Variations in Helicobacter pylori lipopolysaccharide to evade the innate immune component surfactant protein D

Helicobacter pylori is a common and persistent human pathogen of the gastric mucosa. Surfactant protein D (SP-D), a component of innate immunity, is expressed in the human gastric mucosa and is capable of aggregating H. pylori. Wide variation in the SP-D binding affinity to H. pylori has been observed in clinical isolates and laboratory-adapted strains. The aim of this study was to reveal potential mechanisms responsible for evading SP-D binding and establishing persistent infection. An escape variant, J178V, was generated in vitro, and the lipopolysaccharide (LPS) structure of the variant was compared to that of the parental strain, J178. The genetic basis for structural variation was explored by sequencing LPS biosynthesis genes. SP-D binding to clinical isolates was demonstrated by fluorescence-activated cell sorter analyses. Here, we show that H. pylori evades SP-D binding through phase variation in lipopolysaccharide. This phenomenon is linked to changes in the fucosylation of the O chain, which was concomitant with slipped-strand mispairing in a poly(C) tract of the fucosyltransferase A (fucT1) gene. SP-D binding organisms are predominant in mucus in vivo (P = 0.02), suggesting that SP-D facilitates physical elimination. Phase variation to evade SP-D contributes to the persistence of this common gastric pathogen.     

Home Versus Clinic Blood Pressure Measurements

To evaluate the cost effectiveness of home versus clinic blood pressure 11 patients with mild untreated hypertension were instructed in self-measurement of blood pressure with mercury manometers. The lower total cost of using home readings as well as problems of bias and blinding are discussed. Home blood pressure is a promising technique for clinical and epidemiologic research.     

Correlation of optic nerve sheath diameter measurements by computed tomography and magnetic resonance imaging

BackgroundTraditionally, intracranial pressure is measured by direct ventriculostomy, which is invasive. Noninvasive measures such as bedside ultrasound and magnetic resonance imaging have been advocated and utilized recently to assess the intracranial pressure. The role of this study is to determine the degree of agreement between measurements of the optic nerve sheath diameter by computed tomography (CT) and magnetic resonance imaging (MRI).Materials and MethodsRetrospective chart review of 100 consecutive patients who had both MRI and CT scan of the head from January 1, 2011, until March 31, 2013, at our center was performed. A discrepancy of 0.2 mm between the 2 measurements was set as acceptable difference. The measurements of optic nerve sheath diameter (ONSD) were compared for agreement between the 2 modalities using the method by Bland and Altman.ResultsA total of 100 patients with both MRI and CT scan of the head were selected. Of these 100 patients, 24 were male and 76 were female. The average age was 63 years. No ONSD abnormality was detected in any of the patients. The discrepancy in measurements of the ONSD between CT and MRI in transverse plane was less than the predetermined cut-off value of 0.2 mm. Within-subject variance was estimated at 0.0058 for both CT and MRI.ConclusionComparable results without significant discrepancy as predetermined by the study groups were obtained from CT scan. Measurement of ONSD by CT scan can be used to indirectly asses the intracranial pressure in addition to clinical assessment and other signs of increased intracranial pressure on CT scan.     

Real time optic nerve sheath diameter measurement during lumbar puncture

Measurement of optic nerve sheath diameter (ONSD) using point of care ultrasound has been used to indirectly assess the intracranial pressure (ICP) particularly in conditions where it is raised. Direct pressure measurements using probes reaching the ventricle system correlated with ONSD using ultrasound. Attempts were made to measure the ONSD pre and post lumbar puncture (LP) after draining cerebrospinal fluid (CSF) as well as post ventricular shunt placement. We report ONSD measurement and demonstrate dynamic changes during LP in a patient with known idiopathic intracranial hypertension (IIH).     

Prediction of early (4-week) mortality in acute myeloid leukemia with intensive chemotherapy

The progress with intensive chemotherapy and supportive care measures has improved survival in patients with newly diagnosed acute myeloid leukemia (AML). Given the recent development of effective low intensity therapies, an optimal decision on the therapy intensity may improve survival through the avoidance of early mortality. We reviewed the outcome of 3728 patients with newly diagnosed AML who received intensive chemotherapy between August 1980 and May 2020. Intensive chemotherapy was defined as a cumulative cytarabine dose ≥ 700 mg/m² during induction therapy. We divided the whole cohort into a training and validation group at a 3:1 ratio. The population was divided into a training (2790 patients) and a validation cohort (938 patients). The median age was 55 years (range, 15-99). Among them, 442 patients (12%) had core-binding factor AML. Binary logistic regression identified older age, worse performance status, hyperbilirubinemia, elevated creatinine, hyperuricemia, cytogenetic abnormalities other than CBF and -Y, and pneumonia as adverse prognostic factors for an early 4-week mortality. This risk classification for early mortality was verified in the validation cohort of patients. In the validation cohort of more recently treated patients from 2000 to 2017, the 4-week mortality rates with intensive chemotherapy were 2%, 14%, and 50% in the low-, high-, and very high-risk group, respectively. The mortality rates with low intensity therapies were 3%, 9%, and 20%, respectively. The risk classification guides treatment intensity by the assessment of age, frailty, organ dysfunction, cytogenetic abnormality, and infection to avoid early mortality.     

Effects of acrylic resin monomers on porcine coronary artery reactivity

The purpose of the present investigation was to assess the reactivity of porcine coronary arteries under in vitro conditions following their exposure to methyl methacrylate (MMA) and hydroxyethyl methacrylate (HEMA) monomers. Confirming previous studies using rat aortas, both MMA and HEMA induced acute/direct relaxation of coronary ring preparations, which was partly dependent on the endothelium. With prolonged tissue exposure, both monomers caused time- and concentration-dependent inhibition of receptor-mediated contraction of the vascular smooth muscle caused by prostaglandin F_2∝ (PGF_2∝), with HEMA causing more inhibition than MMA. Hydroxyethyl methacrylate, but not MMA, also produced impairment of non-receptor-mediated contraction of the coronary smooth muscle induced by KCl. On the other hand, neither HEMA nor MMA altered relaxation of the smooth muscle produced by the direct-acting pharmacological agent, sodium nitroprusside (SNP). While exposure to HEMA impaired endothelium-dependent vasorelaxation caused by bradykinin (BK), MMA markedly enhanced this endothelial-mediated response of the arteries. The enhanced endothelial response produced by MMA was linked to nitric oxide (NO) release. In conclusion, with prolonged tissue exposure, MMA causes less pronounced effects/adverse consequences on coronary smooth muscle function relative to the effect of HEMA, while enhancing vasorelaxation associated with release of NO from the endothelium. Accordingly, MMA-containing resin materials appear to be safer for human applications than materials containing HEMA.     

Increased resistance of Streptococcus pneumoniae isolates to antimicrobial drugs, at a referral hospital in north-west Ethiopia

Beta lactam antibiotics were very effective against Streptococcus pneumoniae. However, resistance to this class of antibiotics has become an increasing problem. Reports of penicillin resistant and multidrug resistant strains are being made in many parts of the world. We examined the drug sensitivity pattern of S. pneumoniae isolates in a retrospective analysis of laboratory records of S. pneumoniae isolates between March 2001 and April 2005 at Gondar University Hospital, Ethiopia. A significant proportion of the isolates were found to be resistant to one or more of the commonly used antibiotics. Furthermore, the isolates appear to be acquiring an increasing resistance to crystalline penicillin, cotrimoxazole and ampicillin. This situation needs immediate attention.