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1.
Brain Stimul ; 17(1): 35-38, 2024.
Article in English | MEDLINE | ID: mdl-38128826

ABSTRACT

BACKGROUND: Essential tremor (ET) can be debilitating. Treatments for ET include beta-blockers and surgical interventions. Low-intensity focused ultrasound (LIFU) may offer an office-based non-invasive alternative. OBJECTIVE: This pilot open label clinical trial explores safety, feasibility, and potential efficacy of LIFU in treatment of ET. METHODS: We report outcomes from the first 10 participants in this IRB-approved trial of LIFU for treatment of ET. The ventral intermediate nucleus of the thalamus (Vim) was targeted using structural and functional MRI. Participants underwent eight 10-min sessions of LIFU targeting the contralateral (Vim) to the most affected hand. Safety was closely monitored; Global Rating of Change (GRC) and The Essential Tremor Rating Scale (TETRAS) scores were collected. RESULTS: No adverse effects were reported. Eight participants reported a GRC ≥2. TETRAS performance subscale demonstrated clinically significant improvement in all participants. CONCLUSION: Preliminary findings support LIFU's safety and feasibility. The potential efficacy encourages additional sham-controlled studies.


Subject(s)
Essential Tremor , Tremor , Humans , Essential Tremor/diagnostic imaging , Essential Tremor/therapy , Magnetic Resonance Imaging , Thalamus/diagnostic imaging , Treatment Outcome , Pilot Projects
2.
Psychol Med ; 44(8): 1639-51, 2014 Jun.
Article in English | MEDLINE | ID: mdl-23930595

ABSTRACT

BACKGROUND: Research in bipolar disorder (BD) implicates fronto-limbic-striatal dysfunction during face emotion processing but it is unknown how such dysfunction varies by task demands, face emotion and patient age. METHOD: During functional magnetic resonance imaging (fMRI), 181 participants, including 62 BD (36 children and 26 adults) and 119 healthy comparison (HC) subjects (57 children and 62 adults), engaged in constrained and unconstrained processing of emotional (angry, fearful, happy) and non-emotional (neutral) faces. During constrained processing, subjects answered questions focusing their attention on the face; this was processed either implicitly (nose width rating) or explicitly (hostility; subjective fear ratings). Unconstrained processing consisted of passive viewing. RESULTS: Pediatric BD rated neutral faces as more hostile than did other groups. In BD patients, family-wise error (FWE)-corrected region of interest (ROI) analyses revealed dysfunction in the amygdala, inferior frontal gyrus (IFG), anterior cingulate cortex (ACC) and putamen. Patients with BD showed amygdala hyperactivation during explicit processing (hostility ratings) of fearful faces and passive viewing of angry and neutral faces but IFG hypoactivation during implicit processing of neutral and happy faces. In the ACC and striatum, the direction of dysfunction varied by task demand: BD demonstrated hyperactivation during unconstrained processing of angry or neutral faces but hypoactivation during constrained processing (implicit or explicit) of angry, neutral or happy faces. CONCLUSIONS: Findings suggest amygdala hyperactivation in BD while processing negatively valenced and neutral faces, regardless of attentional condition, and BD IFG hypoactivation during implicit processing. In the cognitive control circuit involving the ACC and putamen, BD neural dysfunction was sensitive to task demands.


Subject(s)
Amygdala/physiopathology , Attention/physiology , Bipolar Disorder/physiopathology , Facial Expression , Gyrus Cinguli/physiopathology , Prefrontal Cortex/physiopathology , Putamen/physiopathology , Adolescent , Adult , Child , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Young Adult
3.
Psychophysiology ; 45(3): 435-44, 2008 May.
Article in English | MEDLINE | ID: mdl-18221443

ABSTRACT

Increasing evidence suggests that emotion regulation (ER) strategies modulate encoding of information presented during regulation; however, no studies have assessed the impact of cognitive reappraisal ER strategies on the processing of stimuli presented after the ER period. Participants in the present study regulated emotions to unpleasant pictures and then judged whether a word was negative or neutral. Electromyographic measures (corrugator supercilli) confirmed that individuals increased and decreased negative affect according to ER condition. Event-related potential analyses revealed smallest N400 amplitudes to negative and neutral words presented after decreasing unpleasant emotions and smallest P300 amplitudes to words presented after increasing unpleasant emotions whereas reaction time data failed to show ER modulations. Results are discussed in the context of the developing ER literature, as well as theories of emotional incongruity (N400) and resource allocation (P300).


Subject(s)
Cognition/physiology , Emotions/physiology , Adult , Data Interpretation, Statistical , Electroencephalography , Electromyography , Event-Related Potentials, P300/physiology , Evoked Potentials/physiology , Female , Humans , Male , Photic Stimulation , Psychomotor Performance/physiology , Reaction Time/physiology
4.
Dis Esophagus ; 20(3): 269-73, 2007.
Article in English | MEDLINE | ID: mdl-17509126

ABSTRACT

The long-term effects of gastric banding on esophageal function are not well described. This report describes a 28-year-old woman who developed signs and symptoms of abnormal esophageal motility and lower esophageal sphincter hypotension after gastric banding for morbid obesity. The current literature addressing the effects of gastric banding on esophageal function in light of this case report is discussed.


Subject(s)
Esophageal Motility Disorders/etiology , Gastroplasty/adverse effects , Obesity, Morbid/surgery , Adult , Female , Humans
5.
Surg Endosc ; 21(9): 1593-9, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17294310

ABSTRACT

BACKGROUND: Non-alcoholic steatohepatitis (NASH) is a major cause of liver disease in morbidly obese patients. Clinical predictors of NASH remain elusive, as do molecular mechanisms of pathogenesis. METHODS: A series of 35 morbidly obese patients undergoing bariatric surgery had a liver biopsy performed for standard histologic analysis. In addition, RNA was obtained from liver tissue and analyzed for leptin receptor gene expression. Regression analysis was used to correlate clinical variables, including serum leptin levels and hepatic leptin receptor gene expression, with the presence of histologically confirmed NASH. RESULTS: Of the 35 subjects enrolled, 29% had steatosis only, 60% had NASH, and 11% had normal liver histology. Among the clinical variables studied, only diabetes mellitus was an independent predictor of NASH. There was a trend toward lower levels of mRNA encoding the long form of the leptin receptor in hepatic tissue from patients with NASH compared to those with steatosis only. CONCLUSIONS: Diabetes mellitus is associated with an increased risk of NASH in obese patients. Downregulation of hepatic leptin receptor may play a role in the pathogenesis of NASH.


Subject(s)
Bariatric Surgery , Fatty Liver/diagnosis , Leptin/blood , Liver/metabolism , Obesity, Morbid/complications , Receptors, Cell Surface/metabolism , Adult , Biomarkers/blood , Fatty Liver/etiology , Female , Humans , Male , Middle Aged , Obesity, Morbid/metabolism , Obesity, Morbid/surgery , Receptors, Cell Surface/genetics , Receptors, Leptin , Risk Factors , Transcription, Genetic
6.
Clin Exp Immunol ; 146(1): 39-46, 2006 Oct.
Article in English | MEDLINE | ID: mdl-16968396

ABSTRACT

Obesity is characterized by alterations in immune and inflammatory function. In order to evaluate the potential role of cytokine expression by peripheral blood mononuclear cells (PBMC) in obesity-associated inflammation, we studied serum protein levels and mRNA levels in PBMC of interleukin (IL)-6, IL-1beta, tumour necrosis factor (TNF)-alpha and IL-1Ra in nine lean and 10 obese subjects. Serum IL-1beta was undetectable, IL-1Ra serum levels were elevated, serum levels of TNF-alpha were decreased and serum levels of IL-6 were similar in obese subjects compared to lean subjects, while transcript levels of IL-6, IL-1beta and TNF-alpha, but not IL-1Ra, were decreased in PBMC from obese subjects. PBMC from obese subjects did, however, up-regulate cytokine expression in response to leptin. Thus, obesity-associated changes in IL-1Ra serum levels and IL-6 mRNA levels were not correlated with changes in cognate mRNA and serum levels, respectively, while TNF-alpha serum levels and PBMC mRNA levels were both decreased in obese patients. While immune alterations in obesity are manifest in peripheral blood lymphocytes, the general lack of correlation between altered serum levels and altered PBMC gene expression suggests that PBMC may not be the source of aberrant serum cytokine levels in obesity.


Subject(s)
Cytokines/biosynthesis , Leukocytes, Mononuclear/immunology , Obesity, Morbid/immunology , Adult , Body Mass Index , Cells, Cultured , Cytokines/blood , Cytokines/genetics , Enzyme-Linked Immunosorbent Assay/methods , Female , Gene Expression Regulation/drug effects , Gene Expression Regulation/immunology , Humans , Leptin/pharmacology , Leukocytes, Mononuclear/drug effects , Male , Middle Aged , Obesity, Morbid/physiopathology , RNA, Messenger/genetics , Reverse Transcriptase Polymerase Chain Reaction/methods
7.
Surg Endosc ; 17(10): 1566-9, 2003 Oct.
Article in English | MEDLINE | ID: mdl-12874692

ABSTRACT

BACKGROUND: We sought to determine the learning curve for laparoscopic adrenalectomy (LA), current use of the procedure, and if indications for adrenalectomy had changed in the past decade. METHODS: A retrospective chart review was performed for all adrenalectomies after 1990. Practicing community surgeons in Oregon were mailed a questionnaire. RESULTS: Seventy-five LAs were performed at the Oregon Health and Sciences University and Portland VA Medical Center. Average operating room (OR) time was 161 min and average estimated blood loss (EBL) was 84 ml. There were four complications and two conversions. Comparing the first 20 to the last 20 patients, OR times were 154 vs 159 min (not significant), and EBL was 102 vs 47 ml ( p < 0.05). There were two vs one complications ( p > 0.05) and one conversion each. Most residents completed less than two procedures during training, and community surgeons performed none during training. Of 17 currently performing LA, 14 had postresidency training. Open technique was used more often for hormonal ablation and malignancy. CONCLUSION: Operative time and complications do not decrease with experience, but EBL does. Few, if any, residents acquire enough experience to perform LA in practice. The procedure is performed laparoscopically more often for benign disease.


Subject(s)
Adrenalectomy/education , Adrenalectomy/methods , Internship and Residency/statistics & numerical data , Laparoscopy/statistics & numerical data , Adrenal Gland Neoplasms/surgery , Adrenalectomy/statistics & numerical data , Blood Loss, Surgical/statistics & numerical data , Cushing Syndrome/surgery , Humans , Length of Stay , Oregon , Pheochromocytoma/surgery , Population Surveillance , Treatment Outcome
8.
Am J Surg ; 181(5): 459-62, 2001 May.
Article in English | MEDLINE | ID: mdl-11448443

ABSTRACT

BACKGROUND: Persistent stricturing or anastomotic leakage at the cervical esophagogastric anastomosis can be a troublesome complication of gastric pull-up procedures. When the stricture is the result of ischemia of the stomach, the strictures are long and often not responsive to dilatation and require large operations such as jejunal interposition or replacement with colonic pull-up. In this report we describe the use of a radial forearm flap to patch strictures. METHODS: The radial forearm flap is a fascia cutaneous flap taken from the forearm and based on the radial artery and its venae comitantes. The advantages of this flap are that it is thin and pliable, conforms easily, has excellent reliability due to the size of the feeding vessels, and has a relatively long pedicle. The vascular anastomosis can be made to several arteries and veins within the neck. The epithelial component can be made in sizes up to 10 by 20 cm. RESULTS: We have used the radial forearm flap to patch strictures in 6 patients with persistent complex strictures in the cervical region after esophagectomy. Results were excellent in 4 patients (able to eat liquids and solids without problems) and good in 1 patient (liquids okay, some problem with solids), and 1 patient died postoperatively. Follow-up is 4 months to 7 years. CONCLUSIONS: The radial forearm flap is an excellent option for handling persistent stricture after esophagogastrectomy. In many instances, this flap can be used in lieu of a jejunal interposition flap and obviates a laparotomy to harvest jejunum. The flap fits easily into the neck and conforms to the space.


Subject(s)
Esophageal Stenosis/etiology , Esophagectomy/methods , Gastrectomy/methods , Surgical Flaps , Adult , Esophageal Stenosis/surgery , Female , Follow-Up Studies , Forearm/surgery , Humans , Ischemia/prevention & control , Male , Middle Aged , Postoperative Complications/prevention & control , Radial Artery/transplantation , Treatment Outcome
9.
Am J Surg ; 181(5): 440-4, 2001 May.
Article in English | MEDLINE | ID: mdl-11448438

ABSTRACT

BACKGROUND: Neoadjuvant chemoradiotherapy is administered to patients with esophageal carcinoma with the belief that this will both downstage the tumor and improve survival. Endoscopic ultrasound (EUS) is currently the most accurate method of staging esophageal cancer for tumor (T) and lymph node (N) status. Because both EUS and neoadjuvant therapy for esophageal carcinoma are relatively new, there are few data examining the relationship between EUS stage and histological stage (the stage after resection) in patients receiving neoadjuvant therapy. METHODS: To determine the effect of neoadjuvant chemoradiotherapy on T and N stage as determined by EUS, we retrospectively compared two groups of patients with esophageal cancer staged by EUS. One group (33 patients) underwent neoadjuvant therapy (Walsh protocol: 5-fluorouracil, cisplatin, and 4000 rads of external beam radiation) followed by resection. The second group (22 patients), a control group, underwent resection without neoadjuvant therapy. We then compared histological stage to determine if there was a downstaging in the patients receiving neoadjuvant therapy. Survival was evaluated as well. RESULTS: EUS accurately predicted histologic stage. In the control group EUS overestimated T stage in 3 of 22 (13%), underestimated N stage in 2 of 22 (9%), and overestimated N stage in 2 of 22 (9%) of patients. Preoperative radiochemotherapy downstaged (preoperative EUS stage versus pathologic specimen) 12 of 33 (36%) of patients whereas only 1 of 22 (5%) of patients in the control group was downstaged. Complete response (no tumor found in the surgical specimen) was observed in 5 of 33 (15%) of patients receiving radiochemotherapy. Survival was prolonged significantly in patients receiving radiochemotherapy: 20.6 months versus 9.6 months for those (stage II or III) patients not receiving radiochemotherapy (P <0.01). Operative time, operative blood loss, and length of stay were not significantly different between groups. Perioperative mortality was higher in the radiochemotherapy group (13%) compared with the no radiochemotherapy group (5%) but did not achieve statistical significance. CONCLUSIONS: EUS accurately stages esophageal carcinoma. Neoadjuvant radiochemotherapy downstages esophageal carcinoma for T and N status. In our nonrandomized study, neoadjuvant therapy conferred a significant survival advantage. Operative risk appears to be increased in patients receiving neoadjuvant radiochemotherapy prior to esophagectomy.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Endosonography , Esophageal Neoplasms/therapy , Neoplasm Staging , Adult , Aged , Aged, 80 and over , Cisplatin/administration & dosage , Combined Modality Therapy , Esophageal Neoplasms/pathology , Female , Fluorouracil/administration & dosage , Humans , Male , Middle Aged , Neoadjuvant Therapy , Predictive Value of Tests , Preoperative Care , Prognosis , Radiotherapy, Adjuvant , Retrospective Studies , Sensitivity and Specificity , Survival Analysis , Treatment Outcome
10.
J Abnorm Psychol ; 110(2): 267-81, 2001 May.
Article in English | MEDLINE | ID: mdl-11358021

ABSTRACT

Mood-congruent working memory biases were examined in a delayed matching to sample paradigm using the slow wave (SW) event-related brain potential (ERP) component. Mood-congruent working memory biases, indexed by SW amplitudes, were demonstrated among individuals experiencing a major depressive episode (MDE) and nondepressed controls but not individuals with dysthymia. However, analyses of symptom severity demonstrated that those with dysthymia exhibited significantly less negative SW amplitudes with increasing depressive mood severity, whereas individuals with major depression demonstrated more negative SW amplitudes with increasing depressive mood severity. These results are discussed in the context of diagnostic specificity for cognitive biases associated with working memory of mood-disordered individuals.


Subject(s)
Electroencephalography , Memory Disorders/diagnosis , Memory Disorders/etiology , Mood Disorders/psychology , Adult , Electrooculography , Female , Humans , Male , Middle Aged , Reaction Time , Severity of Illness Index
11.
Surg Endosc ; 15(1): 34-7, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11178758

ABSTRACT

BACKGROUND: The gold standard for the surgical treatment of Zenker's diverticulum is diverticulectomy and cricopharyngeal myotomy by an external approach. Unfortunately, many of the patients who present with this entity are elderly and have significant comorbidities that increase operative risk. Traditional minimally invasive approaches have not met with widespread success. However, by combining the exposure afforded by the otolaryngologist's newer bivalved operating laryngoscopes with the operative techniques made possible by the general surgeon's laparoscopic instrumentation and staplers, it is possible to achieve reliable and safe endoscopic outpatient management of this disease entity, with resumption of a normal diet on the same day. METHODS: We reviewed the physiologic basis, instrumentation, and technical considerations for this endoscopic procedure. We also documented our operative experience with 21 patients treated over an 18-month period. RESULTS: Successful minimally invasive management of Zenker's diverticulum was possible in 18 of 21 patients. In two patients, anatomic limitations of mouth and neck anatomy precluded exposure of the diverticulum; in another patient, the diverticulum was too small. Small operative perforations of the apex of the diverticulum occurred in three cases. Two of these perforations were repaired primarily with minimally invasive techniques; in the other case, treatment consisted of observation alone. In all but this last patient, oral diet was resumed on the day of the operation. Eleven of the patients were discharged from the hospital on the same day; the remaining patients went home the following morning. CONCLUSIONS: With proper patient selection, minimally invasive management of Zenker's diverticulum is a safe and effective surgical technique that allows for outpatient management of the majority of patients who present with this disease.


Subject(s)
Cricoid Cartilage/surgery , Endoscopy , Pharynx/surgery , Zenker Diverticulum/surgery , Humans , Laryngoscopy
12.
Arch Surg ; 135(8): 902-6, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10922249

ABSTRACT

HYPOTHESIS: Laparoscopic Heller myotomy with anterior fundoplication will alleviate the symptoms of achalasia and result in excellent patient satisfaction. DESIGN: Retrospective study of consecutive patients who underwent laparoscopic Heller myotomy with anterior fundoplication for achalasia between October 1995 and July 1999. A telephone survey assessed symptoms and satisfaction. Patients were asked to quantitate their symptoms on a scale of 0 to 3 (0 = none; 1, mild; 2, moderate; and 3, severe). SETTING: University referral center. PATIENTS: Twenty-four patients who underwent laparoscopic Heller myotomy with anterior fundoplication for achalasia. MAIN OUTCOME MEASURES: Postoperative symptoms and satisfaction. RESULTS: Twenty-one patients (88%) were successfully contacted. Mean follow-up was 16.5 months. The laparoscopic approach was successful in all but 3(88%). The mean dysphagia score was 2.81 preoperatively and 0.81 postoperatively (P<.000). The mean chest pain score was 1. 57 preoperatively and 0.86 postoperatively (P<.015). The mean supine regurgitation score was 2.10 preoperatively and 0.57 postoperatively (P<.000). The mean upright regurgitation score was 1.57 preoperatively and 0.52 postoperatively (P<.000). The mean heartburn score was 1.57 preoperatively and 0.57 postoperatively (P<.000). Postoperatively, 18 (86%) of 21 patients could swallow bread without difficulty and 17 (89%) of 19 patients could eat meat without difficulty (2 were excluded as they were vegetarians). Twenty (95%) of 21 patients reported improvement after the operation. CONCLUSIONS: Laparoscopic Heller myotomy with anterior fundoplication significantly relieves the symptoms of achalasia without causing the symptoms of gastroesophageal reflux disease. This procedure results in excellent overall patient satisfaction.


Subject(s)
Esophageal Achalasia/surgery , Esophagogastric Junction/surgery , Fundoplication/methods , Laparoscopy/methods , Patient Satisfaction , Adolescent , Adult , Aged , Aged, 80 and over , Bread , Chest Pain/physiopathology , Deglutition/physiology , Deglutition Disorders/physiopathology , Esophageal Achalasia/physiopathology , Female , Follow-Up Studies , Fundoplication/psychology , Gastroesophageal Reflux/physiopathology , Heartburn/physiopathology , Humans , Interviews as Topic , Laparoscopy/psychology , Male , Meat , Middle Aged , Retrospective Studies , Treatment Outcome
13.
Surg Endosc ; 13(11): 1121-4, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10556451

ABSTRACT

BACKGROUND: Anecdotal reports of port site tumor recurrence have dampened the enthusiasm for laparoscopic colectomy for cancer. We developed a rat model that creates a high incidence of port site metastasis following laparoscopic intervention. Our goal was to assess the feasibility of minimizing implantations using port site irrigation prior to wound closure. METHODS: Colon cancer carcinomatosis was established in 46 female BD9 rats using intraperitoneal injections of 10(6) DHD-K12-TRb rat colon cancer cells. This preparation yielded an 81% incidence of port site metastasis in a control group. Laparoscopic sham surgery was performed using four ports and a CO(2) pneumoperitoneum. Four treatment groups were studied by irrigating each port site as follows: Group I, sterile water; group II, normal saline; group III, heparin; group IV, 5-fluorouracil (5-FU). The animals were killed at 4 weeks, and the port sites were examined for tumors. RESULTS: There were no differences in port site metastasis between controls and groups I, II, and III. The 5-FU group showed a significant decrease (30% vs 81%) in metastasis. CONCLUSIONS: Port site irrigation with 5-FU at the time of laparoscopy reduces the incidence of port site tumor implantation in a rat colon cancer model. This finding may have utility in patients at high risk of such metastasis who undergo laparoscopy for colon cancer.


Subject(s)
Colonic Neoplasms/surgery , Fluorouracil/therapeutic use , Laparoscopy/adverse effects , Neoplasm Seeding , Administration, Topical , Animals , Colectomy/methods , Female , Fluorouracil/administration & dosage , Male , Rats , Risk Factors
14.
Am J Physiol ; 277(3): G662-70, 1999 09.
Article in English | MEDLINE | ID: mdl-10484392

ABSTRACT

The purpose of the present study was to determine whether human gastric mucous epithelial cells express a functional Ca2+-sensing receptor (CaR). Human gastric mucous epithelial cells were isolated from surgical tissues and cultured on glass coverslips, plastic dishes, or porous membrane filters. Cell growth was assessed by the MTT assay, CaR localization was detected by immunohistochemistry and confocal microscopy, CaR protein expression was assessed by Western immunoblotting, and intracellular Ca2+ concentration ([Ca2+]i) was determined by fura 2 spectrofluorometry. In paraffin sections of whole stomach, we found strong CaR immunohistochemical staining at the basolateral membrane, with weak CaR-staining at the apical membrane in mucous epithelial cells. Confocal microscopy of human gastric mucous epithelial cell cultures showed abundant CaR immunofluorescence at the basolateral membrane and little to no CaR immunoreactivity at the apical membrane. Western immunoblot detection of CaR protein in cell culture lysates showed two significant immunoreactive bands of 140 and 120 kDa. Addition of extracellular Ca2+ to preconfluent cultures of human gastric mucous epithelial cells produced a significant proliferative response. Changes in [Ca2+]i were also observed in response to graded doses of extracellular Ca2+ and Gd3+. The phospholipase C inhibitor U-73122 specifically inhibited Gd3+-induced changes in [Ca2+]i in the gastric mucous epithelial cell cultures. In conclusion, we have identified the localization of a functional CaR in human gastric mucous epithelial cells.


Subject(s)
Gastric Mucosa/metabolism , Receptors, Cell Surface/metabolism , Blotting, Western , Calcium/physiology , Cell Division/physiology , Cells, Cultured , Extracellular Space/metabolism , Gadolinium/metabolism , Gastric Mucosa/cytology , Humans , Immunohistochemistry , Microscopy, Confocal , Receptors, Calcium-Sensing , Reference Values
15.
Pancreas ; 19(2): 183-92, 1999 Aug.
Article in English | MEDLINE | ID: mdl-10438166

ABSTRACT

It has been reported that various mutants of the E1A-adenovirus can activate quiescent differentiated cells to start proliferating. The aim of this study was to determine whether transfection with E1A-12S could extend the life span and functionality of pancreatic islets in culture. Rat pancreatic islets were isolated and transfected with retrovirus containing the adenovirus E1A-12S, E1A-13S, or control vectors. Transfection with the retroviral E1A-13S mutant produced extensive islet necrosis compared with nontransfected islets. Islets transfected with the control E1A mutant Ad5-dl312 vector (containing no E1A-12S or E1A-13S segments) were similar to nontransfected islets in their characteristics. We found that the E1A-12S transfected islets maintained greater viability, insulin granule structure, and glucose-induced insulin responsiveness over a 6-week period compared with mock or control islets. At 6 weeks of culture, the E1A-12S transfected islets also had fewer apoptotic cells compared with nontransfected islets. These data suggest that adenovirus E1A-12S can extend the functional life span of cultured rat pancreatic islets.


Subject(s)
Adenovirus E1A Proteins/metabolism , Adenoviruses, Human/genetics , Insulin/metabolism , Islets of Langerhans/cytology , Islets of Langerhans/physiology , 3T3 Cells , Adenovirus E1A Proteins/genetics , Animals , Cell Line , Cell Survival , Cells, Cultured , Cytoplasmic Granules/physiology , Cytoplasmic Granules/ultrastructure , Genetic Vectors , Humans , Insulin Secretion , Mice , Peptide Fragments/metabolism , Rats , Recombinant Proteins/metabolism , Time Factors , Transfection
16.
Cancer ; 85(7): 1454-64, 1999 Apr 01.
Article in English | MEDLINE | ID: mdl-10193934

ABSTRACT

BACKGROUND: The specific paclitaxel dose or time course in the treatment of colon carcinoma without the disruption of normal colonic cell proliferation is currently not known. The aim of this study was to determine the effects of paclitaxel on the growth of human colonic epithelial cells using cultures of normal, polyposis, and cancerous cells. METHODS: Normal, polyposis, and cancerous human colonic cells (Caco-2, T-84, and LoVo cell lines) were cultured, then treated with paclitaxel (10(-9)-10(-5) M) for 0-7 days.[AU: Please verify all dosages throughout.] Cell proliferation was assayed using either a Coulter-Counter or MTT-growth assay. Immunofluorescence and Western immunoblotting measured P-glycoprotein. RESULTS: Low paclitaxel doses (1 x 10(-9)-10(-8) M) were more effective than higher paclitaxel doses (>1 x 10(-8) M) in the growth inhibition of polyposis, Caco-2, and LoVo cancer (but not T-84) cell lines. Low paclitaxel doses had little effect on normal colonic cell growth over 7 days. Higher paclitaxel doses (>1 x 10(-8)-10(-5) M) produced a dose-dependent inhibitory effect on the growth of normal human colonic epithelial cells over 7 days but had no effect on the growth of polyposis, Caco-2, and LoVo cells over 3-7 days of treatment. Immunofluorescence and Western immunoblotting of cultures showed that 1 x 10(-6) M paclitaxel increased P-glycoprotein expression in Caco-2 and LoVo cells. There was no effect of paclitaxel on P-glycoprotein expression in T-84 cancer cells, which were found to have high endogenous basal levels of P-glycoprotein. P-glycoprotein expression in Caco-2 cells was found on plasma membranes and in perinuclear areas. CONCLUSIONS: Lower paclitaxel doses are more effective over time for the growth inhibition of polyposis and cancerous colonic cells, with minimal effects on the growth of normal colonic epithelial cells. Increased P-glycoprotein expression appears to be correlated with paclitaxel resistance in polyposis and cancerous colonic cells.


Subject(s)
Adenomatous Polyposis Coli/pathology , Antineoplastic Agents, Phytogenic/pharmacology , Colon/drug effects , Colonic Neoplasms/pathology , Paclitaxel/pharmacology , ATP Binding Cassette Transporter, Subfamily B, Member 1/analysis , Cells, Cultured , Dimethyl Sulfoxide/pharmacology , Dose-Response Relationship, Drug , Epithelial Cells/drug effects , Humans , Tumor Cells, Cultured
17.
Arch Surg ; 134(3): 278-81; discussion 282, 1999 Mar.
Article in English | MEDLINE | ID: mdl-10088568

ABSTRACT

BACKGROUND: Two of us (B.C.S. and C.W.D.) began performing laparoscopic fundoplication in 1992. We have always designated the resident as the operating surgeon. OBJECTIVE: To determine the time necessary for both experienced surgeons and residents to become proficient in laparoscopic fundoplication. DESIGN: The medical records of 241 consecutive patients undergoing laparoscopic fundoplication were reviewed. This period started with the implementation of the procedure in January 1992 and ended in March 1998. For 3 consecutive years, residents were given a questionnaire regarding their confidence in performing laparoscopic fundoplication. RESULTS: Laparoscopic fundoplication was attempted in 241 patients and completed in 203 patients (84%). Comparing the first 25 attempted laparoscopic fundoplications with the second 25, there were 14 conversions (56%) vs 4 conversions (16%) (P<.01). Average operative times decreased from 236 to 199 minutes (P<.05), and the intraoperative complication rates were 5 (20%) and 1 (4%), respectively. Subsequently, the conversion rate stabilized at 2%. The operative time continued to decline to an average of 99 minutes for the last 25 laparoscopies. Senior residents and recent graduates returning the questionnaire performed an average of 112 laparoscopic procedures, including 15.7 laparoscopic fundoplications. They felt comfortable with the procedure after performing an average of 10.6 operations. CONCLUSIONS: The learning curve is very steep for the first 25 laparoscopic fundoplications for experienced surgeons. However, improvements, as judged by decreases in operative time, conversion rate, and intraoperative complications, continue to occur after 100 cases. Under supervision, residents can become comfortable with this procedure after about 10 to 15 procedures.


Subject(s)
Clinical Competence , Fundoplication/methods , Internship and Residency , Laparoscopy , Female , Humans , Male , Middle Aged , Surveys and Questionnaires , Time Factors
19.
Am J Gastroenterol ; 93(11): 2257-60, 1998 Nov.
Article in English | MEDLINE | ID: mdl-9820410

ABSTRACT

Endoscopic ultrasound (EUS) of the esophagus has been used primarily in staging biopsy-proven cancers. Its use as a primary diagnostic modality for esophageal malignancy has not been previously described. We report our recent experience in four patients with dysphagia and endoscopic biopsies negative for malignancy, including one patient with clinical and manometric features suggestive of achalasia. In all cases, EUS revealed a large infiltrating tumor invading through the esophageal wall into the surrounding tissues, and in one case into the aorta. Computed tomography suggested the possibility of a tumor in only one of the cases. Two patients underwent esophagectomy and were found to have adenocarcinoma. Two patients underwent repeat biopsy with alternative aggressive biopsy techniques and were found to have squamous cell carcinoma. We conclude that EUS is useful in the diagnosis of esophageal cancer and should be performed in selected patients with esophageal strictures whose biopsies are negative for malignancy; i.e., those with suspicious endoscopic or radiographic appearance, atypical presentation (e.g., profound weight loss, short duration of symptoms, or advanced age), and failure to respond to treatment.


Subject(s)
Adenocarcinoma/diagnosis , Carcinoma, Squamous Cell/diagnosis , Endosonography , Esophageal Neoplasms/diagnosis , Esophageal Stenosis/diagnosis , Adenocarcinoma/complications , Adenocarcinoma/surgery , Aged , Biopsy , Carcinoma, Squamous Cell/complications , Carcinoma, Squamous Cell/surgery , Esophageal Neoplasms/complications , Esophageal Neoplasms/surgery , Esophageal Stenosis/etiology , Esophagectomy , Humans , Male , Middle Aged
20.
Am J Surg ; 175(5): 371-4, 1998 May.
Article in English | MEDLINE | ID: mdl-9600280

ABSTRACT

BACKGROUND: We reviewed Nissen fundoplications performed in a single practice from January 1989 to March 1997, encompassing our transition from open to laparoscopic procedures. Because all operations were done by two surgeons in the same two hospitals, the study is well controlled for comparisons. METHODS: Records of 271 consecutive patients were reviewed. RESULTS: From 1989 to 1992 all patients underwent open fundoplication (n = 78). Thereafter, with increasing frequency, laparoscopic fundoplication was performed. The laparoscopic group was slightly younger (48 +/- 14 years) than the open group (54 +/- 13 years), but gender distribution and body mass index (BMI) did not differ. Mean operating time for laparoscopic cases was 163 +/- 58 minutes compared with 148 +/- 59 minutes for open cases (NS). Intraoperative complication rate was 8% for both groups. Length of hospitalization was shorter for patients undergoing laparoscopic surgery (2.4 days versus 7.2 for open procedures, P <0.05). In follow-up, 82% of the open Nissen group were asymptomatic compared with 84% of the laparoscopic Nissen group. The same proportion of patients required reoperation for dysphagia (3% for each group). Of patients who had the open procedure, 21% had wound complications. None of those treated laparoscopically had long-term morbidity from trocar insertion sites. CONCLUSION: Equal effectiveness in treating reflux combined with shorter hospitalization and absence of wound complications makes the laparoscopic approach the preferred method for performing fundoplication.


Subject(s)
Fundoplication/methods , Laparoscopy/methods , Adult , Aged , Analysis of Variance , Evaluation Studies as Topic , Female , Follow-Up Studies , Fundoplication/statistics & numerical data , Gastroesophageal Reflux/diagnosis , Gastroesophageal Reflux/surgery , Humans , Intraoperative Complications/epidemiology , Laparoscopy/statistics & numerical data , Male , Middle Aged , Patient Satisfaction , Postoperative Complications/epidemiology , Time Factors , Treatment Outcome
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