Showing papers by "Erasmus University Medical Center published in 2000"

Segmental bronchial provocation induces nasal inflammation in allergic rhinitis patients

Abstract: Allergic rhinitis and asthma often coexist and share a genetic background. Pathophysiologic connections between the nose and lungs are still not entirely understood. This study was undertaken to compare allergic inflammation and clinical findings in the upper and lower airways after segmental bronchial provocation (SBP) in nonasthmatic allergic rhinitis patients. Eight nonasthmatic, grass pollen-sensitive patients with allergic rhinitis and eight healthy controls were included. Bronchial biopsies and blood samples were taken before (T 0 ) and 24 h (T 24 ) after SBP. Nasal biopsies were obtained at T 0 , 1 h after SBP (T 1 ), and T 24 . Immunohistochemical staining was performed for eosinophils (BMK13), interleukin (IL)-5, and eotaxin. The number of eosinophils increased in the challenged and unchallenged bronchial mucosa (p , 0.05) and in the blood (p 5 0.03) of atopic subjects at T 24 . We detected an increase of BMK13-positive and eotaxin-positive cells in the nasal lamina propria and enhanced expression of IL-5 in the nasal epithelium of atopic subjects only at T 24 (p , 0.05). SBP induced nasal and bronchial symptoms as well as reductions in pulmonary and nasal function in the allergic group. No significant changes could be observed in healthy controls. The study shows that SBP in nonasthmatic allergic rhinitis patients results in peripheral blood eosinophilia, and that SBP can induce allergic inflammation in the nose. Epidemiologic (1), pathophysiologic (2, 3), and clinical studies (4, 5) strongly suggest a link between rhinitis and asthma. Asthma and rhinitis, which are considered to be manifestations of the atopic syndrome, often coexist and share a common genetic background. Although several studies have shown that asthma and rhinitis are characterized by a similar inflammatory process (6‐9), pathophysiologic interactions between upper and lower airways are not entirely understood. It is clear that the condition of the upper airways definitely influences the lower airways. In allergic rhinitis patients without bronchial hyperreactivity (BHR), signs of allergic inflammation of the lower airways have been found in induced sputum, bronchoalveolar lavage fluid (BALF), and bronchial biopsy specimens (10‐13). The nasal-bronchial reflex, an altered breathing pattern, pulmonary aspiration of nasal contents, and increased levels of inflammatory factors in the blood are possible mechanisms for lower airway dysfunction among patients with rhinitis (14). To shed more light on the role of systemic induction in the allergic inflammatory response, we designed a study in which blood samples and nasal and bronchial mucosal biopsy specimens were taken from a group of nonasthmatic allergic rhinitis patients with an isolated grass pollen allergy after segmental bronchial provocation (SBP) at a time other than the grass pollen season. The aim of the study was to compare allergic mucosal inflammation and clinical findings in the upper and lower airways. Eosinophils, major effector cells in allergic inflammation, interleukin (IL)-5‐positive cells and eotaxin-positive cells (necessary for eosinophil survival and chemotaxis), were chosen as markers of mucosal allergic inflammation.

Determinants of peripheral arterial disease in the elderly: The Rotterdam Study

Abstract: Objective To examine which atherosclerotic risk factors are determinants for peripheral arterial disease (PAD), we performed a population-based study in 6450 subjects (40% men, 60% women) aged 55 years and older. Methods The presence of PAD was assessed by measuring the ankle-arm systolic blood pressure index (AAI); PAD was considered present if the AAI was lower than 0.90 in either leg. In addition, a threshold AAI of 0.70 in either leg defined severe PAD. Results Determinants strongly and independently associated with PAD were age of at least 75 years (odds ratio [OR], 1.2; 95% confidence interval [CI], 1.0-1.6), fibrinogen level (OR, 1.5; 95% CI, 1.3-1.7), cigarette smoking (OR, 2.8; 95% CI, 2.3-3.4), diabetes mellitus (OR, 2.0; 95% CI, 1.6-2.5), and systolic blood pressure (OR, 1.2; 95% CI, 1.1-1.2). An inverse relation of high-density lipoprotein cholesterol level with PAD (OR, 0.7; 95% CI, 0.5-0.8) was found. Similar results were demonstrated for severe PAD. Separate analyses for men and women did not demonstrate differences in risk factors for PAD. Conclusions Assessment of a wide range of atherosclerotic risk factors enabled us to quantify the relative importance of each factor as determinant for PAD. In total, 69% of the occurrence of PAD is attributable to cardiovascular risk factors measured in our study; smoking accounted for most (etiologic fraction, 18.1%). The results suggest that preventive management of PAD should be directed at systolic blood pressure, fibrinogen level, smoking, high-density lipoprotein cholesterol level, and diabetes mellitus.

Application of germline IGH probes in real-time quantitative PCR for the detection of minimal residual disease in acute lymphoblastic leukemia

Abstract: Large-scale clinical studies on detection of minimal residual disease (MRD) in acute lymphoblastic leukemia (ALL) have shown that quantification of MRD levels is needed for reliable MRD-based risk group classification. Recently, we have shown that 'real-time' quantitative PCR (RQ-PCR) can be applied for this purpose using patient-specific immunoglobulin (Ig) and T cell receptor (TCR) gene rearrangements as PCR targets with TaqMan probes at the position of the junctional region and two germline primers. Now, we tested an alternative approach on 35 immunoglobulin heavy chain (IGH) gene rearrangements, by designing three germline JH TaqMan probes to be used in combination with one of six corresponding germline JH primers and one allele specific oligonucleotide (ASO) primer complementary to the junctional region. In nine cases in which both approaches were compared, at least similar (n = 4) or slightly higher (n= 5) maximal sensitivities were obtained using an ASO primer. The ASO primer approach reached maximal sensitivities of at least 10(-4) in 33 out of 35 IGH rearrangements. The reproducible range for accurate quantification spanned four to five orders of magnitude in 31 out of 35 cases. In 13 out of 35 rearrangements the stringency of PCR conditions had to be increased to remove or diminish background signals; this only concerned the frequently occurring JH4, JH5 and JH6 gene rearrangements. After optimization of the conditions (mainly by increasing the annealing temperature), only occasional aspecific amplification signals were observed at high threshold cycle (CT) values above 42 cycles and at least six cycles above the CT value of the detection limit. Hence, these rare aspecific signals could be easily discriminated from specific signals. We conclude that the here presented set of three germline JH Taq-Man probes and six corresponding germline JH primers can be used to develop patient-specific RQ-PCR assays, which allow accurate and sensitive MRD analysis in almost all IGH gene rearrangements. These results will facilitate standardized RQ-PCR analysis for MRD detection in large clinical studies.

Randomized clinical trial of adenosine 5'-triphosphate in patients with advanced non-small-cell lung cancer

Abstract: textBACKGROUND: Extracellular adenosine 5'-triphosphate (ATP) is involved in the regulation of a variety of biologic processes, including neurotransmission, muscle contraction, and liver glucose metabolism, via purinergic receptors. In nonrandomized studies involving patients with different tumor types including non-small-cell lung cancer (NSCLC), ATP infusion appeared to inhibit loss of weight and deterioration of quality of life (QOL) and performance status. We conducted a randomized clinical trial to evaluate the effects of ATP in patients with advanced NSCLC (stage IIIB or IV). METHODS: Fifty-eight patients were randomly assigned to receive either 10 intravenous 30-hour ATP infusions, with the infusions given at 2- to 4-week intervals, or no ATP. Outcome parameters were assessed every 4 weeks until 28 weeks. Between-group differences were tested for statistical significance by use of repeated-measures analysis, and reported P values are two-sided. RESULTS: Twenty-eight patients were allocated to receive ATP treatment and 30 received no ATP. Mean weight changes per 4-week period were -1.0 kg (95% confidence interval [CI] = -1.5 to -0.5) in the control group and 0.2 kg (95% CI = -0.2 to +0.6) in the ATP group (P =.002). Serum albumin concentration declined by -1.2 g/L (95% CI= -2.0 to -0.4) per 4 weeks in the control group but remained stable (0.0 g/L; 95% CI = -0.3 to +0.3) in the ATP group (P =.006). Elbow flexor muscle strength declined by -5.5% (95% CI = -9.6% to -1. 4%) per 4 weeks in the control group but remained stable (0.0%; 95% CI= -1.4% to +1.4%) in the ATP group (P =.01). A similar pattern was observed for knee extensor muscles (P =.02). The effects of ATP on body weight, muscle strength, and albumin concentration were especially marked in cachectic patients (P =.0002, P =.0001, and P =. 0001, respectively, for ATP versus no ATP). QOL score changes per 4-week period in the ATP group showed overall less deterioration than in the control group-physical scores (-0.2% versus -2.4%; P =. 0002); functional scores (+0.4% versus -5.5%; P =.02); psychologic scores (-0.7% versus -2.4%; P =.11); overall QOL score (+0.1% versus -3.5%; P =.0001). CONCLUSIONS: This randomized trial demonstrates that ATP has beneficial effects on weight, muscle strength, and QOL in patients with advanced NSCLC.

Normal anal sphincter anatomy and age- and sex-related variations at high-spatial-resolution endoanal MR imaging.

Abstract: PURPOSE: To describe the various patterns of normal sphincter anatomy as seen at endoanal magnetic resonance (MR) imaging and to assess sex- and age-related variations in the dimensions of the anal sphincter to refine the diagnosis of sphincter disorders. MATERIALS AND METHODS: Endoanal MR imaging (1.5 T) was performed in 100 healthy volunteers (50 women, 50 men) evenly distributed between ages 20 and 85 years. The essential anatomic structures were evaluated, and various patterns in men and women were recorded. The thickness of the anal sphincter muscles and the length of the anal canal were measured, and age- and sex-related correlations were studied. RESULTS: Sex-related differences included a significantly shorter external sphincter in women than in men both laterally (mean, 27.1 mm ± 5.4 vs 28.6 mm ± 4.3; P < .05) and anteriorly (mean, 14.0 mm ± 3.0 vs 27.0 mm ± 53.0; P < .051). The superficial transverse perineal muscle is located more superiorly in women than in men. The central perineal tendon in ...

Free androgen index and leptin are the most prominent endocrine predictors of ovarian response during clomiphene citrate induction of ovulation in normogonadotropic oligoamenorrheic infertility.

Abstract: We have previously demonstrated that obese hyperandrogenic amenorrheic women are less likely to ovulate after clomiphene citrate (CC) medication. The present study was designed to identify whether additional endocrine screening characteristics, all potentially involved in ovarian dysfunction in 182 normogonadotropic oligoamenorrheic infertile women, are associated with ovarian response, which may improve overall prediction of CC-resistant anovulation. Standardized endocrine screening took place before initiation of CC medication (50 mg/day; increasing doses up to 150 mg/day if required) from cycle days 3-7. Screening included serum assays for fasting insulin and glucose, insulin-like growth factor I (IGF-I), IGF-binding protein-1 (IGFBP-1), IGFBP-3, free IGF-I, inhibin B, leptin, and vascular endothelial growth factor. Forty-two women (22% of the total group) did not ovulate at the end of follow-up (a total number of 325 cycles were analyzed). Fasting serum insulin, insulin/glucose ratio, IGFBP-1, and leptin were all significantly different in univariate analyses (P < or = 0.02), comparing CC responders vs. nonresponders. Forward stepwise multivariate analyses in combination with factors reported earlier for prediction of patients remaining anovulatory after CC revealed a prediction model including 1) free androgen index (FAI = testosterone/sex hormone-binding globulin ratio), 2) cycle history (oligomenorrhea or amenorrhea), 3) leptin level, and 4) mean ovarian volume. These data suggest that decreased insulin sensitivity, hyperandrogenemia, and obesity, all associated with polycystic ovary syndrome, are prominent factors involved in ovarian dysfunction, preventing these ovaries from responding to stimulation by raised endogenous FSH levels due to CC medication. By using leptin instead of body mass index or waist to hip ratio, the previous model for prediction of patients remaining anovulatory after CC medication could be slightly improved (area under the curve from 0.82-0.85). This may indicate that leptin is more directly involved in ovarian dysfunction in these patients. The capability of insulin and IGFBP-1 to predict patients who remain anovulatory after CC disappears when FAI enters into the model due to a significant correlation between FAI and these endocrine parameters. This suggests that markers for insulin sensitivity (e.g. IGFBP-1 and insulin) are associated with abnormal ovarian function through its correlation with androgens, whereas leptin is directly involved in ovarian dysfunction.

Molecular characterization of Campylobacter jejuni from patients with Guillain-Barré and Miller Fisher syndromes.

Abstract: Campylobacter jejuni has been identified as the predominant cause of antecedent infection in Guillain-Barre ´ syndrome (GBS) and Miller Fisher syndrome (MFS). The risk of developing GBS or MFS may be higher after infection with specific C. jejuni types. To investigate the putative clonality, 18 GBS- or MFS-related C. jejuni strains from The Netherlands and Belgium and 17 control strains were analyzed by serotyping (Penner and Lior), restriction fragment length polymorphism analysis of PCR products of the flaA gene, amplified fragment length polymorphism analysis, pulsed-field gel electrophoresis, and randomly amplified polymorphic DNA analysis. Serotyping revealed 10 different O serotypes and 7 different Lior serotypes, thereby indicating a lack of serotype clustering. Two new O serotypes, O:35 and O:13/65, not previously associated with GBS or MFS were found. Serotype O:19 was encountered in 2 of 18 strains, and none was of serotype O:41. The results of all genotypic methods also demonstrated substantial heterogeneity. No clustering of GBS- or MFS-related strains occurred and no molecular marker capable of separating pathogenic GBS or MFS from non-GBS- or non-MFS-related enteritis strains could be identified in this study. Sialic-acid-containing lipopolysaccharides (LPS) are thought to be involved in the triggering of GBS or MFS through molecular mimicry with gangliosides in human peripheral nerves. Therefore, further characterization of GBS- or MFS-related C. jejuni should target the genes involved in the synthesis of LPS and the incorporation of sialic acid.

Population Studies of Methicillin-Resistant and -Sensitive Staphylococcus aureus Strains Reveal a Lack of Variability in the agrD Gene, Encoding a Staphylococcal Autoinducer Peptide

Abstract: The virulence of Staphylococcus aureus is controlled by the accessory gene regulator (agr) system, including an extracellular inducer encoded by agrD. Variable agr PCR restriction fragment length polymorphism (RFLP) patterns of unique S. aureus strains (n = 192) were determined for a region comprising agrD and parts of the neighboring agrC and agrB genes. Twelve unique RFLP patterns were identified among S. aureus strains in general; these patterns were further specified by sequencing. All sequences could be catalogued in the three current agr groups. A major proportion of the S. aureus strains belong to agr group 1, whereas only 6% of the methicillin-susceptible S. aureus strains and 5% of the methicillin-resistant S. aureus strains belong to agr groups 2 and 3, respectively. The homology between groups varied from 75 to 80%, and within groups it varied from 96 to 100%. Different levels of sequence variability were observed in the different agr genes. agr-related bacterial interference among colonizing S. aureus strains in the noses of persistent and intermittent human carriers was studied. S. aureus strains belonging to different agr groups were encountered in the same individual. This may suggest that the activity of the agrD gene product does not define colonization dynamics, which is further substantiated by the rarity of agr group 2 and 3 strains.

Lipolysis and lipid oxidation in weight-losing cancer patients and healthy subjects☆

Abstract: Increased lipolysis has been suggested as one of the possible mechanisms underlying cancer cachexia. The study aim was to assess whether lipolysis is increased in weight-losing cancer patients, considering their differences in food intake and body composition. Sixteen healthy subjects and 18 cancer patients with different tumor types and a weight loss of at least 5% in the previous 6 months were included in the study. Food intake was recorded for 4 days. After an overnight fast, [1,1,2,3,3-2H5]glycerol was infused to determine the rate of appearance (Ra) of glycerol as a measure of whole-body lipolysis, and [1-13C]palmitic acid was infused to determine the Ra of palmitate as a measure of adipocyte fatty acid release. Palmitate oxidation was determined by measuring 13CO2 enrichment in breath samples, and body composition was measured by bioelectrical impedance analysis. After adjustment for energy intake, whole-body lipolysis was significantly higher in cancer patients versus healthy subjects (6.46 +/- 0.63 and 4.67 +/- 0.46 micromol/kg +/- min, respectively, P < .05). The difference in adipocyte fatty acid release did not reach statistical significance. The rate of palmitate oxidation was also significantly higher in patients than in healthy subjects (1.15 +/- 0.10 and 0.93 +/- 0.07 )micromol/kg x min, respectively, P < .05). No differences in body composition were observed between groups. In conclusion, whole-body lipolysis (as measured by the Ra of glycerol) and palmitate oxidation were elevated in weight-losing cancer patients, but fatty acid release was not significantly different.

Follicular and luteal phase characteristics following early cessation of gonadotrophin-releasing hormone agonist during ovarian stimulation for in-vitro fertilization

Abstract: Gonadotrophin-releasing hormone agonists (GnRHa) are widely used in in-vitro fertilization (IVF) for the prevention of a premature rise in luteinizing hormone (LH) concentrations. However, the administration of GnRHa during the follicular phase may also impair subsequent luteal function due to retarded recovery of pituitary gonadotrophin secretion. Therefore, luteal supplementation is generally applied. The present study was designed to determine whether a premature LH surge would still be prevented after early cessation of GnRHa during ovarian stimulation and whether subsequent luteal phase LH production would be sufficient to support progesterone synthesis by the corpus luteum. Sixty patients were randomized for three groups: (i) A long GnRHa/human menopausal gonadotrophin (HMG) protocol with luteal support by repeated human chorionic gonadotrophin (HCG) (n = 20), (ii) early follicular phase cessation of GnRHa without luteal support (n = 20), and (iii) a long GnRHa protocol without luteal support (n = 20). Frequent ultrasound and blood sampling was performed during the entire IVF cycle. Forty normo-ovulatory women served as controls. No premature LH surges were found after early cessation of GnRHa. In this group, some pituitary recovery occurred during the late luteal phase, but this did not affect corpus luteum function. Progesterone concentrations were shown to be dependent on disappearance of the pre-ovulatory bolus of HCG. Pregnancies occurred in all three groups. In conclusion, early follicular phase cessation of GnRHa is still effective in the prevention of a premature rise in LH. Although some pituitary recovery was observed thereafter, corpus luteum function is still abnormal due to early luteolysis.

Tumor necrosis factor-alpha enhances mRNA expression and secretion of interleukin-6 in cultured human airway smooth muscle cells.

Abstract: Airway smooth muscle (ASM) is considered to be an end-target cell for the effects of mediators released during airway wall inflammation. Several reports suggest that activated ASM may be capable of generating various proinflammatory cytokines. We investigated the effects of tumor necrosis factor (TNF)- α , a potent proinflammatory cytokine, on cultured human ASM cells by examining the expression and release of the cytokine interleukin (IL)-6, cell proliferation, and the expression pattern of c-fos and c-jun, two nuclear proto-oncogenes constituting the activator protein-1 transcription factor. Growth-arrested cell monolayers were stimulated with human recombinant TNF- α in a concentration- and time-dependent manner. TNF- α stimulated the expression of IL-6 messenger RNA (mRNA), which was detected after 15 min, reaching a maximum at 1 h. IL-6 protein was readily detected in ASM cell–conditioned medium after 2 h of TNF- α stimulation. Protein levels increased in a time- and concentration-dependent manner. R...

Regulation of follicle development and novel approaches to ovarian stimulation for IVF

Abstract: Current ovarian stimulation regimens for IVF are complex and not without risk. Increasing our knowledge of the physiology of follicle development and dominant follicle selection may enable the design of less complex, safer and cheaper ovarian stimulation regimens for IVF. Decremental serum FSH concentrations during the follicular phase of the menstrual cycle are required for single dominant follicle selection. Only the most mature follicle will continue its development due to increased sensitivity for stimulation by FSH. FSH stimulation becomes insufficient for less mature follicles and remaining cohort follicles will therefore go into atresia. The number of days during which FSH is above the threshold for stimulation of follicle development is limited, resulting in a narrow FSH window. More medium sized and large pre-ovulatory follicles and increased oestradiol output can be induced by the administration of small doses of exogenous FSH during the mid- to late follicular phase, preventing the physiological decrease in FSH stimulation. Intervention with decremental serum FSH concentrations in combination with gonadotrophin-releasing hormone (GnRH) antagonists to prevent a premature rise in serum LH may induce ongoing growth of multiple follicles sufficient for IVF. The benefits and risks of these minimal hyperstimulation protocols require further evaluation.

Somatostatin and somatostatin receptors in retinal diseases.

Abstract: Somatostatin is a small neuropeptide that is producedin the central nervous system, where it acts as aneurotransmitter. This neuropeptide also has animportant role in the neuroendocrine system as aninhibitor of hormone release, the most strikingexample of which is the inhibition of growth hormonerelease. The role of somatostatin in eye diseaserecently became of interest because of its role inproliferative diabetic retinopathy and cystoid macularoedema (1–3). In this paper, we discuss the role ofsomatostatin in the retina and also present prelimin-ary results of treatment of exudative age-relatedmacular disease with the somatostatin analogue,octreotide.

New developments in the diagnosis and management of invasive fungal infections.

Abstract: Invasive fungal infections in cancer patients are on the increase. Candidemia is now the fourth leading cause of bloodstream infections in many intensive care units (ICUs). Although a number of risk factors have been identified, antifungal therapy should not be started in non-neutropenic patients until a diagnosis of invasive candidiasis or candidemia is made or presumed in order to avoid the development of resistance. Even a single positive blood culture should be treated, and requires removal of intravascular lines. Fluconazole is the first line agent for treatment candidemia other than that caused by Candida glabrata or C. krusei. High-resolution CT scan pictures showing a halo sign or crescent air sign are helpful for establishing the diagnosis of invasive aspergillosis. Sandwich ELISA can be used to detect circulating galactomannan in serial serum samples. Polymerase chain reaction (PCR) of blood samples may also be used. There are only a few randomized studies of newly developed antifungal drugs compared to conventional amphotericin B (AmB). So far, both AmB colloidal dispersion and AmB lipid complex have failed to show more favorable efficacy or lesser toxicity rates, except for nephrotoxicity. Liposomal AmB, used during febrile neutropenia, did have a significantly lower toxicity rate. In neutropenic patients with invasive fungal infections liposomal AmB proved to be better than conventional AmB in terms of clinical efficacy, mortality and nephrotoxicity rates. The use of tests to achieve an earlier diagnosis combined with more potent treatment formulations such as liposomal AmB may be significant steps towards successful management of invasive fungal infections.

Prostate cancer schemes for androgen escape.

Abstract: A double mutation in the androgen receptor allows prostate cancer cells to become responsive to glucocorticoids. This discovery sheds light on a new pathway by which prostate cancer cells can escape androgen dependence ( pages 703–706 ).

Comparison of conventional and molecular methods for the detection of bacterial pathogens in sputum samples from cystic fibrosis patients.

Abstract: The nature of the micro-flora present in sputa of six different cystic fibrosis (CF) patients was assessed using routine microbiological culture and molecular methods. Bacterial genes for the small subunit ribosomal RNA (ssu rDNA) were specifically amplified from DNA extracted from the sputum samples, cloned and characterised by hybridisation and DNA sequencing. A large number of clones from six sputa were screened. Initially, oligonucleotide hybridisation was performed with five probes, specific for Gram-positives and Gram-negatives in general and the main pathogens for the CF patient (Staphylococcus aureus, Pseudomonas aeruginosa and Haemophilus influenzae). For a single sputum sample, the results were fully congruent when culture and molecular methods were compared. In the other five sputa, discrepancies for S. aureus and/or H. influenzae were documented. Although S. aureus DNA and H. influenzae DNA was detected in three and four sputa, respectively, strains could not be cultured. Although the PCR approach is not capable of distinguishing viable from dead bacteria, all of the CF patients had a history of S. aureus infections, while one of the CF patients once had cultivable H. influenzae in the sputum as well. A number of clones for probe-unidentified Gram-negative or Gram-positive bacterial species were further analysed by sequencing and additional potential pathogens were identified. Although routine culture of sputum frequently points to mono-specific exacerbations, our molecular data indicate that the other CF-related pathogens appear to be persistently present as well. We conclude that routine culture for bacterial pathogens from CF sputa yields limited microbiological information since it frequently fails to identify a number of pathogenic bacterial species that are potentially present in a viable status in the lungs of these patients.

Lipoprotein Lipase Activity Is Associated With Severity of Angina Pectoris

Abstract: Background—Raised triglyceride-rich lipoproteins significantly increase the risk for cardiovascular disease. Variation in the activity of the enzyme lipoprotein lipase (LPL), which is crucial in the removal of these lipoproteins, may therefore modulate this risk. Methods and Results—Postheparin levels of LPL activity and mass were measured in a large cohort of male coronary artery disease patients participating in the Regression Growth Evaluation Statin Study (REGRESS), a lipid-lowering regression trial. In addition, the relationships between LPL activity and mass and severity of angina pectoris according to the NYHA classification and silent ischemia on 24-hour ambulatory ECG monitoring were assessed. Patients in different LPL activity quartiles and mass had different severities of angina; a total of 47% of patients in the lowest LPL quartile reported class III or IV angina. In contrast, only 29% in the highest activity quartile (P=0.002) had severe angina. These parameters were supported by ambulatory E...

Molecular Epidemiology of Methicillin-Resistant Staphylococcus aureus Strains: State of Affairs and Tomorrow's Possibilities

Abstract: Methicillin-resistant strains of Staphylococcus aureus (MRSA) have posed a clinical threat for nearly 40 years. During these years, an array of additional technologies suited for identification of MRSA below the species level has become available. The technologies, whether they assess phenotype or genotype, provide data that can be used for elucidation of the routes of dissemination of individual MRSA types. This review summarizes the current state of affairs with respect to the quality of the various laboratory techniques and includes descriptions of novel strategies such as binary typing and multilocus sequence typing (MLST). Drawbacks of procedures will be compared, and the value of molecular typing in the elucidation of complex biological phenomena, such as epidemicity, carriage, and reduced vancomycin susceptibility, will be indicated. Means for integrated assessment of bacterial biology, epidemiology, and population structure will be discussed.

Distinguishing Species of the Burkholderia cepacia Complex and Burkholderia gladioli by Automated Ribotyping

Abstract: Several species belonging to the genus Burkholderia are clinically relevant, opportunistic pathogens that inhabit major environmental reservoirs. Consequently, the availability of means for adequate identification and epidemiological characterization of individual environmental or clinical isolates is mandatory. In the present communication we describe the use of the Riboprinter microbial characterization system (Qualicon, Warwick, United Kingdom) for automated ribotyping of 104 strains of Burkholderia species from diverse sources, including several publicly accessible collections. The main outcome of this analysis was that all strains were typeable and that strains of Burkholderia gladioli and of each species of the B. cepacia complex, including B. multivorans, B. stabilis, and B. vietnamiensis, were effectively discriminated. Furthermore, different ribotypes were discerned within each species. Ribotyping results were in general agreement with strain classification based on restriction fragment analysis of 16S ribosomal amplicons, but the resolution of ribotyping was much higher. This enabled automated molecular typing below the species level. Cluster analysis of the patterns obtained by ribotyping (riboprints) showed that within B. gladioli, B. multivorans, and B. cepacia genomovar VI, the different riboprints identified always clustered together. Riboprints of B. cepacia genomovars I and III, B. stabilis, and B. vietnamiensis did not show distinct clustering but rather exhibited the formation of loose assemblages within which several smaller, genomovar-specific clusters were delineated. Therefore, ribotyping proved useful for genomovar identification. Analysis of serial isolates from individual patients demonstrated that infection with a single ribotype had occurred, despite minor genetic differences that were detected by pulsed-field gel electrophoresis of DNA macrorestriction fragments. The automated approach allows very rapid and reliable identification and epidemiological characterization of strains and generates an easily manageable database suited for expansion with information on additional bacterial isolates.

Complement-resistant Moraxella catarrhalis forms a genetically distinct lineage within the species

Abstract: Moraxella catarrhalis is a bacterial species that has been implicated in 15^20% of all cases of otitis media in the USA and the complementresistantvariant of M. catarrhalis has been considered particularly pathogenic. A collection of geographically diverse, complement-sensitive (n = 28) and -resistant strains (n = 47) of M. catarrhalis was assembled in order to analyse the bacterial population structure. All strains were identified as M. catarrhalis by conventional microbiological and biochemical methods. Amplification of the small subunit (ssu) ribosomal RNA gene followed by restriction fragment length polymorphism (RFLP) analysis did not reveal consistent differences between serumsusceptible and -resistant M. catarrhalis isolates. Interestingly, upon automated ribotyping using the Qualicon RiboPrinter0 microbial characterisation system, the complement-sensitive and -resistant strains segregated into two groups. This suggested the existence of two clearly distinguishable lineages within the species M. catarrhalis. This observation was corroborated by pulsed field gel electrophoresis (PFGE) of DNA macro-restriction fragments, a non-ribosomal PCR RFLP procedure and random amplification of polymorphic DNA (RAPD) analysis. All procedures grouped the two variants similarly. Redefinition of the taxonomic status of complement-resistant M. catarrhalis or even the definition of a new species may be opportune. Chemicals/CAS: Complement System Proteins, 9007-36-7; DNA, Bacterial; DNA, Ribosomal

Use of human GH in elderly patients with accidental hip fracture.

Abstract: Objective: To investigate whether early intervention with recombinant human growth hormone (hGH) after hip fracture improves functional recovery and long-term outcome. Subjects and methods: Functional recovery after hip fracture is often incomplete. The catabolic situation that develops after the hip fracture accident, and a state of malnutrition either pre-existing or developing after surgery, are main contributing factors for the poor clinical outcome. hGH has been used to promote anabolism in a variety of clinical catabolic situations. The study design was randomized, double-blind and placebo-controlled. A total of 111 patients older than 60 years with an accidental hip fracture (mean age 78:5 ^ 9: 1( S.D.) years) were randomized to receive either hGH (20 mg/kg per day) or placebo for a period of 6 weeks, starting within 24 h after the hip fracture accident. Thereafter patients were followed up for an additional period of 18 weeks. Efficacy was assessed by comparing the changes in the Barthel Index score of activities of daily living and in a patient’s living situation between the hGH- and the placebo-treated subjects. Results: Eighty-five (78.5%) patients completed the first 8 weeks of the study and 76 (68.5%) the entire study period of 24 weeks. When split according to age, a trend was found that for patients older than 75 years the changes in Barthel Index score from baseline were less in the hGH group than in the placebo groupO218:6 ^ 18 vs 228:1 ^ 26U at 6 weeks after surgeryOP , 0:075U: There was an overall trend to a higher rate of return to the pre-fracture independent living situation in the hGH group than in the placebo group. Analysis by age revealed a significantly higher proportion of hGHthan placebo-treated patients returning to the pre-fracture living situation for subjects older than 75 years (93.8 vs 75.0%, Pa 0:034U: hGH treatment increased IGF-I values to levels in the range of those of normal subjects of 50‐60 years of age. Conclusions: A 6 week treatment with hGH (20 mg/kg per day) of otherwise healthy patients after an accidental hip fracture may be of benefit if given to subjects older than 75 years of age. The rate of return to the pre-fracture living situation in subjects of this age treated with hGH was significantly increased when compared with the placebo-treated group. The treatment intervention was well tolerated and no safety issues were recorded. European Journal of Endocrinology 143 585‐592

Peritoneal adhesions to prosthetic materials: choice of mesh for incisional hernia repair.

Abstract: Background: In many cases, incisional hernia repair requires the use of prosthetic materials. The aim of this experimental study in a rat model was to assess the role of polyglactin 910 mesh and fluoropassivated polyester mesh in preventing the formation of adhesions. Methods: In the first experiment, the formation of peritoneal adhesions was assessed after insertion of polypropylene, polypropylene combined with polyglactin 910, or no mesh. In the second experiment, adhesion formations were compared after insertion of fluoropassivated polyester, polypropylene, and no mesh. Results: The first experiment showed no significant difference in adhesion formations between the polypropylene mesh and the combined mesh; however, when no mesh was used, there were significantly fewer adhesions in both experiments (p < 0.01). The second experiment showed a significantly lower degree of adhesions and a lower Adhesion Index after insertion of fluoropassivated polyester mesh than when polypropylene mesh was used (p = 0.04). Conclusions: Adding polyglactin 910 mesh to polypropylene mesh to prevent the formation of adhesions is not an effective measure. Fluoropassivated polyester meshes appear to provide a better alternative to the use of polypropylene meshes for incisional hernia repair in humans in terms of the formation of adhesions.