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D Mack

Publications and source records attributed to D Mack.

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

The ablative effect of quarter dose bacillus Calmette-Guerin on a papillary marker lesion of the bladder.

PURPOSE: Low dose bacillus Calmette-Guerin (BCG) for stage TaT1 transitional cell carcinoma of the bladder has been given in various studies with the aim of decreasing side effects while maintaining the same efficacy as full dose bacillus Calmette-Guerin. However, its application in clinical practice remains controversial. We examined the ablative activity and incidence of side effects of intravesical quarter dose BCG given for a papillary marker lesion of the bladder. MATERIALS AND METHODS: Included in our study were 44 patients with primary or recurrent, multiple but no more than 10 lesions of stage pTaT1, grades 1 to 2 transitional cell carcinoma of the bladder. Intravesical treatment begun 14 days after the complete transurethral resection of all visible tumors except 1 marker lesion no larger than 1 cm. consisted of instillations of 30 mg. Connaught strain BCG diluted in 50 ml. saline once weekly for 6 consecutive weeks. Two weeks after the last instillation any residual tumor was completely resected. In cases of complete disappearance of the marker lesion deep biopsy of the tumor area was done. Urine cytology was also performed. RESULTS: There was a complete response in 27 of the 44 patients (61%), no response in 12 (27%) and progression to carcinoma in situ in 1 (2%), while the response was not evaluable in 4. Local side effects included dysuria in 54% of cases and macroscopic hematuria in 39%. Neither BCG induced infection nor BCG sepsis was observed. CONCLUSIONS: Quarter dose BCG has a clear ablative effect on superficial bladder cancer with a 61% response rate. Phase III trials are now required to compare its efficacy and toxicity to those of full dose BCG.

Adjuvants, Immunologic↗
PubMed2001

Biofilm formation by Staphylococcus epidermidis depends on functional RsbU, an activator of the sigB operon: differential activation mechanisms due to ethanol and salt stress.

Staphylococcus epidermidis is a common pathogen in medical device-associated infections. Its major pathogenetic factor is the ability to form adherent biofilms. The polysaccharide intercellular adhesin (PIA), which is synthesized by the products of the icaADBC gene cluster, is essential for biofilm accumulation. In the present study, we characterized the gene locus inactivated by Tn917 insertions of two isogenic, icaADBC-independent, biofilm-negative mutants, M15 and M19, of the biofilm-producing bacterium S. epidermidis 1457. The insertion site was the same in both of the mutants and was located in the first gene, rsbU, of an operon highly homologous to the sigB operons of Staphylococcus aureus and Bacillus subtilis. Supplementation of Trypticase soy broth with NaCl (TSB(NaCl)) or ethanol (TSB(EtOH)), both of which are known activators of sigB, led to increased biofilm formation and PIA synthesis by S. epidermidis 1457. Insertion of Tn917 into rsbU, a positive regulator of alternative sigma factor sigma(B), led to a biofilm-negative phenotype and almost undetectable PIA production. Interestingly, in TSB(EtOH), the mutants were enabled to form a biofilm again with phenotypes similar to those of the wild type. In TSB(NaCl), the mutants still displayed a biofilm-negative phenotype. No difference in primary attachment between the mutants and the wild type was observed. Similar phenotypic changes were observed after transfer of the Tn917 insertion of mutant M15 to the independent and biofilm-producing strain S. epidermidis 8400. In 11 clinical S. epidermidis strains, a restriction fragment length polymorphism of the sigB operon was detected which was independent of the presence of the icaADBC locus and a biofilm-positive phenotype. Obviously, different mechanisms are operative in the regulation of PIA expression in stationary phase and under stress induced by salt or ethanol.

Bacterial Proteins↗
PubMed2001

Rapid detection of methicillin resistance in coagulase-negative staphylococci by a penicillin-binding protein 2a-specific latex agglutination test.

The detection of PBP 2a by the MRSA-Screen latex agglutination test with 201 clinical coagulase-negative staphylococci had an initial sensitivity of 98% and a high degree of specificity for Staphylococcus epidermidis strains compared to PCR for mecA. Determination of oxacillin MICs evaluated according to the new breakpoint (0.5 microg/ml) of the National Committee for Clinical Laboratory Standards exhibited an extremely low specificity for this population.

Bacterial Proteins↗
PubMed2001

Frequency of positive biopsies after visual disappearance of superficial bladder cancer marker lesions.

INTRODUCTION AND OBJECTIVES: In phase II trials in superficial bladder cancer, marker lesions have been used to test the ablative activity of intravesical chemo- or immunotherapy. These studies provide important knowledge about drug activity and toxicity without exposing hundreds of patients in phase III trials to drugs which ultimately may not be successful in preventing tumour recurrence or progression. After treatment a deep biopsy was necessary at the site of the marker lesion even in the absence of any visual tumour. The question is if this biopsy, in the absence of any visual tumour, should be done. MATERIAL AND METHODS: The ablative effect of MMC, epirubicin, and quarter dose BCG instillations was evaluated in three different studies on a papillary marker lesion. Patients with multiple, primary or recurrent superficial bladder tumours were included. All visible Ta-T1 lesions were resected except for one marker lesion not exceeding 1 cm. TIS was excluded. In the last study, patients with T1 G3 tumours or multiple tumours >10 were also excluded. If the marker lesion disappeared completely, a deep biopsy was performed at the scar in order to prove histological disappearance of the tumour. RESULTS: 185 patients were evaluated. No visual tumours were seen in 110 patients and a TUR was performed in 101 of them. It revealed only 3 Ta lesions. In the 9 others no biopsy was performed but follow-up cystoscopy revealed no lesions. CONCLUSIONS: In the absence of any visual tumors, TUR and deep biopsy at the site of the scar of the marker lesion only rarely revealed (3 out of 110) the histological presence of a tumour. Therefore, this biopsy can be omitted in new marker lesion protocols in patient with Ta-T1, G1 G2 papillary superficial bladder tumours at intermediate risk for recurrence and low risk for progression.

Administration, Intravesical↗
PubMed2000

Virulence factors of Enterococcus faecalis and Enterococcus faecium blood culture isolates.

Known and potential virulence factors of enterococcal blood culture isolates were studied using 89 Enterococcus faecalis and 24 Enterococcus faecium isolates. The prevalence of the respective factors was (Enterococcus faecalis vs. Enterococcus faecium): hemolysin 16% vs. 0%, gelatinase 55% vs. 0%, aggregation substance 63% vs. 13%, lipase 35% vs. 4%, hemagglutinin 97% vs. 0%. Deoxyribonuclease was not detected in any isolate. The study showed that hemagglutinin and lipase may represent additional virulence factors of Enterococcus faecalis but not Enterococcus faecium. The significance of these factors in the pathogenesis of enterococcal infection needs to be elucidated in further studies.

Bacterial Proteins↗
PubMed2000

Nosocomial outbreak of vancomycin-resistant Enterococcus faecium at a German university pediatric hospital.

Nosocomial Infections caused by vancomycin-resistant enterococci (VRE) are an emerging threat to critically ill patients. At the University Hospital Eppendorf, VRE were isolated from 38 patients between August 1993 and April 1997, of whom 32 were hospitalized at the Department of Pediatrics. Pulsed-field gel electrophoresis revealed that 26 Enterococcus faecium isolates from patients of the Department of Pediatrics were identical or closely related, and that isolates from three additional patients of the same department were possibly related. All of these isolates were of vanA genotype. They were resistant to glycopeptides, ampicillin, ciprofloxacin, clindamycin, and erythromycin. Most isolates displayed high-level resistance to gentamicin, but all remained susceptible to quinupristin/dalfopristin. Implementation of stringent hand disinfection and environmental disinfection policies, as well as measures for patient isolation contained this first outbreak of VRE at a German Children's hospital, which emphasizes the importance of hygienic measures for the control of nosocomial spread of these organisms.

Child, Preschool↗
PubMed2000

Identification of three essential regulatory gene loci governing expression of Staphylococcus epidermidis polysaccharide intercellular adhesin and biofilm formation.

The formation of adherent multilayered biofilms embedded into a glycocalyx represents an essential factor in the pathogenesis of Staphylococcus epidermidis biomaterial-related infections. Using biofilm-producing S. epidermidis 1457 and transposon Tn917 carried on plasmid pTV1ts, we isolated nine isogenic biofilm-negative transposon mutants. Transduction by S. epidermidis phage 71 was used to prove the genetic linkage of transposon insertions and altered phenotypes. Mapping of the different transposon insertions by Southern hybridization and pulsed-field gel electrophoresis indicated that these were inserted in four unlinked genetic loci. According to their phenotypes, including quantitative differences in biofilm production in different growth media, in the amount of the polysaccharide intercellular adhesin (PIA) produced, in the hemagglutination titers, and in the altered colony morphology, the mutants could be separated into four phenotypic classes corresponding with the genetic classes. Synthesis of PIA was not detectable with class I and II mutants, whereas the amount of PIA produced reflected the residual degree of biofilm production of class III and IV mutants in different growth media. Chromosomal DNA flanking the transposon insertions of five class I mutants was cloned and sequenced, and the insertions were mapped to different locations of icaADBC, representing the synthetic genes for PIA. Expression of icaADBC from a xylose-dependent promoter in the different isogenic mutant classes reconstituted biofilm production in all mutants. In a Northern blot analysis no icaADBC-specific transcripts were observed in RNA isolated from mutants of classes II, III, and IV. Apparently, in addition to icaADBC, three other gene loci have a direct or indirect regulatory influence on expression of the synthetic genes for PIA on the level of transcription.

Adhesins, Bacterial↗
PubMed2000

Confidentiality of medical records: an overview for the Connecticut physician.

An ongoing concern for physicians and their patients is protecting the confidentiality of medical records. The proliferation of electronic methods for collecting and storing medical information, along with the growing complexity of the health-care system, has created the need for new means to protect confidentiality. Currently, a patchwork of protections requires that physicians keep patients' medical information confidential. This article reviews the three major sources of medical confidentiality protections: Connecticut law, federal law, and professional standards, all of which provide an array of protections. A brief summary of proposed federal and state legislation is also included. The challenge of effectively maintaining confidentiality in today's electronic age has prompted the Connecticut General Assembly, Congress, and other federal agencies to consider additional safeguards. The article summarizes the relevant legal framework in order to orient medical professionals to the complexities, practice challenges, and legal aspects of maintaining confidentiality.

Confidentiality↗
PubMed1999

Broad patterns of gene expression revealed by clustering analysis of tumor and normal colon tissues probed by oligonucleotide arrays.

Oligonucleotide arrays can provide a broad picture of the state of the cell, by monitoring the expression level of thousands of genes at the same time. It is of interest to develop techniques for extracting useful information from the resulting data sets. Here we report the application of a two-way clustering method for analyzing a data set consisting of the expression patterns of different cell types. Gene expression in 40 tumor and 22 normal colon tissue samples was analyzed with an Affymetrix oligonucleotide array complementary to more than 6,500 human genes. An efficient two-way clustering algorithm was applied to both the genes and the tissues, revealing broad coherent patterns that suggest a high degree of organization underlying gene expression in these tissues. Coregulated families of genes clustered together, as demonstrated for the ribosomal proteins. Clustering also separated cancerous from noncancerous tissue and cell lines from in vivo tissues on the basis of subtle distributed patterns of genes even when expression of individual genes varied only slightly between the tissues. Two-way clustering thus may be of use both in classifying genes into functional groups and in classifying tissues based on gene expression.

Adenocarcinoma↗
PubMed1999

Liver-specific inactivation of the abetalipoproteinemia gene completely abrogates very low density lipoprotein/low density lipoprotein production in a viable conditional knockout mouse.

Conventional knockout of the microsomal triglyceride transfer protein large subunit (lMTP) gene is embryonic lethal in the homozygous state in mice. We have produced a conditional lMTP knockout mouse by inserting loxP sequences flanking exons 5 and 6 by gene targeting. Homozygous floxed mice were born live with normal plasma lipids. Intravenous injection of an adenovirus harboring Cre recombinase (AdCre1) produced deletion of exons 5 and 6 and disappearance of lMTP mRNA and immunoreactive protein in a liver-specific manner. There was also disappearance of plasma apolipoprotein (apo) B-100 and marked reduction in apoB-48 levels. Wild-type mice showed no response, and heterozygous mice, an intermediate response, to AdCre1. Wild-type mice doubled their plasma cholesterol level following a high cholesterol diet. This hypercholesterolemia was abolished in AdCre1-treated lMTP-/- mice, the result of a complete absence of very low/intermediate/low density lipoproteins and a slight reduction in high density lipoprotein. Heterozygous mice showed an intermediate lipoprotein phenotype. The rate of accumulation of plasma triglyceride following Triton WR1339 treatment in lMTP-/- mice was <10% that in wild-type animals, indicating a failure of triglyceride-rich lipoprotein production. Pulse-chase experiments using hepatocytes isolated from wild-type and lMTP-/- mice revealed a failure of apoB secretion in lMTP-/- animals. Therefore, the liver-specific inactivation of the lMTP gene completely abrogates apoB-100 and very low/intermediate/low density lipoprotein production. These conditional knockout mice are a useful in vivo model for studying the role of MTP in apoB biosynthesis and the biogenesis of apoB-containing lipoproteins.

Abetalipoproteinemia↗
PubMed1999

Gastric tonometry accurately predicts mortality in experimental peritonitis in both laparoscopic and conventional surgery.

OBJECTIVES: Tonometry is widely used in the diagnosis of sepsis and splanchnic ischemia. This study was devised to analyze the predictive value of gastric tonometry for outcome of experimental viscus perforation-induced peritonitis. The impact of conventional and laparoscopic intervention on tonometric measurements was the main scope. METHODS: This randomized controlled intervention trial was performed in a University experimental laboratory, using 24 female Duroc pigs. Pigs were subjected to gastric perforation followed by a 12 h interval of peritonitis, and then to either laparoscopic or conventional surgical repair of the defect with peritoneal lavage. Gastric tonometry and cardiocirculatory monitoring were performed. RESULTS: Septic shock associated with peritonitis and subsequent lethal outcome was accurately predicted with gastric tonometry. Changes of gastric mucosal pH correlated significantly with decreases of MAP (r2=0.880; P<0.001) and SVR (r2=0.678; P<0.001), increase of QT (r2=0.486; P=0.013), and mortality (r=0.752; P<0.001). Mortality was significantly higher in laparoscopically treated animals compared to those subjected to the open procedure (78% vs 22%; P<0.045). CONCLUSIONS: Gastric tonometry accurately predicted mortality in experimental peritonitis. The decline of gastric mucosal pH in the laparoscopic group was more than double that of to conventionally treated animals. This finding not only reflected the increase of systemic CO2 due to higher absorption during CO2-pneumoperitoneum, but probably also indicated a more severe form of splanchnic ischemia during laparoscopic surgery. Even though tonometry can be used to accurately predict mortality and separate the high risk group, extreme caution should be applied under conditions associated with severe peritonitis.

Animals↗
PubMed1999

Three cases of Arcanobacterium haemolyticum associated with abscess formation and cellulitis.

Arcanobacterium haemolyticum has been described as an unusual pathogen causing pharyngotonsillitis and systemic disease in patients with predisposing conditions. A case of soft tissue abscess with no apparent portal of entry is reported in a healthy 31-year-old man who presented with a breast tumor. A second case of abscess formation in a 50-year-old patient with complicated wound healing is presented. In addition, a case of Arcanobacterium haemolyticum cellulitis in a 25-year-old female is reported. Due to its innocuous, coryneform appearance, this pathogen is probably underreported; therefore, the diagnostic evaluation of this organism is emphasized.

Abscess↗
PubMed1999

Molecular mechanisms of Staphylococcus epidermidis biofilm formation.

Coagulase-negative staphylococci, mainly Staphylococcus epidermidis, are the predominant cause of implanted medical-device related infections. The formation of adherent multi-layered biofilms embedded into a glycocalyx composed of exopolysaccharides on implanted devices is believed to be essential for the pathogenesis of S. epidermidis infections. Biofilm formation may be separated into primary attachment of bacteria to native or modified polymer surfaces followed by proliferation of attached bacterial cells leading to accumulation of multi-layered cell-clusters and glycocalyx formation. Recent progress in the understanding of the molecular mechanisms cooperating in S. epidermidis biofilm formation is reviewed and current thinking on the relevance of these mechanisms for S. epidermidis device-related infections is discussed.

Bacterial Adhesion↗
PubMed1999

Early infections in patients undergoing bone marrow or blood stem cell transplantation--a 7 year single centre investigation of 409 cases.

Infections are a major cause of morbidity and mortality in patients undergoing high-dose therapy and subsequent autologous or allogeneic haemopoietic stem cell transplantation, despite the change from topical to systemic anti-infection prophylaxis and the introduction of growth factors and new antimicrobial drugs. We report our single centre experience with data from 409 patients treated at our unit from its opening in 1990 until May 1997. Three hundred and seventy-eight patients were transplanted for the first time, 12 patients were retransplanted or boosted and 19 patients were readmitted for miscellaneous reasons. 245 patients were allografted and 157 autografted. Antimicrobial prophylaxis was mainly quinolones, fluconazole plus amphotericin-B orally, aciclovir, and TMP/SMX or pentamidine. Three hundred and nineteen (78%) developed fever of significantly longer duration in the allogeneic setting with anti-CMV seropositivity. The most frequent infection was fever of unknown origin (50.6%), followed by septicaemia (12.5%) and pneumonia (11.0%). Pathogens isolated in 24.6% of the infections were mostly gram-positive bacteria (57.9%), followed by non-fermenting rods (11.2%), Aspergillus spp. and Candida spp. (10.3%, each). Cumulative response rate to antimicrobial therapy was 66.9%. Infections were responsible for 62.5% (25/40) of deaths after transplantation. Predominant pathogens were Aspergillus spp. (11), Candida spp. (four), and Pseudomonas spp. (three). None of the patients died from gram-positive bacterial infection. The risk of dying from infection was 11.2% after allografting and 0.8% after autotransplantation. Infections remain a major risk for early death after allogeneic transplantation of haemopoietic stem cells. Infection with gram-negative bacteria can be prevented by quinolone prophylaxis. Predominant pathogens are Aspergillus spp. Candida spp. and nonfermenting rods. Systemic infection with these pathogens is associated with a poor prognosis. Antimycotic prophylaxis and the therapy must be improved.

Adolescent↗