Antibody testing in Indian children with celiac disease.

BACKGROUND: We prospectively evaluated the usefulness of IgA tissue transglutaminase antibodies (IgA tTG) in the initial diagnosis of celiac disease (CD) and compared its diagnostic potential with that of IgA anti-endomysial antibodies (IgA EMA) and anti-IgA and IgG gliadin antibodies (AGA and AGG, respectively). METHODS: Sera of 23 untreated children fulfilling the revised ESPGHAN criteria for diagnosis of CD (Group I; mean age 10.8 y); 19 disease controls (Group II; mean age 8.5 y) presenting with chronic diarrhea, short stature or both; and 22 healthy children (Group III; mean age 8.8 y) were studied. These were tested in a blinded manner for AGA, AGG, IgA tTG (guinea pig as antigen) and IgA EMA. RESULTS: In Group I, IgA EMA was positive in 19, IgA tTG in 17, AGA in 14 and AGG in 17 patients. In Group II, these tests were positive in 1, 0, 2 and 14 patients, respectively and in Group III, in 0, 0, 0 and 1 child, respectively. Analyzing data from Group I and II, IgA EMA, IgA tTG, AGA and AGG had sensitivity rates of 83%, 74%, 61% and 74%, respectively; the specificity rates were 95%, 100%, 89% and 26%; positive predictive values were 95%, 100%, 88% and 55% and negative predictive values were 82%, 74%, 65% and 45%, respectively. CONCLUSION: IgA tTG is useful for the diagnosis of CD, with sensitivity and specificity rates comparable to those of EMA and this test is well suited for use in tropical countries like India.     

Assessment of extraocular muscles position and anatomy by 3-dimensional ultrasonography: a trial in craniosynostosis patients.

PURPOSE: To determine whether 3-dimensional ultrasonography (3D US) provides information about anatomy and position of extraocular muscles to better guide surgeons approaching strabismus in patients with craniosynostosis who often have anomalous or absent eye muscles. METHODS: The 4 rectus eye muscles were imaged using 3D US for 7 children with craniosynostosis before or after strabismus surgery. Reconstructed 3D images were interpreted as having normal or abnormal anatomy and position, based on comparison with images acquired from 6 normal eyes. Interpretation was validated against the intraoperative findings from strabismus surgery. RESULTS: A total of 34 scans from the study group were used for comparison and validation purposes. Accuracy of anatomical assessments was 85% +/- 12% (percentage +/- confidence interval) and of positional assessments was 62% +/- 16%. Sensitivity and specificity of anatomical assessments was 80% +/- 14% and 88% +/- 10%, respectively. Anatomic anomalies detected by 3D US included excessively thick, thin, scarred and fibrotic, and absent muscles. Sensitivity and specificity of positional assessments was 48% +/- 17% and 85% +/- 12%, respectively. Positional anomalies such as muscle displacement off the normal clock hour axis or posteriorly displaced insertion were also detected. CONCLUSIONS: The 3D US may have an adjunctive role in determining anatomy and position of rectus muscles in patients with craniosynostosis, although it was more accurate in assessing anatomic features rather than positional features of rectus muscles.     

The interaction of cocaine and alcohol on schedule-controlled responding

 Within a number of physiological preparations, the effects of alcohol and cocaine in combination are reported to be greater than the effects of either drug given alone. Little has been reported, however, on the behavioral effects of the interaction. The present study investigated this issue by assessing the effects of cocaine and alcohol (alone and in combination) on schedule-controlled responding. Specifically, rats were trained to respond on an FR20 schedule for a water reinforcer. They were then administered cumulative doses of cocaine or alcohol. Following this, subjects were administered ineffective doses of alcohol prior to further dose-response assessments with cocaine and with ineffective doses of cocaine prior to further dose-response assessments with alcohol. Cocaine and alcohol alone produced dose-related decreases in responding. Furthermore, the dose-response function for cocaine was shifted to the left by alcohol and the dose-response function for alcohol was shifted to the left by cocaine. An isobolographic analysis revealed that the interaction between cocaine and alcohol was additive in nature. The possible bases for the interaction (e.g., changes in cocaine pharmacokinetics by alcohol and the formation of cocaethylene following co-administration of cocaine and alcohol) were discussed. Received: 22 February 1996 / Final version: 23 August 1996     

Multicenter retrospective development and validation of a clinical prediction rule for nosocomial invasive candidiasis in the intensive care setting

The study presented here was performed in order to create a rule that identifies subjects at high risk for invasive candidiasis in the intensive care setting. Retrospective review and statistical modelling were carried out on 2,890 patients who stayed at least 4 days in nine hospitals in the USA and Brazil; the overall incidence of invasive candidiasis in this group was 3% (88 cases). The best performing rule was as follows: Any systemic antibiotic (days 1–3) OR presence of a central venous catheter (days 1–3) AND at least TWO of the following—total parenteral nutrition (days 1–3), any dialysis (days 1–3), any major surgery (days −7–0), pancreatitis (days −7–0), any use of steroids (days −7–3), or use of other immunosuppressive agents (days −7–0). The rate of invasive candidiasis among patients meeting the rule was 9.9%, capturing 34% of cases in the units, with the following performance: relative risk 4.36, sensitivity 0.34, specificity 0.90, positive predictive value 0.01, and negative predictive value 0.97. The rule may identify patients at high risk of invasive candidiasis. Results of this project were partially presented at Focus on Fungal Infections 14, New Orleans, LA, USA, 2004. Abstract no. 51.     

Mediators of induction of augmented expression of plasminogen activator inhibitor type-1 in Hep G2 cells by platelets.

Plasminogen activator inhibitor type-1 (PAI-1) is a physiologic modulator of the fibrinolytic system. We have shown previously that PAI-1 biosynthesis in cultured cells depends on several factors in serum. Because platelets are richly endowed with specific growth factors and because the release reaction is an integral part of thrombosis, the present study was performed to determine whether platelets augment PAI-1 production and if so, to define mediators responsible. Hep G2 cells were used to determine whether platelet lysates increased PAI-1 synthesis in a dose and time-dependent manner. In cells labeled metabolically with 35S-methionine for 6 h, an increase in labeled PAI-1 was elicited indicative of de novo synthesis as well as increased secretion of PAI-1 mediated by platelet lysates. Steady state levels of both the 3.2 and 2.2 kb forms of PAI-1 mRNA increased after 2 h and peaked in 3-5 h in a dose-dependent fashion as well. Incubation of Hep G2 cells with collagen activated platelets resulted in a similar induction of PAI-1 mRNA. The increase in PAI-1 mRNA occurred with exposure of the cells to platelet lysates for intervals as brief as 15 min and was not inhibited by cycloheximide indicating its independence of new protein synthesis. In order to identify the factors in platelets responsible for the induction of PAI-1 synthesis in the Hep G2 cell model system, neutralizing antibodies were used to inhibit specific platelet associated growth factors. Antibodies to transforming growth factor-beta (TGF-beta) and to the epidermal growth factor (EGF)/transforming growth factor alpha (TGF-alpha) receptor inhibited the platelet lysate-mediated increase in PAI-1 protein by 77%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dependence of metabolic and structural heterogeneity of cholesterol ester-rich very low density lipoproteins on the duration of cholesterol feeding in rabbits.

Cholesterol ester-rich (CER) VLDL accumulate rapidly in the plasma of rabbits fed cholesterol-enriched diets. However, the major loci of enhanced synthesis of subfractions of CER-VLDL, their interaction with macrophages, and their relative contribution to atherogenesis have not yet been elucidated. To determine whether anabolism is hepatic or intestinal, subfractions of CER-VLDL were characterized at selected intervals from day 0 to 60 of cholesterol feeding. Rate zonal ultracentrifugation of CER-VLDL from rabbits fed cholesterol for 4 and 60 d demonstrated an early increase of the proportion of cholesterol carried in the intestinally-derived fraction (designated as Fx-I) of VLDL compared with that in hepatically-derived particles (Fx-H). Quantification by size exclusion HPLC also demonstrated that Fx-I was a prominent CER-VLDL component at day 4, while Fx-H particles became increasingly prominent with further cholesterol feeding. At both 4 and 60 d Fx-I stimulated cholesterol esterification and intracellular cholesterol content in macrophages more than the corresponding Fx-H did. In fact, Fx-H harvested at 4 d produced no cholesterol ester deposition. In contrast, Fx-H harvested at 60 d markedly stimulated cholesterol esterification and intracellular cholesterol content. Thus, both compositional and metabolic characteristics of CER-VLDL changed as a function of the duration cholesterol feeding.     

Peroneal tendon subluxation in a case of anomalous peroneus brevis muscle.

We report a case of peroneal tendon subluxation as a result of an anomalous extension of the peroneus brevis muscle into the fibular groove, causing an encroachment phenomenon, stretching-out of the superior peroneal retinaculum, longitudinal splitting of the peroneus brevis tendon, subluxation of the peroneal tendons, and peroneal tenosynovitis. We describe a simple surgical technique for tendon stabilization, after decompression of the fibular groove.     

Adult medulloblastoma: review of 13 cases with emphasis on MRI

Medulloblastomas are generally associated with childhood, but 14–30% occur in adults, accounting for 1% of adult central nervous system tumors. While approximately one third of adult medulloblastomas present as vermian tumors similar to those seen in childhood, the majority differ substantially from the childhood variety. In this series of 13 patients, 5 had lateral, seemingly extra-axial masses in the cerebellopontine angle or at the tentorium, simulating meningiomas or acoustic neuromas, but angiographic hypovascularity in 2 of the latter suggested a diagnosis other than meningioma. Of 4 paramedian tumors, 3 diffusely infiltrated the cerebellar white matter, showed little or no gadolinium enhancement and were not associated with hydrocephalus. Hydrocephalus was present in less than half of our patients; in childhood the reported incidence is 85–100%. A possible association with pregancy was noted.