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Biomedical subjects

R E Clark

Publications and source records attributed to R E Clark.

At least 379 records · Page 21Linked to original sources
PubMedDate not supplied

Future devices and directions.

This article summarizes the status of left ventricular assist devices currently in the stages of bench testing, animal experiments, and pilot clinical trials. The major design features and estimate of costs for 17 devices are described under 3 major categories of indications for use: destination therapy, bridge to transplant, and bridge to recovery. A sleeved piston pump located in the aorta and a unique, magnetically suspended centrifugal pump are described in the destination therapy section. Eight centrifugal and 4 axial flow devices are listed in the bridge to transplant category, and an external cup and a very low-cost centrifugal pump with a left atrium-to-aorta circuit are described in the bridge to recovery section. The key design features of the future, which will be required for success in both the clinical and marketplace arenas, will be simplicity, safety, low-power requirements, and low cost.

Animals↗
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End organ function with prolonged nonpulsatile circulatory support.

The hypothesis tested in these studies was that long-term circulatory support with a nonpulsatile device is safe and causes no end organ dysfunction. An inexpensive, small centrifugal pump with a 7 L/min capacity was implanted in 6 sheep (15 acute implants have previously been reported). The inlet cannula was placed in the left atrium and the outlet graft anastomosed to the descending aorta. A percutaneous cable supplied DC power and heparinized saline (10 ml/hr) for lubrication. Outputs of pump flow, stator, animal core temperature, pump power consumption, and RPM were monitored throughout the course of each experiment. The sheep moved freely within a large pen using an overhead swivel/tether system that carried all input and output lines. Four sheep survived longer than 4 weeks, and the indices of end organ function were analyzed at 28 days. No animal revealed any neurologic dysfunction. Hemoglobin was 9.075 +/- 0.78 g/dl at 28 days, as opposed to 7.475 +/- 0.68 (p = 0.002) before surgery. The blood urea nitrogen was 9.250 +/- 4.57 versus 14 +/- 5.72 mg/dl (p = 0.041), creatinine was 0.775 +/- .10 versus 0.775 +/- 0.05 mg/dl (p > or = 0.999), total bilirubin was 0.425 +/- 0.2 versus 0.225 +/- 0.05 mg/dl (p = 0.092), serum glutamic oxaloacetic transaminase was 74.75 +/- 24 versus 106.25 +/- 15.84 IU/L (p = 0.015), serum glutamic pyruvic transaminase was 36 +/- 28.7 versus 28.3 +/- 5.7 IU/L (p = 0.25), and total protein was 6.675 +/- 0.49 versus 5.47 +/- 0.15 g/dl (p = 0.025). It is concluded that these animals adapted very well to pulseless circulatory support. The results of these studies support the concept of an inexpensive, implantable, centrifugal pump as a ventricular assist device.

Animals↗
PubMedDate not supplied

AB-180 circulatory support system: summary of development and phase I clinical trial.

The AB-180 Circulatory Support System (AB-180 CSS; Cardiac Assist Technologies, Pittsburgh, PA) is a left ventricular assist system for investigational use in patients with postcardiotomy cardiogenic shock who are refractory to standard treatment with an intra-aortic balloon pump, pharmacologic treatment, or both. The intent of the AB-180 CSS is to provide temporary (up to 14 days) mechanical circulatory support until the heart recovers adequate mechanical function. The system consists of a small implantable centrifugal pump and a controller. A unique infusion system produces a hydrodynamic bearing between rotational and stationary components of the AB-180 CSS pump. This infusion system also provides a source of heparin for localized anticoagulation. Extensive bench and animal work has illustrated anticoagulation requirements, established operating guidelines, and demonstrated safety and efficacy. An investigational device exemption has been granted for a Phase I, five patient feasibility study at Allegheny General Hospital in Pittsburgh, Pennsylvania. To date, the pump has been implanted in one patient. The results from this first case are presented here.

Feasibility Studies↗
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Left ventricular support with the implantable AB-180 centrifugal pump in sheep with acute myocardial infarction.

A small, 257 g centrifugal pump was tested as a left ventricular assist device (LVAD) in sheep given a myocardial infarction. Pump performance, hemolysis, end organ function, weaning, explant procedure, and the incidence of thromboemboli at autopsy were studied over intervals of 1 to 44 days. Twelve sheep were given acute myocardial infarction by ligation of the anterior descending coronary artery and 11 had insertion of the AB-180 Circulatory Support System (CSS). One sheep served as a control for the space occupying effects of the pump in the left chest. Inflow was from the left atrium and outflow was to the descending thoracic aorta. Heparin (57-83 U/ml) in sterile water was infused into the pump at a rate of 10 ml/hr. Pump flows of 1-5.7 L/min were tested. The AB-180 CSS supported 73.5% of the total cardiac output (pump + heart) of 3.89 L/min, with a mean arterial pressure of 86 +/- 7 mmHg at a pump speed of 4,162 +/- 276 rpm immediately after implant. Hemolysis was <10 mg/dl and activated partial thromboplastin time (aPTT) values were in the normal range for sheep (<52 sec) after 48 hr of pumping. Liver enzyme concentrations returned to normal within 2 weeks. There was no evidence of thrombocytopenia. No signs of infection were present during assist and none was found at autopsy. The device was successfully removed three times without the use of pressor agents or blood transfusion. Alarm systems performed appropriately. During the 106 days of cumulative pumping, two sheep showed small (<1.5 cm) renal infarcts. Both were associated with intervals of pump stasis. The AB-180 CSS pump was easily implanted into the left chest without the use of cardiopulmonary bypass. It appears to have a low thromboembolic potential in sheep, without the need for large doses of heparin to elevate aPTT values. This characteristic may ameliorate the excessive bleeding seen clinically with current LVAD systems used for post cardiotomy cardiogenic shock, which require anticoagulation with heparin. The small size and weight of the device permit implantation within the chest and allow chest closure. This may reduce the incidence of infection associated with temporary left ventricular assist and an open sternum.

Animals↗
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The learning-related activity that develops in the pontine nuclei during classical eye-blink conditioning is dependent on the interpositus nucleus.

A growing body of research now implicates the cerebellum in the formation and storage of the critical neural plasticity that subserves the classically conditioned eye-blink response. Previous anatomical, physiological, and behavioral research suggests that auditory-conditioned stimulus information is routed to the cerebellum by the pontine nuclei. However, it has also been observed from multiple unit recordings that some populations of pontine cells, in addition to showing auditory-evoked responses, also show changes in activity that is learning-related. It is unknown whether this learning-related activity is generated by the pontine cells or whether it is generated by some other structure and projected to the pontine nuclei. Because the cerebellum has been implicated in the formation of the essential plasticity that subserves this learned behavior, we examined how multiple unit recordings of learning-related activity within the pontine nuclei are affected by reversible inactivation of the interpositus nucleus of the cerebellum. The results indicated clearly that when the interpositus nucleus was inactivated, the learning-related activity in the pontine nuclei was abolished completely and the auditory stimulus-evoked activity was unaffected. In contract, when the facial nucleus was inactivated, both the auditory stimulus and the learning-related activity were still present. These results indicate that the learning-related activity exhibited by some populations of pontine nuclei cells is dependent on the interpositus nucleus and may represent feedback from the cerebellum.

Animals↗
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Parallel acquisition of awareness and trace eyeblink classical conditioning.

Trace eyeblink conditioning (with a trace interval >/=500 msec) depends on the integrity of the hippocampus and requires that participants develop awareness of the stimulus contingencies (i.e., awareness that the conditioned stimulus [CS] predicts the unconditioned stimulus [US]). Previous investigations of the relationship between trace eyeblink conditioning and awareness of the stimulus contingencies have manipulated awareness or have assessed awareness at fixed intervals during and after the conditioning session. In this study, we tracked the development of knowledge about the stimulus contingencies trial by trial by asking participants to try to predict either the onset of the US or the onset of their eyeblinks during differential trace eyeblink conditioning. Asking participants to predict their eyeblinks inhibited both the acquisition of awareness and eyeblink conditioning. In contrast, asking participants to predict the onset of the US promoted awareness and facilitated conditioning. Acquisition of knowledge about the stimulus contingencies and acquisition of differential trace eyeblink conditioning developed approximately in parallel (i.e., concurrently).

Aged↗
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Dissociation between the effects of damage to perirhinal cortex and area TE.

Perirhinal cortex and area TE are immediately adjacent to each other in the temporal lobe and reciprocally interconnected. These areas are thought to lie at the interface between visual perception and visual memory, but it has been unclear what their separate contributions might be. In three experiments, monkeys with bilateral lesions of the perirhinal cortex exhibited a different pattern of impairment than monkeys with bilateral lesions of area TE. In experiment 1, lesions of the perirhinal cortex produced a multimodal deficit in recognition memory (delayed nonmatching to sample), whereas lesions of area TE impaired performance only in the visual modality. In experiment 2, on a test of visual recognition memory (the visual paired comparison task) lesions of the perirhinal cortex impaired performance at long delays but spared performance at a very short delay. In contrast, lesions of area TE impaired performance even at the short delay. In experiment 3, lesions of the perirhinal cortex and lesions of area TE produced an opposite pattern of impairment on two visual discrimination tasks, simple object discrimination learning (impaired only by perirhinal lesions), and concurrent discrimination learning (impaired only by TE lesions). Taken together, the findings suggest that the perirhinal cortex, like other medial temporal lobe structures, is important for the formation of memory, whereas area TE is important for visual perceptual processing.

Animals↗
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Ectrodactyly, soft-tissue syndactyly, and nodulocystic acne: coincidence or association?

We report severe nodulocystic acne in a 21-year-old man associated with ectrodactyly of the right foot and soft-tissue syndactyly of the third and fourth left fingers, and the first to fourth left toes. His acne was resistant to conventional topical (clindamycin phosphate, erythromycin, tretinoin, peeling agents) and systemic (tetracycline, erythromycin) antiacne medications. Moderate improvement was achieved with systemic isotretinoin. Apart from presenting this case, we imply the disparity of the clinical characteristics of our case and those of Apert syndrome, a rare congenital condition with craniofacial anomalies, symmetric syndactyly of the digits, and acneiform eruption. We discuss the possible explanation for the association of acne lesions and bone deformities based on recent reports of mutations of fibroblast growth factor receptor 2 in the great majority of patients with this syndrome, as well as current experimental data on the involvement of the keratinocyte growth factor in the process of hair follicle growth, development, and differentiation.

Acne Vulgaris↗
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A comparative in vitro study of GK-101 and GK-101E in caries removal.

(1) This study indicated that both GK-101 and GK-101E exerted a statistically significant chemical action in the removal of carious material, in addition to any mechanical effects of the delivery system and applicator tip. (2) The superiority of GK-101E over saline in caries removal was noted, regardless of lesion consistency. (3) GK-101 was statistically superior to saline in caries removal in medium-hard lesions; it was not statistically superior to saline in lesions of medium consistency.

Aminobutyrates↗
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BCR-ABL fusion peptides and cytotoxic T cells in chronic myeloid leukaemia.

The BCR-ABL gene that arises in chronic myeloid leukaemia (CML) is a neoantigen. Peptides derived from the BCR-ABL fusion junction may therefore be immunogenic, if appropriately presented to the immune system. This article reviews data demonstrating that certain junctional peptides will bind to HLA molecules, and that these peptides will elicit specific T-lymphocyte responses in vitro, in both normal subjects and in CML patients. The clinical relevance of these observations is discussed.

Antigen Presentation↗