Cell cycling and patterned cell proliferation in the Drosophila wing during metamorphosis.

In metamorphosing wing discs, progression through the cell cycle takes place, as in larval discs, in nonclonally derived clusters of cells synchronized in the same cell cycle stage. Contrary to early discs, there are temporal and spatial heterogeneities in cell proliferation associated with wing margin, vein, intervein, and middle intervein territories. Within these territories, there are no indications of a wave progression of the cell cycle. Mitotic orientations are, as in early discs, at random but there is a preferential allocation of postmitotic cells along the proximodistal axis, thus explaining the elongated shape of the resulting clones along this axis. Shapes of clones in mature discs and in evaginated wings are similar, thus excluding major morphogenetic movements during evagination. After the proliferative period, all the cells are arrested in G1 phase. The final number of cells of the wing is fixed independently of experimental perturbations that alter the cell division schedule. These results are discussed in the context of a model of wing morphogenesis.     

Phenotypical study of human lymphokine-activated killer (LAK) cells

In the present study, T-cell enriched lymphocyte populations were stimulated with recombinant interleukin-2 (IL-2) to obtain lymphokine-activated killer (LAK) cells, and their cytotoxicity was tested against different target cells. The expression of phenotypical markers with a panel of monoclonal antibodies (Moabs) using indirect immunofluorescence techniques and cytofluorometric analysis was studied. The results showed slight variations in T-cell antigen expression and an increase in the expression of immature NK and proliferation associated antigens.     

Successful rescue therapy with darunabir (TMC114) in HIV-infected patients who have failed several ritonavir-boosted protease inhibitors

Darunabir, formerly TMC114, is a new protease inhibitor (PI) under clinical development designed to be active against HIV strains resistant to currently available PI. The virological and immunological response to ritonavir-boosted darunabir was assessed in four heavily antiretroviral-experienced patients who had failed enfuvirtide and two or more previous ritonavir-boosted PI regimens, including tipranavir in one instance. All four patients reached undetectable plasma HIV-RNA levels within 8 weeks of therapy and experienced significant CD4 cell count gains.     

Coexistent primary open-angle glaucoma and cataract: Preliminary analysis of treatment by cataract surgery and the iStent trabecular micro-bypass stent

INTRODUCTION: Reducing intraocular pressure (IOP) is the only proven treatment modality for reducing the risk of glaucomatous progression. In this study, we evaluated the safety and efficacy of a new tool in IOP reduction, implanted with cataract surgery: the Glaukos iStent trabecular micro-bypass stent. METHODS: This was a prospective, 24-month, uncontrolled, non-randomised, multicentre study. Subjects with uncontrolled primary open-angle glaucoma (including pseudoexfoliation and pigmentary) and a cataract underwent clear cornea phacoemulsification cataract extraction with ab-interno gonioscopically guided implantation of the study stent. Subjects who had completed at least 6 months of follow-up were included in this interim analysis (n=47). RESULTS: At baseline, mean (+/-standard deviation) IOP was 21.5+/-3.7 mmHg, and subjects were taking a mean of 1.5+/-0.7 ocular hypotensive medications. Six months after implantation of the study stent the mean IOP was 15.8+/- 3.0 mmHg, a mean IOP reduction of 5.7+/-3.8 mmHg (25.4%, P<0.001). The mean number of patient medications after 6 months was 0.5+/-0.8 medications, a mean decrease of 1.0+/-0.8 medications (66.7%, P<0.001). Most subjects (70%) were able to discontinue all glaucoma medications. There were no complications traditionally associated with filtering surgery, and no serious adverse events were reported. CONCLUSION: In this interim analysis of subjects with glaucoma and cataracts, this novel stent implantation in subjects undergoing cataract surgery represents a new surgical approach to provide clinically significant decreases in IOP and drug burden.     

Ruptured gastrointestinal stromal tumors: radiologic findings in six cases

Background Gastrointestinal stromal tumors (GISTs) are characterized by the expression of c-KIT (antigen CD 117) and are the most common mesenchymal tumors of the digestive tract. An important complication, although infrequently described in the literature, is the rupture of these tumors with accompanying hemoperitoneum. Methods We performed a retrospective evaluation of the clinical history and radiologic records of 23 patients with a diagnosis of GIST and anatomopathologic and immunohistochemical confirmation at our hospital between 1999 and 2004. Results In five cases there was rupture of the primary tumor (four gastric and one jejunal). In all five cases ultrasonographic and computed tomographic examinations showed a heterogenic tumor of laminated or whirled appearance, associated with echogenic or dense ascites. No relation was found between histologic criteria of malignancy and the rupture. Four patients underwent surgical intervention, three of them urgently. Two of five patients died. There was a sixth case with rupture of a hepatic metastasis, with accompanying hemoperitoneum and subcapsular hematoma. This patient died at 3 months, after recurrence of bleeding. Conclusions The finding of a heterogeneous tumor of laminated or whirled appearance associated with ascites with characteristics compatible with hemoperitoneum in an appropriate context must lead to a suspicion of the existence of a ruptured GIST.     

Increased serum S-100B and neuron specific enolase - Potential markers of early nervous system involvement in essential hypertension

ObjectivesTo investigate the occurrence of subclinical neurologic involvement in patients with essential hypertension employing serum biochemical markers.Design and methodsFifty patients with essential hypertension and 42 controls with no clinical evidence of neurological disease were recruited. Serum S100B protein and neuron specific enolase (NSE) were determined by employing immunoassay kits from CanAg Diagnostics AB (Sweden). Brain MRI and fundoscopic exploration were conducted.ResultsS-100B and NSE levels were significantly higher in hypertensive patients than in controls. In hypertensive patients, multivariate analysis revealed that NSE was independently associated with two variables expressing severity of hypertension: diastolic blood pressure and grade of retinopathy. Brain MRI studies demonstrated higher NSE levels in patients with more severe white matter lesions.ConclusionsRaised NSE levels are associated with a higher severity of hypertension and of white matter lesions, providing preliminary evidence that suggests the presence of silent brain damage in a subset of hypertensive patients.     

Comparative in vitro activity of the new quinolone gemifloxacin (SB-265805) with other fluoroquinolones against respiratory tract pathogens

The in vitro activity of gemifloxacin (SB-265805) was compared with that of other fluoroquinolones against 302 clinical isolates of Streptococcus pneumoniae, 300 clinical isolates of Haemophilus influenzae and 28 clinical isolates of Moraxella catarrhalis, including multiply resistant strains. Gemifloxacin at 0.12 mg/L inhibited all microorganisms tested. MIC(90) values of gemifloxacin, trovafloxacin, grepafloxacin and levofloxacin against all (630) isolates tested were 0.03, 0.12, 0.12 and 1 mg/L, respectively. MIC(90) values of the same fluoroquinolones against S. pneumoniae were 0.06, 0.25, 0.12 and 1 mg/L, respectively.     

Effect of a catecholamine-induced increase in cardiac output on extravascular lung water

OBJECTIVE: To determine the influence of dopamine- and dobutamine-induced increases in cardiac output on the extravascular lung water in an experimental model of pulmonary edema. DESIGN: Animal experimental study. SETTING: Animal experimental laboratory of a tertiary hospital. SUBJECTS: Mixed-race pigs (n = 20) weighing 28-32 kg. INTERVENTIONS: After the animals were anesthetized and tracheotomized, they were injected with 0.1 mL/kg of oleic acid, producing a pulmonary edema by increased permeability. The animals then were randomized into two groups: Group I (n = 10) received no medication to alter cardiac output and remained on mechanical ventilation during the 240 mins of the experiment; group II (n = 10) received a continuous infusion of dopamine and dobutamine to produce a cardiac output increase of >or=30% the basal value and underwent the same mechanical ventilation regimen as group I. MEASUREMENTS AND MAIN RESULTS: Hemodynamic and respiratory variables were measured at 0 (baseline) and 30, 60, 120, 180, and 240 mins after the infusion of oleic acid. At 30 mins, the cardiac output of group II (5.40 +/- 0.94 L/min) was significantly (p < .005) higher than that of group I (3.65 +/- 1.02 L/min), and a similar significant increase was recorded at all measurement times until the end of the experiment. The mean pulmonary arterial pressure was similar in both groups except that at 240 mins it was significantly higher in group I (normal cardiac output) than in group II (high cardiac output; 34.9 +/- 7.9 mm Hg vs. 27.2 +/- 3.8 mm Hg, p = .01). The extravascular lung water was calculated by gravimetric method after the death of the animal. The extravascular lung water of group I (13.8 +/- 3.6 mL/kg) did not significantly differ from that of group II (11.5 +/- 4.0 mL/kg). CONCLUSIONS: An increase in cardiac output experimentally produced by the infusion of dopamine and dobutamine does not modify the amount of extravascular lung water.