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1.
Nature ; 568(7752): 357-359, 2019 04.
Article in English | MEDLINE | ID: mdl-30996316

ABSTRACT

During the dawn of chemistry1,2, when the temperature of the young Universe had fallen below some 4,000 kelvin, the ions of the light elements produced in Big Bang nucleosynthesis recombined in reverse order of their ionization potential. With their higher ionization potentials, the helium ions He2+ and He+ were the first to combine with free electrons, forming the first neutral atoms; the recombination of hydrogen followed. In this metal-free and low-density environment, neutral helium atoms formed the Universe's first molecular bond in the helium hydride ion HeH+ through radiative association with protons. As recombination progressed, the destruction of HeH+ created a path to the formation of molecular hydrogen. Despite its unquestioned importance in the evolution of the early Universe, the HeH+ ion has so far eluded unequivocal detection in interstellar space. In the laboratory the ion was discovered3 as long ago as 1925, but only in the late 1970s was the possibility that HeH+ might exist in local astrophysical plasmas discussed4-7. In particular, the conditions in planetary nebulae were shown to be suitable for producing potentially detectable column densities of HeH+. Here we report observations, based on advances in terahertz spectroscopy8,9 and a high-altitude observatory10, of the rotational ground-state transition of HeH+ at a wavelength of 149.1 micrometres in the planetary nebula NGC 7027. This confirmation of the existence of HeH+ in nearby interstellar space constrains our understanding of the chemical networks that control the formation of this molecular ion, in particular the rates of radiative association and dissociative recombination.

2.
Astrophys J Lett ; 868(1)2018.
Article in English | MEDLINE | ID: mdl-30778373

ABSTRACT

Sulfur has been observed to be severely depleted in dense clouds leading to uncertainty in the molecules that contain it and the chemistry behind their evolution. Here, we aim to shed light on the sulfur chemistry in young stellar objects (YSOs) by using high-resolution infrared spectroscopy of absorption by the ν 3 rovibrational band of SO2 obtained with the Echelon-Cross-Echelle Spectrograph on the Stratospheric Observatory for Infrared Astronomy. Using local thermodynamic equilibrium models we derive physical parameters for the SO2 gas in the massive YSO MonR2 IRS3. This yields a SO2/H abundance lower limit of 5.6 ± 0.5 × 10-7, or >4% of the cosmic sulfur budget, and an intrinsic line width (Doppler parameter) of b < 3.20 km s-1. The small line widths and high temperature (T ex = 234 ± 15 K) locate the gas in a relatively quiescent region near the YSO, presumably in the hot core where ices have evaporated. This sublimation unlocks a volatile sulfur reservoir (e.g., sulfur allotropes as detected abundantly in comet 67P/Churyumov-Gerasimenko), which is followed by SO2 formation by warm, dense gas-phase chemistry. The narrowness of the lines makes formation of SO2 from sulfur sputtered off grains in shocks less likely toward MonR2 IRS3.

3.
Isr Med Assoc J ; 16(11): 714-7, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25558702

ABSTRACT

BACKGROUND: Discharge summaries after hospitalization provide the most reliable description and implications of the hospitalization. A concise discharge summary is crucial for maintaining continuity of care through the transition from inpatient to ambulatory care. Discharge summaries often lack information and are imprecise. Errors and insufficient recommendations regarding changes in the medical regimen may harm the patient's health and may result in readmission. OBJECTIVES: To evaluate a quality improvement model and training program for writing postoperative discharge summaries for three surgical procedures. METHODS: Medical records and surgical discharge summaries were reviewed and scored. Essential points for communication between surgeons and family physicians were included in automated forms. Staff was briefed twice regarding required summary contents with an interim evaluation. Changes in quality were evaluated. RESULTS: Summaries from 61 cholecystectomies, 42 hernioplasties and 45 colectomies were reviewed. The average quality score of all discharge summaries increased from 72.1 to 78.3 after the first intervention (P < 0.0005) to 81.0 following the second intervention. As the discharge summary's quality improved, its length decreased significantly. CONCLUSIONS: Discharge summaries lack important information and are too long. Developing a model for discharge summaries and instructing surgical staff regarding their contents resulted in measurable improvement. Frequent interventions and supervision are needed to maintain the quality of the surgical discharge summary.


Subject(s)
Continuity of Patient Care/standards , Family Practice , Interdisciplinary Communication , Patient Discharge Summaries/standards , Specialties, Surgical , Education , Elective Surgical Procedures/statistics & numerical data , Hospitals, Teaching/methods , Humans , Inservice Training/organization & administration , Israel , Models, Organizational , Needs Assessment , Quality Improvement
4.
Chem Rev ; 113(12): 9043-85, 2013 Dec 11.
Article in English | MEDLINE | ID: mdl-24261880
5.
J Phys Chem A ; 117(39): 10018-26, 2013 Oct 03.
Article in English | MEDLINE | ID: mdl-23869910

ABSTRACT

The opening of the submillimeter sky with the Herschel Space Observatory has led to the detection of new interstellar molecular ions, H2O(+), H2Cl(+), and HCl(+), which are important intermediates in the synthesis of water vapor and hydrogen chloride. In this paper, we report new observations of H2O(+) and H2Cl(+) performed with both Herschel and ground-based telescopes, to determine the abundances of their ortho and para forms separately and derive the ortho-to-para ratio. At the achieved signal-to-noise ratio, the observations are consistent with an ortho-to-para ratios of 3 for both H2O(+) and H2Cl(+), in all velocity components detected along the lines-of-sight to the massive star-forming regions W31C and W49N. We discuss the mechanisms that contribute to establishing the observed ortho-to-para ratio and point to the need for a better understanding of chemical reactions, which are important for establishing the H2O(+) and H2Cl(+) ortho-to-para ratios.

6.
Isr Med Assoc J ; 15(5): 226-30, 2013 May.
Article in English | MEDLINE | ID: mdl-23841242

ABSTRACT

BACKGROUND: Laparoscopic repair of giant diaphragmatic hernias (GDH) can be challenging, especially when partial or complete volvulus of the herniated stomach is encountered. OBJECTIVES: To review our experience with laparoscopic repair of GDH, emphasizing preoperative investigation, technical aspects, and outcome. METHODS: We conducted a retrospective review of patients operated on for GDH who were diagnosed when at least half the stomach was found in the mediastinum at surgery. Technical aspects and surgical outcomes were evaluated. RESULTS: Fifty patients underwent laparoscopic GDH repair during an 8 year period. Four patients admitted with acute symptomatic volvulus of the stomach were initially treated by endoscopic decompression followed by surgery during the same admission. Two cases were converted to open surgery. Initial surgery was successful in 45 patients; 3 had an immediate recurrence, 1 was reoperated for dysphagia during the same admission, and 1 had a mediastinal abscess. During long-term follow-up, six patients required reoperation for recurrent hernias. Another four patients had asymptomatic partial herniation of the stomach. The main reason for failure was incomplete reduction of the hernia sac, especially the posterior component. No correlation was found between the type of repair and surgical failure. Most patients who did not undergo an anti-reflux procedure had postoperative reflux unrelated to their preoperative workup. CONCLUSIONS: Laparoscopic repair of GDH is challenging, but practical and safe. It should be the treatment of choice for this potentially life-threatening condition. Careful attention to pitfalls, such as the posterior element of the sac, and routine performance of an anti-reflux procedure are crucial.


Subject(s)
Gastroesophageal Reflux/surgery , Hernia, Diaphragmatic/surgery , Laparoscopy/methods , Stomach Volvulus/surgery , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Hernia, Diaphragmatic/pathology , Humans , Laparoscopy/adverse effects , Male , Middle Aged , Recurrence , Reoperation/statistics & numerical data , Retrospective Studies , Stomach Volvulus/pathology , Treatment Outcome
7.
Eur J Gastroenterol Hepatol ; 24(11): 1254-8, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22872077

ABSTRACT

BACKGROUND: Diverticulosis of the right colon occurs in a small percentage of patients in Western countries. Clinical presentation of right-sided colon diverticulitis is indistinguishable from that of acute appendicitis, and the majority of patients undergo surgical intervention for presumed appendicitis. The liberal use of diagnostic radiological modalities whenever appendicitis was suspected led to correct diagnosis and also to more preoperative diagnosis of right-sided diverticulitis, which consented conservative medical therapy in cases of uncomplicated right-sided diverticulitis. The aim of the study was to report the outcome in patients with right-sided diverticulitis diagnosed nonoperatively using computed tomography scanning and treated conservatively. METHODS: Patients with clinical and radiological diagnosis of cecal or right colon diverticulitis treated conservatively between January 2005 and December 2007 were included. The demographic and clinical data were retrospectively analyzed. RESULTS: Fifteen patients were included in this study. The median age was 52 years (range, 34-72 years) and the duration of symptoms was 4 days (range, 1-9 days) before the diagnosis. The median hospital stay was 5 days (range, 1-9 days). All patients were successfully treated with medical therapy. During a median follow-up of 32 months (range, 24-52 months) only one patient (6.6%) had a recurrent attack, and he was successfully treated again with medical therapy. CONCLUSION: The routine use of the computed tomography scan for abdominal pain in the right lower quadrant, and whenever right-sided diverticulitis is suspected, improves diagnosis and reduces surgical interventions. The current study provides additional data in support of conservative therapy as the initial treatment in acute right-sided diverticulitis, even in cases of recurrence.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Diverticulitis, Colonic/therapy , Fluid Therapy , Abdominal Pain/etiology , Adult , Aged , Appendicitis/diagnostic imaging , Colonoscopy , Combined Modality Therapy , Diagnosis, Differential , Diverticulitis, Colonic/complications , Diverticulitis, Colonic/diagnostic imaging , Female , Hospitalization , Humans , Length of Stay , Male , Middle Aged , Predictive Value of Tests , Recurrence , Retrospective Studies , Time Factors , Tomography, X-Ray Computed , Treatment Outcome , Unnecessary Procedures
8.
Harefuah ; 150(2): 84-6, 209, 208, 2011 Feb.
Article in Hebrew | MEDLINE | ID: mdl-22164931

ABSTRACT

INTRODUCTION: Peritoneal dialysis (PD) is one of the established methods for the management of patients with end-stage renal failure. Laparoscopy has been used to assist in the insertion of new catheters as well as for the salvage of malfunctioning peritoneal dialysis catheters (PDC). OBJECTIVES: The purpose of this retrospective study was to review our experience in the utilization of laparoscopy for the management of PDC. METHODS: We reviewed the charts of all consecutive patients who had undergone either a ap-assisted insertion of a PDC utilizing a modified peritoneoscopic Y-TEC [Medigroup, Inc, Oswego, Ill) technique (YT) under direct laparoscopic vision or laparoscopic-assisted procedures for the salvage of a malfunctioning PD catheter. RESULTS: Twenty nine patients had undergone 43 procedures that included the insertion of a new PD catheter using the modified YT technique, YT with simultaneous adhesiolysis and omentectomy; YT with repair of an epigastric hernia, omentectomy, adhesiolysis and repositioning of PDC; and ravage and repositioning of the obstructed PD catheter in all patients who needed repositioning of the catheter, the PDC was fixed with an intraperitoneal suture to the lower anterior abdominal wall. Postoperatively, malfunction of the catheter was found in one patient due to reclotting of PDC caused by oozing as a result of extensive adhesiolysis. One patient needed emergent laparotomy due to small bowel perforation that was missed during a difficult laparoscopic adhesiolysis. CONCLUSIONS: Laparoscopic surgery may be helpfuL for the diagnosis and the management of a malfunctioning PDC. A modified YT technique is safe and may be one of the alternative methods for the placement of a PDC.


Subject(s)
Catheterization , Laparoscopy/methods , Peritoneal Dialysis/methods , Equipment Failure , Humans , Kidney Failure, Chronic/therapy , Omentum/surgery , Retrospective Studies , Tissue Adhesions/etiology , Tissue Adhesions/surgery
9.
Science ; 334(6054): 338-40, 2011 Oct 21.
Article in English | MEDLINE | ID: mdl-22021851

ABSTRACT

Icy bodies may have delivered the oceans to the early Earth, yet little is known about water in the ice-dominated regions of extrasolar planet-forming disks. The Heterodyne Instrument for the Far-Infrared on board the Herschel Space Observatory has detected emission lines from both spin isomers of cold water vapor from the disk around the young star TW Hydrae. This water vapor likely originates from ice-coated solids near the disk surface, hinting at a water ice reservoir equivalent to several thousand Earth oceans in mass. The water's ortho-to-para ratio falls well below that of solar system comets, suggesting that comets contain heterogeneous ice mixtures collected across the entire solar nebula during the early stages of planetary birth.


Subject(s)
Ice , Planets , Stars, Celestial , Steam , Evolution, Planetary , Extraterrestrial Environment
10.
Dis Colon Rectum ; 54(10): 1279-83, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21904143

ABSTRACT

BACKGROUND: Instillation of fibrin glue, a simple and safe procedure, has been shown to have a moderate short-term success rate in the treatment of cryptogenic perianal fistulas. OBJECTIVE: This study aimed to assess the long-term outcome of this procedure. DESIGN: This study included a retrospective chart review and telephone interviews. SETTINGS: This study was conducted at 4 university-affiliated medical centers. PATIENTS: Patients were included who underwent fibrin glue instillation for complex cryptogenic fistula between 2002 and 2003 within a prospective trial and had successful healing. INTERVENTIONS: Fibrin glue was instilled for complex cryptogenic fistula. MAIN OUTCOME MEASURES: The main outcome measure was long-term fistula healing. RESULTS: Sixty patients participated in the initial trial; the fistulas in 32 of these patients were healed at 6 months. We have located and interviewed 23 (72%) of those patients. Seventeen (74%) patients remained disease free at a mean follow-up of 6.5 years. Six (26%) patients had variable degrees of recurrence; 4 needed further surgical intervention and 2 were treated with antibiotics only. Recurrent disease occurred at an average of 4.1 years (range, 11 mo to 6 y) from surgery, and on several occasions was at a different location in the perianal region. None of the patients experienced incontinence following the procedure. LIMITATIONS: The retrospective nature of this long-term follow-up was a limitation. Twenty-eight percent of the potentially eligible patients were lost to long-term follow-up. CONCLUSIONS: Short-term success of fibrin glue in the treatment of cryptogenic perianal fistula is predictive of long-term healing, but a quarter of those healed in the short term may develop recurrent symptoms in the long run. Injection of fibrin glue remains a safe and simple procedure and may preclude extensive surgery.


Subject(s)
Fibrin Tissue Adhesive/therapeutic use , Rectal Fistula/therapy , Tissue Adhesives/therapeutic use , Adult , Aged , Female , Follow-Up Studies , Humans , Male , Middle Aged , Recurrence , Retrospective Studies , Time Factors , Treatment Outcome , Young Adult
11.
Pediatr Surg Int ; 26(2): 167-71, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19844725

ABSTRACT

The pre-operative diagnosis of acute appendicitis (AA) has markedly changed during the last couple of decades due to the advent of modern imaging technology. Nowadays, the use of imaging has dramatically changed the way we approach children admitted to emergency room for abdominal pain with suspected AA. This change is mainly manifested in our diagnostic strategy.


Subject(s)
Appendicitis/diagnosis , Diagnostic Imaging/standards , Practice Guidelines as Topic , Acute Disease , Adolescent , Appendectomy , Appendicitis/surgery , Child , Child, Preschool , Diagnosis, Differential , Diagnostic Imaging/methods , Female , Follow-Up Studies , Humans , Male , Reproducibility of Results , Retrospective Studies
12.
Hepatology ; 50(2): 601-11, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19575449

ABSTRACT

UNLABELLED: Thymus cell antigen-1 (Thy-1)-expressing cells proliferate in the liver during oval cell (OC)-mediated liver regeneration. We characterized these cells in normal liver, in carbon tetrachloride-injured liver, and in several models of OC activation. The gene expression analyses were performed using reverse-transcriptase polymerase chain reaction (RT-PCR), quantitative RT-PCR (Q-RT-PCR) of cells isolated by fluorescence-activated cell sorting (FACS), and by immunofluorescent microscopy of tissue sections and isolated cells. In normal liver, Thy-1(+) cells are a heterogeneous population: those located in the periportal region do not coexpress desmin or alpha smooth muscle actin (alpha-SMA). The majority of Thy-1(+) cells located at the lobular interface and in the parenchyma coexpress desmin but not alpha-SMA, i.e., they are not resident myofibroblasts. Although Thy-1(+) cells proliferate moderately after carbon tetrachloride injury, in all models of OC-mediated liver regeneration they proliferate quickly and expand significantly and disappear from the liver when the OC response subsides. Activated Thy-1(+) cells do not express OC genes but they express genes known to be expressed in mesenchymal stem cells (CD105, CD73, CD29), genes considered specific for activated stellate cells (desmin, collagen I-a2, Mmp2, Mmp14) and myofibroblasts (alpha-SMA, fibulin-2), as well as growth factors and cytokines (Hgf, Tweak, IL-1b, IL-6, IL-15) that can affect OC growth. Activated in vitro stellate cells do not express Thy-1. Subcloning of Thy-1(+) cells from OC-activated livers yield Thy-1(+) fibroblastic cells and a population of E-cadherin(+) mesenchymal cells that gradually discontinue expression of Thy-1 and begin to express cytokeratins. However, upon transplantation these cells do not differentiate into hepatocytes or cholangiocytes. Activated Thy-1(+) cells produce predominantly latent transforming growth factor beta. CONCLUSION: Thy-1(+) cells in the OC niche are activated mesenchymal-epithelial cells that are distinct from resident stellate cells, myofibroblasts, and oval cells.


Subject(s)
Liver Regeneration , Liver/cytology , Thy-1 Antigens/metabolism , Actins/metabolism , Animals , Carbon Tetrachloride , Cells, Cultured , Desmin/metabolism , Extracellular Matrix/metabolism , Gene Expression , Intercellular Signaling Peptides and Proteins/metabolism , Male , Rats , Rats, Inbred F344 , Transforming Growth Factor beta/metabolism
13.
Surg Endosc ; 23(3): 629-32, 2009 Mar.
Article in English | MEDLINE | ID: mdl-19067054

ABSTRACT

BACKGROUND: Benign colonic polyps not amenable to colonoscopic resection or those containing carcinoma require surgical excision. Traditionally, formal colectomy with clearance of the lymphatic basin has been performed. The aim of this study was to review our experience with the laparoscopic approach for retrieval of colonic polyps with specific emphasis on safety, feasibility, and tumor localization. METHODS: Retrospective chart review of all patients who underwent laparoscopic colectomy for colonic polyps was performed. Initial colonoscopic biopsies were compared with the postoperative pathology report of the resected specimen. RESULTS: Forty-nine patients (22 males, 27 males, mean age 66 years) underwent laparoscopic colectomy for colonic polyps. Indications for surgery were presumably benign polyps in 38 patients, and superficial carcinoma in a polyp, diagnosed by colonoscopy, in 11; twenty-three patients underwent preoperative localization procedures. In 19% of patients who did not have preoperative localization, difficulties locating the polyp were encountered during surgery, requiring intraoperative endoscopy or conversion to laparotomy. In 7 of the 38 patients with presumably benign lesion, colon cancer was diagnosed in the colectomy specimen. None of the 18 patients who had cancerous lesions had any positive lymph nodes. CONCLUSIONS: Laparoscopic surgery for the treatment of colonic polyps seems to be feasible and safe, with a low complication rate. Tumor localization is crucial for adequate resection. Although one-fifth of presumably benign polyps harbored cancer, none of these patients had positive lymph nodes. These preliminary results may question the need for radical lymph node clearance in these patients.


Subject(s)
Colectomy/methods , Colonic Polyps/surgery , Laparoscopy/methods , Adult , Aged , Aged, 80 and over , Colonic Polyps/pathology , Female , Humans , Male , Middle Aged , Postoperative Complications , Retrospective Studies , Treatment Outcome
14.
Int Surg ; 92(3): 155-60, 2007.
Article in English | MEDLINE | ID: mdl-17972471

ABSTRACT

The objective of this study was to determine whether there is a correlation between the length of the sigmoid colon removed and the number of harvested lymph nodes (LNs). Pathology charts of 137 sigmoid resections that were done over a 5-year period were reviewed. The length of removed sigmoid specimen reported in the pathology reports was correlated with the number of LNs retrieved from the specimen. The mean and median numbers of retrieved LNs were 9 and 10, respectively. There was an increase in the number of retrieved LNs with increasing length of resected sigmoid colon. For Dukes' B patients, the average length of the resected specimen was 15.1 cm for those with < 12 LNs and 20.3 cm for those with > 12 LNs (P = 0.01). Our data suggest that the surgeon may play an important role in determining the extent of LN harvesting during large bowel resection for cancer.


Subject(s)
Colon, Sigmoid/pathology , Lymph Node Excision , Lymph Nodes/pathology , Sigmoid Neoplasms/surgery , Aged , Female , Humans , Male , Middle Aged , Neoplasm Staging , Sigmoid Neoplasms/pathology
15.
J Gastrointest Surg ; 10(3): 445-9, 2006 Mar.
Article in English | MEDLINE | ID: mdl-16504894

ABSTRACT

Abdominal wall abscess due to Crohn's Disease used to be one of the definitive indications for operative treatment. The advent of interventional radiology, the accessibility to percutaneous drainage, and the availability of new medications raised the possibility of nonoperative treatment of this condition. The clinical presentation, treatment, and follow-up of 13 patients with abdominal wall abscesses secondary to Crohn's Disease were retrospectively reviewed. During a 10-year period (1993-2003), 13 patients with abdominal wall abscess were treated. Five patients had an anterolateral abdominal wall abscess and eight had a posterior abscess (psoas). In 11 patients, 17 drainage procedures were performed: 12 percutaneous and 5 operative. Despite initial adequate drainage and resolution of the abscess, all 13 patients eventually needed resection of the offending bowel segment, which was undertaken in 12 patients. The mean time between abscess presentation and definitive operation was 2 months. Percutaneous drainage is an attractive option in most cases of abdominal abscesses. However, in Crohn's Disease patients with an abdominal wall abscess, we found a high failure rate despite initial adequate drainage. We suggest that surgical resection of the diseased bowel segment should be the definitive therapy.


Subject(s)
Abdominal Abscess/etiology , Abdominal Abscess/therapy , Crohn Disease/complications , Adolescent , Adult , Combined Modality Therapy , Contrast Media , Drainage , Female , Follow-Up Studies , Humans , Male , Middle Aged , Retrospective Studies , Tomography, X-Ray Computed , Treatment Outcome
16.
Dis Colon Rectum ; 48(12): 2167-72, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16258708

ABSTRACT

PURPOSE: The surgical management of complex perianal fistulas is challenging and may be associated with the risk of sphincter injury. Instillation of fibrin glue to the fistula tract is a simple procedure that does not involve any muscle division, and potentially results in healing of the fistula. This study was designed to assess the use of highly concentrated fibrin glue with intra-adhesive antibiotics in the treatment of complex cryptogenic perianal fistulas. METHODS: Patients with complex perianal fistulas of cryptogenic origin were prospectively included in this multicenter study. Injection of the fibrin glue mixed with antibiotics was performed in a uniform fashion. After the procedure, patients were actively examined at fixed time intervals; in cases of recurrent fistula, reinjection of fibrin glue was offered. RESULTS: Sixty patients were enrolled; complete healing of the fistula was achieved in 32 patients (53 percent). Eight of 28 patients (29 percent) who were not completely healed had significant symptomatic improvement. All patients resumed normal daily activity the day after surgery and none had any deterioration in continence related to the procedure. The majority of the 26 (43 percent) adverse events were considered mild and spontaneously resolved; 2 patients (3 percent) with perianal septic complications were successfully treated by drainage. CONCLUSIONS: Injection of fibrin glue for the treatment of perianal fistulas is safe, simple, and associated with early return to normal activity. Although moderately successful, it may preclude extensive surgery in more than one-half of these patients.


Subject(s)
Fibrin Tissue Adhesive/therapeutic use , Rectal Fistula/therapy , Tissue Adhesives/therapeutic use , Activities of Daily Living , Adult , Aged , Female , Fibrin Tissue Adhesive/administration & dosage , Fibrin Tissue Adhesive/adverse effects , Humans , Male , Middle Aged , Prospective Studies , Tissue Adhesives/administration & dosage , Tissue Adhesives/adverse effects , Treatment Outcome
17.
Cell Transplant ; 12(8): 907-19, 2003.
Article in English | MEDLINE | ID: mdl-14763511

ABSTRACT

Studies were conducted to develop a new DPPIV(-/-)/Rag2(-/-) mouse model for hepatocyte transplantation by allogeneic and xenogeneic cells and to compare the proliferative capacity of p27 null hepatocytes versus normal hepatocytes in this system. Dipeptidyl peptidase IV (DPPIV) gene knockout mice, in which wild-type (wt) DPPIV+ donor hepatocytes can be readily identified by enzyme histochemistry, were bred with Rag2 null mice to prepare immunotolerant DPPIV(-/-)/Rag2(-/-) double knockout mice. DPPIV(-/-)/Rag(-/-) mice were transplanted with wt hepatocytes or p27 null mouse hepatocytes, which show enhanced cell cycle activity due to disruption of the Kip1 cyclin kinase inhibitor gene, and liver repopulation was assessed under nonproliferative versus proliferative experimental conditions. After their initial engraftment, transplanted wt hepatocytes did not proliferate in untreated livers or increase significantly in response to an acute liver regenerative stimulus. p27 null hepatocytes engrafted with the same efficiency as wt hepatocytes, but showed a noticeable, although not statistically significant, increase in proliferation in response to partial hepatectomy or acute CCl4 administration. Repeated treatments with CCl4 substantially increased proliferation and liver repopulation by p27 null hepatocytes but not by wt hepatocytes. These results suggest that p27 gene inactivation does not overcome proliferative restrictions imposed on hepatocytes by the normal liver, but that after repeated episodes of toxic liver injury, the augmented proliferative capacity of p27 null hepatocytes leads to significant liver repopulation compared with wt hepatocytes. These properties of p27-deficient hepatocytes could prove useful as a target for liver repopulation in patients with intermittent or a low level of chronic liver injury.


Subject(s)
Cell Cycle Proteins/metabolism , Cell Division/physiology , DNA-Binding Proteins/metabolism , Dipeptidyl Peptidase 4/metabolism , Gene Silencing , Hepatocytes/physiology , Hepatocytes/transplantation , Liver Regeneration , Liver/physiology , Tumor Suppressor Proteins/metabolism , Animals , Carbon Tetrachloride/administration & dosage , Carbon Tetrachloride/pharmacology , Cell Cycle Proteins/genetics , Cyclin-Dependent Kinase Inhibitor p27 , DNA-Binding Proteins/genetics , Dipeptidyl Peptidase 4/genetics , Hepatectomy , Hepatocytes/cytology , Hepatocytes/drug effects , Liver/cytology , Liver/drug effects , Mice , Mice, Inbred C57BL , Mice, Knockout , Tumor Suppressor Proteins/genetics
18.
Anticancer Res ; 23(6D): 5153-7, 2003.
Article in English | MEDLINE | ID: mdl-14981982

ABSTRACT

BACKGROUND: Angiogenesis is activated in numerous physiological and pathological conditions. We examined whether new vessel formation exists in the earliest stages of colonic tumorigenesis. MATERIALS AND METHODS: Microvascular density (MVD) was examined in 176 formalin-fixed and paraffin-embedded aberrant crypt foci (ACF) dissected from macroscopically-normal mucosa obtained from patients with colorectal cancer. ACF were classified as non-hyperplastic, non-dysplastic (NH-ACF, n = 80), hyperplastic (H-ACF, n = 72) and dysplastic (D-ACF, n = 24). Mucosal strips were stained with methylene blue solution and screened under x 40 magnification for ACF. The identified ACF were microdissected and stained with an anti-CD-34 monoclonal antibody. MVD in ACF were compared to that of normal corresponding mucosa. RESULTS: The mean MVD for normal mucosa and ACF were 13.7 +/- 7.7 and 23 +/- 13, respectively. Microvessel counts increased in NH-ACF versus normal mucosa (18.7 +/- 10 vs. 13.7 +/- 7.7, p = 0.05), in H-ACF versus NH-ACF (24.8 +/- 14 vs. 18.7 +/- 10, p = 0.002) and in D-ACF versus H-ACF (31.7 +/- 10 vs. 24.8 +/- 14, p = 0.014). We further evaluated the effect of low-dose aspirin on MVD in ACF. No effect of aspirin on microvessel counts could be detected. CONCLUSION: Our data suggest that angiogenesis occurs in ACF which are the earliest morphologically identifiable preneoplastic and early neoplastic lesions in colonic mucosa. With progression from NH-ACF to D-ACF there is a progressive, statistically significant increase in MVD, suggesting active angiogenesis during the earliest steps of colorectal tumorigenesis.


Subject(s)
Colonic Neoplasms/blood supply , Neovascularization, Pathologic/pathology , Precancerous Conditions/blood supply , Aspirin/pharmacology , Humans , Intestinal Mucosa/blood supply , Neovascularization, Pathologic/drug therapy
19.
Acta cir. bras ; 13(4)out.-dez. 1998.
Article in English | LILACS-Express | LILACS, VETINDEX | ID: biblio-1455855

ABSTRACT

Background: Somatostatin has an inhibitory effect on the endocrine and exocrine secretions of the gut. It may have a beneficial effect in the conservative treatment of intestinal obstruction. The aim of the present study is to investigate the effect of octreotide in mechanical intestinal obstruction in rats. Method: Intestinal obstruction was induced in rats by ligation of a segment of the distal ileum. Animals were treated with the somatostatin analogue octreotide (n=16), or saline (n=16). Eight rats were operated but their intestine was not ligated (n=8) serving as sham controls. Forty eight hours after the operation, the animals were operated upon again and blood samples from the femoral vein were tested for electrolytes, urea, glucose, lactic acid, amylase, ph and bicarbonate. Portal vein blood samples were also obtained and tested for lactic acid and amylase. Results: Intestinal obstruction resulted, after 48 hours, in severe dilatation of bowel loops. A significant increase in plasma levels of urea, amylase and lactic acid was observed. Plasma pH decreased. In blood samples from the portal vein, a significant increase in lactic acid was observed, indicating metabolic acidosis, probably secondary to bowel ischemia. Octreotide treatment, resulted in less acidosis, with concomitant lower urea and lactic acid levels in the plasma and especially in the portal vein. Conclusion: Octreotide treatment may have a beneficial effect in the conservative treatment of selected cases of intestinal obstruction.


Objetivo: A somatostatina tem efeito inibidor nas secrees endcrina e excrina do intestino. Poderß ter efeito benfico no tratamento conservador da obstruo intestinal. O objetivo do presente estudo investigar o efeito do octreotide na obstruo mecnica do intestino delgado de ratos. Mtodo: A obstruo intestinal foi induzida em ratos pela ligadura do segmento distal do ileum. Os animais foram tratados com somatostatina anßloga octreotide (n=16) ou com soluo salina (n=16). Oito ratos foram operados mas o intestino delgado no foi ligado (n=8) servindo como o grupo sham. Quarenta oito horas aps a operao os animais foram re-operados e submetidos a colheita de sangue da veia femoral a fim de verificar os eletrlitos, uria, glicose, ßcido lßtico, amilase, pH e bicarbonato. Obteve-se tambm amostra de sangue da veia porta para verificar os nveis de ßcido lßtico e amilase. Resultados: Aps 48 horas de obstruo houve intensa dilatao das alas intestinais. Observou-se aumento significante dos nveis plasmßticos de uria, amilase e ßcido lßtico. Diminuiu o pH plasmßtico. Observou-se aumento do ßcido lßtico no sangue portal, indicando acidose metablica, provavelmente secundßria a isquemia intestinal. O tratamento com octreotide resultou em menos acidose, com nveis baixos de uria e ßcido lßtico no plasma, e especialmente na veia porta. Concluso: O emprego de octreotide pode ter efeito benfico no tratamento conservador de casos selecionados de obstruo intestinal.

20.
Acta cir. bras ; 9(3): 109-12, jul.-set. 1994.
Article in English | LILACS | ID: lil-139489

ABSTRACT

Várias investigaçöes revelaram que a somatostatina e análogas baixam o fluxo sanguíneo esplâncnico e portal em cirróticos e em modelos experimentais de hipertensäo portal. Tem sido experimentado habitualmente no tratamento de varizes sangrantes. O mecanismo pelo qual o hormônio age permanece obscuro. No presente estudo investigou-se o efeito da açäo prolongada do octreotide, somatostatina análoga, no fluxo sanguíneo mesentérico e portal, em ratos sadios. A administraçäo intravenosa do octreotide näo teve efeito significante na circulaçäo esplânic. Em alguns animais registrou-se, após a infusäo inicial da droga, queda pequena no fluxo venoso portal. Infusöes adicionais näo alteraram o fluxo portal. O fluxo sangüíneo mesentérico superior permaneceu inalterado. Conclui-se que o octreotide näo influiu na circulaçäo espâncnica, em ratos sadios, e que novos estudos se fazem necessários para explicar os seus efeitos em modelos de hipertensäo portal


Subject(s)
Animals , Male , Rats , Splanchnic Circulation , Octreotide/pharmacology , Portal System/drug effects , Injections, Intravenous , Rats, Wistar
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