Core genome multi-locus sequence typing as an essential tool in a high-cost livestock-associated meticillin-resistant Staphylococcus aureus CC398 hospital outbreak.

BACKGROUND: Livestock-associated meticillin-resistant Staphylococcus aureus (LA-MRSA) clonal complex (CC) 398 may be transmitted and cause morbidity and mortality in hospitals. The economic cost of stopping hospital transmission of LA-MRSA CC398 is poorly described. Early detection of transmission may limit the extent of the intervention. AIM: To evaluate core genome multi-locus sequence typing (cgMLST) for detecting transmission chains and to estimate the costs for interventions to prevent further spread after discovery of hospital transmission of LA-MRSA CC398. METHODS: Five patients were involved in two episodes of transmission of LA-MRSA CC398 in a hospital. Standard interventions including MRSA screening of patients and healthcare workers were initiated. Whole genome sequences of the five isolates and 17 epidemiologically unrelated MRSA CC398 isolates from other hospitalized patients were analysed by single nucleotide polymorphism (SNP) comparisons and cgMLST. The economic costs of constraining transmission were calculated from relevant sources. FINDINGS: The five isolates suspected to be involved in hospital transmission clustered with ≤2 SNPs in the draft genome sequences with some distance to other isolates. cgMLST allocated the five isolates to the same type, which was different from all but two of the sporadic isolates. Furthermore, cgMLST separated the five transmission isolates from all other isolates. The economic costs of the outbreak interventions exceeded €11,000 per patient. CONCLUSION: LA-MRSA CC398 is transmittable in hospitals, and intervention against transmission may reach considerable costs. cgMLST is useful in surveillance of hospital transmission of LA-MRSA.

Cerebral blood flow, oxygen metabolism, and lactate during hypoxia in patients with obstructive sleep apnea.

Study Objectives: Obstructive sleep apnea (OSA) is associated with increased risk of stroke but the underlying mechanism is poorly understood. We suspect that the normal cerebrovascular response to hypoxia is disturbed in patients with OSA. Methods: Global cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), and lactate concentration during hypoxia were measured in patients with OSA and matched controls. Twenty-eight patients (82.1% males, mean age 52.3 ± 10.0 years) with moderate-to-severe OSA assessed by partial polysomnography were examined and compared with 19 controls (73.7% males, mean age 51.8 ± 10.1 years). Patients and controls underwent magnetic resonance imaging (MRI) during 35 min of normoxia followed by 35 min inhaling hypoxic air (10%-12% O2). After 3 months of continuous positive airway pressure (CPAP) treatment, 22 patients were rescanned. Results: During hypoxia, CBF significantly increased with decreasing arterial blood oxygen concentration (4.53 mL (blood)/100 g/min per -1 mmol(O2)/L, p < 0.001) in the control group, but was unchanged (0.89 mL (blood)/100 g/min per -1 mmol(O2)/L, p = 0.289) in the patient group before CPAP treatment. The CBF response to hypoxia was significantly weaker in patients than in controls (p = 0.003). After 3 months of CPAP treatment the CBF response normalized, showing a significant increase during hypoxia (5.15 mL (blood)/100 g/min per -1 mmol(O2)/L, p < 0.001). There was no difference in CMRO2 or cerebral lactate concentration between patients and controls, and no effect of CPAP treatment. Conclusions: Patients with OSA exhibit reduced CBF in response to hypoxia. CPAP treatment normalized these patterns.

No association between q-angle and foot posture with running-related injuries: a 10 week prospective follow-up study.

BACKGROUND/PURPOSE: There is a paucity of knowledge on the association between different foot posture quantified by Foot Posture Index (FPI) and Quadriceps angle (Q-angle) with development of running-related injuries. Earlier studies investigating these associations did not include an objective measure of the amount of running performed. Therefore, the purpose of this study was to investigate if kilometers to running-related injury (RRI) differ among novice runners with different foot postures and Q-angles when running in a neutral running shoe. METHODS: A 10 week study was conducted including healthy, novice runners. At baseline foot posture was evaluated using the foot posture index (FPI) and the Q-angle was measured. Based on the FPI and Q-angle, right and left feet / knees of the runners were categorized into exposure groups. All participants received a Global Positioning System watch to allow them to quantify running volume and were instructed to run a minimum of two times per week in a conventional, neutral running shoe. The outcome was RRI. RESULTS: Fifty nine novice runners of mixed gender were included. Of these, 13 sustained a running-related injury. No significant difference in cumulative relative risk between persons with pronated feet and neutral feet was found after 125 km of running (Cumulative relative risk = 1.65 [0.65; 4.17], p = 0.29). Similarly, no difference was found between low and neutral Q-angle (Cumulative relative risk = 1.25 [0.49; 3.23], p = 0.63). CONCLUSION: Static foot posture as quantified by FPI and knee alignment as quantified by Q-angle do not seem to affect the risk of injury among novice runners taking up a running regimen wearing a conventional neutral running shoe. These results should be interpreted with caution due to a small sample size. LEVEL OF EVIDENCE: 2a.

A study of subunit selectivity, mechanism and site of action of the delta selective compound 2 (DS2) at human recombinant and rodent native GABA(A) receptors.

BACKGROUND AND PURPOSE: Most GABA(A) receptor subtypes comprise 2α, 2ß and 1γ subunit, although for some isoforms, a δ replaces a γ-subunit. Extrasynaptic δ-GABA(A) receptors are important therapeutic targets, but there are few suitable pharmacological tools. We profiled DS2, the purported positive allosteric modulator (PAM) of δ-GABA(A) receptors to better understand subtype selectivity, mechanism/site of action and activity at native δ-GABA(A) receptors. EXPERIMENTAL APPROACH: Subunit specificity of DS2 was determined using electrophysiological recordings of Xenopus laevis oocytes expressing human recombinant GABA(A) receptor isoforms. Effects of DS2 on GABA concentration-response curves were assessed to define mechanisms of action. Radioligand binding and electrophysiology utilising mutant receptors and pharmacology were used to define site of action. Using brain-slice electrophysiology, we assessed the influence of DS2 on thalamic inhibition in wild-type and δ(0/0) mice. KEY RESULTS: Actions of DS2 were primarily determined by the δ-subunit but were additionally influenced by the α, but not the ß, subunit (α4/6ßxδ > α1ßxδ >> γ2-GABA(A) receptors > α4ß3). For δ-GABA(A) receptors, DS2 enhanced maximum responses to GABA, with minimal influence on GABA potency. (iii) DS2 did not act via the orthosteric, or known modulatory sites on GABA(A) receptors. (iv) DS2 enhanced tonic currents of thalamocortical neurones from wild-type but not δ(0/0) mice. CONCLUSIONS AND IMPLICATIONS: DS2 is the first PAM selective for α4/6ßxδ receptors, providing a novel tool to investigate extrasynaptic δ-GABA(A) receptors. The effects of DS2 are mediated by an unknown site leading to GABA(A) receptor isoform selectivity.

Escherichia coli challenge in newborn pigs.

Escherichia coli F18 is a common porcine enteric pathogen causing diarrhea and edema in weaned pigs. An essential step in the pathogenesis of this enteric colibacillosis is a fimbria-receptor interaction in the small intestine, involving the α(1,2)-fucosyltransferase gene (FUT1) enzyme for bacterial receptor binding to the epithelium. Enzyme expression is genetically determined and increases after weaning at 3 to5 wk, probably due to age- and/or diet-related intestinal maturation. We hypothesized that artificially reared piglets, deprived of sow's milk from birth, show susceptibility to F18 already in the neonatal period. First we verified the intestinal expression of FUT1 in preterm, term, and weaned pigs by quantitative real-time polymerase chain reaction. Then age-related F18 susceptibility (degree of diarrhea) was evaluated in 3-, 10-, and 20-d-old pigs after inoculation of 10(10) cfu E. coli F18 per day for 12 d. Finally, F18 susceptibility was evaluated in caesarean-delivered 0- to 7-d-old piglets inoculated daily with F18 as above. For all pigs, their sows were genotyped to ensure expression of the FUT1 enzyme. FUT1 expression was detected in the proximal and distal small intestine with no apparent differences in levels among preterm, term, and weaned pigs. No consistent F18-induced diarrhea was detected in any of the 3 groups of 3- to 20-d-old pigs. In contrast, 0- to 7-d-old caesarean-delivered pigs showed a higher score of diarrhea in pigs inoculated with F18 compared with controls (2.4 ± 0.1 vs. 1.8 ± 0.1 respectively; P < 0.001). Caesarean-delivered piglets deprived of sow milk are highly susceptible to diarrhea induced by E. coli F18. Lack of the protective effects of birth colonization and sow milk may contribute to high intestinal F18 sensitivity. The newborn pig may be a useful model to investigate factors in maternal milk that protect against F18 diarrhea.

Causes of death among diabetic patients in Denmark.

AIMS/HYPOTHESIS: To study the distribution of causes of death in the Danish population, and its variation by diabetes status, sex, age and calendar year as well as the years of life lost from the specific causes of death. METHODS: Persons aged 30-98 years were followed from 1995 to 2008 by linkage of Danish registers. Poisson regression was used to model cause-specific mortality rates by age and calendar time for each specific cause of death, according to sex and diabetes status. The mortality rates were also modelled as a function of age and birth cohort. We computed the distribution of causes of death and years of life lost from specific causes of death due to diabetes. RESULTS: During the 14-year study period, patients with diabetes contributed 2.3 million person-years of follow-up and 124,210 deaths, whereas persons without diabetes contributed 45.1 million person-years and 648,020 deaths. The mortality was higher among individuals with diabetes, and the mortality ratio (diabetes vs no diabetes) decreased with age and for all causes and cardiovascular diseases also by calendar time. The effect of sex on the association between diabetes and mortality varied with age and cause of death. About 9 years of life were lost to diabetes at age 30 years, and 3 years at age 70 years. CONCLUSIONS/INTERPRETATION: Age-specific mortality is higher among people with diabetes, and rate ratios vary with age, sex, calendar period and cause of death. The distribution of causes of death was similar for persons with and without diabetes.

The testing effect on skills learning might last 6 months.

In a recent study we found that testing as a final activity in a skills course increases the learning outcome compared to spending an equal amount of time practicing. Whether this testing effect measured as skills performance can be demonstrated on long-term basis is not known. The research question was: does testing as a final activity in a cardio-pulmonary resuscitation (CPR) skills course increase learning outcome when assessed after half a year, compared to spending an equal amount of time practicing? The study was an assessor-blinded randomised controlled trial. A convenient sample of 7th semester medical students attending a mandatory CPR course was randomised to intervention course or control course. Participants were taught in small groups. The intervention course included 3.5 h skills training plus 30 min of skills testing. The practice-only control course lasted 4 h. Both groups were invited to a retention assessment of CPR skills half a year later. Participants included 89/180 (50%) of those invited to participate in the study. Mean performance score was 75.9 (SD 11.0) in the intervention group (N = 48) and 70.3 (SD 17.1) in the control group, effect size 0.4. The difference between groups was not statistically significant, P = 0.06. This study suggests that testing as a final activity in a CPR skills course might have an effect on long-term learning outcome compared to spending an equal amount of time practicing the skills. Although this difference was not statistically significant, the identified effect size of 0.4 can have important clinical and educational implications.

Leisure time physical exercise during pregnancy and the risk of miscarriage: a study within the Danish National Birth Cohort.

OBJECTIVE: To examine the association between leisure time physical exercise during pregnancy and the risk of miscarriage. DESIGN: Prospective study with elements of retrospective data collection. SETTING: Denmark 1996-2002. POPULATION: A total of 92,671 pregnant women enrolled in the Danish National Birth Cohort and interviewed subsequently. METHODS: Data on exercise during pregnancy and potential confounders were obtained through computer-assisted telephone interviews either during pregnancy or after an early miscarriage. Outcome of pregnancy was identified by register linkage. Using Cox regression analysis, we estimated the hazard ratio (HR) of miscarriage according to weekly amount of exercise and the type of exercise. The HR was estimated for <11, 11-14, 15-18, and 19-22 weeks of gestation, respectively. MAIN OUTCOME MEASURES: Miscarriage, defined as fetal loss before 22 completed weeks of gestation. RESULTS: A stepwise increasing relation was found between amount of exercise and risk of miscarriage, where risk of miscarriage increased by amount of exercise up to HR = 3.7 (95% CI 2.9-4.7) for women who exercised more than 7 hours per week compared with nonexercisers. Particularly 'high-impact exercise' was associated with an increased risk of miscarriage. No association was seen between exercise and risk of miscarriage after 18 weeks of gestation. CONCLUSIONS: This study suggests that exercise early in pregnancy is associated with an increased risk of miscarriage. The results should, however, be interpreted cautiously as potential bias arising from retrospective data collection may explain part of the association.

Assessment of Advanced Life Support competence when combining different test methods--reliability and validity.

UNLABELLED: Robust assessment of Advanced Life Support (ALS) competence is paramount to the credibility of ALS-provider certification and for estimating the learning outcome and retention of ALS competence following the courses. The European Resuscitation Council (ERC) provides two sets of MCQs and four Cardiac Arrest Simulation Test (CASTest) scenarios for the assessments according to guidelines 2005. AIMS: To analyse the reliability and validity of the individual sub-tests provided by ERC and to find a combination of MCQ and CASTest that provides a reliable and valid single effect measure of ALS competence. METHODS: Two groups of participants were included in this randomised, controlled experimental study: a group of newly graduated doctors, who had not taken the ALS course (N=17) and a group of students, who had passed the ALS course 9 months before the study (N=16). Reliability in terms of inter-rater agreement and generalisability across skills scenarios were estimated. Validity was studied in terms of equality of test difficulty and ability to discriminate performance between the groups. RESULTS: Inter-rater agreement on checklist scores were generally high, Intraclass Correlation Coefficients between 0.766 and 0.977. Inter-rater agreements on pass/fail decisions were not perfect. The one MCQ test was significantly more difficult than the other. There were no significant differences between CASTests. Generalisability theory was use to identify a composite of MCQ and CASTest scenarios that possessed high reliability, equality of test sets, and ability to discriminate between the two groups of supposedly different ALS competence. CONCLUSIONS: ERC sub-tests of ALS competence possess sufficient reliability and validity. A combined ALS score with equal weighting of one MCQ and one CASTest can be used as a single measurement of ALS competence.

Comparison of cerebral pharmacokinetics of buprenorphine and norbuprenorphine in an in vivo sheep model.

The pharmacokinetics and time course of blood-brain equilibration of buprenorphine (BUP) and norbuprenorphine (norBUP) in sheep were characterized. Sheep were administered 0.04 mg kg(-1) BUP or 0.6 mg kg(-1) norBUP as 4-min i.v. infusions. The cerebral kinetics were inferred from arterio-sagittal sinus concentration gradients and changes in cerebral blood flow. These data were fitted to physiologically based pharmacokinetic models. BUP cerebral kinetics were best described by a membrane-limited model with a large equilibration delay (half-life of 20 min) between brain and blood due to intermediate permeability (47 ml min(-1)) and a large cerebral distribution volume (595 ml). Significant limitation in permeability (6 ml min(-1)) characterized the cerebral kinetics of norBUP with a cerebral distribution volume (157 ml) giving a blood-brain equilibration half-life (21 min) similar to that for BUP. The logD of BUP and norBUP were 3.93 +/- 0.08 and 1.18 +/- 0.04 (mean +/- SD), respectively. Both compounds revealed slow cerebral equilibration with variations in degree of permeability and distribution volume reflecting the difference in lipophilicity. It is possible that norBUP contributes to the central effects seen after chronic BUP administration as this study demonstrated its entry into the brain.

Transvaginal sonography combined with saline contrast sonohysterography in evaluating the uterine cavity in premenopausal patients with abnormal uterine bleeding.

OBJECTIVES: To evaluate whether saline contrast sonohysterography (SCSH) adds additional information to that obtained by transvaginal sonography (TVS) for predicting endometrial abnormality in premenopausal patients with abnormal uterine bleeding. PATIENTS AND METHODS: This was a two-center prospective study at a university clinic and a central hospital in Denmark. The uterine cavity was evaluated with TVS and SCSH in 470 premenopausal patients with abnormal uterine bleeding. One hundred and eighty-nine of the patients had operative hysteroscopy or hysterectomy within 4 months which provided a detailed description of the uterine cavity and was used as the true value for exclusion of polyps and submucous myomas. RESULTS: Based on normal endometrial morphology alone, the results for detection of an abnormal uterine cavity were as follows: sensitivities of TVS 0.92, SCSH 0.99; specificities of TVS 0.62, SCSH 0.72; positive predictive values of TVS 0.80, SCSH 0.85; negative predictive values of TVS 0.82, SCSH 0.98. Transvaginal sonography combined with SCSH was superior to TVS for detection of intracavitary abnormalities (McNemar test, P = 0.008). The post-test probability of there being an abnormal cavity after normal findings on TVS alone was 0.18 (0.10-0.32) and after TVS and SCSH it was 0.02 (0.01-0.11). When normal endometrial morphology was combined with an endometrial thickness of < 12 mm for evaluation of all abnormalities including hyperplasia, the diagnostic potential of TVS or SCSH was almost unchanged except for specificities, which were markedly lower (TVS 0.54; SCSH 0.57). In all the patients referred, TVS had a negative predictive value of 0.94 for identification of polyps and myomas when findings at subsequent SCSH were accepted as the true value. Transvaginal sonography reduced the pretest probability of polyps or submucous myomas from 0.35 to a post-test probability of 0.06, but missed 21% of the polyps. CONCLUSIONS: Sonohysterography was a sensitive tool and was superior to TVS used alone for evaluation of the uterine cavity in patients who underwent operative surgery for abnormal uterine bleeding. All abnormalities except one were found at SCSH, while TVS alone missed polyps and had almost one in four equivocal findings. The use of TVS, without saline contrast, left one in five of the polyps undiagnosed in referred patients with abnormal bleeding.

Can the endometrial thickness as measured by trans-vaginal sonography be used to exclude polyps or hyperplasia in pre-menopausal patients with abnormal uterine bleeding?

BACKGROUND: To combine findings of normal mid-line echoes from TVS (trans-vaginal sonography) with cut-off levels for endometrial thickness, in order to examine the associated risk of abnormalities in the uterine cavity. DESIGN AND SETTING: Two center prospective study at a university clinic and a central hospital in Denmark. PARTICIPANTS: Three hundred and fifty-five pre-menopausal patients with abnormal uterine bleeding, and indications for endometrial sampling or surgery. INTERVENTIONS: The thickness of the endometrium was measured, and the mid-line echoes were evaluated using TVS. The findings from the endometrial sampling, combined with the evaluation of the uterine cavity using operative hysteroscopy (115), hysterectomy (74) or HSE (hysterosonographic examination) (166), were used as the true values. RESULTS: The mean (+/-s.d.) endometrial thickness was significantly different in patients with hyperplasia 11.5 mm (+/-5.0), polyps 11.8 mm (+/-5.1), sub-mucous myomas 7.1 mm (+/-3.4) and in patients without these abnormalities 8.37 (+/-3.9) (p<0.001). Hyperplasia and/or polyps were present in 20% of all patients, and in 8% of 143 patients with an endometrial thickness of < or =7 mm. This proportion did not decrease with lower cut-off levels for endometrial thickness. Receiver operating characteristic (ROC) curves were not optimal for excluding hyperplasia or polyps by endometrial thickness. In 173 cases with a distinct, regular midline echo without echo-dense foci in TVS the proportion of patients with abnormalities was 16% (11-23). This proportion did not decrease with cut-off levels for endometrial thickness. CONCLUSIONS: Using TVS, low levels of endometrial thickness reduced the possibility of abnormalities such as polyps and hyperplasia, but did not exclude them. Low cut-off levels for endometrial thickness did not increase the diagnostic performance in cases with normal sonograms.

Effect of oral drenching with zinc oxide or synthetic zeolite A on total blood calcium in dairy cows.

Danish Holstein dairy cows in late lactation and milked in the morning only were used as a model for dry pregnant cows to determine the effect of oral drenching with zeolite A and zinc oxide, respectively, on total serum calcium. Ten cows were assigned randomly to two groups of five cows each, given either synthetic zeolite A (group A) or zinc oxide (group B). Blood samples were drawn daily at 10 a.m. and 10 p.m. during the whole experiment, and total serum calcium was determined. Daily fluctuations in blood calcium were recorded, with morning values being consistently lower than evening values. Oral drenching with a single dose of zinc oxide of 100 mg/kg of body weight as well as with zeolite in doses of 500 g of zeolite/cow twice a day for 2.5 d was reflected in serum calcium levels. In the group given zeolite A, there was a depression in evening values of total serum calcium although the difference did not reach statistical significance. It was followed by an increase above baseline level ("overshooting"). This was interpreted as a response from the calcium homeostatic mechanisms. In the group given a single dose of zinc oxide, a decrease in total serum calcium occurred. This decrease was not followed by overshooting, indicating that the single treatment with zinc oxide did not stimulate the calcium homeostatic mechanisms. The perspective of this first attempt to reduce dry cow ration calcium availability may be seen in relation to difficulties in formulating dry cows rations from home grown forage sufficiently low in calcium to elicit a hypocalcemia protective response at calving.

[Comparison of monolayer specimens and conventional smears]. / Sammenligning af monolagsprøver og konventionelle "smears".

INTRODUCTION: Monolayer specimens were compared with conventional smears in a split sample study. The quality of the specimens, sensitivity, time consumption, and costs were elucidated. METHOD: Conventional smears and fixated residual material from 1701 women were available. RESULTS: The number of inadequate/less adequate specimens was reduced significantly (p < 0.001). Diagnostic agreement was found in 1531 (90%) of the 1701 cases (kappa = 0.52, SE (kappa) = 0.026). Dysplasia (NOS) was diagnosed in seven monolayer specimens (0.4%) versus 33 smears (1.9%) and ratio atypia/low grade was reduced by 33%, which indicates greater accuracy in diagnosis in monolayers. Histological follow-up showed sensitivities of 95% (monolayers) and 94% (smears). The time consumed (laboratory work, screening) on a smear versus a monolayer specimen was 11.5 minutes versus 9.3 minutes. Utensil costs of a smear are kr. 10.69. compared to kr. 26.50 for a monolayer specimen. CONCLUSION: The higher costs should be set against the saving in significantly improved specimen quality, improved diagnostic accuracy, and shorter time consumption. The use of the monolayer technique (direct to vial) is recommended to replace the conventional smear.

[Partial re-screening of all negative smears. A method of quality control of pathology department concerning smear screening against cervix cancer]. / Partiel rescreening af alle negative "smears". En metode til patologiafdelingens kvalitetskontrol af "smear"-screening mod livmoderhalskraeft.

Partial rescreening of all negative smears is recommended as the most cost-effective method of internal quality control. The method was tested by eight cytotechnologists and the average diagnostic sensitivity, assessed upon their answering of 200 test-smears (150 negative and 50 positive) was 80%, while specificity vas calculated to 95%. Partial rescreening has here-upon been used in daily routine. After one year 21,000 smears have been re-screened. Twenty-nine cases of false negatives, 16 with atypia, eight with koilocytosis, and five cases with dysplasia have been detected, which corresponds to an overall false negative rate on 3%. In five of the 29 false negative cases with dysplasia histological follow-up has shown three cases of CIN III (two carcinoma in situ, one severe dysplasia), one case with CIN II (moderate dysplasia) and one case with CIN I (mild dysplasia). Conclusively, partial rescreening of all negative smears implies an improved quality with reduction of the number of false negative specimens.

MIB-1 expression in breast carcinomas with medullary features. An immunohistological study including correlations with p53 and bcl-2.

Typical medullary carcinoma (TMC) is usually considered to have a more favourable prognosis than other types of infiltrating breast carcinomas. This is a biological paradox, since its clinical behaviour is not in agreement with its anaplastic morphology and high mitotic rate. It should be remembered that neoplastic growth reflects cell production minus cell loss, the latter being achieved by apoptosis. At present, bcl-2 oncogene (apoptosis inhibitor) and p53 gene are assumed to be involved in the regulation of cell death and tumour proliferation. Sixty breast carcinomas, initially indexed as medullary carcinomas, were re-classified using the diagnostic criteria given by Ridolfi. This review yielded 13 typical (TMC), 24 atypical (AMC), and 23 non-medullary carcinomas (NMC). Following antigen retrieval by microwave treatment, immunohistochemical analyses, using MIB-1, p53 and bcl-2 monoclonal antibodies were performed on serial sections from formalin-fixed, paraffin-embedded specimens. TMC revealed the highest incidence of intense p53 positivity, and the highest mean MIB-1 index, and absence of the apoptosis-inhibitor protein bcl-2. These results suggest the presence of a higher overall cell turnover in TMC than in AMC and NMC. Increased apoptosis balancing the increased cell proliferation might be among the possible explanations for the more favourable prognosis in TMC.

Prognostic comparison of three classifications for medullary carcinomas of the breast.

The aim of this study was to make prognostic comparisons between the modified scheme of Pedersen et al. the definitions of Tavassoli and the Ridolfi criteria for medullary carcinomas. Sixty breast carcinomas primarily diagnosed as medullary carcinomas were reclassified into typical medullary carcinoma (TMC), atypical medullary carcinoma (AMC) and non-medullary carcinoma (NMC) according to the three classifications. The Ridolfi classification proved to be superior to the two other schemes in discriminating survival differences between the three groups TMC, AMC and NMC. All 13 patients with TMC are still alive indicating an excellent prognosis, while 29% and 39% of the 47 patients in the AMC and NMC category, respectively, have died of their disease. In the simplified system of Pedersen et al. the survival at 10 years for TMC patients decreased to 75% and no significant survival difference between the three groups could be demonstrated. As the prognosis for AMC proved to be worse compared to TMC and in fact was similar to NMC with values of 43% at 10 years in the Ridolfi classification, we find no reasons to maintain this category. We conclude that as long as no alternative and more easily applicable diagnostic method exists, pathologists should still apply the Ridolfi criteria on these tumours with medullary features leaving two diagnostic possibilities: TMC or NMC (i.e. poorly differentiated ductal carcinoma). Only lesions that fulfil all six criteria without any doubt should be diagnosed as TMC, thus avoiding overdiagnosis and a resulting risk of undertreatment.

Inclusion body myositis and transitional cell carcinoma of the bladder: significant resolution of symptoms after tumor excision.

Inclusion body myositis (IBM) is a separate class of the inflammatory myopathies with recently proposed clinical and pathological diagnostic criteria. An association between inflammatory myopathies and malignancy has been questioned in the literature. Recent reviews of the inflammatory myopathies suggest that only dermatomyositis is associated with malignancy. The largest study to date of patients with IBM found that 15% had a malignancy (6 of 40). We report the first documented case of IBM and concurrent transitional cell carcinoma of the bladder. We suggest that a causal relationship between IBM and malignancy may exist because of significantly improved functional strength gained after tumor removal.

Intradermal and subcutaneous leiomyosarcoma: a clinicopathological and immunohistochemical study of 41 cases.

Superficial leiomyosarcomas are rare tumours. The lesions confined to the dermis, contrary to those involving the subcutis, have been reported to carry a favourable prognosis. A retrospective study of 41 consecutive cases of surgically treated intradermal and subcutaneous leiomyosarcomas was undertaken in order to determine the prognostic factors that may influence the survival of these patients. Seven tumours were predominantly intradermal and 34 involved the subcutaneous tissue. Fifty-four percent of the tumours were located in the lower extremities. All cases stained positively for smooth muscle antigen and 66% for desmin. The tumours were classified with regard to tumour grade I (low grade, 3%), II (intermediate, 12%), IIIA (high grade, 46%) and IIIB (high grade, 39%). In all patients, follow-up information was available. Mean follow-up time was 5 years. The patients with intradermal tumours were all alive without signs of recurrence, whereas 14 of those with leiomyosarcomas involving the subcutis have died with pulmonary metastases. Our study confirms that "pure" intradermal leiomyosarcomas independent of tumour grade behave in a benign fashion, probably due to small tumour size. Tumour size > or = 5 cm, deep localization with fascia involvement, and high malignancy grade (IIIB) were found to deteriorate survival based on a univariate analysis. However, in a multivariate analysis only tumour size was found to be an independent prognostic factor.