy-three children ages 4 months to 19 years received LT between January 1987 and December 1992. Patient survival was 85% (62/73), with graft survival of 73%, at one year. Triple therapy with prednisone, cyclosporine, and azathioprine begun at transplant was tapered as follows: 1-2 mg/kg prednisone at discharge was reduced by .2 mg/kg every 2 months until a .2 mg/kg total was reached. Alternate-day steroids (.2 mg/kg) were begun at 1 year and discontinued at 1.5 years. AZA (1 mg/kg) was begun posttransplant and discontinued after any serious viral illness or by 1 year. Currently 37 survivors are > 18 months post-LT and were considered candidates for monotherapy. Monotherapy was attempted in 28 (76%), and 25 of these remain on monotherapy an average of 2 years later. All have normal liver function. After monotherapy and alternate-day steroids were achieved, 66% of children < 5th percentile for height at the time of transplant improved to greater than the 5th percentile. There were 3 (11%) patients who rejected while on monotherapy an average of 1.15 years after it was started. These patients had the following predisposing factors that decreased cyclosporine levels and led to rejection: common bile duct stricture, chronic and intermittent antibiotic administration for urinary tract infection, and noncompliance. In the 9 potential candidates not tapered to monotherapy, 6 have had recurrent acute or chronic rejection; 2 of these now receive FK506. We conclude that the majority of stable pediatric LT recipients may be safely tapered to chronic cyclosporine monotherapy. Increased growth is a major benefit of decreased steroid dosing in these children. Cyclosporine absorption and adequate levels are crucial for success of this approach.

Rapid detection of experimental E. coli endophthalmitis by the Limulus lysate test.

Experimental E. coli endophthalmitis was produced in rabbits. The Limulus lysate test was applied to aqueous and vitreous samples at various intervals after the intravitreal injection of E. coli organisms. Results indicated that this test is feasible using vitreous and aqueous samples. The Limulus test was positive for E. coli endotoxin within hours after infection, requiring only 1 hr to determine the presence of endotoxin after sampling. This test may have some value in the rapid diagnosis of gram-negative endophthalmitis.

tetra-O-methylnordihydroguaiaretic acid inhibits melanoma in vivo.

tetra-O-methylnordihydroguaiaretic acid is a derivative of a naturally-occurring lignan, nordihydroguaiaretic acid, that has previously been shown to inhibit various cancer types in vitro and in vivo. Additionally, nordihydroguaiaretic acid has been shown to have nephrotoxic effects in the rat. Here we show that tetra-O-methylnordihydroguaiaretic acid inhibits the growth of a number of tumor cell lines in vitro by inducing apoptosis in a non-schedule-dependent manner. Further, this compound inhibits the synthesis of DNA by melanoma cells and causes cell cycle arrest in G0/G1 and G2/M phases of the cell cycle. tetra-O-Methylnordihydroguaiaretic acid also inhibits the growth of both murine and human melanomas and human colon cancer in vivo without apparent hepatic or renal toxicity.

The usefulness of diagnostic tests on pericardial fluid.

STUDY OBJECTIVES: To determine the physical, chemical, and cellular characteristics of pericardial fluid in various disease states and to assess their diagnostic accuracies. SETTING: A metropolitan university hospital. DESIGN: Consecutive case series. PATIENTS: One hundred seventy-five hospital patients, aged 1 month to 87 years, who had undergone pericardiocentesis (n = 165) or control subjects who had undergone open heart surgery (n = 10) between 1984 and 1996. MEASUREMENTS: The appearance of pericardial fluid and results of chemistry tests, cell counts, cytologic studies, Gram's stain, and microbial cultures were obtained by chart review. The etiology of each pericardial fluid sample was determined using prospective diagnostic criteria. RESULTS: Exudates differed from transudates by higher leukocyte counts and ratios of fluid to serum lactate dehydrogenase levels. Fluid glucose levels were significantly less in exudates. Sensitivity for detecting exudates was high for specific gravity > 1.015 (90%), fluid total protein > 3.0 g/dL (97%), fluid to serum protein ratio > 0.5 (96%), fluid lactate dehydrogenase ratio > 0.6 (94%), and fluid to serum glucose ratio < 1.0 (85%). None of these indicators were specific. Fluid total protein and specific gravity were moderately correlated (r = 0.56). Fluid cytologic study had a sensitivity of 92% and specificity of 100% for malignant effusion. No other test was diagnostic for a specific etiology. Among infection-associated effusions, culture-positive fluid had more neutrophils, higher lactate dehydrogenase levels, and lower ratios of fluid to serum glucose than culture-negative (parainfective) fluid. CONCLUSIONS: Evaluation of pericardial fluid might be limited to cell count, glucose, protein, and lactate dehydrogenase determinations plus bacterial culture and cytology. While not used routinely, other tests that may be highly specific for particular diseases should be ordered only to confirm a high clinical suspicion.

Comparative pharmacokinetic study of high-dose etoposide and etoposide phosphate in patients with lymphoid malignancy receiving autologous stem cell transplantation.

The pharmacokinetics of two etoposide (E) formulations were evaluated in patients with refractory hematologic malignancies receiving high-dose conditioning with autologous stem cell transplantation. Patients were randomized to either E at 800 mg/m(2) (containing polysorbate 80 and polyethylene glycol) or etoposide phosphate (EP) at 910 mg/m(2) on days -7 and -5, prior to melphalan, 80 mg/m(2) on day -5. On day -3, EP was repeated. Plasma E was analyzed after each formulation on days -7 and -5 to compare intrapatient pharmacokinetics. In total, 10 patients were treated: four each with multiple myeloma or Hodgkin's disease and two with non-Hodgkin's lymphoma. Mucositis was the major toxicity with seven patients. EP first produced grade 3 mucositis. There was no procedure-related mortality and eight patients remained alive 1 year post-transplant. Cumulative etoposide exposure (AUC) was slightly greater with EP (P=0.056). Conversely, the volume of distribution was slightly, 33%, larger (P=0.052) and clearance was increased with the E infusion (P=0.14). As none of the differences reached statistical significance, both E formulations appear to be pharmacokinetically equivalent in the high-dose transplant setting. The combination of high-dose EP with melphalan is an active preparative regimen prior to ABMT for hematologic malignancies.

Development and testing of a process measure of nursing home quality of care.

OBJECTIVE: To develop and test quality of care process measures for three medical conditions of nursing home patients: fever, shortness of breath, and chest pain. DESIGN: Flowsheets designed to capture the critical elements of care for the above conditions were developed by an expert panel. Nursing home residents charts were reviewed retrospectively using the flow sheets. The reviews were translated into clinical scenarios, and the quality of care the scenarios represented was rated by an expert panel. SETTING: All nursing homes in Hennepin County, MN, that care for Medicaid patients. PATIENTS: A random sample of 1405 Medicaid nursing home residents from 1984 and 1988. MEASURES: Measures of quality of physician assessment and intervention, quality of nurse assessment and intervention, and global quality were developed and the intra- and interrater reliability were tested. The measures' validity was assessed by their ability to predict resident death. RESULTS: Intrarater reliability was measured as the correlation of the ratings of blinded duplicates. The correlation for the global scale and the four subscales ranged from .74 to .88 (P < .001 for all). Interrater reliability was tested by examining what percentage of the quality ratings were within one unit (1-5 scale) for all three raters. All three raters were within one unit for more than 72% scenarios for all scales. The subscale of quality of physician assessment was able to predict resident death when the worst episode of care (OR = .47, 95% CI(.31-.74)) or the mean episode of care (OR .54, 95% CI(.30-.99)) was used. None of the other subscales or the global measure predicted death. CONCLUSIONS: Through the use of an expert panel, measures of nursing home quality of care were developed for shortness of breath, fever, and chest pain. These measures have reasonable reliability and significant face validity. Their validity is supported further by the ability of one of the measures to predict resident death.

Do-not-resuscitate orders in an extended-care study group.

We examined the charts of 911 nursing home patients in Hennepin County, Minnesota, to determine the prevalence of written do-not-resuscitate (DNR) orders. Information regarding demographic characteristics, and whether a surrogate decisionmaker was available and participated in the decision, was also collected. Twenty-seven percent of patients had DNR orders. Ninety percent of all patients had potentially available surrogate decisionmakers. However, for 31% of patients with DNR orders, there was no documentation of patient or surrogate participation in the DNR decision. Univariate analysis identified female sex; increased age, level of care (skilled versus intermediate), presence of a potential surrogate decisionmaker, and increasing length of time since nursing home admission as factors associated with presence of DNR orders. When a logistic regression model was used, increased age, increased length of time since nursing home admission, skilled versus intermediate level of care, and presence of a surrogate decisionmaker were independently associated with presence of DNR status. Several variables are independently associated with written DNR orders; their relationship to the factors physicians use in decision making requires further study.

Immunology of herpesvirus infection: immunity to herpes simplex virus in eye infections.

A gereral, overall pattern of the temporal relationship and interaction between cell and antibody-mediated immune responses following herpes simplex virus infection of the rabbit cornea can be synthesized from our studies. Cell-mediated immunity (CMI) appears early following infection, at a time when mononuclear and lymphocytic cellular proliferation occur at the limbus. Interaction between specifically immune lymphocytes with virus antigens are detected by lymphocyte blastogenesis and migration inhabiting factor. During stromal keratitis, a second phase of CMI involves transient virus-specific cytotoxic lymphocytes, which destroy cells that display viral-induced antigens on their surface. Chemotatic factors generated by viral antigens alone or with antiviral antibody or by virus-sensitized lymphocytes play a role in attracting polymorphonuclear leukocytes to the cornea during stromal keratitis. Soluble mediators of CMI secreated by activated lymphocytes act both specifically and nonspecifically on virus-infected cells, allowing cell destruction and making intracellular virus available for neutralization by antiviral antibody. Cell-mediated immunity in the acute infection, diminishes with the appearance of significant antiviral antibody titers. The late phase of the corneal immune response results from a local antigen-antibody interaction and is characterized by cells predominantly of the plasmacytic type. The presence of complement-dependent cytotoxic antibodies capable of destroying virus-infected cells provide an additional factor in restriction of infection.