Inter- and intraobserver variability in the histopathological diagnosis of medullary carcinoma of the breast,and its prognostic implications

Summary One hundred thirty-one breast carcinomas with medullary features, registered in the Danish Breast Cancer Cooperative Group from 1977–1982, have been histopathologically reviewed by two senior pathologists and classified as typical medullary carcinoma (TMC), atypical medullary carcinoma (AMC), and non-medullary carcinoma (NMC). Diagnostic criteria were based on those put forward by Ridolfiet al. and Fisheret al. The procedure was repeated with an interval of about one year by both pathologists. The diagnostic interobserver agreement was 72% with a Kappa of 0.55. The intraobserver agreement was 77% and 63% with Kappa values of 0.64 and 0.44, respectively. To see whether the observed inter- and intraobserver variability had any prognostic implications, diagnostic subgroups for both pathologists were analyzed with Kaplan Meier plots for recurrence-free survival (RFS) and with log rank tests. In the first evaluation pathologist 1 segregated a group of TMC with a significantly better RFS than for the NMC group, and pathologist 2 segregated a group of TMC with a corresponding strong trend. These findings could not, however, be reproduced in the second evaluation. The study indicates that the criteria of TMC and AMC as proposed by Ridolfiet al. need to be sharpened and simplified in order to reduce inter-and intraobserver variability. Larger studies with a control group of infiltrating ductal carcinomas are mandatory to elucidate the clinical importance of the diagnoses of Typical and Atypical Medullary Carcinoma of the breast.     

How often do asymptomatic healthcare workers cause methicillin-resistant Staphylococcus aureus outbreaks? A systematic evaluation.

A systematic search was performed to identify outbreaks of methicillin-resistant Staphylococcus aureus infection and colonization caused by healthcare workers (HCWs). Of 191 outbreaks identified, 11 had strong epidemiological evidence that HCWs were the source. In 3 of these outbreaks, asymptomatic carriers were the cause. The frequent practice of screening asymptomatic HCWs should be reconsidered.     

Heart Rate Variability Predicts Severe Hypotension after Spinal Anesthesia for Elective Cesarean Delivery

Background: Hypotension due to vasodilation during subarachnoid block (SAB) for elective cesarean delivery may be harmful. Heart rate variability (HRV), reflecting autonomic control, may identify patients at risk of hypotension.

Methods: Retrospectively, HRV was analyzed in 41 patients who were classified into one of three groups depending on the decrease in systolic blood pressure (SBP): mild (SBP > 100 mmHg), moderate (100 > SBP > 80 mmHg), or severe (SBP < 80 mmHg). Prospectively, HRV and hemodynamic data of 19 patients were studied. Relative low frequency (LF), relative high frequency (HF), and LF/HF ratio were analyzed.

Results: Retrospective analysis of HRV showed a significantly higher sympathetic and lower parasympathetic drive in the groups with moderate and severe compared with mild hypotension before SAB (median, 25th/75th percentiles): LF/HF: mild: 1.2 (0.9/1.8), moderate: 2.8 (1.8/4.6), P < 0.05 versus mild; severe: 2.7 (2.0/3.5), P < 0.05 versus mild. Results were confirmed by findings of LF and HF. Prospectively, patients were grouped according to LF/HF before SAB: low-LF/HF: 1.5 (1.1/2.0) versus high-LF/HF: 4.0 (2.8/4.7), P < 0.05; low-LF: 58 +/- 9% versus high-LF: 75 +/- 10%, P < 0.05; low-HF: 41 +/- 10% versus high-HF: 25 +/- 10%, P < 0.05. High-risk patients had a significantly lower SBP after SAB (76 +/- 21 vs. 111 +/- 12 mmHg; P < 0.05).     

Intra-operative quick insulin assay to confirm complete resection of insulinomas guided by selective arterial calcium injection (SACI)

Background and aims Insulinomas are rare endocrine disorders. Pre-operatively, conventional imaging techniques often fail to localise the tumor. In addition, due to the lack of quick insulin assays, intra-operative confirmation of complete resection was impossible until recently. Materials and methods Six patients with biochemical evidence of an insulinoma underwent pre-operative localisation studies and selective arterial calcium injection (SACI). In addition, insulin was measured before surgery and every 10–15 min after resection of the tumor using a quick insulin assay. Results Pre-operative localisation studies identified the tumor correctly as follows: endosonography: three of four, magnetic resonance imaging: two of four and SACI: six of six. Tumors in the head and body were enucleated while those in the tail were resected (n = 2, each). Those three patients, in whom magnetic resonance imaging and/or endosonography could localise the tumors pre-operatively, underwent laparoscopic surgery while the remaining three patients underwent open surgery. Intra-operatively, insulin dropped to normal levels within 20 min in all cases. After a follow-up of 0.8–3 years, all patients remained biochemically cured. Conclusions Pre-operatively, SACI appears to be a very sensitive localisation technique and may be most helpful in guiding the surgeon if conventional imaging techniques fail to localise the tumor. Complete removal of an insulinoma can be reliably predicted using a quick insulin assay. This paper was presented at the 2nd Biennial Meeting of the European Society of Endocrine Surgeons (ESES), May 18–20, 2006, Krakow, Poland.     

Exanthematous infantile psoriasis

Childhood psoriasis is a disease with manifold clinical presentations which can make the correct diagnosis sometimes difficult. In a female infant, slightly itching, erythematous papules and plaques with discrete scaling spread over large parts of the integument starting from age three months. Histological examination supported the diagnosis of exanthematous infantile psoriasis. Topical treatment with dithranol in petrolatum led to slow clearance of the skin lesions.     

Tacrolimus versus cyclosporine induction therapy in pulmonary transplantation in miniature swine.

OBJECTIVE: Tacrolimus has been shown to provide superior immunosuppression in various solid organ transplant settings. The purpose of our study was to compare the survival of porcine lung allografts after induction with either cyclosporine A (CsA) or tacrolimus. METHODS: Single lung transplantation from MHC mismatched donors was performed in 10 minipigs. Immunosuppression included 1.5 mg/kg per day methylprednisolone and 1.0 mg/kg per day azathioprine. CsA (n=5) was adjusted to trough levels of 300-500 ng/ml, tacrolimus (n=5) was adjusted to 16-26 ng/ml. All immunosuppressive drugs were discontinued on postoperative day (POD) 28. Allograft survival was monitored by sequential chest radiographs, bronchoscopy and transbronchial biopsy histology. Peripheral blood leukocytes were scanned for donor chimerism and CD3, CD4, CD8 and CD25 expression. RESULTS: The animals survived a 4-week course of immunosuppression without radiological or histological signs of rejection on POD 28. Median allograft survival in CsA-treated animals was 55+/-15 days and all animals rejected their grafts within 42 days after withdrawal of immunosuppression. In tacrolimus-treated animals, median survival was 152+/-65 days with the longest survivor being electively sacrificed on POD 390 (P=0.0064). The degree of donor leukocyte chimerism and the frequency of CD4+CD25+ T-cells were higher in the tacrolimus group, however, these differences were not statistically significant. CONCLUSION: The results of our study show that primary immunosuppression with tacrolimus is superior to cyclosporine after pulmonary allotransplantation in a large animal model.     

Response-time corrected averaging of event-related potentials.

OBJECTIVE: The present study presents a novel approach to averaging of event-related potentials (ERPs). Acknowledging latency variability of late ERP components as related to performance fluctuations across trials should improve the assessment of late portions of the ERP. METHODS: Prior to the averaging procedure stimulus-to-response epochs in the electroencephalogram (EEG) were expanded/compressed in time to match mean RT in a certain condition and participant. By means of several mathematical functions RT variability was differentially distributed over late vs. early portions of the ERP. Data from 20 participants from two conditions of an identity-based priming task were analyzed using traditional stimulus- and response-locked averaging, as well as four different RT-corrected averaging procedures. RESULTS: Area under the curve as an index of precision of LPC assessment was reliably enhanced for certain RT-corrected procedures relative to traditional ERP averaging. Moreover, a priming effect on amplitude of a distinct LPC subcomponent which could not be confirmed with traditional stimulus-locked averaging was reliably born out using a cubic RT-correction procedure. CONCLUSIONS: RT-corrected ERP averaging can outperform traditional ERP averaging in the assessment of late portions of the ERP, and experimental effects upon. SIGNIFICANCE: Cognitive ERP researchers may take advantage of the improved capability of RT-corrected averaging to establish experimental effects on amplitudes in the late ERP range.     

Intra-observer and inter-observer agreement of the manual examination of the lumbar spine in chronic low-back pain

Examination is a cornerstone in the manual procedures leading to mobilisation/manipulation of the low back. The observer variation of the more specific segmental tests remains to be investigated. Two skilled specialists in manual medicine examined the segmental changes in the lumbar spine. The patients were unknown to the examiners and no information of the case history was given. All test results were recorded by an observer present in the room who ensured that no conversation was allowed during the examination. The primary outcome measures were the kappa values for each test. The matching was defined as acceptable (acc) within two neighbouring levels and perfect (per) on the same level. Intra-observer variation (tested in 33 patients and 10 subjects without low-back pain): The agreement between first and second segmental diagnosis examination was 70% (per) and 82% (per + acc). Kappa values were: segmental diagnosis 0.60 (per) and 0.70 (per + acc), multifidus test 0.51 (per) and 0.60 (per + acc), sideflexion 0.57 (per) and 0.69 (per + acc), and ventral flexion 0.31 (per) and 0.45 (per + acc). Inter-observer variation (tested in 60 patients): The agreement for segmental diagnosis between the examiner A and B was 42% (per) and 75% (per + acc). Kappa values were: segmental diagnosis 0.21 (per) and 0.57 (acc), multifidus test 0.12 (per) and 0.48 (acc), sideflexion 0.22 (per) and 0.45 (acc), and ventralflexion 0.22 (per) and 0.44 (acc). By manual tests, skilled examiners seem to be able to diagnose segmental dysfunctions in the low back. The clinical implication of these dysfunctions remains to be clarified.     

In vivo gene transfer: focus on the kidney

Renal gene transfer techniques are being developed as a novelexperimental approach to understand the pathogenesis of renaldisease and to potentially develop new therapeutic tools. Wereview the currently available technology to introduce foreigngenetic material into renal tissue, i.e., retroviral, adenoviral,and liposomal transfer systems with their respective advantagesand caveats. Today, the transfer efficiency of these methodsappears to be sufficiently high to study the effects of transducedgenes on renal function and morphology in rat kidney. This willallow (i) the elucidation of the function of genes on the courseof renal disease in experimental animal models and (ii) themodulation of local expression of endogenous genes which presumptivelycontribute to renal pathology in these models. One strategyto accomplish this aim is the use of recombinant DNA technologyto design antisense DNA constructs or oligonucleotides, whichinterfere with the renal expression of target genes. We willalso discuss some of the shortcomings of the currently usedtechniques with respect to potential therapeutic use of genetransfer systems and gene modulation.