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D E Low

Publications and source records attributed to D E Low.

At least 55 records · Page 3Linked to original sources

Direct esophageal metastasis from a distant primary tumor is a submucosal process: a review of six cases.

Malignant esophageal stricture secondary to invasion from a tumor arising in a contiguous organ is a relatively rare finding; even more uncommon is a direct metastasis to the esophagus from a distant primary carcinoma. We present six cases, the largest current series, of esophageal strictures secondary to metastases from a separate primary cancer. We reviewed the records of 20 patients treated at Virginia Mason Medical Center between 1972 and 2000 with a diagnosis of malignant esophageal stricture secondary to an extraesophageal primary carcinoma. Patients whose stricture appeared to be secondary to esophageal invasion or compression from a contiguous tumor or lymph nodes were excluded. The remaining six patients who had metastases to the esophagus itself were reviewed with respect to the nature of the primary tumor, presentation, radiologic and endoscopic findings, and treatment. Among the 20 patients reviewed, 14 were excluded owing to either contiguous involvement from a nearby primary malignancy, regional nodal involvement, or complications of external beam radiation treatment. Six patients were considered to have direct metastasis to the esophagus from distant primary malignancies. The mean age of these patients was 72 years (range 68-74). Two of the primary lesions were lung carcinoma, while four primaries were breast cancers. The average time interval from the diagnosis of a primary tumor to esophageal involvement was 7 years in patients with breast cancer and 5 months in patients with lung cancer. Three patients were palliated with endoscopic dilation and stent placement. The other three patients have died secondary to upper gastrointestinal bleeding. Metastatic cancer to the esophagus is a rare occurrence. The process is usually submucosal and can be difficult to diagnose. The diagnosis should be considered when a patient presents with malignant dysphagia and has a background of distant carcinoma.

Adenocarcinoma↗

Phenotypic and genotypic characterization of macrolide-resistant group A Streptococcus strains in the province of Quebec, Canada.

Resistance to macrolides among group A streptococci is an increasing problem worldwide. We examined 496 strains phenotypically and genotypically for resistance to erythromycin and clindamycin. Strains were isolated in five different geographical areas representing about 45% of the total Quebec population. The overall resistance rate was 4.6% but varied from 0% in rural areas to 9.4% in Montreal. Of the 23 strains showing resistance to erythromycin, 15 (65%) had an identical pulsed-field gel electrophoresis pattern, were of serotype M28T28 and harboured the erm(TR) gene, suggesting the spread of a single clone. Of the remaining eight strains, two strains had the erm(B) gene, five had the mef gene and one with a different serotype also had the erm(TR) gene.

Anti-Bacterial Agents↗

In vitro activity of a novel ketolide ABT-773 against invasive strains of Streptococcus pneumoniae.

New ketolides such as ABT-773 are a promising group of antibiotics in an era of increasing antibiotic resistance. We tested 704 invasive strains of Streptococcus pneumoniae collected from 1990 to 1998. Overall resistance was 8.3, 4.6, 4.5 and 3.6% for penicillin, cefuroxime, erythromycin and clarithromycin, respectively. By using a recommended breakpoint for susceptibility of <0.5 mg/L, no strains showed reduced susceptibility to ABT-773. ABT-773 was very active against all penicillin-resistant strains (MIC > 2 mg/L, with a mean geometric mean <0.06 mg/L), and against all 33 erythromycin-resistant strains, irrespective of the mode of resistance [mef- or erm(B)-mediated]. ABT-773 is a very active and promising agent against invasive strains of S. pneumoniae, including multiresistant strains.

Anti-Bacterial Agents↗

Prevalence and mechanisms of macrolide resistance in invasive and noninvasive group B streptococcus isolates from Ontario, Canada.

Macrolide resistance has been demonstrated in group B streptococcus (GBS), but there is limited information regarding mechanisms of resistance and their prevalence. We determined these in GBS obtained from neonatal blood cultures and vaginal swabs from pregnant women. Of 178 isolates from cases of neonatal GBS sepsis collected from 1995 to 1998, 8 and 4.5% were resistant to erythromycin and clindamycin, respectively, and one isolate showed intermediate penicillin resistance (MIC, 0.25 microg/ml). Of 101 consecutive vaginal or rectal/vaginal isolates collected in 1999, 18 and 8% were resistant to erythromycin and clindamycin, respectively. Tetracycline resistance was high (>80%) among both groups of isolates. Of 32 erythromycin-resistant isolates, 28 possessed the erm methylase gene (7 ermB and 21 ermTR/ermA) and 4 harbored the mefA gene; one isolate harbored both genes. One isolate which was susceptible to erythromycin but resistant to clindamycin (MIC, 4 microg/ml) was found to have the linB gene, previously identified only in Enterococcus faecium. The mreA gene was found in all the erythromycin-resistant strains as well as in 10 erythromycin-susceptible strains. The rate of erythromycin resistance increased from 5% in 1995-96 to 13% in 1998-99, which coincided with an increase in macrolide usage during that time.

Adult↗

Evaluation of susceptibility testing to detect fluoroquinolone resistance mechanisms in Streptococcus pneumoniae.

To determine if susceptibility testing of Streptococcus pneumoniae could detect those isolates that had one of the recognized mechanisms of fluoroquinolone resistance, 101 isolates were selected; the levofloxacin MIC for 28 of these isolates was > or =4 microg/ml. Only isolates with both parC and gyrA mutations or with no recognized resistance mechanisms were reliably identified by using these results. Isolates with only a parC mutation could not be detected reliably using any susceptibility testing method.

Anti-Infective Agents↗

Interspecies recombination contributes minimally to fluoroquinolone resistance in Streptococcus pneumoniae.

Analysis of 71 ciprofloxacin-resistant (MIC > or = 4 microg/ml) Streptococcus pneumoniae clinical isolates revealed only 1 for which the quinolone resistance-determining regions of the parC, parE, and gyrB genes were genetically related to those of viridans group streptococci. Our findings support the occurrence of interspecies recombination of type II topoisomerase genes; however, its contribution to the emergence of quinolone resistance among pneumococci appears to have been minimal.

Amino Acid Sequence↗

Streptococcus iniae virulence is associated with a distinct genetic profile.

Streptococcus iniae causes meningoencephalitis and death in commercial fish species and has recently been identified as an emerging human pathogen producing fulminant soft tissue infection. As identified by pulsed-field gel electrophoresis (PFGE), strains causing disease in either fish or humans belong to a single clone, whereas isolates from nondiseased fish are genetically diverse. In this study, we used in vivo and in vitro models to examine the pathogenicity of disease-associated isolates. Strains with the clonal (disease-associated) PFGE profile were found to cause significant weight loss and bacteremia in a mouse model of subcutaneous infection. As little as 10(2) CFU of a disease-associated strain was sufficient to establish bacteremia, with higher inocula (10(7)) resulting in increased mortality. In contrast, non-disease-associated (commensal) strains failed to cause bacteremia and weight loss, even at inocula of 10(8) CFU. In addition, disease-associated strains were more resistant to phagocytic clearance in a human whole blood killing assay compared to commensal strains, which were almost entirely eradicated. Disease-associated strains were also cytotoxic to human endothelial cells as measured by lactate dehydrogenase release from host cells. However, both disease-associated and commensal strains adhered to and invaded cultured human epithelial and endothelial cells equally well. While cellular invasion may still contribute to the pathogenesis of invasive S. iniae disease, resistance to phagocytic clearance and direct cytotoxicity appear to be discriminating virulence attributes of the disease-associated clone.

Animals↗

Reciprocal, temporal expression of SpeA and SpeB by invasive M1T1 group a streptococcal isolates in vivo.

The streptococcal pyrogenic exotoxins (Spes) play a central role in the pathogenesis of invasive group A streptococcal (GAS) infections. The majority of recent invasive GAS infections have been caused by an M1T1 strain that harbors the genes for several streptococcal superantigens, including speA, speB, speF, speG, and smeZ. However, considerable variation in the expression of Spe proteins among clonal M1 isolates has been found, and many of the speA-positive M1 strains do not produce detectable amounts of SpeA in vitro. This study was designed to test the hypothesis that speA gene expression can be induced in vivo. A mouse infection chamber model that allows sequential sampling of GAS isolates at various time points postinfection was developed and used to monitor the kinetics of Spe production in vivo. Micropore Teflon diffusion chambers were implanted subcutaneously in BALB/c mice, and after 3 weeks the pores became sealed with connective tissue and sterile fluid containing a white blood cell infiltrate accumulated inside the infection chambers. Representative clonal M1T1 isolates expressing no detectable SpeA were inoculated into the implanted chambers, and the expression of SpeA in the aspirated aliquots of the chamber fluid was analyzed on successive days postinfection. Expression of SpeA was detected in the chamber fluid as early as days 3 to 5 postinfection in most animals, with a significant increase in expression by day 7 in all infected mice. Isolates recovered from the chamber and grown in vitro continued to produce SpeA even after 21 passages in vitro, suggesting stable switch on of the speA gene. A temporal relation between the upregulation of SpeA expression and the downregulation of SpeB expression was observed in vivo. These data suggest that in vivo host and/or environmental signals induced speA gene expression and suppressed speB gene expression. This underscores the role of the host-pathogen interaction in regulating the expression of streptococcal virulence factors in vivo. The model described here should facilitate such studies.

Animals↗

Streptococcal meningitis resulting from contact with an infected horse.

We report a case of group C streptococcal meningitis in a woman with a history of close animal contact as well as head trauma as a result of a kick by a horse. Blood and cerebrospinal fluid cultures grew Streptococcus equi subsp. zooepidemicus, as did a throat culture taken from the colt that had kicked her 2 weeks prior to admission.

Animals↗

Human immune response to streptococcal inhibitor of complement, a serotype M1 group A Streptococcus extracellular protein involved in epidemics.

Streptococcal inhibitor of complement (Sic) is a highly polymorphic extracellular protein made by serotype M1 group A Streptococcus strains that contributes to bacterial persistence in the mammalian upper respiratory tract. New variants of the Sic protein arise very rapidly by positive selection in human populations during M1 epidemics. The human antibody response to Sic was analyzed. Of 636 persons living in diverse localities, 43% had anti-Sic serum antibodies, but only 16.4% had anti-M1 protein serum antibody. Anti-Sic antibody was also present in nasal wash specimens in high frequency. Linear B cell epitope mapping showed that serum antibodies recognized epitopes located in structurally variable regions of Sic and the amino terminal hypervariable region of the M1 protein. Phage display analyses confirmed that the polymorphic regions of Sic are primary targets of host antibodies. These results support the hypothesis that selection of Sic variants occurs on mucosal surfaces by a mechanism that involves acquired host antibody.

Adolescent↗

The validity of a sore throat score in family practice.

BACKGROUND: Reducing the number of antibiotic prescriptions given for common respiratory infections has been recommended as a way to limit bacterial resistance. This study assessed the validity of a previously published clinical score for the management of infections of the upper respiratory tract accompanied by sore throat. The study also examined the potential impact of this clinical score on the prescribing of antibiotics in community-based family practice. METHODS: A total of 97 family physicians in 49 Ontario communities assessed 621 children and adults with a new infection of the upper respiratory tract accompanied by sore throat and recorded their prescribing decisions. A throat swab was obtained for culture. The sensitivity and specificity of the score approach in this population were compared with previously published results for patients seen at an academic family medicine centre. In addition, physicians' prescribing practices and their recommendations for obtaining throat swabs were compared with score-based recommendations. RESULTS: Of the 621 cases of new upper respiratory tract infection and sore throat, information about prescriptions given was available for only 619; physicians prescribed antibiotics in 173 (27.9%) of these cases. Of the 173 prescriptions, 109 (63.0%) were given to patients with culture-negative results for group A Streptococcus. Using the score to determine management would have reduced prescriptions to culture-negative patients by 63.7% and overall antibiotic prescriptions by 52.3% (both p < 0.01). Culturing of throat samples would have been reduced by 35.8% (p < 0.01). There was no statistically significant difference in the sensitivity or specificity of the score approach between this community-based population (sensitivity 85.0%, specificity 92.1%) and an academic family medicine centre (sensitivity 83.1%, specificity 94.3%). INTERPRETATION: An explicit clinical score approach to the management of patients presenting with an upper respiratory tract infection and sore throat is valid in community-based family practice and could substantially reduce the unnecessary prescribing of antibiotics for these conditions.

Adolescent↗

Host variation in cytokine responses to superantigens determine the severity of invasive group A streptococcal infection.

Cytokines elicited by superantigens have been suggested to play a central role in severe systemic clinical manifestations of gram-positive sepsis. Here we provide evidence for a potent inflammatory cytokine response in acute invasive group A streptococcal infections, and show a direct correlation between the magnitude of this response and the severity of systemic manifestations of the disease. Severe invasive cases suffering from toxic shock and/or necrotizing fasciitis had significantly higher frequencies of IL-2-, IL-6-, and TNF-alpha-producing cells in their circulation as compared to non-severe invasive cases (p=0.05-0.01). This difference was even more accentuated when severe and non-severe cases infected with a clonal M1T1 strain were compared (p=0.03-0. 004). To determine whether host factors were responsible for this difference in magnitude of cytokine responses, paired age- and gender-matched severe and non-severe M1T1 cases (n=8) were tested in vitro during their convalescent phase for immune response to superantigens produced by their infecting isolate. The results showed persistent and inherent differences in the magnitude of proliferative and cytokine responses of severe and non-severe patients to the streptococcal superantigens to which they had been exposed during infection. Thus, the study provides evidence that patients with a propensity to produce higher levels of inflammatory cytokines in response to streptococcal superantigens develop significantly more severe systemic manifestations than patients who have a propensity to produce lower levels of inflammatory cytokines to the same superantigens. We therefore conclude that host factors influence the magnitude of cytokine responses to superantigens and consequently the clinical outcome of the infection.

Cytokines↗

Vancomycin-resistant enterococci.

Over the last 2 decades, enterococci, formerly viewed as organisms of minimal clinical impact, have emerged as important hospital-acquired pathogens in immunosuppressed patients and intensive care units (ICUs). Vancomycin resistance in enterococci is increasing steadily. Vancomycin-resistant enterococci (VRE) composed 26% of nosocomial enterococci in 1999, a 47% increase from 1994 to 1998. More that 25% of ICU enterococci are resistant to vancomycin. Antimicrobial therapy is problematic for all VRE, but particularly when bactericidal activity is necessary. Quinipristin-dalfopristin and linezolid are 2 new approved antimicrobials for the treatment of recalcitrant infections caused byVRE. Control of the transmission of VRE, although successful in preventing infections, is neither simple nor inexpensive, and VRE has become endemic in many hospitals. However, endemicity poses serious risks to the health of current and future patients, and of itself, is expensive. Data on the cost-effectiveness of VRE prevention programs are currently lacking and urgently needed; however, because the added cost of a single VRE infection far exceeds those of gowns, gloves, and screening, it seems likely that such control programs represent significant cost savings for those hospitals willing to undertake them.

Cross Infection↗

Antibiotic resistance in respiratory tract isolates of Haemophilus influenzae and Moraxella catarrhalis collected from across Canada in 1997-1998.

Between September 1997 and November 1998 respiratory tract isolates of Haemophilus influenzae (n = 1352) and Moraxella catarrhalis (n = 428) were collected by 18 Canadian medical centres. beta-Lactamase was produced by 24.0 and 94.2% of H. influenzae and M. catarrhalis isolates, respectively. Resistance rates for H. influenzae were highest for ampicillin (24.0%), trimethoprim/sulphamethoxazole (13. 7%), loracarbef (6.1%) and cefaclor (4.2%), and </= 1% for amoxycillin/clavulanate, cefotaxime, cefprozil, cefixime, imipenem, ciprofloxacin, levofloxacin, grepafloxacin, trovafloxacin and chloramphenicol. M. catarrhalis resistance rates, derived using NCCLS breakpoint criteria for Haemophilus spp., were </= 1% for all antibiotics tested except ampicillin (49.5%) and trimethoprim/sulphamethoxazole (1.6%).

Anti-Bacterial Agents↗

Fluoroquinolone resistance in clinical isolates of Streptococcus pneumoniae: contributions of type II topoisomerase mutations and efflux to levels of resistance.

We report on amino acid substitutions in the quinolone resistance-determining region of type II topisomerases and the prevalence of reserpine-inhibited efflux for 70 clinical isolates of S. pneumoniae for which the ciprofloxacin MIC is >/=4 microgram/ml and 28 isolates for which the ciprofloxacin MIC is </=2 microgram/ml. The amino acid substitutions in ParC conferring low-level resistance (MICs, 4 to 8 microgram/ml) included Phe, Tyr, and Ala for Ser-79; Asn, Ala, Gly, Tyr, and Val for Asp-83; Asn for Asp-78; and Pro for Ala-115. Isolates with intermediate-level (MICs, 16 to 32 microgram/ml) and high-level (MICs, 64 microgram/ml) resistance harbored substitutions of Phe and Tyr for Ser-79 or Asn and Ala for Asp-83 in ParC and an additional substitution in GyrA which included either Glu-85-Lys (Gly) or Ser-81-Phe (Tyr). Glu-85-Lys was found exclusively in isolates with high-level resistance. Efflux contributed primarily to low-level resistance in isolates with or without an amino acid substitution in ParC. The impact of amino acid substitutions in ParE was minimal, and no substitutions in GyrB were identified.

Amino Acid Substitution↗

A Canadian national surveillance study of urinary tract isolates from outpatients: comparison of the activities of trimethoprim-sulfamethoxazole, ampicillin, mecillinam, nitrofurantoin, and ciprofloxacin. The Canadian Urinary Isolate Study Group.

Ampicillin, trimethoprim-sulfamethoxazole, mecillinam, nitrofurantoin, and ciprofloxacin mean resistance rates for 2,000 urinary tract isolates collected from outpatients across Canada in 1998 were 41.1, 19.2, 14.7, 5.0, and 1.8%, respectively. For Escherichia coli isolates alone (n = 1,681) comparable rates were 41. 0, 18.9, 7.4, 0.1, and 1.2%, respectively. The majority of E. coli isolates resistant to ampicillin, trimethoprim-sulfamethoxazole, or ciprofloxacin were susceptible (MIC, <16 microg/ml) to mecillinam.

Amdinocillin↗