Monoclonal anti-CD52 antibodies: a potential mode of therapy for parvovirus B(19) hepatitis.
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Biomedical subjects
Publications and source records attributed to E Granot.
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PURPOSE: To assess the long-term efficacy of combined vitamin A and E treatment in preventing retinal degeneration in patients with abetalipoproteinaemia (ABL) or homozygous hypobetalipoproteinaemia (HBL). METHODS: Ten patients with ABL and 3 with homozygous HBL who were treated with oral supplements of vitamins A and E were studied. Systemic, ophthalmological and electroretinographic follow-up for a mean of 11.7 years (range 4-20 years) after onset of treatment was evaluated. RESULTS: Despite vitamin A and E treatment, 7 of 10 patients who began treatment prior to 2 years of age and all 3 patients who began treatment later in life manifested unusual fundoscopic pigmentary changes over time. At the end of follow-up, 11 of 13 patients had subnormal mixed cone-rod electroretinogram amplitudes. Seven of 10 patients for whom perimetry was available had mild to severe constriction of the visual fields. CONCLUSIONS: Combined oral vitamin A and E supplementation that is initiated prior to 2 years of age can markedly attenuate the severe retinal degeneration that is associated with untreated ABL or homozygous HBL. Yet, fundoscopic and functional retinal changes do occur despite early initiation of vitamin treatment. Therefore, the adequacy of the present treatment protocol for ABL and homozygous HBL should be re-evaluated.
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OBJECTIVE: Cell adhesion molecules (intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1)) and hyaluronic acid, markers of inflammation and fibrosis were monitored in hepatitis C patients to determine whether changes in plasma levels, during antiviral treatment, can predict long-term response to therapy. METHODS: In 55 patients with chronic hepatitis C virus (HCV), 33 treated with interferon (IFN) and 22 treated with IFN + ribavirin, sera was collected prior to treatment, at 3 + 6 months of therapy and 6 months post-treatment. Levels of ICAM-1, VCAM-1 and hyaluronic acid were correlated with alanine aminotransferase levels, HCV-RNA-polymerase chain reaction status and histological fibrosis scoring. RESULTS: A decrease in ICAM-1 levels at 3 and 6 months of therapy, compared with pretreatment levels, was observed in responders to IFN + ribavirin therapy but this decrease in ICAM-1 levels was not evident following cessation of treatment. Hyaluronic acid levels, in both treatment groups, did not differ significantly between responders and non-responders. Hyaluronic acid levels did correlate, significantly, with degree of fibrosis whereas VCAM-1 levels were marginally increased only in patients with moderate (grade III) fibrosis. CONCLUSIONS: Monitoring of VCAM-1 and hyaluronic acid, during antiviral therapy, does not differentiate between responders and non-responders. A decrease in ICAM-1 levels during IFN + ribavirin treatment is associated with response to therapy, and its efficacy in predicting long-term response should be further substantiated.
Increased concentrations of reactive oxygen species (ROS) and depleted antioxidant defences have been implicated in a cycle of infection, malabsorption and malnutrition, leading to persistent diarrhea. In order to determine whether in non-malnourished children oxidative stress predisposes to the development of persistent diarrhea, infants with acute diarrhea (< 7 days) (n = 39) were compared to infants with persistent diarrhea (> 14 days) (n = 38). Lipid peroxidation was assessed by the TBARs assay and expressed as malondialdehyde equivalent content (nmol MDA/ml plasma), and levels of plasma antioxidants vitamin A and vitamin E were determined. In infants with acute and persistent diarrhea nutritional status, as assessed by weight/height and height-for-age, hemoglobin levels, serum albumin and immunoglobulin levels, did not differ between groups. Serum vitamin A and vitamin E levels did not differ in infants with acute or persistent diarrhea. TBARs, expressed as nmol MDA/ml plasma did not differ between infants with acute or persistent diarrhea and furthermore did not differ from levels in a healthy, similar age, control group. Non-malnourished infants with persistent diarrhea do not exhibit plasma antioxidant depletion or enhanced lipid peroxidation. In these infants, oxidative stress, as reflected in plasma, does not play a role in the pathogenesis of persistent diarrhea.
The authors report the case of an 8-year-old girl who underwent a liver transplant at the age of 18 months because of biliary atresia. She was treated with cyclosporin for more than 5 years. Increased hirsutism prompted a change to tacrolimus therapy. During 11 months the mean tacrolimus level was 8.2 ng/mL. The patient was hospitalized because of an episode of Shigella infection and a threefold increase in tacrolimus level was measured. Despite a reduction of tacrolimus dose, the trough tacrolimus levels were in the range of 16.5 to 22.0 ng/mL during the subsequent 2 weeks. On resolution of the diarrhea, tacrolimus levels returned to those observed before the Shigella infection. It is suggested that the marked increase in tacrolimus levels observed in this patient is a direct result of the damage produced to the gastrointestinal mucosa by the Shigella infection.
Ultrasound modulated light for optical tomography is very useful, since it can provide three-dimensional data with minimal mathematical processing. Although several experimental studies have shown the potential of this method, the link between the ultrasound location and the modulated signal intensity at the detector is not yet fully understood. We derive an analytical formula relating the position of the ultrasound transducer and the optical signal at the detector. We also derive an expression for the signal-to-shot-noise ratio as a function of the transducer position. We show that in certain conditions this ratio is only slowly decreasing as a function of the light penetration depth, which makes this technique attractive for optical tomography.
Four children with familial short stature were diagnosed with celiac disease (CD) by positive serology for antigliadin and antiendomysial antibodies and characteristic intestinal biopsy findings. These patients complied well with their diet as evidenced by their parents' reports, increase in weight standard deviation scores in all but one child, and reversion to seronegativity for antigliadin and antiendomysial antibodies in all four. However, typical catch-up for linear growth did not occur. In our view, the poor response of linear growth is evidence that the original stunting was not due to CD. Since the advent of sensitive tests for antiendomysial antibodies, many asymptomatic children have been diagnosed as having CD. Some of these children are short and despite a history of familial short stature their growth stunting may be wrongly attributed to CD. This report highlights this new problem and emphasizes the need for caution when predicting growth response to a gluten-free diet.
Substance P content was determined by radioimmunoassay in rectal mucosa of 17 children with idiopathic constipation and 9 with normal bowel movements who were used as controls. In children with chronic idiopathic constipation, rectal mucosa substance P levels were lower than levels in the control group: 47.6 +/- 11 vs. 79.4 +/- 11 pg/mg net weight respectively (differences not statistically significant). Substance P levels in rectal mucosa of children with soiling (11/17) did not differ from those of chronically constipated children without soiling (46.0 +/- 16 vs. 50.5 +/- 19 pg/mg net weight). In children with constipation, substance P levels did not correlate either with age or duration of symptoms. Substance P levels in normal controls were similar to levels previously observed in non-constipated adults, whereas levels in constipated children were intermediate between levels observed in healthy subjects and levels in adults with chronic constipation. These findings may point to a motility derangement as a possible factor in the pathogenesis of chronic constipation in childhood.
Acetaminophen toxicity after repeated administration of amounts that only moderately exceed recommended doses, is being increasingly reported in alcoholic or fasting adults. Pediatric experience with this pattern of acetaminophen toxicity is sparse. We present 2 children who developed severe hepatic damage, with renal insufficiency as well in 1, after 15-20 mg/kg of acetaminophen, given at 4-hour intervals for 3-4 days during an intercurrent febrile illness. When given in doses as low as 20 mg/kg at frequent intervals for a number of days, the drug puts children who are vomiting or have sharply reduced caloric intakes at increased risk for severe toxicity. Increased caution and awareness of the toxic effects of acetaminophen are needed, and it should be dispensed with appropriate package-label warnings.
A study was performed in Israel to determine the rate of mother-to-infant HCV transmission in newborns at risk. A group of 22 HCV-infected mothers and their 23 newborns were followed up from early after birth by testing their serum for the presence of HCV antibodies and HCV-RNA. Antibody against HCV was detected in the blood of all newborns immediately after birth, but dropped to low or undetectable levels by 7 months of age. HCV-RNA was detected 2 days after birth in the blood of five infants (22%) but fell to undetectable levels by 6 months. HCV-HVR1 sequence analysis performed in one mother-infant pair on the second day after birth revealed two nucleotide changes. Two months later the same sequence was detected again in the HVR1, suggesting a very low replication rate. Thus, the study showed that vertically transmitted HCV was eliminated in all newborn infants by 6 months after delivery, with concomitant disappearance of HCV antibodies. The mechanism of HCV elimination in newborns at risk remains to be elucidated.
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BACKGROUND: Nitric oxide is thought to play an important role in modulating chronic inflammatory responses as well as in immune-mediated inflammation. We reproduced a gluten-mediated mucosal response in the rectum of celiac and control subjects in order to determine the role of inducible and constitutive nitric oxide synthases in the pathogenesis of this process. MATERIAL: Nine patients with confirmed celiac disease and five healthy controls underwent a long-term rectal gluten challenge (48 h) after an enema of 6 g of crude gluten, and constitutive and inducible nitric oxide synthase activity were determined in rectal biopsies. The histological localization of inducible nitric oxide synthase was determined by immunohistochemistry. RESULTS: Activity of both isoforms of nitric oxide synthase in control subjects did not change significantly after gluten instillation. In celiac patients, constitutive nitric oxide synthase on rectal mucosa also showed no significant changes after challenge with gluten. Inducible nitric oxide synthase isoform exhibited a modest increase 4 h after gluten instillation in celiac patients (mean increase 35% compared with baseline levels) but, 8 h after challenge, generation of iNO synthase was significantly higher: 54% more than pre-challenge production (P < 0.05) and higher than control values (P < 0.05). Inducible nitric oxide synthase staining was mostly localized in mononuclear cells of the epithelium and the lamina propria. After gluten instillation, the enhanced staining was mainly localized in subepithelial areas of the lamina propria. CONCLUSION: Our data suggest a role for nitric oxide, generated by inducible nitric oxide synthase, in the process of rectal mucosa injury by local gluten instillation in sensitized patients. We could not, however, determine if the role of nitric oxide in the ensuing injury of this gluten-induced immune inflammation model is a protective one, or merely a by-product generated by the activation of the inflammatory cells.
Th1 derived cytokines IFN-gamma and IL-2, Th2 cytokine IL-4, and ICAM-1 have been implicated in liver allograft rejection. In order to determine whether monitoring of cytokine profiles during the first days post-liver transplant can predict early rejection we measured IFN-gg, IL-2, sIL-2 receptor, IL-4 and ICAM-1 in 22 patients, in plasma samples obtained within 4 h after liver perfusion (baseline) and between postoperative days (POD) 3-6. ICAM-1 and sIL-2R levels at POD 3-6 were significantly higher than at baseline but did not differ in presence or absence of rejection. Mean percentage increase of ICAM-1 levels was significantly lower in patients with Muromonab-C3 Orthoclone OKT3 (J.C. Health Care) (OKT3) whereas percentage increase of sIL-2R levels was higher in OKT3-treated patients. IFN-gamma levels at POD 3-6 increased from baseline while IL-4 levels were unchanged. Levels of IFN-gamma, IL-4 and their ratios did not correlate with rejection or immunosuppressive therapy. Thus, Th1/Th2 cytokine monitoring during the first week post-transplant does not predict early rejection and immunosuppressive therapy is the predominant factor affecting ICAM and sIL-2R levels after liver transplantation.
BACKGROUND: Breast-fed and formula-fed infants differ in the amount and type of polyunsaturated fatty acids consumed. The fatty acid composition of cell membranes is related to dietary fatty acids and, in adults, changes in membrane fatty acid composition are accompanied by changes in monocyte cytokine production and hence a modification of the immunologic response. OBJECTIVE: Our objective was to determine whether production by immunocompetent cells of the proinflammatory cytokines interleukin 1 (IL-1) and tumor necrosis factor (TNF) differs between breast-fed and formula-fed infants. DESIGN: Twenty-six healthy infants (13 breast-fed and 13 fed modified cow-milk formula) aged 2-4 mo were studied. The fatty acid composition of red blood cell (RBC) membrane phospholipids was measured by gas-liquid chromatography and IL-1 and TNF release were measured in whole blood culture in bacterial-endotoxin-stimulated and unstimulated cells. RESULTS: The infants' ages, weights, hemoglobin concentrations, and white blood cell counts did not differ significantly between groups. The percentage of n-3 fatty acids of total RBC phospholipid fatty acids was significantly higher in breast-fed than in formula-fed infants (6.31 +/- 2.5% compared with 2.98 +/- 0.97%); docosahexaenoic acid (22:6n-3) concentrations were also markedly higher in breast-fed infants (5.1 +/- 1.2% compared with 2.2 +/- 0.9%, P: < 0.001), but eicosapentaenoic acid (20:5n-3) and docosapentaenoic acid (22:5n-3) concentrations did not differ significantly between groups. The percentage of n-6 fatty acids was not significantly different between groups. The percentage of oleic acid (18:1) was higher in formula-fed than in breast-fed infants (16.2 +/- 0.7% compared with 20.6 +/- 1.1%; P: < 0.001). IL-1 and TNF release in whole blood culture did not differ significantly between groups. CONCLUSION: The release of proinflammatory cytokines by immunocompetent cells does not differ significantly in breast-fed and formula-fed infants despite differences in cell membrane fatty acid composition.