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Biomedical subjects

Amy Smith

Publications and source records attributed to Amy Smith.

9 recordsLinked to original sources
PubMed2006

Temozolomide and oral VP-16 for children and young adults with recurrent or treatment-induced malignant gliomas.

BACKGROUND: Children and young adults with recurrent or treatment-induced malignant gliomas have limited responses to temozolomide or oral VP-16 when either is administered as a single agent. We postulated that a combination of these two drugs for patients with recurrent or treatment-induced malignant gliomas might result in better and more prolonged responses. A retrospective analysis was performed on patients treated with the combination of temozolomide and VP-16. PROCEDURE: Eleven patients with recurrent or treatment-induced malignant gliomas were treated with varying combinations of temozolomide (150-210 mg/m2/d for 5 days) and oral VP-16 (50 mg/m2/d for 4-12 days). Responses were assessed by MRI scan, and data on clinical course and toxicity were retrospectively obtained from the medical record. RESULTS: The median age of the 11 patients was 17 years (range 5-23 years). Diagnoses included recurrent brain stem glioma (2), recurrent anaplastic astrocytoma (2), and glioblastoma (7) (3 treatment-induced, 2 malignant transformations of lower grade tumors, 1 recurrence, and 1 second tumor arising 10 months after diagnosis of medulloblastoma). All 11 patients had received radiotherapy (including 4 who received craniospinal radiation), and 7 had prior chemotherapy. Nine patients were treated at first recurrence, two at second recurrence. One patient had a complete response (CR), six had partial responses (PR), and four had progressive disease (PD). The median progression-free survival for the seven responding patients was 6 months (range 4-15+ months). There was one grade 4 neutropenia, but no other grade 3 or 4 toxicities. CONCLUSIONS: These data suggest there is activity of temozolomide in combination with oral VP-16 for children and young adults with recurrent malignant gliomas.

Administration, Oral↗
PubMed2006

Brainstem stereotactic biopsy sampling in children.

OBJECT: Although it is widely accepted that biopsy sampling is not indicated for the diagnosis and empiric treatment of diffuse pontine glioma, it is common to encounter patients with brainstem lesions that cannot be diagnosed on the basis of imaging studies alone. In cases not amenable to resection, a tissue diagnosis may still be necessary to make appropriate treatment recommendations. The authors retrospectively reviewed their institutional experience with stereotactic biopsy procedures in pediatric patients during a 4-year period. METHODS: A three-dimensional graphics workstation was used for trajectory planning to obtain biopsy samples of brainstem lesions in 10 patients. One patient experienced mild diplopia postoperatively. No other morbidity was noted; no patient died as a result of the procedure. The biopsy procedure yielded a pathological diagnosis in all cases. A later resection in one patient resulted in a change in diagnosis. Overall, the pathological findings were varied, and in some cases the tissue diagnosis altered the treatment recommendations. CONCLUSIONS: The findings in this small series suggest that brainstem stereotactic biopsy sampling in children is a safe procedure with a high diagnostic yield. In patients in whom radiographic findings are not consistent with diffuse pontine glioma and resection is not appropriate, stereotactic biopsy sampling should be considered.

Adolescent↗
PubMed2005

Central venous recanalization in patients with short gut syndrome: restoration of candidacy for intestinal and multivisceral transplantation.

PURPOSE: To assess feasibility and success of venous recanalization in patients with short gut syndrome who have lost their traditional central venous access and required intestinal or multivisceral transplantation. MATERIALS AND METHODS: Twelve patients between the ages of 7 and 55 years with short gut syndrome and long-standing total parenteral nutrition (TPN) dependency and/or hypercoagulability were treated. All had extensive chronic central venous occlusions and survival was dependent on restoration of access and planned transplantation. Central venous recanalizations were obtained via sharp needle recanalization techniques, venous reconstructions with stents, and/or extraanatomic access to the central venous system for placement of central venous tunneled catheters. RESULTS: Central venous access was restored in all patients without operative-related mortality. Three major hemodynamic perioperative technical complications were recorded and successfully treated. There were three self-limited early infectious complications. With a mean follow-up of 22 months, eight of the 12 patients were alive with successful small bowel or multivisceral transplantation; six of those became independent of TPN. The remaining four patients died of complications related to TPN (n = 3) or transplantation (n = 1). With a mean follow-up of 20 months, all but two of the recanalized venous accesses were maintained, for a success rate of 83%. CONCLUSIONS: Recanalizations of extensive chronic vein occlusions are feasible but associated with high risk. The technique is life-saving for TPN-dependent patients and can restore candidacy for intestinal and multivisceral transplantation. This approach is likely to be increasingly requested because of the current clinical availability of the transplant procedure.

Adolescent↗
PubMed2005

Replacing calcineurin inhibitors with mTOR inhibitors in children.

A highly selected subject group comprising pediatric recipients of liver (n = 36) and small intestine alone (n = 1) or multivisceral graft (n = 2) were converted to sirolimus maintenance therapy for tacrolimus-related side effects (n = 32) or by primary intent (n = 7). Indications were nephrotoxicity (n = 14), primary intent (n = 7), post-transplant lymphoproliferative disorder (n = 6), seizures (n = 4), recurrent acute rejection (n = 2), and cardiomyopathy (n = 1). Thirty subjects (78%) experienced successful conversion, with one subject requiring atorvastatin for hypercholesterolemia and hypertriglyceridemia. Nine subjects (22%) were converted back to tacrolimus for serious adverse events including acute rejection (n = 2), elevated liver function tests (n = 1), severe leucopenia (n = 1), non-compliance (n = 2), recurrent malignancy/death (n = 1), steatohepatitis (n = 1), and thrombocytopenic thrombotic purpura (n = 1). Among subjects with nephrotoxicity, significant benefit was seen only in those subjects with shorter time to rescue after transplantation (n = 8 of 14 subjects). Additional benefits included a significant decrease in mean serum creatinine from pretransplant values for the entire population, and elimination of antihypertensive treatment in all five subjects receiving it prior to conversion. Hemoglobin, serum cholesterol and triglycerides, white cell counts and platelets remained within normal limits for the duration of follow-up (36 month). Conversion from tacrolimus to sirolimus is successful in selected pediatric liver and intestine recipients. Chronic nephrotoxicity may be ameliorated by early conversion. Improvement in renal function and hypertension management, and absence of sirolimus-related adverse events argue for prospective evaluation of regimens in which mTOR inhibitors are used without calcineurin inhibitors in children.

Calcineurin Inhibitors↗
PubMed2004

Tissue distribution of cholinesterases and anticholinesterases in native and transgenic tomato plants.

Acetylcholinesterase, a major component of the central and peripheral nervous systems, is ubiquitous among multicellular animals, where its main function is to terminate synaptic transmission by hydrolyzing the neurotransmitter, acetylcholine. However, previous reports describe cholinesterase activities in several plant species and we present data for its presence in tomato plants. Ectopic expression of a recombinant form of the human enzyme and the expression pattern of the transgene and the accumulation of its product in transgenic tomato plants are described. Levels of acetylcholinesterase activity in different tissues are closely effected by and can be separated from alpha-tomatine, an anticholinesterase steroidal glycoalkaloid. The recombinant enzyme can also be separated from the endogenous cholinesterase activity by its subcellular localization and distinct biochemical properties. Our results provide evidence for the co-existence in tomato plants of both acetylcholinesterase activity and a steroidal glycoalkaloid with anticholinesterase activity and suggest spatial mutual exclusivity of these antagonistic activities. Potential functions, including roles in plant-pathogen interactions are discussed.

Acetylcholinesterase↗
PubMed2003

The absence of chronic rejection in pediatric primary liver transplant patients who are maintained on tacrolimus-based immunosuppression: a long-term analysis.

BACKGROUND: Although the outcome of liver transplantation has improved significantly during the past two decades, graft loss caused by chronic rejection after liver transplantation still occurs in 2% to 20% of recipients. The overall incidence of chronic rejection is also reported to be low in adult recipients, and risk factors have been identified. Chronic rejection is associated with the inability to maintain baseline immunosuppression. Additionally, the diagnoses of primary biliary cirrhosis, primary sclerosing cholangitis, autoimmune hepatitis, hepatitis B virus, and hepatitis C virus, common indications for liver transplantation in adults, are associated with a higher incidence of chronic rejection. Fortunately, these diagnoses are rarely seen in children. Little is known about chronic rejection in long-term pediatric liver transplant survivors. The purpose of this longitudinal study was to examine the incidence of biopsy-proven chronic rejection in long-term survivors of primary pediatric liver transplantation under tacrolimus-based immunosuppression. METHODS: From October 1989 to December 1992, 166 children (boys=95, girls=71; mean age=5.0+/-2.9 years) received a primary liver transplant. These patients were followed until March 2000 with a mean follow-up of 9+/-0.8 (range, 7.4-10.4) years. All liver biopsy specimens and explanted grafts were evaluated for evidence of chronic rejection using the International Banff Criteria. RESULTS: The mortality rate during the follow-up period was 15% (n=25). Retransplantation was required in 11% (n=18) of recipients. Actuarial patient and graft survival rates at 10 years were 84.9% and 80.1%, respectively. There were 535 liver biopsy samples available for evaluation, including the 18 explanted allografts. Biopsy specimens of three other functioning allografts showed evidence of chronic rejection. Immunosuppression had been discontinued or drastically reduced in these recipients because of life-threatening infections, noncompliance, or both. On restoring baseline immunosuppression, all three children had normalized liver function and the allografts were maintained; the liver transplant patients who are alive currently have normal liver functions. CONCLUSION: The findings of this study suggest that chronic rejection does not occur in pediatric liver transplant recipients receiving tacrolimus-based immunosuppression, provided baseline immunosuppression is maintained.

Biopsy↗
PubMed2003

Effectiveness of sensory and motor rehabilitation of the upper limb following the principles of neuroplasticity: patients stable poststroke.

Based on the principles of neuroplasticity, the purpose of this crossover study was to determine if improvement in upper extremity (UE) function and independence could be achieved in patients 6 months to 7 years poststroke following an outpatient rehabilitation program (supervised 1.5 hours per week for 8 weeks reinforced with home gloving unaffected side and attended, graded, repetitive sensory and motor training activities). Twenty-one subjects (right or left hemiparesis; able to walk 100 feet with or without a cane; partially opened and closed the hand; partially elevated the shoulder and elbow against gravity) were randomly assigned to Group A (sensory training 4 weeks, motor training 4 weeks) or Group B (motor training 4 weeks, sensory training 4 weeks). Greater than 20% (P < 0.01) improvement was measured in functional independence and UE function (fine motor, sensory discrimination, and musculoskeletal performance). Gains were hemispheric and training specific and maintained over 3 months. This study provides evidence documenting significant improvement in function in the late poststroke recovery period following 12 hours of supervised learning based sensory motor training.

Adult↗
PubMed2002

Cloning and expression of a Helicobacter bilis immunoreactive protein.

In an effort to identify immunoreactive Helicobacter bilis antigens with potential for serodiagnosis, sera from mice experimentally infected with H. bilis were used to screen an H. bilis genomic DNA expression library. Among 17 immunoreactive clones, several contained sequences that encoded a predicted 167-kDa protein (P167). Five overlapping P167 peptides (P167A to P167E) of approximately 40 kDa each were generated and tested. Immune sera reacted with fragments P167C and P167D at dilutions of 1:1,600 and 1:6,400, respectively, and reacted with an H. bilis membrane extract at a dilution of 1:800 in an enzyme-linked immunosorbent assay. Sera from mice experimentally infected with H. hepaticus did not react with P167C and P167D. Sera from mice naturally infected with H. bilis but not sera from mice naturally infected with H. hepaticus reacted with P167C and P167D. Hyperimmune sera against P167C peptide reacted with recombinant P167C and with a 120-kDa band in H. bilis lysates but did not react with a protein of the same size on immunoblots prepared from H. hepaticus, H. muridarum, or unrelated Borrelia burgdorferi and Campylobacter jejuni whole-cell lysates. Nevertheless, the P167A, P167B, P167C, and P167D primers, but not the P167E primers, amplified DNA from H. hepaticus, and all five primer sets amplified DNA from H. muridarum. These results suggest that P167 is an immunodominant, H. bilis-specific antigen that may have potential for use in serodiagnosis.

Animals↗