Urinary organ specific neoantigen

Urinary organ-specific neoantigen from colorectal cancer patients has been used to make a monoclonal antibody, BAC 18.1. In this study we assessed the potential of this antibody for the diagnosis of colorectal cancer. We evaluated binding in both urine and effluent samples and compared it with effluent carcinoembryonic antigen standardized for both volume (nanograms per milliliter) and protein. Urinary organ-specific antigen as detected by BAC 18.1 was significantly greater in 29 cancer patients (A₄₀₅:0.717±0.500) vs 27 controls [0.121 ±0.273 (P<0.05)]. Considerable overlap of binding of BAC 18.1 was observed in the colonic effluent of patients with CRC (N=13), adenomas (N=26), inflammatory bowel disease (N=8), or having a normal colonoscopic examination (N=24). CEA levels (nanograms per milliliter) were significantly elevated in the effluent samples of patients with a past history of colorectal cancer, as compared to that of normal individuals (P<0.05). The presence of the Mr 30,000 organ-specific neoantigen in colonic effluent was also demonstrated by western blot. Organ-specific neoantigen originates in the colon and is excreted into the urine, so the BAC 18.1 binding levels in the urine may be a diagnostic aid for CRC.The work reported in this paper was supported in part by a grant from the Israeli Cancer Association and Tel Aviv University, and in part by grants from the Israel Cancer Association and the Sackler School of Medicine, Tel Aviv, Israel.     

Clinical experiences using the FilterWire EX for distal embolic protection during complex percutaneous coronary interventions

BACKGROUND: Distal embolization during coronary angioplasty may result in vessel occlusion, no reflow and myonecrosis. This study tested the authors' clinical experiences using a guidewire system designed to preserve distal flow during angioplasty.

METHODS AND RESULTS: The FilterWire EX? (Boston Scientific, Natick, MA, USA) consists of a 0.014‐inch guidewire on which an expandable loop structure is attached to a porous polyurethane membrane. The assembly is delivered across the target lesion, followed by deployment of the filter distal to the lesion. Procedural and angiographic outcome data were obtained from patients undergoing saphenous vein grafts (SVGs) (n?=?16) or native coronary (n?=?4) interventions. The mean age was 62?±?10 years. All four patients with native coronary lesions sustained acute myocardial infarction while 15/16 patients with degenerated SVGs presented with accelerated angina pectoris. The mean proximal reference diameter was 3.62?±?0.32?mm, percentage diameter stenosis was 72?±?13%, and lesion length was 16.3?±?5.7?mm. Angiographic visible thrombus was detected in 12/20 (60%) cases. Stents were used in 19/20 patients (95%) with average stent diameter/length equal to 3.81?±?0.42/23?±?7?mm. Overall procedural success was obtained in 93.3% as no‐reflow and total CK elevation occurred in 1/16 treated patients (6.7%) despite distal embolic filtration. In‐hospital and 30‐day survival was 100% with no episodes of target vessel thrombosis and/or myocardial infarction.

CONCLUSIONS: The use of the FilterWire EX seems to be feasible and safe in suitable lesion subsets and in relatively large‐sized vessels among patients who are at high risk for distal embolization. (Int J Cardiovasc Intervent 2004; 1:?28–32)     

Predicting risk severity and response of fetal neonatal alloimmune thrombocytopenia

Fetal neonatal alloimmune thrombocytopenia (FNAIT) is a devastating bleeding disorder in the fetus or neonate caused by transplacental transport of maternal alloantibodies to paternal‐derived antigen on fetal platelets. In Caucasians, up to 80% of FNAIT cases result from maternal immunization to human platelet antigen (HPA)‐1a. New methods have developed facilitating detection of common and private antibodies against HPAs triggering FNAIT. Understanding the pathogenesis of FNAIT made it possible to develop a novel strategy to treat this disorder. To date, recombinant monoclonal antibodies directed against the β3 integrin and Fc receptors have been tested in a mouse model of FNAIT, and seem to be promising. Whether those novel treatments will eventually replace the conventional high dose immunoglobulin G in women with FNAIT is yet unknown.     

Effect of hyperbaric oxygen on survival of composite grafts in rats.

Most treatment with hyperbaric oxygen (HBO) in plastic surgery is for wounds, burns, crush injuries, and infections. We aimed to find out if HBO increases the survival of composite grafts in rats. Twenty Sprague-Dawley rats were randomly assigned to two equal groups (treatment and control). A template 30 x 30 mm was placed on the skin and a composite graft taken from the upper back was harvested and then resutured to the fascia in situ. The treated group was placed in a hyperbaric chamber set at 202 kPa and 100% oxygen for 90 minutes daily for two weeks. Control animals were given no treatment. After death the mean surviving internal surface area of the graft was 372.5 (117.9) mm2 in the control group and 561.3 (85.7) mm2 in the experimental group (p=0.001). Treatment with HBO improved the surviving area of composite grafts in rats, and the beneficial effect was prominent only on the inner surface of the graft.     

The involvement of matrix metalloproteinases 2 and 9 in rat retinal ischemia

Background The involvement of matrix metalloproteinases (MMPs) in ischemic tissue damage and remodeling has been reported by many investigators. Our study was designed to investigate the involvement of MMPs and of tissue inhibitors of metalloproteinases (TIMPs) in rat retinal ischemic injury, the effect of nitric oxide synthase (NOS) inhibitors on MMPs’ activity in this model and whether minocycline (an MMP inhibitor) is protective in retinal ischemia. Methods Ninety-four rats were used in the study. Ischemia was induced by 90 min elevation of intraocular pressure. MMPs’ activities and the effect of NOS inhibitors [aminoguanidine (AG) or N-nitro-L-arginine (NNA)] and minocycline on MMPs’ activities were assessed by zymography and TIMPs expression by Western analysis. Morphological damage was quantified by morphometry of hematoxylin and eosin-stained retinal sections. Results Retinal extracts exhibited activities of proMMP-9 and proMMP-2. The activity of proMMP-9 increased immediately post ischemia (PI) and peaked to 4.6 times that of normal untreated controls in ischemic retinas and to 2.6 times that of controls in retinas of fellow sham-treated eyes at 24 h PI. The relative amount of TIMP-1 increased to 1.9-fold following ischemia and 2.5-fold in fellow sham-treated eyes at 24 h PI. ProMMP-2 activity increased more than two-fold immediately, at 24 h and at 48 h PI in ischemic retinas, and insignificantly in fellow sham-treated eyes. Treatment with 25 mg/kg AG or NNA caused a non-significant increase in proMMP-9 activity at 24 h PI (3.7- and 2.9-fold, respectively, p>0.6). There was no effect of AG or NNA on the activity of proMMP-2. Minocycline significantly attenuated the retinal ischemic damage, primarily by partially preserving ganglion cells and the inner plexiform layer. Minocyline (0.5 mg/ml or 5 mg/ml) inhibited MMPs’ activities in ischemic retinal extracts in vitro. Conclusions MMPs participated in morphological ischemic damage to rat retina. Treatment with minocycline dramatically attenuated damage to the retina.     

Effect of ranitidine on secretion of gastric intrinsic factor and absorption of vitamin B 12

The effects of ranitidine, a new potent histamine H2-receptor antagonist, on gastric intrinsic factor (IF) secretion and protein-bound cobalamin absorption were evaluated in 6 patients with duodenal ulcer, before, during and after discontinuation of ranitidine therapy. Oral ranitidine (150 mg twice a day) resulted in a non significant decrease of IF concentration and IF output but was responsible for malabsorption of protein-bound cobalamin. This malabsorption was reversible upon discontinuation of ranitidine. These results indicate that occurrence of cobalamin deficiency cannot be excluded during long-term ranitidine treatment and emphasize the need for careful follow-up in these patients.     

A side-by-side prospective study of intense pulsed light and Nd:YAG laser treatment for vascular lesions

Recently, lasers and light systems are used more for the treatment of vascular lesions due to their noninvasiveness, ease of use, and short recovery time. This side-by-side prospective study compares results, satisfaction, and complications after intense pulsed light (IPL) and Nd:Yag laser treatment of small vascular lesions. Twenty-five patients with telangiectases, leg veins, or cherry angiomas underwent treatment of the same category of lesion in the same area. One year after completing treatment, patients were asked to report their satisfaction level after comparing digital photos before and after treatment; 72% felt they had good to excellent results after Nd:Yag treatment, while only 48% felt the same after IPL. The most common side effect after Nd:Yag was hyperpigmentation. Satisfaction level was significantly higher after Nd:Yag than after IPL. Patients with telangiectases, cherry angiomas, or leg veins <1 mm were more satisfied after IPL, while those with leg veins >1 mm were more satisfied after Nd:Yag. Overall, satisfaction with treatment of vascular lesions was greater with Nd:Yag although this method was more painful.     

New therapeutic strategies for systemic sclerosis--a critical analysis of the literature

Systemic sclerosis (SSc) is a multi-system disease characterized by skin fibrosis and visceral disease. Therapy is organ and pathogenesis targeted. In this review, we describe novel strategies in the treatment of SSc. Utilizing the MEDLINE and the COCHRANE REGISTRY, we identified open trials, controlled trials, for treatment of SSc from 1999 to April 2005. We used the terms scleroderma, systemic sclerosis, Raynaud's phenomenon, pulmonary hypertension, methotrexate, cyclosporin, tacrolimus, relaxin, low-dose penicillamine, IVIg, calcium channel blockers, losartan, prazocin, iloprost, N-acetylcysteine, bosentan, cyclophosphamide, lung transplantation, ACE inhibitors, anti-thymocyte globulin, and stem cell transplantation. Anecdotal reports were omitted. Methotrexate, cyclosporin, tacrolimus, relaxin, low-dose penicillamine, and IVIg may be beneficial in improving the skin tightness in SSc. Calcium channel blockers, the angiotensin II receptor type 1 antagonist losartan, prazocin, the prostacyclin analogue iloprost, N-acetylcysteine and the dual endothelin-receptor antagonist bosentan may be beneficial for Raynaud's phenomenon. Epoprostenol and bosentan are approved for therapy of pulmonary hypertension (PAH). Other options under investigation include intravenous or aerolized iloprost. Cyclophosphamide (CYC) pulse therapy is effective in suppressing active alveolitis. Stem cell and lung transplantation is a viable option for carefully selected patients. Renal crisis can be effectively managed when hypertension is aggressively controlled with angiotensin converting enzyme (ACE) inhibitors. Patients should continue taking ACE inhibitors even after beginning dialysis in hope of discontinuing dialysis. Antithymocyte globulin and mycophenolate mofetil appear safe in SSc. The improvement in skin score and the apparent stability of systemic disease during the treatment period suggest that controlled studies of these agents are justified. Stem cell transplantation is under investigation for severe disease. Novel therapies are currently being tested in the treatment of SSc and have the potential of modifying the disease process and overall clinical outcome. The evaluation of these studies is still a difficult process.     

Long-term intraocular pressure control after clear corneal phacoemulsification in glaucoma patients

PURPOSE: To evaluate long-term IOP control after sutureless clear corneal phacoemulsification in eyes with preoperatively controlled glaucoma. SETTING: Institutional study. METHODS: The charts of 345 patients who had uneventful sutureless clear corneal phacoemulsification with acrylic foldable lens (IOL) implantation were retrospectively reviewed. Included were 58 patients with medically controlled open-angle glaucoma and 287 normal controls. Follow-up was 1 to 2 years. Outcome measures were postoperative IOP and number of glaucoma medications. RESULTS: Postoperatively, there was an insignificant decrease in IOP in the glaucoma group; the mean decrease was 1.5 mm Hg +/- 4.4 (SD) at 12 months and 1.9 +/- 4.9 mm Hg at 24 months. The mean number of medications decreased significantly at 12 months (0.53 +/- 0.86) and at 24 months (0.38 +/- 0.9) (P=.04). The control group also had a significant decrease in IOP, with a mean decrease of 0.72 +/- 3.7 mm Hg at 12 months (P=.01) and 1.33 +/- 3.2 mm Hg at 24 months (P<.0001). The decrease in IOP was more pronounced in eyes with a higher preoperative IOP in both the glaucoma and control groups. CONCLUSIONS: These findings suggest that sutureless clear corneal phacoemulsification with foldable acrylic IOL implantation is a relatively simple and efficient surgical option in patients with cataract and well-controlled glaucoma. The approach combines long-term IOP control with fewer medications and leads to rapid visual rehabilitation.