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Biomedical subjects

Michael Rice

Publications and source records attributed to Michael Rice.

14 recordsLinked to original sources

Rituximab for lymphoproliferative disease prior to haematopoietic stem cell transplantation for X-linked severe combined immunodeficiency.

Lymphoproliferative disease (LPD) is a complication of congenital and acquired immunodeficiency states. There are a number of treatment options for LPD arising after haematopoietic stem cell or solid organ transplantation including reduction of immunosuppression, targeted therapies, such as the anti-CD20 monoclonal antibody, rituximab, and EBV specific cytotoxic lymphocytes. Treatment of LPD in children with congenital immunodeficiency syndromes remains unsatisfactory and is associated with a high mortality rate. We recently managed an infant found to have polymorphic LPD concurrent with X-linked severe combined immunodeficiency (SCID). Haematopoietic stem cell transplantation (HSCT) had to be deferred because of progressive LPD. Treatment with rituximab resulted in regression of the LPD following which the patient received a 5/6 HLA matched umbilical cord blood (UCB) transplant. The patient remains well 20 months following transplantation. Rituximab treatment may have a useful role in the control of LPD associated with congenital immunodeficiency prior to HSCT.

Antibodies, Monoclonal↗

Patients with overactive bladders deserve better.

Tolterodine is an effective agent used to treat symptoms of overactive bladder. It is well tolerated and its selectivity for the bladder results in less side effects overall compared to many other agents. Many patients in New Zealand with symptoms of overactive bladder do not have access to tolterodine due to restrictions on its funding by PHARMAC. Alternative treatments are not as well tolerated and are less clinically useful. This leaves many patients vulnerable to significant compromise of their quality of life.

Benzhydryl Compounds↗

Challenging the spliceosome machine.

BACKGROUND: Using cDNA copies of transcripts and corresponding genomic sequences from the Berkeley Drosophila Genome Project, a set of 24,753 donor and acceptor splice sites were computed with a scanning algorithm that tested for single nucleotide insertion, deletion and substitution polymorphisms. Using this dataset, we developed a progressive partitioning approach to examining the effects of challenging the spliceosome system. RESULTS: Our analysis shows that information content increases near splice sites flanking progressively longer introns and exons, suggesting that longer splice elements require stronger binding of spliceosome components. Information also increases at splice sites near very short introns and exons, suggesting that short splice elements have crowding problems. We observe that the information found at individual splice sites depends upon a balance of splice element lengths in the vicinity, including both flanking and non-adjacent introns and exons. CONCLUSION: These results suggest an interdependence of multiple splicing events along the pre-mRNA, which may have implications for how the macromolecular spliceosome machine processes sets of neighboring splice sites.

Animals↗

Unilateral cervical surgical exploration aided by intraoperative parathyroid hormone monitoring in patients with primary hyperparathyroidism and equivocal sestamibi scan results.

HYPOTHESIS: Equivocal parathyroid technetium Tc 99m sestamibi scan results are likely to demonstrate the correct location for parathyroid adenomas. DESIGN: Patients with primary hyperparathyroidism prospectively consented to participate in an institutional review board-approved study. The parathyroid technetium Tc 99m sestamibi scan results were classified as positive, negative, or equivocal. SETTING: A tertiary private hospital in which university faculty practice. PATIENTS: Technetium Tc 99m sestamibi imaging was performed for 464 patients with primary hyperparathyroidism. Eighty-four of these patients had scan results considered equivocal for unilateral adenomas. The algorithm for this group of patients specified that they should receive an injection with technetium Tc 99m sestamibi prior to parathyroidectomy and that an intraoperative parathyroid hormone (iPTH) level decrease of more than 50% be used to define intraoperative success. Seventy-two patients had postoperative calcium levels measured at least 2 weeks after their surgical procedure and defined the study group. The mean follow-up was more than 6 months. INTERVENTION: Parathyroidectomy. MAIN OUTCOME MEASURE: Correlation of equivocal scan interpretation with operative findings and biochemical cure of hyperparathyroidism. RESULTS: Of the 72 patients, 39 underwent unilateral surgical explorations and 33 underwent bilateral surgical explorations; 67 (93%) of the patients were initially cured and 68 (94%) were ultimately cured. In the unilateral group, 38 (97%) of the patients were cured. The 1 failure was associated with a false-positive iPTH level decrease. In the bilateral group, 29 (88%) of the patients were initially cured and 30 (91%) were ultimately cured. Two failures were associated with a false-positive iPTH level decrease and 2 with failure to find the adenoma. Of the 33 patients in the bilateral group, surgical exploration of the opposite side was purely by surgeon choice in 11 cases. Of the other 22 patients, in addition to the 3 failures, 7 had 4-gland hyperplasia, 4 had double adenomas, and 6 had false-negative iPTH level results with iPTH level decreases of less than 50%. CONCLUSION: Overall, between 48 (67%) and 54 (75%) of the 72 patients would have been cured with unilateral surgical exploration alone.

Adenoma↗

Organization of fibroblasts in the heart.

Cardiac fibroblasts are organized into a three-dimensional network in the heart. This organization follows the endomysial weave network that surrounds groups of myocytes. Reverse transcriptase-polymerase chain reaction, Western blots, and immunohistochemistry were used to show that discoidin domain receptor 2 (DDR2) was specific for cardiac fibroblasts and not expressed on endothelial cells, smooth muscle cells, or cardiac myocytes. DDR2 is expressed early in development and in the adult heart. High voltage electron microscopy (HVEM), scanning electron microscopy, and laser scanning confocal microscopy document the three-dimensional organization of fibroblasts in the heart. Antibodies against connexin 43 and 45 showed different patterns but confirmed, along with HVEM, that fibroblasts are connected to each other as well as cardiac myocytes. The implications of this arrangement of fibroblasts can be important to cardiac function. The signaling of DDR2 and the expression of matrix metalloproteinase 2 in relation to collagen turnover and remodeling is discussed.

Animals↗

Ordered partitioning reveals extended splice-site consensus information.

Using recently available cDNA and genomic data (Berkeley Drosophila Genome Project; http://www.fruitfly.org), we computed a large sample of 10,057 Drosophila splice sites. An information-theoretic analysis of the nucleotide sequences adjacent to these splice sites showed a strong correlation between the sizes of introns and exons and the levels of information, which is a measure of sequence conservation. The strong correlation permitted us to determine extensive consensus sequences at the donor and acceptor sites of longer introns. These sequences were further refined and extended by examining the information in regions around splice sites that only partially matched the consensus. The correlation between length and information provided the basis for determining alternative consensus arrangements associated with shorter introns, as well as general base-composition preferences that likely promote spliceosome function. We also observed a correlation between information near splice sites and the lengths of nonadjacent introns, indicating that there are long-range effects spanning multiple introns. The ordered partitioning approach used in this analysis may become increasingly useful as large genomic data sets become available.

Animals↗

Relational databases: a transparent framework for encouraging biology students to think informatically.

We discuss how relational databases constitute an ideal framework for representing and analyzing large-scale genomic data sets in biology. As a case study, we describe a Drosophila splice-site database that we recently developed at Wesleyan University for use in research and teaching. The database stores data about splice sites computed by a custom algorithm using Drosophila cDNA transcripts and genomic DNA and supports a set of procedures for analyzing splice-site sequence space. A generic Web interface permits the execution of the procedures with a variety of parameter settings and also supports custom structured query language queries. Moreover, new analytical procedures can be added by updating special metatables in the database without altering the Web interface. The database provides a powerful setting for students to develop informatic thinking skills.

Algorithms↗

Acute lymphoblastic leukemia characterized by t(8;14)(q11.2;q32).

The t(8;14)(q11.2;q32) is emerging as an uncommon, though recurrent cytogenetic finding. As of yet, too few cases of acute lymphoblastic leukemia (ALL) characterized by this translocation have been studied to determine its prognostic significance with confidence. We therefore report three new patients (two male children and one adult female) and present their hematologic, immunophenotypic, and clinical data. The clinical and laboratory characteristics of 26 other patients with t(8;14)(q11.2;q32) are summarized. The total number of patients now reported in the literature is 29 with a mean age of 14 years. Early relapse, that is, relapse within 6 months, does not appear to be a common feature of this group. The gender distribution is 19 males: 9 females (gender not reported in one case). Twenty-three t(8;14) patients show a pre-B immunophenotype and 24 of 24, on whom information is available, achieved complete remission after induction chemotherapy for B-ALL. Approximately one third of patients with t(8;14) have Down syndrome, 19 of 27 have additional acquired cytogenetic abnormalities, 5 of these have the t(9;22), and 4 show duplication of the abnormal chromosome 14, which is derived from the t(8;14). Hemoglobin and platelet counts are low at presentation in 10 of 10 and 8 of 9 patients, respectively, and the average white blood count is 38.9 x 10(9)/L. Of the 7 patients for whom IgH status has been determined, all show rearrangement of the IgH locus. Two of the present three patients are included in this group; their IgH rearrangement was demonstrated by fluorescence in situ hybridization with IgH break-apart probes.

Adolescent↗

The role of [18F]fluorodeoxyglucose positron emission tomography imaging in the evaluation of hepatocellular carcinoma.

It has been well established that hepatocellular carcinomas (HCCs) accumulate [18F]fluorodeoxyglucose (FDG) to varying degrees; this is thought to be due to differing amounts of FDG-6-phosphatase activity. The purpose of this study was to evaluate the impact of FDG imaging on the management of patients diagnosed with hepatocellular carcinoma. We conducted a retrospective review of the clinical data of 91 consecutive patients diagnosed with HCC who underwent FDG-positron emission tomography (PET) imaging between August 1993 and March 2001. The patients were divided into two groups. In Group one 67 of 91 (74%) patients were evaluated for proven but untreated hepatic lesions using PET. In Group two the remaining 24 patients (26%) were referred for evaluation of HCC recurrence but did not have prior PET. The FDG images were acquired with two dedicated PET tomographs [Siemens ECAT 933, CTI (Knoxville, TN) and GE Advance, General Electric Medical Systems (Milwaukee, WI)] one hour after the intravenous administration of 10 mCi of FDG. Tumor biopsy or resection specimens were available for review from 34 patients and were evaluated for histologic grade, presence of cirrhosis, tumor necrosis, and intratumoral fibrosis. In group one 43 of 67 (64%) of the HCCs accumulated FDG. Sixteen of the 43 patients in whom FDG was accumulated had multiple subsequent FDG-PET scans either for monitoring therapy or for detection of recurrence. FDG-PET imaging had an impact on the management of 20 of these patients: by guiding the biopsy at the metabolically active site of a large necrotic tumor (one), by identifying distant metastases (five), by monitoring the response to treatment with hepatic chemoembolization and guiding additional regional therapy (12), and by detecting recurrence (two). In group two recurrence and/or metastases were demonstrated with FDG-PET imaging in six of 24 (25%) patients, three of whom had multiple subsequent FDG-PET scans to monitor their treatment. Higher histopathologic grade and intratumoral fibrosis but not necrosis or cirrhosis correlated with PET positivity. In this study only 64 per cent of HCCs accumulated FDG. Despite this limitation FDG-PET imaging remains a useful tool in the diagnosis and treatment of HCC. FDG-PET imaging had a clinically significant impact in 26 of 91 (28%) patients with HCC. This includes detection of unsuspected metastatic disease in high-risk patients-including liver transplant candidates-and monitoring response to hepatic-directed therapy. FDG-PET should be considered as part of the workup and management of selected patients with HCC.

Adult↗

Renal toxicity after total body irradiation.

PURPOSE: To evaluate the incidence of renal dysfunction after total body irradiation (TBI). METHODS AND MATERIALS: Between 1990 and 1997, 64 patients (median age 50 years) received TBI as part of the conditioning regimen before bone marrow transplantation (BMT). Five patients with abnormal renal function at the beginning of treatment or with incomplete data were excluded. All patients received a total of 12 Gy (6 fractions twice daily for 3 consecutive days) prescribed to the peak lung dose (corrected for lung transmission) at a dose rate of 7.5 cGy/min. Renal shielding was not used. Renal dysfunction was assessed on the basis of the serum creatinine levels measured at the start and end of TBI and at 6, 12, 18, and 24 months after completion of BMT. Cox proportional hazard analysis was used to evaluate the various factors known to affect renal function. RESULTS: Only 4 patients had elevated serum creatinine levels at 12 months and subsequently only 2 of the 33 surviving patients had persistent elevated renal serum creatinine levels 24 months after BMT. A fifth patient developed proteinuria and mildly elevated serum creatinine levels at 2.5 years. In 2 patients, the elevation coincided with disease relapse and normalized once remission was achieved. In the third patient, the elevation in serum creatinine levels coincided with relapse of multiple myeloma and the presence of Bence-Jones proteinuria. The fourth patient was the only patient who developed chronic renal failure secondary to radiation nephritis at 2 years. The etiology of the fifth patient's rise in creatinine was unknown, but may have been secondary to radiation nephritis. On univariate analysis, but not on multivariate analysis, a significant correlation was found between TBI-related renal dysfunction and hypertension before and after BMT. CONCLUSION: A dose of 12 Gy at 2 Gy/fraction resulted in only 1 case of radiation nephritis in the 59 patients studied 24 months after the completion of TBI and BMT.

Adolescent↗

Results of consecutive trials for children newly diagnosed with acute myeloid leukemia from the Australian and New Zealand Children's Cancer Study Group.

Despite improvements in the treatment of acute myeloid leukemia (AML), approximately 50% of children die of the disease. Clinical trials in adult patients with AML indicate that idarubicin may have superior efficacy when compared to daunorubicin in the remission-induction phases of chemotherapy. We conducted consecutive clinical trials in children with newly diagnosed AML in which daunorubicin (group 1, n = 102) or idarubicin (group 2, n = 160) was used during the remission-induction (RI) and the early consolidation phases of chemotherapy. Idarubicin was given at a dose of either 10 mg/m(2) (group 2A, n = 106) or 12 mg/m(2) (group 2B, n = 53). A high rate of RI was achieved for all groups (95% group 1, 90% group 2A, 94% group 2B). There were no significant differences in 5-year event-free survival (EFS) or in overall survival (OS) when the 3 groups were compared (group 1: EFS 50%, OS 56%; group 2A: EFS 50%, OS 60%; group 2B: EFS 34%, OS 50%). RI deaths resulting from treatment toxicity were low-2% for group 1 and 5% for group 2. More gastrointestinal, pulmonary, and renal toxicity but fewer infections were observed in patients receiving idarubicin (P <.001, P =.04, P =.03, respectively). Following RI chemotherapy, all patients received 3 to 4 more courses of identical chemotherapy and then underwent either autologous (n = 156) or an allogeneic bone marrow transplantation (BMT) (n = 35). OS was higher in allogeneic BMT patients than in autologous BMT patients (79% vs 63%; P =.23). We conclude that daunorubicin is as effective as idarubicin for remission-induction therapy for childhood AML and has reduced toxicity.

Adolescent↗

Childbearing experiences of abused Hispanic women.

Previous research has documented that abused childbearing women have longer and more difficult labors than non-abused women. Prevalence of abuse differs depending on the ethnic group involved. Hispanic women experience higher rates of abuse and endure higher rates before reporting abuse than do Caucasian women. The purpose of this study was to explore the experience of childbearing for abused Hispanic women to provide guidance for clinical practice and further research. Cognitive dissonance theory guided the study. A sample of seven abused Hispanic women was recruited from a rural prenatal clinic. Criteria for selection of subjects included self-identification as Hispanic, less than 24 months postpartum, disclosure of abuse status, and willingness to be interviewed in English or Spanish. An acculturation scale and demographic form were completed. Interviews were conducted individually, and data were analyzed by using Van Kaam's 12-step psychophenomenologic technique. Findings indicated that subjects experienced the normal responses associated with having a baby. However, the women also demonstrated a kindled neuroendocrine trauma response that was based on, and often similar to, their prior abuse experiences. The kindled emotional response was triggered by the normative events of childbearing. Understanding of the childbearing experiences of abused Hispanic women will facilitate the development of cultural-specific interventions that may ease the difficulties associated with birth for these women.

Adult↗

The relationship between abuse, sexually transmitted diseases, & group B streptococcus in childbearing women.

PURPOSE: To examine the relationship between abuse, sexually transmitted diseases (STDs) and group B (GBS) infection among childbearing women using Selye's (1978) stress response theory. DESIGN AND METHODS: Retrospective chart review (n = 205) from two different clinical sites in Washington State, using the Childbearing Health Questionnaire to guide data collection. The women in the sample had an average age of 26.4 years and represented Anglo (81.4%), Hispanic (12%), Native American (3.9%), and African American (2.5%) ethnic groups. Thirty-eight percent ( = 78) reported experiencing physical and/or sexual abuse during their lifetimes and 31% had been diagnosed with an STD. RESULTS: Abuse was significantly related to STDs, and ethnicity emerged as a significant variable for the Hispanic women participating in this study. Findings indicated that infection with group B was also related to abuse status ( r=.60, p < or =.002) and to presence of herpes simplex virus-2 (r =.468, p<or =.01). Total prevalence of STDs was positively related to abuse ( r=.78, p <or =.000). Abused Hispanic women were more likely to be positive for STDs than were their nonabused counterparts ( p <or =.03). CLINICAL IMPLICATIONS: The findings support previously published results that abuse is widespread in the United States and that abused women are at increased risk for STDs. These results highlight the need for regular screenings for abuse during healthcare, for abuse is a critical variable to consider when screening for STDs and GBS. STD screening typically occurs during the first prenatal visit and may need to be repeated for high-risk groups.

Adult↗

Further development of the Postpartum Depression Predictors Inventory-Revised.

OBJECTIVES: To describe the newly developed item coding and computation of the total score for the Postpartum Depression Predictors Inventory-Revised along with recommended cutoff points. DESIGN: Methodologic research. SETTING: Obstetrician and gynecologist offices in the Pacific Northwest. PARTICIPANTS: This longitudinal study included 139 women; the study began in the participant's third trimester of pregnancy and ended at 8 months after childbirth. METHODS: The participants completed the Postpartum Depression Predictors Inventory-Revised in their third trimester of pregnancy and again at 2 and 6 months after childbirth. Postpartum depression symptoms were measured by the Edinburgh Postnatal Depression Scale and psychiatric nurse practitioner interview at 2 and 6 months after childbirth. MAIN OUTCOME MEASURES: Sensitivity and specificity of the Postpartum Depression Predictors Inventory-Revised at three points: prenatal and 2 and 6 months after childbirth. RESULTS: The receiver operating characteristic curve analysis indicated that the Prenatal Postpartum Depression Predictors Inventory-Revised performed well and explained 67% of the variance of postpartum depressive symptomatology as measured by Edinburgh Postnatal Depression Scale scores. The Prenatal Postpartum Depression Predictors Inventory-Revised yielded a sensitivity of .76 and a specificity of .54 at a cutoff score of 10.5. CONCLUSIONS: A cutoff score of 10.5 is recommended when using the Postpartum Depression Predictors Inventory-Revised during pregnancy. Further research needs to be conducted on recommended cutoff scores for use of the Postpartum Depression Predictors Inventory-Revised during the postpartum period.

Analysis of Variance↗