Results of fundus perimetry after resorbed premacular hemorrhages under the internal limiting membrane in 10 patients

BACKGROUND: During their acute phase, premacular hemorrhages under the internal limiting membrane induce an absolute scotoma. It is generally suspected that extravasal blood has a toxic effect on the neuroretina. The objective of this study is to investigate whether one can indeed detect sensoric defects after resorbed hemorrhages under the internal limiting membrane. MATERIALS AND METHODS: Our patient group consisted of 10 patients with resorbed premacular hemorrhages, which had been caused by either Vasalva-Manouver or arterial macroaneurysms. In order to avoid visual field defects due to other causes, patients with diabetes, retinal vein occlusion and glaucoma were excluded from this study. The investigation was carried out with the Scotometry Programme Vers. 2.01 of the Rodenstock Scanning Laser Ophthalmoscope. Furthermore, fundus photographs were taken. RESULTS: Under condition of no pre-existing retinal pathologies, no scotomas could be revealed at the site of the preretinal hemorrhage after full resorption. Relative or absolute scotomas could only be found in cases of pre-existing epiretinal gliosis, pigmentepitheliumdefect, persistent subretinal hemorrhages or scars. CONCLUSION: Since no sensoric defects of the retinal receptors could be detected, the hypothesis of the extravasal blood having a direct toxic effect on the neuroretina, could not be confirmed in this patient group.     

Leukoaraiosis in stroke patients

Pathogenesis of leukoaraiosis (LA) is not clearly understood and its significance in patients with stroke remains undetermined. In the Neurology Department of Ankara Hospital, computed tomography (CT) examination of brain was performed for various reasons in 288 patients. LA was detected in 178 patients by the use of brain CT. Patients with LA had a higher incidence of hypertension history (70.8%) when compared with the non-LA group (57.3%; p <.05). There was no statistically significant difference in terms of sex, mean age, smoking, diabetes mellitus, history of cerebrovascular disease, cardiac failure, ischemic cardiac disease between patients with and without LA. We showed that LA is related to hypertension but not related to age, diabetes mellitus, or cardiac disease in our patient population.     

Inhibition of human endothelial cell proliferation by ShIF, a vacuolar H(+)-ATPase-like protein

ShIF is a bone marrow stroma cell-derived factor originally identified to support proliferation of bone marrow cells in vitro. This protein shares high sequence homology to the yeast vacuolar H(+)-ATPase subunit, Vph1p, and the 116 kDa proton pump of the rat and bovine synaptic vesicle, Vpp1. We examined the function of ShIF in the proliferation of human umbilical vein endothelial cells (HUVEC). ShIF inhibited HUVEC proliferation in a dose-dependent manner. Recombinant ShIF added at 10 and 20 ng/ml inhibited HUVEC proliferation by 21.6 and 44.3%, respectively and increasing the concentration of ShIF to 100 ng/ml inhibited proliferation by as much as 55.5%. When HUVEC cells were cultured at various concentrations of ShIF in the presence of anti-ShIF antibody, the inhibitory effects of ShIF to HUVEC proliferation were abrogated by 89-91% indicating that the activity of ShIF to HUVEC was specific. HUVEC cultured in the presence of ShIF and bafilomycin, a specific inhibitor of ATPase, resulted to a 90% growth inhibition. Thus, ShIF may act as an antagonist to the ATPase complex by disrupting the production of cellular ATP thereby decreasing the ability of HUVEC to proliferate.     

Studies on the vascular effects of the fractions and phenolic compounds isolated from Viscum album ssp. album

Viscum album L. has been used in the indigenous system of medicine for treatment of various diseases such as atherosclerosis and hypertension. In the literature, phenylpropan and flavonoid derivatives were suggested to play a role in the inhibition of cyclic adenosine monophosphate (cAMP)-phosphodiesterase (PDE) and a correlation was proposed between the in vitro inhibition of PDE and in vivo pharmacological activity. The vascular effects of the phenolic compounds and subfractions isolated from n-butanolic fraction of V. album ssp. album were studied on noradrenaline-contracted rat aortic rings. Isolated phenolic compounds (Syringin (VA-1), Coniferin (VA-9), 5, 7-dimethoxy-flavanone-4'-O-[beta-D-apiofuranosyl(1-->2)]-beta-D-gl uco pyranoside (VA-4)) produced concentration-dependent contractions in rat aortic rings. Only one compound (Kalopanaxin D (VA-15)) displayed very slight relaxant response. The weak concentration-dependent relaxing effect of the subfractions gave the idea that vasodilator activity were observed in the less polar subfractions. In addition, there was no clear correlation between the weak relaxant effects of subfractions and an inhibitory effect on cAMP-PDE.     

Pharmacokinetics and clinical evaluation of 125I-radiolabeled humanized CC49 monoclonal antibody (HuCC49deltaC(H)2) in recurrent and metastatic colorectal cancer patients

INTRODUCTION: CC49 is an antitumor monoclonal antibody that is promising for use in radioimmunoguided surgery (RIGS). However, the murine antibody has been limited by human antimouse antibody (HAMA) response and slow clearance. This study examined the pharmacokinetics and tissue localization of a humanized domain-deleted CC49 antibody (HuCC49DeltaC(H)2 MAb) in humans. METHODS: Twenty-one patients with colorectal carcinoma were given 1 mg intravenous (I.V.) bolus of HuCC49DeltaC(H)2 MAb radiolabeled with 2 mCi (125)I after thyroid blockade. The level of circulating HuCC49DeltaC(H)2 MAb was measured daily as precordial counts using a handheld gamma-detecting probe. Each patient underwent an exploratory laparotomy on postinjection days 3-20. Gamma counts were measured at normal organs, aortic bifurcation (AB), and both clinically evident and occult tumors. RESULTS: Precordial and AB gamma counts showed an excellent linear correlation. HuCC49DeltaC(H)2 MAb followed a two-compartment pharmacokinetic model. Normal organs and AB showed similar exposures to HuCC49DeltaC(H)2 MAb, while HuCC49DeltaC(H)2 MAb favorably distributed into tumors from day 3. Intestinal and metastatic liver lesions showed the highest partition coefficients. All patients showed no HAMA response. DISCUSSION: C(H)2 region deletion of HuCC49DeltaC(H)2 MAb did not alter the pharmacokinetics compared to murine CC49. The favorable partition coefficient K of HuCC49DeltaC(H)2 MAb into tumors supports its use in RIGS.     

The roles of HRCT and clinical parameters in assessing activity of suspected smear negative pulmonary tuberculosis

BACKGROUND: Smear-negative pulmonary tuberculosis (SNPTB) constitutes a major problem in countries with a moderate or high TB prevalence. The value of high-resolution computed tomography (HRCT), chest x-ray and other clinical findings in determining activity of SNPTB were investigated. METHODS: The study population consisted of 85 patients with suspected SNPTB, of whom 52 were confirmed as active pulmonary TB according to either culture positivity for Mycobacteriun tuberculosis or demonstration of caseous granulomatous inflammation. The remaining 33 patients accepted inactive TB sequel. RESULTS: Cough and expectoration were significantly frequent in inactive group whereas chest pain was detected higher in active patients. Sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of HRCT in detecting disease activity were 88, 88, 92, 83 and 88%, respectively. Centrilobular nodules, other non-calcified nodules, consolidation and cavity were significantly higher on HRCT in active group. Chest x-ray scores that were graded 1 to 3 showed a linear trend for the disease activity. CONCLUSIONS: HRCT has good diagnostic value in detecting activity of SNPTB, and some clinical findings may help in predicting the activity.     

Antithrombin III attenuates pulmonary tissue injury caused by mesenteric ischemia-reperfusion

BACKGROUND: Mesenteric ischemia-reperfusion (I/R) is a well-known event causing both local and remote organ injuries, including the lungs. Recently, several studies indicated that activated leukocyte-endothelial cell interactions play an important role in the mechanisms of these injuries. As a natural inhibitor of serine proteases, antithrombin was shown previously to attenuate the tissue damage after local I/R in several organ systems. Here, we examined the effects of antithrombin on pulmonary injury after mesenteric I/R. METHODS: Wistar albino rats underwent median laparotomy and were randomized into 3 groups: (1) sham-operated control (n = 12), (2) 60 minutes of mesenteric ischemia and 3 hours of reperfusion (n = 12), and (3) antithrombin-pretreated (250 U/kg) group before the I/R (n = 12). At the end of reperfusion, animals were killed and neutrophil sequestration, myeloperoxidase (MPO) activity, and Evans blue dye extravasation in the lung parenchyma were assessed and compared. RESULTS: There was a statistically significant increase in the quantity of Evans blue dye concentration, leukocyte sequestration, and MPO activity in the I/R group when compared with the control group. The pretreatment of animals with antithrombin significantly decreased the pulmonary injury characterized by increased Evans blue dye extravasation, leukocyte sequestration, and MPO activity. CONCLUSION: The data of the present study suggest that mesenteric ischemia and reperfusion induces pulmonary injury characterized by activated neutrophil sequestration and increased microvascular leakage in the lungs. A significant attenuation of intestinal I/R-related lung injury with the use of antithrombin concentrate warrants further studies to elucidate the potential role of this natural serine protease inhibitor in clinical settings.