延胡索对缺血再灌注损伤大鼠局灶性脑梗死的作用

目的：探讨延胡索对局灶性脑梗死的作用。方法：总共有30只Sprague-Dawley(SD)大鼠被用来研究。局灶性脑梗死动物模型的建立是将两侧的颈总动脉和右侧的中大脑动脉的血流阻断90min后,再经24h的灌注,然后评估它们的神经状态,大鼠被牺牲取脑,并作成切片用2,3,5-triphenyl-tetrazolium chloride染色。以神经的状态和脑梗死面积的变化作为指标来评估延胡索对脑梗死的作用。另外,24只SD大鼠腹腔注射延胡索,经24h后从心脏采血测量血液的变化。结果：延胡索100mg/kg腹腔注射能够改善大鼠神经缺损的症状和减少脑梗死的面积以及能增加全血中红血球的数目和提高血比容（hematocrit)。结论：延胡索在缺血再灌流损伤大鼠能改善神经状态和减少脑梗死面积。     

The cytotoxic effect of neonatal lupus erythematosus and maternal sera on keratinocyte cultures is complement-dependent and can be augmented by ultraviolet irradiation

Summary To elucidate the role of autoantibodies and ultraviolet (UV) exposure in the pathogenesis of the skin lesions in neonatal lupus erythematostis (NLE). keratinocytes were cultured, as the target cells, from a patient with NLE and from a normal neonate. We demonstrated that the expression of nuclear/cytoplasmic Ro/SSA and La/SSB molecules on to the surface of NLE keratinocytes occurred to a much greater extent than that on normal keratinocytes. A dose of 200 ml/cm² UVB irradiation on NLE keratinocytes induced a 2.5–3-fold increase in Ro/SSA and La/SSB expression compared to non-irradiated cells. Sera derived from both the NLE patient and from his mother exhibited a cytotoxie effect on NLE keratinocytes, but not on control cells, in the presence of complement. Furthermore, the cytotoxieity of the sera was enhanced on UVB-irradiated NLE keratinocytes. whereas it had no cytotoxie efects on UVB-irradiated control cells. This suggests that the abnormal expression of both Ro/SSA and La/SSB on the surface membrane of NLE keratinocytes induces the autoantibodies and complements to injure the cells. This complement-mediated cytotoxic effect can be augmented by UV irradiation, a concept not incompatible with the exacerbation of the skin eruption in sun-exposed skin sites.     

Clinico-pathological correlates in IgA nephropathy

Summary: There were 2758 biopsies of glomerulonephritis diagnosed in the Department of Pathology in the 20 years from 1976 to 1995. Of these 1893 (76.1%) were of primary glomerulonephritis while 577 (23.2%) were of secondary glomerulonephritis. Immunofluorescence studies were available in 1494 (80%) cases. Predominantly mesangial IgA staining was seen in 49.1% of cases, thus identifying them as IgA nephropathy. Mesangial glomerulonephritis was found in 79.1% of cases whilst 17.7% had sclerotic lesions either focal or global. One hundred and fifty-one patients were followed up. Of these, 98 (65%) were detected through health screening while 53 (35%) presented with symptoms. Uncontrolled hypertension, proteinuria of more than 2 g, the presence of crescents and glomerulosclerosis on biopsy were unfavourable prognostic factors. Hypertensive patients also had a higher incidence of medial hyperplasia of the blood vessels. However IgA nephropathy is a benign disease with a cumulative renal survival of 91% after 6 years.     

Therapeutic effect of transurethral needle ablation in non-bacterial prostatitis: Chronic pelvic pain syndrome type IIIa

AIM: Non-bacterial prostatitis is difficult to manage with conventional treatment. This study was undertaken to evaluate the therapeutic effect of transurethral needle ablation (TUNA) on men with chronic inflammatory non-bacterial prostatitis. METHODS: Thirty-two patients with non-bacterial prostatitis (type IIIa) were treated with TUNA. The TUNA procedure, which uses radiofrequency energy, heats the prostate tissue to approximately 90-110 degrees C over a 5-min period. Evaluation consisted of a prostatitis symptom severity score chart, the monitoring of the leukocyte count in the expressed prostatic secretion (EPS) and a subjective global assessment. RESULTS: The decrease in the prostate symptom severity score chart at 3 and 6 months compared with the baseline assessment was statistically significant. Analysis of the leukocyte levels in the EPS in 14 patients was available. All 14 patients had a decrease in the EPS leukocyte count 3 months after treatment. However, six of these men (43%) still had EPS leukocyte levels above the normal indices (>10 white blood cells per high-power field). A second session of TUNA on these partial responders resulted in three of the six men obtaining a normal EPS leukocyte count. At 6 months following treatment, complete, partial and poor improvement in terms of subjective global assessment were noted in 60, 35 and 5% of patients, respectively. No major complications, including those of sexual dysfunction or retrograde ejaculation, were noted in this cohort. CONCLUSIONS: Transurethral needle ablation appears to be an easy, safe and effective treatment for men with chronic inflammatory non-bacterial prostatitis.     

Molecular characterization of hepatitis B virus surface antigen mutants in Singapore patients with hepatocellular carcinoma and hepatitis B virus carriers negative for HBsAg but positive for anti‐HBs and anti‐HBc

Background and Aims : Mutations on the a‐determinant of hepatitis B virus surface antigen (HBsAg), capable of escaping detection and vaccination, are identified in HBsAg‐positive/anti‐HBs‐positive vaccinated infants. We studied the prevalence of these mutants in HBsAg‐negative/anti‐HBc‐positive chronic HBV carriers and patients with hepatocellular carcinoma (HCC). Methods : DNA sequence coding for the antigenic a‐determinant of HBsAg was amplified from either HCC genomic DNA or serum samples of the selected patients and sequenced. The replicative mutant genomes were reconstituted in vitro and their reactivity to commercial kits measured. Results : Mutations within and/or outside the a‐determinant were identified in patients seronegative for HBsAg. They were then reconstituted in vitro and transiently transfected into HepG2 cells. Culture medium containing secreted HBV viral particles was collected and assayed for their binding to commercial kits. Drastic decrease of reactivity to these kits was seen with most of the identified mutations, including those located outside the a‐determinant. Conclusion : The existence of a more complex antigenic structure of HBsAg is indicated by the decreased reactivity to detection of mutations, some of which are outside the a‐determinant, escape vaccination and may persist in seronegative patients. The high proportion of HBsAg mutants that are integrated in HCC genomes suggests a role of these mutants in hepatocarcinogenesis, possibly leading to mutant HBV‐related HCC. © 2002 Blackwell Publishing Asia Pty Ltd     

Bilateral zosteriform extragenital lichen sclerosus et atrophicus: A new clinical presentation

We report a 13‐year‐old female child with sequentially occurring lesions of extragenital zosteriform lichen sclerosus et atrophicus (LSA). The skin lesions first appeared at the right waist when she was 8 years and gradually extended inferiorly and medially along the dermatome of the right L1–2. Subsequently, another skin lesion occurred along the dermatome of the left L5–S1 from the left buttock to left dorsum of the foot in the following 5 years. Microscopic findings obtained from the right inguinal sclerotic plaque revealed typical features of LSA. We report the first case of bilateral zosteriform LSA and remind clinicians of including lichen sclerosus in the differential diagnoses of cutaneous zosteriform lesions.     

Digital Signal Processing Chip Implementation for Detection and Analysis of Intracardiac Electrograms

The adoption of digital signal processing (DSP) microchips for detection and analysis of electrocardiographic signals offers a means for increased computational speed and the opportunity for design of customized architecture to address real-time requirements. A system using the Motorola 56001 DSP chip has been designed to realize cycle-by-cycle detection (triggering) and waveform analysis using a time-domain template matching technique, correlation waveform analysis (CWA). The system digitally samples an electrocardiographic signal at 1000 Hz, incorporates an adaptive trigger for detection of cardiac events, and classifies each waveform as normal or abnormal. Ten paired sets of single-chamber bipolar intracardiac electrograms (1–500 Hz) were processed with each pair containing a sinus rhythm (SR) passage and a corresponding arrhythmia segment from the same patient. Four of ten paired sets contained intraatrial electrograms that exhibited retrograde atrial conduction during ventricular pacing; the remaining six paired sets of intraventricular electrograms consisted of either ventricular tachycardia (4) or paced ventricular rhythm (2). Of 2,978 depolarizations in the test set, the adaptive trigger failed to detect 6 (99.8% detection sensitivity) and had 11 false triggers (99.6% specificity). Using patient dependent thresholds for CWA to classify waveforms, the program correctly identified 1,175 of 1,197 (98.2% specificity) sinus rhythm depolarizations and 1,771 of 1.781 (99.4% sensitivity) abnormal depolarizations. From the results, the algorithm appears to hold potential for applications such as realtime monitoring of electrophysiology studies or detection and classification of tachycardias in implantable antitachycardia devices.     

Impact of Filtering Upon Ventricular Tachycardia Identification by Correlation Waveform Analysis

Signal analysis of digitized waveforms has been postulated as a method for improving sensitivity and specificity of ventricular tachycardia (VTJ detection in implantable antitachycardia devices. Such improvement may alleviate the problem of unwarranted delivery of therapy by adding precision to the identification of the pathological VT. Morphological analysis could also allow distinct therapies to be initialized for multiple VTs in the same patient. Correlation waveform analysis (CWA) has been demon-struted to be effective in separating benign rhythms from VT in wideband recordings (1–500 Hz) but the effect of filtering has not been previously examined. Bipolar (1 cm) intraventricular recordings (1–500 Hz) of sinus rhythm (SR) and 25 distinct VTs in 18 patients were analyzed by CWA using a signal-averaged SR template. Passages contained 65.9 ± 19.8 VT depolarizations (range 45–108). Digital filtering was performed on all data passages with varying passbands. Results for passages with a bandwidth of 1–250 Hz were equivalent to wideband results, i.e., ≥92% paired sets of SR and VT were separable at a 95% confidence level. A bandwidth of 1–100 Hz decreased discrimination to 84%. At a bandwidth of 1–80 Hz, 80% of cases were successfully separated, but at 10–80 Hz these results improved to 88%. Bandwidths of 20–80 and 30–80 Hz reduced reliability of CWA performance to 72% and 60%, respectively. Filtering at typical pace-maker/defibrillator passbands produced morphological analysis results equivalent to those yielded at wideband settings. Differences in the range between SR versus VT decreased in filtered recordings but overall detection of VT was not degraded.     

Drug‐resistant tuberculosis: Past,present, future

In a population of Mycobacterium tuberculosis, random chromosomal mutation that results in genetic resistance to anti‐tuberculosis (TB) drugs occurs at a relatively low frequency. Anti‐TB drugs impose selection pressure so that mycobacterial mutants gradually outnumber susceptible bacilli and emerge as the dominant strains. Resistance to two or more anti‐TB drugs represents cumulative results of sequential mutation. The fourth report on global anti‐TB drug resistance provides the latest data on the extent of such problem in the world. The median prevalence of multi‐drug‐resistant TB (MDR‐TB) in new TB cases was 1.6%, and in previously treated TB cases 11.7%. Of the half a million MDR‐TB cases estimated to have emerged in 2006, 50% were in China and India. The optimal duration of any given combination of anti‐TB drugs for treatment of MDR‐ and extensively drug‐resistant TB (XDR‐TB) has not been defined in controlled clinical trials. Standardized treatment may be feasible for MDR‐TB patients not previously treated with second‐line drugs, but a different strategy needs to be applied in the treatment of MDR‐TB patients who have received second‐line drugs before. Unfortunately, the reliability of drug susceptibility testing of most second‐line anti‐TB drugs is still questionable. Drug‐resistant TB is not necessarily less virulent. Findings from modelling exercise warned that if MDR‐TB case detection and treatment rates increase to the World Health Organization target of 70%, without simultaneously increasing MDR‐TB cure rates, XDR‐TB prevalence could increase exponentially. Prevention of development of drug resistance must be accorded the top priority in the era of MDR‐/XDR‐TB.     

Bluetongue Virus and Double-Stranded RNA Increase Human Vascular Permeability: Role of p38 MAPK

Endothelial cell (EC) involvement in viral hemorrhagic fevers has been clearly established. However, virally activated mechanisms leading to endothelial activation and dysfunction are not well understood. Several different potential mechanisms such as direct viral infection, alterations in procoagulant/anticoagulant balance, and increased cytokine production have been suggested. We utilized a model of EC barrier dysfunction and vascular endothelial leakage to explore the effect of bluetongue virus (BTV), a hemorrhagic fever virus of ruminants, on human lung endothelial cell barrier properties. Infection of human lung EC with BTV induced a significant and dose-dependent decrease in trans-endothelial electrical resistance (TER). Furthermore, decreases in TER occurred in conjunction with cytoskeletal rearrangement, suggesting a direct mechanism for viral infection-mediated endothelial barrier disruption. Interestingly, double-stranded RNA (dsRNA) mimicked the effects of BTV on endothelial barrier properties. Both BTV- and dsRNA-induced endothelial barrier dysfunction was blocked by treatment with a pharmacological inhibitor of p38 MAPK. The induction of vascular permeability by dsRNA treatment or BTV infection was concomitent with induction of inflammatory cytokines. Taken together, our data suggest that the presence of dsRNA during viral infections and subsequent activation of p38 MAPK is a potential molecular pathway for viral induction of hemorrhagic fevers. Collectively, our data suggest that inhibition of p38 MAPK may be a possible therapeutic approach to alter viral-induced acute hemorrhagic diseases.