82-rubidium positron emission tomography determined myocardial flow reserve and outcomes following cardiac revascularisation - A multicentre registry study.

BACKGROUND: Finding patients with chronic coronary syndromes (CCS) whom revascularization could benefit, is complicated. Myocardial flow reserve (MFR), a measurement of myocardial perfusion, has proven prognostic value on survival and risk of major adverse cardiac events (MACE). We investigated if MFR identifies who may benefit from revascularization. METHODS: Among 7462 patients from Danish hospitals examined with 82Rb PET between January 2018 and August 2020, patients with ≥5% reversible perfusion defects were followed for MACE and all-cause mortality. Associations between revascularisation (within 90 days) and outcomes according to MFR (< and ≥ 2) was assessed by Cox regression adjusted by inverse probability weighting for demographics, cardiovascular risk factors, comorbidities, and 82Rb PET variables. RESULTS: Of 1806 patients with ≥5% reversible perfusion defect, 893 (49%) had MFR < 2 and 491 underwent revascularisation (36.6% in MFR < 2 versus 17.9% MFR ≥ 2, p < 0.001). During a median follow-up of 37.0 [31.0-45.8 IQR] months, 251 experienced a MACE and 173 died. Revascularisation was associated with lower adjusted risk of all-cause mortality (hazard ratio [HR], 0.51 [95% CI, 0.30-0.88], p = 0.015) and MACE (HR, 0.54 [0.33-0.87], p = 0.012) in patients with MFR < 2 but not MFR ≥ 2 for all-cause mortality (HR 1.33 [0.52-3.40], p = 0.542) and MACE (HR 1.50 [0.79-2.84], p = 0.211). MFR significantly modified the association between revascularisation and MACE, but not all-cause mortality (interaction p-value 0.021 and 0.094, respectively). CONCLUSIONS: Revascularization was associated with improved prognosis among patients with impaired MFR. No association was seen in patients with normal MFR. In patients with regional ischemia, MFR may identify patients with a prognostic benefit from revascularization.

Guiding early revascularization using [15O]H2O PET myocardial perfusion imaging - Impact of atrial fibrillation.

AIMS: Myocardial perfusion imaging (MPI) using [15O]H2O positron emission tomography (PET) is used to guide the selection of patients with angina for invasive angiography and possible revascularization. Our study evaluated whether atrial fibrillation (AF): 1) reduces global hyperemic myocardial blood flow (MBF) and 2) whether [15O]H2O PET MPI effectively guides revascularization procedures for patients with ongoing AF. METHODS AND RESULTS: We prospectively recruited 346 patients with angina and persistent or paroxysmal AF referred for baseline/hyperemic [15O]H2O PET MPI. The primary outcome was revascularization within 3 months of MPI. In the analyses, patients were divided into four groups based on whether they had ongoing AF or sinus rhythm (SR) and whether they had previously documented coronary artery disease (CAD) or not. Thus, four groups were compared: SR-noCAD, AF-noCAD, SR-CAD and AF-CAD. Hyperemic MBF was affected by both ongoing AF and prior CAD [MBF (mL/min/g): 2.82 (SR-noCAD) vs. 2.12 (AF-noCAD) vs. 2.22 (SR-CAD) vs. 1.80 (AF-CAD), two-way ANOVA p<0.0001]. In multiple linear regression ongoing AF was independently associated with reduced hyperemic MBF. Every 0.1 mL/min/g decrease in hyperemic MBF was associated with a 23% increase in odds of early revascularization. ROC-analysis of vessel specific hyperemic MBF to predict early revascularization yielded the following areas under the ROC curve (AUC): SR-noCAD: 0.95 (p<0.0001); AF-noCAD: 0.79 (p<0.0001); SR-CAD: 0.78 (p<0.0001); AF-CAD: 0.88 (p<0.0001). CONCLUSION: Ongoing AF is associated with 19-25 % reduced global hyperemic MBF as measured by [15O]H2O MPI PET. Regardless, vessel specific hyperemic MBF still predicts early revascularization in patients with AF.

Prenatal detection of orofacial clefts in Denmark from 2009 to 2018.

OBJECTIVE: To investigate the overall and type-specific prenatal detection rates (DRs) of orofacial clefts in a national cohort in Denmark. METHODS: This study was based on data from the Danish Fetal Medicine Database and included all fetuses and children from singleton pregnancies diagnosed with an orofacial cleft prenatally and/or postnatally between 2009 and 2018. The types of cleft included unilateral, bilateral or median cleft lip (CL); unilateral, bilateral or median cleft lip with secondary cleft palate (CLP); and cleft palate (CP). The clefts were grouped as cleft lip with or without cleft palate (CL(P)) or as all clefts (including CP). All cases with discordance between prenatal and postnatal diagnoses were validated in the local patient files (Astraia). Cases without prenatal validation of the postnatal diagnosis were marked as undetected. Postnatally diagnosed cases with a strong prenatal suspicion of a cleft but without an International Classification of Diseases-10 code were registered as prenatally detected. Termination of pregnancy and intrauterine death were registered as true positives even if no autopsy could be performed. Liveborn cases with a prenatal diagnosis but without a postnatal validation were excluded. RESULTS: A total of 994 cases were included in the study, of which 933 were liveborn. The prevalence of orofacial cleft was 1.6 per 1000 live births. There were no differences in the baseline characteristics between detected and undetected cases. The DR for CL(P) was 71.7% (95% CI, 64.8-78.9%), with an increase from 60.0% in 2009 to 73.0% in 2018 (P = 0.018). The type-specific DRs for the entire period were 56.4% (95% CI, 45.0-67.6%) for unilateral CL; 76.6% (95% CI, 71.7-82.9%) for unilateral CLP; 70.5% (95% CI, 52.1-87.6%) for bilateral CL; 82.3% (95% CI, 70.6-93.6%) for bilateral CLP; 0% (0/6) for median CL; 75.0% (3/4) for median CLP; and 3.3% (95% CI, 0.6-5.7%) for CP. A total of 20.9% (208/994) of the cases had associated findings, of which 33.2% (69/208) were genetic aberrations. CONCLUSIONS: The DR for CL(P) has improved in Denmark over the last decade. The DR for CLP is high, with the highest DR for bilateral CLP. However, prenatal detection of CP remains a challenge. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Global parental leave in surgical careers: differences according to gender, geographical regions and surgical career stages.

BACKGROUND: There is a lack of information regarding the provision of parental leave for surgical careers. This survey study aims to evaluate the experience of maternity/paternity leave and views on work-life balance globally. METHODS: A 55-item online survey in 24 languages was distributed via social media as per CHERRIES guideline from February to March 2020. It explored parental leave entitlements, attitude towards leave taking, financial impact, time spent with children and compatibility of parenthood with surgical career. RESULTS: Of the 1393 (male : female, 514 : 829) respondents from 65 countries, there were 479 medical students, 349 surgical trainees and 513 consultants. Consultants had less than the recommended duration of maternity leave (43.8 versus 29.1 per cent), no paid maternity (8.3 versus 3.2 per cent) or paternity leave (19.3 versus 11.0 per cent) compared with trainees. Females were less likely to have children than males (36.8 versus 45.6 per cent, P = 0.010) and were more often told surgery is incompatible with parenthood (80.2 versus 59.5 per cent, P < 0.001). Males spent less than 20 per cent of their salary on childcare and fewer than 30 hours/week with their children. More than half (59.2 per cent) of medical students did not believe a surgical career allowed work-life balance. CONCLUSION: Surgeons across the globe had inadequate parental leave. Significant gender disparity was seen in multiple aspects.

Severity and 1-month outcome of SARS-CoV-2 infection in patients with solid cancers: a Danish nationwide cohort study.

BACKGROUND: Cancer patients are vulnerable to infections, are older and often have comorbidities in comparison to the general population, which increases the risk for severe outcomes related to COVID-19 diagnosis. METHODS: This study is a prospective, nationwide study in patients with solid cancer and SARS-CoV-2 infection included between 10 March to 15 June 2020. Patient's baseline characteristics were collected. The study's primary outcome was overall survival within 30 days of verified SARS-CoV-2 infection. Secondary outcomes were hospital admission, admission to an ICU, and need for supplemental oxygen. RESULTS: A total of 112 patients with a cancer diagnosis and verified SARS-CoV-2 infection were identified. After one month of follow up, hospitalization was required for 54% (n = 61) and 21% of the patients had died and 14 of the 23 deceased cancer patients were ≥70 years. Most patients were classified with mild COVID-19 symptoms (66%, n = 74); however, 48% (n = 23) of the ≥70-year-olds patients were classified with severe or critical COVID-19 symptoms. Among the total study population, 61% (n = 68) had comorbidities and comorbidity were more frequently observed among the deceased (91%, n = 21) and older cancer patients (≥70 years, 81%, n = 39). CONCLUSIONS: Acknowledging the low sample size in this study, our work shows that age and comorbidities, but not recent cytotoxic therapy, are associated with adverse outcomes of SARS-CoV-2 infection for patients with solid cancer. Particularly, patients with progressive disease seem to be at greater risk of a fatal outcome from COVID-19.HighlightsAge, performance status, and comorbidities are strong predictors of adverse outcome in cancer patients with SARS-CoV-2 infection.Patients with progressive cancer disease seem to be at greater risk of a fatal outcome from COVID-19.Recent cytotoxic therapy, however, did not seem to be associated with increased risk for adverse outcomes of SARS-CoV-2 infection for patients with solid cancer.

Human walk-to-run transition in the context of the behaviour of complex systems.

This study had two main aims: 1) to investigate if the walk-to-run (WR-) transition occurs when the speed of locomotion is kept constant below the WR-transition speed (speed clamp) and the stride rate is increased monotonously using a metronome and 2) to investigate if diversion of attention and awareness from the locomotion process influences the position of the WR-transition in stride rate, stride length, and locomotion speed (SrSlLs) space. Eighteen healthy individuals (13 men and 5 women) were recruited (age: 23.9 ±â€¯1.5 years, height: 1.77 ±â€¯0.10 m and body mass: 77.3 ±â€¯12.8 kg). Stride-by-stride stride rates, stride lengths, locomotion speeds, and duty factors were determined on a treadmill in 4 different tests: 1) reference WR-transition, 2) preferred walking speed, 3) dual-task test including arithmetic calculations and 4) four speed clamp bouts with different initial velocities. Walk-to-run transitions were elicited in all participants in the speed clamp bouts. When the stride rate ramp was clamped at preferred walking speed the WR-transition stride rate was not significantly different from the WR-transition stride rate during the reference test (t = 2.2, p = 0.312). However, in the SrSlLs space the speed clamp WR-transitions all deviated from the position of the reference WR-transition. Additionally, it was demonstrated that intensive attentional diversion using a dual-task paradigm had very little influence on the position of the WR-transition in the SrSlLs space. It is argued that these observations can be explained in the context of the behavior of complex systems.

Urine composition in pigs is regulated in both the ureter and the bladder.

The former perception of the urothelium as an impermeable barrier has been revised during the last decade, as increasing evidence of changes in urine composition during its passage of the urinary tract has been presented. Since differences in urothelial permeability between upper and lower urinary tract have been found, our aim is to demonstrate whether changes in urine composition occur during passage through the ureter. We studied consecutive urine samples from both renal pelvises in six pigs and compared them to samples from the bladder and distal ureter. We further sampled urine during storage in the bladder at a fixed volume. All samples were analysed by measuring osmolality and pH, along with the concentration of the following parameters: Na(+), K(+), Cl(-), creatinine, urea. Urine alkalinity increased significantly during passage of the ureter. Creatinine concentration, pH and K(+) increased significantly during the passage from pelvis to the bladder. All other parameters increased non-significantly during the passage to the bladder. The increase in concentration was more pronounced at low concentrations in the pelvis. During storage in the bladder, there was a significant increase in urea concentration. Changes in the composition of urine occur during its passage from the renal pelvis to the bladder and during storage in the bladder. Despite the brief transit time, significant changes in alkalinity were found already during passage through the ureter.

Aquaporin expression in the fetal porcine urinary tract changes during gestation.

The expression of aquaporins (AQPs) in the fetal porcine urinary tract and its relation to gestational age has not been established. Tissue samples from the renal pelvis, ureter, bladder and urethra were obtained from porcine fetuses. Samples were examined by RT-PCR (AQPs 1-11), QPCR (AQPs positive on RT-PCR), and immunohistochemistry. Bladder samples were additionally examined by Western blotting. RNA was extracted from 76 tissue samples obtained from 19 fetuses. Gestational age was 60 (n=11) or 100 days (n=8). PCR showed that AQP1, 3, 9 and 11 mRNA was expressed in all locations. The expression of AQP3 increased significantly at all four locations with gestational age, whereas AQP11 significantly decreased. AQP1 expression increased in the ureter, bladder and urethra. AQP9 mRNA expression increased in the urethra and bladder, but decreased in the ureter. AQP5 was expressed only in the urethra. Immunohistochemistry showed AQP1 staining in sub-urothelial vessels at all locations. Western blotting analysis confirmed increased AQP1 protein levels in bladder samples during gestation. Expression levels of AQP1, 3, 5, 9 and 11 in the urinary tract change during gestation, and further studies are needed to provide insights into normal and pathophysiological water handling mechanisms in the fetus.

Gastrointestinal tolerance and plasma status of carotenoids, EPA and DHA with a fiber-enriched tube feed in hospitalized patients initiated on tube nutrition: Randomized controlled trial.

BACKGROUND & AIMS: During the first days of tube feeding (TF) gastrointestinal (GI) complications are common and administration of sufficient nutrition is a challenge. Not all standard nutritionally complete formulas contain dietary fiber, fish oil or carotenoids, key dietary nutrients for health and wellbeing. The aim of this study was to investigate the effects of a fiber, fish oil and carotenoid enriched TF formula on diarrhea, constipation and nutrient bioavailability. METHODS: A multi-center randomized, double-blind, controlled, parallel trial compared the effects of a dietary fiber, fish oil and carotenoid-enriched TF formula (test) with an isocaloric non-enriched formula (control) in 51 patients requiring initiation of TF. Incidence of diarrhea and constipation (based on stool frequency and consistency) was recorded daily. Plasma status of EPA, DHA and carotenoids was measured after 7 days. RESULTS: The incidence of diarrhea was lower in patients receiving the test formula compared with the control group (19% vs. 48%, p = 0.034). EPA and DHA status (% of total plasma phospholipids) was higher after 7 days in test compared with control group (EPA: p = 0.002, DHA: p = 0.082). Plasma carotenoid levels were higher after 7 days in the test group compared with control group (lutein: p = 0.024, α-carotene: p = 0.005, lycopene: p = 0.020, ß-carotene: p = 0.054). CONCLUSIONS: This study suggests that the nutrient-enriched TF formula tested might have a positive effect on GI tolerance with less diarrhea incidence and significantly improved EPA, DHA and carotenoid plasma levels during the initiation of TF in hospitalized patients who are at risk of diarrhea and low nutrient status. CLINICAL TRIAL REGISTRATION: This trial was registered at trialregister.nl; registration number 2924.

What is a representative voiding pattern in children with lower urinary tract symptoms? Lack of consistent findings in ambulatory and conventional urodynamic tests.

BACKGROUND: Conventional urodynamics (CU) is a highly standardized evaluation of lower urinary tract function. However, in pediatric patients there is concern that the reliability of measurements could be influenced by development effects and measurement variability, as well as by the unfamiliar clinical environment. Ambulatory urodynamics (AU) provides an alternative to this - it uses natural filling, is measured over a prolonged period, and is conducted in a child-friendly environment. OBJECTIVE: The aim of this study was to conduct a comparative analysis of AU and CU to evaluate the consistency in voiding patterns obtained with these two methods of urodynamic testing. STUDY DESIGN: Urodynamic parameters obtained by AU and CU methods in 50 pediatric patients aged >5 years were retrospectively analyzed. Voiding patterns were categorized into six types: coordinated contraction, detrusor after-contraction, fluctuated contraction, pre-void contraction, relief voiding, and weak or absent contraction. Voiding patterns were used to determine the repeatability within urodynamic tests and to identify consistency between AU and CU tests. Five urodynamic parameters were quantified and compared between AU and CU: voided volume, flow rate, maximum detrusor pressure, and detrusor pressure at peak flow rate. For inter-observer variation analysis, 100 voiding curves were randomly selected and categorized by two independent observers; inter-observer agreement was evaluated using the kappa statistic. RESULTS: A single pattern of voiding was identified in five patients using AU and 37 using CU. Consistency of a single pattern between AU and CU was identified in three patients, and consistency between a predominant pattern with AU, defined by one type of voiding occurring >50% of one's voids, and a single pattern with CU was identified in 10 patients (summary table). Flow rates were similar between methods; however, higher maximum detrusor pressure and detrusor pressure at peak flow and lower voided volume were recorded with AU. DISCUSSION: AU resulted in more diverse voiding patterns. Along with the differences in measured urodynamic parameters challenges the application of findings from one method to form a clinical diagnosis. Furthermore, CU may not be as sensitive as AU to the variability in lower urinary tract pathophysiology. CONCLUSIONS: More diverse voiding patterns were identified in AU compared with CU, with a lack of consistency in identified voiding pattern in both methods. Therefore, the urodynamic findings in children may have to be analyzed in more detail, taking the variations into account.

Escherichia coli clonal group A causing bacteraemia of urinary tract origin.

Escherichia coli clonal group A (CgA) causes disease in humans. This is the first study investigating the prevalence of CgA among E. coli from non-urine, extraintestinal infections in a northern European country. E. coli blood (n = 196) and paired urine (n = 195) isolates from the same patients with bacteraemia of urinary tract origin were analysed. The isolates were collected from January 2003 through May 2005 at four hospitals in Copenhagen, Denmark. Pulsed-field gel electrophoresis (PFGE) patterns, antimicrobial resistance and patient characteristics were determined for all CgA isolates; presence of virulence-associated genes (VAGs) and serotypes were determined for the blood CgA isolates. Thirty blood isolates (15%) belonged to CgA. CgA blood isolates were associated with female patients and sulfamethoxazole-trimethoprim resistance and they harboured a distinctive VAG profile. The blood and urine isolates from each pair were found to be related in 26 of 27 CgA blood/urine pairs, confirming a urinary tract origin of infection. Furthermore, a relationship between the PFGE patterns of CgA blood/urine isolates and CgA isolates from UTI patients in general practice and a CgA isolate from a community-dwelling human reported previously, was found, suggesting a community origin of CgA. The finding of CgA strains in 15% of the E. coli bloodstream infections with a urinary tract origin in Denmark suggests that CgA constitutes an important clonal lineage among extraintestinal pathogenic E. coli. A reservoir of this pathogenic E. coli group in the community causing not only UTI but also more severe infections such as bacteraemia has implications for public health.

Genetic studies in congenital anterior midline cervical cleft.

Congenital anterior midline cervical cleft (CAMCC) is a rare anomaly, with less than 100 cases reported. The cause of CAMCC is unknown, but genetic factors must be considered as part of the etiology. Three cases of CAMCC are presented. This is the first genetic study of isolated CAMCC. Conventional cytogenetics, array-comparative genomic hybridization (CGH) and whole exome sequencing were performed, including a search of relevant syndromes in the Online Mendelian Inheritance in Man (OMIM) database. Array CGH indicated a loss of the PAPPA gene in one of the patients, while exome sequencing showed a mutation in SIX5 in another patient. Both aberrations were inherited from unaffected parents. These results most likely imply that the identified mutations are not disease-causing, although they may be contributing factors if CAMCC has a polygenic inheritance.

Is Escherichia coli urinary tract infection a zoonosis? Proof of direct link with production animals and meat.

Recently, it has been suggested that the Escherichia coli causing urinary tract infection (UTI) may come from meat and animals. The purpose was to investigate if a clonal link existed between E. coli from animals, meat and UTI patients. Twenty-two geographically and temporally matched B2 E. coli from UTI patients, community-dwelling humans, broiler chicken meat, pork, and broiler chicken, previously identified to exhibit eight virulence genotypes by microarray-detection of approximately 300 genes, were investigated for clonal relatedness by PFGE. Nine isolates were selected and tested for in vivo virulence in the mouse model of ascending UTI. UTI and community-dwelling human strains were closely clonally related to meat strains. Several human derived strains were also clonally interrelated. All nine isolates regardless of origin were virulent in the UTI model with positive urine, bladder and kidney cultures. Further, isolates with the same gene profile also yielded similar bacterial counts in urine, bladder and kidneys. This study showed a clonal link between E. coli from meat and humans, providing solid evidence that UTI is zoonosis. The close relationship between community-dwelling human and UTI isolates may indicate a point source spread, e.g. through contaminated meat.

Faecal carriage of extended-spectrum ß-lactamase-producing and AmpC ß-lactamase-producing bacteria among Danish army recruits.

During May and June 2008, 84 Danish army recruits were tested for faecal carriage of extended-spectrum ß-lactamase (ESBL)-producing and AmpC ß-lactamase-producing bacteria. Three ESBL-producing (CTX-M-14a) Escherichia coli isolates, two AmpC-producing (CMY-2) E. coli isolates and one AmpC-producing (CMY-34) Citrobacter freundii isolate were detected. Two of the CTX-M-14a E. coli isolates had similar pulsed-field gel electrophoresis and multilocus sequence typing profiles, indicating the same origin or transmission between the two army recruits. The bla(CTX-M-14a) genes were transferable to an E. coli recipient. These commensal bacteria therefore constitute a reservoir of resistance genes that can be transferred to other pathogenic bacteria in the intestine.

Circulating levels of mannan-binding lectin (MBL) and MBL-associated serine protease 2 in endemic pemphigus foliaceus.

Endemic pemphigus foliaceus (EPF) is an autoimmune disease, which occurs in Brazil and other regions of South America. Mannose-binding lectin (MBL) and MBL-associated serine protease (MASP-2) play a key role in innate immunity, and its deficiency has been related to increased susceptibility to infection and autoimmune diseases. MBL and MASP-2 serum levels were measured in 114 patients with EPF and in 100 healthy individuals in Brazil. MBL and MASP-2 levels were measured by sandwich assays (time-resolved immunofluorimetic assay) using monoclonal antibodies. No difference was observed in the MBL level in patients with EPF compared with controls [mean +/- SEM 1230.07 +/- 132.18 ng/mL (median 789.0 ng/mL) vs. 1036.98 +/- 117.99 ng/mL (median 559.5 ng/mL), P = 0.32]. Non-significant lower MASP-2 levels were observed in EPF [274.34 +/- 15.66 ng/mL (median 239.5 ng/mL ) vs. 304.72 +/- 15.28 ng/mL [median 261.0 ng/mL ), P = 0.06]. MBL deficiency (< 10 ng/mL) or MASP-2 deficiency (< 100 ng/mL) did not differ significantly between patients and controls. These data indicate that MBL and MASP-2 deficiency are not associated with susceptibility to EPF.

Gentamicin susceptibility in Escherichia coli related to the genetic background: problems with breakpoints.

In total, 120 Escherichia coli isolates positive for one of the gentamicin resistance (GEN(R)) genes aac(3)-II, aac(3)-IV or ant(2'')-I were tested for gentamicin susceptibility by the agar dilution method. Isolates positive for aac(3)-IV or ant(2'')-I had an MIC distribution of 8-64 mg/L, whereas isolates positive for aac(3)-II had MICs of 32 to >512 mg/L, suggesting a relationship between the distribution of MICs and the specific GEN(R) mechanism. The MIC distribution, regardless of the GEN(R) mechanism, was 8 - >512 mg/L, which supports the clinical breakpoint of MIC >4 mg/L suggested by EUCAST and questions the breakpoint recommended by the CLSI (> or =16 mg/L).

Macrolide resistance by ribosomal mutation in clinical isolates of Streptococcus pneumoniae from the PROTEKT 1999-2000 study.

Sixteen (1.5%) of the 1,043 clinical macrolide-resistant Streptococcus pneumoniae isolates collected and analyzed in the 1999-2000 PROTEKT (Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin) study have resistance mechanisms other than rRNA methylation or efflux. We have determined the macrolide resistance mechanisms in all 16 isolates by sequencing the L4 and L22 riboprotein genes, plus relevant segments of the four genes for 23S rRNA, and the expression of mutant rRNAs was analyzed by primer extension. Isolates from Canada (n = 4), Japan (n = 3), and Australia (n = 1) were found to have an A2059G mutation in all four 23S rRNA alleles. The Japanese isolates additionally had a G95D mutation in riboprotein L22; all of these originated from the same collection center and were clonal. Three of the Canadian isolates were also clonal; the rest were not genetically related. Four German isolates had A2059G in one, two, and three 23S rRNA alleles and A2058G in two 23S rRNA alleles, respectively. An isolate from the United States had C2611G in three 23S rRNA alleles, one isolate from Poland had A2058G in three 23S rRNA alleles, one isolate from Turkey had A2058G in four 23S rRNA alleles, and one isolate from Canada had A2059G in two 23S rRNA alleles. Erythromycin and clindamycin resistance gradually increased with the number of A2059G alleles, whereas going from one to two mutant alleles caused sharp rises in the azithromycin, roxithromycin, and rokitamycin MICs. Comparisons of mutation dosage with rRNA expression indicates that not all alleles are equally expressed. Despite their high levels of macrolide resistance, all 16 isolates remained susceptible to the ketolide telithromycin (MICs, 0.015 to 0.25 microg/ml).

The specific enhancement of interferon alpha induced growth inhibition by BCR/ABL only occurs in multipotent cells.

INTRODUCTION: The causative oncogene in CML is the BCR/ABL protein tyrosine kinase. This stem cell disease is often treated with interferon alpha (IFN-alpha) which can initiate haematological and cytological remission which is associated with increased survival. There is however no clear indication of why CML cells are more responsive to IFN-alpha. MATERIALS AND METHODS: To establish if BCR/ABL increases the sensitivity of multipotent cells to IFN-alpha a temperature sensitive mutant of BCR/ABL was expressed in the multipotent haemopoietic stem cell line FDCP-Mix. The effect of IFN-alpha in terms of proliferation, induction of apoptosis, changes in cell cycle inhibitor proteins, and differentiation was assessed by [3H]thymidine incorporation, Annexin V and Western blot analysis. RESULTS: When the BCR/ABL tyrosine kinase was activated, the IFN-alpha-induced inhibition on the growth rate of the FDCP-Mix cell population was more marked than in control populations. The BCR/ABL-mediated effect was due to decreased rates of DNA synthesis. There was no IFN-alpha-mediated induction of apoptosis. This enhanced BCR/ABL mediated growth inhibition occurred over a range of growth factor concentrations and was independent of changes in p21(Cip1) and p27(Kip) levels. When FDCP-Mix cells were induced to differentiate into mature macrophages and neutrophils in the presence of IFN-alpha, there was increased sensitivity to IFN-alpha that was independent of BCR/ABL activity. CONCLUSION: BCR/ABL PTK expression in this primitive multipotent haematopoietic cell line results in an enhanced response to IFN-alpha. In contrast, the more mature myeloid progenitor cells are equally responsive to this growth inhibitor. This data may explain some of the clinical effects of IFN-alpha.

[Spontaneous infrapatellar tendon rupture in a patient with systemic lupus erythematosus]. / Spontan infrapatellar seneruptur hos patient med systemisk lupus erythematosus.

A case is described of a 33-year old woman with systemic lupus erythematosus (SLE) in longterm treatment with corticosteroids who experienced spontaneous rupture of the left patellar tendon. A comparative study of 28 previously reported cases of SLE patients with spontaneous tendon rupture in weight bearing joints is performed. It is suggested that renal disease may be an etiological factor for spontaneous tendon rupture in patients with systemic lupus erythematosus.