Fever, rash, and pancytopenia following vancomycin rechallenge in the presence of ceftazidime.
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Adult↗
Biomedical subjects
S Levi
Publications and source records attributed to S Levi.
Immunohistochemistry of HFE in the duodenum of C282Y homozygotes with antisera for recombinant HFE protein.
BACKGROUND AND OBJECTIVE: HFE is a class-I MHC related protein which carries the C282Y mutation in most patients with hereditary hemochromatosis, an iron overload disease. HFE protein is expected to have a relevant role in the regulation of duodenal iron absorption, and HFE protein was immunohistochemically identified in the crypt cells. The aim of the work was to analyze whether the C282Y mutation affects HFE accumulation in the duodenum. DESIGN AND METHODS: We developed antisera for the extracellular portion of recombinant human HFE protein expressed in E. coli. The antisera were specific for HFE protein and the C282Y mutant in immunoblotting, immunoprecipitation and immunocytochemistry experiments of transfected cells, and they did not cross react with HLA antigens in various analyses. The antisera gave positive results in the staining of paraffin-fixed sections of duodenal slices of subjects with hemochromatosis. RESULTS: The antisera stained evident supranuclear granules in all enterocytes of 7 C282Y homozygous subjects, and a dark area in the same region in 3 other C282Y homozygotes. Granular bodies were absent from the duodenal sections of 8 C282Y negative subjects, from 2 C282Y heterozygotes and 3 C282Y homozygotes, with or without hemochromatosis. INTERPRETATION AND CONCLUSIONS: The detection of HFE-protein in granular bodies in the enterocytes of the large majority (77%) of C282Y homozygotes and not in other subjects suggests that the mutation facilitates protein accumulation in the duodenum.
Amino Acid Substitution↗
[Fetal echocardiography volume mode (3 dimensions)].
About 10 out of 100 newborns are affected by congenital heart defects that remain the least easy to detect remain prenatally, despite the relatively high detection rate of fetal malformations. Antenatal diagnosis of congenital heart defects depends on operator experience and skill, but recent techniques of computer assisted ultrasound imaging should be useful by allowing easier recognition of fetal heart anomalies. New imaging procedures include a set of internal fetal views by volume rendering and post acquisition slice selection. Internal views are nearly similar to those obtained during open-heart surgery. In practice, from typical long axis and apical views, two volumes are stored for further examination. Fetal movement, fetal spine and maternal obesity are unfavorable circumstances for useful examination. The routine use of cardiac volume sampling for malformations screening should be possible with increasing speed in image acquisition and in data storage to display real-time 3D imaging.
Echocardiography↗
Independence for people with disabilities. A physician's primer on assistive technology.
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Persons with Disabilities↗
Overexpression of the hereditary hemochromatosis protein, HFE, in HeLa cells induces and iron-deficient phenotype.
A transfectant HeLa cell clone expressing HFE under the control of a tetracycline-repressible promoter was generated. HFE expression was fully repressed by the presence of doxycycline, while it was strongly induced by growth in the absence of doxycycline. HFE accumulation was accompanied by a large (approximately 10-fold) decrease in H- and L-ferritin levels, by a approximately 3-4-fold increase in transferrin receptor, and a approximately 2-fold increase in iron regulatory protein activity. These indices of cellular iron deficiency were reversed by iron supplementation complexes. The overexpressed HFE immunoprecipitated together with transferrin receptor, indicating a physical association which is the likely cause for the observed approximately 30% decrease in 55Fe-transferrin incorporation after 18 h incubation. In the HFE-expressing cells the reduction in transferrin-mediated iron incorporation was partially compensated by a approximately 30% increase in non-transferrin iron incorporation from 55Fe-NTA, evident after prolonged, 18 h, incubations. The findings indicate that HFE binding to transferrin receptor reduces cellular iron availability and regulates the balance between transferrin-mediated and non-transferrin-mediated cellular iron incorporation.
Apoferritins↗
The performance of routine ultrasonographic screening of pregnancies in the Eurofetus Study.
OBJECTIVES: The purpose of the Eurofetus Study was to evaluate the accuracy of the antenatal detection of malformations by routine ultrasonographic examination in unselected populations. STUDY DESIGN: All ultrasonographic diagnoses of malformations and the outcomes of the fetuses were prospectively recorded in 61 European obstetric units over a 3-year period (1990-1993). Also recorded were all cases of malformation diagnosed after abortion or birth for the mothers who underwent follow-up in these centers. RESULTS: Of 3685 malformed fetuses, 2262 had received diagnoses during pregnancy (sensitivity, 61.4%). Of a total number of 4615 malformations, 2593 were detected (sensitivity, 56.2%). The detection sensitivity was higher for the major than for the minor abnormalities (73.7% vs 45.7%), and the diagnosis was made earlier in the pregnancy (24.2 weeks vs 27.6, P <. 01). Overall, 55% of the major abnormalities were detected within 24 gestational weeks. Within each severity group the accuracy of detection depended on the system. For the major abnormalities it was better for the central nervous system (88.3%) and urinary tract (84. 8%) but lower for the heart and great vessels (38.8%). Detection of minor abnormalities was also effective for the urinary tract (89.1%) but not for the heart and great vessels (20.8%) or the musculoskeletal system (18%). Detection of abnormalities had an influence on the rate of termination of pregnancy. The rate of live births for the mothers bearing fetuses with major abnormalities was lower than that for the mothers in whom no abnormalities were detected, mainly because of the higher rate of elective terminations of pregnancy in the former group. CONCLUSION: Systematic ultrasonographic screening during pregnancy can now detect a large proportion of fetal malformations, although some still escape detection.
Blood Vessels↗
A single centre's 20 years' experience of columnar-lined (Barrett's) oesophagus diagnosis.
BACKGROUND: The pattern of oesophageal carcinoma type has been changing for some time in a number of countries, with adenocarcinoma becoming more frequent OBJECTIVE: To investigate the prevalence of columnar-lined (Barrett's) oesophagus and oesophageal adenocarcinoma in Barrett's oesophagus during a 20-year period in a single centre. METHODS: All upper gastrointestinal endoscopy and histology reports for the period January 1977 to December 1996 inclusive were reviewed. Data were analysed from patients who had histologically proven Barrett's oesophagus. The data were analysed as a single cohort and in five-year bands according to the date of diagnosis. RESULTS: Of 44,721 endoscopies, 636 Barrett's oesophagus cases were diagnosed; 508 (323 males 185 females; M:F ratio 1.7) were histologically proven. The frequency of Barrett's oesophagus detection increased steadily from 0.2% to 1.6% of all endoscopies per five-year band. The M:F ratio and the mean ages at diagnosis (61 years, range 60-63 for males and 69 years, range 68-79 for females) remained constant throughout. Barrett's oesophagus was diagnosed at a younger age in males (peak 60-69 years) compared to females (peak 70-79 years). The male oesophageal adenocarcinoma incidence (11.1%) was almost twice that in females (6.5%). In the majority (81%), the initial diagnosis of oesophageal adenocarcinoma and Barrett's oesophagus was made concurrently. CONCLUSIONS: The increasing Barrett's oesophagus frequency may reflect an increasing incidence or recognition of this condition or both. Barrett's oesophagus males are more likely to develop oesophageal adenocarcinoma than females.
Adenocarcinoma↗
Routine ultrasound screening of congenital anomalies. An overview of the European experience.
Results from ultrasound in low-risk pregnant women are significant when routine screening is performed on a large population because the anomalies are rare. Professionals expect from routine ultrasound objective information that cannot usually be obtained by clinical procedures. Parents seek reassurance about the absence of fetal congenital anomalies and overall fetal health. Therefore, Europeans view routine ultrasound as a part of obstetrical care, capable of filling important gaps by delivering much key information for improving obstetrical practice. Fetal anomalies screening (FAS) requires higher education and qualifications than obstetrical ultrasound. The health insurance systems support ultrasound screening and allow its spread in most European countries; approximately 98% of pregnant women are examined by ultrasound and, frequently, two to three times (usually once per trimester). Detection rate of congenital anomalies is about 28% in geographical areas (private practice and hospitals), 60 to 80% in Ob/Gyn's ultrasound labs. Routine ultrasound screening policy has not proved to result in an immoderate use of ultrasound; on the contrary, chaotic use of routine ultrasound can lead to an unproductive and excessive number of scans. New trends in FAS, such as the early detection of fetal defects and chromosomal anomalies, bring more arguments for routine screening. Effectiveness should increase by enhancing education and training and the systematic referral for FAS to accredited laboratories.
Congenital Abnormalities↗
Eurofetus: an evaluation of routine ultrasound screening for the detection of fetal defects. Aims and method.
The aims of this study are (1) to evaluate the efficiency of ultrasound in detecting CA in low-risk populations of pregnant women by routine screening performed in hospital ultrasound labs (level II); (2) to highlight the areas where improvement could be obtained; (3) to determine efficient timing and number of examinations; (4) to evaluate the psychological returns of detection and nondetection of CA; and (5) to evaluate the cost-effectiveness ratio of antenatal screening of CA. A European collaboration was supposed to help in meeting these objectives because results concerning the analysis of individual CAs or groups of CAs can only be statistically significant when their number is sufficiently large. It was estimated that it was necessary to collect nearly 5,000 CA; this corresponds to about 200,000 pregnant women, the prevalence of malformations at birth being estimated at 2.5%. These conditions yield worthy conclusions, given the following circumstances: a large variety of CA, the extremely low incidence of each CA, the multiple approaches for diagnosis and management, the manifold classes of defects, the differences in gestational age when anomalies are detectable and detected. We study prospectively (1) the reliability of ultrasound in detecting antenatal malformations by recording all CA, ultrasonically suspected and not; (2) the gestational age of anomaly recognition; (3) the response to antenatal diagnosis of CA; (4) the individual outcome of pregnancies; (5) the financial cost of the screening program; and (6) the psychological consequences for the parents.
Congenital Abnormalities↗
Sensitivity of routine ultrasound screening of pregnancies in the Eurofetus database. The Eurofetus Team.
In this prospective study, we recorded details on 3,685 fetuses with congenital structural abnormalities from an unselected population of women who underwent routine ultrasound examinations during their pregnancies. Overall, 2,262 fetuses were diagnosed as being abnormal before birth (sensitivity = 61.4%). The total number of abnormalities was 4,615, of which 1,733 (37.5%) were major abnormalities. The overall number of detected abnormalities was 2,593 (sensitivity = 56.2%). If only major abnormalities were considered, the sensitivity rose to 73.7%, compared to only 45.7% for the minor abnormalities. Within each severity group, the accuracy of detection varied across systems. For the major abnormalities, it was higher for the central nervous system (88.3%) and urinary tract (84.8%), but lower for heart and great vessels (38.8%). Detection of minor abnormalities was also effective for the urinary tract (89.1%), but not for the heart and great vessels (20.8%) and the musculoskeletal system (18%).
Congenital Abnormalities↗
Sensitivity of fetal anomaly detection as a function of time.
In this paper, we show that the ratio of the number of fetal anomalies detected by ultrasounds (US) to the total number of cases is not a consistent estimator of the US sensitivity. As Eddy pointed out, when the disease evolves over time, the sensitivity of a test also varies over time according to the development of the disease. To assess correctly the detection capability of a test, it is therefore necessary to estimate a time continuous function (sensitivity function) instead of a single parameter. From a methodological point of view, by considering the "detectability" time of a fetal anomaly as a random variable and parametrizing its distribution function, we estimate the probability that an anomaly is detected conditional upon the precise timing of actually performed US during pregnancy. We fit this model with Eurofetus data (about 7,300 abnormal fetuses), and we compare estimations for different kinds of anomalies (classification based on the system involved and/or severity of the handicap). To allow for heterogeneity of anomalies regarding the detectability time, we generally adopt mixture models. For instance, we select a bi-gamma distribution for major malformations and estimate that 63% of such anomalies are detectable quite early in pregnancy (conditional mean: 15.2 weeks of amenorrhea (WA) +/- 4.2 WA), the others becoming detectable later (30.3 WA +/- 6.4 WA). Such results are then integrated in a cost-effectiveness analysis.
Congenital Abnormalities↗
Detection of chromosomal abnormalities, an outcome of ultrasound screening. The Eurofetus Team.
Chromosomal abnormalities were recorded from all the fetuses of women who benefited from sonographic examinations in the Eurofetus centers, excluding those for whom karyotyping was motivated by age or personal history. Among the 378 chromosomal abnormalities recorded, 210 were detected before birth (sensitivity = 55.6%). Down syndrome (trisomy 21) represented 197 cases, or which 68 were detected before birth (sensitivity = 34.5%). Eighty-two of the cases of Down syndrome had associated structural abnormalities; the sensitivity in these cases increased to 57%. Among the 115 cases of Down syndrome without structural abnormalities, 21 (18.3%) had associated abnormal ultrasound findings that led to prenatal detection. Sensitivity of prenatal detection was 58.1% for trisomy 13 and 79% for trisomy 18. For the abnormalities detected before birth, spontaneous fetal death occurred in 27% of cases, and an early termination of pregnancy was decided in 53% of cases.
Chromosome Aberrations↗
Analysis of ferritins in lymphoblastoid cell lines and in the lens of subjects with hereditary hyperferritinemia-cataract syndrome.
Hereditary hyperferritinemia-cataract syndrome (HHCS) is an autosomal and dominant disease caused by heterogeneous mutations in the iron responsive element (IRE) of the 5' untranslated flanking region of ferritin L-chain mRNA, which reduce the binding to the trans iron regulatory proteins and make L-chain synthesis constitutively upregulated. In the several families identified so far, the serum and tissue L-ferritin levels are fivefold to 20-fold higher than in nonaffected control subjects, iron metabolism is apparently normal, and the only relevant clinical symptom is early onset, bilateral cataract. Some pathogenetic aspects of HHCS remain obscure, with particular reference to the isoferritins produced by HHCS cells, as well as the mechanism of cataract formation. We analyzed lymphoblastoid cell lines obtained from two nonaffected control subjects and from HHCS patients carrying the substitution A40G (Paris-1), G41C (Verona-1), and the deletion of the residues 10-38 (Verona-2) in the IRE structure. Enzyme-linked immunosorbent assays specific for the H- and L-type ferritins showed that L-ferritin levels were up to 20-fold higher in HHCS than in control cells and were not affected by iron supplementation or chelation. Sequential immunoprecipitation experiments of metabolically-labeled cells with specific antibodies indicated that in HHCS cells about half of the L-chain was assembled in L-chain homopolymers, which did not incorporate iron, and the other half was assembled in isoferritins with a high proportion of L-chain. In control cells, all ferritin was assembled in functional heteropolymers with equivalent proportion of H- and L-chains. Cellular and ferritin iron uptake was slightly higher in HHCS than control cells. In addition, we analyzed the lens recovered from cataract surgery of a HHCS patient. We found it to contain about 10-fold more L-ferritin than control lens. The ferritin was fully soluble with a low iron content. It was purified and partially characterized. Our data indicate that: (1) in HHCS cells a large proportion of L-ferritin accumulates as nonfunctional L-chain 24 homopolymers; (2) the concomitant fivefold to 10-fold expansion of ferritin heteropolymers, with a shift to L-chain-rich isoferritins, does not have major effects on cellular iron metabolism; (3) L-chain accumulation occurs also in the lens, where it may induce cataract formation by altering the delicate equilibrium between other water-soluble proteins (ie, crystallins) and/or the antioxidant properties.
Antioxidants↗
Response of monocyte iron regulatory protein activity to inflammation: abnormal behavior in genetic hemochromatosis.
In genetic hemochromatosis (GH), iron overload affects mainly parenchymal cells, whereas little iron is found in reticuloendothelial (RE) cells. We previously found that RE cells from GH patients had an inappropriately high activity of iron regulatory protein (IRP), the key regulator of intracellular iron homeostasis. Elevated IRP should reflect a reduction of the iron pool, possibly because of a failure to retain iron. A defect in iron handling by RE cells that results in a lack of feedback regulation of intestinal absorption might be the basic abnormality in GH. To further investigate the capacity of iron retention in RE cells of GH patients, we used inflammation as a model system as it is characterized by a block of iron release from macrophages. We analyzed the iron status of RE cells by assaying IRP activity and ferritin content after 4, 8, and 24 hours of incubation with lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma). RNA-bandshift assays showed that in monocytes and macrophages from 16 control subjects, IRP activity was transiently elevated 4 hours after treatment with LPS and IFN-gamma but remarkably downregulated thereafter. Treatment with NO donors produced the same effects whereas an inducible Nitric Oxide Synthase (iNOS) inhibitor prevented them, which suggests that the NO pathway was involved. Decreased IRP activity was also found in monocytes from eight patients with inflammation. Interestingly, no late decrease of IRP activity was detected in cytokine-treated RE cells from 12 GH patients. Ferritin content was increased 24 hours after treatment in monocytes from normal subjects but not in monocytes from GH patients. The lack of downregulation of IRP activity under inflammatory conditions seems to confirm that the control of iron release from RE cells is defective in GH.
Adult↗
Transient overexpression of human H- and L-ferritin chains in COS cells.
The understanding of the in vitro mechanisms of ferritin iron incorporation has greatly increased in recent years with the studies of recombinant and mutant ferritins. However, little is known about how this protein functions in vivo, mainly because of the lack of cellular models in which ferritin expression can be modulated independently from iron. To this aim, primate fibroblastoid COS-7 cells were transiently transfected with cDNAs for human ferritin H- and L-chains under simian virus 40 promoter and analysed within 66 h. Ferritin accumulation reached levels 300-500-fold higher than background, with about 40% of the cells being transfected. Thus ferritin concentration in individual cells was increased up to 1000-fold over controls with no evident signs of toxicity. The exogenous ferritin subunits were correctly assembled into homopolymers, but did not affect either the size or the subunit composition of the endogenous heteropolymeric fraction of ferritin, which remained essentially unchanged in the transfected and non-transfected cells. After 18 h of incubation with [59Fe]ferric-nitrilotriacetate, cellular iron incorporation was similar in the transfected and non-transfected cells and most of the protein-bound radioactivity was associated with ferritin heteropolymers, while H- and L-homopolymers remained iron-free. Cell co-transfection with cDNAs for H- and L-chains produced ferritin heteropolymers that also did not increase cellular iron incorporation. It is concluded that transient transfection of COS cells induces a high level of expression of ferritin subunits that do not co-assemble with the endogenous ferritins and have no evident activity in iron incorporation/metabolism.
Animals↗
Acute hepatitis C during pregnancy. Case report and review of the literature.
Treatment of chronic hepatitis C with interferon is well established (Fried 1995, Zein 1995) though not very successful. We report a case of a pregnant doctor who developed acute hepatitis C six weeks after accidental needle-stick injury from a hepatitis C virus positive patient. We review the literature that deals with such cases.
Adult↗
Excessive dietary protein and suboptimal caloric intake have a negative effect on the growth of children with chronic renal disease before and during growth hormone therapy.
Although diet and nutrition are an integral part of the management of individuals with chronic renal failure (CRF), little has been written on the effect of nutrition on the growth response to growth hormone (GH) in CRF. We studied the GH axis and nutritional status of 31 prepubertal children aged 8.7 +/- 0.5 years with a height standard deviation score (SDS) of -3.2 +/- 0.2 (mean +/- SEM) with CRF. Sixteen CRF patients on hemodialysis and 15 on peritoneal dialysis were studied. Forty-four age-matched normal short children without GH deficiency served as controls. Spontaneous 12-hour GH and stimulated GH values were significantly higher and GH binding protein (GHBP) was significantly lower in the CRF patients than in the normal short children. Both before the initiation of GH therapy and after the first year of treatment, the growth velocity (SDS) was inversely correlated with dietary protein intake and positively correlated with caloric intake. GH was administered at a dosage of 28 and 21 IU/m2/wk to the CRF group and the normal short children, respectively, divided into seven daily doses. The growth response of the normal short children was significantly greater than that of the CRF patients. GH therapy induced a smaller increment in GHBP and IGF-I in the CRF patients versus the normal short children (8.8 +/- 2.2 and 10.2 +/- 2.7 v 24.8 +/- 1.3 and 27.6 +/- 2.5 nmol/L, respectively, P < .01). The 1-year growth velocity of the CRF children was most closely correlated with dietary protein and caloric intake. The nutritional status of CRF patients is concluded to be a major factor in growth both before and during GH therapy.
Alkaline Phosphatase↗
Incidence of duodenal ulcer healing after 1 week of proton pump inhibitor triple therapy for eradication of Helicobacter pylori. The Lansoprazole Helicobacter Study Group.
BACKGROUND: A number of clinical studies have assessed the efficacy of short-term twice-daily Helicobacter pylori eradication regimens but few have investigated the proportion of patients in whom duodenal ulcer disease was healed with these regimens. AIM: To compare the safety and efficacy of four 1-week H. pylori eradication regimens in the healing of H. pylori associated duodenal ulcer disease. METHODS: Following endoscopic confirmation of duodenal ulcer disease and a positive CLO test, patients underwent a 13C-urea breath test to confirm H. pylori status. Treatment with one of four regimens: LAC, LAM, LCM or OAM, where L is lansoprazole 30 mg b.d., A is amoxycillin 1 g b.d., M is metronidazole 400 mg b.d., C is clarithromycin 250 mg b.d., and O is omeprazole 20 mg b.d., was assigned randomly to those patients who were H. pylori positive, with 62 (LAC), 64 (LAM), 61 (LCM) and 75 (OAM) patients in each treatment group. Follow-up breath tests and endoscopies were performed at least 28 days after the end of treatment. RESULTS: Duodenal ulcer disease was healed 28 days after treatment in 53/62 (85.5%) patients who were treated with LAC, 52/64 (81.3%) of patients treated with LAM, 49/61 (80.3%) of patients treated with LCM and 60/75 (80.0%) of patients treated with OAM (intention-to-treat analysis, n = 262, assumed unhealed if no follow-up endoscopy was performed). All the treatments were of similar efficacy (P = 0.85, chi-squared test) with regard to the healing of duodenal ulcer disease. CONCLUSIONS: The four 1-week treatment regimens were equally effective in healing H. pylori associated duodenal ulcer disease.
2-Pyridinylmethylsulfinylbenzimidazoles↗