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Biomedical subjects

J Coleman

Publications and source records attributed to J Coleman.

At least 19 recordsLinked to original sources
PubMed2000

High levels of sequence polymorphism and linkage disequilibrium at the telomere of 12q: implications for telomere biology and human evolution.

The human Xp/Yp telomere-junction region exhibits high levels of sequence polymorphism and linkage disequilibrium. To determine whether this is a general feature of human telomeres, we have undertaken sequence analysis at the 12q telomere and have extended the analysis at Xp/Yp. A total of 22 single-nucleotide polymorphisms (SNPs) and one 30-bp duplication were detected in the 1,870 bp adjacent to the 12q telomere. Twenty polymorphic positions were in almost complete linkage disequilibrium, creating three common diverged haplotypes accounting for 80% of 12q telomeres in the white population. A further 6% of 12q telomeres contained a 1,439-bp deletion in the DNA flanking the telomere. The remaining 13% of 12q telomeres did not amplify with the primers used (nulls). The distribution of telomere (TTAGGG) and variant repeats within 12q telomeres was hypervariable, but alleles with similar distribution patterns were associated with the same haplotype in the telomere-adjacent DNA. These data suggest that 12q telomeres, like Xp/Yp telomeres, exhibit low levels of homologous recombination and evolve along haploid lineages. In contrast, high levels of homologous recombination occur in the adjacent proterminal regions of human chromosomes. This suggests that there is a localized telomere-mediated suppression of recombination. In addition, the genetic characteristics of these regions may provide a source of deep lineages for the study of early human evolution, unaffected by both natural selection and recombination. To explain the presence of a few diverged haplotypes adjacent to the Xp/Yp and 12q telomeres, we propose a model that involves the hybridization of two archaic hominoid lineages ultimately giving rise to modern Homo sapiens.

Base Sequence↗
PubMed1999

Characterization of the self association of Avian sarcoma virus integrase by analytical ultracentrifugation.

Retroviral integration protein (IN) has been shown to be both necessary and sufficient for the integration of reverse-transcribed retroviral DNA into the host cell DNA. It has been demonstrated that self-assembly of IN is essential for proper function. Analytical ultracentrifugation was used to determine the stoichiometry and free energy of self-association of a full-length IN in various solvents at 23.3 degrees C. Below 8% glycerol, an association stoichiometry of monomer-dimer-tetramer is observed. At salt concentrations above 500 mM, dimer is the dominant species over a wide range of protein concentrations. However, as physiological salt concentrations are approached, tetramer formation is favored. The addition of glycerol to 500 mM NaCl, 20 mM Tris (pH 8.4), 2 mM beta-mercaptoethanol significantly enhances dimer formation with little effect on tetramer formation. Furthermore, as electrostatic shielding is increased by increasing the ionic strength or decreasing the cation size, dimer formation is strengthened while tetramer formation is weakened. Taken together, the data support a model in which dimer formation includes favorable buried surface interactions which are opposed by charge-charge repulsion, while favorable electrostatic interactions contribute significantly to tetramer formation.

Avian Sarcoma Viruses↗
PubMed1999

Overview of sleep disorders: where does obstructive sleep apnea syndrome fit in?

Otolaryngologists deal primarily with the disorders of obstructive sleep apnea and primary snoring. It is important to realize that although these two disorders are common in the general population, they make up only a small segment of the entire field of sleep disorders medicine. This article attempts to introduce the otolaryngologist to the complexity of this field, help to gain respect and understanding of those practitioners dealing with this entire field, and learn why there is such a broad appeal of this field of medicine to so many subspecialists. Also presented are a table describing the classification of sleep disorders and a short tribute to those individuals who founded this relatively new field of medicine.

Animals↗
PubMed1999

Sleep studies. Current techniques and future trends.

Diagnosis of obstructive sleep apnea has been termed a laboratory diagnosis rather than a clinical diagnosis because one may not be able to make the diagnosis based on the history and physical examination alone. The polysomnogram was developed to give clinicians and researchers objective data on physiologic events occurring during the patient's sleep. From this, obstructive breathing patterns can be diagnosed and if pathologic, appropriate treatment can be instituted. Although the polysomnogram has been the gold standard for diagnosis for more than two decades, it is an expensive and time-consuming procedure. Current technologies for polysomnogram are reviewed, as well as proposals for alternatives that may be more cost and time effective.

Diagnostic Techniques and Procedures↗
PubMed1999

Disordered breathing during sleep in newborns, infants, and children. Symptoms, diagnosis, and treatment.

Although the polysomnographic findings of sleep-disordered breathing in children are similar to those in adults, the underlying causes will vary significantly from adults, depending on whether one is dealing with a newborn, infant, or child. How they react to the disease process is also at times different than seen in the adult and subsequent testing and treatment will also vary considerably. These differences and similarities are reviewed in this article.

Aging↗
PubMed1999

Complications of snoring, upper airway resistance syndrome, and obstructive sleep apnea syndrome in adults.

The complications of sleep-disordered breathing can be separated into two categories. First are those disorders that primarily are brought on by the sleep disorder itself. The second category is those pre-existing medical problems that are aggravated by the sleep disorder. This article examines the consequences of obstructive breathing disorders during sleep and reviews some of the current theories as to the pathophysiology of those problems directly resulting from the sleep disorder.

Adult↗
PubMed1999

Oral and maxillofacial surgery for the management of obstructive sleep apnea syndrome.

The initial reports of treating obstructive sleep apnea using the uvulopalatopharyngoplasty were encouraging; however, as further trials of this procedure were reported, it began to show disappointing results. It was found that the retropalatal airway was not the only site of obstruction and procedures would need to be developed that would address obstruction in the other portions of the airway involved, notably in the retrolingual or hypopharyngeal portion of the airway. It was first reported by oral surgeons that mandibular surgery could also improve sleep apnea and through their work and the work of others, techniques have been developed using skeletal surgery to enhance the patency of the airway during sleep. This article describes some of these techniques and their indications, complications, and results.

Humans↗
PubMed1999

Oropharyngeal surgery in the management of upper airway obstruction during sleep.

In the surgical management of snoring and sleep apnea, surgery to the oropharynx was the initial procedure used to treat sleep-related disorders. This article reviews both the various procedures available for this and the benefits and drawbacks of these procedures so the practitioner may be able to choose which type would be most beneficial for a particular patient.

Airway Obstruction↗
PubMed1999

Suspension sutures for the treatment of obstructive sleep apnea and snoring.

Treatment of airway collapse in the retrolingual airway for obstructive sleep apnea syndrome and snoring has been a frequently frustrating exercise. There are several procedures that have been used with varying degrees of success for some time. These procedures include genioglossus advancement and hyoid suspension, as well as various forms of lingual plasty and lingual reduction. A new technique was introduced at the 1998 meeting of the American Academy of Otolaryngology-Head and Neck Surgery in San Antonio that consisted of using a suspension screw to support the hypopharyngeal soft tissues, specifically, the base of the tongue, to prevent its posterior displacement during sleep. Some of the initial results of these studies have been promising and are reviewed here.

Animals↗
PubMed1999

Pancreatic cancer: a continuum of care.

OBJECTIVES: To provide information about the etiology, clinical manifestations, treatment, and symptom management of pancreatic cancer. DATA SOURCES: Textbook chapters, research studies, and review articles. CONCLUSIONS: Cancer of the pancreas is a devastating disease. A diagnosis of pancreatic cancer causes a person to consider both quantity as well as quality of life. Hope for improved quality of life and survival relies on the efforts of a co-operative multidisciplinary team approach. IMPLICATIONS FOR NURSING PRACTICE: Numerous nursing challenges exist in providing care for the patient with pancreatic cancer. Treatment, symptom management, and psychological, social, and spiritual support are essential in meeting the needs of the patient and family through the eventuality of the disease.

Aged↗
PubMed1999

Balanced biosynthesis of major membrane components through regulated degradation of the committed enzyme of lipid A biosynthesis by the AAA protease FtsH (HflB) in Escherichia coli.

The suppressor mutation, named sfhC21, that allows Escherichia coli ftsH null mutant cells to survive was found to be an allele of fabZ encoding R-3-hydroxyacyl-ACP dehydrase, involved in a key step of fatty acid biosynthesis, and appears to upregulate the dehydrase. The ftsH1(Ts) mutation increased the amount of lipopolysaccharide at 42 degrees C. This was accompanied by a dramatic increase in the amount of UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase [the IpxC (envA) gene product] involved in the committed step of lipid A biosynthesis. Pulse-chase experiments and in vitro assays with purified components showed that FtsH, the AAA-type membrane-bound metalloprotease, degrades the deacetylase. Genetic evidence also indicated that the FtsH protease activity for the deacetylase might be affected when acyl-ACP pools were altered. The biosynthesis of phospholipids and the lipid A moiety of lipopolysaccharide, both of which derive their fatty acyl chains from the same R-3-hydroxyacyl-ACP pool, is regulated by FtsH.

ATP-Dependent Proteases↗
PubMed1999

Multiple lysophosphatidic acid acyltransferases in Neisseria meningitidis.

Lysophosphatidic acid (LPA) and phosphatidic acid (PA) are critical phospholipid intermediates in the biosynthesis of cell membranes. In Escherichia coli, LPA acyltransferase (1-acyl-sn-glycerol-3-phosphate acyltransferase; EC 2.3.1.51) catalyses the transfer of an acyl chain from either acyl-coenzyme A or acyl-acyl carrier protein onto LPA to produce PA. While E. coli possesses one essential LPA acyltransferase (PlsC), Neisseria meningitidis possesses at least two LPA acyltransferases. This study describes the identification and characterization of nlaB (neisserial LPA acyltransferase B), the second LPA acyltransferase identified in N. meningitidis. The gene was located downstream of the Tn916 insertion in N. meningitidis mutant 469 and differed in nucleotide and predicted amino acid sequence from the previously characterized neisserial LPA acyltransferase homologue nlaA. NlaB has specific LPA acyltransferase activity, as demonstrated by complementation of an E. coli plsC(Ts) mutant in trans, by decreased levels of LPA acyltransferase activity in nlaB mutants and by lack of complementation of E. coli plsB26,X50, a mutant defective in the first acyltransferase step in phospholipid biosynthesis. Meningococcal nlaA mutants accumulated LPA and demonstrated alterations in membrane phospholipid composition, yet retained LPA acyltransferase activity. In contrast, meningococcal nlaB mutants exhibited decreased LPA acyltransferase activity, but did not accumulate LPA or display any other observable membrane changes. We propose that N. meningitidis possesses at least two LPA acyltransferases to provide for the production of a greater diversity of membrane phospholipids.

1-Acylglycerol-3-Phosphate O-Acyltransferase↗
PubMed1999

The plasticity of human telomeres demonstrated by a hypervariable telomere repeat array that is located on some copies of 16p and 16q.

Human telomeres are composed of tandem arrays of TTAGGG repeats with many variant repeats at the proximal ends. Comparison of the interspersion of variant and TTAGGG repeats between alleles can be used to study telomere instability, but the difficulty in identifying chromosome-specific sequences close to the start of autosomal telomeres has hampered such investigations. A chromosome end, including a telomere and adjacent sequence, that is polymorphic for its presence or absence in unrelated individuals has been identified. The telomere-adjacent DNA shows strong homology (92-99%) to sequences, including two expressed sequence tags, that are usually located in subterminal regions of human chromosomes but not adjacent to telomeres. Since this chromosome end arose, it has relocated at least once. In Caucasians, it forms the telomere of approximately 6% of 16q and 2% of 16p chromosome arms. The mechanism of relocation is unknown but must have involved the telomere-adjacent DNA rather than the telomere itself, as copies on 16p and 16q share the same telomere-adjacent sequence. The interspersion patterns of TTAGGG with TGAGGG, TTGGGG and non-amplifying repeat sequences revealed extensive allelic variation, such that 47 different alleles were observed among the 50 alleles mapped. Closely related alleles differ by small changes in copy number at blocks of adjacent like repeats, as seen at the Xp/Yp pseudoautosomal telomere. Such differences are compatible with a model in which the majority of mutations arise by intra-allelic mechanisms, in individuals hemizygous for a single copy of the chromosome end.

Base Sequence↗
PubMed1999

Pancreaticoduodenectomy with or without extended retroperitoneal lymphadenectomy for periampullary adenocarcinoma: comparison of morbidity and mortality and short-term outcome.

OBJECTIVE: This prospective, randomized, single-institution trial was designed to evaluate the end points of mortality, morbidity, and survival in patients undergoing standard versus radical (extended) pancreaticoduodenectomy (including distal gastrectomy and retroperitoneal lymphadenectomy). SUMMARY BACKGROUND DATA: Numerous retrospective reports and one prospective randomized trial have suggested that the performance of an extended lymphadenectomy in association with a pancreaticoduodenal resection may improve long-term survival for some patients with pancreatic and other periampullary adenocarcinomas. Many of these previously published studies can be criticized for their retrospective and nonrandomized designs, for the inclusion of nonconcurrent control groups, and for their small numbers. METHODS: Between April 1996 and December 1997, 114 patients with periampullary adenocarcinoma were enrolled in an ongoing, prospective, randomized trial at The Johns Hopkins Hospital. After intraoperative verification of completely resected periampullary adenocarcinoma, the patients were randomized to receive either a standard pancreaticoduodenectomy (removing only the peripancreatic lymph nodes en bloc with the specimen) or a radical pancreaticoduodenectomy (standard resection plus distal gastrectomy and retroperitoneal lymphadenectomy). All pathology specimens were reviewed and categorized. The postoperative morbidity, mortality, and short-term outcomes were examined. RESULTS: Of the 114 patients randomized, 56 underwent a standard pancreaticoduodenectomy and 58 a radical pancreaticoduodenectomy. The two groups were statistically similar with regard to age and gender, but there was a higher percentage of white patients in the radical group. All the patients in the radical group underwent distal gastric resection, whereas 86% of the patients in the standard group underwent pylorus preservation. The mean operative time in the radical group was 6.8 hours, compared with 6.2 hours in the standard group. There were no significant differences between the two groups with respect to the intraoperative blood loss, transfusion requirements, location of primary tumor, mean tumor size, positive lymph node status, or positive margin status. There were three deaths in the standard group and two in the radical group. The complication rates were 34% for the standard group and 40% for the radical group. Patients undergoing radical resection had a higher incidence of early delayed gastric emptying but had similar rates of other complications, such as pancreatic fistula, wound infection, intraabdominal abscess, and need for reoperation. The mean total number of lymph nodes resected was higher in the radical group. Of the 58 patients in the radical group, only 10% had metastatic carcinoma in the resected retroperitoneal lymph nodes, and none of those patients had the retroperitoneal nodes as the only site of lymph node involvement. The 1-year actuarial survival rate for patients surviving the immediate postoperative periods was 77% for the standard resection group and 83% for the radical resection group. CONCLUSIONS: These data demonstrate that radical pancreaticoduodenectomy (with the addition of a distal gastrectomy and extended retroperitoneal lymphadenectomy to a standard pancreaticoduodenectomy) can be performed with similar morbidity and mortality to standard pancreaticoduodenectomy. However, the survival data are not sufficiently mature and the numbers of patients enrolled are not adequate to allow firm conclusions to be drawn regarding survival benefit.

Adenocarcinoma↗
PubMed1999

Is prophylactic gastrojejunostomy indicated for unresectable periampullary cancer? A prospective randomized trial.

OBJECTIVE: This prospective, randomized, single-institution trial was designed to evaluate the role of prophylactic gastrojejunostomy in patients found at exploratory laparotomy to have unresectable periampullary carcinoma. SUMMARY BACKGROUND DATA: Between 25% and 75% of patients with periampullary cancer who undergo exploratory surgery with intent to perform a pancreaticoduodenectomy are found to have unresectable disease. Most will undergo a biliary-enteric bypass. Whether or not to perform a prophylactic gastrojejunostomy remains unresolved. Retrospective reviews of surgical series and prospective randomized trials of endoscopic palliation have demonstrated that late gastric outlet obstruction, requiring a gastrojejunostomy, develops in 10% to 20% of patients with unresectable periampullary cancer. METHODS: Between May 1994 and October 1998, 194 patients with a periampullary malignancy underwent exploratory surgery with the purpose of performing a pancreaticoduodenectomy and were found to have unresectable disease. On the basis of preoperative symptoms, radiologic studies, or surgical findings, the surgeon determined that gastric outlet obstruction was a significant risk in 107 and performed a gastrojejunostomy. The remaining 87 patients were thought by the surgeon not to be at significant risk for duodenal obstruction and were randomized to receive either a prophylactic retrocolic gastrojejunostomy or no gastrojejunostomy. Short- and long-term outcomes were determined in all patients. RESULTS: Of the 87 patients randomized, 44 patients underwent a retrocolic gastrojejunostomy and 43 did not undergo a gastric bypass. The two groups were similar with respect to age, gender, procedure performed (excluding gastrojejunostomy), and surgical findings. There were no postoperative deaths in either group, and the postoperative morbidity rates were comparable (gastrojejunostomy 32%, no gastrojejunostomy 33%). The postoperative length of stay was 8.5+/-0.5 days for the gastrojejunostomy group and 8.0+/-0.5 days for the no gastrojejunostomy group. Mean survival among those who received a prophylactic gastrojejunostomy was 8.3 months, and during that interval gastric outlet obstruction developed in none of the 44 patients. Mean survival among those who did not have a prophylactic gastrojejunostomy was 8.3 months. In 8 of those 43 patients (19%), late gastric outlet obstruction developed, requiring therapeutic intervention (gastrojejunostomy 7 patients, endoscopic duodenal stent 1 patient; p < 0.01). The median time between initial exploration and therapeutic intervention was 2 months. CONCLUSION: The results from this prospective, randomized trial demonstrate that prophylactic gastrojejunostomy significantly decreases the incidence of late gastric outlet obstruction. The performance of a prophylactic retrocolic gastrojejunostomy at the initial surgical procedure does not increase the incidence of postoperative complications or extend the length of stay. A retrocolic gastrojejunostomy should be performed routinely when a patient is undergoing surgical palliation for unresectable periampullary carcinoma.

Adenocarcinoma↗
PubMed1999

Clinical pathway implementation improves outcomes for complex biliary surgery.

BACKGROUND: Complex biliary surgery is associated with significant morbidity, prolonged hospital stay, and high cost. Clinical pathway implementation has the potential to standardize treatment and improve outcomes. Therefore the aim of this analysis was to determine whether clinical pathway implementation and/or feedback of outcome data would alter hospital stay, charges, and mortality rates for complex biliary surgery at an academic medical center METHODS: Pre- and postoperative length of stay, hospital charges, and mortality rates were monitored for 36 months before (period 1) and for 2 18-month periods (periods 2 and 3) after implementation of a clinical pathway for hepaticojejunostomy. Outcome data were provided to the surgeons 18 months after pathway implementation to determine whether further clinical practice improvement was possible. RESULTS: From 1991 to 1997, 339 patients underwent hepaticojejunostomy at The Johns Hopkins Hospital for malignant and benign biliary obstruction. Total length of stay was 13.3 +/- 0.9 days for period 1 compared with 12.5 +/- 0.8 days for period 2 (not significant) and 10.1 +/- 0.3 days for period 3 (P < .01 vs period 1; P < .03 vs period 2). Hospital charges averaged $24,446 during period 1 compared with $23,338 during period 2 and $20,240 during period 3 (P < .01 vs periods 1 and 2). Hospital mortality rate was 4.5% during period 1 compared with 0.7% during periods 2 and 3 (P < .05). CONCLUSIONS: These data suggest that implementation of a clinical pathway for hepaticojejunostomy reduces hospital mortality rates and that feedback of outcome data to surgeons results in further clinical practice improvement. Thus clinical pathway implementation and feedback are effective methods to control costs at an academic medical center.

Academic Medical Centers↗