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Biomedical subjects

J D Hill

Publications and source records attributed to J D Hill.

At least 19 recordsLinked to original sources

Left ventricular dysfunction resulting from frequent unifocal ventricular ectopics with resolution following radiofrequency ablation.

A case is presented, in which asymptomatic but persistent right ventricular outflow tract (RVOT) ectopics resulted in left ventricular (LV) dilatation and systolic dysfunction. The patient underwent extensive investigation with no other cause for the cardiomyopathy being found. Successful ablation of the RVOT ectopic focus resulted in normalization of LV size and function. This case suggests that frequent ventricular ectopy should be considered as a potentially remediable cause of LV dysfunction.

Adult↗

Modafinil reduces excessive somnolence and enhances mood in patients with myotonic dystrophy.

OBJECTIVE: To evaluate the potential of modafinil in reducing excessive daytime somnolence (EDS) and enhancing indexes of quality of life and mood in patients with myotonic dystrophy (DM). METHODS: Forty patients with DM were randomized to receive modafinil and placebo for 14 days each, using a double-blind, cross-over design. Before and after each trial, subjects completed handgrip strength testing, spirometry, and quality-of-life measures (RAND). On days 7 and 14, each subject completed the Epworth Sleepiness Scale (ESS), the Stanford Sleepiness Scale (SSS), and the Profile of Mood States (POMS). RESULTS: ESS scores were lower while taking modafinil (mean 248 mm; 95% confidence limit 220 to 276 mm) as compared with placebo (309 mm; 281 to 336 mm) (p < 0.001). Mean SSS scores were also lower during the modafinil trial (3.05; 2.77 to 3.33) than during the placebo trial (3.45; 3.18 to 3.71) (p < 0.05). The POMS indicated that modafinil decreased fatigue-inertia (p < 0.001) and increased vigor-activity and tension-anxiety (p < 0.001) indexes. The total mood disturbance score was also decreased during the modafinil trial as compared with placebo (p < 0.05). The RAND quality-of-life measures of energy (p < 0.001) and health change (p < 0.05) were both significantly enhanced during the modafinil treatment phase. No changes in maximal grip strength or forced expired volume in 1 second were detected over the course of the study. Headache was the most frequently reported adverse event. Four patients withdrew from the study, three because of side effects (two during modafinil ingestion and one during placebo ingestion). CONCLUSION: Modafinil reduces somnolence and improves mood in patients with DM.

Activities of Daily Living↗

Clonogenic analysis reveals reserve stem cells in postnatal mammals: I. Pluripotent mesenchymal stem cells.

Clonal populations of lineage-uncommitted pluripotent mesenchymal stem cells have been identified in prenatal avians and rodents. These cells reside in the connective tissue matrices of many organs and tissues. They demonstrate extended capabilities for self-renewal and the ability to differentiate into multiple separate tissues within the mesodermal germ line. This study was designed to determine whether such cells are present in the connective tissues of postnatal mammals. This report describes a cell clone derived by isolation from postnatal rat connective tissues, cryopreservation, extended propagation, and serial dilution clonogenic analysis. In the undifferentiated state, this clone demonstrates a high nuclear-to-cytoplasmic ratio and extended capacity for self-renewal. Subsequent morphological, histochemical, and immunochemical analysis after the induction of differentiation revealed phenotypic markers characteristic of multiple cell types of mesodermal origin, such as skeletal muscle, smooth muscle, fat cells, cartilage, and bone. These results indicate that this clone consists of pluripotent mesenchymal stem cells. This report demonstrates that clonal populations of reserve stem cells are present in mammals after birth. Potential roles for such cells in the maintenance, repair, and regeneration of mesodermal tissues are discussed.

Animals↗

Cardiac surgery in the octogenarian: evaluation of risk, cost, and outcome.

BACKGROUND: Nationwide, cardiac surgery is being performed more frequently in patients aged 80 years and older. METHODS: One hundred four octogenarians undergoing a variety of heart-lung procedures were prospectively studied between 1995 and 1998 for comparison with similar patients aged 65 to 75 years (n = 351). RESULTS: Octogenarians were more likely to be of female gender, and be nondiabetic than the younger group. The 30-day mortality rate for patients aged 65 to 75 years was 3.4% (12 of 351 patients), versus 13.5% (14 of 104) for patients aged 80+ (p = 0.0004), which ranged from 2% (1 of 50) in nonemergent coronary artery bypass grafting to 75% (3 of 4) in double valve procedures. Complications occurring more frequently in octogenarians were severe low output state, reintubation, and atrial fibrillation. Elders experienced a longer intensive care (69.2 versus 43.3 hours, p = 0.002) and postoperative stay (10.09 versus 7.45 days, p = 0.001), and were discharged to a skilled nursing facility more often than younger patients (47% versus 21.1%, p = 0.0001). Total direct costs were $4,818 higher in the octogenarian group (p = 0.0007). CONCLUSIONS: Although emergency operations and complex procedures carried high risks for the octogenarian, the majority of these patients can be offered operation with short-term morbidity, mortality, and resource use that only modestly exceeds that of younger patients.

Aged↗

A versatile intracorporeal ventricular assist device based on the thoratec VAD system.

BACKGROUND: As patients are supported for longer durations with paracorporeal Thoratec left ventricular and biventricular assist devices (longest durations: 515 and 457 days, respectively), there is a need for implantable options. METHODS: We are developing a small, simple, and versatile intracorporeal ventricular assist device (IVAD) for left, right, or biventricular support as an alternative to the large, implantable, pulsatile left ventricular assist device (LVAD) systems available today. The new device is based on the Thoratec paracorporeal VAD that has been used in more than 1,400 patients weighing from 17 to 144 kg and for durations exceeding 1 year including patient discharge (using the portable driver). RESULTS: The IVAD has the same blood flow path and Thoralon polyurethane blood pumping sac as the paracorporeal VAD, but the housing is a smooth contoured, polished titanium alloy. The IVAD has a new sensor to detect when the pump is full and empty, and is controlled with the Thoratec TLC-II portable VAD driver, which is a small, briefcase-sized, battery-powered, pneumatic control unit. A small flexible (9 mm OD) percutaneous pneumatic driveline for each VAD is tunneled out of the body from the LVAD or right VAD in a pre- or intraperitoneal position. Small size and simplicity are the major advantages of the new device. The IVAD weight (339 g) and implanted volume (252 mL) are approximately one-half that of the current implantable pulsatile electromechanical LVAD systems. CONCLUSIONS: The small size of the IVAD should not only allow support of a large range of patient sizes and body habitus, but also provide options for implantable left, right, or biventricular support. By implanting only the mechanically simple blood pump, the more complex control unit is external, where it can be serviced and replaced without surgery. The IVAD with the portable driver will be a viable alternative to large implanted electromechanical systems and should address a larger segment of the physically diverse patient population.

Animals↗

Distribution and dynamics of two ferns: Dennstaedtia punctilobula (Dennstaedtiaceae) and Thelypteris noveboracensis (Thelypteridaceae) in a Northeast mixed hardwoods-hemlock forest.

Dennstaedtia punctilobula and Thelypteris noveboracensis are two native species that often arrest forest succession and reduce understory diversity. As part of a project to examine the feedback between forest understory and canopy dynamics, we studied the patterns of distribution and dynamics of these two fern species in an oak-transition hardwoods-hemlock forest. Dennstaedtia was least abundant under shade-tolerant tree species and most abundant in small (1-2 trees) canopy gaps, but did not show any distinct patterns across the sampled moisture regime. The light response was verified using light manipulation experiments and examination of plant size-abundance patterns across light environments. Thelypteris tended to be most prevalent under maple canopies and appeared to be more sensitive to soil moisture regime being restricted to more mesic sites than Dennstaedtia. Seasonal and year-to-year changes in abundance of established clones of both fern species were small, suggesting that once established, both species can maintain a strong hold on a site. Further work on the niche requirements of the two species is warranted, but any event that maintains or promotes canopy openness (tree death by disease or windthrow, forest harvesting, or the elimination of a shrub layer by browsing) will promote persistence of Dennstaedtia.

Journal Article↗

Controlled clinical trial of a novel hemostatic agent in cardiac surgery. The Fusion Matrix Study Group.

BACKGROUND: We performed a prospective randomized trial to compare FloSeal Matrix (Fusion Medical Technologies, Inc, Mountain View, CA), a gelatin-based hemostatic sealant, with Gelfoam-Thrombin (Gelfoam, Pharmacia and Upjohn, Kalamazoo, MI; Thrombin, Gentrac Inc, Middeton, WI) (control group) to control perioperative bleeding. METHODS: A total of 93 patients undergoing cardiac operations were randomized into the FloSeal or control group after standard surgical means to control bleeding had failed. The bleeding site was evaluated at 1, 2, 3, 6, and 10 minutes after applying the hemostatic agent. If bleeding stopped within 10 minutes, the application was considered to be successful. In the case of a failure, the surgeon could use any means preferred (except FloSeal) to achieve hemostasis. All bleeding sites in a patient were treated with the hemostatic agent to which the patient was randomized. Follow-up evaluation was performed at 12 to 36 hours and 6 to 8 weeks after operation. RESULTS: FloSeal stopped bleeding in 94% of the patients (first bleeding site only) within 10 minutes, compared to 60% in the control group (p = 0.001). At 3 minutes, successful hemostasis was achieved in 72% of the FloSeal group compared with 23% in the control group (p = 0.0001). There was no difference in the adverse event profile between the two groups. CONCLUSIONS: FloSeal Matrix demonstrated efficacy superior to that of Gelfoam-Thrombin and had a safety profile similar to that of Gelfoam-Thrombin when used as a topical hemostatic agent during cardiac surgery procedures.

Blood Loss, Surgical↗

Less invasive Thoratec LVAD insertion: a surgical technique.

Left Ventricular Assist Device (LVAD) implantation is historically a complicated, invasive operation performed on critically ill patients and is often associated with bleeding and multiorgan morbidity. The purpose of this investigation was to devise an LVAD insertion technique, utilizing the concepts of less invasive cardiac surgery, that would be a less complicated operation, with low morbidity, and still meet all the goals of the standard procedure. We describe the technical details of a "less invasive" LVAD implantation.

Adult↗

Twenty-year, three-institution evaluation of the Hancock Modified Orifice aortic valve durability. Comparison of actual and actuarial estimates.

BACKGROUND: Information regarding the incidence of structural valve deterioration (SVD) is used in selecting the type of valve for patients. Standard actuarial statistical techniques have been used widely but do not provide the most appropriate information for patient populations experiencing competing hazards. "Actual," or cumulative incidence, methods may provide a better estimate of the durability of tissue valves for these patients. The purpose of this article is to compare actuarial and actual estimates of the durability of the Hancock Modified Orifice bioprosthesis aortic valve in a multi-institutional study. METHODS AND RESULTS: Valves were implanted between 1976 and 1985 in 3 institutions. This sample contains follow-up data on 727 patients (42% female) with a mean age of 63 +/- 13 years. The difference between actuarial and actual rates of SVD became more important over time. At 5 years, the difference is significant only in the elderly (aged > or = 65 and > or = 70), whereas at 17 years, the difference was significant for all patients. Similarly, the magnitude of the difference increases over time. Freedom from SVD for patients > 65 at 5 years is estimated at 98 +/- 0.01% by actuarial methods and 100 +/- 0.00% actual methods. The difference between estimates is larger at 10 years, 93 +/- 0.02% versus 96 +/- 0.01%. This difference is greater at 17 years, 78 +/- 0.04% versus 93 +/- 0.01%. CONCLUSIONS: The results of this study demonstrate that the particular statistical analysis method used to calculate SVD can provide strikingly different conclusions. These observations indicate that the actual method is able to identify the lower risk of SVD in older patients. Generalizability issues must be considered, however, when using actual SVD rates to make decisions regarding valve selection in larger populations.

Actuarial Analysis↗

Importance of preoperative liver function as a predictor of survival in patients supported with Thoratec ventricular assist devices as a bridge to transplantation.

UNLABELLED: Patient selection is crucial for the success of ventricular assist devices as a bridge to heart transplantation. PURPOSE: The objective of this study was to identify preoperative markers for survival and end-organ recovery in patients having a ventricular assist device. METHODS: A retrospective study was performed on 32 severely ill patients with end-stage cardiac failure being mechanically bridged to heart transplantation with the Thoratec Ventricular Assist Device System (Thoratec Laboratories Corporation, Pleasanton, Calif) in a single center between 1984 and 1995. The preoperative cardiac index averaged 1.6 L/min per square meter with a pulmonary capillary wedge pressure of 29 mm Hg. Because of a high incidence of hepatic or renal dysfunction, or both (total bilirubin: 3.5 +/- 6.2 mg/dL; creatinine: 2.0 +/- 1.3 mg/dL), biventricular support was used in most patients (28/32). A total of 30 preoperative and 4 perioperative variables were evaluated for their association with survival and liver recovery. RESULTS: Nineteen patients (59.4%) survived to transplantation and 13 died. All 19 patients undergoing transplantation were discharged alive with a 1-year survival of 94.4%. All patients without liver recovery died of multiorgan failure. Direct and indirect bilirubin measurements were the only significant predictors for survival to discharge (P = .036, .045); all other factors failed to show significance. As direct bilirubin levels increased (normal range, 3 times normal, and >3 times normal), patient survival decreased (82 %, 56%, and 33 %, respectively). In addition, bilirubin and liver enzyme levels before insertion of the assist device were significantly associated with liver recovery during support with the device. CONCLUSION: In our patient population with ventricular assist devices, liver function is the most predictive factor of patient survival in bridging to transplantation.

Adult↗

Preoperative and postoperative comparison of patients with univentricular and biventricular support with the thoratec ventricular assist device as a bridge to cardiac transplantation.

OBJECTIVES: The goal of this study was to determine whether there are differences in populations of patients with heart failure who require univentricular or biventricular circulatory support. METHODS: Two hundred thirteen patients who were in imminent risk of dying before donor heart procurement and who received Thoratec left (LVAD) and right (RVAD) ventricular assist devices at 35 hospitals were divided into three groups: group 1 (n = 74), patients adequately supported with isolated LVADs; group 2 (n = 37), patients initially receiving an LVAD and later requiring an RVAD; and group 3 (n = 102), patients who received biventricular assistance (BiVAD) from the beginning. RESULTS: There were no significant differences in any preoperative factors between the two BiVAD groups. In the combined BiVAD groups, pre-VAD cardiac index (BiVAD, 1.4 +/- 0.6 L/min per square meter, vs LVAD, 1.6 +/- 0.6 L/min per square meter) and pulmonary capillary wedge pressure (BiVAD, 27 +/- 8 mm Hg, vs LVAD, 30 +/- 8 mm Hg) were significantly lower than those in the LVAD group, and pre-VAD creatinine levels were significantly higher (BiVAD, 1.9 +/- 1.1 mg/dl, vs LVAD, 1.4 +/- 0.6 mg/dl). In addition, greater proportions of patients in the BiVAD groups required mechanical ventilation before VAD placement (60% vs 35%) and were implanted under emergency conditions than in the LVAD group (22% vs 9%). The survival of patients through heart transplantation was significantly better in patients who had an LVAD (74%) than in those who had BiVADs (58%). However, there were no significant differences in posttransplantation survival through hospital discharge (LVAD, 89%; BiVAD, 81%). CONCLUSION: Patients who received LVADs were less severely ill before the operation and consequently were more likely to survive after the operation. As the severity of illness increases, patients are more likely to require biventricular support.

Heart Transplantation↗

Randomized, double-blind, placebo-controlled crossover trial of modafinil in the treatment of excessive daytime sleepiness in narcolepsy.

Seventy-five patients meeting international diagnostic criteria for narcolepsy enrolled in a 6-week, three-period, randomized, crossover, placebo-controlled trial. Patients received placebo, modafinil 200 mg, or modafinil 400 mg in divided doses (morning and noon). Evaluations occurred at baseline and at the end of each 2-week period. Compared with placebo, modafinil 200 and 400 mg significantly increased the mean sleep latency on the Maintenance of Wakefulness Test by 40% and 54%, with no significant difference between the two doses. Modafinil, 200 and 400 mg, also reduced the combined number of daytime sleep episodes and periods of severe sleepiness noted in sleep logs. The likelihood of falling asleep as measured by the Epworth Sleepiness Scale was equally reduced by both modafinil dose levels. There were no effects on nocturnal sleep initiation, maintenance, or architecture, nor were there any effects on sleep apnea or periodic leg movements. Neither dose interfered with the patients' ability to nap voluntarily during the day nor with their quantity or quality of nocturnal sleep. Modafinil produced no changes in blood pressure or heart rate in either normotensive or hypertensive patients. The only significant adverse effects were seen at the 400-mg dose, which was associated with more nausea and more nervousness than either placebo or the 200-mg dose. As little as a 200-mg daily dose of modafinil is therefore an effective and well-tolerated treatment of excessive daytime somnolence in narcoleptic persons.

Adult↗

Noninvasive measurement of tissue magnesium and correlation with cardiac levels.

BACKGROUND: Intracellular magnesium ([Mg]i) plays an important role in the regulation of myocardial metabolism, contractility, and the maintenance of transsarcolemmal and intracellular ionic gradients. An understanding of the role of magnesium in the clinical setting, however, is hampered by the lack of an assay of intracellular tissue magnesium levels. METHODS AND RESULTS: We used energy-dispersive x-ray analysis to measure [Mg]i in sublingual epithelial cells and to correlate the level with those in atrial biopsy specimens from the same patients during cardiopulmonary bypass. Levels were also measured in acute myocardial infarction (AMI) patients before and after intravenous magnesium sulfate administration and compared with those from intensive care unit (ICU) patients and healthy individuals. A strong correlation between sublingual epithelial cell (mean, 32.1 +/- 0.3 mEq/L) and atrial tissue (mean, 32.1 +/- 0.3 mEq/L) [Mg]i was present in 18 cardiac surgery patients (r = .68, P < .002). Epithelial and atrial [Mg]i levels were lower than in healthy individuals (33.7 +/- 0.5 mEq/L, P < .01) studied at that time and correlated poorly with serum magnesium. Mean [Mg]i in 22 AMI patients was 30.7 +/- 0.4 mEq/L, which was significantly lower than in 21 ICU patients and 15 healthy individuals (35.0 +/- 0.5 mEq/L and 34.5 +/- 0.7 mEq/L, respectively, P < .001). Intravenous magnesium sulfate was administered to most of the AMI patients (mean dose, 36 +/- 6 mmol). [Mg]i rose significantly in the AMI patients over the first 24 hours, and the magnitude of the increase was greater in those who received higher doses of intravenous magnesium sulfate. CONCLUSIONS: Sublingual epithelial cell [Mg]i correlates well with atrial [Mg]i but not with serum magnesium. [Mg]i levels are low in patients undergoing cardiac surgery and those with AMI. Intravenous magnesium sulfate corrects low [Mg]i levels in AMI patients. Energy-dispersive x-ray analysis determination of sublingual cell [Mg]i may expedite the investigation of the role of magnesium deficiency in heart disease.

Aged↗