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Biomedical subjects

M Flannery

Publications and source records attributed to M Flannery.

At least 19 recordsLinked to original sources

Low incidence of myocardial recovery after left ventricular assist device implantation in patients with chronic heart failure.

BACKGROUND: Mechanical, histological, and biochemical improvement has been described in patients after left ventricular assist device (LVAD) support. Explantation of the LVADs without heart transplantation has been described in selected patients who received this therapy as a bridge to transplantation. METHODS AND RESULTS: A retrospective review of patients receiving a mechanical bridge to transplantation at Columbia Presbyterian Hospital after July 21, 1991, was performed to determine the incidence of patients in whom the device was successfully explanted. From August 1, 1996, to February 1, 1998, we prospectively attempted to identify potential explant candidates by the use of exercise testing. During this time, we recruited 39 consecutive patients after insertion of the Thermo Cardiosystems vented electric device to participate in the following study. Approximately 3 months after device implantation, a maximal exercise test with hemodynamic monitoring and respiratory gas analysis was performed with the LVAD in the automated mode. The electric device was interfaced with a pneumatic console such that the rate could be decreased to 20 cycles/min. Hemodynamic measurements were recorded as the device rate was decreased. A repeat exercise test was then performed if the patient remained hemodynamically stable. A retrospective chart review of 111 LVAD recipients at our institution identified only 5 successful explant patients. Eighteen of the 39 patients were studied. Fifteen patients exercised with maximal device support. At peak exercise, VO2 averaged 14.5+/-3.6 mL. kg-1. min-1; LVAD flow, 8.0+/-1.3 L/min; Fick cardiac output, 11.4+/-3.3 L/min; and pulmonary capillary wedge pressure, 13+/-4 mm Hg. Seven patients remained normotensive and could exercise at a fixed rate of 20 cycles/min. In these patients, peak VO2 declined from 17.3+/-3.9 to 13.0+/-6.1 mL. kg-1. min-1. In one of these patients, the device was explanted. CONCLUSIONS: Significant myocardial recovery after LVAD therapy in patients with end-stage congestive heart failure occurs in a small percentage of patients. Most of these patients have dilated cardiomyopathy. Exercise testing may be a useful modality to identify those patients in whom the device can be explanted.

Adolescent

A murine AP-endonuclease gene-targeted deficiency with post-implantation embryonic progression and ionizing radiation sensitivity.

Apurinic/apyrimidinic endonuclease (here designated APE/REF) carries out repair incision at abasic or single-strand break damages in mammals. This multifunctional protein also has putative role(s) as a cysteine 'reducing factor' (REF) in cell-stress transcriptional responses. To assess the significance of APE/REF for embryonic teratogenesis we constructed a more precisely targeted Ape/Ref-deficient genotype in mice. Ape/Ref gene replacement in ES cells eliminated the potential of APE/REF protein synthesis while retaining the Ape/Ref bi-directional promoter that avoided potential inactivation of an upstream gene. Chimeric animals crossed into Tac:N:NIHS-BC produced germline transmission. Homozygous null Ape/Ref-embryos exhibited successful implantation and nearly normal developmental progression until embryonic day 7.5 followed by morphogenetic failure and adsorption of embryos by day 9.5. We characterized the cellular events proceeding to embryonic lethality and examined ionizing radiation sensitivity of pre-implantation Ape/Ref-null embryos. After intermating of heterozygotes, Mendelian numbers of putative Ape/Ref-null progeny embryos at day 6.5 displayed a several-fold elevation of pycnotic, fragmenting cell nuclei within the embryo proper-the epiblast. Increased cell-nucleus degeneration occurred within epiblast cells while mitosis continued and before obvious morphogenetic disruption. Mitogenic response to epiblast cell death, if any, was ineffective for replacement of lost cells. Extra-embryonic yolk sac, a trophectoderm derived lineage retained normal appearance to day 9. Explanted homozygous Ape/Ref-null blastocysts displayed increased sensitivity to gamma-irradiation, most likely a manifestation of APE/REF incision defect. Our study establishes that this new Ape/Ref deficiency genotype is definitely capable of post-implantation developmental progression to the onset of gastrulation. Function(s) of APE/REF in base damage incision and also conceivably in mitogenic responses towards epiblast cell death are critical for transit through the gastrulation stage of embryonic growth and development.

Alleles

Comparison of exercise performance in patients with chronic severe heart failure versus left ventricular assist devices.

BACKGROUND: Left ventricular assist devices (LVADs) are frequently used as a bridge to cardiac transplantation and may be useful as long-term therapy. The purpose of this study was to compare the exercise performance of LVAD patients with that of ambulatory heart failure patients. METHODS AND RESULTS: Exercise testing with hemodynamic and respiratory gas measurements was performed in 65 congestive heart failure (CHF) patients (age 53+/-10 years) and 20 LVAD patients (age 49+/-8 years). Peak Vo2 was significantly higher in the LVAD than the CHF patients (CHF, 12+/-3; LVAD, 15. 9+/-3.8 mL . kg-1 . min-1; P<0.001), as was the Vo2 at the anaerobic threshold (CHF, 8.1+/-2.1; LVAD, 12.2+/-2.9 mL . kg-1 . min-1; P<0.001). At rest, mean arterial blood pressure (CHF, 87+/-11; LVAD, 94+/-9 mm Hg) and cardiac output (CHF, 4+/-1; LVAD, 4. 9+/-0.9 L/min) were increased, whereas mean pulmonary artery pressure (CHF, 28+/-11; LVAD, 18+/-4 mm Hg) and pulmonary artery wedge pressure (CHF, 16+/-10; LVAD 5+/-3 mm Hg) were reduced (all P<0.01). At peak exercise, heart rate (CHF,125+/-24; LVAD, 148+/-24 bpm), blood pressure (CHF, 87+/-14; LVAD,96+/-12 mm Hg), and cardiac output (CHF, 7.6+/-2.2; LVAD, 11.2+/-2.6 L/min) were higher (all P<0. 01), whereas mean pulmonary artery pressure (CHF, 48+/-12; LVAD, 30+/-5 mm Hg) and mean pulmonary capillary wedge pressure (CHF, 31+/-11; LVAD, 14+/-6 mm Hg) were lower in the LVAD group (both P<0. 001). In the LVAD patients, Fick cardiac output was higher than LVAD flow sensor value measurements (Fick, 11.6+/-2.5; LVAD, 8.1+/-1.2 L/min; P<0.001). CONCLUSIONS: Hemodynamic measurements at rest and during exercise are significantly improved in patients with devices compared with those in ambulatory heart failure patients awaiting cardiac transplantation. Similarly, the exercise capacity of device patients is better than that of transplant candidates and in the majority of patients is similar to that of patients with mild CHF.

Adult

Victims no more: preventing home care aide abuse.

Home care aides are especially susceptible to abuse because of their unique workplace situation. It's up to their employers--the home care agencies--to take deliberate steps to prevent on-the-job abuse. The aides, nurses, and supervisors of the home care team also play an important role in keeping care situations safe for all involved.

Contract Services

Implantable left ventricular assist devices provide an excellent outpatient bridge to transplantation and recovery.

OBJECTIVES: Our recent experience with outpatient left ventricular assist device (LVAD) support is presented to demonstrate the possibilities and limitations of long-term outpatient mechanical circulatory assistance. BACKGROUND: The experience with inpatient LVAD support as a bridge to transplantation has proved the efficacy of such therapy in improving circulatory hemodynamic status, restoring normal end-organ function and facilitating patient rehabilitation. With miniaturization of the power supplies and controllers, such mechanical circulatory support can now be accomplished in an outpatient setting. METHODS: Between March 1993 and February 1997, 32 patients (26 male, 6 female, mean [+/-SEM] age 49 +/- 15 years) underwent implantation of the ThermoCardiosystems (TCI) Heartmate vented electric (VE) LVAD. The VE LVAD is powered by batteries worn on shoulder holsters and is operated by a belt-mounted system controller, allowing unrestricted patient ambulation and hospital discharge. RESULTS: Mean duration of support was 122 +/- 26 days (range 3 to 605), with a survival rate to transplantation or explantation of 78%. Nineteen patients were discharged from the hospital on mean postoperative day 41 +/- 4 (range 17 to 68), for an outpatient support time of 108 +/- 30 days (range 2 to 466). Four patients underwent early transplantation and could not participate in the discharge program, and three patients currently await discharge. The complication rate was not statistically different from that encountered in our previous 52 patients with a pneumatic LVAD. CONCLUSIONS: Outpatient LVAD support is safe and provides improved quality of life for patients awaiting transplantation. Wearable and totally implantable LVADs should be studied as permanent treatment options for patients who are not candidates for heart transplantation.

Ambulatory Care

Defective chorioallantoic fusion in mid-gestation lethality of parthenogenone<-->tetraploid chimeras.

Previous studies of parthenogenetic embryos revealed severe perturbations of both embryonic and extraembryonic tissue lineages during postimplantation development. The majority of pure parthenogenetic concepti have no recognizable axis and exhibit preferential terminal differentiation of their trophectoderm and primitive endoderm. To further define the role of the extraembryonic lineages in parthenogenetic development, we provided them with zygote-derived extraembryonic tissues by aggregating them with fertilized tetraploid embryos. On Day 12 of combined in vitro and in vivo development, most of the embryos proper in these chimeras were entirely derived parthenogenetically, whereas their trophectoderm and primitive endoderm tissues were derived from the tetraploid component. No Igf2 expression was detected in the parthenogenetic embryo proper, indicating that imprinting was manifested in such chimeras. Typical development of the parthenogenetic embryo proper was markedly improved in comparison with pure parthenogenetic concepti, with such chimeras attaining an average of 23 somites (range, 10 to 35). However, most of the chimeras died abruptly at Day 13, and all were being resorbed at Day 14 of development. The gross normality of axial structures and organ development suggests that a major cause of failure of these chimeric parthenogenones to survive beyond mid-gestation was due to defective chorioallantoic fusion. Our results indicate that the severe perturbation of axial development seen in most pure parthenogenetic concepti is a secondary consequence of the effects of parthenogenesis on the trophectoderm and primitive endoderm lineages. Moreover, the mid-gestation death of parthenogenetic embryos proper despite the presence of zygote-derived tetraploid tissues implicates extraembryonic mesoderm in manifesting the effects of genomic imprinting.

Allantois

Malignant transformation in a fatal case of giant cell tumour of the sacrum.

Most giant cell tumours can be treated by local surgery and only rarely are they life threatening. We report a case of a giant cell tumour of the sacrum causing irresectable and fatal small bowel obstruction following malignant transformation of the tumour. The role of radiotherapy in this transformation is discussed.

Adolescent

Power wheelchair range testing and energy consumption during fatigue testing.

The range of a power wheelchair depends on many factors including: battery type, battery state, wheelchair/rider weight, terrain, the efficiency of the drive train, and driving behavior. The purpose of this study was to evaluate the feasibility of three methods of estimating power wheelchair range. Another significant purpose was to compare the current draw on pavement to current draw on an International Standards Organization (ISO) Double Drum tester at one m/sec. Tests were performed on seven different power wheelchairs unloaded, and loaded with an ISO 100 kg test dummy. Each chair was configured according to the manufacturer's specifications, and tires were properly inflated. Experienced test technicians were used for the tennis court tests, and treadmill tests. An ISO 100 kg test dummy was used for the ISO Double Drum test. Energy consumption was measured over a distance of 1500 m for each of the three test conditions. The rolling surface was level in all cases. Repeated measure analysis of variance (ANOVA) revealed a significant difference (p = 0.0001) between the predicted range at maximum speed for the three tests. Post hoc analysis demonstrated a significant difference (p < 0.01) in estimated range at maximum speed between the Double Drum test and the treadmill test, as well as between the Double Drum test and the tennis court test. Our results indicate no significant difference (p > 0.05) between the predicted range at maximal speed between the treadmill and tennis court tests. A simple relationship does not exist between the results of range testing with the Double Drum tester and the tennis court. An alternative would be to permit the use of a treadmill for range testing as simple relationships between all pertinent treadmill and tennis court range data were found. For the Double Drum tester used, the current demand is higher than under normal usage. This presents a problem as current is related to load torque in a power wheelchair. Hence, the Double Drum tester friction must be reduced. The predicted range for the tennis court test at maximum speed ranges from a low of 23.6 km to a high of 57.7 km. The range of the power wheelchair can be improved by the use of wet lead acid batteries in place of gel lead acid batteries.

Electric Power Supplies

Insuring comfort for homemaker-home health aides: delivering services to the AIDS population.

New York City's Partners in Care, a subsidiary of the Visiting Nurse Service of New York, has implemented several innovative programs involving education, training, and followup support for their homemaker-home health aides providing care to patients with HIV or AIDS. These programs have proved essential to the development of a successful community care program for persons with AIDS.

Acquired Immunodeficiency Syndrome

Midgestational exposure of pregnant BALB/c mice to magnetic resonance imaging conditions.

The potential for producing reproductive toxicity or teratogenesis in mice by exposure to magnetic resonance imaging (MRI) conditions was evaluated by means of reproduction studies and the homeotic shift test. Embryos from pregnant BALB/c mice were exposed in vivo for 16 hours beginning on gestation day 8.75 to MRI conditions of modest field strength (static field, 0.35 tesla (T); pulsed gradients, 2.3 X 10(-4) T/cm for 2.5 to 10 msec; and radio frequency, 15 MHz at an average of 61.2 mW). Unexposed, sham-exposed (both MRI and X-ray) and X-irradiated (0.5 Gy) animals were the control groups. Neither placental resorptions nor stillbirths were increased by MRI. Fetal weight at birth and crown-rump length were proportional; however, crown-rump length was significantly less (p less than 0.001) in the MRI-exposed fetuses (respective mean values for MRI-exposed fetuses were 21.8 +/- 0.2 mm compared to 22.4 +/- 0.1 for sham-exposed fetuses). Both crown-rump length and fetal weight were significantly reduced after X-irradiation. The percentage of homeotic skeletal shifts was scored for each of eight anatomic sites. Only X-radiation produced significant increases in skeletal shifts. Prolonged midgestational exposure of mice to MRI conditions currently used for human clinical imaging, therefore, failed to reveal overt embryotoxicity (resorptions, stillbirths) or teratogenicity (homeotic shifts), consistent with the non-ionizing properties of MR. However, the slight but significant reduction in fetal crown-rump length after prolonged exposure justifies further study of higher MRI energy levels and consideration of other endpoints for establishing with greater confidence the safety of MRI during pregnancy.

Animals