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L Bailey

Publications and source records attributed to L Bailey.

At least 37 records · Page 2Linked to original sources

In vivo characterization of sustained-release formulations of human growth hormone.

Long-acting formulations of recombinant human growth hormone (rhGH) were prepared by stabilizing and encapsulating the protein into three different injectable, biodegradable microsphere formulations composed of polymers of lactic and glycolic acid. The formulations were compared in juvenile rhesus monkeys by measuring the serum levels of rhGH and two proteins induced by hGH, insulin-like growth factor-I and IGF binding protein-3 (IGFBP-3) after single s.c. administration. All three formulations, which differed principally in the composition of the polymer, provided sustained elevated levels of all three proteins for several weeks, and the rate of release of rhGH differed among the formulations consistent with the molecular weight of the polymer used. All three formulations induced a higher level of insulin-like growth factor-I and insulin-like growth factor binding protein than was induced by daily injections of the same amount of rhGH in solution. After three monthly injections of one of the formulations, both the rhGH and IGF-I levels remained elevated for nearly 90 days. Immunogenicity of the rhGH released from this formulation, as assessed by the incidence of seroconversion to hGH and the titer of anti-hGH antibody in both the rhesus monkeys and transgenic mice expressing rhGH, was no greater than that of the unencapsulated protein. In addition, the microsphere injection sites appeared normal by macroscopic evaluation between 1 to 2 mo after microsphere administration and by microscopic evaluation between 2 to 3 mo. These results show that serum levels of a therapeutic protein can be sustained for an extended period when encapsulated into different formulations of injectable, biodegradable microspheres.

Animals↗

Polymorphism at the glutathione S-transferase locus GSTM3: interactions with cytochrome P450 and glutathione S-transferase genotypes as risk factors for multiple cutaneous basal cell carcinoma.

The influence of polymorphism in the glutathione S-transferase, GSTM3 gene on susceptibility to cutaneous basal cell carcinoma (BCC) has been investigated. We have reported previously two GSTM3 alleles, GSTM3*A and GSTM3*B, distinguished by a recognition motif for the YY1 transcription factor in GSTM3*B. In this study, immunohistochemistry was used to identify GSTM3 expression in the epidermis of skin samples from 11 controls and 9 patients with BCC. A PCR method was used to identify GSTM3*A and GSTM3*B and thereby the GSTM3 AA, GSTM3 AB, and GSTM3 BB genotypes in 300 controls and 286 Caucasians with 1-35 primary BCCs. Genotypes at GSTM1, GSTT1, and the cytochrome P450 CYP1A1 and CYP2D6 loci were also determined. Frequencies of GSTM3, GSTM1, GSTT1, CYP2D6, and CYP1A1 genotypes in the cases and controls were not different. Dividing the BCC cases into groups of 92 patients with 1 lesion and 194 patients with 2-35 lesions showed that the frequencies of GSTM3 BB (2.6%) and GSTM1 A/B (1.3%) in the group with 2-35 tumors were almost significantly lower than in the group with 1 lesion (7.6%, exact P = 0.0601, chi 2(1) = 3.390; 6.5%, exact P = 0.055, chi 2(1) = 4.946, respectively). Within the cases with 2-35 tumors, a Poisson regression model was used to identify genotypes, characteristics such as skin type, and interactions between genotypes and characteristics associated with increasing numbers of tumors. This showed, after correction for male gender and age, that GSTM3 AA was not associated with risk of increased numbers of tumors, although in combination with skin type 1, GSTM1 null, and CYP1A1 m1m1, the genotype did confer increased risk (P < 0.001, rate ratio, 2.058; P < 0.001, rate ratio, 1.606; P < 0.001, rate ratio, 1.470 respectively). The data suggest that, like other allelic GST, GSTM3 influences cancer risk. As GSTM3 AA was associated with increased tumor numbers, it appears that YY1 acts as an activator of the recognition motif in GSTM3*B.

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Employment↗

Coronary stenting with a novel stainless steel balloon-expandable stent: determinants of neointimal formation and changes in arterial geometry after placement in an atherosclerotic model.

OBJECTIVES: This study evaluated the delivery characteristics and vascular response to placement of a novel balloon-expandable stent in swine with experimentally induced atherosclerosis. BACKGROUND: The Multi-Link stent is a balloon-expandable stainless steel stent with an interconnected ring structure designed to provide a high degree of compressive resistance while preserving longitudinal flexibility. The placement characteristics and vascular response to this stent in atherosclerotic coronary arteries have not been characterized. METHODS: We tested the delivery characteristics and vascular response to the Multi-Link stent in 19 miniature swine with experimentally induced coronary atherosclerosis created in 37 coronary artery segments by overstretch balloon injury and high cholesterol diet. Quantitative coronary angiography was used to define stent performance characteristics, such as lesion dilation and compressive resistance. Pathologic assessment of the stented arteries was used to evaluate the immediate and long-term vascular response to stent placement. RESULTS: Nineteen (95%) of 20 stents were successfully implanted in the left anterior descending (n = 11), left circumflex (n = 7) or right (n = 1) coronary artery. The baseline angiographic minimal lumen diameter of the stented coronary segment was 2.48 +/- 0.09 mm (reference diameter 2.87 +/- 0.06 mm, mean +/- SE) and increased to 2.82 +/- 0.05 mm (p < 0.001) after stent placement. The balloon-inflated stent diameter was 2.98 +/- 0.06 mm with minimal recoil to a final minimal lumen diameter of 2.82 +/- 0.06 mm at 15 min after implantation (p = 0.001). Angiographic and histologic follow-up at 72 h (n = 7), 14 days (n = 4) and 56 days (n = 8) demonstrated that all stents were patent, without evidence of migration, intraluminal filling defects or side branch occlusion. At 56 days, mean neointimal thickness was significantly greater at the stent wire sites in the region of the plaque where the media was absent than the stent wire sites, where the internal elastic lamina was intact with underlying normal media (0.48 +/- 0.01 vs. 0.27 +/- 0.02 mm, p < 0.0001). Compared with the nonstented atherosclerotic lesions, after 56 days the stented vessels had a mildly reduced lumen area when normalized to the proximal reference vessel (2.81 +/- 0.27 vs. 2.68 +/- 0.30 mm2, p = 0.07). The mean change in the area within the external elastic lamina relative to a normal proximal reference segment was significantly greater in stented vessels (1.45 +/- 0.34 mm2) than nonstented atherosclerotic vessels (0.44 +/- 0.28 mm2, p = 0.033). CONCLUSIONS: Morphologic data confirm that the principal beneficial effect of stent placement is vessel expansion and attenuation of constrictive remodeling. In vessels with eccentric atherosclerotic fibrocellular plaques, the presence of normal media underlying the stent determines the degree of neointimal formation. These data may be useful in understanding the mechanism of stent restenosis in patients with prior percutaneous transluminal coronary angioplasty.

Angioplasty, Balloon, Coronary↗

Proton magnetic resonance spectroscopy in the evaluation of children with congenital heart disease and acute central nervous system injury.

We studied nine infants and children, aged 1 week to 42 months, with severe acute central nervous system injuries associated with cardiac disease or corrective operations by means of single-voxel proton magnetic resonance spectroscopy to determine whether this technique would be useful in predicting neurologic outcome. Proton magnetic resonance spectroscopic data were acquired from the occipital gray and parietal white matter (8 cm3 volume, stimulated echo-acquisition mode sequence with echo time of 20 msec and repetition time of 3.0 seconds) a median of 9 days after operation (range 3 to 42 days). Data were expressed as ratios of areas under metabolite peaks, including N-acetyl compounds, choline-containing compounds, creatine and phosphocreatine, and lactate. Four patients had cerebral insults before operation, one had both a preoperative and a perioperative insult, three had perioperative insults, and one had a prolonged cardiac arrest 2 days after operation. Outcomes (Glasgow Outcome Scale scores) were assigned at discharge and 6 to 12 months after injury. Six patients were in a vegetative state or had severe impairment at discharge, and two still had severe impairment at 6- to 12-month follow-up. Proton magnetic resonance spectroscopy showed lactate in these two patients, along with markedly reduced ratios of N-acetyl compounds to creatine compounds. The other four patients with severe impairment recovered to a level of mild disability at follow-up. Proton magnetic resonance spectroscopy showed no lactate in these four patients; however, one patient showed moderately reduced ratio of N-acetyl compounds to creatine compounds. The three patients who had mild or moderate impairment at discharge showed no lactate and mild or no changes in metabolite ratios; follow-up revealed normal or mild outcomes. Overall, we found that the presence of lactate and markedly reduced ratios of N-acetyl compounds to creatine compounds were predictive of severe outcomes at discharge and long-term follow-up, whereas no lactate and mild or no changes in ratios suggested potential for recovery with at least a mild disability. Continuing investigations are in progress to determine the optimal selection of candidates and timing of proton magnetic resonance spectroscopic studies.

Aspartic Acid↗

Bypass coaptation procedures for cervical nerve root avulsion.

In the past, patients with cervical spinal nerve root avulsions were resigned to accept a natural crippling from upper extremity neurological deficits. Recently, bypass coaptation procedures have resulted in functional return of denervated muscles after such avulsions, much to the appreciation of patients. Presented are 12 patients with avulsion of cervical spinal nerve roots that form either the brachial plexus upper trunk (n = 7), lower trunk (n = 1), or all three trunks (n = 4). The patients underwent the new bypass coaptation procedures with complete or partial return of motor and sensory function, which otherwise would be totally nonfunctional. The most dramatic results were noted in those patients who underwent operations within 6 weeks of injury. The results of these procedures offer patients a valid therapeutic modality for an enhanced quality of life after cervical nerve root avulsion.

Adult↗

Gene amplification of the Menkes (MNK; ATP7A) P-type ATPase gene of CHO cells is associated with copper resistance and enhanced copper efflux.

Three copper-resistant variants of cultured Chinese hamster ovary (CHO) cells were isolated and each was shown to accumulate less intracellular copper than the parental cells when grown in copper-supplemented media. The reduced copper accumulation was related to enhanced copper efflux. As cultured cells from patients with Menkes disease (mutations in MNK; ATP7A gene) accumulate copper, probably due to defective copper efflux, we investigated the possible role of the MNK gene in the molecular basis of copper resistance. We found increased MNK mRNA and MNK protein in all three resistant variants. The MNK protein, which has not been previously demonstrated experimentally in mammalian cells, was observed to have an apparent molecular weight of 178 kDa on SDS gels. The degree of increase in MNK mRNA and protein correlated well with the level of copper resistance and extent of copper efflux. By Southern blot and FISH analysis we determined that the molecular basis for overexpression of MNK was genomic amplification of the MNK gene. These data, combined with the clinical and cellular phenotype in Menkes disease, provide strong evidence that the MNK protein is involved in transmembrane copper efflux, and demonstrate a new system of gene amplification in mammalian cells.

Adenosine Triphosphatases↗

Analysis of condylar position change on digitally subtracted Orthophos P-4 and Sectograph zonogram images.

The purpose of this study was to compare the accuracy of two single-image techniques that provide parasagittal views of the temporomandibular joint. Orthophos program 4 and Sectograph zonographic techniques were evaluated using digital subtraction to measure 1-, 2-, and 3-mm shifts of condylar position in horizontal or vertical planes. Precise repositioning of a human skull was facilitated by laser alignment beams. Statistically significant differences between radiographic techniques reflected the tendency for overestimating of shifts with program 4 and underestimation with zonographic techniques. Pooled mean difference values were 0.12 mm for program 4 images of -0.17 mm for zonograms. Program 4 images and zonograms produced with precise repositioning of anatomy approached the accuracy of tomograms and may prove useful for evaluating parasagittal alterations in condylar position in pretreatment and posttreatment radiographs.

Analysis of Variance↗

Analysis of condylar position changes: a test of validity of posteroanterior cephalometric and 20-degree lateral cephalometric techniques enhanced by digital subtraction.

This preclinical study was designed to evaluate 20-degree lateral cephalometric and posteroanterior cephalometric techniques with digital subtraction enhancement for their ability to detect 1-, 2-, and 3-mm shifts in condylar position in two of three planes of space (horizontal or transverse and vertical). The model used was a dry human skull with a complete mandible mounted on a microscopic stage with positioning accuracy to 0.1 mm in x, y, and z planes. Analysis of variance showed no significant difference from expected values in the transverse plane (posteroanterior cephalogram only). There were significant differences in the sagittal plane (20-degree lateral cephalogram only) for the 2- and 3-mm shifts (P < .001). There were no significant differences among expected values in the vertical plane for individual increments or for increment comparisons. The magnitude of standard deviations and of the absolute value of differences indicates markedly increased variability for both techniques as compared to tomograms produced with cephalostat repositioning. The authors conclude that even with precise repositioning and digital subtraction enhancement, cephalometric radiographs are inadequate for clinical monitoring of condylar position.

Analysis of Variance↗

Pseudoaneurysms of the aorta after cardiac surgery or chest trauma.

Between March 1982 and June 1992, 17 patients (age: 21-76 years) were diagnosed with pseudoaneurysm of the thoracic aorta (PTA). Four PTAs developed post-trauma while 13 developed after aortic or cardiac surgery. Unusual presentations included: dyspnea, hoarseness, dysphagia, massive hemoptysis (2 degrees to aortobronchial fistula), massive hematemesis (2 degrees to aorto-esophageal fistula), superior vena cava syndrome, paralyzed right hemidiaphragm, and herald bleeding from the sternotomy. The interval between initial operation and recognition of PTA varied from three months to eight years while the four posttraumatic PTAs presented 5 to 26 years postinjury. The sites of postoperative PTA were: the aortotomy (3), proximal vein graft anastomosis (4), aortic cannulation site (2), and distal anastomosis of ascending aortic graft replacement (4). Aortography was very sensitive, outlining the false aneurysm in 13/13. Five patients had transesophageal echo-cardiography with one false negative. Seven patients died (41%), three from postoperative PTAs from massive hemorrhage intraoperatively and four from sepsis and multiorgan failure following repair. We conclude that patients who have previously had aortic or cardiac surgery or a history of blunt chest trauma presenting with unusual cardiorespiratory symptoms should be aggressively evaluated for PTA. Due to the magnitude of the operative problems encountered, repair of PTA is associated with a significantly high rate of mortality.

Adult↗

A major outbreak of foodborne gastroenteritis among Air Force personnel during Operation Desert Storm.

An outbreak of foodborne gastroenteritis affected 648 United States Air Force personnel stationed in Jeddah, Saudi Arabia during Operation Desert Storm. The implicated food source was a locally catered meal. Despite the presence of an aggressive Air Force public health program, foodborne illness had a major impact on manpower and medical resources during a critical phase of military operations. It is the recommendation of the authors that the Air Force not rely on local caterers during future deployments.

Aerospace Medicine↗

Survey of 3765 cardiopulmonary resuscitations in British hospitals (the BRESUS Study): methods and overall results.

OBJECTIVE: To determine the circumstances, incidence, and outcome of cardiopulmonary resuscitation in British hospitals. DESIGN: Hospitals registered all cardiopulmonary resuscitation attempts for 12 months or longer and followed survival to one year. SETTING: 12 metropolitan, provincial, teaching, and non-teaching hospitals across Britain. SUBJECTS: 3765 patients in whom a resuscitation attempt was performed, including 927 in whom the onset of arrest was outside the hospital. MAIN OUTCOME MEASURE: Survival after initial resuscitation, at 24 hours, at discharge from hospital, and at one year, calculated by the life table method. RESULTS: There were 417 known survivors at one year, with 214 lost to follow up. By life table analysis for every eight attempted resuscitations there were three immediate survivors, two at 24 hours, 1.5 leaving hospital alive, and one alive at one year. Survival at one year was 12.5% including out of hospital cases and 15.0% not including these cases. Each hospital year averaged 30 survivors at one year: three who had an arrest outside hospital, seven who had one in the accident and emergency department, seven in the cardiac care unit, 10 in the general wards, and three in other, non-ward areas. Within the hospitals survival rates were best in those who had an arrest in the accident and emergency department, the cardiac care unit, or other specialised units. Outcome varied 12-fold in subgroups defined by age, type of arrest, and place of arrest. CONCLUSION: 71% of the mortality at one year in patients undergoing attempted resuscitation occurred during the initial arrest. Hospital resuscitation is life saving and cost effective and warrants appropriate attention, training, coordination, and equipment.

Age Factors↗