12 research outputs found
Duodenal Bulb Mucosa with Hypertrophic Gastric Oxyntic Heterotopia in Patients with Zollinger Ellison Syndrome
Objectives.
Zollinger-Ellison Syndrome (ZES) results in
hypersecretion of gastric acid (via gastrinoma)
leading to peptic ulcers, diarrhea, and abdominal
pain. We describe the novel discovery of
hypertrophic, heterotopic gastric mucosa in the
proximal duodenal bulb in patients with ZES,
which we hypothesize results in an increased
incidence of postbulbar ulcers in patients with
ZES (a mechanism previously unreported). We
determined the incidence of the novel finding of
duodenal gastric oxyntic hypertrophic
heterotopia (GOH) in patients with ZES.
Methods. Seven patients with
ZES were enrolled. The diagnosis of ZES was
established by hypergastrinemia, gastric acid
hypersecretion, and a positive secretin test or
based on biopsy specimens (evaluated via tissue
staining). Basal acid output (BAO) and baseline
gastrin secretion were determined by established
methods. Endoscopic examinations with methylene
blue staining and biopsy of the gastric and
duodenal mucosa were conducted in all patients
every 3–6 months for an average of 5
years. Results. The duodenal
mucosa demonstrated hypertrophic GOH in 5 out of
7 patients with ZES and an intact stomach and
duodenum. Biopsies from the bowel mucosa
demonstrated patchy replacement of surface
epithelium by gastric-type epithelium with
hypertrophic oxyntic glands in the lamina
propria in 5 patients. Two of the patients had
no evidence of GOH in the duodenal bulb.
Patients with GOH had an average serum gastrin
level of 1245 pg/mL and BAO of
2.92 mEq/hr versus 724 pg/mL and
0.8 mEq/hr in patients without GOH.
Conclusions. This study
demonstrated the presence of duodenal mucosa
with GOH in 5 out of 7 patients with ZES and an
intact stomach and duodenum. The presence of
hypertrophic and heterotopic gastric mucosa is
proposed to result from increased gastrin levels
and may contribute to the increased incidence of
postbulbar ulcers in these
patients
Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial
Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie
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Duodenal bulb mucosa with hypertrophic gastric oxyntic heterotopia in patients with zollinger ellison syndrome.
Objectives. Zollinger-Ellison Syndrome (ZES) results in hypersecretion of gastric acid (via gastrinoma) leading to peptic ulcers, diarrhea, and abdominal pain. We describe the novel discovery of hypertrophic, heterotopic gastric mucosa in the proximal duodenal bulb in patients with ZES, which we hypothesize results in an increased incidence of postbulbar ulcers in patients with ZES (a mechanism previously unreported). We determined the incidence of the novel finding of duodenal gastric oxyntic hypertrophic heterotopia (GOH) in patients with ZES. Methods. Seven patients with ZES were enrolled. The diagnosis of ZES was established by hypergastrinemia, gastric acid hypersecretion, and a positive secretin test or based on biopsy specimens (evaluated via tissue staining). Basal acid output (BAO) and baseline gastrin secretion were determined by established methods. Endoscopic examinations with methylene blue staining and biopsy of the gastric and duodenal mucosa were conducted in all patients every 3-6 months for an average of 5 years. Results. The duodenal mucosa demonstrated hypertrophic GOH in 5 out of 7 patients with ZES and an intact stomach and duodenum. Biopsies from the bowel mucosa demonstrated patchy replacement of surface epithelium by gastric-type epithelium with hypertrophic oxyntic glands in the lamina propria in 5 patients. Two of the patients had no evidence of GOH in the duodenal bulb. Patients with GOH had an average serum gastrin level of 1245 pg/mL and BAO of 2.92 mEq/hr versus 724 pg/mL and 0.8 mEq/hr in patients without GOH. Conclusions. This study demonstrated the presence of duodenal mucosa with GOH in 5 out of 7 patients with ZES and an intact stomach and duodenum. The presence of hypertrophic and heterotopic gastric mucosa is proposed to result from increased gastrin levels and may contribute to the increased incidence of postbulbar ulcers in these patients
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Strategic sequences in adipose-derived stem cell nerve regeneration.
BACKGROUND: Peripheral nerve injuries (PNI) are a major source of morbidity worldwide. The development of cellular regenerative therapies has the potential to improve outcomes of nerve injuries. However, an ideal therapy has yet to be found. The purpose of this study is to examine the current literature key points of regenerative techniques using human adipose-derived stem cells (hADSCs) for nerve regeneration and derive a comprehensive approach to hADSC therapy for PNI. METHODS: A literature review was conducted using the electronic database PubMed to search for current experimental approaches to repairing PNI using hADSCs. Key search elements focused on specific components of nerve regeneration paradigms, including (1) support cells, (2) scaffolds, and (3) nerve conduits. RESULTS: Strategic sequences were developed by optimizing the components of different experimental regenerative therapies. These sequences focus on priming hADSCs within a specialized growth medium, a hydrogel matrix base, and a collagen nerve conduit to achieve neuromodulatory nerve regeneration. hADSCs may exert their neuroregenerative influence through paracrine effects on surrounding Schwann cells in addition to physical interactions with injured tissue. CONCLUSIONS: hADSCs may play a key role in nerve regeneration by acting primarily as support for local neurotrophic mediation and modulation of nerve growth rather than that of a primary neuronal differentiation agent
"Strategic sequences"� in adipose-derived stem cell nerve regeneration
BACKGROUND: Peripheral nerve injuries (PNI) are a major source of morbidity worldwide. The development of cellular regenerative therapies has the potential to improve outcomes of nerve injuries. However, an ideal therapy has yet to be found. The purpose of this study is to examine the current literature key points of regenerative techniques utilizing human adipose derived stem cells (hADSCs) for nerve regeneration, and derive a comprehensive approach to hADSC therapy for PNI. METHODS: A literature review was conducted using the electronic database PubMed to search for current experimental approaches to repairing peripheral nerve injuries using hADSCs. Key search elements focused on specific components of nerve regeneration paradigms, including, 1) support cells, 2) scaffolds and 3) nerve conduits. RESULTS: Strategic sequences were developed by optimizing the components of different experimental regenerative therapies. These sequences focus on priming hADSCs within a specialized growth medium, a hydrogel matrix base, and a collagen nerve conduit to achieve neuromodulatory nerve regeneration. Human ADSCs may exert their neuroregenerative influence through paracrine effects on surrounding Schwann cells in addition to physical interactions with injured tissue. CONCLUSIONS: hADSCs may play a key role in nerve regeneration by acting primarily as support for local neurotrophic mediation and modulation of nerve growth rather than that of a primary neuronal differentiation agent
Discovery-based science education: functional genomic dissection in Drosophila by undergraduate researchers.
How can you combine professional-quality research with discovery-based undergraduate education? The UCLA Undergraduate Consortium for Functional Genomics provides the answe
Discovery-Based Science Education: Functional Genomic Dissection in Drosophila by Undergraduate Researchers
Discovery-Based Science Education: Functional Genomic Dissection in Drosophila by Undergraduate Researcher
Representative Pictures from the Laboratory Section of the Course
<p>Representative Pictures from the Laboratory Section of the Course</p