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T Sullivan

Publications and source records attributed to T Sullivan.

At least 19 recordsLinked to original sources
PubMed2003

Preclinical safety profile of plasma prepared using the INTERCEPT Blood System.

BACKGROUND AND OBJECTIVES: The newly developed INTERCEPT Blood System for plasma uses the addition of a new psoralen, amotosalen HCl (AMOTOSALEN), followed by illumination with ultraviolet A light, to inactivate viruses, bacteria, protozoa and leucocytes that may contaminate fresh-frozen plasma (FFP). Extensive toxicology studies were performed to characterize the safety of the photochemical treatment process for its intended use with plasma. MATERIALS AND METHODS: The studies of general toxicology, safety pharmacology, phototoxicity, reproductive toxicity and venous irritation, summarized in this review, provide a comprehensive toxicology profile for photochemically treated 100% plasma. RESULTS: No specific target organ toxicity (based on clinical or histological pathology), phototoxicity, or reproductive toxicity was observed. CONCLUSIONS: The results of an extensive series of studies have demonstrated no toxicologically relevant effects of photochemically treated 100% plasma prepared using the INTERCEPT Blood System for plasma.

Animals↗
PubMed2001

Weekly docetaxel in the treatment of elderly patients with advanced breast cancer: a Minnie Pearl Cancer Research Network phase II trial.

PURPOSE: To evaluate the efficacy and toxicity of docetaxel administered weekly to elderly or poor-performance status patients with advanced breast cancer. PATIENTS AND METHODS: Forty-one patients with advanced breast cancer who were either over the age of 65 or considered to be poor candidates for combination chemotherapy received docetaxel 36 mg/m2 weekly for 6 consecutive weeks, followed by 2 weeks without treatment. The median age of patients in this trial was 74 years, and 73% of patients had one or more visceral sites of metastases. Seventy-five percent of patients received weekly docetaxel as first-line treatment for metastatic breast cancer, and the other 25% received it as second-line treatment. Thirty-six patients were assessable for efficacy, and all patients were assessed for toxicity. RESULTS: A total of 448 doses of weekly docetaxel were administered to 41 patients. Thirteen patients (36%) had objective responses to treatment, and an additional 13 patients (36%) had stable disease or minor response. Median time to progression for responding and stable patients was 7 months (range, 3 to 27 months). Median survival for the entire group was 13 months, with 1- and 2-year actuarial survival rates of 61% and 29%, respectively. Severe neutropenia occurred in only 0.4% of courses, and no other hematologic toxicity was observed. Grade 3/4 fatigue was the most common toxicity, occurring in 20% of patients. CONCLUSION: Weekly docetaxel therapy is active and well tolerated by elderly and/or poor-performance status patients with advanced breast cancer. This treatment can be administered with minimal myelosuppression. Weekly docetaxel provides an additional option for treatment in this difficult subgroup of patients with metastatic breast cancer. Well-tolerated combination regimens containing weekly docetaxel merit evaluation for this patient population.

Aged↗
PubMed2001

Occurrence of HIV-1 reverse transcriptase gene mutation at codon 215 in HIV-infected infants.

BACKGROUND: The nucleoside reverse transcriptase inhibitor Zidovudine (ZDV) decreases mother to child transmission of HIV infection. Nevertheless, significant proportions of mothers who are treated during pregnancy with ZDV still transmit the virus. Along with other factors, failure of ZDV prophylaxis may be due to maternal infection with ZDV-resistant strains and their consequent vertical transmission. OBJECTIVES: The purpose of the study was to investigate the occurrence of mutations at codon 215 in HIV-1 infected infants and its association with clinical status and virological parameters. STUDY DESIGN: The cohort consisted of 49 HIV-1 infected infants. Mononuclear cell DNA was isolated from whole blood and served as the input DNA for both a qualitative DNA PCR and the codon 215 assay (nested PCR). HIV-1 viral load (RNA PCR) was measured in plasma by the Roche Amplicor Monitor assay. RESULTS: Twelve of the 49 (24.5%) demonstrated viral strains with mutation at codon 215. A significant difference was found in infants born between 1992 and 1994 (6.3%) compared to those born in 1998-1999 (33.3%). Furthermore, in those infants born in 1998-1999, there was a trend toward an increase in the frequency of zidovudine resistant mutations at codon 215 corresponding to an increase in maternal zidovudine treatment. The mixture of wild and mutant HIV-1 strains was detected in two of 14 infants (14.3%) with a low viral load (<750000 c/ml) compared to nine of 19 (47.4%) infants with extremely high levels of HIV-1 RNA concentration (>750000 c/ml). Only two of 33 tested infants were HIV symptomatic and in both, a mixture of wild and mutant HIV-1 strains was detected. In both infants, the viral load was >750000 c/ml. CONCLUSIONS: This study showed that the overall frequency of ZDV resistant strains in infants born in 1998-1999 was significantly higher than that found in infant samples from 1992 to 1994. By 1998, the standard of care for mothers known to be infected with HIV was treatment with either monotherapy using ZDV or combined therapy using a variety of antiretroviral agents including ZDV. Although the exact role of ZDV resistance in limiting the effectiveness of therapies aimed at blocking vertical transmission of HIV remains to be defined, it is clear that drug resistant strains of HIV are occurring more frequently in all types of HIV infection, including infants.

Anti-HIV Agents↗
PubMed2001

Metachromatic leukodystrophy and nonverbal learning disability: neuropsychological and neuroradiological findings in heterozygous carriers.

Metachromatic leukodystrophy (MLD) is an autosomal recessive neurodegenerative disorder due to deficiency of the enzyme arylsulfatase A that leads to progressive, diffuse demyelination. The syndrome of nonverbal learning disability has been attributed to white matter abnormality and has been reported in children with this disorder and in some healthy family member carriers of gene. We examined the neuropsychologic profiles and MRIs of eight members of the family of a 7-year-old girl with this disease, all of whom were heterozygous carriers of the mutation and five of whom were also carriers of the MLD pseudodeficiency gene. All had low normal levels of arylsulfatase A, and seven of the eight had average or better profiles across all assessed neuropsychological domains. The patient's younger sister had a profile with features of the syndrome of nonverbal learning disability despite a normal MRI, whereas two members with minor white matter findings did not. This family does not provide evidence for the syndrome of nonverbal learning disability in heterozygous carriers of the gene for MLD, even when associated with the MLD pseudodeficiency gene.

Adolescent↗
PubMed2001

Preparation and achievement of American College of Surgeons level I trauma verification raises hospital performance and improves patient outcome.

OBJECTIVE: The purpose of this study was to assess the impact on patient outcome and hospital performance of preparing for and achieving American College of Surgeons (ACS) Level I trauma verification. METHODS: The center was a previously designated state regional trauma center located adjacent to a major metropolitan area. Preparation for ACS verification began in early 1996 and was completed in early 1998. Final verification took place in April 1999. Data were analyzed before (1994) and after (1998) the process. There was a marked increase in administrative support with trauma named one of the hospital's six centers of excellence. Two full-time board-certified trauma/critical care surgeons were added to the current six trauma surgeons. Their major focus was trauma care. Trauma support staff was also increased with case managers, a trauma nurse practitioner, additional trauma registrars, and administrative support staff. Education and continuous quality improvement were markedly expanded starting in 1996. RESULTS: There were 1,098 trauma patients admitted in 1994, and 1,658 in 1998. Overall mortality decreased (1994, 7.38%; 1998, 5.37%; p < 0.05). There was a marked decrease in mortality for severely injured (Injury Severity Score > 30) patients (1994, 44% mortality [38 of 86]; 1998, 27% [22 of 80]; p < 0.04). Average length of stay also decreased (1994, 12.22 days; 1998, 9.87 days; p < 0.02). This yielded an estimated cost savings for 1998 of greater than $4,000 per patient (total saving estimate of $7.4 million). CONCLUSION: Trauma system improvement as related to achieving ACS Level I verification appeared to have a positive impact on survival and patient care. There were cost savings realized that helped alleviate the added expense of this system improvement. The process of achieving ACS Level I verification is worthwhile and can be cost effective.

Adolescent↗
PubMed2001

Tutorial on risk adjusted X-bar charts: applications to measurement of diabetes control.

Two data elements are needed for constructing a risk-adjusted X-bar chart. They are a continuous observed outcome collected over time across a sample of patients, and an expected outcome for each patient. The authors selected blood glucose levels to reflect diabetes control. They then reviewed data showing blood glucose levels of 60 Type 2 diabetes patients in a family practice clinic of five providers. The data covered a period of 21 consecutive months. They present the data relating to two of the providers using this set of data to demonstrate how to create a risk-adjusted X-bar control chart.

Analysis of Variance↗
PubMed2001

Nuclear envelope defects associated with LMNA mutations cause dilated cardiomyopathy and Emery-Dreifuss muscular dystrophy.

Nuclear lamin A and C alleles that are linked to three distinct human diseases have been expressed both in HeLa cells and in fibroblasts derived from Lmna null mice. Point mutations that cause dilated cardiomyopathy (L85R and N195K) and autosomal dominant Emery-Dreifuss muscular dystrophy (L530P) modify the assembly properties of lamins A and C and cause partial mislocalization of emerin, an inner nuclear membrane protein, in HeLa cells. At the same time, these mutant lamins interfere with the targeting and assembly of endogenous lamins and in this way may cause significant changes in the molecular organization of the nuclear periphery. By contrast, lamin A and C molecules harboring a point mutation (R482W), which gives rise to a dominant form of familial partial lipodystrophy, behave in a manner that is indistinguishable from wild-type lamins A and C, at least with respect to targeting and assembly within the nuclear lamina. Taken together, these results suggest that nuclear structural defects could contribute to the etiology of both dilated cardiomyopathy and autosomal dominant Emery-Dreifuss muscular dystrophy.

Animals↗
PubMed2000

Fine mapping of the neurally expressed gene SOX14 to human 3q23, relative to three congenital diseases.

Members of the Sox gene family encode transcription factors that have diverse and important functions during development. We have recently described the cloning of chick and mouse Sox14 and the expression of these genes in a population of ventral interneurons in the embryonic spinal cord. We report here the cloning and sequencing of the human orthologue of Sox14. Human SOX14 shows remarkable sequence conservation compared with orthologues from other vertebrate species and probably mirrors the expression of these genes in the developing brain and spinal cord. Using radiation hybrid mapping and fluorescence in situ hybridisation, we have localised SOX14 close to the sequence tagged site D3S1576 on human chromosome 3q23. Three congenital disorders have been localised to this region: blepharophimosis-ptosis-epicanthus inversus syndrome (BPES), Charcot-Marie-Tooth neuropathy type IIB (CMT2B) and Mobius syndrome type 2 (MBS2). We have found that SOX14 is unlikely to be involved in any of these disorders because of the position of SOX14 proximal to a BPES breakpoint and the lack of SOX14 coding region alterations in BPES, CMT2B and MBS2 patients.

Amino Acid Sequence↗
PubMed2000

An artificial neural network as a model for prediction of survival in trauma patients: validation for a regional trauma area.

BACKGROUND: To develop and validate an artificial neural network (ANN) for predicting survival of trauma patients based on standard prehospital variables, emergency room admission variables, and Injury Severity Score (ISS) using data derived from a regional area trauma system, and to compare this model with known trauma scoring systems. PATIENT POPULATION: The study was composed of 10,609 patients admitted to 24 hospitals comprising a seven-county suburban/rural trauma region adjacent to a major metropolitan area. The data was generated as part of the New York State trauma registry. Study period was from January 1993 through December 1996 (1993-1994: 5,168 patients; 1995: 2,768 patients; 1996: 2,673 patients). METHODS: A standard feed-forward back-propagation neural network was developed using Glasgow Coma Scale, systolic blood pressure, heart rate, respiratory rate, temperature, hematocrit, age, sex, intubation status, ICD-9-CM Injury E-code, and ISS as input variables. The network had a single layer of hidden nodes. Initial network development of the model was performed on the 1993-1994 data. Subsequent models were generated using the 1993, 1994, and 1995 data. The model was tested first on the 1995 and then on the 1996 data. The ANN model was tested against Trauma and Injury Severity Score (TRISS) and ISS using the receiver operator characteristic (ROC) area under the curve [ROC-A(z)], Lemeshow-Hosmer C-statistic, and calibration curves. RESULTS: The ANN showed good clustering of the data, with good separation of nonsurvivors and survivors. The ROCA(z) was 0.912 for the ANN, 0.895 for TRISS, and 0.766 for ISS. The ANN exceeded TRISS with respect to calibration (Lemeshow-Hosmer C-statistic: 7.4 for ANN; 17.1 for TRISS). The prediction of survivors was good for both models. The ANN exceeded TRISS in nonsurvivor prediction. CONCLUSION: An ANN developed for trauma patients using prehospital, emergency room admission data, and ISS gave good prediction of survival. It was accurate and had excellent calibration. This study expands our previous results developed at a single Level I trauma center and shows that an ANN model for predicting trauma deaths can be applied across hospitals with good results

Adolescent↗
PubMed2000

HET/SAF-B overexpression causes growth arrest and multinuclearity and is associated with aneuploidy in human breast cancer.

HET/SAF-B was originally cloned as a nuclear matrix protein that bound to matrix attachment regions and as a transcriptional repressor of the small heat shock protein hsp27. In addition, we have found recently that HET/SAF-B is also a corepressor of estrogen receptor activity. Estrogen receptor has a very well-described role in breast cancer, and aberrant expression of nuclear matrix and heat shock proteins has also been implicated in breast tumorigenesis. Therefore, we asked whether HET/SAF-B itself could be important in breast cancer. Toward this goal we examined its expression in breast cancer cell lines and asked whether HET/SAF-B can affect breast cancer cell proliferation. Finally, we studied HET/SAF-B expression in clinical breast cancer samples. HET/SAF-B protein and mRNA were detected at varying levels in all of the eight breast cancer cell lines examined. Using a number of different approaches to modulate the level of HET/SAF-B protein in the cell, we found that HET/SAF-B levels are inversely correlated with cell proliferation. In addition,transfection of HET/SAF-B fused to the green fluorescent protein led to the formation of multinucleated cells not observed in cells transfected with green fluorescent protein alone, suggesting that this effect is a direct result of HET/SAF-B overexpression. Western blot analysis of HET/SAF-B in 61 human breast tumors revealed widely varying levels of HET/SAF-B expression, with some tumors (16%) lacking any detectable HET/SAF-B. Statistical analysis showed that high HET/SAF-B expression in these tumors was associated with low S-phase fraction and with aneuploidy, consistent with our results from transfection experiments in tissue culture cells. We conclude that HET/SAF-B plays an important role in breast cancer, and we discuss possible mechanisms of the involvement of HET/SAF-B in cell proliferation and division.

3T3 Cells↗
PubMed1999

Loss of A-type lamin expression compromises nuclear envelope integrity leading to muscular dystrophy.

The nuclear lamina is a protein meshwork lining the nucleoplasmic face of the inner nuclear membrane and represents an important determinant of interphase nuclear architecture. Its major components are the A- and B-type lamins. Whereas B-type lamins are found in all mammalian cells, A-type lamin expression is developmentally regulated. In the mouse, A-type lamins do not appear until midway through embryonic development, suggesting that these proteins may be involved in the regulation of terminal differentiation. Here we show that mice lacking A-type lamins develop to term with no overt abnormalities. However, their postnatal growth is severely retarded and is characterized by the appearance of muscular dystrophy. This phenotype is associated with ultrastructural perturbations to the nuclear envelope. These include the mislocalization of emerin, an inner nuclear membrane protein, defects in which are implicated in Emery-Dreifuss muscular dystrophy (EDMD), one of the three major X-linked dystrophies. Mice lacking the A-type lamins exhibit tissue-specific alterations to their nuclear envelope integrity and emerin distribution. In skeletal and cardiac muscles, this is manifest as a dystrophic condition related to EDMD.

Animals↗
PubMed1999

Regulation of IFN consensus sequence binding protein expression in murine macrophages.

Recent work has demonstrated that the transcription factor, IFN consensus sequence binding protein (ICSBP), plays a critical role in the capacity of mice to control infection with Toxoplasma gondii and Leishmania major, agents that require highly activated macrophages for their elimination. In this report the regulation of ICSBP mRNA and protein were analyzed in murine macrophages stimulated with LPS and/or IFN-gamma. Like induction of leishmaniacidal activity, LPS and IFN-gamma synergize to induce ICSBP mRNA and protein. Deletion analysis of the ICSBP promoter identified regions that were IFN-gamma responsive, regions that mediate the ability of LPS and IFN-gamma to activate this promoter synergistically, as well as regions that normally repress ICSBP transcription. Finally, exogenous expression of ICSBP, found in previous studies to down-regulate MHC I gene expression, failed to repress basal or IFN-gamma-induced ICSBP transcription. This demonstrates that ICSBP can selectively suppress the expression of IFN-responsive genes. These findings extend in a significant way our understanding of the regulation of ICSBP by LPS and IFN-gamma and provide important clues as to its role in macrophage activation.

Animals↗
PubMed1999

Stereolithographic modelling as an aid to orbital brachytherapy.

PURPOSE: This paper describes the technique of stereolithographic biomodelling and its application to a patient who was treated using orbital brachytherapy. METHODS AND MATERIALS: The process uses a moving laser beam, directed by a computer, to draw cross-sections of the model onto the surface of photo-curable liquid plastic. Using a stereolithographic apparatus (SLA), solid or surface data is sliced by software into very thin cross-sections. A helium cadmium (HeCd) laser then generates a small intense spot of ultraviolet (UV) light that is moved across the top of a vat of liquid photo monomer by a computerised optical scanning system. The laser polymerises the liquid into a solid where it touches, precisely printing each cross-section. A vertical elevator lowers the newly formed layer, and a recoating and levelling system establishes the next layer's thickness. Successive cross-sections (0.25 mm thick), each one adhering to the one below, are built one on top of the other, to form the part from the bottom up. The biomodel allowed the implant to be planned in detail prior to the surgery. The accurate placement of brachytherapy catheters was assured, and the dosimetry could be determined and optimised prior to the definitive procedure. CONCLUSIONS: Stereolithography is a useful technique in the area of orbital brachytherapy. It allows the implant to to be carried out with greater accuracy and confidence. For the patient, it minimises the risk to the eye and provides them with a greater understanding of the procedure.

Adult↗
PubMed1999

Comparison of human immunodeficiency virus 1 DNA polymerase chain reaction and qualitative and quantitative RNA polymerase chain reaction in human immunodeficiency virus 1-exposed infants.

BACKGROUND: HIV-1 RNA PCR is a widely available and sensitive assay but has not been studied for use in early diagnosis of HIV-1 infection in infants. METHODS: Research HIV-1 DNA PCR and HIV-1 RNA PCR were performed on peripheral blood mononuclear cells and plasma, respectively, from 284 blood samples from 204 infants. A commercially available HIV-1 quantitative RNA PCR was also performed on plasma from the 132 samples from HIV-1-infected infants and 22 of the samples from HIV-1-uninfected infants. RESULTS: Sensitivities of all assays varied with infant age. HIV-1 DNA PCR had a sensitivity of 27% in the < or = 3-week age group (n = 11) whereas qualitative and quantitative RNA PCR had sensitivities of 64 and 55%, respectively (P not significant). Each assay had a sensitivity of 96.2% at 4 to 6 weeks (n = 26) and 100% at > or = 7 weeks of age (n = 95). Specificity of HIV-1 DNA PCR for all age groups was 100%, whereas specificities of qualitative and quantitative RNA PCR assay were 96.1 and 95.5%, respectively. CONCLUSIONS: HIV-1 RNA PCR may offer a slight advantage in sensitivity over DNA PCR in the diagnosis of HIV infection in young infants. Positive RNA results can be found in a small number of infants who are not HIV-1-infected. HIV-1 RNA detection should not be routinely used alone for the diagnosis of HIV infection in young infants.

Chi-Square Distribution↗
PubMed1999

Reduction of the cardiotoxicity of doxorubicin in rabbits and dogs by encapsulation in long-circulating, pegylated liposomes.

The relative cardiotoxicity of pegylated (STEALTH) liposomal doxorubicin (PL-DOX; Doxil) was compared to nonliposomal doxorubicin (Adriamycin) in rabbits and dogs treated i.v. for up to 22 weeks. No histological evidence of cardiotoxicity was seen in dogs treated with placebo liposomes or PL-DOX every 3 weeks for a total of 10 doses (cumulative doxorubicin dose = 10 mg/kg) either 1 or 5 weeks post-treatment. All dogs treated with the same cumulative dose of free doxorubicin showed marked cardiotoxicity (vacuolization and myofibrillar loss in the myocardium) at both time points. In rabbits, progressive cardiomyopathy was seen in both treatment groups, but was more frequent and severe with free doxorubicin (67% of doxorubicin-treated rabbits, cumulative dose = 12 to 14 mg/kg versus 16% of PL-DOX-treated animals, cumulative dose = 14 to 21 mg/kg). Five doxorubicin-treated rabbits died of congestive heart failure or with histologic evidence of cardiotoxicity (median severity score = 6). No PL-DOX-treated rabbits died of congestive heart failure, although two animals that died early showed microscopic evidence of mild cardiotoxicity (median severity score = 2.5). Cardiotoxicity increased during the post-treatment period in both treatment groups. Rabbits received up to 50% more PL-DOX with no increase in cardiotoxicity. Thus, results in two species demonstrate that the cardiotoxicity of doxorubicin is significantly decreased when administered as PL-DOX. Significantly more PL-DOX can be given without incurring an increased risk of cardiomyopathy. Recent clinical studies have confirmed that PL-DOX is also less cardiotoxic than the same dose of unencapsulated doxorubicin in humans.

Animals↗