Search PubMed⌕ Search

Biomedical subjects

W R Jacobs

Publications and source records attributed to W R Jacobs.

140 records · Page 8Linked to original sources

Echocardiographic interpretation of pericardial effusion.

Echocardiography has proved to be quite useful in the detection of pericardial effusion. As little as 15 ml of fluid within the pericardial space can be detected. Specific signs of pericardial effusion, such as electrical alternans and paradoxical pulse, have become better understood by echocardiographic study. Yet, with all the benefits of echocardiography, the detection of pericardial effusion still may be quite difficult if careful attention is not given to technique. False-positive diagnosis of anterior pericardial effusion can be seen with epicardial fat pad, pericardial cyst, or foramen of Morgagni hernia. False-positive posterior pericardial effusion can be seen in large left pleural effusion, calcified mitral anulus, or excessively medial transducer angulation. New "switched-gain" circuits have helped detection of pericardial effusion by enhancement of pericardial echoes.

Echocardiography↗

Comparative responses to dobutamine and nitroprusside in patients with chronic low output cardiac failure.

The acute hemodynamic effects of dobutamine and nitroprusside were compared in 19 patients with low output cardiac failure. At dosage levels yielding similar increases in cardiac index (12 patients), nitroprusside resulted in significantly lower arterial systolic and wedge pressures and did not increase heart rate suggesting advantages over dobutamine when reduction in myocardial oxygen requirement or pulmonary congestion is a major goal. Systemic arterial mean and diastolic pressures were minimally changed with dobutamine, but fell significantly with nitroprusside suggesting advantages of dobutamine over nitroprusside in patients where hypotension could limit coronary blood flow or perfusion of other vital organs. Reduction in pulmonary arteriolar resistance occurred only with nitroprusside. Arterial hypoxemia developed in three patients during nitroprusside infusion suggesting the possibility of increased right-to-left intrapulmonary shunting resulting from a direct vasodilating effect of nitroprusside on pulmonary arteriole smooth muscle. Although both inotropic and vasodilator drugs can result in hemodynamic improvement when administered to patients with chronic low output cardiac failure, significant differences of potential clinical importance exist between these two modes of therapy.

Adult↗

Recombinant BCG as a candidate oral vaccine vector.

Bacille Calmette-Guerin (BCG), currently the most widely used vaccine in the world, was originally administered for many years as an oral vaccine. The low frequency of serious complications, inexpensive production, and adjuvanticity make BCG an ideal candidate for a recombinant vaccine vehicle. Although mycobacteria are slow growing and not yet well characterized genetically, we have recently developed technology for the genetic manipulation of BCG and other mycobacteria. Phage and plasmid systems based on a shuttle strategy to manipulate DNA in Escherichia coli and transfer it to mycobacteria have been developed. We have established that the aminoglycoside phosphotransferase gene can be used as an effective selectable marker in the mycobacteria and that a foreign antigen from Mycobacterium leprae can be expressed in BCG. Furthermore, a thorough analysis of mycobacterial expression sequences has been undertaken to optimize the expression of foreign antigens in BCG. We constructed an expression probe shuttle plasmid with beta-galactosidase as reporter gene, and have used it successfully to identify multiple mycobacteriophage DNA sequences with varying levels of constitutive or regulable promoter activity. Further genetic advances required for development of recombinant BCG into an effective recombinant vaccine vehicle, including possibilities for oral administration, are adumbrated.

Administration, Oral↗

The natural history of left ventricular spontaneous contrast.

Spontaneous contrast in the left ventricle is an unusual entity. We retrospectively studied 16 patients who were found to have spontaneous contrast present on two-dimensional echocardiograms, specifically noting their clinical characteristics, the reproducibility of this phenomenon, the presence of thrombi and embolic events, and prognostic implications. Diagnoses included ischemic heart disease in nine patients, dilated cardiomyopathy in six patients, and hypertensive cardiomyopathy in one patient. The mean ejection fraction was 17.6%. There were six thromboembolic events in four patients. The spontaneous contrast was reproducible for periods of time up to 39 months. Patients who had improvement in their left ventricular dysfunction or who underwent aneurysmectomy had disappearance of the spontaneous contrast. Those patients who had spontaneous contrast reproduced on subsequent echocardiograms did not seem to have a worse prognosis than patients with similarly depressed ventricular function, but a larger study is necessary to verify this.

Cardiomyopathy, Dilated↗

Introduction of foreign DNA into mycobacteria using a shuttle phasmid.

Mycobacteria are major pathogens of man and animals. There are approximately 10 million cases of tuberculosis world wide with an annual mortality of three million people. Leprosy, caused by Mycobacterium leprae, afflicts over ten million people, primarily in developing countries. M. tuberculosis and mycobacteria of the M. avium-intracellulare-scrofulaceum (MAIS) group are major opportunistic pathogens of patients with acquired immune deficiency syndrome (AIDS). M. paratuberculosis is the cause of Jöhne's disease in cattle. Yet, BCG (Bacille Calmette-Guerin), an avirulent strain of M. bovis, is the most widely used human vaccine in the world, having been administered to about 2.5 X 10(9) people since 1948 (ref. 4). BCG was highly protective against tuberculosis in England, but has been found not to be effective in preventing pulmonary tuberculosis in adults in Southern India. We have initiated studies to develop the methodology for efficient gene transfer in mycobacteria. We have constructed recombinant shuttle phasmids which are chimaeras containing mycobacteriophage DNA into which an E. coli cosmid is inserted. They can replicate in E. coli as plasmids and in mycobacteria as phages, and transfer DNA across both genera. These shuttle vectors permit for the first time the introduction of foreign DNA by infection into M. smegmatis and BCG. By introducing and ultimately expressing genes for protective antigens for a variety of pathogens, it may be possible to develop cultivatable mycobacteria into useful multivaccine vehicles.

Bacteriophages↗

Mycobacteriophage vector systems.

Successful application of molecular genetic approaches to the study of mycobacteria necessitates the introduction of recombinant DNA molecules into mycobacterial cells. Efficient methods of introducing DNA into Mycobacterium smegmatis protoplasts have been developed, and the construction of mycobacteriophage recombinant DNA vectors has been initiated. Novel Escherichia coli-Mycobacterium shuttle vectors, termed shuttle phasmids, have been constructed. These vectors were constructed by inserting E. coli cosmids into nonessential regions of mycobacteriophage DNAs. Shuttle phasmids are multifunctional vectors that replicate in E. coli as plasmids and replicate in mycobacteria as phage. The presence of the bacteriophage lambda cos sequences permits the use of the lambda in vitro packaging system for efficient cloning of additional genes into these vectors. Temperate shuttle phasmids have been constructed that can infect and lyse mycobacterial cells or lysogenize mycobacterial cells to stably integrate and express cloned DNA into mycobacterial genomes. Shuttle phasmids can be transduced into a wide variety of mycobacterial species and thus should permit the development of molecular genetic systems for the mycobacteria.

Cloning, Molecular↗

Coughing and central venous catheter dislodgement.

Silastic central venous catheters are subject to dislodgement from a variety of causes. Only one occurrence of catheter dislodgement has been previously reported in connection with coughing. We report four additional cases of silastic central venous catheter dislodgement associated with forceful coughing paroxysms, alone or in combination with emesis or rectal tenesmus. Three episodes of catheter dislodgement occurred in adolescents or young adults with cystic fibrosis, who may constitute a particularly high-risk group. Dislodgement in two patients was asymptomatic. These case suggest that patients with frequent or severe paroxysms of increased intrathoracic pressure may be at higher risk of catheter dislodgement. Since dislodgement may be initially asymptomatic and can cause serious complications, a high index of suspicion for dislodgement in patients with silastic central venous catheters and coughing paroxysms is advised.

Adolescent↗