Ovine forestomach matrix biomaterial is a broad spectrum inhibitor of matrix metalloproteinases and neutrophil elastase

Proteases play a critical role in the ordered remodelling of extracellular matrix (ECM) components during wound healing and tissue regeneration. However, the usually ordered proteolysis is compromised in chronic wounds due to over‐expression and high concentrations of matrix metalloproteinase's (MMPs) and neutrophil elastase (NE). Ovine forestomach matrix (OFM) is a decellularised extracellular matrix‐based biomaterial developed for tissue regeneration applications, including the treatment of chronic wounds, and is a heterogeneous mixture of ECM proteins and proteoglycans that retains the native structural and functional characteristics of tissue ECM. Given the diverse molecular species present in OFM, we hypothesised that OFM may contain components or fragments that inhibit MMP and NE activity. An extract of OFM was shown to be a potent inhibitor of a range of tissue MMPs (IC₅₀s = 23 ± 5 to 115 ± 14 µg/ml) and NE (IC₅₀ = 157 ± 37 µg/ml), and was more potent than extracts prepared from a known protease modulating wound dressing. The broad spectrum activity of OFM against different classes of MMPs (i.e. collagenases, gelatinases and stromelysins) may provide a clinical advantage by more effectively addressing the protease imbalance seen in chronic wounds.     

Capillary transit time heterogeneity and flow-metabolism coupling after traumatic brain injury

Most patients who die after traumatic brain injury (TBI) show evidence of ischemic brain damage. Nevertheless, it has proven difficult to demonstrate cerebral ischemia in TBI patients. After TBI, both global and localized changes in cerebral blood flow (CBF) are observed, depending on the extent of diffuse brain swelling and the size and location of contusions and hematoma. These changes vary considerably over time, with most TBI patients showing reduced CBF during the first 12 hours after injury, then hyperperfusion, and in some patients vasospasms before CBF eventually normalizes. This apparent neurovascular uncoupling has been ascribed to mitochondrial dysfunction, hindered oxygen diffusion into tissue, or microthrombosis. Capillary compression by astrocytic endfeet swelling is observed in biopsies acquired from TBI patients. In animal models, elevated intracranial pressure compresses capillaries, causing redistribution of capillary flows into patterns argued to cause functional shunting of oxygenated blood through the capillary bed. We used a biophysical model of oxygen transport in tissue to examine how capillary flow disturbances may contribute to the profound changes in CBF after TBI. The analysis suggests that elevated capillary transit time heterogeneity can cause critical reductions in oxygen availability in the absence of ‘classic'' ischemia. We discuss diagnostic and therapeutic consequences of these predictions.     

The effect of hormone replacement therapy on bone mass in patients with ovarian failure due to bone marrow transplantation

Long permanent remissions in malignant hematopoietic disorders can often be achieved by autologous bone marrow transplantation (ABMT) or by allogenic bone marrow transplantation (BMT). Previous studies have shown that such therapies may induce osteoporosis due to iatrogenic ovarian failure. The administration of hormone replacement therapy (HRT) in these women could prevent the adverse effects of long-term ovarian failure without remarkable side effects. The aim of this study was to evaluate how the bone mass is affected by HRT in patients undergoing ABMT or BMT adjusting the results for age, weight, and height. Subjects and methods: Thirteen women with previous ABMT/BMT were treated with a standard dose (0.625 mg/day) of conjugated equine estrogen (CEE) or with 50 μg/day of 17-β-estradiol in transdermal therapeutic systems (TTS) plus 5 mg/day of medroxyprogesterone acetate sequentially added to the last 12 days of estrogen therapy. Bone mass was measured prior to and 12 months following HRT. Blood samples were collected before therapy and during the 6th and 12th treatment months. Results: The mean time elapsed between bone transplantation and HRT initiation was 13.0 months (range 3–26 months). Before treatment nine patients were osteopenic and after HRT bone mass increased in all cases. Following ABMT/BMT, hepatic hyperenzymemia was detected in three patients. After 6 and 12 months of treatment no significant changes were observed in hepatic enzymes. Conclusion: Although hepatic hyperenzymemia is commonly considered as a contraindication for HRT, our results suggest that HRT is safe for these patients and that such therapy should be initiated after transplantation in women to prevent adverse effects of long-term ovarian failure.     

The clinical and pathological characteristics of Chinese patients with pauci-immune crescent golmerulonephritis

Objective　To investigate the clinical and pathological characteristics of pauci-immune crescent glomerulo～nephritis (PICGN) in Chinese patients. Methods　During 13 years (1985-1998), 6400 patients underwent non-transplanting renal biopsy. Twenty-four patients were diagnosed as PICGN. All clinical and laboratory data of these patients were collected from the patients’ records and used for detailed analysis. The diagnosis is based on clinico-pathologic findings. Results　Of the 24 patients, 16 were females and 8 were males, with median age of 33 years (ranged 10-76 years). Microscopic polyarteritis (MPA) (33.3%) and systemic vasculitis (8.3%) were the secondary diseases. The incidence of PICGN was 0.38% in renal biopsies and 22.9% in crescentic glomerulonephritis. Clinically, most patients (75.0%) showed rapidly progressive nephritis with enlarged kidneys. At onset, gross hematuria was noted in 58.3% of patients, hypertension in 45.8%, nephrotic syndrome in 41.7%, and oliguria in 25.0%. However, systemic symptoms were rare except for anemia. Pathologically, necrosis of glomerular capillaries (62.5%), infiltration of monocytes and neutrophil cells in glomeruli (66.7%), and vasculitis in the interstitium (53.3%) were observed. In addition, glomerulosclerosis was noted in 45.8%, severe tubular atrophy in 83.3% and interstitial fibrosis in 75.0%. Anti-neutrophil cytoplasmic antibodies (ANCAs) were positive in 52.2%. All patients except two received intensively immunosuppressive therapy. Sixteen patients were available for long-term follow up (median 29.8 months, range 8-92 months). Twelve of them had life-sustaining renal function, four had normal serum creatinine (<124?μmol/L) and only 4 patients were dialysis-dependent. Conclusion　PICGN is not rare in China. Early diagnosis and administration of immunosuppressive therapy, particularly in patients with rapidly progressive glomerulonephritis (RPGN), are important for good prognosis.     

Second‐look endoscopy with thermal coagulation or injections for peptic ulcer bleeding: A meta‐analysis

Background and Aims: In the management of peptic ulcer bleeding, the benefits of second‐look endoscopic treatment with thermal coagulation or injections in controlling recurrent bleeding is unsure. This study set out to compare efficacy of routine second‐look endoscopy with treatment using either thermal coagulation or injections versus single endoscopy by pooling data from published work. Methods: Full publications in the English‐language published work as well as abstracts in major international conferences were searched over the past 10 years, and six trials fulfilling the search criteria were found. Outcome measurements included: (i) recurrent bleeding; (ii) requirement of surgical intervention; and (iii) mortality. We examined heterogeneity of trials and pooled the effects by meta‐analysis. The quality of studies was graded according to the prospective randomization, methods of patient allocation, the list of exclusion criteria, outcome definitions and the predefined salvage procedures for uncontrolled bleeding. Results: Among 998 patients recruited in these five randomized trials, 119 received routine second‐look endoscopy with thermal coagulation, and 374 received second‐look with endoscopic injection and 505 had single endoscopic therapy. Less recurrent bleeding was reported after thermal coagulation (4.2%) than single endoscopy (15.7%) (relative risk [RR] = 0.29; 95% confidence interval [CI] = 0.11–0.73), but no reduction was reported for the requirement of surgical intervention and all‐cause mortality. Injection therapy did not reduce re‐bleeding (17.6%) when compared to single endoscopy (20.8%; RR = 0.85; 95% CI = 0.63–1.14), requirement for surgery and mortality. Conclusion: Routine second‐look endoscopy with thermal coagulation, but not injection therapy, reduced recurrent peptic ulcer bleeding. There is no proven benefit in reducing surgical intervention and overall mortality.     

穴位注射治疗尖锐湿疣及对免疫功能的影响

目的：探讨穴位注射治疗CA的临床疗效及对CA患者免疫功能的影响。方法：149例患者随机分为治疗组（A组）、药物对照组（B组）和空白对照组（C组）。运用激光治疗消除疣体后，A组用卡介菌多糖核酸穴位注射，B组用卡介菌多糖核酸肌肉注射，C组仅行激光消除疣体治疗。分别于治疗前及6个月以后检测患者细胞免疫功能。另设健康人对照组40例，检测项目同上。结果：治疗前与健康人相比，CA患者CD4^＋百分率降低，CD8^＋百分率升高，CD4^＋／CD8^＋比值降低，NK细胞活性降低（P〈0．05或P〈0．01）。运用穴位注射卡介菌多糖核酸治疗后，治疗组CD4^＋百分率升高，CD8^＋百分率降低，CD4^＋／CD8^＋比值升高，NK细胞活性升高（P〈0．05或P〈0．01）。结论：穴位注射卡介菌多糖核酸疗法对CA的T淋巴细胞亚群、自然杀伤（NK）细胞有良性调节作用；可明显降低尖锐湿疣复发率，提高细胞免疫调节作用，是防止尖锐湿疣复发的机制之一。     

Anti-neutrophil cytoplasmic antibodies in Japanese children with ulcerative colitis

Objective: To investigate the diagnostic value of anti-neutrophil cytoplasmic antibodies (ANCA) in the diagnosis of ulcerative colitis (UC) in Japanese children.
Methodology Serum samples from 23 children with UC (17 Japanese, 6 non-Japanese), 27 children with Crohn's disease (CD) (10 Japanese, 17 non-Japanese), 10 children with other diarrhoeal diseases, and 33 normal, healthy adult volunteers were assayed for ANCA using an indirect immunofluorescence technique.
Results ANCA were detected in 6/17 (35%) UC patients and 0/10 (0%) CD patients in Japanese children, and in 3/6 (50%) UC patients and 3/17 (18%) CD patients in non-Japanese children. The difference in prevalence between Japanese and non-Japanese children with UC was not statistically significant ( P >0.05). ANCA were not found in other diarrhoeal patients and volunteers.
Conclusions Although ANCA have been reported to be useful in the diagnosis of UC in adults, they may be of limited use in Japanese children. This might reflect the heterogeneity of UC.     

Discordant pursuit asymmetry and esotropia in monozygous twins

PURPOSE: To report the relationship between infantile esotropia and asymmetry of monocular pursuit tracking. DESIGN: Observational family case series. METHODS: A twin pair discordant for infantile esotropia was confirmed by DNA analysis to be monozygous at 99.95% probability. Digitally sampled electro-oculographic recordings of monocular horizontal pursuit eye movements were performed for the twins and their orthophoric father. RESULTS: Mean directional asymmetry for right and left eyes was 31% and 5% for the esotropic twin, 10% and 8% for the orthophoric twin, and 5% and 6% for the father. The asymmetry was statistically significant only for the deviating right eye of the esotropic twin (P = 0.0217). CONCLUSION: In this family, monocular pursuit asymmetry is probably not a heritable predisposition to infantile esotropia, but a consequence of early strabismus. Discordance of infantile esotropia and pursuit asymmetry in monozygous twins implicates environmental in addition to genetic causes.     

Red cell adenylate kinase deficiency: molecular study of 3 new mutations (118G>A, 190G>A,and GAC deletion) associated with hereditary nonspherocytic hemolytic anemia

We report here 2 patients with chronic nonspherocytic hemolytic anemia (CNSHA) and severe red blood cell (RBC) adenylate kinase (AK) deficiency. One of these patients, a boy of Spanish origin, exhibited a neonatal icterus and splenomegaly and required blood transfusions until the age of 2 years. The other patient was a white, American infant born to parents who were first cousins; he also presented with neonatal icterus and anemia. In neither case was psychomotor impairment observed. The first patient was found to be a compound heterozygote for 2 different missense mutations, 118G>A(Gly40Arg) and 190G>A(Gly64Arg) (cDNA sequence first described by Matsuura et al, 1989). The second patient was homozygous for an in-frame deletion (GAC) from nucleotide (nt) 498 to 500 or nt 501 to 503 of the cDNA sequence, predicting deletion of either aspartic acid (Asp) 140 or 141. The crystal structure of porcine cytosolic AK was used as a molecular model to investigate how these mutations may affect enzyme structure and function.