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Biomedical subjects

C Baird

Publications and source records attributed to C Baird.

18 recordsLinked to original sources

Sirolimus for rescue and primary immunosuppression in transplanted children receiving tacrolimus.

AIMS: The role of sirolimus (SRL) as a rescue agent (n=42) and as a component of primary immunosuppression (n=8) was evaluated in a mixed population of 50 transplanted children receiving tacrolimus (liver: 26, heart: 5, intestinal: 5, liver-intestine: 9, lung: 1, bone marrow: 1, liver-kidney: 1, multivisceral: 1). Rescue indications for tacrolimus (TAC) failure were recurrent acute rejection and acute rejection complicating withdrawal of immunosuppression in posttransplant lymphoproliferative disorder (PTLD). Rescue indications for TAC toxicity were nephrotoxicity, pancreatitis, seizures, hypertrophic cardiomyopathy, and graft-versus-host disease. RESULTS: Mean age at rescue was 11.5 years and mean follow-up was 204 (range 18-800) days. As primary immunosuppression, SRL+TAC prevented early acute rejection in 7/8 children. The indication for rescue resolved in 33/42 children. In children with TAC toxicity, this was associated with decrease in TAC doses by 50%, significant improvements in renal function, and continuing decline in Epstein-Barr virus (EBV) viral load in PTLD patients. Serious adverse events led to discontinuation of SRL in 9/42 rescue patients, 3 of them also experienced acute rejection. Three additional children also experienced acute rejection on SRL therapy (overall incidence 6/50, 12%). Pharmacokinetic analysis in the first week of SRL administration suggested a short half-life (11.8+/-5.5 hr, n=21). CONCLUSIONS: SRL and reduced-dose TAC may achieve adequate immunosuppression without compromising renal function or enhancing EBV viremia significantly.

Acute Disease↗

Cranial vault expansion: a comparison of magnetic coupled distraction to traditional surgical repositioning.

We compared the effectiveness of transcutaneously activated magnetic distraction of an osteotomized cranial bone flap to surgical repositioning of the flap with immediate, rigid internal fixation. Thirty immature rabbits were studied. All 30 rabbits underwent complete circumferential osteotomies of both parietal bones and postoperatively all were fitted with head frames. The rabbits were divided into 4 groups. The experimental magnetic distraction group consisted of 10 animals (group 1). In these rabbits magnets were secured to both parietal bones and magnets of opposite polarity were placed in the headframes. Each morning, the magnets in the head-frames were moved 0.25 mm farther away from the skull; this continued for 20 days for a total setback of 5 mm. Five animals served as the magnetic distraction controls; in these animals magnets were placed on the parietal bones but none were attached to the headframes (group 2). The experimental surgical repositioning group consisted of 10 rabbits (group 3). In each the parietal bones were elevated and fixed 5 mm above the rest of the skull using vitallium mesh and screws. Five rabbits made up the surgical respositioning control group (group 4). In these animals, parietal osteotomies were performed but the bones were secured to the skull in their original positions using hardware identical to that used in the experimental group. Six weeks later all of the animals were sacrificed. Two significant differences were identified between the experimental groups: (1) the cranial contours of the animals in the magnetic distraction group were rounded while those of the surgically repositioned group were acutely angled; (2) the osteotomies in rabbits in the magnetic distraction group were essentially completely ossified while in rabbits in the surgically repositioned group there were obvious gaps at the osteotomy sites that were filled with fibrous tissue. These conclusions support the potential utility of magnetically activated distraction as an alternative to current methods of cranial vault remodeling.

Animals↗

Late shunt infections.

We reviewed the records of the 957 shunt-related operations performed at Cardinal Glennon Children's Hospital over a 10-year period. During that time, 94 shunt infections were recognized. Eight of the infections occurred more than 9 months postoperatively. These differed from early infections in two ways: (1) Staphylococcus aureus was not found to be a pathogen in any late infection. (2) Abdominal pseudocysts were much more frequently found in patients with late-developing infections. In addition, the pathogens involved and the temporal distribution of cases suggest most infections that occur more than 9 months postoperatively are more likely caused by secondary bacterial seeding than by bacterial inoculation at the time of operation.

Adolescent↗

An aortic aneurysm model for the evaluation of endovascular exclusion prostheses.

PURPOSE: The purpose of this study was to develop an aortic aneurysm (AA) model with a predictable tendency for rupture for the evaluation of the efficacy of endovascular prostheses in preventing rupture and their long-term outcome after implantation. METHODS: An infrarenal AA measuring two to three times the diameter of the proximal aorta was created in 18 dogs with a full-thickness patch of jejunum. Seven dogs were allowed to survive without aneurysm exclusion. In 11 dogs the aneurysm was immediately excluded with a stented 8 mm Dacron graft mounted in a 14F delivery system introduced through the femoral artery with aortographic guidance. The pressure differential between the aorta and the excluded aneurysm was measured, and angiography, necropsy, and histologic examination were performed at 3- and 6-month survival. RESULTS: All animals survived aneurysm implantation. Without aneurysm exclusion, six dogs died of rupture within 1 to 6 days of surgery. In three dogs the exclusion failed because of graft-to-aorta size mismatch or misplacement demonstrated on angiography and by a low pressure differential between the aorta and the aneurysm (< 5 mm Hg); all three dogs died of rupture within 4 days. In eight dogs the aneurysm was successfully excluded on the basis of angiography results, with a mean aorta-to-aneurysm pressure differential of 51 mm Hg. Two dogs were killed at 1 and 6 days after surgery because of paraplegia produced by graft thrombosis because of kinking but without evidence of aneurysm rupture. Six dogs survived on a long-term basis, and angiography and necropsy performed at 3 and 6 months revealed patent grafts without migration, reduction in aneurysm size, no flow in the excluded lumbar arteries in five of six animals, and complete incorporation of Dacron graft and stents. No evidence of graft infection was found in any animal. The survival rate was significantly better (p < 0.023) in dogs with successfully excluded aneurysms (n = 6) compared with that in dogs without exclusion or with failed aneurysm exclusion (n = 7). CONCLUSION: This aneurysm model demonstrates that without effective aneurysm exclusion all animals die of rupture and that successfully placed endovascular prostheses can prevent AA rupture with long-term graft patency and stability. Endovascular aortic Dacron grafts in dogs undergo complete incorporation at 3 months from implantation. This aneurysm model is useful for the evaluation of endovascular devices designed for the treatment of AAs.

Animals↗

Anaerobic activation of the entire denitrification pathway in Pseudomonas aeruginosa requires Anr, an analog of Fnr.

The Pseudomonas aeruginosa gene anr, which encodes a structural and functional analog of the anaerobic regulator Fnr in Escherichia coli, was mapped to the SpeI fragment R, which is at about 59 min on the genomic map of P. aeruginosa PAO1. Wild-type P. aeruginosa PAO1 grew under anaerobic conditions with nitrate, nitrite, and nitrous oxide as alternative electron acceptors. An anr deletion mutant, PAO6261, was constructed. It was unable to grow with these alternative electron acceptors; however, its ability to denitrify was restored upon the introduction of the wild-type anr gene. In addition, the activities of two enzymes in the denitrification pathway, nitrite reductase and nitric oxide reductase, were not detectable under oxygen-limiting conditions in strain PAO6261 but were restored when complemented with the anr+ gene. These results indicate that the anr gene product plays a key role in anaerobically activating the entire denitrification pathway.

Anaerobiosis↗

Isolation, organization and expression of the Pseudomonas aeruginosa threonine genes.

Three genes from Pseudomonas aeruginosa involved in threonine biosynthesis, hom, thrB and thrC, encoding homoserine dehydrogenase (HDH), homoserine kinase (HK) and threonine synthase (TS), respectively, have been cloned and sequenced. The hom and thrc genes lie at the thr locus of the P. aeruginosa chromosome map (31 min) and are likely to be organized in a bicistronic operon. The encoded proteins are quite similar to the Hom and TS proteins from other bacterial species. The thrB gene was located by pulsed-field gel electrophoresis experiments at 10 min on the chromosome map. The product of this gene does not share any similarity with other known ThrB proteins. No phenotype could be detected when the chromosomal thrB gene was inactivated by an insertion. Therefore the existence of isozymes for this activity is postulated. HDH activity was feedback inhibited by threonine; the expression of all three genes was constitutive. The overall organization of these three genes appears to differ from that in other bacterial species.

Amino Acid Sequence↗

Pseudomonad replication origins: a paradigm for bacterial origins?

Structural features of three analysed bacterial DNA replication origin classes (six enteric origins, three pseudomonad origins, and the Bacillus subtilis origin region) are compared in order to deduce characteristics common to all bacterial origins and characteristics that distinguish the three origin classes. The two Pseudomonas aeruginosa origins are shown to map within 10 kb of each other, and correlations are drawn with four potential origin regions in B. subtilis. The enteric origin class is further distinguished from the other two classes by its genetic organization, the presence of GATC sites, and the role of Dam methylation in enteric initiation. The pseudomonad origin class has the most features that are common to all of these bacterial origins, and hence may be the paradigm bacterial origin class.

Amino Acid Sequence↗

Prevention of spinal osteoporosis in oophorectomised women.

100 women who had taken part in a prospective controlled trial of oestrogen therapy for prevention of post-oophorectomy bone loss were reviewed after a median follow-up period of nine years. A significant reduction in height occurred among the placebo-treated group, but not in the group treated with mestranol (mean 23 x 3 micrograms/day). The placebo-treated group had a higher spine score, lower central vertebral height, and larger wedge-angle than the oestrogen group. Within each group none of these spinal morphometric changes correlated with changes in mineral content of metacarpal or radial bones as measured by photon absorptiometry or X-ray densitometry, although both peripheral and central measurements showed highly significant differences between groups. Oestrogen treatment, therefore, prevents against central, as well as peripheral, bone loss, and reduces the incidence of vertebral compression.

Body Height↗

Two year sequential haemodynamic data on polytetrafluoroethylene (PTFE) grafts used for haemodialysis.

Forty-one PTFE grafts were studied prospectively with measurement of intragraft pressure and flow. As well, cardiac function was assessed by measuring cardiac output, ejection times and ejection fraction. It was shown that graft failure was associated with changes in graft pressures and flow. No untoward effects of graft flows of 1-2L/min were found on cardiac function.

Brachial Artery↗

Interaction of hyperthermia and chemotherapy agents; cell lethality and oncogenic potential.

Hyperthermia was combined with bleomycin, melphalan and cis-platinum in order to examine cell lethality and oncogenic transformation in C3H10T1/2 cells from the adjuvant use of heat with chemotherapy agents. When cells were exposed concurrently to 42.5 degrees C and each of the three chemotherapy agents, heat enhanced both the cytotoxic and oncogenic potential of the drugs. Hyperthermia-enhanced ratios were largest for bleomycin-treated cells. Examination of transformation incidences expressed as a function of surviving fraction, i.e. the cytotoxicity of treatment and therefore drug-heat efficacy, showed that for a given level of cell killing the combination of heat and cis-platinum resulted in fewer transformants per surviving cell than for cis-platinum alone. Hyperthermia appears to reduce the oncogenic potential of low concentrations of melphalan but has no effect on bleomycin-induced oncogenic transformation.

Animals↗

The pilot study.

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Humans↗