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Biomedical subjects

G Jacobs

Publications and source records attributed to G Jacobs.

At least 199 records · Page 11Linked to original sources

Durability testing of components for the Jarvik 2000 completely implantable axial flow left ventricular assist device.

A cable-lead tester and real time bearing tester have been developed with provisions to test future implantable electronics, transcutaneous energy transfer system (TETS), and related interconnect cabling designs. The cable/lead tester, used in 1997 to test a previously considered implantable bellows-connector-cabling system, can test up to 10 samples at a time. X-Y-Z-theta motions are applied to the proximal end of the test specimen with its distal end fixed. The real time bearing tester is of a mock loop configuration with the bearings under test housed in a fully functional, Good Manufacturing Practices assembled axial pump. A simulated left ventricular pulsatile preload is applied to the inflow of the axial pump, while its outflow is subjected to an 80 mmHg aortic afterload by pumping into a fixed height tube with no outflow restriction. The heated blood bath saline used in this system is UV sterilized and mechanically filtered by use of a commercial salt water conditioning system attached external to the main preload fluid reservoir. The cable-lead tester and real time bearing tester design include provisions to house a complete Jarvik 2000 left ventricular assist device (Transicoil Medical, Norristown, PA) for in vitro system testing.

Equipment Design↗

Possible late potentials in 4 dogs with sustained ventricular tachycardia.

Signal-averaged electrocardiograms (SAEKGs) were performed on 4 dogs with sustained ventricular tachycardia. Quantitative and qualitative analyses of SAEKGs were consistent with the presence of late potentials. Two of the 4 dogs subsequently died suddenly, and ventricular tachycardia and ventricular fibrillation were observed in 1 dog. High-frequency QRS durations (75-90 milliseconds), duration of low amplitude (less than 40 microV) signals during the terminal QRS complex (LAS40) (28-40 milliseconds), root mean square voltages of the terminal 40 milliseconds of the QRS complex (RMS40) (124-6.5 microV), and root mean square voltages of the terminal 30 milliseconds of the QRS complex (RMS30) (13-2.1 microV) differed from results obtained in 68 of 70 control dogs. Echocardiographic data suggested dilated cardiomyopathy in 2 dogs and the cause of the arrhythmia in 2 dogs was not determined. The SAEKG may be a useful adjunct in identifying a subset of dogs with ventricular tachyarrhythmias that are at high risk for sustained ventricular tachycardia and sudden death. The sensitivity, specificity, and predictive accuracies of the technique remain to be determined.

Animals↗

Hepatopathy in 4 dogs treated with amiodarone.

Amiodarone is a class III antiarrhythmic drug used in dogs with dilated cardiomyopathy and ventricular tachyarrhythmias. Hepatopathy is one of the more commonly reported adverse effects of amiodarone use in people. We describe 4 dogs that developed hepatopathy associated with amiodarone administration; 2 dogs also developed neutropenia. Three dogs had clinical signs of anorexia and lethargy; 1 did not show signs until impaired liver function had developed. Clinical signs or biochemical abnormalities developed 1.5-8 months after amiodarone treatment was started. Clinical signs resolved within 2 weeks of discontinuing amiodarone, but biochemical abnormalities did not resolve for 6-8 weeks. The delay between onset of liver disease and overt clinical signs suggests that serial evaluation of liver enzyme activities following amiodarone use in does is important.

Amiodarone↗

HIV nephropathy and the Duffy antigen/receptor for Chemokines in African Americans.

BACKGROUND AND OBJECTIVES: HIV nephropathy (HIVAN) is markedly racially biased in its distribution, occurring in about 10% of HIV infected African Americans according to some studies. Based upon previous laboratory and epidemiological studies, the Duffy promoter polymorphism, which occurs almost exclusively in individuals of African descent, has been postulated to be the predisposing factor. We aimed to explore that relationship by directly genotyping individuals with HIV nephropathy to determine the proportion homozygous for this mutation to test the hypothesis it was responsible for the genetic component of this disease. We anticipated that if the polymorphism was associated with HIV nephropathy all individuals would be homozygous for this mutation. METHOD: Individuals with HIVAN proven on biopsy were identified from previous studies and a pre-existing clinical database. This diagnosis was confirmed by an experienced pathologist examining the biopsies in a blinded fashion. PCR and RFLP strategies were used on the biopsy samples to genotype for the Duffy promoter polymorphism. The cases were compared to a control population of HIV seronegative African Americans. RESULTS: Twenty African American individuals with HIV nephropathy were successfully genotyped. Only nine were homozygous for the promoter mutation. Nine were heterozygous and two homozygous wild type. Furthermore, the frequency of the polymorphism did not differ from the background rate in the African American population (OR = 0.788 95% confidence intervals 0.378-1.64). CONCLUSION: The Duffy promoter polymorphism was not disproportionately represented in persons with HIVAN calling into question any significant role in the pathogenesis of HIVAN.

AIDS-Associated Nephropathy↗

Palliative treatment of advanced pancreatic carcinoma in community-based oncology group practices.

This study was aimed at evaluating the feasibility, effectiveness, and toxicity of palliative chemotherapy/supportive care in patients with advanced pancreatic cancer being treated on an outpatient basis. A retrospective analysis was performed on 127 consecutive, unselected patients with advanced pancreatic cancer in four community-based oncology group practices. Median age was 63 years and WHO performance status ranged from 0 to 3. Forty-three patients (34%) had locally advanced disease, and 84 patients (66%) had distant metastases; 94 patients (74%) received cytotoxic treatment during the course of their disease, and 33 (26%) received best supportive care only. First-line treatment consisted of gemcitabine (1,000 mg/m2 on days 1, 8, and 15 of a 28-day cycle) in 81 patients (86%), 5-fluorouracil (5-FU) in 8 patients (9%), radiochemotherapy in 4 patients (4%), and radiation therapy only in 1 patient (1%). A total of 1,501 gemcitabine treatments were given during the study period. Toxicity was moderate. Four patients (3%) required hospitalization for treatment-related side effects, and 111 patients (88%) died during the observation period. Symptom control, as measured by reduction of pain medication, was seen in 25% of patients receiving gemcitabine, whereas no reduction in pain medication was seen in the best supportive care group. The median survival of patients receiving cytotoxic treatment (mainly gemcitabine) was 42 weeks, and the median survival of patients receiving best supportive care was 21 weeks. The overall survival rate at 6, 12, 24, and 36 months was 65%, 32%, 14%, and 7%, respectively. Based on these outcomes, it appears that patients with locally advanced and metastatic pancreatic cancer benefit from adequate palliative treatment, including cytotoxic chemotherapy with gemcitabine, and this can be accomplished on an outpatient basis.

Adult↗

Lymphocytic-plasmacytic enteritis in 24 dogs.

Lymphocytic-plasmacytic enteritis (LPE) was diagnosed by intestinal biopsy in 24 dogs with chronic small intestinal diarrhea. Vomiting, weight loss, and reduced appetite were frequent. Breed predispositions were not documented, although four patients were German Shepherd dogs. Hypoproteinemia, hypoalbuminemia, and hypoglobulinemia were common and most likely a result of protein-losing enteropathy. Other biochemical abnormalities were uncommon. Intestinal malabsorption was common. Neutrophilia (sometimes with increased band neutrophils), monocytosis, lymphopenia, and eosinopenia were the most consistent hematologic abnormalities. The severity of the lymphocytic-plasmacytic infiltration was not significantly different (P greater than 0.05) between regions of small intestine. However, the severity of cellular infiltration often varied among different regions of small intestine in the same dog. Changes in villous architecture and lacteal dilation were common. Intestinal nematode infestation was diagnosed in five dogs, and pancreatic exocrine insufficiency was diagnosed in one dog. In the remaining 18 dogs, besides LPE, no other associated or concurrent intestinal disease was diagnosed.

Animals↗

Light microscopic and ultrastructural findings in failed epikeratoplasty.

Corneal buttons from two patients with failed epikeratoplasties requiring penetrating keratoplasty were examined by light and transmission electron microscopy. Penetrating keratoplasty was performed for lenticule scarring in the first case (adult aphakia) and inadequate best corrected visual acuity in the second case (keratoconus). Findings included decreased lenticule keratocytes and electron-dense, fibrillogranular material associated with either lenticule or recipient keratocytes in both corneas and defects in Bowman's layer in one cornea. In addition, light and electron microscopic evidence consistent with recipient keratocyte migration into the lenticule was demonstrated in one case. These findings were compared with three previous cases.

Adult↗

In vitro low frequency electromagnetic field effect on fast axonal transport.

The objective of this study was to evaluate the effects of a low frequency electromagnetic field on fast axonal transport for future neuroprosthetic applications. Changes in speeds and densities of retrograde fast organelle transport in rat sciatic nerve preparations were measured in vitro upon exposure to 15 and 50 Hz pulsed magnetic fields with peak intensities of 4.4 and 8.8 mT. Maximum current density of the induced eddy current was calculated to be about 40 microA/cm2. Video enhanced differential interference contrast microscopy was used to record axons supporting active organelle transport. Strong effects were observed in myelinated axons (cessation of transport in up to 10 min). Such effects may eventually be used as part of a neuroprosthesis to noninvasively modify or couple to various parts of the nervous system.

Animals↗

Development of an epicardial circulatory assist device.

The overall purpose of this project was to develop a circulatory assist device that could be used as a bridge to heart transplantation. Although heart muscle damage was one of the disadvantages with the original epicardial assist devices, as long as no bleeding occurs, such trauma would be of secondary importance in this particular application. The development of the proposed epicardial circulatory assist device (ECAD) was evolutionary in nature, with the second prototype design based on the lessons learned from that of the first. In vivo results from both phases of the project are reported. ECAD prototype 1 (ECAD-1) was composed of a flexible outer housing and two driving balloons. Fixation to the heart was adjustable for various heart sizes using Velcro fasteners. The design of the ECAD prototype 2 (ECAD-2) was based on the results of ECAD-1. Fixation to the heart was accomplished by suturing the outer housing onto the heart along the anterior descending artery and at the posterior atrioventricular groove. Each device was tested in five dogs. ECAD-1 was able to maintain the systemic circulation for 5 hours. However, unstable fixation and myocardial damage due to rubbing were the major problems. ECAD-2 passive effects on natural heart filling were acceptable. Under conditions of severe heart failure, a flow of more than 85% of control was obtained with a driving rate of 90-110 beats/min and 30% systole. The longest pumping was conducted for 8 hours. The ECAD was demonstrated to be a device useful in assisting the failing heart for short periods. Proper design will play a fundamental role in successful extended use.

Animals↗

Development of a completely implantable total artificial heart.

In conjunction with engineering and physiologic requirements, anatomic fit is a fundamental problem that must be carefully addressed in the design of a truly feasible implantable total circulatory support system. To facilitate the conceptualization, a three-dimensional anatomic model of an average adult thorax was developed from a data bank of 14 human cadavers, 100 radiographs, 18 computerized tomographs, 4 nuclear magnetic resonance (NMR) studies, and 31 cineangiograms. The location and orientation of the valves, the atrial chambers, venae cavae, and pulmonary hili were found to be the most critical information. As a result, configuration of a one piece, completely implantable total artificial heart (E4T system) with the hydraulic actuator placed between the two ventricles was defined and sized to provide an output of 8 L/min at 120 beats/min. The device was designed to be positioned through a midsternotomy similar to the natural ventricles (in the pericardial sac toward the left chest cavity), and the ports were carefully designed to eliminate the risk of compression of critical cardiovascular structures. Validation of the design was conducted with an E4T model implanted in three human adult cadavers, two of which were submitted to NMR imaging after the device was implanted and the incision closed. Excellent fit was observed in all cadavers, and analysis of the several sagittal, transverse, and coronal NMR images showed no compression of the natural internal structures.

Heart, Artificial↗

Electrical control of intestinal reservoirs in a chronic dog model.

Pouches constructed from small intestine are used to replace reservoir function after extirpative surgery of the colon. Such pouches empty in an involuntary and uncontrolled fashion. To see whether emptying could be voluntarily controlled, ileal and jejunal reservoirs were constructed in eight dogs under general anesthesia. Four pairs of stainless steel electrodes were attached to the serosa at 5 cm intervals, and the pouches were intubated for pressure measurements with 1.67 mm polyethylene catheters. All lines were brought subcutaneously to the neck where they were maintained under a protective jacket. One to four weeks later, the pouches were stimulated with trains of square wave pulses at frequencies between 3 Hz and 1.67 KHz. The pouches were injected with contrast, and the results were monitored by fluoroscopy. Intrapouch pressure increases as high as 80 mmHg were seen after stimulation at 3 Hz, 100 msec and 6 Hz, 50 msec (10 to 25 mA) and emptying was induced. Pressure increases were also seen after stimulation with 330 Hz, 1 msec and 10 Hz, 1 msec pulse trains, but emptying was not documented. Abdominal wall contraction during stimulation was a problem but could be inhibited by interposing an insulating silastic sheet. The conclusion was made that it is possible to electrically induce emptying of intestinal reservoirs in a chronic dog model.

Animals↗