ABSTRACT
Sarcoidosis is an insidious disorder that virtually affects every body organ. Lungs are the site most often affected (in up to 90% of patients) followed by intra thoracic more often than peripheral lymph nodes and other sites can be involved in different percentages. The evaluation of pulmonary sarcoidosis is best performed with high-resolution computed tomography (HRCT), as traditional chest X-ray has a low resolution and can be negative or give non-significant results. Disorders such as interstitial lung diseases (ILDs), tuberculosis, lung cancer and lymphangitis carcinomatosis can manifest with similar radiological findings that can deceive clinics and radiologists. The need of a clear distinction between these conditions is important not only for diagnostic purposes but also because treatment differs significantly in different conditions. However, conventional Ultrasound (US) can be negative if small lesions are present and false negative images can result if US is not followed by a contrast-imaging technique. Contrast enhanced computed tomography (CECT) and magnetic resonance imaging (CEMRI) are preferred to detect single or multiple masses, which appear hypodense and hypointense after contrast agent administration, respectively. We think that a correct algorithm should include a thorough clinical and radiological evaluation, a definite biopsy of affected tissues revealing classical non-caseating granulomas and a certain exclusion of conditions that can give similar clinical/histophatological patterns before considering the diagnosis of sarcoidosis. Only in these cases, a diagnosis of sarcoidosis can be sufficiently achieved before starting an appropriate treatment.
Subject(s)
Sarcoidosis, Pulmonary/diagnostic imaging , Sarcoidosis/diagnostic imaging , Tomography, X-Ray Computed , Diagnosis, Differential , Diagnostic Errors , Humans , Lung/diagnostic imaging , Magnetic Resonance ImagingABSTRACT
We report the case of a 67-year-old female with a rare variant of interstitial granulomatous dermatitis showing multiple skin-colored papules. Clinically, numerous skin-colored or reddish papules were distributed on her back and posterior thighs with itchy scaly erythema on the upper back. After topical steroid application, skin-colored papules still remained after the disappearance of itchy scaly erythema. Histopathologically, perivascular and interstitial infiltration of lymphocytes and histiocytes with occasional multinucleated giant cells were observed in the superficial and mid reticular dermis, accompanied by mild mucin deposition. Interstitial granulomatous dermatitis is similar to interstitial granuloma annulare, but can be differentiated from it by lesser degrees of collagen degeneration with mucin deposition and frequent association with arthritis or rheumatic diseases. As previously reported, multiple asymptomatic skin-colored papules are considered a rare but distinct variant of interstitial granulomatous dermatitis. Although no apparent underlying disorder has developed in the presented case, careful follow-up needs to be continued.
Subject(s)
Dermatitis/pathology , Granuloma/pathology , Skin Pigmentation , Skin/pathology , Aged , Autoimmune Diseases/diagnosis , Autoimmune Diseases/pathology , Dermatitis/diagnosis , Female , Granuloma/diagnosis , HumansABSTRACT
Lyme boreliosis is caused by the spirochete Borrelia burdorferi, which is transmitted by ticks. A 59 year-old woman developed pyrexia, strong headaches, ataxia, dysarthria and tremor of the limbs after a tick bite. She was unable to work and eat on her own. She was hospitalized three times and diagnosed with cerebellar intention tremor, cerebellar ataxia, dysarthria, bilateral horizontal gaze paralysis and a central lesion of the left facial nerve. There were no pyramidal, sensory or psychiatric disturbances. The brain MRI showed multifocal leucoencephalopathy with many hyperintense areas in both hemispheres, as well as in the left superior pedunculus cerebellaris. Diagnosis was confirmed by serologic examination. Treatment with cephtriaxone, doxycycline, methylprednisolone, cephixime and ciprofloxacine was administered without effect on the tremor, ataxia and horizontal gaze paralysis. Treatment was then administered with 5-hydroxytriptamine (5-HT) in increased doses. The result of the three-month treatment with 5-HT was a gradual diminution of the tremor and the ataxia and an increase in the ability to eat, walk and work independently.
Subject(s)
Lyme Disease/drug therapy , Lyme Disease/physiopathology , Serotonin/therapeutic use , Tremor/drug therapy , Tremor/physiopathology , Cerebellar Ataxia/complications , Cerebellar Ataxia/drug therapy , Cerebellar Ataxia/physiopathology , Female , Humans , Lyme Disease/complications , Lyme Disease/diagnostic imaging , Magnetic Resonance Imaging , Middle Aged , Tremor/complicationsABSTRACT
AIMS: This article reports current evidence on the association between Lp(a) and cardiovascular (CV) disease and on pathophysiological mechanisms. The available information on therapy for reduction of lipoprotein(a) is also discussed. DATA SYNTHESIS: Although some evidence is conflicting, Lp(a) seems to increase CV risk through stimulation of platelet aggregation, inhibition of tissue factor pathway inhibitor, alteration of fibrin clot structure and promotion of endothelial dysfunction and phospholipid oxidation. Lp(a) 3.5-fold higher than normal increases the risk of coronary heart disease and general CV events, particularly in those with LDL cholesterol ≥ 130 mg/dl. High Lp(a) values represent also an independent risk factor for ischemic stroke (more relevant in young stroke patients), peripheral artery disease (PAD) and aortic and mitral stenosis. Furthermore, high Lp(a) levels seem to be associated with increased risk of cardiovascular events in patients with chronic kidney disease, particularly in those undergoing percutaneous coronary intervention. CONCLUSIONS: Lipoprotein (a) (Lp[a]) seems to significantly influence the risk of cardiovascular events. The effects of statins and fibrates on Lp(a) are limited and extremely variable. Nicotinic acid was shown effective in reducing Lp(a) but, due to its side effects and serious adverse events during clinical trials, it is no longer considered a possible option for treatment. To date, the treatment of choice for high levels of Lp(a) in high CV risk patients is represented by LDL-Apheresis. Thanks to innovative technologies, new selectively inhibiting LPA drugs are being developed and tested.
Subject(s)
Cardiovascular Diseases/etiology , Dyslipidemias/complications , Lipoprotein(a)/blood , Biomarkers/blood , Blood Component Removal , Blood Platelets/metabolism , Cardiovascular Diseases/blood , Cardiovascular Diseases/physiopathology , Cardiovascular Diseases/prevention & control , Dyslipidemias/blood , Dyslipidemias/physiopathology , Dyslipidemias/therapy , Endothelium, Vascular/metabolism , Endothelium, Vascular/physiopathology , Fibrin/metabolism , Humans , Hypolipidemic Agents/therapeutic use , Lipoproteins/blood , Oxidation-Reduction , Phospholipids/blood , Platelet Aggregation , Risk Assessment , Risk FactorsABSTRACT
Differentiation between sarcoidosis and sarcoid type reactions at the present time remains problematic, if not impossible. Criteria for clinical behavior and/or a systematic diagnostic approach in cases of proven epithelioid cell granulomas in lesional tissue do not currently exist. This is probably the main reason for chronicity of the sarcoid-type reactions within a specific disease or for their progression with the application of incorrect therapy. The refinement of the diagnostic criteria and the classification of both conditions remain objects of further consideration. We present a model for recommendations for an optimal diagnostic approach in patients with epitheloid cell granulomas, aiming to facilitate the differentiation between sarcoidosis and sarcoid type reactions, hopefully leading to optimization of subsequent therapy.
ABSTRACT
IMP-3 is generally considered as an oncofetal protein, which plays a critical role in regulation of cell proliferation via an IGF-II-dependent pathway in K562 leukemia cells. IMP-3 expression has been detected in malignancies with various origins, while its appearance in adult tissue is generally considered abnormal, with some exceptions. IMP3 is also considered a prognostic biomarker in patients with renal cell carcinoma and clear-cell type ovarian carcinoma, hepatocellular carcinoma, pancreatic ductal adenocarcinoma and in patients with poorly differentiated thyroid carcinoma and uterine cervical carcinomas, testicular cancer and malignant melanoma. To our knowledge, no more than 4 PubMed-indexed studies have investigated the expression of IMP-3 in melanocytic lesions, namely its role in the differentiation between benign and malignant neoplasms. We investigated the expression of IMP-3 in a small series of benign melanocytic lesions, dysplastic nevi and melanomas, aiming to establish its significance as a marker for their distinction, comparing the results with those from the literature. IMP- 3 immunostaining was performed in 30 melanocytic lesions: 10 malignant melanomas, 10 dysplastic nevi and 10 benign melanocytic nevi. Our results revealed expression in 20% of dysplastic lesions and 40% of melanoma cases, while none of the benign nevi showed positive expression. These data contradict some of the results from other studies and raise some questions regarding the correlation between IMP- 3 and the degree of dysplasia of melanocytic nevi, as well as its potential relationship with prognostic parameters in melanoma, including tumor thickness and mitotic rate. Our results suggest that IMP-3 expression could be only an auxiliary marker for differentiation between dysplastic nevi and benign nevi, since although it is not expressed in all dysplastic lesions, staining correlates with the degree of dysplasia/atypia. It seems that IMP-3 expression is not a useful discriminator between dysplastic nevi and melanoma nor a good prognostic marker in melanoma.
Subject(s)
Biomarkers, Tumor/metabolism , Dysplastic Nevus Syndrome/metabolism , Gene Expression Regulation, Neoplastic , Melanoma/metabolism , Nevus, Pigmented/metabolism , RNA-Binding Proteins/biosynthesis , Adult , Bulgaria , Dysplastic Nevus Syndrome/diagnosis , Dysplastic Nevus Syndrome/pathology , Female , Humans , K562 Cells , Male , Melanoma/diagnosis , Melanoma/pathology , Nevus, Pigmented/diagnosis , Nevus, Pigmented/pathology , PrognosisABSTRACT
The differentiation between sarcoidosis and sarcoid-type reactions remains a clinical and histopathologic diagnostic dilemma. A definitive distinction is yet to be determined according to the current literature data. Sarcoid-like tissue reactions with identifiable infectious or other immunogenic antigens, should be classified as non-specific clinical manifestations of a specific disease. The current assignment of this type of reaction under the generic umbrella of sarcoidosis is incorrect and may result in the subsequent misinterpretation of the definition of the disease in general. On the other hand, this may lead to clinical studies with incorrectly selected inclusion criteria and, therefore, contradictory statements regarding the epidemiology and pathogenesis of the disease. Thus we propose the introduction of new criteria for exclusion of sarcoidosis as an autonomous disease. Recent trials on patients with probable sarcoidosis have focused on ideal criteria, or have provided information about the genetic and immunological profile of patients with specific infections or other diseases, which manifest themself as sarcoidal granulomas. This could explain the heterogeneous clinical and/or genetic profiles of the reported patients, who in fact were not affected by the autonomous disease sarcoidosis. The simplification of the current available data regarding this issue will be of fundamental importance for the correct direction of future studies, whose aim is to unravel the pathogenesis of the immunological cascade in patients with sarcoidosis and sarcoid-like type of reaction. It is expected that the introduction of exclusion criteria will inevitably lead to a change in the approach to diagnosis as well as the fundamental understanding of this mysterious disease, known as sarcoidosis.
ABSTRACT
Nevus depigmentosus is a congenital, non-progressive, well-circumscribed hypopigmented macule, seen usually at birth, or within the first years of life. Its incidence is considered as rare, with prevalence from 0.4% to 3%. The etiopathogenesis in not fully understood, although a defect in the transfer of melanosomes from melanocytes to keratinocytes has been reported. In contrast, a sharply margined hyperpigmented macule of various sizes and shapes is known as Nevus spilus - the congenital type of a Becker's nevus. The association between nevus depigmentosus and nevus spilus is extremely rare, as the incidence, as well as the etiopathogenesis of this unilateral coexistence of such double presented pigmented disorder is unknown, due to the limited literature data reported as an example of twin spotting. We present an unusual case of nevus depigmentosus in association with nevus spilus. As far as our knowledge, this is the first report of such presentation in a young female patient. Various regiments are described as therapeutic options, such as PUVA, excimer laser, intensive pulsed light, Q-switched Alexandrite laser, Q-switched alexandrite laser and different grafting techniques, are reported as successful treatment of Nevus spilus, however not always effective in other Nevus depigmentosus.
Subject(s)
Nevus, Pigmented/diagnosis , Skin Neoplasms/diagnosis , Asymptomatic Diseases , Child, Preschool , Female , Humans , Keratinocytes/pathology , Melanocytes/pathology , Nevus, Pigmented/classification , Nevus, Pigmented/pathology , Skin Neoplasms/classification , Skin Neoplasms/pathologyABSTRACT
Cutaneous angiomyolipoma (AMP) of the ear is an extremely rare benign mesenchymal tumour. Angiomyolipomas are the most common benign tumour of the kidney and could be associated in 20% of the cases with the tuberous sclerosis complex (TBC), in which condition, most of the patients have several angiomyolipomas affecting both of the kidneys. We report the rare case of a 66-year-old female who had an asymptomatic, solitary, nodule on the helix of the right ear for several years, which was histologically assessed as angiomyolipoma. There were no clinical signs of the tuberous sclerosis complex (TBC) or renal AML. A surgical excision was performed with an excellent therapeutic result. In contrast to renal AMLs or PEComas, which are often invasive and may involve regional nodes, cutaneous AMLs are solitary, non-invasive, and not associated with tuberous sclerosis, and are curable by simple elliptical excision.
Subject(s)
Angiomyolipoma/surgery , Ear Neoplasms/surgery , Skin Neoplasms/surgery , Aged , Angiomyolipoma/pathology , Ear Neoplasms/pathology , Female , Humans , Skin Neoplasms/pathologyABSTRACT
The reason why the cutaneous form of sarcoidosis is well known in the literature is because of its spectrum of manifestations granting it the fame of a Great Imitator. The mystery shrouding the pathogenesis of this rare cutaneous disease is still there (in spite of the fundamental progress of the various diagnostic methods in current day medicine). The production of the morphological substrate - the epithelioid cell granuloma - which is considered to be characteristic of skin sarcoidosis, could, however, also be the end result of a reaction to i) various specific infectious agents such as Leishmaniasis cutis, coccidioidomycosis, etc., ii) certain residual bacterial or other mycobacterial antigens which, at the moment of setting the diagnosis are - by definition - non-infectious but still immunogenic, as well as iii) different tumor antigens in lesional tissue or other location. Often, differentiating between sarcodiosis and a sarcoid-like reaction, based on the updated criteria for cutaneous sarcoidosis, is problematic to downright impossible. A future characterization of the genetic signature of the two conditions, as well as the implementation of additional mandatory panels for i) the identification of certain infectious or ii) non-infectious but immunogenic and iii) tumor antigens in the epithelioid cell granuloma (or in another location in the organism), could be a considerable contribution to the process of differentiating between the two above-mentioned conditions. This will create conditions for greater accuracy when setting the subsequent therapeutic approaches.
Subject(s)
Sarcoidosis/etiology , Skin Diseases/etiology , Diagnosis, Differential , Humans , Sarcoidosis/diagnosis , Sarcoidosis/genetics , Sarcoidosis/therapy , Skin Diseases/diagnosis , Skin Diseases/genetics , Skin Diseases/therapyABSTRACT
For several decades the mystery of sarcoidosis has continued to evade revelation. Nowadays, due to medical progress and the opportunity of performing highly specialized tests which assist the identification of this condition as a separate disease, the understanding of the eternal mystery appears closer. Nevertheless, many contemporary studies focus on the putative link between sarcoidosis and infectious antigens isolated from skin lesions. On the other hand, a golden rule to differentiate sarcoidosis from other conditions such as tuberculosis and sarcoid-like reactions is the sterility of granulomas. However, there are hypotheses which state that sarcoidosis could be related to tuberculosis and, in particular, to the Mycobacterium species. The similarities that many authors identify between the genetic signatures of the two conditions definitely raise concerns regarding: i) the inability to categorize every single case in a clear-cut way, namely in inflammatory/autoimmune or infectious; ii) the need of new criteria to clearly differentiate sarcoid-type reactions in the context of infectious diseases from sarcoidosis as an autonomous disease. We report the case of a 35-year-old male patient with histopathological evidence of sarcoid-like granulomas in cutaneous lesions on the face and imaging studies consistent with a systemic form of sarcoidosis. However, a positive QuantiFERON-TB Gold test and Ziehl-Neelsen staining was found, leading to the diagnosis of a rare case of TBC with histopathological evidence of sarcoid-like lesions. The following are also discussed: i) the potential role of tuberculosis antigens in the context of occult tuberculosis as generators of sarcoid-type of reaction; and ii) the necessity of additional diagnostic panels as a standard procedure in patients with suspected sarcoid granulomas of unknown origin.
Subject(s)
Sarcoidosis/diagnosis , Skin Diseases/diagnosis , Tuberculosis/diagnosis , Adult , Diagnosis, Differential , Humans , Male , Sarcoidosis/pathology , Skin Diseases/pathology , Tuberculosis/pathologyABSTRACT
Liver failure (LF) continues to be a serious problem due to different underlying disorders. Not only hepatocytes but Kupffer cells (KCs) and dendritic cells (DCs) are of importance in this instance. We wanted to investigate the possible role of KCs and liver DCs in the development of liver injury in patients with liver failure. Liver specimens from 23 patients who died after liver failure were examined for the presence and distribution of CD68-positive KCs and CD83-positive DCs by immunohistochemistry. The distribution of the CD83-positive DC in the sinusoidal and the periportal spaces was not even. While 39.1% of patients had a high sinusoidal density of CD83-positive cells, 60.9% demonstrated a high density of CD83-positive cells in the periportal tract. The number of CD83-positive DCs in periportal tracts in patients with advanced liver fibrosis (n=5) were high, while those with mild liver fibrosis (n=18) had low numbers of mature dendritic cells (χ2=4.107; p=0.043). In addition, all patients with intensive fibrosis had low counts of CD68-positive KCs in portal tracts vs patients with mild fibrosis of which 67% had high counts (χ2=6.97; p=0.008). In seven of the patients with moderate steatosis (87.5%) low numbers of CD68-positive KCs were found in sinusoids, in contrast to those with severe steatosis, where 12 patients (80%) had high KC counts (χ2=13.4; p less than 0.001). The distribution and number of CD68-positive KC and CD83-positive DC reflect the progression of liver fibrosis leading to liver failure.
Subject(s)
Dendritic Cells/physiology , Fatty Liver/complications , Kupffer Cells/physiology , Liver Cirrhosis/complications , Liver Failure/etiology , Adult , Aged , Female , Humans , Male , Middle AgedABSTRACT
The hypothesis of a relationship between sarcoidosis and malignancy was firstly formulated in 1972 by Brincker. He documented an association of sarcoid reactions or sarcoidosis with 19 lymphomas and associated malignancies. Based on various epidemiological studies, for more than 20 years sarcoidosis has been considered as a condition at increased risk for cancer, particularly lymphoproliferative disorders. The existence of a sarcoidosis-lymphoma syndrome was therefore proposed, highlighting, as a potential mechanism, the uncontrolled lymphocyte proliferation and mitotic activity. A reduced ability to eliminate an antigen and chronic inflammation have been suggested as triggering events. Leading to a reduced tumor immune surveillance, a diminished myeloid dendritic cells (mDC) function, despite up-regulated co-stimulatory and maturation markers, was also raised as potential mechanism. However, some subsequent studies have questioned the presence of a close association between the two entities and have explained those previously published as the result of selection bias and misclassification. Recently, a Swedish population-based cohort study documented a significant overall excess incidence of cancer among sarcoidosis patients, especially those with multiple hospitalizations or admission in older age, emphasizing again a potential neoplastic risk. Therefore, currently, whether these patients have an increased risk of developing malignant lesions is still debated. Larger and unbiased studies are needed before drawing definite conclusions.
Subject(s)
Neoplasms/immunology , Sarcoidosis/immunology , Animals , Bias , Cell Transformation, Neoplastic/immunology , Humans , Neoplasms/blood supply , Neoplasms/epidemiology , Neovascularization, Pathologic , Risk Assessment , Risk Factors , Sarcoidosis/epidemiology , T-Lymphocytes/immunologyABSTRACT
The main function of the eyelids is to support and protect the globe. The lower eyelid and medial canthus are often the location of malignant tumors that can be locally aggressive and require disfiguring surgeries. Chronic epiphora often appears in cases of inadequate reconstruction in this location and can require secondary procedures. We report four cases of medial canthus repair after tumor removal with loss of the inferior canaliculus. The ipsilateral superior canaliculus was removed before being transposed into the lower eyelid. This simple method allows for complete canalicular reconstruction. It obviates the need for artificial material and its potential associated complications. It has the advantage of a one-step eyelid and canalicular reconstruction and prevents epiphora after tumor resection.
Subject(s)
Eyelid Neoplasms , Lacrimal Apparatus Diseases , Lacrimal Apparatus , Plastic Surgery Procedures , Humans , Lacrimal Apparatus/surgery , Eyelids/surgery , Lacrimal Apparatus Diseases/diagnosis , Lacrimal Apparatus Diseases/etiology , Lacrimal Apparatus Diseases/surgery , Eyelid Neoplasms/surgeryABSTRACT
LAY ABSTRACT: Supporting use of evidence-based practice in public service programs for autistic individuals is critical. The California Autism Professional Training and Information Network (CAPTAIN) brings together best practices from intervention and implementation research to support scale up of autism services. The current study was designed to evaluate the impact of CAPTAIN on provider-level outcomes including attitude toward, knowledge, fidelity, and use of autism EBPs and overall classroom quality. Overall, results indicated variability across measures, with some significant differences between CAPTAIN-trained and non-CAPTAIN-trained providers. These preliminary findings show promise for the efficacy of the CAPTAIN model to increase dissemination and implementation of EBP at the classroom level.
Subject(s)
Autism Spectrum Disorder , Autistic Disorder , Autism Spectrum Disorder/therapy , Autistic Disorder/therapy , California , Evidence-Based Practice , Humans , Information ServicesABSTRACT
Point-of-care ultrasound (POCUS) is increasingly used to assess medical patients. It has many uses in daily clinical practice, including improved diagnostic timeliness and accuracy, and providing information about a patient's prognosis and follow-up. It has been integrated into numerous specialities, but remains relatively undefined in internal medicine training programs. Ultrasonography is a useful tool in the standard clinical practice of internists in numerous clinical scenarios (Emergency Department, hospital ward, general and specific consultations, and home care). Although POCUS has been recently included in the European curriculum of internal medicine, there are differences between European internists in its use, ranging from not at all to well structured educational programs. The use of POCUS needs to be widespread in internal medicine departments, and to accomplish this we must encourage structured training. This document details the consensus-based recommendations by the European Federation of Internal Medicine (EFIM) Ultrasound working group. We establish POCUS core competencies and clinical settings for internists in a symptom-based approach. We also propose training requirements, providing a framework for training programs at a national level.
Subject(s)
Internal Medicine , Point-of-Care Systems , Curriculum , Humans , Internal Medicine/education , Point-of-Care Testing , UltrasonographyABSTRACT
By observing the real-time behavior of focal liver lesions at three vascular phases (arterial, portal-venous, and late), contrast-enhanced ultrasound (CEUS) has been successfully applied to differentiate benign from malignant hepatic nodules. In recent years, numerous studies highlighted the usefulness of CEUS also for other applications such as abdominal trauma, renal, pancreatic, thyroid, and inflammatory bowel diseases, supporting its role even in differentiating benign from malignant splenic nodules. Therefore, the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) recently updated the guidelines for the use of ultrasound contrast agents in clinical practice, pointing out the indication to characterize splenic parenchymal inhomogeneity or suspected lesions found on conventional ultrasound (BUS). We describe the case of a patient with a history of colon cancer and finding, at BUS and CEUS, of hypoechoic lesions with a highly suggestive pattern for metastases, subsequently histologically proved to be splenic localizations of a benign and multisystemic granulomatous disease such as sarcoidosis. We therefore reviewed the current literature focusing on the role of CEUS in differentiating benign from malignant splenic lesions, emphasizing on the lack of data and numerical shortage of sarcoidosis derived-lesions in the available studies. We conclude that sarcoidosis remains a diagnosis of exclusion and new studies are needed before defining precise indications of CEUS in these patients.
ABSTRACT
BACKGROUND: The 5-HT(4) receptor agonist, mosapride citrate, accelerates gastric emptying. However, the effect of mosapride on colonic function has not been well investigated. We examined whether mosapride changes rectosigmoid motility and perception in patients with irritable bowel syndrome (IBS). METHODS: Thirty-seven patients with IBS and 18 healthy subjects were studied. All subjects underwent a rectosigmoid barostat test to measure pain perception to intraluminal distention and resting smooth muscle motility for 20 min in the fasting state. Irritable bowel syndrome patients were then randomly assigned to receive either mosapride 15 mg (n=19) or placebo (n=18) orally with 200 mL water. Rectosigmoid motility and perception were measured again for 60 min following dosing. Rectosigmoid tone and contractility were evaluated in each 10-min period. KEY RESULTS: The pain threshold in the patients was significantly lower than that in controls (P<0.01). There were no differences between mosapride and placebo groups in pain threshold, barostat bag volume, or number of contractions at baseline. Mosapride significantly decreased the mean bag volume (P<0.01; group × period interaction by two-way anova) and increased the mean number of contractions (P<0.05) compared with placebo, but did not affect the perception. In IBS patients with constipation (i.e., excluding diarrhea-predominant subjects), mosapride (n=13) increased rectosigmoid tone (P<0.01) and contractions (P<0.05) more than placebo (n=14). CONCLUSIONS & INFERENCES: Mosapride stimulates colonic motility without any adverse effect. These findings suggest that mosapride may have the potential to treat IBS patients with constipation and/or functional constipation. Further clinical trials are warranted to confirm the efficacy of this agent.
Subject(s)
Benzamides , Colon, Sigmoid/drug effects , Gastrointestinal Motility/drug effects , Irritable Bowel Syndrome , Morpholines , Pain Perception/physiology , Rectum/drug effects , Serotonin 5-HT4 Receptor Agonists , Adult , Animals , Benzamides/pharmacology , Benzamides/therapeutic use , Colon, Sigmoid/physiopathology , Female , Humans , Irritable Bowel Syndrome/drug therapy , Irritable Bowel Syndrome/physiopathology , Male , Manometry , Morpholines/pharmacology , Morpholines/therapeutic use , Receptors, Serotonin, 5-HT4/metabolism , Rectum/physiopathology , Serotonin 5-HT4 Receptor Agonists/pharmacology , Serotonin 5-HT4 Receptor Agonists/therapeutic use , Serotonin Plasma Membrane Transport Proteins/genetics , Young AdultABSTRACT
BACKGROUND: The profile of intestinal organic acids in irritable bowel syndrome (IBS) and its correlation with gastrointestinal (GI) symptoms are not clear. We hypothesized in this study that altered GI microbiota contribute to IBS symptoms through increased levels of organic acids. METHODS: Subjects were 26 IBS patients and 26 age- and sex-matched controls. Fecal samples were collected for microbiota analysis using quantitative real-time polymerase chain reaction and culture methods, and the determination of organic acid levels using high-performance liquid chromatography. Abdominal gas was quantified by image analyses of abdominal X-ray films. Subjects completed a questionnaire for GI symptoms, quality of life (QOL) and negative emotion. KEY RESULTS: Irritable bowel syndrome patients showed significantly higher counts of Veillonella (P = 0.046) and Lactobacillus (P = 0.031) than controls. They also expressed significantly higher levels of acetic acid (P = 0.049), propionic acid (P = 0.025) and total organic acids (P = 0.014) than controls. The quantity of bowel gas was not significantly different between controls and IBS patients. Finally, IBS patients with high acetic acid or propionic acid levels presented with significantly worse GI symptoms, QOL and negative emotions than those with low acetic acid or propionic acid levels or controls. CONCLUSIONS & INFERENCES: These results support the hypothesis that both fecal microbiota and organic acids are altered in IBS patients. A combination of Veillonella and Lactobacillus is known to produce acetic and propionic acid. High levels of acetic and propionic acid may associate with abdominal symptoms, impaired QOL and negative emotions in IBS.