Search PubMed⌕ Search

Biomedical subjects

R B Adams

Publications and source records attributed to R B Adams.

At least 19 recordsLinked to original sources
PubMed2006

Endoscopic ultrasound drainage of pancreatic pseudocyst: a prospective comparison with conventional endoscopic drainage.

BACKGROUND AND STUDY AIMS: Pancreatic pseudocysts are a complication in up to 20% of patients with pancreatitis. Endoscopic management of pseudocysts by a conventional transenteric technique, i. e. conventional transmural drainage (CTD), or by endoscopic ultrasound-guided drainage (EUD), is well described. Our aim was to prospectively compare the short-term and long-term results of CTD and EUD in the management of pseudocysts. PATIENTS AND METHODS: A total of 99 consecutive patients underwent endoscopic management of pancreatic pseudocysts according to this predetermined treatment algorithm: patients with bulging lesions without obvious portal hypertension underwent CTD; all remaining patients underwent EUD. Patients were followed prospectively, with cross-sectional imaging during clinic visits. We compared short-term and long-term results (effectiveness and complications) at 1 and 6 months post procedure. RESULTS: 46 patients (37 men) underwent EUD and 53 patients (39 men) had CTD. The mean age of the entire group was 50 +/- 13 years. There were no significant differences between the two groups regarding short-term success (93% vs. 94%) or long-term success (84% vs. 91%); 68 of the 99 patients completed 6 months of follow-up. Complications occurred in 19% of EUD vs. 18% of CTD patients, and consisted of bleeding in three, infection of the collection in eight, stent migration into the pseudocyst in three, and pneumoperitoneum in five. All complications but one could be managed conservatively. CONCLUSIONS: No clear differences in efficacy or safety were observed between conventional and EUS-guided cystenterostomy. The choice of technique is likely best predicated by individual patient presentation and local expertise.

Adult↗
PubMed2001

Alterations in the focal adhesion kinase/Src signal transduction pathway correlate with increased migratory capacity of prostate carcinoma cells.

Focal adhesion kinase (FAK) has been implicated in the regulation of cell migration. In addition, FAK expression is increased in a number of highly metastatic tumor cell lines. Therefore, we investigated the role of FAK in regulating migration of prostate carcinoma cell lines with increasing metastatic potential. We show that highly tumorigenic PC3 and DU145 cells exhibit intrinsic migratory capacity, while poorly tumorigenic LNCaP cells require a stimulus to migrate. Increased metastatic potential of PC3 and DU145 cells correlates with increased FAK expression, overall tyrosine phosphorylation and activity, as measured by autophosphorylation of tyrosine 397. However, in PC3 and DU145 cells, FAK autophosphorylation is adhesion dependent whereas a second site of tyrosine phosphorylation, tyrosine 861, a Src specific site, is uncoupled from adhesion-dependent signaling events. Finally, inhibiting the FAK/Src signal transduction pathway by over expressing FRNK (Focal adhesion kinase-Related Non-Kinase), an inhibitor of FAK activation, or treatment with PP2, a Src family kinase inhibitor, significantly inhibited migration of prostate carcinoma cell lines, demonstrating that tumor cell migration continues to be dependent on signals emanating from this pathway.

Adenoviridae↗
PubMed2001

Outpatient laparoscopic cholecystectomy: patient outcomes after implementation of a clinical pathway.

OBJECTIVE: To determine the success of a clinical pathway for outpatient laparoscopic cholecystectomy (LC) in an academic health center, and to assess the impact of pathway implementation on same-day discharge rates, safety, patient satisfaction, and resource utilization. SUMMARY BACKGROUND DATA: Laparoscopic cholecystectomy is reported to be safe for patients and acceptable as an outpatient procedure. Whether this experience can be translated to an academic health center or larger hospital is uncertain. Clinical pathways guide the care of specific patient populations with the goal of enhancing patient care while optimizing resource utilization. The effectiveness of these pathways in achieving their goals is not well studied. METHODS: During a 12-month period beginning April 1, 1999, all patients eligible for an elective LC (n = 177) participated in a clinical pathway developed to transition LC to an outpatient procedure. These were compared with all patients undergoing elective LC (n = 208) in the 15 months immediately before pathway implementation. Successful same-day discharges, reasons for postoperative admission, readmission rates, complications, deaths, and patient satisfaction were compared. Average length of stay and total hospital costs were calculated and compared. RESULTS: After pathway implementation, the proportion of same-day discharges increased significantly, from 21% to 72%. Unplanned postoperative admissions decreased as experience with the pathway increased. Patient characteristics, need for readmission, complications, and deaths were not different between the groups. Patients surveyed were highly satisfied with their care. Resource utilization declined, resulting in more available inpatient beds and substantial cost savings. CONCLUSIONS: Implementation of a clinical pathway for outpatient LC was successful, safe, and satisfying for patients. Converting LC to an outpatient procedure resulted in a significant reduction in medical resource use, including a decreased length of stay and total cost of care.

Academic Medical Centers↗
PubMed2000

Association of infiltrating lobular carcinoma with positive surgical margins after breast-conservation therapy.

OBJECTIVE: To determine whether infiltrating lobular carcinoma (ILC) is associated with high positive-margin rates for single-stage lumpectomy procedures, and to define clinical, mammographic, or histologic characteristics of ILC that might influence the positive-margin rate, thereby affecting treatment decisions. SUMMARY BACKGROUND DATA: Infiltrating lobular cancer represents approximately 10% of all invasive breast carcinomas and is often poorly defined on gross examination. METHODS: A group of 47 patients with biopsy-proven ILC undergoing breast-conservation therapy (BCT) at the University of Virginia Health Sciences Center between 1975 and 1999 was compared with a group of 150 patients with infiltrating ductal cancer undergoing BCT during the same time period. The pathology of the lumpectomy specimen was reviewed for each patient to confirm surgical margin status. Office and surgical notes as well as mammography reports were examined to determine whether the lesions were deemed palpable before and during surgery. Patients were stratified according to age, family history, tumor size, tumor location, and histologic features of the tumor. RESULTS: The incidence of positive margins was greater in the ILC group compared with the infiltrating ductal cancer group. Patient age, family history, and preoperative palpability of the tumor did not correlate with surgical margin status. Of the mammographic features identified, including spiculated mass, calcifications, architectural distortion, and other densities, only architectural distortion predicted positive surgical margin status. Tumor grade, tumor size, lymph node status, and receptor status were not predictive of surgical margin status. CONCLUSIONS: For patients with ILC, BCT is feasible, but these patients are at high risk of tumor-positive resection margins (51% incidence) after the initial resection. Only the mammographic finding of architectural distortion was identified as a preoperative marker reliably identifying a subgroup of ILC patients at especially high risk for a positive surgical margin. For all patients with ILC considering BCT, careful counseling about the potential need for a second procedure to treat the positive margin should be included in the treatment discussion.

Breast Neoplasms↗
PubMed2000

Genetic syndromes and genetic tests in colorectal cancer.

Our understanding of the biology of colon cancer has matured to the point that it is a useful general paradigm for understanding solid tumor development. Recent advances provide insight into the genetic alterations underlying the development of colon cancer. These insights provide unique opportunities for genetic testing in predisposed, asymptomatic patients that can direct screening efforts and their clinical management. This review examines several inherited colon cancer predispositions, well described clinically for a century, that are now amenable to genetic testing. Additional discussion focuses on colon cancer predisposition traits that occur with high frequency but low penetrance characteristics. Finally, genetic tests for tumor markers that potentially have prognostic or therapeutic implications are reviewed.

Adenomatous Polyposis Coli↗
PubMed1997

Identification of integrin-stimulated sites of serine phosphorylation in FRNK, the separately expressed C-terminal domain of focal adhesion kinase: a potential role for protein kinase A.

Focal adhesion kinase (pp125(FAK)) is a protein tyrosine kinase that is localized to focal adhesions in many cell types and which undergoes tyrosine phosphorylation after integrin binding to extracellular matrix. In some cells the C-terminal non-catalytic domain of pp125(FAK) is expressed as a separate protein referred to as FRNK (FAK-related, non-kinase). We have previously shown that overexpression of FRNK inhibits tyrosine phosphorylation of pp125(FAK) and its substrates as well as inhibiting cell spreading on fibronectin. In this report we identify Ser148 and Ser151 as residues in FRNK that are phosphorylated after tyrosine phosphorylation of pp125(FAK) and in response to integrin binding to fibronectin. Tyrosine phosphorylation of pp125(FAK) appears to be an early event after integrin occupancy, and serine phosphorylation of FRNK occurs significantly later. Treatment of fibroblasts with a series of protein kinase A inhibitors delayed serine phosphorylation of FRNK as well as cell spreading on fibronectin and tyrosine phosphorylation of pp125(FAK). However, these PKA inhibitors are unlikely to delay cell spreading simply by preventing serine phosphorylation of FRNK, as overexpression of FRNK containing mutations of Ser148 and Ser151 either singly or jointly to either alanine or glutamate residues did not significantly alter the ability of FRNK to act as an inhibitor of pp125(FAK).

Animals↗
PubMed1996

Laparoscopic percutaneous jejunostomy for long term enteral access.

BACKGROUND: Patients suffering from upper gastrointestinal pathology may require jejunal feeding for adequate nutrition. A laparoscopically guided percutaneous jejunostomy offers a minimally invasive means of obtaining such feeding access. METHODS: Laparoscopic jejunostomy was performed in 32 patients. The most common indications were gastroparesis (n = 16), neurological deficits (n = 7), and proximal obstruction (n = 5). The proximal jejunum was affixed to the abdominal wall using intracorporeal and extracorporeal transabdominal sutures, allowing safe insertion of an 18-Fr Silastic dual-lumen tube. RESULTS: Laparoscopic jejunostomy was successfully completed for 28 patients; the procedure was converted to an open operation in four cases. Three of these four were among 14 patients undergoing the procedure who had a history of previous abdominal surgery. Major complications were observed in seven patients, including one reoperation and one death from aspiration pneumonia. Tube feeding was accomplished in all patients; progression to full enteral feeding proceeded without interruption in 20 patients. CONCLUSION: Laparoscopic jejunostomy can be performed with relative safety. Morbidity, though high, is usually related to preexisting disease. Previous abdominal surgery is not necessarily a contraindication to laparoscopic jejunostomy.

Enteral Nutrition↗
PubMed1996

Correlation of peripheral blood lymphocyte and intragraft cytokine mRNA expression with rejection in orthotopic liver transplantation.

BACKGROUND: Regulation of allograft rejection mediated by CD4+ T lymphocytes is dependent on the pattern of cytokines produced by these cells. The purpose of this study was to examine liver transplant recipients to determine whether peripheral blood lymphocyte (PBL), intragraft cytokine production, or both correlated with histologic assessment of graft rejection. METHODS: PBL and liver biopsy specimens from transplant recipients were examined at varying times after transplantation. Biopsy samples were examined histologically. Messenger RNA was extracted from PBL and liver biopsy specimens and was then amplified by polymerase chain reaction with oligo-specific primer pairs for interleukin (IL)-2, IL-4, IL-6, transforming growth factor-beta, interferon-gamma, and beta-actin. RESULTS: PBL transcription of IL-2, IL-6, and interferon-gamma was significantly increased in transplant recipients with rejection compared with that in recipients without rejection or healthy individuals who did not undergo transplantation (p < 0.05). Equivalent transcription of IL-4 and transforming growth factor-beta was observed in all patients regardless of rejection status. Graft specimens exhibited quantitative increases in IL-2 and interferon-gamma transcription during rejection with increased IL-4 transcription in the absence of rejection. CONCLUSIONS: Our data show that specific patterns of peripheral and intragraft cytokine production play a role in the regulation of rejection in liver transplantation.

Adult↗
PubMed1995

CD4+ T cells mediate preexposure-induced increases in murine intraabdominal abscess formation.

We have previously shown that an increased number of Escherichia coli/Bacteroides fragilis intraabdominal abscesses are produced in mice after preexposure to small numbers of live E. coli or B. fragilis. Splenic lymphocyte subset changes and the importance of different elements of the immune response in this system were studied. Preexposure to bacteria induced a significant increase in the percentage of splenic T cells without altering the CD4/CD8 ratio. The passive transfer of either 10(7) mixed splenic lymphocytes, 5 x 10(6) mixed T cells, or 2.5 x 10(6) CD4+ T cells from preexposed animals to naive siblings 24 hr prior to abscess induction resulted in increased abscess formation. Transfer of serum, B cells, < 10(7) lymphocytes, CD8+ T cells, or any cell type from naive animals did not change abscess number. The bacterial composition of abscesses changed only in animals receiving either serum or B cells from donors preexposed to B. fragilis, where an increased number of B. fragilis per abscess was found. The CD4+ T cell response can be altered by transient infections and is critical to subsequent abscess formation, and a concurrent humoral response may play a role in determining an abscess' ultimate bacterial composition.

Abdominal Abscess↗
PubMed1995

The role of Candida albicans in the pathogenesis of experimental fungal/bacterial peritonitis and abscess formation.

The recovery of Candida albicans along with bacteria from the abdomen in the setting of peritonitis is becoming increasingly common. It is not known whether the interactions between the fungal and bacterial elements of these infections are synergistic, competitive, or neutral. To study this question, we have examined the effects of both the addition of C. albicans to a solely bacterial infection caused by Escherichia coli and Bacteroides fragilis, and the deletion of various components of this system using directed antimicrobial therapy. In a mixed infection, both C. albicans and bacteria contributed to mortality, since only the combination of cefoxitin and amphotericin B improved survival (from 50% to 90%). The addition of C. albicans to the bacterial inoculum increased the recovery of abscesses, but only to the number seen with fungal infection alone, implying two fairly independent processes. Although the number of bacteria recovered from abscesses at 10 days postinfection was unchanged with the addition of fungi, the deletion of the bacterial component of mixed infections led to the overgrowth of C. albicans. We conclude that this model of mixed C. albicans/E. coli/B. fragilis peritonitis is best characterized as two nonsynergistic, parallel infections with incomplete competition, allowing the survival of all three organisms to eventual abscess formation.

Abscess↗
PubMed1994

Cryptosporidium parvum infection of intestinal epithelium: morphologic and functional studies in an in vitro model.

A monolayer of mature polarized colonic epithelial cells (T84) able to generate and maintain a barrier to macromolecular flow was used to study pathophysiologic events that occur on microvillus cell exposure to Cryptosporidium parvum. By 24-48 h, several life cycle forms were seen in parasitophorous vacuoles near the apical cell surface, along with a time- and oocyst dose-dependent reduction in epithelial barrier function. As few as 10(5) organisms constituted a successful infecting dose, and heat inactivation of organisms markedly reduced the monolayer barrier alteration. Horseradish peroxidase flux studies demonstrated a substantial increase in macromolecular permeability of the monolayer, and lactate dehydrogenase determinations indicated modest injury of the T84 epithelial cells on exposure to oocysts. Thus, disruption of the epithelial cell barrier, not just opening of transcellular channels for ion flow as reported previously, is responsible for the effects of C. parvum oocysts on intestinal epithelium.

Animals↗
PubMed1994

Aztreonam vs. gentamicin in experimental peritonitis and intra-abdominal abscess formation.

The activity of gentamicin is known to be decreased in acidic environments, and both the peritoneum during peritonitis and the interior of abscesses have been shown to be acidic and hypoxic. The activity of beta-lactam antibiotics is felt to be relatively less diminished under the same circumstances. We determined that the minimum inhibitory concentration of gentamicin against one pathogenic strain of Escherichia coli increased eight-fold, to 8 mugm/mL, when testing conditions were changed from normoxic and neutral to hypoxic and acidic, whereas the MIC of aztreonam doubled under the same conditions, to 0.25 mugm/mL. In further experiments in a murine model of mixed Escherichia coli/Bacteroides fragilis intra-abdominal abscesses, we demonstrated that a combination of aztreonam and clindamycin was superior to a combination of gentamicin and clindamycin in terms of completely preventing abscess formation (33% vs. 0%) and eliminating Escherichia coli from abscesses that did form (100% vs. 61%).

Abdominal Abscess↗
PubMed1993

IFN-gamma modulation of epithelial barrier function. Time course, reversibility, and site of cytokine binding.

The single cell-thick intestinal epithelium forms a crucial barrier between the host and environment, and is modeled in vitro by a monolayer of polarized, highly differentiated T84 epithelial cells impermeable to most macromolecules because of functional intercellular tight junctions. Absence of a permeability defect across the monolayer, either transcellular or paracellular, is indicated by development of a transepithelial electrical resistance of > or = 1000 ohm-cm2, reported to be markedly diminished by exposure to a T lymphocyte cytokine, IFN-gamma. We sought to define this phenomenon in four ways by determining its duration and reversibility; the uniqueness of type II (gamma) IFN as opposed to type I (alpha) IFN; the surface of the polarized columnar epithelium likely involved in responding to IFN-gamma; and whether a specific surface membrane receptor on the epithelial cell participates in the response. Using a special apparatus that allows differential cytokine exposure of monolayer surfaces, our data demonstrate 1) only the monolayer's basolateral surface is IFN-gamma responsive, whereas the apical (microvillous) surface is no; 2) the alteration in electrical resistance of epithelium is prolonged (5 days), even after a single (24 h) exposure to IFN-gamma, but nevertheless is reversible; 3) the effect is likely receptor-ligand mediated, because it can be partially blocked by IFN-gamma receptor-specific monoclonal Ig; 4) an alteration in tight junction function (a paracellular pathway) rather than cell necrosis or a transcellular pathway is responsible for IFN-gamma-induced monolayer dysfunction because permeability to a 44,000-Da macromolecule (horseradish peroxidase) did not increase, and intracytoplasmic T84 cell enzymes were not released into the media; and 5) the biologic phenomenon could not be induced by a species (alpha) of class I IFN, making IFN-gamma reasonably unique in this regard. Given the proximity; activation status, and capacity of T lymphocytes for cytokine production in mucosa, we suggest that IFN-gamma-induced changes in epithelial permeability may be a major cause of altered intestinal barrier function in vivo.

Antibodies, Monoclonal↗
PubMed1993

Anti-tumor necrosis factor antibody reduces mortality in the presence of antibiotic-induced tumor necrosis factor release.

The systemic tumor necrosis factor (TNF) response has been extensively studied during infection. In addition, antibiotics that cause cell-wall lysis have been associated with endotoxinemia and, therefore, could trigger TNF release. We studied the effects of pretreatment with cefoxitin and/or anti-TNF antibody on mortality and early (90 minutes) and delayed (6 hours) serum TNF levels in a murine model of mixed Escherichia coli/Bacteroides fragilis peritonitis. At low and intermediate inocula levels, cefoxitin, but not anti-TNF antibody, prevented death, and low serum TNF levels were noted in all groups. At the highest inoculum level, mortality was uniform in control, cefoxitin, and anti-TNF antibody groups, and a significant elevation in serum TNF levels was seen only at the 6-hour point in animals receiving cefoxitin. The addition of anti-TNF antibody to cefoxitin at this inoculum level abrogated the 6-hour rise in serum TNF levels and reduced mortality to 40%. These results emphasize that the cytokine response in disease is dependent on both the nature of the insult and other forms of therapeutic interventions.

Animals↗
PubMed1993

A radon generator/delivery system.

A radon-generating system is described in which 222Rn, emanating from 226Ra stored in an aluminum containment vessel, may be pumped into a syringe for subsequent injection into a standard spinner flask containing tissue culture medium. The radium-containment vessel is sealed by an indium gasket and three metal bellows valves, one of which was used to fracture the glass capsule that contained 2.9 GBq of radium salt. A rotating piston pump transfers radon-enriched air from the radium-containment vessel to a delivery loop that includes a transfer syringe. The flow of air and radon through the loop is manipulated by three crossover ball valves, one of which may be set to fill the syringe. A charcoal trap is provided to collect residual radon left in the delivery loop after the transfer syringe has been filled. The protocol used to expose cells to radon and its progeny is described as well as the dosimetry that is used to estimate the dose delivered to the cells. A description of safety precautions taken in fabricating the generator and in conducting radiobiological studies is also presented.

Radiation Protection↗
PubMed1992

A controlled trial of scheduled replacement of central venous and pulmonary-artery catheters.

BACKGROUND: The incidence of infection increases with the prolonged use of central vascular catheters, but it is unclear whether changing catheters every three days, as some recommend, will reduce the rate of infection, It is also unclear whether it is safer to change a catheter over a guide wire or insert it at a new site. METHODS: We conducted a controlled trial in adult patients in intensive care units who required central venous or pulmonary-artery catheters for more than three days. Patients were assigned randomly to undergo one of four methods of catheter exchange: replacement every three days either by insertion at a new site (group 1) or by exchange over a guide wire (group 2), or replacement when clinically indicated either by insertion at a new site (group 3) or by exchange over a guide wire (group 4). RESULTS: Of the 160 patients, 5 percent had catheter-related bloodstream infections, 16 percent had catheters that became colonized, and 9 percent had major mechanical complications. The incidence rates (per 1000 days of catheter use) of bloodstream infection were 3 in group 1, 6 in group 2, 2 in group 3, and 3 in group 4; the incidence rates of mechanical complications were 14, 4, 8, and 3, respectively. Patients randomly assigned to guide-wire-assisted exchange were more likely to have bloodstream infection after the first three days of catheterization (6 percent vs. 0, P = 0.06). Insertions at new sites were associated with more mechanical complications (5 percent vs. 1 percent, P = 0.005). CONCLUSIONS: Routine replacement of central vascular catheters every three days does not prevent infection. Exchanging catheters with the use of a guide wire increases the risk of bloodstream infection, but replacement involving insertion of catheters at new sites increases the risk of mechanical complications.

Antisepsis↗