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Biomedical subjects

R Krause

Publications and source records attributed to R Krause.

At least 37 records · Page 2Linked to original sources

Molecular typing of coagulase-negative staphylococcal blood and skin culture isolates to differentiate between bacteremia and contamination.

In order to determine whether a blood culture positive for coagulase-negative staphylococci (CNS) represents bacteremia or contamination, a prospective study was conducted using molecular typing to analyze CNS blood culture isolates and corresponding CNS skin isolates collected after skin disinfection from 431 subjects. CNS bacteremia was not found in any of the 301 subjects not suspected of having bacteremia. In 130 patients suspected of having bacteremia, the rate of actual CNS bacteremia was 6%. The overall rate of CNS blood culture contamination was 1%. Chart analysis showed good agreement between our microbiological definitions of bacteremia and the clinical definitions previously published. Bacteremia and contamination can be differentiated using pulsed-field gel electrophoresis and molecular typing of CNS isolates obtained from cultures of blood and corresponding skin samples.

Adult↗

Bacteremia with Mycoplasma hominis and Ureaplasma urealyticum in patients undergoing hysterectomy.

In the study presented here, the aim was to investigate the frequency and clinical significance of bacteremia with urogenital mycoplasmas in immunocompetent patients following gynecological surgery. Among 56 patients undergoing elective hysterectomy (mean age, 55 years; range, 32-82 years), Mycoplasma hominis and Ureaplasma urealyticum were detected in urine by PCR in 2 and 11 patients, respectively. Pre- and postoperative blood samples of the colonized patients were investigated for the colonizing species by PCR. In 4 of the 11 patients colonized by Ureaplasma urealyticum the pathogen was also detected from one of the postoperative blood samples, while no case of bacteremia with Mycoplasma hominis was detected. The postoperative course was uncomplicated in all patients.

Adult↗

Monoclonal and biclonal gammopathy in two patients infected with Bartonella henselae.

Two immunocompetent patients with cat-scratch disease due to infection with Bartonella henselae developed monoclonal and biclonal gammopathy. Neither patient had evidence of any other known cause of plasma cell dyscrasia, and antibiotic eradication of Bartonella henselae infection resulted in the prompt disappearance of the gammopathy. Hence, cat-scratch disease should be added to the list of possible underlying disorders in individuals presenting with monoclonal and biclonal gammopathy.

Adult↗

Initial experience with radiofrequency ablation for hepatic tumours in the Netherlands.

AIMS: The aim of this study is to report initial experience with radiofrequency thermoablation (RFA) of malignant hepatic tumours. METHODS: From June 1999 to November 2001, a seven centre study of 50 patients who had undergone RFA, included 102 primary or metastatic tumours. Multimodality therapy, complications, disease free survival and location of recurrence were recorded. Histopathologic examination was performed in a number of tumours treated with RFA and subsequently resected to determine the effect of RFA on the tissue level. RESULTS: 11 tumours (seven patients) were resected after prior treatment with RFA; NADH-diaphorase staining in all these tumours demonstrated non-viable tumour. Postoperative morbidity and mortality occurred in 14 patients and one patient, respectively, in three cases related to the RFA procedure. Median follow-up of 41 patients with non-resected RF ablated tumours was 11 months (range 1-24 months). 26 patients developed a recurrence of which three at the RFA site after 6-12 months. CONCLUSIONS: RFA provides a simple method for local treatment of liver tumours. The introduction of this technique nevertheless involves morbidity and mortality.

Adult↗

Laboratory diagnosis of Mycoplasma pneumoniae infection.

Diagnosis of Mycoplasma pneumoniae infection is challenging due to the fastidious nature of the pathogen, the considerable seroprevalence, and the possibility of transient asymptomatic carriage. During recent years, various new techniques have been adapted for the diagnosis of M. pneumoniae infection, notably in the field of molecular biology. Standard polymerase chain reaction (PCR) is currently the method of choice for direct pathogen detection, but several PCR-related methods provide enhanced sensitivity or more convenient handling procedures, and have been successfully applied for research purposes. Among these techniques are real-time PCR, nested PCR, reverse transcriptase PCR (RT-PCR) and multiplex PCR. Generally, amplification-based methods have replaced hybridization assays and direct antigen detection. Serology, which is the basic strategy for mycoplasma diagnosis in routine clinical practice, has been improved by the widespread availability of sensitive assays for separate detection of different antibody classes. For the diagnosis of mycoplasma pneumonia, serology and direct pathogen detection should be combined. Extrapulmonary diseases may be diagnosed by direct pathogen detection alone, but the value of this diagnostic approach is limited by the probably immunologically mediated pathogenesis of some manifestations. This review summarizes the current state of Mycoplasma pneumoniae diagnosis, with special reference to molecular techniques. The value of different methods for routine diagnosis and research purposes is discussed.

Culture Media↗

Infectious complications after autologous hematopoietic stem cell transplantation: comparison of patients with acute myeloid leukemia, malignant lymphoma, and multiple myeloma.

It is yet undetermined whether patients with different hematological malignancies have different propensities to infectious complications after high-dose chemotherapy (HDC) and autologous hematopoietic stem cell transplantation (HSCT). We retrospectively analyzed 136 cycles of HDC and autologous HSCT in 114 patients with acute myeloid leukemia (AML, 24 cycles), non-Hodgkin's lymphoma/Hodgkin's disease (NHL/HD, 55 cycles), and multiple myeloma (MM, 57 cycles) with respect to early infectious complications. Median duration of neutropenia was longer in patients with AML and NHL/HD than in patients with MM (11 days vs 8 days) and after conditioning including total body irradiation (TBI) compared with chemotherapy only preparative regimens (11 days vs 7 days). Fever requiring antimicrobial therapy was observed in 88 percent of cycles, with fever of unknown origin (FUO) accounting for 60 percent of febrile episodes. There was no proven fungal infection, but one case of probable invasive pulmonary aspergillosis. Microbiologically documented infections were seen in 29 percent and clinically documented infections in 11 percent. Response to first-line empirical antibiotic therapy was better for FUO than for documented infections (70 percent vs 40 percent). Patients with TBI as part of their conditioning regimen had more overall infections than patients without TBI (96 percent vs 82 percent). There were no differences with respect to the type or incidence of infections between patients with AML, NHL/HD, and MM. Patients with different hematological malignancies have similar rates of early infectious complications after HDC and autologous HSCT. TBI may be associated with an increased risk for infections in the early post-transplant period.

Acute Disease↗

A case of lung transplantation following Mycoplasma pneumoniae infection.

Reported here is a case of severe necrotizing pneumonia following Mycoplasma pneumoniae infection that occurred in a 55-year-old man. The histological changes of lung parenchyma included granulomas and bronchiolitis obliterans. Mycoplasma infection was diagnosed by repeated antibody determination (complement fixation test) and confirmed using the polymerase chain reaction to detect the pathogen from a tracheal aspirate. Prior to this episode of pneumonia, the patient had been healthy, except for Reiter's disease that had been diagnosed 18 years previously. In addition to severe pulmonary involvement, the patient developed rhabdomyolysis with subsequent acute renal failure, Stevens-Johnson syndrome, biochemical pancreatitis, severe anemia, and an effusion of the right knee. Contrary to the symptoms of pulmonary disease, all of the extrapulmonary manifestations except anemia were transient. Due to persistent respiratory insufficiency and long-term failure to wean the patient from a respirator, a lung transplantation was performed. Five weeks after transplantation the patient died as a result of intrapulmonary hemorrhage. To the best of our knowledge, this is the first report of pneumonia due to Mycoplasma pneumoniae leading to lung transplantation. Furthermore, the multiple extrapulmonary manifestations in this case make it exceptional.

Anti-Bacterial Agents↗

Efficacy of a motilin receptor agonist (ABT-229) for the treatment of gastro-oesophageal reflux disease.

BACKGROUND: ABT-229 is a potent motilin agonist without significant antibiotic activity. It has been shown to improve gastric emptying in humans and to increase lower oesophageal sphincter pressure in cats. AIM: To assess the efficacy of four different doses of ABT-229 (1.25 mg, 2.5 mg, 5 mg, 10 mg b.d.) compared to placebo in the treatment of gastro-oesophageal reflux disease, and to determine its safety in patients with gastro-oesophageal reflux disease. METHODS: In a double-blind, multicentre study, 324 patients with heartburn were randomized to receive four different doses of ABT-229 or placebo for 8 weeks. The efficacy was evaluated by Patient Symptom Questionnaire, daily diary, endoscopy and global evaluation of efficacy. RESULTS: There were no statistically significant improvement scores for any of the ABT-229 treatment groups vs. the placebo group in any of the efficacy parameters. Reflux symptom scores were significantly worse after treatment in the dyspeptic group. ABT-229 appeared to be well tolerated and safe in total daily doses up to 20 mg. CONCLUSION: ABT-229 appears to have limited, if any, clinical utility in the treatment of gastro-oesophageal reflux disease.

Dose-Response Relationship, Drug↗

A randomized, double-blind, placebo-controlled trial of tegaserod in female patients suffering from irritable bowel syndrome with constipation.

BACKGROUND: Irritable bowel syndrome is a common functional gastrointestinal disorder which affects up to 20% of the population, with a predominance in females. AIM: To evaluate the efficacy and safety of tegaserod in female patients with irritable bowel syndrome characterized by symptoms of abdominal pain/discomfort and constipation. METHODS: In a randomized, double-blind, multicentre study, 1519 women received either tegaserod, 6 mg b.d. (n = 767), or placebo (n = 752) for 12 weeks, preceded by a 4-week baseline period without treatment and followed by a 4-week open withdrawal period. The primary efficacy evaluation was the patient's symptomatic response as measured by the Subject's Global Assessment of Relief. Other efficacy variables included abdominal pain/discomfort, bowel habits and bloating. RESULTS: Tegaserod produced significant (P < 0.05) improvements in the Subject's Global Assessment of Relief and other efficacy variables. These improvements were seen within the first week, and were maintained throughout the treatment period. After withdrawal of treatment, the symptoms rapidly returned. Overall, tegaserod was well tolerated. Diarrhoea was the most frequent adverse event; however, this led to discontinuation in only 1.6% of tegaserod-treated patients. CONCLUSIONS: Tegaserod, 6 mg b.d., produced rapid and sustained improvement of symptoms in female irritable bowel syndrome patients and was well tolerated.

Adult↗

Role of Candida in antibiotic-associated diarrhea.

To quantitatively assess the role of Candida species in antibiotic-associated diarrhea (AAD), stool samples from a total of 395 patients and control subjects were cultured in differential isolation medium: 98 patients had AAD, 93 patients were taking antibiotics but did not have diarrhea (A(+)D(-)), 97 patients were not taking antibiotics but had diarrhea (A(-)D(+)), and 107 patients were control subjects (A(-)D(-)). In addition, secreted aspartyl proteinase (Sap) production was tested. In AAD patients, Candida positivity (77/98) and Candida overgrowth (62/98) were not different from that among A(+)D(-) patients (75/93 [P= .860] and 52/93 [P= .375], respectively). Candida overgrowth among A(-)D(+) patients (40/97, P= .003) was less frequent than among AAD patients, but Candida positivity was not different (80/97, P= .612). In control subjects, Candida positivity and overgrowth were less common than in all other groups. Production of Sap did not differ between patients with AAD and control subjects (P= .568 and P= .590, respectively). Data indicate that elevated Candida counts are a result of antibiotic treatment or diarrhea rather than a cause of AAD.

Age Distribution↗

Functional specialization of calreticulin domains.

Calreticulin is a Ca2+-binding chaperone in the endoplasmic reticulum (ER), and calreticulin gene knockout is embryonic lethal. Here, we used calreticulin-deficient mouse embryonic fibroblasts to examine the function of calreticulin as a regulator of Ca2+ homeostasis. In cells without calreticulin, the ER has a lower capacity for Ca2+ storage, although the free ER luminal Ca2+ concentration is unchanged. Calreticulin-deficient cells show inhibited Ca2+ release in response to bradykinin, yet they release Ca2+ upon direct activation with the inositol 1,4,5-trisphosphate (InsP3). These cells fail to produce a measurable level of InsP3 upon stimulation with bradykinin, likely because the binding of bradykinin to its cell surface receptor is impaired. Bradykinin binding and bradykinin-induced Ca2+ release are both restored by expression of full-length calreticulin and the N + P domain of the protein. Expression of the P + C domain of calreticulin does not affect bradykinin-induced Ca2+ release but restores the ER Ca2+ storage capacity. Our results indicate that calreticulin may play a role in folding of the bradykinin receptor, which affects its ability to initiate InsP3-dependent Ca2+ release in calreticulin-deficient cells. We concluded that the C domain of calreticulin plays a role in Ca2+ storage and that the N domain may participate in its chaperone functions.

Animals↗

Effect of vitamin C on neutrophil function after high-intensity exercise.

High-intensity exercise leads to an increased risk of upper respiratory tract infections in athletes, which had been related to an exercise-induced impairment of neutrophil function. In this study, several indices of neutrophil function were analysed before and after a biathlon and the effect of oral vitamin C on neutrophil function was determined. Six athletes took 2 g vitamin C daily for 1 week prior to a biathlon and four athletes did not take any supplementation. Neutrophil phagocytosis was analysed by fluorescence microscopy and flow cytometry. Cytosolic calcium kinetics were assessed fluorometrically and neutrophil bactericidal ability was assessed by fluorescence microscopy. Reactive oxygen production was analysed by flow cytometry. Catecholamines were analysed by high-performance liquid chromatography. After high-intensity exercise there were significant reductions in the number of phagocytosed Escherichia coli per neutrophil and in neutrophil bactericidal ability. There was a significant exercise-dependent increase of catecholamines. There was no difference between the two groups of athletes. These results do not support the concept that vitamin C supplementation corrects neutrophil dysfunction after strenuous exercise.

Adult↗

The effect of fosfomycin on neutrophil function.

Fosfomycin (cis-1,2-epoxypropyl phosphonic acid) is a cell wall synthesis-inhibiting antibiotic. We investigated the effect of fosfomycin on several indices of neutrophil function. Neutrophil phagocytosis was analysed by flow cytometry. Cytosolic calcium kinetics were assessed fluorometrically and neutrophil bactericidal ability was assessed by fluorescence microscopy. Intracellular reactive oxygen intermediate (ROI) production was analysed by flow cytometry and extracellular ROI by cytochrome c reductase assay. After fosfomycin incubation, phagocytosis was unaffected as assessed by the FACS assay. Fosfomycin incubation resulted in enhanced bactericidal ability, in increased intracellular calcium concentrations, elevated extracellular ROI production and decreased chemotaxis but it did not affect intracellular ROI production and chemokinesis.

Anti-Bacterial Agents↗

Assessment of neutrophil function in patients with septic shock: comparison of methods.

Patients with septic shock are shown to have decreased neutrophil phagocytic function by multiple assays, and their assessment by whole-blood assays (fluorescence-activated cell sorter analysis) correlates with assays requiring isolated neutrophils (microscopic and spectrophotometric assays). For patients with similar underlying conditions but without septic shock, this correlation does not occur.

Adult↗

Antifungal susceptibility testing of fluconazole by flow cytometry correlates with clinical outcome.

Susceptibility testing of fungi by flow cytometry (also called fluorescence-activated cell sorting [FACS]) using vital staining with FUN-1 showed a good correlation with the standard M27-A procedure for assessing MICs. In this study we determined MICs for blood culture isolates from patients with candidemia by NCCLS M27-A and FACS methods and correlated the clinical outcome of these patients with in vitro antifungal resistance test results. A total of 24 patients with candidemia for whom one or more blood cultures were positive for a Candida sp. were included. Susceptibility testing was performed by NCCLS M27-A and FACS methods. The correlation of MICs (NCCLS M27-A and FACS) and clinical outcome was calculated. In 83% of the cases, the MICs of fluconazole determined by FACS were within 1 dilution of the MICs determined by the NCCLS M27-A method. For proposed susceptibility breakpoints, there was 100% agreement between the M27-A and FACS methods. In the FACS assay, a fluconazole MIC of <1 microg/ml was associated with cure (P < 0.001) whereas an MIC of > or =1 microg/ml was associated with death (P < 0.001). The M27-A-derived fluconazole MICs did not correlate with outcome (P = 1 and P = 0.133).

Adolescent↗

Effect of age on human neutrophil function.

Neutrophil phagocytosis, reactive oxygen intermediate production (intra- and extracellular), neutrophil bactericidal activity, and chemotaxis/chemokinesis were assessed in three age groups: 21-36, 38-56, and 62-83 years. A significant age-dependent reduction in the number of phagocytized Escherichia coli per neutrophil (measured by acridine orange staining) and Staphylococcus aureus phagocytosis (measured by flow cytometry) was seen (r = 0.669 and r = 0.684, P<0.001 for both). These findings correlated with an age-dependent increase in intracellular calcium concentrations in resting neutrophils (r = 0.698, P<0.001) and a reduced hexose uptake (r = 0.591, P<0.01). In addition, a significant reduction in the intracellular reactive oxygen production was seen after stimulation with S. aureus (P<0.001) with increasing age. In contrast, no differences between the groups in reactive oxygen production was seen after stimulation with E. coli. The neutrophil bactericidal activity was impaired with increasing age (64+/-4% of the phagocytized bacteria were killed in group 1; 66+/-2 in group 2, and 59+/-6 in group 3; P<0.01). In addition, a trend toward a reduced neutrophil chemotaxis was seen with increasing age (P = 0.022). The findings suggest that increased intracellular calcium concentrations in resting neutrophils and/or a reduced hexose uptake result in reduced phagocytic ability and decreased bactericidal activity of neutrophils in the elderly.

Adult↗

Osteomyelitis of the hip joint associated with systemic cat-scratch disease in an adult.

Reported here is the case of a 29-year-old male with cervical lymphadenopathy, fever and weight loss, followed by acute painful osteomyelitis of the left hip joint due to cat-scratch disease. The diagnosis was established by detection of IgG antibodies to Bartonella henselae in serum and histologic examination of a lymph node including a positive polymerase chain reaction test. Treatment consisted of clarithromycin and cefotiam for 2 weeks. Four weeks after discharge, all of the patient's symptoms had completely resolved. Magnetic resonance imaging of the left hip joint showed marked regression of bone inflammation 4 months later and normalization after 8 months. Cat-scratch disease should be considered in the differential diagnosis of osteomyelitis in an adult, especially when lymphadenitis is present.

Adult↗