Pathogenesis of severe acute respiratory syndrome

Severe acute respiratory syndrome (SARS) is a zoonotic infectious disease caused by a novel coronavirus (CoV). The tissue tropism of SARS-CoV includes not only the lung, but also the gastrointestinal tract, kidney and liver. Angiotensin-converting enzyme 2 (ACE2), the C-type lectin CD209L (also known L-SIGN), and DC-SIGN bind SARS-CoV, but ACE2 appears to be the key functional receptor for the virus. There is a prominent innate immune response to SARS-CoV infection, including acute-phase proteins, chemokines, inflammatory cytokines and C-type lectins such as mannose-binding lectin, which plays a protective role against SARS. By contrast there may be a lack of type 1 interferon response. Moreover, lymphopenia with decreased numbers of CD4+ and CD8+ T cells is common during the acute phase. Convalescent patients have IgG-class neutralizing antibodies that recognize amino acids 441-700 of the spike protein (S protein) as the major epitope.     

Automatic measurement of long-term heart rate variability by implanted single-chamber devices

Heart rate variability (HRV) measurement is an established technology for the assessment of cardiac autonomic status. Recently 24 h HRV has been shown to correlate with disease severity in heart failure. This potentially makes continuous 24 h HRV measurement suitable for monitoring of heart-failure patients. Day-to-day 24 h measurement of HRV is, in principle, feasible when implemented using implanted devices (pacemakers and defibrillators) used in patients who are predominantly in the sinus rhythm. However, a number of such devices used in heart-failure patients are single-chamber devices, in which the distinction between sinus rhythm beats and ectopic beats is problematic. The study investigates whether a reasonably accurate 24 h HRV measurement can be achieved by automatic algorithms, suitable for implementation using implanted devices, without the need for identification of ectopic beats. A set of 5321 nominal 24 h Holter recordings of cardiac patients are used. Each of the recordings contains at least one ectopic beat; approximately 30% of the recordings have more than 1% of ectopic beats. Conventional 24 h measures of HRV, that is the SDNN, HRV index, and SDANN indices, are obtained from each recording after elimination of the ectopic beats and are approximated by HRV measures computed by the same formulas without exclusion of the ectopic beats. The SDANN values are also approximated by the standard deviation of 5 min medians of all RR intervals (SDMRR measure). The errors introduced by including the ectopic beats in the HRV computation were evaluated using the Bland-Altman statistics and by Cohen's kappa statistics investigating the precision of identifying patients with depressed and preserved 24 h HRV. The SDNN measure is very sensitive to the quality of the RR interval sequence and cannot be reasonably used without distinction between sinus rhythm and ectopic beats. The HRV index measure is marginally more acceptable when used without ectopic elimination. The SDANN is rather insensitive, and its replacement by SDMRR values leads to relative errors in the region of 2-5% that are almost independent of the number of ectopic beats included. Even in recordings with a substantial proportion of ectopic beats, a practically acceptable (kappa > 0.9) identification of depressed and preserved SDANN values is possible without ectopic elimination. Thus, continuous monitoring of 24 h HRV is technically feasible within implanted devices, provided the SDANN measure is monitored and either computed from the sequence of all RR intervals or, potentially preferably, replaced by the SDMRR measure.     

Massive small bowel infarction and duodenal perforation due to abdominal polyarteritis nodosa: a case report

A 37-year-old Chinese male presented with an acute abdomen. Surgical exploration revealed duodenal perforation, extensive small bowel infarction and peritonitis. Histopathology of the resected bowel showed characteristic features of classic polyarteritis nodosa. The latter also involved mesenteric arteries in the form of tiny aneurysms. Steroids could not be started due to: (i) overwhelming microbial infections and (ii) fear of more perforations in other areas of the bowel. Such a presentation of polyarteritis nodosa is uncommon. Its recognition prior to surgery, management and prognosis is discussed.     

ROLE OF ACULASER THERAPY IN CEREBRAL PALSY CHILDERN （INITIAL DATA ＆ RESULTS）

1　BACKGROUNDTheincidenceofCPis 0 .7per 1 0 0 0livebirths[1 ] .Becausecerebralpalsyinfluencesthewaychildrendevelop,itoftenresultsindevelop mentaldisability .Today ,more peoplehavecerebralpalsythananyotherdevelopmentaldis ability ,includingDownsyndrome,epilepsy ,andautism .Accordingtoasurveyconductedin1 986,2 .6%ofthepopulationofPakistaniaredisabled (includingbothphysicalandmentaldis abilities) .Childrenbetween 0～1 4 yearsinageconstitute 40 %ofthedisabled populationinPakistan .Routineme…     

Serum protein profiles to identify head and neck cancer.

PURPOSE: New and more consistent biomarkers of head and neck squamous cell carcinoma (HNSCC) are needed to improve early detection of disease and to monitor successful patient management. The purpose of this study was to determine whether a new proteomic technology could correctly identify protein expression profiles for cancer in patient serum samples. EXPERIMENTAL DESIGN: Surface-enhanced laser desorption/ionization-time of flight-mass spectrometry ProteinChip system was used to screen for differentially expressed proteins in serum from 99 patients with HNSCC and 102 normal controls. Protein peak clustering and classification analyses of the surface-enhanced laser desorption/ionization spectral data were performed using the Biomarker Wizard and Biomarker Patterns software (version 3.0), respectively (Ciphergen Biosystems, Fremont, CA). RESULTS: Several proteins, with masses ranging from 2778 to 20800 Da, were differentially expressed between HNSCC and the healthy controls. The serum protein expression profiles were used to develop and train a classification and regression tree algorithm, which reliably achieved a sensitivity of 83.3% and a specificity of 100% in discriminating HNSCC from normal controls. CONCLUSIONS: We propose that this technique has potential for the development of a screening test for the detection of HNSCC.     

Pharmacodynamic evaluation of the epidermal growth factor receptor inhibitor OSI-774 in human epidermis of cancer patients.

BACKGROUND: OSI-774 is an inhibitor of the epidermal growth factor receptor tyrosine kinase (EGFR-TK) currently in clinical development. In preclinical models, the antitumor activity of OSI-774 was directly related to its ability to inhibit the EGFR-TK. On the basis of these data, we hypothesized that inhibition of the EGFR-TK will be required for this agent to be effective in the clinic. This study evaluated the pharmacodynamic effects of OSI-774 in normal skin tissues collected from patients treated with the agent in a Phase I study. METHODS: Patients with advanced cancer who were treated in a Phase I study of OSI-774 underwent a biopsy of normal skin epidermis at baseline and after the last dose of drug in the first course of treatment. The expression and activation of the EGFR, downstream signaling extracytoplasmatic-regulated kinase (Erk), and cell cycle regulator p27 were determined in paraffin-embedded skin tissues using an immunohistochemical method (IHC). The IHC data were analyzed using both a semiquantitative scoring system and an automatic absorbance quantitative IHC method. The number of cells with nuclear staining of p27 per 500 cells was determined. Plasma samples were collected to quantitate OSI-774 plasma concentrations. RESULTS: A total of 56 skin specimens was collected from 28 patients treated with OSI-774 at doses ranging from 25 to 200 mg/day. There was a significant decrease in phospho-EGFR (Tyr 1173) expression as determined semiquantitatively with OSI-774 treatment [2.75 +/- 0.51 (mean +/- SD) pretreatment versus 2.36 +/- 0.76 after treatment, pair comparison P = 0.01]. The quantitative ratio [(phopho-EGFR/EGFR) x 100] of phospho-EGFR (Tyr1173) decreased from 64.16 +/- 36.58 pretreatment to 48.87 +/- 35.37 post-treatment (pair comparison, P = 0.02). No significant differences were observed in phospho-Erk (Thr202/Tyr204) expression. The mean number of cells with nuclear staining for p27 increased from 185 +/- 101 (mean +/- SD) pretreatment to 253 +/- 111 post-treatment (pair comparison P = 0.02). A total of 12 (42.8%), 7 (25%), and 14 (50%) patients had >25% variation in the ratio of phospho-EGFR (Tyr1173), phospho-Erk (Thr202/Tyr204), and p27 expression, respectively. Only changes in p27 expression were related to the administered dose of OSI-774. CONCLUSIONS: OSI-774 exerted pharmacodynamic effects in skin tissues of 30-50% of patients treated with the agent. Up-regulation of p27, which is a downstream effect of EGFR inhibition, was dose related. Although there was a significant decrement in phospho-EGFR (Tyr1173), it was not related to the administered dose of OSI-774. On the basis of these findings and the relatively simple and reliable method to measure p27 expression, this biomarker appears to be the most promising and is being evaluated in Phase II studies as a predictor of clinical outcome.