- Pathology of Gastrointestinal and Liver Complications of Hematopoietic Stem Cell Transplantation. [Journal Article]
- APArch Pathol Lab Med 2019 Mar 06
- CONCLUSIONS: The final histopathologic diagnosis requires the integration of clinical and histologic findings and the exclusion of other competing causes of injury. Review of the clinical data, including the original disease pretransplant, the type of transplant, the timing of the gastrointestinal and/or liver manifestations, the timing of the biopsy after transplant, the presence of graft-versus-host disease in other organs and sites, the list of drug regimens, and the clinical and laboratory evidence of infection, is the key to reaching the proper histologic diagnosis.
- Metronidazole-induced encephalopathy during treatment for refractory diarrhea after cord blood transplantation. [Journal Article]
- CJClin J Gastroenterol 2019 Mar 05
- A 56-year-old man underwent cord blood transplantation for angioimmunoblastic T-cell lymphoma. He developed severe diarrhea and abdominal pain that persisted for more than 4 months. We suspected that…
A 56-year-old man underwent cord blood transplantation for angioimmunoblastic T-cell lymphoma. He developed severe diarrhea and abdominal pain that persisted for more than 4 months. We suspected that he might have cord colitis syndrome (CCS), so metronidazole (MNZ) was administered. The patient's abdominal pain and diarrhea showed some improvement after the initiation of MNZ therapy, but they worsened on the cessation of MNZ, which prompted us to resume MNZ treatment. After the patient had taken MNZ (1500-2000 mg/day) for 78 days, he developed somnolence and dysarthria. We diagnosed him with metronidazole-induced encephalopathy (MIE) based on the characteristic magnetic resonance imaging findings and the clinical course. The patient's dysarthria and somnolence improved within a few days after the discontinuation of MNZ. CCS is a recently proposed clinical entity defined as a persistent diarrheal illness that is culture-negative, antibiotic-responsive, and not attributable to any known cause. Patients with CCS often have recurrent diarrhea after the discontinuation of MNZ and may require prolonged treatment for a median of 120 days. When treating CCS with MNZ, physicians should be alert for the development of MIE.
- Chronic linaclotide treatment reduces colitis-induced neuroplasticity and reverses persistent bladder dysfunction. [Journal Article]
- JIJCI Insight 2018 10 04; 3(19)
- Irritable bowel syndrome (IBS) patients suffer from chronic abdominal pain and extraintestinal comorbidities, including overactive bladder (OAB) and interstitial cystitis/painful bladder syndrome (IC…
Irritable bowel syndrome (IBS) patients suffer from chronic abdominal pain and extraintestinal comorbidities, including overactive bladder (OAB) and interstitial cystitis/painful bladder syndrome (IC-PBS). Mechanistic understanding of the cause and time course of these comorbid symptoms is lacking, as are clinical treatments. Here, we report that colitis triggers hypersensitivity of colonic afferents, neuroplasticity of spinal cord circuits, and chronic abdominal pain, which persists after inflammation. Subsequently, and in the absence of bladder pathology, colonic hypersensitivity induces persistent hypersensitivity of bladder afferent pathways, resulting in bladder-voiding dysfunction, indicative of OAB/IC-PBS. Daily administration of linaclotide, a guanylate cyclase-C (GC-C) agonist that is restricted to and acts within the gastrointestinal tract, reverses colonic afferent hypersensitivity, reverses neuroplasticity-induced alterations in spinal circuitry, and alleviates chronic abdominal pain in mice. Intriguingly, daily linaclotide administration also reverses persistent bladder afferent hypersensitivity to mechanical and chemical stimuli and restores normal bladder voiding. Linaclotide itself does not inhibit bladder afferents, rather normalization of bladder function by daily linaclotide treatment occurs via indirect inhibition of bladder afferents via reduced nociceptive signaling from the colon. These data support the concepts that cross-organ sensitization underlies the development and maintenance of visceral comorbidities, while pharmaceutical treatments that inhibit colonic afferents may also improve urological symptoms through common sensory pathways.
- Stent-assisted, balloon-induced intimal disruption and relamination of aortic dissection in patients with Marfan syndrome: Midterm outcomes and aortic remodeling. [Journal Article]
- JTJ Thorac Cardiovasc Surg 2018; 156(5):1787-1793
- CONCLUSIONS: Stent-assisted, balloon-induced intimal disruption and relamination of aortic dissection in patients with Marfan syndrome is feasible, safe, and associated with an immediate and midterm persisting thoracoabdominal aortic remodeling.
- Successful Treatment of a Case of Late-onset Colitis after Umbilical Cord Transplantation with Metronidazole: A Case Report and Literature Review. [Case Reports]
- IMIntern Med 2017 Dec 01; 56(23):3219-3223
- Diarrhea after hematopoietic stem cell transplantation (HSCT) can be life-threatening, and its etiology includes conditioning regimens, graft-versus-host disease (GVHD), infections, and transplantati…
Diarrhea after hematopoietic stem cell transplantation (HSCT) can be life-threatening, and its etiology includes conditioning regimens, graft-versus-host disease (GVHD), infections, and transplantation-associated microangiopathy (iTAM). Cord colitis syndrome (CCS) has been described as a syndrome of culture-negative and antibiotic-responsive persistent watery and non-bloody diarrhea of uncertain pathogenesis and occurs in umbilical cord blood transplantation (UCBT) recipients. We encountered a case similar to CCS that developed severe watery diarrhea after UCBT without any signs of GVHD or infection and responded well to metronidazole (MNZ) treatment. Since CCS is very rare, we herein describe a case of MNZ-effective diarrhea after UCBT.
- Hermansky-Pudlak syndrome in pregnancy: A case report. [Case Reports]
- OMObstet Med 2016; 9(4):171-173
- Hermansky-Pudlak syndrome is a rare autosomal recessive disorder estimated to affect 1 in 500,000 to 1,000,000 individuals worldwide. Clinically, it presents as oculocutaneous albinism combined with …
Hermansky-Pudlak syndrome is a rare autosomal recessive disorder estimated to affect 1 in 500,000 to 1,000,000 individuals worldwide. Clinically, it presents as oculocutaneous albinism combined with bleeding diathesis. This is due to the absence of dense bodies in platelets causing a delayed secondary response resulting in prolonged bleeding time despite normal platelet count and coagulation factors. This has consequences for major bleeding, the risk of which is high at delivery. In the longer term, the condition is also associated with the development of pulmonary fibrosis, inflammatory bowel disorders caused by granulomatous colitis and renal failure. We present a case of a patient with Hermansky-Pudlak syndrome diagnosed and managed through her second pregnancy by the Obstetric Haematology team in a Tertiary Unit. During her previous pregnancy at a District Hospital, they had not been aware of the diagnosis; she then had a forceps delivery and her haemoglobin dropped to 69 g/L. During this pregnancy, she was managed in a multidisciplinary setting involving obstetrics, haematology, anaesthesia and neonatology. She was induced at 39 weeks and had human leukocyte antigen-matched platelets prepared for her delivery. Her platelet count was normal throughout the pregnancy. She had a normal vaginal delivery under platelet cover and also received tranexamic acid at the time of cord clamping. Her blood loss was moderate and her haemoglobin dropped from 115 to 97 g/L. She recovered well. We discuss the diagnosis, pathology and management of this very rare condition in pregnancy and thereafter.
- Concise Review: Stem Cell Trials Using Companion Animal Disease Models. [Review]
- SCStem Cells 2016; 34(7):1709-29
- Studies to evaluate the therapeutic potential of stem cells in humans would benefit from more realistic animal models. In veterinary medicine, companion animals naturally develop many diseases that r…
Studies to evaluate the therapeutic potential of stem cells in humans would benefit from more realistic animal models. In veterinary medicine, companion animals naturally develop many diseases that resemble human conditions, therefore, representing a novel source of preclinical models. To understand how companion animal disease models are being studied for this purpose, we reviewed the literature between 2008 and 2015 for reports on stem cell therapies in dogs and cats, excluding laboratory animals, induced disease models, cancer, and case reports. Disease models included osteoarthritis, intervertebral disc degeneration, dilated cardiomyopathy, inflammatory bowel diseases, Crohn's fistulas, meningoencephalomyelitis (multiple sclerosis-like), keratoconjunctivitis sicca (Sjogren's syndrome-like), atopic dermatitis, and chronic (end-stage) kidney disease. Stem cells evaluated in these studies included mesenchymal stem-stromal cells (MSC, 17/19 trials), olfactory ensheathing cells (OEC, 1 trial), or neural lineage cells derived from bone marrow MSC (1 trial), and 16/19 studies were performed in dogs. The MSC studies (13/17) used adipose tissue-derived MSC from either allogeneic (8/13) or autologous (5/13) sources. The majority of studies were open label, uncontrolled studies. Endpoints and protocols were feasible, and the stem cell therapies were reportedly safe and elicited beneficial patient responses in all but two of the trials. In conclusion, companion animals with naturally occurring diseases analogous to human conditions can be recruited into clinical trials and provide realistic insight into feasibility, safety, and biologic activity of novel stem cell therapies. However, improvements in the rigor of manufacturing, study design, and regulatory compliance will be needed to better utilize these models. Stem Cells 2016;34:1709-1729.
- Evaluating the patient with low back pain. [Journal Article]
- PPractitioner 2015; 259(1788):21-4, 2-3
- In the UK, low back pain is the most common cause of disability in young adults and every year 6-9% of adults consult their GP about back pain. A thorough history and examination is required to exclu…
In the UK, low back pain is the most common cause of disability in young adults and every year 6-9% of adults consult their GP about back pain. A thorough history and examination is required to exclude an alternative diagnosis, such as pain arising from the hip or trochanteric bursa and to categorise patients as having: serious spinal pathology, nerve root/radicular pain or non-specific back pain. Inflammatory back pain is often missed, particularly in the early stages when examination may be normal. The primary features are pain arising in patients under 40, thoracolumbar or sacroiliac pain and alternating buttock pain. Stiffness in the early morning and after rest is a hallmark of inflammatory back pain. There may also be peripheral joint involvement with evidence of inflammatory arthritis as well as extra-articular manifestations such as iritis, psoriasis and colitis. Sphincter disturbance leading to loss of bladder or bowel control should also be explored as it is a sign of spinal cord compression or cauda equina syndrome. Both of these are neurosurgical emergencies and need urgent referral for further investigation and possible intervention. The majority of patients with low back pain can be managed in primary care as the pain will usually be self-limiting. Patients with suspected inflammatory back pain should be referred to rheumatology as soon as possible in order to institute early management and prevent long-term deformity and disability. Patients with suspected serious spinal pathology should be referred urgently for further investigation. Red flag symptoms should raise concerns regarding a possible sinister cause such as malignancy and more than one red flag mandates urgent further investigation.
- Probiotics: a proactive approach to health. A symposium report. [Congress]
- BJBr J Nutr 2015; 114 Suppl 1:S1-15
- This report summarises talks given at the 8th International Yakult Symposium, held on 23-24 April 2015 in Berlin. Two presentations explored different aspects of probiotic intervention: the small int…
This report summarises talks given at the 8th International Yakult Symposium, held on 23-24 April 2015 in Berlin. Two presentations explored different aspects of probiotic intervention: the small intestine as a probiotic target and inclusion of probiotics into integrative approaches to gastroenterology. Probiotic recommendations in gastroenterology guidelines and current data on probiotic efficacy in paediatric patients were reviewed. Updates were given on probiotic and gut microbiota research in obesity and obesity-related diseases, the gut-brain axis and development of psychobiotics, and the protective effects of equol-producing strains for prostate cancer. Recent studies were presented on probiotic benefit for antibiotic-associated diarrhoea and people with HIV, as well as protection against the adverse effects of a short-term high-fat diet. Aspects of probiotic mechanisms of activity were discussed, including immunomodulatory mechanisms and metabolite effects, the anti-inflammatory properties of Faecalibacterium prausnitzii, the relationship between periodontitis, microbial production of butyrate in the oral cavity and ageing, and the pathogenic mechanisms of Campylobacter. Finally, an insight was given on a recent expert meeting, which re-examined the probiotic definition, advised on the appropriate use and scope of the term and outlined different probiotic categories and the prevalence of different mechanisms of activity.
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- Endotext: Corticotropin Releasing Hormone And The Immune/Inflammatory Response [BOOK]
- BOOKMDText.com, Inc.: South Dartmouth (MA)
- The immune/inflammatory (I/I) response is a reaction of the vascularized connective tissue, characterized by the accumulation of fluid and leukocytes in extravascular tissues. In this process cellula…
The immune/inflammatory (I/I) response is a reaction of the vascularized connective tissue, characterized by the accumulation of fluid and leukocytes in extravascular tissues. In this process cellular (leukocytes and lymphocytes T, B, NK) and extra-cellular elements participate in a complex co-operative network. The balance between Th1 and Th2 is important for the immune system homeostasis. Glucocorticoids and catecholamines have a significant effect on this balance. The (I/I) response is influenced by the brain via regulation of peripheral nervous system functions and endocrine responses. The hypothalamic-pituitary-adrenal (HPA) axis is particularly involved in this regulation. Hypothalamic corticotropin-releasing hormone (CRH) is pivotal in the HPA axis response to stress while it acts indirectly in an anti-inflammatory fashion because it leads to cortisol production, an anti-inflammatory hormone. CRH in plasma is bound to a high-affinity binding protein (CRH-BP) which limits its distribution and activity. The biological effects of CRH are mediated by CRH-Receptor (R)1 and CRH-R2. Receptors for a number of hormones, neurotransmitters and neuropeptides are carried by cells of the immune system. In their turn, immune cells produce CRH and corticotropin (ACTH) which act locally as autacoids during both the early and late stages of the I/I process. This locally produced CRH, so-called ‘peripheral CRH’, is found in the adrenal medulla, the testes, the ovaries, the cardiovascular system, the gastrointestinal tract, the pancreas, the lung, the spinal cord, the endometrium and the placenta, as well as in diverse inflammatory sites. In the latter it acts in a pro-inflammatory fashion while most of the CRH effects in the female reproductive tract seem to be pro-inflammatory as well. This is the case in ovulation, luteolysis and blastocyst implantation. Ovarian CRH is found in the theca and stroma and in the cytoplasm of the oocyte. CRH suppresses ovarian steroidogenesis in vitro. Endometrial CRH participates in the early maternal tolerance of the semiallograft embryo. Placental CRH is synthesized in syncytiotrophoblast cells, in placental decidua and fetal membranes and is secreted into the maternal circulation during gestation. Its concentrations increase as pregnancy progresses and it participates in the physiology of pregnancy and the onset of parturition. The placental CRH/CRH-R system has been associated with the pathological mechanisms leading to preeclampsia. The expression of CRH and CRH-Rs in several components of the immune system and their participation in the regulation of inflammatory phenomena led researchers to suggest CRH antagonists/inhibitors as potential therapeutic agents of such conditions. Αntalarmin, has been proposed as a therapeutic tool for both CNS and inflammatory disorders associated with central and peripheral CRH hypersecretion. Astressin B, a nonspecific CRH receptor antagonist, accelerates the return to normal cyclicity. Thus, it emerges as a potential therapeutic agent in stress-related endocrine dysfunction, including the functional hypothalamic chronic anovulation syndrome or the persistent inadequate luteal phase syndrome, and therefore in the treatment of infertility. CRH-R1 antagonists could be considered for the treatment of allergic conditions (asthma, eczema, urticaria) and in the treatment of lower gastro-intestinal inflammatory diseases associated to CRH (chronic inflammatory bowel syndromes, irritable bowel disease and ulcerative colitis). For complete coverage of this and related topics, please visit www.endotext.org.