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L Bailey

Publications and source records attributed to L Bailey.

At least 19 recordsLinked to original sources

Lemierre syndrome: a complication of acute pharyngitis.

Lemierre syndrome, otherwise known as postanginal sepsis or necrobacillosis, is an illness that originates as an acute pharyngitis or tonsillitis which progresses to sepsis, usually fusobacterial, due to suppurative thrombophlebitis of the internal jugular vein. Septic thromboemboli then seed various organs, resulting in multiple organ system pathology, most commonly affecting pulmonary and hepatic systems and joints. Although rare in the age of antibiotics, this disease typically affects previously healthy adolescents with varied clinical manifestations depending upon organ system involvement (A. Lemierre, Lancet March (1936) 701-703; J. Barker, H.T. Winer-Muram, S. Grey, Southern Med. J. 89 (1996) 1021-1023). Prompt diagnosis based on clinical presentation, radiologic findings, particularly CT scanning with contrast and a high index of suspicion, is necessary in order to institute often life saving therapy (J. Barker, H.T. Winer-Muram, S. Grey, Southern Med. J. 89 (1996) 1021-1023). We will present two cases of Lemierre syndrome, review it's clinical presentation, anatomic considerations, particularly it's relationship to the parapharyngeal space, radiographic findings, potential life threatening complications and finally, a unique approach to therapy.

Adolescent

Progressive vascular remodeling and reduced neointimal formation after placement of a thermoelastic self-expanding nitinol stent in an experimental model.

Despite the improvements afforded by intracoronary stenting, restenosis remains a significant problem. The optimal physical properties of a stent have not been defined. We compared the vascular response to a thermoelastic self-expanding nitinol stent with a balloon-expandable tubular slotted stainless steel stent in normal porcine coronary arteries. Twenty-two stents (11 nitinol and 11 tubular slotted) were implanted in 11 miniature swine. The nitinol stents were deployed using the intrinsic thermal properties of the metal, without adjunctive balloon dilation. The tubular slotted stents were implanted using a noncompliant balloon with a mean inflation pressure of 12 atm. Intravascular ultrasound (IVUS) and histology were used to evaluate the vascular response to the stents. The mean cross-sectional area (CSA) of the nitinol stents (mm2) as measured by IVUS increased from 8.13 +/- 1.09 at implant to 9.10 +/- 0.99 after 28 days (P = 0.038), while the mean CSA of the tubular slotted stents was unchanged (7.84 +/- 1.39 mm2 vs. 7.10 +/- 1.07 mm2, P = 0.25). On histology at 3 days, the tubular slotted stents had more inflammatory cells adjacent to the stent wires (5.7 +/- 1.5 cells/0.1 mm2) than the nitinol (3.9 +/- 1.3 cells/0.1 mm2, P = 0.016). The tubular slotted also had increased thrombus thickness (83 +/- 85 microm) than the nitinol stents (43 +/- 25 microm, P = 0.0014). After 28 days, the vessel injury score was similar for the nitinol (0.6 +/- 0.3) and the tubular slotted (0.5 +/- 0.1, P = 0.73) designs. The mean neointimal area (0.97 +/- 0.46 mm2 vs. 1.96 +/- 0.34 mm2, P = 0.002) and percent area stenosis (15 +/- 7 vs. 33 +/- 7, P = 0.003) were significantly lower in the nitinol than in the tubular slotted stents, respectively. We conclude that a thermoelastic nitinol stent exerts a more favorable effect on vascular remodeling, with less neointimal formation, than a balloon-expandable design. Progressive intrinsic stent expansion after implant does not appear to stimulate neointimal formation and, therefore, may provide a mechanical solution to prevent in-stent restenosis.

Alloys

Rethinking breast cancer risk and the environment: the case for the precautionary principle.

The World Health Organization recently reported that breast cancer has become the most common cancer in women throughout the world. Known risk factors account for less than half of all cases of breast cancer, and inherited germ line mutations occur in at most only 10% of all cases. Cumulative exposure to estradiol and other hormones links many of the established risk factors for breast cancer. This paper reviews epidemiologic and toxicologic evidence on breast cancer risks and presents a comprehensive construct of risk factors intended to focus on the identification of those factors that can be controlled or modified. We attempt to provide a framework for interpreting the etiologic interplay of endogenous metabolic changes and environmental changes in the etiology of breast cancer. The construct we develop distinguishes between those risk factors that are directly causal, such as ionizing radiation and inherited germ cell defects, those vulnerability factors that extend the time period during which the breast undergoes development, and those contributing factors that increase total hormonal stimulation of the breast. Some hormonally active compounds, such as those in soy and broccoli and other phytoestrogen-containing foods, can be protective against breast cancer, while others, such as some environmental contaminants, appear to increase the risk of the disease by increasing levels of harmful hormones. Efforts to explain patterns of breast cancer should distinguish between these different risk factors. Identification of vulnerability and contributing risk factors can foster the development of public policy to reduce the burden of this prevalent cancer. Prudent precautionary principles suggest that reducing exposure to avoidable or modifiable risk factors should receive high priority from the public and private sectors.

Breast Neoplasms

Polymorphism in cytochrome P450 CYP2D6, CYP1A1, CYP2E1 and glutathione S-transferase, GSTM1, GSTM3, GSTT1 and susceptibility to tobacco-related cancers: studies in upper aerodigestive tract cancers.

Glutathione S-transferase GSTM1, GSTM3 and GSTT1 and cytochrome P450 CYP2D6, CYP1A1 and CYP2E1 loci are susceptibility candidates for cancers of the upper aerodigestive tract because putatively protective and risk genotypes have been identified from studies in other diseases associated with alcohol and tobacco consumption. We describe genotype frequencies in 398 oral, pharyngeal and laryngeal squamous cell carcinoma patients and 219 control individuals. Of the genotypes presumed to be protective, only GSTM1 A/B influenced susceptibility; the GSTM1 A/B frequency was lower in the patients than the control individuals both before [odds ratio = 0.3, 95% confidence interval (CI) 0.1-0.7] and after correction for imbalances in age, sex, smoking and alcohol consumption (odds ratio = 0.2, 95% CI 0.1-0.5). Of the putatively risk genotypes, GSTM3 AA, previously associated with susceptibility to skin cancer, was higher in the cases (odds ratio = 1.6, 95% CI 1.1-2.4). Dividing cases into oral/pharyngeal and laryngeal squamous cell carcinoma showed the GSTM3 AA frequency was higher in laryngeal squamous cell carcinoma than control individuals (odds ratio = 1.6, 95% CI 1.1-2.5) and the difference between control individuals and oral/pharyngeal squamous cell carcinoma approached significance (odds ratio = 1.7, 95% CI 1.0-2.8). The putatively protective GSTM3 BB genotype was lower in patients with glottic (1.0%) than supraglottic (3.0%) squamous cell carcinoma. We identified no differences between patients and control individuals in the frequencies of presumed risk genotypes (e.g. CYP2D6 EM, CYP1A1 m1/m1, CYP1A1 Ile/Ile, CYP2E1 DD, CYP2E1 c1c1, GSTT1 null) or, interactions between genotypes and smoking or alcohol consumption. We conclude, first, that mu class glutathione S-transferase influence risk of upper aerodigestive tract cancers thereby complementing studies in skin cancer patients showing GSTM1 A/B is protective, while GSTM3 AA moderately increases risk. The influence of GSTM1 A/B, but not GSTM1 A or GSTM1 B (mostly heterozygotes with GSTM1*0) suggests that two expressed alleles may attenuate risk. While we found immunohistochemical evidence of GSTM3 expression in the cilia lining the larynx, the biochemical consequences of the polymorphism are unclear. Indeed, the influence of the gene may reflect linkage disequilibrium with another gene. However, we did not find an association with GSTM1 genotypes. Second, we conclude that the CYP2D6, CYP2E1, CYP1A1 and GSTT1 alleles studied, although putatively good candidates, either do not determine the effectiveness of detoxification of tobacco-derived carcinogens in the upper aerodigestive tract or, that chronic consumption of tobacco and alcohol overwhelms enzyme defences, irrespective of genotype.

Aged

The stabilization and encapsulation of human growth hormone into biodegradable microspheres.

PURPOSE: To produce and evaluate sustained-acting formulations of recombinant human growth hormone (rhGH) made by a novel microencapsulation process. METHODS: The protein was stabilized by forming an insoluble complex with zinc and encapsulated into microspheres of poly (D,L-lactide co-glycolide) (PLGA) which differed in polymer molecular weight (8-31 kD), polymer end group, and zinc content. The encapsulation procedure was cryogenic, non-aqueous, and did not utilize surfactants or emulsification. The rhGH extracted from each of these microsphere formulations was analyzed by size-exclusion, ion-exchange and reversed-phase chromatography, SDS-polyacrylamide gel electrophoresis, peptide mapping, and cell proliferation of a cell line expressing the hGH receptor. In addition, the in vivo release profile was determined after subcutaneous administration of the microspheres to rats and juvenile rhesus monkeys. RESULTS: Protein and bioactivity analyses of the rhGH extracted from three different microsphere formulations showed that the encapsulated protein was unaltered relative to the protein before encapsulation. In vivo, microsphere administration to rats or monkeys induced elevated levels of serum rhGH for up to one month, more than 20-fold longer than was induced by the same amount of protein injected subcutaneously as a solution. The rate of protein release differed between the three microsphere formulations and was determined by the molecular weight and hydrophobicity of the PLGA. The serum rhGH profile, after three sequential monthly doses of the one formulation examined, was reproducible and showed no dose accumulation. CONCLUSIONS: Using a novel process, rhGH can be stabilized and encapsulated in a solid state into PLGA microspheres and released with unaltered properties at different rates.

Administration, Cutaneous

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.

Aged

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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