Alagille syndrome and optic pit

Background Optic disc anomalies are frequently associated with Alagille syndrome. We report here the first case of a patient with Alagille syndrome combined with optic pit and serous macular detachment. Methods A male patient with Alagille syndrome was referred from the pediatric hepatology department for investigation of visual loss in the right eye. Anterior segment examination showed evidence of posterior embryotoxon, confirmed by gonioscopic evaluation. Dilated fundus examination revealed serous macular detachment and optic pit. Results OCT 3 scans confirmed the clinical findings. Conclusions Optic pit is uncommon and should prompt a search for genetic disorders or development abnormalities. The association between the two syndromes in this patient might be due to failure of correct neuroectodermal development, for which a common genetic pathway is likely.     

Computerized follow-up of discrepancies in image interpretation between emergency and radiology departments

Radiographs are ordered and interpreted for immediate clinical decisions 24 hours a day by emergency physicians (EP’s). The Joint Commission for Accreditation of Health Care Organizations requires that all these images be reviewed by radiologists and that there be some mechanism for quality improvement (QI) for discrepant readings. There must be a log of discrepancies and documentation of follow up activities, but this alone does not guarantee effective Q.I. Radiologists reviewing images from the previous day and night often must guess at the preliminary interpretation of the EP and whether follow up action is necessary. EP’s may remain ignorant of the final reading and falsely assume the initial diagnosis and treatment were correct. Some hospitals use a paper system in which the EP writes a preliminary interpretation on the requisition slip, which will be available when the radiologist dictates the final reading. Some hospitals use a classification of discrepancies based on clinical import and urgency, and communicated to the EP on duty at the time of the official reading, but may not communicate discrepancies to the EP’s who initial read the images. Our computerized radiology department and picture archiving and communications system have increased technologist and radiologist productivity, and decreased retakes and lost films. There are fewer face-to-face consultations of radiologists and clinicians, but more communication by telephone and electronic annotation of PACS images. We have integrated the QI process for emergency department (ED) images into the PACS, and gained advantages over the traditional discrepancy log. Requisitions including clinical indications are entered into the Hospital information System and then appear on the PACS along with images and readings. The initial impression, time of review, and the initials of the EP are available to the radiologist dictating the official report. The radiologist decides if there is a discrepancy, and whether it is category I (potentially serious, needs immediate follow-up), category II (moderate risk, follow-up in one day), or category III (low risk, follow-up in several days). During the working day, the radiologist calls immediately for category I discrepancies. Those noted from the evening, night, or weekend before are called to the EP the next morning. All discrepancies with the preliminary interpretation are communicated to the EP and are kept in a computerized log for review by a radiologist at a weekly ED teaching conference. This system has reduced the need for the radiologist to ask or guess what the impression was in the ED the night before. It has reduced the variability in recording of impressions by EP’s, in communication back from radiologists, in the clinical follow-up made, and in the documentation of the whole QI process. This system ensures that EP’s receive notification of their discrepant readings, and provides continuing education to all the EP’s on interpreting images on their patients.     

In vitro activity of ceftriaxone and other cephalosporins against 602 clinical isolates of staphylococci from geographically diverse medical centers

The in vitro activity of ceftriaxone and six additional antimicrobial agents (ceftizoxime, cefoperazone, cefuroxime, fleroxacin, ciprofloxacin, and trimethoprim/sulfamethoxazole) was assessed or 602 recent clinical isolates of staphylococci from six geographically distinct medical centers in North America. All seven antimicrobial agents were active (90–100% of strains susceptible) against oxacillin-susceptible (OS) strains of Staphylococcus aureus (OSSA) and coagulase-negative staphylococci (OSCNS) but had limited activity against oxacillin resistant (OR) staphylococci. Our assessment of the in vitro antistaphylococcal activity of ceftriaxone against contemporary isolates of Staphylococcus aureus and coagulase-negative staphylococci indicates that the activity versus OS staphylococci has not changed over the past decade despite widespread use of the drug. It appears that these agents will continue to be useful for empiric therapy in those centers in which OR strains are uncommon.Corresponding author.     

Metabolism of methyl-branched iodo palmitic acids in cultured hepatocytes

The metabolic fate of methyl-branched iodo fatty acids was studied in primary culture of rat hepatocytes. We compared 16-iodo-2-R,S-methyl palmitic acid (2-Me), which can be oxidized, with 16-iodo-3-R,S-methyl palmitic acid (3-Me) which can be oxidized only after an initial oxydation and with 16-iodo-2,2-dimethyl palmitic acid (2,2-Me₂) and 16-iodo-3,3-dimethyl palmitic acid (3,3-Me₂) which cannot be oxidized at all. The normal fate of natural fatty acids was given by comparative experiments with [1-¹⁴C] palmitic acid. Monomethyl-branched iodo fatty acids were taken up in the same range as palmitic acid but more than dimethyl-branched iodo fatty acids. After a 15-h incubation, acido-soluble products (ASP) accounted for 75% of the radioactivity taken up as 16-iodo-2-methyl palmitic acid, 50% as other methyl-branched iodo fatty acids and only 30% as palmitic acid, which indicated that all the methyl-branched iodo fatty acids underwent a strong deiodination process. Fatty acids were esterified in the following order: palmitic acid >16-iodo-3-R,S-methyl palmitic acid>16-iodo-2-R,S-methyl palmitic acid>16-iodo-2,2-dimethyl palmitic acid>16-iodo-3,3-dimethyl palmitic acid. Cultured hepatocytes, labelled for 3 h with the various fatty acids and reincubated for 12 h without fatty acid, secreted large amounts of free dimethylbranched iodo fatty acids as compared to the monomethyl ones and palmitic acid. Only hepatocytes prelabelled with 16-[¹²⁵I]iodo-2,2-dimethyl palmitic acid exhibited an appreciable secretion of labeled triglycerides, but at a lower rate than with [1-¹⁴C] palmitic acid. Conversely, the 16-iodo-monomethyl palmitic acids remained chiefly in hepatocyte triglycerides. Minute amounts of 16-iodo-methyl-branched-palmitic acids were found in hepatocyte or secred phospholipids as compared with palmitic acid. This metabolic fate of methyl-branched iodo palmitic acids argues against their utilization as imaging probes to monitor in vivo the synthesis and the secretion of triglycerides by the liver.     

Investigations on the biology,epidemiology, pathology and control of<Emphasis Type="Italic"> Tunga penetrans</Emphasis> in Brazil: I. Natural history of tungiasis in man

Tungiasis is an important health problem in poor communities in Brazil and is associated with severe morbidity, particularly in children. The causative agent, the female flea Tunga penetrans, burrows into the skin of its host, where it develops, produces eggs and eventually dies. From the beginning of the penetration to the elimination of the carcass of the ectoparasite by skin repair mechanisms, the whole process takes 4-6 weeks. The present study is based on specimens from 86 patients, for some of whom the exact time of penetration was known. Lesions were photographed, described in detail and biopsied. Biopsies were examined histologically and by means of scanning electron microscopy (SEM). Based on clinical, SEM and histological findings, the "Fortaleza classification" was elaborated. This allows the natural history of tungiasis to be divided into five stages: (1) the penetration phase, (2) the phase of beginning hypertrophy, (3) the white halo phase, (4) the involution phase and (5) residues in the host's skin. Based on morphological and functional criteria, stages 3 and 4 are divided into further substages. The proposed Fortaleza classification can be used for clinical and epidemiological purposes. It allows a more precise diagnosis, enables the assessment of chemotherapeutic approaches and helps to evaluate control measures at the community level.     

Non-heparan sulfate-binding interactions of endostatin/collagen XVIII in murine development.

Knobloch syndrome is characterized by a congenital generalized eye disease and cranial defect. Pathogenic mutations preferentially lead to a deletion or functional alteration of collagen XVIII's most C-terminal endostatin domain. Endostatin can be released from collagen XVIII and is a potent inhibitor of angiogenesis and tumor growth. We show differential expression of binding partners for endostatin, vascular endothelial growth factor (VEGF), and the collagen XV endostatin homologue in murine embryonal development using a set of alkaline phosphatase fusion proteins. Consistent with the human phenotype, vascular mesenchyme in the developing eye was identified as endostatin's primary target. While endostatin predominantly bound to blood vessels, the VEGF164 affinity probe labeled nonvascular tissues such as forebrain, hindbrain, the optic nerve, and the surface ectoderm of the future cornea. Strikingly increased staining specificity was observed with a non-heparin/heparan sulfate-binding endostatin probe. In contrast, elimination of the heparan sulfate binding site from VEGF led to complete loss of binding. The collagen XV endostatin homologue showed a highly restricted binding pattern. Oligomerization with endogenous endostatin was ruled out by use of collagen XVIII knockout mice. Our data provide strong evidence that collagen XVIII's C-terminal endostatin domain harbors a prominent tissue-binding site and that binding can occur in the absence of heparan sulfates in situ.     

Treatment of idiopathic inflammatory myositis associated interstitial lung disease: A systematic review and meta-analysis

Objective

Interstitial lung disease (ILD) is the most severe complication of idiopathic inflammatory myositis (IIM), resulting in significant increase in morbidity and mortality and for which the best treatment remains controversial. We conducted a meta-analysis to evaluate the efficacy of therapies used for the management of IIM-related ILD.

PCR analysis of pulsed-field gel electrophoresis-purified plastid DNA,a sensitive tool to judge the hetero-/homoplastomic status of plastid transformants

The genetic transformation of plastids of higher plants has developed into a powerful approach for both basic research and biotechnology. Due to the high copy number of the plastid genome per plastid and per cell, repeated cycles of shoot regeneration under conditions selective for the modified plastid chromosome are required to obtain transformants entirely lacking wild-type plastid genomes. The presence of promiscuous plastid DNA in nuclear and/or mitochondrial genomes that generally contaminate even gradient-purified plastid fractions reduces the applicability of the highly sensitive PCR approach to monitor the absence of residual wild-type plastid chromosomes in transformed lines. It is therefore difficult, or even impossible, to assess reliably the hetero- or homoplastomic state of plastid transformants in this manner. By analysing wild-type and transplastomic mutants of tobacco, we demonstrate that separation of plastid chromosomes isolated from gradient-purified plastid fractions by pulsed-field gel electrophoresis can overcome the problem of (co)amplification of interfering promiscuous plastid DNA. PCR analyses with primers specific for plastid, mitochondrial and nuclear genes reveal an impressive purity of such plastid DNA fractions at a detection limit of less than one wild-type plastid chromosome copy per ten transplastomic cells.