Efficacy of anticoagulants and platelet inhibitors in cancer-induced thrombosis.

The efficacy of anticoagulants, low-molecular-weight heparins (LMWHs), the antiplatelet glycoprotein IIb/IIIa antagonist, or combinations on cancer-activated thrombosis was determined using thromboelastography. The LMWHs tinzaparin and enoxaparin (0.179, 1.79, 17.9 microg) were incubated in human citrated whole blood (n = 4) and then activated by calcium chloride (11 mmol/l) or Colo205 (cell count 10). Concentrations of 9.9, 17.9 and 179 microg glycoprotein IIb/IIIa antagonist, XV454, and combinations with each LMWH were carried out and activated under the same conditions. The experiment was repeated with tissue factor substituting for the Colo205 to induce platelet/fibrin clot formation. Parameters tested in the thrombelastography analysis included clotting time, rate of clot formation due to fibrin formation, clot kinetics, and clot strength related to platelet count (maximum amplitude). Tinzaparin (1.79 microg), enoxaparin (1.79 microg), and XV454 (17.9 microg) significantly reduced the angle by 64, 26 and 27%, respectively, in cancer-induced clotting. Significant reductions in the maximum amplitude occurred in tinzaparin 1.79 microg (31%), enoxaparin 1.79 microg (11%), and XV454 17.9 microg (59%). An overall antithrombotic additive effect occurred when each LMWH (1.79 microg) was combined with XV454 (17.9 microg). The results between cancer-activated and tissue factor-activated blood were similar. The study concludes that an additive effect is present between LMWHs and a glycoprotein IIb/IIIa antagonist in reducing cancer-mediated thrombosis.     

Parasite-specific antibody profile in human fascioliasis: application for immunodiagnosis of infection

The antibody isotype response to an adult Fasciola worm antigen preparation (FWAP) was examined in sera from 60 Egyptians with parasitologically confirmed fascioliasis by an ELISA. The FWAP-specific IgG1 and IgG4 antibodies were found in 97-100% of the patients. The ratio of the mean absorbance values between infected patients and healthy controls was 9.7 and 29.7 for IgG1 and IgG4 antibodies, respectively. The IgM, IgA, IgG2, and IgG3 antibodies were less dominant. In contrast to IgG1 antibodies, which were often detected in sera from patients infected with Schistosoma, Echinococcus granulosus, Ascaris lumbricoides, Ancylostoma duodenale, or Hymenolepis nana, FWAP-specific IgG4 antibodies were detected exclusively in the sera of patients with fascioliasis. The data thus support the conclusion that an IgG4/ELISA with crude FWAP as antigen may be used for sensitive and accurate immunodiagnosis of human fascioliasis.     

Effect of ageing on the upper and lower oesophageal sphincters

OBJECTIVE: To determine the effect of ageing on length and resting pressure of the upper and lower oesophageal sphincters (UOSs, LOSs). BACKGROUND: The effectiveness of upper and lower oesophageal sphincters (UOSs and LOSs, respectively) in the control of retrograde trans-sphincteric flow is influenced by sphincteric pressure and length. METHODS: Nine young and nine elderly healthy volunteers were studied. Resting UOS and LOS pressures were measured by sleeve devices and lengths were measured by the station pull-through technique. RESULTS: The length of the UOS high pressure zone in the elderly (2.1 +/- 0.7 cm posterior; 1.9 +/- 0.1 cm anterior) was significantly shorter than that of the young (2.9 +/- 0.1 cm posterior; 3.1 +/- 0.2 cm anterior) (P< 0.01). Resting UOS pressure in the elderly (42 +/- 5 mmHg) was significantly lower than that of the young (62 +/- 7 mmHg) (P< 0.05). The intersphincteric length of the oesophagus in the elderly (21 +/- 0.2 cm) was similar to that of the young (21 +/- 0.4 cm). Total length of the LOS high pressure zone in the young (4.0 +/- 0.1 cm) was similar to that of the elderly (4.1 +/- 0.1 cm). LOS resting pressure was similar between young and elderly subjects (17 +/- 5 mmHg and 15 +/- 3 mmHg, respectively). CONCLUSIONS: Ageing affects the UOS and LOS differently. With regard to resting pressure and length, ageing weakens the UOS, but has no significant effect on the LOS.     

Post-fundoplication symptoms: the role for endoscopic assessment of fundoplication integrity

BACKGROUND: Fundoplication is now almost exclusively a laparoscopic procedure. The aim of this study was the comparison of the diagnostic usefulness of endoscopy and barium esophagram in the detection of fundoplication abnormalities. METHODS: Twenty-two patients presented with symptoms post-laparoscopic (Nissen) fundoplication that included dysphagia (14 patients), heartburn (5 patients), dyspepsia (2 patients), and chest pain (1 patient). Barium esophagram and upper endoscopy were performed in all patients and the results were compared. Key features included presence of esophagitis, resistance to endoscope passage, location of the wrap relative to the diaphragmatic hiatus, location of squamocolumnar junction greater than 1 cm proximal to the wrap zone, and the appearance of the wrap (intact, loose, disrupted, or tight). RESULTS: The key features explained symptoms in 20 of 22 patients. Endoscopy detected twice as many key features as radiography. Disruption of the wrap or excessive proximal location of the squamocolumnar junction proximal to the wrap zone were the most incriminating endoscopic findings. Resistance to endoscope passage was rarely encountered and the esophagram was more accurate in detecting an overly tight wrap. CONCLUSIONS: Endoscopic evaluation is more accurate than barium esophagram in detecting post-fundoplication abnormalities. The appearance of the fundoplication wrap and an abnormal proximal location of the squamocolumnar junction appear to be major endoscopic clues in diagnosis of post-fundoplication problems.     

The Impact of Interleukin 28b Gene Polymorphism on the Virological Response to Combined Pegylated Interferon and Ribavirin Therapy in Chronic HCV Genotype 4 Infected Egyptian Patients Using Data Mining Analysis

Background: Chronic HCV represents one of the common causes of chronic liver disease worldwide with Egypt having the highest prevalence, namely genotype 4. Interleukin IL-28B gene polymorphism has been shown to relate to HCV treatment response, mainly in genotype1.Objectives: We aim to evaluate the predictive power of the rs12979860 IL28B SNP and its protein for treatment response in genotype 4 Egyptian patients by regression analysis and decision tree analysis.Patients and Methods: The study included 263 chronic HCV Egyptian patients receiving peg-interferon and ribavirin therapy. Patients were classified into 3 groups; non responders (83patients), relapsers (76patients) and sustained virological responders (104 patients). Serum IL 28 B was performed, DNA was extracted and analyzed by direct sequencing of the SNP rs 12979860 of IL28B gene.Results: CT, CC and TT represented 56 %, 25 % and 19% of the patients, respectively. Absence of C allele (TT genotype) was significantly correlated with the early failure of response while CC was associated with sustained virological response. The decision tree showed that baseline alpha fetoprotein (AFP ≤ 2.68 ng/ml) was the variable of initial split (the strongest predictor of response) confirmed by regression analysis. Patients with TT genotype had the highest probability of failure of response.Conclusions: Absence of the C allele was significantly associated with failure of response. The presence of C allele was associated with a favorable outcome. AFP is a strong baseline predictor of HCV treatment response. A decision tree model is useful for predicting the probability of response to therapy.     

Phase II study of Didemnin B in central nervous system tumors: A Southwest Oncology Group study

Didemnin B 6.3 mg/m2 was administered intravenously to 48 patients with recurrent or progressive central nervous system tumors. One patient of 39 (2.9%, 95% confidence limits 0.1 to 13.5) eligible patients had a confirmed partial response utilizing standard solid tumor criteria which lasted 14 months. Toxicity was significant. Nausea and vomiting and lethargy were the most frequent toxicities, but multiple severe toxicities were seen. Further investigation of Didemnin B at this dose is not warranted in patients with central nervous system malignancies.     

Rheumatic fever and rubella immunity

Anti-rubella IgG titer was estimated in 106 children: sixty five had acute rheumatic fever and 41 had either a history of rheumatic fever or a definite rheumatic heart disease. Their ages ranged from 6 to 16 years old (11.4 +/- 2.7 years). Sixty two were females and 44 were males. They were compared with 35 control normal subjects of both sexes with no history of rheumatic affection, aged 5 to 14 years (10.2 +/- 3.6 years). The results obtained showed a significantly (p less than 0.001) higher rubella IgG titer level in the controls (1066.5 +/- 8.3) as compared to the rheumatic cases (521.2 +/- 3.0). No differences were found in the rubella antibody titer between cases of acute rheumatic fever and those with history of rheumatic fever or rheumatic heart disease, nor between males and females in either cases or controls. We suggested that the low rubella IgG levels encountered in the rheumatic cases, make them more susceptible to rheumatic fever affection. In other words, a high immunity level against rubella might also produce an immunity against an agent, possibly related to rubella virus, with a specific role in the development of rheumatic fever. Vaccination against rubella could be worth a trial, for prevention of rheumatic fever.