Local overexpression of TIMP-1 prevents aortic aneurysm degeneration and rupture in a rat model

Although matrix metalloproteinases (MMPs) are expressed in abundance in arterial aneurysms, their contribution to arterial wall degeneration, dilation, and rupture has not been determined. We investigated MMP function in a rat model of aneurysm associated with arterial dilation, elastin loss, medial invasion by mononuclear inflammatory cells, and MMP upregulation. Rupture was correlated with increased gelatinase B (MMP-9) and activated gelatinase A (MMP-2). Syngeneic rat smooth muscle cells retrovirally transfected with tissue inhibitor of matrix metalloproteinases (TIMP)-1 cDNA (LTSN) or with the vector alone as a control (LXSN) were seeded onto the luminal surface of the vessels. The seeding of LTSN cells resulted in TIMP-1 local overexpression. The seeding with LTSN cells, but not LXSN cells, decreased MMP-9, activated MMP-2 and 28-kD caseinase and elastase activity, preserved elastin in the media, and prevented aneurysmal degeneration and rupture. We conclude that MMP overexpression is responsible for aneurysmal degeneration and rupture in this rat model and that local pharmacological blockade might be a reasonable strategy for controlling the formation of aneurysms in humans.     

Retinal tears 180 degrees and greater. Management with vitrectomy and intravitreal gas

A new technique for the treatment of giant retinal dialysis of 180 degrees or more has been devised. After the lens and vitreous have been removed via the pars plana, the patient is rotated into a prone position on a special operating table. The retina is unfolded by filling the eye completely with gas and is held in place by gas. The patient is then brought back into the normal supine position, and a scleral encircling procedure is added. The initial success rate of reattachment is 12 out of 14 cases. Afterward, many eyes develop massive periretinal proliferation. After six months or more of follow-up, the retina remained attached in six of 14 cases.     

Veterinary dentistry (15). Apex resection in the horse

Periapical disorders in horses can be treated by resection of the apex. The indications, contraindications, diagnosis, treatment and complications of the intervention are discussed. Four case reports of horses in which apicoectomy with retrograde endodontic treatment was performed are reviewed.     

The discriminative value of patient characteristics and dyspeptic symptoms for upper gastrointestinal endoscopic findings: a study on the clinical presentation of 1,147 patients

The discriminative value of patient characteristics and dyspeptic symptoms for upper gastrointestinal endoscopic findings was prospectively assessed in 1,147 patients attending for their first diagnostic endoscopy and who answered paper (n = 431) or computerized (n = 716) questionnaires. The questionnaires provided detailed information concerning present dyspeptic symptoms, with special attention to provoking and/or relieving factors, and smoking and/or drinking habits. In logistic regression models each of a number of 'specific endoscopic diagnoses' was contrasted with normal endoscopy (n = 390), and 'relevant endoscopic disease' (oesophagitis, peptic ulcers, cancers; n = 269) was contrasted with 'irrelevant' and normal endoscopic findings (n = 878). From the regression model a receiver operating characteristic (ROC) curve could be constructed, and the area under the ROC curve (AUC) was calculated to summarize the discriminative power of the regression model. The best discrimination from patients with a normal endoscopy was achieved for patients with gastric (AUC = 0.86) or duodenal (AUC = 0.85) ulcers, followed by patients with hiatus hernia (AUC = 0.78 or oesophagitis (AUC = 0.77). The discriminative performance of the regression models was somewhat less for duodenitis/bulbitis (AUC = 0.75) and endoscopic gastritis (AUC = 0.73). In an open-access endoscopy unit setting, the value of preinvestigation history-taking for the prediction of clinically relevant endoscopic disease was very limited (AUC = 0.63).     

Iodine-131-anti-B1 radioimmunotherapy for B-cell lymphoma

PURPOSE: The CD20 B-lymphocyte surface antigen expressed by B-cell lymphomas is an attractive target for radioimmunotherapy, treatment using radiolabeled antibodies. We conducted a phase I dose-escalation trial to assess the toxicity, tumor targeting, and efficacy of nonmyeloablative doses of an anti-CD20 monoclonal antibody (anti-B1) labeled with iodine-131 (131I) in 34 patients with B-cell lymphoma who had failed chemotherapy. PATIENTS AND METHODS: Patients were first given tracelabeled doses of 131I-labeled anti-B1 (15 to 20 mg, 5 mCi) to assess radiolabeled antibody biodistribution, and then a radioimmunotherapeutic dose (15 to 20 mg) labeled with a quantity of 131I that would deliver a specified centigray dose of whole-body radiation predicted by the tracer dose. Whole-body radiation doses were escalated from 25 to 85 cGy in sequential groups of patients in 10-cGy increments. To evaluate if radiolabeled antibody biodistribution could be optimized, initial patients were given one or two additional tracer doses on successive weeks, each dose preceded by an infusion of 135 mg of unlabeled anti-B1 one week and 685 mg the next. The unlabeled antibody dose resulting in the most optimal tracer biodistribution was also given before the radioimmunotherapeutic dose. Later patients were given a single tracer dose and radioimmunotherapeutic dose preceded by infusion of 685 mg of unlabeled anti-B1. RESULTS: Treatment was well tolerated. Hematologic toxicity was dose-limiting, and 75 cGy was established as the maximally tolerated whole-body radiation dose. Twenty-eight patients received radioimmunotherapeutic doses of 34 to 161 mCi, resulting in complete remission in 14 patients and a partial response in eight. All 13 patients with low-grade lymphoma responded, and 10 achieved a complete remission. Six of eight patients with transformed lymphoma responded. Thirteen of 19 patients whose disease was resistant to their last course of chemotherapy and all patients with chemotherapy-sensitive disease responded. The median duration of complete remission exceeds 16.5 months. Six patients remain in complete remission 16 to 31 months after treatment. CONCLUSION: Nonmyeloablative radioimmunotherapy with 131I-anti-B1 is associated with a high rate of durable remissions in patients with B-cell lymphoma refractory to chemotherapy.     

Oral L-ornithine-L-aspartate therapy of chronic hepatic encephalopathy: results of a placebo-controlled double-blind study

BACKGROUND/AIMS: In the current state of knowledge of the pathophysiology of hepatic encephalopathy, a reduction in hyperammonemia is the most important evidence of effective treatment. Therefore, the therapeutic efficacy of oral L-ornithine-L-aspartate, which improves impaired ammonia detoxification, was investigated in patients with cirrhosis, hyperammonemia and stable, overt, chronic hepatic encephalopathy, and in subclinical hepatic encephalopathy in a randomized, double-blind, placebo-controlled clinical trial. METHODS: Oral L-ornithine-L-aspartate was administered three times daily at fixed times for 14 consecutive days in a total dose of 18 g per day. The design was chosen to prevent an increase in ammonia induced by a protein meal of 0.25 g/kg body weight, given at the start of the daily treatment period. Efficacy variables were: fasting and postprandial ammonia concentration, Number-Connection-Test time, mental state grades, and a Portosystemic Encephalopathy Index. Analyses were based on the total study sample of 32 placebo- and 34 L-ornithine-L-aspartate-treated patients as well as on the subgroup samples in the overt (20 placebo- and 23 L-ornithine-L-aspartate-treated) and subclinical hepatic encephalopathy (12 placebo- and 11 L-ornithine-L-aspartate-treated) patients. RESULTS: Number Connection Test performance times (p<0.01) as well as fasting (p<0.01) and postprandial (p<0.05) venous blood ammonia concentrations in the L-ornithine-L-aspartate-treated group showed improvement in comparison to placebo. Also, the mental state grade (p<0.05) and the Portosystemic Encephalopathy Index (p<0.01), improved to a much greater degree in the L-ornithine-L-aspartate group than in the placebo group. Adverse events were observed in neither the placebo nor the L-ornithine-L-aspartate-treated patients. CONCLUSION: Oral L-ornithine-L-aspartate is a safe, well-tolerated treatment with a good compliance rate and a beneficial therapeutic effect in patients with cirrhosis and stable, overt, chronic hepatic encephalopathy.     

The role of magnetic resonance imaging in the preoperative assessment of anorectal anomalies

Venous ulcers are common in clinical practice. They are due to end stage skin and subcutaneous damage from sustained venous hypertension. The common cause may be post thrombotic syndrome or primary superficial venous insufficiency. This case illustrates the need to think of inherited thrombophilia as a primary cause.     

Catheter-associated Staphylococcus aureus bacteremia

The majority of cases of Staphylococcus aureus bacteremia are hospital-acquired, and most are associated with infected intravenous catheters. Preventive measures, early detection of infections, and strategies for effective treatment have become matters of increasing urgency.