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Biomedical subjects

P Rosenthal

Publications and source records attributed to P Rosenthal.

At least 19 recordsLinked to original sources

Catheter based intracoronary brachytherapy leads to increased platelet activation.

BACKGROUND: Vascular brachytherapy (VBT) after percutaneous coronary intervention (PCI) is associated with a higher risk of stent thrombosis than conventional treatment. OBJECTIVE: To investigate in vivo periprocedural platelet activation with and without VBT, and to assess a possible direct effect of radiation on platelet activation. DESIGN: Of 50 patients with stable angina, 23 received VBT after PCI, while 27 had PCI only. The 23 patients who received VBT after PCI were pretreated for one month with aspirin and clopidogrel. Platelet activation was assessed by flow cytometry. RESULTS: The two patient groups did not differ in their platelet activation before the intervention. There was a significant increase in activation immediately after VBT, with 21.2% (interquartile range 13.0% to 37.6%) thrombospondin positive and 54.0% (42.3% to 63.6%) CD 63 positive platelets compared with 12.7% (9.8% to 14.9%) thrombospondin positive and 37.9% (33.2% to 45.2%) CD 63 positive platelets before the intervention (p < 0.001 and p < 0.01, respectively). Patients without VBT had no periprocedural difference in platelet activation immediately after PCI. No increase in platelet activation was found after ex vivo irradiation of blood samples obtained from healthy controls. CONCLUSIONS: Catheter based intracoronary VBT carried out according to current standards is highly thrombogenic. The current antithrombotic treatment with aspirin and clopidogrel is not sufficient to suppress platelet activation during the procedure. From in vitro experiments, it appears that platelet activation during brachytherapy is not caused by irradiation but by the procedure of catheter based VBT.

Angina Pectoris↗

Calibration and validation of a quality assurance system for 90Sr/90Y radiation source trains.

A quality assurance system (OPTIDOS, PTW-Freiburg) developed for dose rate verification of 90Sr/90Y radiation source trains (RSTs) was calibrated and validated. These source trains are used in the 5-F-BetaCath system (Novoste Corp.) for the treatment of endovascular diseases. The calibration factor of the OPTIDOS system was obtained empirically and is valid for 90Sr/90Y dose rate measurements at the specification point which is located at 2 mm distance from the source axis. A total of 187 OPTIDOS dose rate verifications of the 5-F-BetaCath system were performed in different hospitals. The histogram of the deviation between the manufacturer's dose rate specification and the dose rate measured using the OPTIDOS dosimetry system is Gaussian shaped with +/- 3% relative width and a mean shift of about +2% with respect to the corresponding dose rate specification. Additionally, 128 OPTIDOS dose rate verifications of the new jacketed RST (3.5-F-BetaCath, Novoste Corp.) were performed using the same calibration factor as derived for the 5-F-BetaCath system. Distribution of the deviation between the certified and the measured dose rate is nearly identical in comparison to the histogram of the 5-F-BetaCath system. The mean value of the deviations is shifted by -1.5% with respect to the certified dose rate. In order to compare the results of the calibrated OPTIDOS dosimetry system with a standard measuring method, separate dose rate measurements were performed using electron accelerator calibrated radiochromic films in which calibration is traceable to PTB (Physikalisch Technische Bundesanstalt, Germany). Deviation between both the methods is less than 3.1%. These results confirm that the calibrated OPTIDOS dosimetry system can be considered suitable for quality assurance of both types of RST used in the BetaCath systems.

Beta Particles↗

The use of an oral fluid immunoglobulin G ELISA for the detection of Helicobacter pylori infection in children.

BACKGROUND: Enzyme linked immunosorbent assay (ELISA) evaluation of oral fluid immunoglobulin G (IgG) antibodies to Helicobacter pylori is a unique approach for both epidemiological studies and the diagnosis of infection, especially in children. The use of oral fluid sampling to evaluate specific H. pylori IgG antibodies has advantages over serum, including reduced biohazard risk and noninvasive collection. Oral fluid sampling is fast and involves minimal patient discomfort. Since children facilitate transmission of H. pylori infection, a simple, accurate, noninvasive diagnostic test is necessary for large epidemiologic studies. The aim of our study was to evaluate a new oral fluid ELISA for detection of IgG antibodies to H. pylori in children. MATERIALS AND METHODS: We compared this new oral fluid ELISA with the HM-CAPTM serum ELISA and gastric biopsy histology using 779 oral fluid samples from children collected at 11 clinical sites across the United States. This cohort included 315 children symptomatic for abdominal pain and 464 asymptomatic. All samples were evaluated in a double blind manner. The oral fluid ELISA demonstrated a sensitivity of 76.2% and a specificity of 94.0% in children 2 months old to 201/2 years, as compared with the HM-CAPTM serologic assay. The assay's sensitivity improved to 81.3% in children aged 5 or greater and the specificity remained at 94.0%. When compared with gastric biopsy histology in the same age group, the oral fluid ELISA demonstrated a sensitivity of 71.7% and a specificity of 90.4%. RESULTS: This new oral fluid ELISA is moderately sensitive and offers a very specific method for detecting H. pylori infection in older children, but it is of little value in children under the age of 5 years. CONCLUSIONS: Overall, we conclude that this oral fluid ELISA does not appear to be a helpful clinical tool for the diagnosis of H. pylori infection in children.

Adolescent↗

Orthotopic liver transplantation for autoimmune hepatitis and cryptogenic chronic hepatitis in children.

BACKGROUND: Autoimmune hepatitis (AIH) and cryptogenic chronic hepatitis (CCH) are important causes of liver failure in children, frequently necessitating orthotopic liver transplantation (OLT). The aim of this study is to review disease progression and potential differences between subgroups of children with AIH and CCH. METHODS: The medical records of 65 children diagnosed with AIH or CCH between 1980 and 1998 were evaluated. RESULTS: The median age at presentation was 9 years, 8 months (range 4 months-19 years), and the median follow-up period was 8 years (range 3 months-18 years, 10 months). Forty-one patients (63%) were female. Twenty-eight patients were Hispanic, 28 were Caucasian, 8 were African-American, and 1 was Asian. Forty-three patients (66%) were diagnosed with type 1 AIH, 8 (12%) with type 2 AIH, and 14 (22%) with CCH. Forty patients (62%) underwent OLT (51% of those with type 1 AIH, 75% of those with type 2 AIH, and 86% of those with CCH). Thirteen (33%) of the transplanted patients experienced disease recurrence. African-American patients experienced a significantly higher rate of disease recurrence post-OLT than did Hispanic patients. Seven patients (11%) died, two without OLT, and five posttransplantation. CONCLUSIONS: AIH and CCH frequently necessitate OLT in children. CCH is a more aggressive disease than Type 1 AIH among children with these disorders. Ethnicity influences the rate of disease recurrence after liver transplantation.

Adolescent↗

Transjugular intrahepatic portosystemic shunt prior to renal transplantation in a child with autosomal-recessive polycystic kidney disease and portal hypertension: A case report.

Autosomal-recessive polycystic kidney disease (ARPKD) can cause renal failure and portal hypertension in children. Portal hypertension may complicate the course of renal transplantation (Tx). We report the successful outcome of a patient with end-stage renal disease (ESRD) and portal hypertension treated with transjugular intrahepatic portosystemic shunt (TIPS), a minimally invasive endovascular technique of portosystemic shunt, prior to renal Tx.

Child↗

Impact of chronic hepatitis B and interferon-alpha therapy on growth of children.

Interferon-alpha (IFN) has been approved as treatment for children with chronic hepatitis B (CHB). The aims of this study were to assess the impact on children's growth of the disease itself and of IFN treatment. The growth of 142 children with CHB (70 IFN-treated, 72 untreated) was monitored for a minimum of one year. Regression analysis models were used to determine which of the variables most affected children's growth. After adjusting for racial differences, the population of 142 children with CHB had a mean baseline height for age percentile of 39 and a mean baseline weight for age percentile of 38, which were significantly different (P < 0.0001) from the 50th percentiles of their respective reference populations. The height for age Z score of untreated children was inversely correlated with serum hepatitis B virus DNA and aspartate aminotransferase levels, and the weight for age Z score was inversely correlated with serum hepatitis B virus DNA levels. While undergoing IFN therapy, children displayed a "U-shaped" growth pattern, such that height for age and weight for age Z scores at 3 or 6 months were lower than scores at baseline or 12 months. In this study the average child with CHB showed compromised growth even in the absence of IFN therapy. During IFN therapy, children's growth was temporarily disrupted.

Adolescent↗

Fitness testing of pediatric liver transplant recipients.

Liver transplantation is accepted as the standard management for end-stage liver disease in children. Pediatric heart and heart-lung transplant recipients have shown significantly diminished exercise capacities compared with age-matched, able-bodied, control subjects. The primary aim of this study is to compare the fitness levels of a group of pediatric liver transplant (LT) recipients (LT group, 20 boys, 9 girls; age, 8.9 +/- 4.8 years; 56 +/- 35 months posttransplantation) with a group of able-bodied control subjects (22 boys, 12 girls; age, 8.4 +/- 3.8 years). The secondary aim is to compare the performance of the LT group against the Fitnessgram criterion standards. We assessed muscular endurance by means of a partial curl-up, flexibility by means of the back-saver sit and reach, and cardiorespiratory fitness by means of the progressive aerobic cardiovascular endurance run (PACER). The only significant (P <.05) difference between the 2 groups was the number of shuttles run in the PACER (control, 16.8 +/- 9.8 v LT, 11.5 +/- 8.4 shuttles). Other differences between the 2 groups were not significant. With regard to satisfying the Fitnessgram criterion standards, only 35% of the LT group achieved the standards for the partial curl-up, 88% of the LT group achieved the criterion standards for flexibility, and 0% achieved the standards for the PACER. These results indicate that the LT group has diminished exercise capacity. The origins of exercise limitations deserve further investigation.

Adolescent↗

Posttransplantation growth in pediatric liver recipients.

The aim of this retrospective analysis was to evaluate the growth of 96 pediatric liver transplant recipients from February 1988 to June 1999. Inclusion criteria were the following: age younger than 18 years, follow-up longer than 1 year, transplantation for a nontumor indication, and no retransplantation. Linear height and growth velocity SD scores were correlated to age, sex, indication for transplantation, immunosuppression, and graft type. Transplant recipients of all ages and indications and both sexes were growth retarded at transplantation. Recipients aged younger than 24 months showed growth within the first year to achieve a height distribution equal to that of an age-matched population. Posttransplantation growth inversely correlated with height standard score at transplantation. Children older than 2 years at transplantation established new growth curves, but remained growth retarded. As children approached the prepubertal growth acceleration, growth deficits frequently were erased. Transplant recipients with biliary atresia and alpha(1)-antitrypsin deficiency showed increased growth performance compared with those who underwent transplantation for chronic hepatitis or fulminant hepatic failure. Boys were less growth retarded at transplantation and showed improved posttransplantation growth performance versus girls. No correlation to immunosuppression or graft type was identified. We conclude that early transplantation of children who show growth retardation is optimal for restoration of growth potential, whereas delaying transplantation in older children impedes potential growth.

Adolescent↗

Posttransplantation lymphoproliferative disorders in pediatric patients undergoing liver transplantation.

OBJECTIVES: To study the clinicopathologic and molecular genetic findings in posttransplantation lymphoproliferative disorders (PTLDs) following pediatric liver transplantation and to determine the applicability of a recently proposed consensus classification system. DESIGN: The clinical, pathologic, and molecular genetic findings of 11 PTLDs that occurred in 10 patients are presented. These 10 patients were derived from a group of 121 pediatric patients who underwent liver transplantation at the University of California, San Francisco. The PTLDs were classified using the proposed Society for Hematopathology scheme. Clonality was determined by immunohistochemical detection of monotypic immunoglobulin or by using polymerase chain reaction-based methods to detect monoclonal immunoglobulin heavy-chain gene rearrangements. Epstein-Barr virus (EBV) was detected by immunohistochemistry, in situ hybridization, or polymerase chain reaction. Epstein-Barr virus typing and the presence of LMP1 gene deletions were also analyzed by polymerase chain reaction. RESULTS: There were 3 early lesions, 4 polymorphic PTLDs, and 4 monomorphic PTLDs. Monoclonality was demonstrated in 8 of 9 cases assessed. Epstein-Barr virus was present in all cases; of 9 cases assessed by polymerase chain reaction, the virus was type A in 8 and type B in 1. No EBV LMP1 gene deletions were identified. The corresponding liver explants were negative for EBV in 8 cases and positive in 1 case. Greater than 3 foci of disease and monomorphic PTLD were associated with decreased actuarial survival (P <.05). CONCLUSIONS: The prognosis of pediatric patients with PTLD is favorable for early lesions and polymorphous PTLD, particularly in patients with localized disease. Multifocal disease and monomorphic PTLD are associated with an unfavorable prognosis.

Child↗

Experience with aggressive therapy in three children with unresectable malignant liver tumors.

BACKGROUND: Children with malignant liver tumors often present with unresectable disease but need not be considered incurable. The advent of effective chemotherapy makes aggressive management feasible, as our experience with three such patients demonstrates. Procedure and Results One child with an unresectable undifferentiated sarcoma of the liver and two others with unresectable primary hepatoblastoma and lung metastases were treated with initial chemotherapy, followed by aggressive surgical management. Treatment with chemotherapy followed by hepatectomy and liver transplantation (cadaveric or live donor) in two children has resulted in disease-free survivals of 79 and 38 months. The third patient is alive and well 24 months following chemotherapy and aggressive resection of the primary and 12 metastatic lesions. CONCLUSIONS: Initial chemotherapy for unresectable liver tumors with or without metastases is supported by the review of the literature. Consideration of orthotopic liver transplantation (OLT) from cadaveric or living related donor is warranted when the malignancy is demonstrably chemosensitive, independent of initial staging. Aggressive resection of primary and metastatic disease may be called for in selected cases.

Child↗

Is there a future for liver-assist devices?

Patients with fulminant hepatic failure fall into two categories: those who will not recover without hepatic replacement, and those with severe but potentially reversible liver injury whose livers have the potential to recover and/or regenerate. Liver support systems must provide physiologic support, rendering the patient hemodynamically stable and "bridging" the patient to transplantation, or allowing the native liver to recover and/or regenerate. Recent limited successes with bioartificial liver support for patients with fulminant liver failure are encouraging. However, these preliminary results come without randomization or control groups and without stratification by disease etiology or severity. It is hoped that randomized, controlled trials will answer important questions about the efficacy of these systems.

Animals↗

Gas-permeable scleral contact lens therapy in ocular surface disease.

PURPOSE: To describe the therapeutic benefits of nonfenestrated gas-permeable scleral contact lenses in the management of patients with ocular surface disease. METHODS: The charts of 49 consecutive patients (76 eyes) with ocular surface disease whose management included the use of gas-permeable scleral contact lenses were reviewed. We also developed a questionnaire to assess the impact of lens wear on subjective aspects of activities of daily living. RESULTS: The mean age of the 49 patients was 44.6 years (range, 3 to 87 years); 31 patients were female and 18 were male. The most common indication for fitting of the lenses was Stevens-Johnson syndrome (54 [71%] of the 76 eyes). Other indications included ocular cicatricial pemphigoid, exposure keratitis, toxic epidermal necrolysis, postherpetic keratitis, congenital deficiency of meibomian glands, superior limbal keratoconjunctivitis, Sjögren syndrome, and inflammatory corneal degeneration. The mean follow-up was 33.6 months (range, 2 to 144 months). Improvement in best-corrected visual acuity (defined as a gain of 2 or more Snellen lines) was observed in 40 (53%) of the eyes. In eight (53%) of the 15 eyes with active corneal epithelial defects at the time of lens fitting, the defects healed, whereas in the remaining seven eyes the corneal epithelial defects remained unchanged. Forty-five (92%) of the 49 patients reported improvement in their quality of life as a result of reduction of photophobia and discomfort. The mean wearing time of the gas-permeable scleral contact lenses was 13.7 hours per day (range, 4 to 18 hours). Many patients had preparatory surgical procedures before lens fitting (for example, punctal occlusion or mucous membrane grafting), and some had visual rehabilitation surgical procedures (for example, keratoplasty and/or cataract surgery) after lens fitting. CONCLUSIONS: Gas-permeable scleral contact lens wear provides an additional effective strategy in the surface management and visual rehabilitation of patients with severe ocular surface disease.

Adolescent↗

Treatment of persistent corneal epithelial defect with extended wear of a fluid-ventilated gas-permeable scleral contact lens.

PURPOSE: To report treatment of persistent corneal epithelial defects unresponsive to other therapies by extended wear of a fluid-ventilated gas-permeable scleral contact lens. METHODS: In this retrospective study, 14 eyes of 13 consecutive patients referred for the treatment of persistent corneal epithelial defects that failed to heal with conventional therapies or developed epithelial defects after penetrating keratoplasty for persistent corneal epithelial defects were fitted with an extended-wear gas-permeable scleral lens. These included seven eyes of six patients with Stevens-Johnson syndrome and seven eyes of seven patients who did not have Stevens-Johnson syndrome. Twelve eyes had undergone recent penetrating keratoplasty. All 14 eyes were fitted with a gas-permeable scleral contact lens designed to avoid the intrusion of air bubbles under its optic. An antibiotic and corticosteroid were added to the lens fluid reservoir or instilled before each lens insertion in 12 of 14 eyes. The lenses were worn continuously except for brief periods of removal for purposes of cleaning, replacement of the lens fluid reservoir, and examination and photography of the cornea. RESULTS: Five of the seven persistent corneal epithelial defects associated with Stevens-Johnson syndrome healed. The persistent corneal epithelial defects of four of these eyes re-epithelialized within 7 days, and a fifth healed in 27 days of gas-permeable scleral lens extended wear. A sixth persistent corneal epithelial defect that failed to heal initially re-epithelialized after a subsequent penetrating keratoplasty and gas-permeable scleral lens extended wear. The seventh eye healed after 3 days of gas-permeable scleral lens extended wear, but the persistent corneal epithelial defect subsequently recurred. Three of seven non-Stevens-Johnson syndrome persistent corneal epithelial defects re-epithelialized within 36 hours, 6 days, and 36 days, respectively. Of the six (six of 14) persistent corneal epithelial defects that failed to heal with a gas-permeable scleral lens extended wear, one subsequently healed after multiple amniotic membrane grafts. Microbial keratitis occurred in four eyes (four of 14) and graft failure in one eye, all of which required repeat penetrating keratoplasty. CONCLUSION: Extended wear of an appropriately designed gas-permeable scleral contact lens was effective in promoting the healing of persistent corneal epithelial defects in some eyes that failed to heal after other therapeutic measures. Re-epithelialization appears to be aided by a combination of oxygenation, moisture, and protection of the fragile epithelium afforded by the scleral lens. However, microbial keratitis represents a significant risk.

Adolescent↗

Current status of pediatric liver transplantation.

Increased survival for young liver transplant recipients has greatly improved. Increasing success has led to broader indications, thereby increasing the number of potential recipients. Pediatric liver centers are developing new strategies to cope with the ever-increasing demands for suitable size appropriate grafts. UNOS is in the process of updating guidelines to regulate the sharing of organs which become available from new surgical techniques. In the future, alternative therapies, such as artificial liver assist devices and techniques of cellular transplantation and genetic modification of hepatocytes, may decrease the number of children who die while waiting for a suitable organ or even obviate the need for the liver transplantation.

Child↗

Statistical models for predicting response to interferon-alpha and spontaneous seroconversion in children with chronic hepatitis B.

To develop prognostic models for identifying children with hepatitis B who are likely to respond to interferon-alpha (IFN-alpha) or to spontaneously seroconvert, we evaluated results of a multinational controlled trial comprising 70 children with chronic hepatitis B who received IFN-alpha and 74 children who did not receive therapy. Prognostic models were developed using SMILES (similarity of least squares), which is a data analysis network that incorporates multidimensional relationships in the clinical data of complex diseases. Commonly collected clinical data included age, gender, serum aminotransferase (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) and hepatitis B virus (HBV) DNA levels, and IFN-alpha dose. Additional data included pretreatment directional information (e.g. increases or decreases in serum aminotransferase and HBV DNA levels), liver biopsy results, race and transmission mode. Using data available prior to initiation of treatment, the SMILES models achieved prospective predictions of 89% for responders, 96% for non-responders, 100% for seroconverters and 93% for non-seroconverters. Although not predictive by themselves, the variables that had the greatest impact on predictions for IFN-alpha response were HBV DNA pretreatment direction, baseline HBV DNA, IFN-alpha dose and gender. The variables that had the greatest impact on predictions for spontaneous seroconversion were ALT pretreatment direction, baseline HBV DNA level, age and AST pretreatment direction. Therefore, these models may be useful in determining, in children with hepatitis B, the likelihood of response to IFN-alpha and spontaneous seroconversion.

Adolescent↗