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Biomedical subjects

C Andrews

Publications and source records attributed to C Andrews.

At least 55 records · Page 3Linked to original sources

Induction of the angiogenic phenotype by Hox D3.

Angiogenesis is characterized by distinct phenotypic changes in vascular endothelial cells (EC). Evidence is provided that the Hox D3 homeobox gene mediates conversion of endothelium from the resting to the angiogenic/invasive state. Stimulation of EC with basic fibroblast growth factor (bFGF) resulted in increased expression of Hox D3, integrin alphavbeta3, and the urokinase plasminogen activator (uPA). Hox D3 antisense blocked the ability of bFGF to induce uPA and integrin alphavbeta3 expression, yet had no effect on EC cell proliferation or bFGF-mediated cyclin D1 expression. Expression of Hox D3, in the absence of bFGF, resulted in enhanced expression of integrin alphavbeta3 and uPA. In fact, sustained expression of Hox D3 in vivo on the chick chorioallantoic membrane retained EC in this invasive state and prevented vessel maturation leading to vascular malformations and endotheliomas. Therefore, Hox D3 regulates EC gene expression associated with the invasive stage of angiogenesis.

Animals↗

CD4 T cell anergy in murine AIDS: costimulation via CD28 and the addition of IL-12 are not sufficient to rescue anergic CD4 T cells.

Murine acquired immunodeficiency syndrome (MAIDS) is a fatal disease induced by a mixture of retroviruses known as BM5. It is characterized by splenomegaly, lymphadenopathy, hypergammaglobulinemia, loss of T and B cell function, and development of B cell lymphomas. As the disease progresses, by wk 8 of infection, CD4 T cell response to Ags and mitogens is severely curtailed and the CD4 T cell population becomes anergic. We examined responses of anergic CD4 T cells upon addition of a costimulatory signal (anti-CD28) and a cytokine (IL-12), which might help to restore the function of cells. We report that proliferation and cytokine production were restored in the early stages of infection by the strategies we tested, but not at later stages when anergy was well established. We also examined the effect of the same treatments on anergy of CD4 T cells from thymectomized, BM5-infected mice to determine whether the rescue seen was due to cells freshly derived from the thymus. We report that proliferation and cytokine production decreased in thymectomized mice even at wk 4 of infection, indicating that cells that are freshly derived from thymus are the ones responding to treatment. This study indicates that once anergy has been established in MAIDS, it cannot be reversed by providing costimulation via CD28 and IL-12. Anergy of CD4 T cells in MAIDS appears to be different from that seen in other systems, both in underlying cause and in the ability of the cells to revert to a normal state.

Animals↗

Simultaneous rapid high-performance liquid chromatographic determination of phenytoin and its prodrug, fosphenytoin in human plasma and ultrafiltrate.

A reversed-phase high-performance liquid chromatographic assay for the simultaneous determination of phenytoin and fosphenytoin, a prodrug for phenytoin, in human plasma and plasma ultrafiltrate is described. For plasma, the method involves simple extraction of drugs with diethyl ether and evaporation of solvent, followed by injection of the reconstituted sample onto a reversed-phase C18 column. Plasma ultrafiltrate is injected directly into the HPLC column. Compounds are eluted using an ion-pair mobile phase containing 20% acetonitrile. The eluent is monitored by UV absorbance at 210 nm. The fosphenytoin standard curves are linear in the concentration range 0.4 to 400 microg/ml for plasma and 0.03 to 80 microg/ml for ultrafiltrate. Phenytoin standard curves are linear from 0.08 to 40 microg/ml for plasma and from 0.02 to 5.0 microg/ml for ultrafiltrate. No interferences with the assay procedure were found in drug-free blank plasma or plasma ultrafiltrate. Relative standard deviation for replicate plasma or ultrafiltrate samples was less than 5% at concentrations above the limit of quantitation for both within- and between-run calculations.

Anticonvulsants↗

Binning clones by hybridization with complex probes: statistical refinement of an inner product mapping method.

Molecular methods that use long-range information to solve genomics problems (i.e., top-down strategies) efficiently have become increasingly prominent in the genomics literature. One such method, an implementation of inner product mapping (IPM), uses noisy, long-range radiation hybrid (RH)/YAC overlap data and relatively noise-free RH/STS overlap data to localize clones to specific chromosomal regions. Because the molecular data are rarely noise-free, statistical models tailored to the top-down molecular methods make the methods far more effective. We develop two statistical models for IPM (or any other top-down strategy of similar form), a parametric logit model and a nonparametric order-restricted model, and show how these models can be implemented within a hierarchical Bayes framework. Using these models, we refine the chromosome 11 map reported in M. Perlin et al. (1995, Genomics 28: 315-327). Our analyses improve the IPM map, both in terms of successful localization of clones and in terms of the confidence with which they are localized.

Chromosome Mapping↗

The ankle clonus test for assessment of the integrity of the spinal cord during operations for scoliosis.

The ankle clonus test, a method for evaluating the integrity of the spinal cord during operations for scoliosis, is predicated on the finding that patients recovering from general anesthesia normally have temporary ankle clonus bilaterally. An absence of transient ankle clonus has been shown to indicate neurological compromise. The test was performed for 1006 patients who were being managed with spinal arthrodesis and instrumentation and 115 control patients who had an operation under general anesthesia because of a condition that was unrelated to the spine. The six patients in whom a neurological deficit developed all had had a so-called positive result on the ankle clonus test (that is, an absence of transient ankle clonus). There were no false-negative results and three false-positive results; the test therefore had a sensitivity of 100 per cent and a specificity of 99.7 per cent. The ankle clonus test was found to be more accurate than the wake-up test and monitoring of somatosensory evoked potentials for predicting neurological compromise.

Adolescent↗

Pancreas transplantation for diabetes mellitus.

Pancreas transplantation has become a viable option for the patient wi th insulin-dependent diabetes mellitus with progressive renal failure. The most common type of pancreas transplantation is a simultaneous pancreas and kidney transplantation performed from a single cadaver donor (SPK). The next most common is pancreas transplantation after successful kidney transplantation (PAK). A few centers are performing pancreas transplantation alone (PTA) in diabetic recipients without renal disease but who have significant complications from their diabetes. Pancreas transplantation is associated with a higher morbidity than kidney transplantation alone. Most pancreas transplantation centers report a significant increase in acute rejection, which can lead to increased hospitalization and risk of opportunistic infection. In addition, the early era of pancreas transplantation was associated with significant surgical complications. However, with bladder drainage of the pancreas exocrine secretions, the surgical complication rate has decreased significantly. Despite medical and surgical complications, the overall results for pancreas transplantation are excellent, with 1 -year graft survival of 75% for SPK transplantations and 48% for PAK and PTA transplant recipients. The effects of a pancreas transplantation on the secondary complications of diabetes have been studied extensively. Most studies have shown a modest improvement in secondary complications with the exception of diabetic retinopathy. The major benefit of pancreas transplantation appears to be enhanced quality of life for patients successfully transplanted. For these reasons, the Kidney-Pancreas Committee of the American Society of Transplant Physicians believes the current results of pancreas-kidney transplantation justify its use as a valid option for insulin-dependent diabetic transplant recipients.

Costs and Cost Analysis↗

Concept formation vs. logistic regression: predicting death in trauma patients.

This study compares two classification models used to predict survival of injured patients entering the emergency department. Concept formation is a machine learning technique that summarizes known examples cases in the form of a tree. After the tree is constructed, it can then be used to predict the classification of new cases. Logistic regression, on the other hand, is a statistical model that allows for a quantitative relationship for a dichotomous event with several independent variables. The outcome (dependent) variable must have only two choices, e.g. does or does not occur, alive or dead, etc. The result of this model is an equation which is then used to predict the probability of class membership of a new case. The two models were evaluated on a trauma registry database composed of information on all trauma patients admitted in 1992 to a Level I trauma center. A total of 2155 records. representing all trauma patients admitted for more than 24 h or who died in the Emergency Department, were grouped into two databases as follows: (1) discharge status of 'died' (containing 151 records), and (2) any discharge status other than 'died' (containing 2004 records). Both databases contained the same variables.

Artificial Intelligence↗

Speech outcomes of a prolonged-speech treatment for stuttering.

It has been shown that people who stutter can speak with greatly reduced stuttering after treatments that use variations of Goldiamond's (1965) prolonged-speech (PS). However, outcome research to date has not taken account of several important issues. In particular, speech outcome measures in that research have been insufficient to show that lasting relief from stuttering has been achieved by clients outside the clinic for meaningful periods. The present study used extensive speech outcome measures across a variety of situations in evaluating the outcome of an intensive PS treatment (Ingham, 1987). The speech of 12 clients in this treatment was assessed on three occasions prior to treatment and frequently-on eight occasions-after discharge from the residential setting. For 7 clients, a further assessment occurred at 3 years posttreatment. Concurrent dependent measures were percent syllables stuttered, syllables per minute, and speech naturalness. The dependent measures were collected in many speaking situations within and beyond the clinic. Dependent measures were based on speech samples of substantive duration, and covert assessments were included in the study. Detailed data were presented for individual subjects. Results showed that 12 subjects who remained with the entire 2-3-year program achieved zero or near-zero stuttering. The majority of subjects did not show a regression trend in %SS or speech naturalness scores during the posttreatment period, either within or beyond the clinic. Some subjects showed higher posttreatment %SS scores during covert assessment than during overt assessment. Results also showed that stuttering was eliminated without using unusually slow and unnatural speech patterns. This treatment program does not specify a target speech rate range, and many clients maintained stutter-free speech using speech rates that were higher than the range typically specified in intensive PS programs. A significant correlation was found between speech rate and perceived posttreatment speech naturalness.

Adolescent↗

Transtelephone monitoring for pacemaker follow-up 1981-1994.

Transtelephone monitoring (TTM) is capable of detecting pacemaker pulse generator malfunction, battery depletion, and lead failure. The accuracy of TTM was analyzed by a review of Montefiore Medical Center records between October 1981 and March 1994. Each group of transmissions from a single patient, starting with implant and ending with a pacemaker operation, was defined as a closed cycle (CLOSE), if undergoing continuing follow-up at the time of analysis, as a continuing cycle (CONT), and if a cycle had ended with death or loss to follow-up, an open cycle (OPEN). TTM records of 2,632 patients were analyzed, providing 3,291 cycles. There were 731 CONT, 433 CLOSE, and 2,127 OPEN cycles; 331 procedures were indicated by TTM, of which 279 were impending depletion, 30 sudden depletion, and 22 lead malfunctions. Of the 102 procedures not indicated by TTM, 85 were for nonurgent reasons (recall: 41; DDD upgrade: 16; patient/MD request: 28) and 17 for urgent reasons. In patients followed by TTM who had a lead problem, 22 were detected by TTM before clinical manifestations and 16 were not. There were no cases in which TTM follow-up did not detect battery depletion. The total number of TTM contacts, available for 3,094 cycles, was 88,654 (range, 1-163, median 19), of which 0.4% yielded a procedure. During the same period, 75% of all secondary interventions during the first 2 years occurred during the first 2 months after implant because of lead malfunction, with a subsequent SI rate of 0.005 per month for the third through the twenty-fourth months.

Electrocardiography↗

Advanced life support in the wilderness: 5-year experience of the Reach and Treat team.

Increasing recreation in the wilderness raises questions about the value of providing advanced life support (ALS) care in the backcountry. Since 1989 the Reach and Treat (RAT) team has provided ALS care in the wilderness area that surrounds Mount Hood, Oregon. The purpose of our study was to describe patient demographics, terrain, injuries, and ALS treatment in the wilderness environment. We utilized a retrospective, observational analysis of RAT missions from 1989 to 1994 based on data sheets maintained by the RAT team, prehospital run sheets, and hospital charts. Of the 114 missions analyzed, the median time of missions was 3 h, 9 min (range, 44 min-76 h) and 20% required technical climbing skills. Of the 74 patients treated, 55 (90%) received ALS care: 8 were intubated, 52 had intravenous lines established, and 24 received morphine for pain. Twenty patients were entered into the local trauma system. The most common injuries were extremity injuries (58), head injuries (18), and hypothermia (15). Mean time from arrival to return to staging area was 95 min. No injuries to RAT team members occurred during these missions, although two minor injuries occurred during training and testing. We found that wilderness-trained paramedics safely provided ALS care in a backcountry environment. This care may improve patient comfort during long extrication and speeds the arrival of potentially life-saving interventions such as advanced airway management.

Adolescent↗

Neural correlates of working memory in a visual letter monitoring task: an fMRI study.

Complex mental operations rely on the coordinated activity of widely distributed brain regions constituting neurocognitive networks. Using multislice echoplanar functional magnetic resonance imaging (fMRI) we have contrasted regional brain activity during a control and an experimental condition which differed with respect to the demands placed on verbal working memory. Subjects were seven right-handed healthy male volunteers. Analysis of group and individual data revealed activation in the anterior and posterior parasagittal cortex in all subjects, left parietal cortex (six subjects) and left dorsolateral prefontal cortex (five subjects). These results suggest that verbal working memory is subserved by a neurocognitive network comprising cortical regions involved in attention, executive function and short term mnemonic processes.

Adult↗

The effect of transfection of the CEA gene on the metastatic behavior of the human colorectal cancer cell line MIP-101.

Carcinoembryonic antigen (CEA) has been shown to increase the metastatic potential of some human colorectal cancer cell lines. To investigate further the mechanisms involved we have produced three clones (6, 8 and 17) from the poorly differentiated human colorectal cancer cell line MIP-101 that have been transfected with the full length cDNA encoding for human carcinoembryonic antigen (CEA). They produce CEA with a mol. wt. of 180000 by Western blotting and secrete it into the culture medium. Clone 6 is a high CEA producer, clones 8 and 17 are intermediate producers. The doubling time for clone 8 was similar to that of the parent cell line while clones 6 and 17 had doubling times nearly twice that of the parent cells. These clones are tumorigenic when injected subcutaneously in nude mice are positive for CEA by immunoperoxidase staining and the mice have elevated blood levels of CEA. Clone 6 formed large aggregates in culture while clone 17 formed smaller aggregates. Clone 8 behaved like the parent cell line with rare cell/cell contact. Clones 6 and 17 also adhered to CEA coated plastic while clone 8, a neo-transfected control and the parent cell line did not. A significant increase in the incidence of hepatic tumors was observed with clone 6 (P < 0.01) and clone 17 (P < 0.02) following intrasplenic injection into nude mice. Immunohistopathology of the hepatic tumors showed strong CEA staining from clones 6 and 17 with weak staining from clone 8. The parent cell line was negative for CEA as were the neo-transfected controls. Of the neo controls none of 10 had liver colonies. Mice injected with clone 6 which developed liver metastasis had the highest plasma levels of CEA (37.3 +/- 8.8 ng/ml). We observed strong CEA staining in Kupffer cells in the normal liver adjacent to the CEA producing tumors. This study provides further evidence for the involvement of CEA in the metastatic process.

Adenocarcinoma↗

Preventing and managing pressure sores in palliative care.

Pressure sore rates were addressed in a palliative care unit by undertaking risk assessment, monitoring wound status and introducing a dressing protocol. A systematic approach to pressure sores in palliative care resulted in a decrease in pressure sore rates in one hospice.

Clinical Nursing Research↗