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Biomedical subjects

K Carroll

Publications and source records attributed to K Carroll.

At least 37 records · Page 2Linked to original sources
PubMed2001

High rates of multiple antibiotic resistance in Streptococcus pneumoniae from healthy children living in isolated rural communities: association with cephalosporin use and intrafamilial transmission.

OBJECTIVE: Streptococcus pneumoniae is one of the most clinically significant pathogens with emerging antibiotic resistance. We performed a surveillance study in isolated rural populations of healthy children to estimate the prevalence of pneumococcal resistance and to contrast factors that predict pneumococcal carriage with those that specifically predict resistant pneumococcal carriage. METHODS: The study was conducted in 1998 in 2 rural communities in Utah. Families were recruited directly for participation through community canvassing. Surveillance nasopharyngeal cultures were obtained from children who were younger than 8 years. Antibiotic usage and information on other potential risk factors were obtained from questionnaires and local pharmacy records. Resistance was determined by testing isolates for susceptibility to penicillin, cefaclor, trimethoprim-sulfamethoxazole, erythromycin, ceftriaxone, and trovafloxacin. Selected resistant isolates were characterized further by serotyping, pulsed field gel electrophoresis, and Southern blot with DNA probes specific for the pneumococcal lytA gene and for antibiotic resistance genes. RESULTS: In April 1998, surveillance nasopharyngeal cultures were obtained from 368 children aged </=8 years in community A and 369 children in community B. The number of antibiotic courses per child within 1 year before culture was higher in community B than A (mean: 2.2 vs 1.7). Conversely, oral cephalosporins were more frequently used in community A than B (community A: 22% received cephalosporins within 4 months; community B: 12%). Colonization with S pneumoniae was detected in 24% of children in community A and 14% in community B; 36% of isolates from community A and 28% of isolates from community B were resistant or intermediately susceptible to at least 1 antibiotic tested. Reduced susceptibility was most common to trimethoprim-sulfamethoxazole and cefaclor (28% and 26%, respectively). Pneumococcal carriage (susceptible or resistant) was independently associated with age <5 years (odds ratio [OR]: 2.2), child care exposure (OR: 2.4), presence of a sibling with a positive culture (OR: 3.3), and residence in community A (OR: 1.7). Among carriers, age <2 years (OR: 2.6), use of cephalosporins within the preceding 4 months (OR: 2.7), and having a sibling colonized with resistant S pneumoniae (OR: 5.5) were independent predictors of reduced susceptibility or resistance. Each pair of resistant isolates from siblings was indistinguishable by pulsed field gel electrophoresis and other molecular typing techniques. Several pneumococcal isolates from these isolated rural areas had the molecular characteristics of international clones of multiple-drug-resistant pneumococci that have been associated with worldwide spread. CONCLUSIONS: Young age and intrafamilial transmission were important risk factors for carriage of both susceptible and resistant S pneumoniae. In contrast, previous cephalosporin use was linked specifically to resistant pneumococcal carriage, which suggests that modifications in antibiotic usage patterns may have salutary effects on antimicrobial resistance. These results extend previous observations in large cities regarding the penetration of multiple-drug-resistant clones of pneumococci into community populations.

Anti-Bacterial Agents↗
PubMed2001

Photobleaching of arterial autofluorescence for immunofluorescence applications.

Immunohistochemical localization of low-level antigens in the arterial vasculature is complicated by the presence of complex molecules such as collagen, elastin, cholesterol, and fluorescent lipids that exhibit autofluorescence over a wide spectrum of wavelengths. UV irradiation of arterial vasculature has remained ineffective in preparing samples for immunofluorescent staining because of the recovery of the endogenous fluorescence within a short time following treatment. Therefore, we sought to further enhance the signal-to-noise ratio in arteries by optimizing the photobleaching of this tissue. We report here that the use of filtered sunlight significantly reduces arterial autofluorescence compared to standard UV shortwave and longwave irradiation and maintains multiple antigen epitopes suitable for immunohistochemical analysis. Using this method, we localized low-level laminin-5 isoform expression in situ, which was previously indistinguishable from endogenous autofluorescence.

Adult↗
PubMed2001

Comorbidity associated with atrial fibrillation: a general practice-based study.

BACKGROUND: [corrected] Atrial fibrillation is an important risk factor for ischaemic stroke. Anticoagulation treatment with warfarin can substantially reduce the risk of stroke in people with atrial fibrillation but concerns about their side-effects have limited their use in clinical practice. However there has been little population-based research on the comorbidity associated with atrial fibrillation and on the prevalence of potential contraindications to anticoagulantion treatment among these patients. AIM: To determine the prevalence of known risk factors for ischaemic stroke and possible contraindications to anticoagulant treatment among patients with atrial fibrillation. METHOD: One-year prospective cohort study in 60 general practices in England and Wales with a total population of 502,493 people. Age and sex specific prevalence rates and relative risks of risk factors for ischaemic stroke and possible contraindications to antithrombotic treatment were calculated. RESULTS: The number of patients who had a diagnosis of atrial fibrillation during the year was 1,414 (0.3%) patients. The prevalence of other nsk factors for ischaemic stroke in patients with atrial fibrillation increased with age in men, from 48% (relative risk [RR] = 3.78, 95% confidence interval [95% CI] = 3.23-4.41) at 45 to 64 years to 64% (RR = 2.21, 95% CI = 2.00-2.44) at 75years and over A similar increase of 50% (RR = 4.36, 95% CI = 3.54-5.38) to 60% (RR = 2.07, 95% CI = 1.91-2.23) was seen in women. The percentage of men with atrial fibrillation with at least one contraindication to antithrombotic treatment was 5% at 45 to 64 years and 14% at 75 years and over. Among women with atrial fibrillation, 7% had a contraindication at 45 to 64 years and 16% at 75 years and over. The all-ages relative risk of a contraindication was 1.17 (95% CI = 0.92-1.48) in men and 1.53 (95% CI = 1.28-1.83) in women. Forty per cent (575) of patients with atrial fibrillation had at least one risk factor for ischaemic stroke and no contraindications to antithrombotic treatment. CONCLUSION: Atrial fibrillation is associated with a substantial increase in the prevalence of risk factors for ischaemic stroke. By contrast, potential contraindications for antithrombotic treatment are more evenly distributed among patients with and without atrial fibrillation. Around 40% of patients with atrial fibrillation in primary care are at high risk of stroke and have no contraindicationsfor antithrombotic treatment.

Aged↗
PubMed2000

Isolation and purification of an epidermal growth factor receptor-related inhibitor of cell growth from cultured rat astrocytes.

Astrocytes rarely undergo mitotic cell division in the developed adult. However, following injury to the central nervous system (CNS), astrocytes undergo rapid cell division and reactive astrocytes encapsulate exposed areas of the CNS producing a glial scar. Studies indicate the existence of a family of epidermal growth factor receptor (EGFr) related glycosidic mitogen inhibitors with growth inhibiting properties for astrocytes. Here, for the first time, we describe the isolation of such a factor from cultured rat astrocytes by ion-exchange and immunoaffinity chromatography. The isolated factor is glycosidic in nature, cross reacts with the anti-EGFr monoclonal antibody Clone 29.1, and inhibits the growth of primary astrocytes and N2a neuroblastoma cells in vitro.

Animals↗
PubMed2000

Acid-fast-positive Legionella pneumophila: a possible pitfall in the cytologic diagnosis of mycobacterial infection in pulmonary specimens.

The acid-fast stain is commonly used in the rapid cytologic assessment of bronchoalveolar lavage (BAL) fluid to detect pulmonary mycobacterial infections, particularly in immunocompromised patients. The identification of acid-fast, rod-shaped organisms may be taken as presumptive evidence of such an infection, in the appropriate clinical setting. However, this determination is made less specific by the occasional acid-fast positivity of microorganisms other than mycobacteria. We report on the occurrence of a fatal pneumonia caused by acid-fast positive Legionella pneumophila detected by BAL. This is a potential pitfall in the rapid diagnosis of pulmonary mycobacterial infections.

Bronchoalveolar Lavage Fluid↗
PubMed2000

Expression and regulation of cytochrome P450 enzymes in primary cultures of human hepatocytes.

The aim of this study was to test suitable culture conditions for maintaining normal cellular cytoarchitecture and inducibility of P450 enzymes in primary cultures of human hepatocytes by prototypical inducers. The selectivity and sensitivity of a sandwich culture system were determined by treating cultures with a number of clinically relevant drugs that are known to be inducers of either rodent and/or human P450 enzymes. The results showed that considerable induction of CYP3A4 activity is observed at DMSO concentrations greater than 0.1% (v/v). No differences in P450 induction response were observed between cultures maintained under different matrix conditions. However, the matrix condition considered to be optimal for maintaining cellular integrity, protein yields, and P450 enzyme induction was a sandwich configuration in combination with modified Chee's medium containing insulin (6.25 microg/mL) and dexamethasone (< or =0.1 microM). Under these conditions, induction of CYP3A4 occurred at clinically relevant drug concentrations, and maximal activities were achieved after 3 days of exposure. Overall, the response of human hepatocyte cultures to treatment with both positive and negative modulators was found to reflect that observed in vivo with respect to both enzyme specificity and potency of enzyme induction, although considerable sample-to-sample variability was observed in the magnitude of induction.

Cells, Cultured↗
PubMed2000

Two-dimensional electrophoresis reveals differential protein expression in high- and low-secreting variants of the rat basophilic leukaemia cell line.

The aim of this investigation was the identification of cellular proteins that confer a high secretory phenotype on subclones of the rat basophilic leukaemia (RBL) cell line as a model of mast cell regulated degranulation. Following protein separation by two-dimensional (2-D) electrophoresis and silver staining, more than 2000 polypeptide "spots" were resolved reproducibly. Higher sample loads and Coomassie blue staining facilitated the identification by delayed extraction-matrix-assisted laser desorption/ionization (DE-MALDI) mass spectrometry of several polypeptides that were differentially expressed in the high- and low-secreting clones. Several proteins were identified whose expression could contribute to the difference in secretory phenotype. Furthermore, silver-stained 2-D gel patterns suggested differential expression of proteins in the 20-25 kDa and the pI 4.5-7.5 range, characteristic of small guanosine 5'-triphosphate (GTP)-binding proteins. By a combination of "GTP overlay" and immunoblotting, we were able to demonstrate differential expression of small GTP binding-proteins, including Rab3 proteins, in high-and low-secreting clones. The sensitivity of this complementary approach facilitated the detection of some GTP binding and Rab3 proteins, whose expression was not evident in silver-stained 2-D gels.

Animals↗
PubMed2000

Does prolonged combined androgen blockade have survival benefits over short-term combined androgen blockade therapy?

OBJECTIVES: To explore whether less than 120 days of an antiandrogen plus a luteinizing hormone-releasing hormone agonist resulted in a different survival outcome than 120 days or more of combined treatment in patients with Stage D2 prostate cancer. METHODS: Survival data were available from a previously published controlled trial that had evaluated the efficacy and tolerability of two antiandrogens, bicalutamide and flutamide, each combined with a monthly depot preparation of leuprolide or goserelin, in 813 patients with Stage D2 prostate cancer. Cox's proportional hazards regression model assessed the relative effects of the length of combined androgen blockade (CAB) therapy on survival. This analysis was repeated in the subset of patients who lived at least 2 years beyond the date of randomization. Data were obtained at a median follow-up of 160 weeks. RESULTS: A survival benefit was demonstrated for patients receiving prolonged CAB therapy, with a hazard ratio of 0.275 (95% confidence interval 0.213 to 0.355, P = 0.0001) in favor of patients who received 120 days or more of CAB therapy (median survival 1035 days versus 302 days for less than 120 days of therapy). This result was confirmed in the patients who lived at least 2 years, in whom the median survival time was increased by 35%. The hazard ratio for 120 days or more of CAB therapy versus less than 120 days was 0.415 (95% confidence interval 0.246 to 0.702, P = 0.001). CONCLUSIONS: The results of the present exploratory analysis suggest that prolonged (120 days or more) antiandrogen treatment as part of CAB therapy may result in a better survival outcome.

Adult↗
PubMed2000

A community pseudo-outbreak of invasive Staphylococcus aureus infection.

Outbreaks of invasive infection caused by methicillin-susceptible and methicillin-resistant Staphylococcus aureus occur in hospitals, long term care institutions, and in patients discharged from these settings. In contrast, epidemic S. aureus infection has not been reported in well persons in the community. Here, we describe a group of healthy young adults who resided in the same neighborhood and participated together in school sports, and who developed serious S. aureus infections within 3 weeks of each other, suggesting a true community outbreak. Timely use of molecular epidemiological tools, however, demonstrated that their illnesses were caused by unrelated bacterial strains.

Adolescent↗
PubMed2000

Regulation of glutathione S-transferase enzymes in primary cultures of rat hepatocytes maintained under various matrix configurations.

Primary rat hepatocytes were cultured under various matrix and media conditions and examined after 1 week for the expression and regulation of cytosolic glutathione S-transferase (GST) enzymes. Striking effects on cell morphology were observed in relation to the different matrix conditions, whereas media effects were less prominent. Hepatocytes cultured in serum-free Dulbecco's modified Eagle's medium (DMEM) or modified Chee's medium (MCM) maintained similar levels of total GST protein regardless of the matrix configuration or corresponding cell integrity. However, HPLC analysis showed a differential expression pattern of individual GST subunits in both a time- and medium-dependent fashion. A variable, but pronounced, matrix and medium effect was observed on the induction of total GST expression by various prototypical inducers. Dexamethasone (10 microM) induced subunits A2, M1 and M2 in a medium- and matrix-dependent fashion, whereas phenobarbital (100 microM) induced significantly only subunit A2. beta-Naphthoflavone (50 microM) suppressed all GST subunit expression except subunit P1, which was induced in a matrix- and medium-dependent fashion. These studies show that total basal level expression of GSTs in vitro is reflective of a concomitant increase in mu and pi class subunits and a decrease in alpha class subunits. Moreover, the matrix and medium conditions influence both the basal and inducible expression of GST subunits in cultured rat hepatocytes.

Animals↗
PubMed2000

Evaluation of BioStar FLU OIA assay for rapid detection of influenza A and B viruses in respiratory specimens.

BACKGROUND: Demand for the rapid diagnosis of influenza infections has increased with the advent of the availability of neuraminidase antiviral therapy for influenza A and B. Several rapid assays that detect both influenza A and B are now available. OBJECTIVES: In this study we compared the performance of the BioStar FLU OIA assay to Bartels Viral Respiratory Screening and Identification Kit (Bartels Inc., Issaquah, WA), and cell culture. STUDY DESIGN: A total of 145 patient specimens for influenza virus detection submitted in either viral transport medium or in sterile containers were evaluated by the three methods. Specimen types included nasal washings, nasal swabs, sputum, throat swabs, and bronchial alveolar lavage (BAL) fluids. RESULTS: Fifty six positive specimens were identified based on culture and/or DFA. Of these, 30 specimens were positive by the OIA assay for an overall sensitivity of 54%. The OIA assay detected 48% (n = 21) of the 44 culture positive specimens and 81% (n = 29) of the 36 DFA positive specimens. Eighty six of the 89 culture/DFA negative samples were negative by the OIA assay (97% specificity). Analysis of the OIA assay sensitivity from samples submitted in M4 transport medium or in sterile containers revealed that M4 transport medium does not reduce the sensitivity of the OIA assay. Fifteen of the 27 positive samples submitted in M4 transport medium were positive by the OIA assay (56% sensitivity) compared to 15 of 29 positive samples transported in sterile containers (52% sensitivity). Twelve specimens were either culture and/or DFA positive for viruses other than influenza, but negative by the OIA assay, suggesting that there was no cross reactivity of the OIA assay with the other virus types recovered in this study. CONCLUSIONS: The overall excellent specificity of the BioStar FLU OIA allows for treatment of positive patients for influenza, however, a negative result should be confirmed by DFA and culture.

Animals↗
PubMed2000

Rectus sheath haematoma: an unusual diagnosis.

Rectus sheath haematoma is a very rare occurrence. There were four cases in this hospital within a three month period. In this article, these cases, their investigation and management arc reported. A review of the literature was undertaken to ascertain how best to diagnose and treat this condition.

Adult↗
PubMed2000

Bicalutamide monotherapy compared with castration in patients with nonmetastatic locally advanced prostate cancer: 6.3 years of followup.

PURPOSE: Nonsteroidal antiandrogen monotherapy may be a treatment option for some patients with advanced prostate cancer. We report a survival and safety update from an analysis of 2 studies in which patients with nonmetastatic (M0) locally advanced disease were treated with either 150 mg. bicalutamide monotherapy or castration. MATERIALS AND METHODS: Data from 2 open label, multicenter studies of identical design were pooled according to protocol. Patients with stage T3/4 prostate cancer were randomized to receive 150 mg. bicalutamide daily or castration (orchiectomy or 3.6 mg. goserelin acetate every 28 days) in a 2:1 ratio. RESULTS: A total of 480 patients with locally advanced prostate cancer were randomized to treatment. After a median followup of 6.3 years mortality was 56%. There was no statistically significant difference between the 2 groups in overall survival (hazard ratio 1.05, upper 1-sided 95% confidence limit 1.31, p = 0.70) or time to progression (1.20, 1.45, p = 0.11). There were statistically significant benefits in the bicalutamide monotherapy group in the 2 quality of life parameters of sexual interest (p = 0.029) and physical capacity (p = 0.046). The highest incidences of adverse events were the pharmacological side effects of hot flashes in the castration group, and breast pain and gynecomastia in the bicalutamide group. The incidences of other types of adverse events were low. Bicalutamide was well tolerated, with few drug related withdrawals from study, and no new safety issues were identified during this longer followup. CONCLUSIONS: Monotherapy with 150 mg. bicalutamide is an attractive alternative to castration in patients with locally advanced prostate cancer for whom immediate hormone therapy is indicated.

Androgen Antagonists↗
PubMed1999

Bacillus cereus infections among oncology patients at a children's hospital.

BACKGROUND: Bacillus cereus can cause severe infections in immunocompromised persons. METHODS: We report 3 cases of bacteremia/septicemia (1 fatal) among oncology patients in a children's hospital. Because all cases occurred during a 10-day period, a common source outbreak was suspected. An epidemiologic investigation was performed. Molecular comparison of patient and environmental isolates was performed by using pulsed-field gel electrophoresis. RESULTS: After an extensive investigation, no common hospital source could be found. Pulsed-field gel electrophoresis proved that the isolates were not related. CONCLUSION: Sporadic infections in immunocompromised persons do occur and can be associated with significant morbidity.

Bacillus cereus↗
PubMed1999

Engineering Chinese hamster ovary cells to maximize sialic acid content of recombinant glycoproteins.

We have engineered two Chinese hamster ovary cell lines secreting different recombinant glycoproteins to express high levels of human beta1,4-galactosyltransferase (GT, E.C. 2.4.1.38) and/or alpha2, 3-sialyltransferase (ST, E.C. 2.4.99.6). N-linked oligosaccharide structures synthesized by cells overexpressing the glycosyltransferases showed greater homogeneity compared with control cell lines. When GT was overexpressed, oligosaccharides terminating with GlcNAc were significantly reduced compared with controls, whereas overexpression of ST resulted in sialylation of >/=90% of available branches. As expected, GT overexpression resulted in reduction of oligosaccharides terminating with GlcNAc, whereas overexpression of ST resulted in sialylation of >/=90% of available branches. The more highly sialylated glycoproteins had a significantly longer mean residence time in a rabbit model of pharmacokinetics. These experiments demonstrate the feasibility of genetically engineering cell lines to produce therapeutics with desired glycosylation patterns.

Animals↗
PubMed1999

Options for managing psychotropic medications in drug-abusing patients participating in behavioral therapies clinical trials.

This manuscript reviews strengths and weaknesses of common design options for managing non-study medications in randomized clinical trials of behavioral treatments for drug abusers. While the principal focus of these trials is on the relative efficacy of different behavioral interventions, drug abusers entering these trials are often either using or in need of prescribed psychotropic medications, which can have a major independent impact on treatment outcome. Options reviewed range from tight to minimal restriction on use of ancillary medications. Generally, major tradeoffs pertain to the balance between internal validity and generalizability. However, experimental rigor can be maintained while allowing subjects to use ancillary medications if steps are taken to monitor and minimize the variability in treatment delivery.

Behavior Therapy↗
PubMed1999

Gastrointestinal zygomycotic infection caused by Basidiobolus ranarum: case report and review.

Basidiobolus species are filamentous fungi belonging to the order Entomophthorales. Unlike other zygomycetes, Basidiobolus species have been mainly associated with a tropical form of subcutaneous zygomycosis in otherwise healthy individuals. Visceral disease caused by this pathogen is rare, but cases of gastrointestinal infection with Basidiobolus ranarum have been reported worldwide. In many of these reports, the inflammatory disease of the colon has been confused with Crohn's disease. We report the third case of B. ranarum gastrointestinal infection in the United States, which was initially treated as inflammatory bowel disease.

Entomophthorales↗