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Biomedical subjects

M Farrell

Publications and source records attributed to M Farrell.

At least 181 records · Page 10Linked to original sources

Multiple purpose central venous access in infants less than 1,000 grams.

The use of central venous catheters in low birthweight infants has been associated with a high rate of infectious and mechanical-related complications. We reviewed our experience with multipurpose central venous catheters in infants less than 1,000 g to determine the rate of catheter-related sepsis and mechanical catheter malfunction. From October 1981 to August 1984, 20 infants (average weight 778 g) underwent placement of 22 central venous Broviac catheters. In addition to parenteral nutrition, antibiotics, aminophylline, and replacement fluids were infused. Total catheter days were 961, with an average of 44 days per catheter. Primary catheter sepsis occurred with two catheters (9%). Mechanical complications occurred with six catheters (exposed cuff, 1; catheter break, 2; catheter reposition, 1; catheter thrombosis, 1; dehiscence of cutdown site, 1). The incidence of catheter-related sepsis was acceptably low. The high incidence of mechanical catheter malfunction (6/22, 27%) resulted in minimal morbidity to the infant and could have been avoided by better operative technique, proper positioning intraoperatively, and meticulous care of the catheter post-operatively. We conclude that multipurpose long-term central venous access can be safely utilized with the Broviac catheter in infants less than 1,000 g.

Catheterization, Central Venous↗

A prophylactic bolus of thiopentone does not protect against prolonged focal cerebral ischaemia.

Barbiturate coma is still recommended for brain protection during periods of temporary focal ischaemia such as during carotid endarterectomy. We tested the hypothesis that a single dose of barbiturate given before a period of protracted severe focal ischaemia would protect against focal cerebral infarction. Sixteen cats had the proximal left middle cerebral artery (MCA) occluded. Eight cats received halothane alone titrated to keep their pulse and blood pressure within the normal range. Eight cats received, in addition to halothane, a bolus of thiopentone sufficient to produce an isoelectric EEG immediately prior to MCA occlusion. Six hours after the occlusions the animals were sacrificed and the brains scored histologically to assess both size and severity of ischaemia. There was no statistically significant difference in the size or severity of the infarcts between the groups. We conclude from this study that the extent of the histological injury was not reduced by a single prophylactic bolus of thiopentone given before prolonged focal cerebral ischaemia.

Animals↗

Isolation of the cDNA for human prostaglandin H synthase.

Prostaglandin H Synthase (PGHS, cyclooxygenase) is a 67 kd protein which catalyzes the first step in prostaglandin synthesis. The primary amino acid sequence and the molecular mechanisms regulating expression are unknown. We report here isolation of a cDNA clone for the enzyme from human vascular endothelial cells for use in such studies. High titre, polyclonal antiserum against PGHS was developed in rabbits. The antiserum was monospecific, reacted with cyclooxygenase on Western blots at a limiting dilution of 1:500,000 and immunoprecipitated cyclooxygenase synthesized by in vitro translation of PGHS messenger RNA. It was used to screen a lambda gt11 cDNA expression library from human endothelial cells. Three positive clones were isolated. Following plaque purification, one clone reacted strongly with two other polyclonal antisera independently raised against highly purified cyclooxygenase and the aspirin-acetylated enzyme. Western blot analysis confirmed production of a large approximately 180 kd fusion protein of cyclooxygenase and beta-galactosidase. The cDNA insert of approximately 2.2 kilo base pairs was excised and subcloned into plasmid pUC8. A 24 nucleotide DNA probe, synthesized according to the amino acid sequence of the aspirin-acetylation site of cyclooxygenase, hybridized strongly with the 2.2 kbp cDNA insert. It is concluded that the 2.2 kbp cDNA insert represents a cDNA clone for human cyclooxygenase, which also expresses the aspirin-acetylation site. This is the first reported isolation of the cDNA for this enzyme, and will facilitate further studies on the primary sequence and on the regulation of the enzyme at the molecular level.

Amino Acid Sequence↗

Analysis of the reliability and validity of the kinetic communicator exercise device.

The Kinetic Communicator (KINCOM), a microcomputer controlled, hydraulically driven device for the test, measurement, and rehabilitation of human joint function, was tested for the reliability and validity of its operating systems. Testing focused on the three primary functions of the KINCOM: lever arm position, lever arm velocity, and force measuring systems. Measurements of the functions were made via external devices and were compared to measurements simultaneously made by the KINCOM system. Tests were performed for both static and dynamic operation of the unit. Force measurements averaged a difference of 3.2% or less, lever arm speed was within 1.5% of the target speed in all cases, and no difference was found in position measurement. These discrepancies were felt to be due to calibration error and were not considered an indication of inaccuracy in the KINCOM system.

Biomechanical Phenomena↗

Monoclonal antibody therapy of malignant melanoma: in vivo localization in cutaneous metastasis after intravenous administration.

The murine antimelanoma monoclonal antibody, 9.2.27, was administered intravenously to eight patients with metastatic malignant melanoma. Biopsies of metastatic nodules clearly demonstrate the selective localization of this antibody on the melanoma cell surface with a dose-response relationship to the quantity of administered antibody. The antibody infusions were clinically well tolerated and the pharmacokinetics of the antibody and the antiglobulin responses are described. This study indicates that murine monoclonal antibodies have potential as selective targeting agents in the design of future therapeutic trials using monoclonal antibodies or conjugates thereof in the treatment of cancer.

Adult↗

Role of small t antigen in the acute transforming activity of SV40.

A plasmid, pHR402, containing SV40 sequences that include a truncated early region bearing an intact t-coding sequence and a functionally intact late region, was introduced into thymidine kinase deficient (tk-) mouse L cells by cotransformation with a cloned tk gene. tk+ cotransformants synthesized SV40 t but not T antigen, and no truncated T-coding sequence products were detected. The viral sequences of pHR402 were reconstituted as a virus in COS1 cells, and acute infection of untransformed mouse cells with this viral stock (SV402) also led to the appearance of t but not T or a truncated T. Abortive transformation assays of such infected cells were negative, as were those performed on the same cells infected with either of two viral mutants (dl883 and dl884), each of which leads to T but not t synthesis. However, mixed infection with SV402 and either dl883 or dl884 led to a clear abortive and permanent transformation response. Thus, at least in part, t and T appear to function in a complementary fashion in eliciting transformation expression by SV40-infected cells.

Animals↗

Reduced alternative complement pathway control protein levels in anorexia nervosa: response to parenteral alimentation.

Serum levels of 16 proteins, including 11 component and control proteins of the complement system were determined before and after nutritional repletion in five female patients with severe malnutrition secondary to anorexia nervosa. Before parenteral alimentation significantly decreased serum levels were found for IgG, IgM, transferrin, Clq, C2, C3, factor B, beta lH, C3b inactivator, properdin, and C4 binding protein. A significant increase in posttreatment serum levels compared with pretreatment levels were found for transferrin, C3, factor B, beta lH, and C3b inactivator. Of the proteins measured, the C3b amplification loop control and component proteins, beta lH, C3b inactivator, C3, and factor B rose to the normal range in response to therapy most rapidly. In the absence of an acute phase reaction, these proteins appear to be particularly good indices of malnutrition and its response to therapy.

Adolescent↗