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The results of caustic ingestions.

BACKGROUND/AIMS: The ingestion of caustic substances is a common condition, which may result in serious injuries of the upper gastrointestinal system. The purpose of this study is to assess the outcomes of patients who had a history of the ingestion of caustic substances. METHODOLOGY: Between January 1995 and May 2002, 53 patients with clinical and/or endoscopic signs of caustic agents injury admitted to the Emergency Surgery Service of University of Istanbul, Istanbul Medical School, were retrospectively evaluated. RESULTS: The group consisted of 29 females and 24 males with a mean age of 33 years (range 15 to 77). Caustic ingestion was accidental in 31 (59%) and suicidal in 22 (41%). Twenty-five (47%) patients had history of acid ingestions, 21 (40%) alkaline and 7 (12%) unknown agents. The findings of upper gastrointestinal tract endoscopy in 37 patients were as follows: i) fourteen patients had Grade I esophagitis, ii) fourteen patients had Grade II esophagitis; four with gastric mucosal burn, three with gastric and duodenal mucosal burn, five with pharyngeal mucosal burns, iii) two patients had gastric and duodenal mucosal burns, iv) four patients had gastric mucosal burn, vi) three patients had esophageal, gastric and duodenal mucosal burn. Eight patients (15%) with signs of acute abdomen underwent urgent surgery (six of these cases were acid ingestions and seven were suicidal ingestions); four of these patients with esophageal necrosis and gastric perforation, two with esophageal, gastric, duodenal and jejunal necrosis, one with local necrosis in the gastric fundus, and one had normal findings at laparotomy. The mean follow-up period was 11.6 months (range 1 to 42 months). During the follow-up one patient presented with pyloric stenosis, which required surgery. The mortality rate was 11%. CONCLUSIONS: Suicidal caustic ingestion and acid ingestion seem to cause more severe injuries. Early admission to the hospital with clinical and endoscopic evaluation and early surgery when required may reduce morbidity and mortality.

Accidents↗

Role of NO mechanism in cardiovascular effects of diaspirin cross-linked hemoglobin in anesthetized rats.

The role of nitric oxide (NO) in the cardiovascular actions of diaspirin cross-linked hemoglobin (DCLHb) was studied in anesthetized rats. The regional circulatory and systemic hemodynamic effects of DCLHb (400 mg/kg iv) were studied using a radioactive microsphere technique in control (untreated) and L-arginine (a NO precursor) pretreated rats. DCLHb produced a significant increase in blood pressure (75%), cardiac output (42%), stroke volume (36%), and total peripheral resistance (45%), without affecting heart rate, when administered to control rats. L-Arginine pretreatment significantly attenuated DCLHb-induced systemic hemodynamic effects. DCLHb-induced increase in blood flow to the skin and spleen was completely blocked, and that to the heart was partially blocked, by L-arginine pretreatment, suggesting that cardiovascular actions induced by DCLHb could be antagonized by the NO precursor L-arginine. The NO synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME) produced significant increases in regional vascular resistance, leading to a decrease in blood flow to all the organs except the heart, where an increase in blood flow and a decrease in vascular resistance was observed. DCLHb, when administered in L-NAME-pretreated rats, accentuated the decrease in blood flow to the gastrointestinal system, spleen, mesentery and pancreas, skin, and musculoskeletal system. These studies provide evidence that the NO precursor L-arginine can attenuate the effects of DCLHb and that DCLHb can potentiate the effect of the NOS inhibitor L-NAME. The role of NO in the mechanism of action of DCLHb was further studied by estimating plasma guanosine 3',5'-cyclic monophosphate (cGMP) in control, DCLHb-treated, L-NAME-treated, and L-NAME followed by DCLHb-treated rats. DCLHb and L-NAME significantly decreased the concentration of circulating cGMP in blood plasma. L-NAME pretreatment potentiated DCLHb-induced decrease in cGMP levels. Because the formation of cGMP is stimulated by NO, these studies provide additional evidence for the involvement of NO in the mechanism of action of DCLHb. It is concluded that NO plays an important role in the cardiovascular effects of DCLHb.

Animals↗

Gastrointestinal cancer in the elderly.

Tumors in the gastrointestinal system are a significant health problem for older adults. If diagnosed at an early stage, many patients are curable. At advanced stages, however, only palliative therapy can be offered. Adjuvant therapy is beneficial only in colorectal carcinoma and a small number of highly selected patients. This article describes the treatment for these cancers as it relates to the older patient population.

Age Factors↗

[Multiple organ dysfunction syndrome].

Multiple organ dysfunction syndrome (MODS) is a clinical situation that has been described as a result of the rapid progress and advances that have been made in recent decades in the physiology, diagnosis, and therapeutic support of critically ill patients. In 1991, in view of the confusing terminology used to characterize processes coursing with systemic inflammatory response syndrome (SIRS), a consensus conference was held. A series of basic definitions were established and the term "multiple organ failure" was replace by MODS. In response to outside aggression, the organism tries to defend itself with two mechanisms: a non-specific humoral and cellular response called inflammation, and a specific antigenic response that modifies the genetic codes of cells of the defense system and constitutes an immunological response. At present it is thought that the inflammatory response is activated (SIRS) in response to an uncontrolled aggression, but an antiinflammatory response syndrome (ARS) exists as well. An exaggerated SIRS can lead to MODS. MODS usually debuts with pulmonary dysfunction. If the aggression persists, cardiovascular, renal, hepatic, coagulation, central nervous system, gastrointestinal metabolism, neuroendocrine and musculoskeletal failure follow. A series of causes often trigger this syndrome and certain factors favor it. Prevention of these causes and factors in fundamental for controlling the occurrence of MODS. At present, there is no clear treatment for MODS, although numerous studies designed to block the release of certain proinflammatory mediators or to neutralize antiinflammatory responses are being carried out.

Consensus Statements as Topic↗

The pharmacology of CP-154,526, a non-peptide antagonist of the CRH1 receptor: a review.

Since CRH has been shown to mediate stress-induced physiological and behavioral changes, it has been hypothesized that CRH receptor antagonists may have therapeutic potential in disorders that involve excessive CRH activity. CP-154,526 and its close analog antalarmin are potent, brain-penetrable, selective nonpeptide CRH1 receptor antagonists that were discovered in an effort to develop compounds with efficacy in CNS disorders precipitated by stress. Since its discovery many investigators have used CP-154,526 as a tool to study the pharmacology of CRH and its receptors and to evaluate its therapeutic potential in a variety of CNS and peripheral disorders. Systemically-administered CP-154,526 has been demonstrated to antagonize CRH- and stress-induced neuroendocrine, neurochemical, electrophysiological, and behavioral effects. These findings support the hypothesis that CRH1 receptor antagonists may have therapeutic utility in a number of neuropsychiatric disorders. CP-154,526, as well as other CRH1 receptor antagonists that have since been discovered, have also shown activity in several preclinical models of anxiety, depression, and substance abuse, while having little effect on locomotor activity and motor function. Although these effects are on occasion inconsistent among different laboratories, clinical evaluation of CRH1 antagonists appears justified on the basis of these and clinical data implicating the involvement of CRH in several CNS disorders. The effects of CRH1 antagonists on cognition, neurodegeneration, inflammation, and the gastrointestinal system have not been as extensively characterized and additional studies will be necessary to evaluate their therapeutic potential in these areas.

Animals↗

Disseminated cryptosporidiosis in Turkey: case report.

Cryptosporidium sp is a protozoan that displays an intracellular settlement primarily in the intestinal systems of humans and can result in diarrhoea. Undernourished children and persons with immunosuppression in developing countries are especially vulnerable to infection with this parasite. A 12-month-old female presented at Ege University, Faculty of Medicine, Department of Paediatrics with complaints of fever, diarrhoea, respiratory distress and growth-development retardation was diagnosed with CD40 deficiency (Hyper IgM Type 3). During the one year investigation process of the case with chronic diarrhoea and necrotic pneumonia, Cryptosporidium sp oocysts were found in nine of the 22 faecal examinations and also in transtracheal aspiration liquid examined using the Kinyoun Acid-fast staining method. In conclusion, it is thought that cryptosporidiosis should also be considered in the distinct diagnosis of immunodeficient infants who are presented with respiratory and gastrointestinal system complaints.

Cryptosporidiosis↗

Gastrointestinal stromal tumours: correlation of F-FDG gamma camera-based coincidence positron emission tomography with CT for the assessment of treatment response--an AGITG study.

BACKGROUND: Malignant gastrointestinal stromal tumours (GISTs) are a rare subset of aggressive mesenchymal tumours specific to the gastrointestinal system. They are both locally aggressive and can metastasize. The aim of this analysis was to report on our experience of the utility of coincidence positron emission tomography (co-PET) based on an 18F-FDG gamma camera in assessing treatment response to imatinib using CT as the comparator and the final clinical outcome as the end point. METHODS: We compared the results of CT and PET scans as predictors of outcome in a consecutive series of patients treated at the Prince of Wales hospital. All patients had biopsy-proven malignant GIST and were on treatment with the targeted pharmacotherapeutic agent imatinib. The majority of the patients were receiving treatment as part of the randomized trial of the European Organization for Research and Treatment of Cancer, the Australian Gastrointestinal Trials Group and the Italian Sarcoma Group, comparing 400 with 800 mg (400 mg b.i.d.). The monitoring of tumour response was achieved by serial CT measurements according to the RECIST criteria. Concurrent 18F-FDG co-PET studies were performed within a mean of 2.8 days from the CT scan and were interpreted by a consensus panel of 2 nuclear medicine physicians. RESULTS: A total of 18 patients were recruited into the study, with a total of 74 lesions. There were 47 liver lesions, 31 of which were identified on the initial 18F-FDG co-PET scans (63%). There were 10 primary lesions (4 stomach, 4 duodenal, 2 small bowel), 9 of which were demonstrated on initial 18F-FDG co-PET examinations (90%). There were 17 extrahepatic metastatic sites, 15 of which were visualized on the initial 18F-FDG study (88%). Of the 18 patients, 8 showed concordant improvement on both CT and (18)F-FDG co-PET criteria. One patient showed concordant worsening and 1 was not FDG avid. Eight patients initially showed discordance. 18F-FDG co-PET studies demonstrated changes preceding CT findings in all 8 patients with subsequent concordant improvement. CONCLUSION: 18F-FDG co-PET is a useful modality to monitor treatment response to imatinib in patients with malignant GIST. Although there is a relatively reduced sensitivity when compared with CT for the detection of lesions especially in the liver, co-PET changes in several instances precede the changes on CT scanning. This modality has the potential to influence clinical decision making and should be considered as part of the standard care of patients on imatinib.

Antineoplastic Agents↗

[Use and importance of cytology for tumor diagnosis in internal medicine].

Many fields of internal medicine give the assumption for the ingenious application of cytodiagnostics. The respiratory tract, the gastrointestinal system and the urinary passage are the most important groups of organs. A technically unobjectionable gaining of material is the basis for this. The examination of exfoliated cells and the fine needle aspiration biopsy are the technical variants. The close cooperation of a morphologically interested clinician with a clinically interested morphologist and the guaranty of the mutual control of cytology and histology yield a promising success method for the clinical differential diagnostics and for the early recognition of cancer.

Biopsy, Needle↗

Distribution of P2Y6 and P2Y12 receptor: their colocalization with calbindin, calretinin and nitric oxide synthase in the guinea pig enteric nervous system.

The distribution of P2Y(6) and P2Y(12) receptor-immunoreactive (ir) neurons and fibers and their coexistence with calbindin, calretinin and nitric oxide synthase (NOS) has been investigated with single and double labeling immunostaining methods. The results showed that 30-36% of the ganglion cells in the myenteric plexus are strongly P2Y(6) receptor-ir neurons; they are distributed widely in the myenteric plexus of stomach, jejunum, ileum and colon, but not in the submucosal plexus, with a typical morphology of multipolar neurons with a long axon-like process. About 42-46% of ganglion cells in both the myenteric and submucosal plexuses show P2Y(12) receptor-ir. About 28-35% of P2Y(6) receptor-ir neurons were found to coexist with NOS and 41-47% of them coexist with calretinin, but there was no coexistence of P2Y(6) receptor-ir with calbindin. In contrast, all P2Y(12) receptor-ir neurons were immunopositive for calbindin, although occasionally P2Y(12) receptor-ir neurons without calbindin immunoreactivity were found, while none of the P2Y(12) receptor-ir neurons were found to coexist with calretinin or NOS in the gastrointestinal system of guinea pig. The P2Y(12) receptor-ir neurons coexpressing calbindin-ir in the small intestine are Dogiel type II/AH, intrinsic primary afferent neurons.

Animals↗

Psychosomatic aspects of gastrointestinal disease.

Gastrointestinal diseases are notoriously protean in their modes of expression. The patient's description of symptoms is particularly important, but psychologic, physiologic, and social factors can cause data-base unreliability. Many of the patients termed crocks have symptoms referable to the gastrointestinal system, and they are at considerable health risk, since they usually alienate health care personnel. Patients with pancreatitis usually have a history of heavy alcohol intake which also needs treatment. Behavioral disturbances are related to toxic psychosis. Pancreatic carcinoma has a higher incidence of associated psychiatric symptoms than other types of cancer. Biologic, psychologic, and environmental factors all interact dynamically to cause peptic ulcer disease. There is a high correlation between the severity of inflammatory bowel disease and degree of emotional disturbances.

Aged↗

Hepatobiliary and gastrointestinal manifestations of acromegaly.

Acromegaly is a unique condition characterized by chronic growth hormone (GH) and insulin-like growth factor-1 (IGF-1) hypersecretion usually due to a pituitary adenoma. Rarely, acromegaly can result from a GH-releasing hormone carcinoid or pancreatic neoplasm which stimulates the normal pituitary to secrete GH. This review describes the interactions between acromegaly and the gastrointestinal system. In contrast to the soft tissue and skeletal changes, clinical organomegaly of the liver, kidney, and spleen is unusual in patients with acromegaly and should warrant further investigations. The prevalence of cholelithiasis is notably increased by the use of the otherwise effective GH-lowering somatostatin analog, octreotide. Patients on long-term therapy with this agent may require anticholelithogenic treatment. The frequency of malignant and premalignant polyps of the colon justify the routine screening for these lesions in newly diagnosed patients with acromegaly.

Acromegaly↗

[Neurogenic inflammation. II. pathophysiology and clinical implications].

Neurogenic inflammation is elicited by activation of unmyelinated sensory neurons through noxious stimuli and subsequent release of neuropeptides such as substance P and calcitonin gene-related peptide (CGRP) from peripheral nerve endings. The nerve-mediated inflammatory responses in the tissue consist of hyperaemia and oedema which under some circumstances may be accompanied by pain. Neurogenic inflammation has been implicated in the pathophysiology of various human diseases with uncertain etiology. Signs of inflammation and hyperalgesia associated with chronic pain syndromes such as migraine, arthritis and complex regional pain syndrome resemble the characteristics of neurogenic inflammation. By extrapolation of convincing evidence obtained in rodent models, neurogenic inflammation is assumed to contribute to diseases of the respiratory system, gastrointestinal tract, urogenital tract, and skin in humans. Since, however, highly selective substance P receptor antagonists, found to be effective against inflammation in rodents, failed to inhibit inflammatory processes in clinical trials, the hypothesis of an involvement of neurogenic inflammation in human diseases is discussed critically in this review. Beyond its primarily inflammatory character neurogenic inflammation can be regarded as a mechanism that activates protective responses, thus bringing about a first line of defence to maintain the integrity of the tissue and to contribute to tissue repair.

Animals↗

A review of the drug events reported by 12,917 patients treated with cephalexin.

This paper reviews the adverse events reported by 12,917 patients treated with cephalexin in formal clinical trials. Six percent of all patients reported adverse events, and in 3% the association with the drug was thought to be definite or probable. In the remaining 3%, the relationship was uncertain. The gastrointestinal system was most commonly involved, with diarrhoea being reported by 164 patients. Patients in the upper and lower age ranges reported more events than those in the middle range, and most events were reported 6-15 days after treatment started. Patients who received cephalexin 4 times a day reported more events than those who were treated twice daily. Four hundred and sixty-two patients had a known sensitivity to penicillin, and all except 21 of these were treated with cephalexin without developing a sensitivity reaction.

Adolescent↗

Copper absorption and bioavailability.

The human gastrointestinal system can absorb 30-40% of ingested copper from the typical diets consumed in industrialized countries. Experimental data support the existence of a carrier-mediated transport mechanism with an affinity constant in the micromolar range. Aging probably decreases the efficiency of copper homeostasis, resulting in higher plasma copper concentrations in the elderly. Physiologic differences may account for the higher cupremia of females. Supplements of minerals with similar chemical characteristics could reduce copper absorption. This property has pharmacologic applications in Wilson disease. Manipulation of the fiber content of the diet may have an indirect effect on copper bioavailability by altering the bioavailability of mineral antagonists. Proteins and soluble carbohydrates tend to improve copper absorption and bioavailability by enhancing its solubility and intestinal bulk flow. Organic acids, other than ascorbic acid, or agents that form low-molecular-weight chelates, are likely to have a positive effect on overall copper absorption. Conditions associated with malabsorption of macronutrients and gastrointestinal disease can impair copper uptake and contribute to suboptimal copper status.

Animals↗

Drug absorption in the elderly: biopharmaceutical considerations for the antiepileptic drugs.

The management of antiepileptic drug (AED) pharmacokinetics remains a challenge in the treatment of patients with epilepsy. Drug characteristics, such as protein binding, mechanisms of drug elimination, and the potential for pharmacokinetic/pharmacodynamic interactions, are important considerations for drug selection and may help determine overall effectiveness. In elderly patients with epilepsy, the likelihood of polytherapy, along with physiological changes associated with aging, can make pharmacokinetic issues even more significant. One aspect of pharmacokinetics that has received less attention is the process of oral drug absorption. Aging can have variable effects on the gastrointestinal system. Some of these physiological changes have the potential to impact absorption patterns of some medications, including AEDs. Altered oral protective reflexes, xerostomia, and delayed esophageal emptying in elderly patients may complicate oral administration of some medications. Altered gastric pH could modify drug absorption, and modified gastric emptying rates can influence the bioavailability of some AEDs. Finally, intestinal transit times may be slower in elderly patients compared to younger patients, possibly altering the absorption of some AEDs. These age-related physiological changes that may affect AED pharmacokinetics should be considered when treating elderly patients with epilepsy.

Absorption↗

TASK-3 immunoreactivity shows differential distribution in the human gastrointestinal tract.

The presence and distribution of TASK-3 immunopositivity (a channel with potential oncogenic significance) was investigated in the human gastrointestinal system. The immunohistochemical reactions were performed with two commercially available polyclonal antibodies, targeting different epitopes of the channel protein. Experiments conducted on frozen and formalin-fixed samples indicated that the application of a suitable antigen retrieval (AR) technique was essential to produce consistent, strong and reproducible TASK-3-specific immunolabelling of the formalin-fixed tissue. The lack of or inappropriate selection of the AR resulted in false-negative reactions. As for the distribution of the TASK-3 channels, strong immunolabelling was observed in the gastric and large intestinal mucosa, with particularly prominent immunoreactivity of the epithelial cells. In contrast, the smooth-muscle layers demonstrated weak TASK-3 positivity. Intense TASK-3 expression was noted in both the exocrine and endocrine pancreas, but the islets of Langerhans exhibited more powerful reactions. The ductal apparatus of the submandibular gland and lymphocytes situated in pericolonic lymph nodes were also TASK-3 positive. Strong TASK-3 positivity could also be observed in malignant gastrointestinal tumours, with intense nuclear-perinuclear labelling of some of the tumour cells. The present findings suggest that TASK-3 channels may have roles in the gastrointestinal functions, including insular hormone secretion.

Biomarkers↗

Colonoscopy is a useful diagnostic tool for transplant recipients with lower abdominal symptoms.

Transplant recipients are at higher risk for infection and malignancy due to therapies aimed at preventing rejection. Early detection and successful treatment of such complications is of pivotal importance for both patient and graft survival. In this study, we evaluated findings of 91 colonoscopies and colonic histopathologic findings in recipients who presented with lower gastrointestinal system complaints between January 1996 and January 2003. The study group included 79 renal and liver transplant patients. The indications for colonoscopy were diarrhea (n = 58), abdominal pain (n = 5), hematochezia (n = 19), unexplained anemia (n = 5), thickening of a colonic segment detected on computerized tomography (n = 2), screening for lymphoma (n = 1), and Kaposi's sarcoma (n = 1). During the procedures, all suspicious lesions were biopsied and specimens of normal-appearing mucosa collected when deemed necessary in relation to the clinical complaints. The endoscopic findings were classified as follows: 0 = "normal," with clear visualization of the vascular network and normal-appearing mucosa; 1 = "erythema", with tissues showing erythema, edema, hyperemia, and loss of normal vascular network; 2 = "ulcerative," with tissues exhibiting ulceration and fragility; and 3 = "coincidental findings," such as polyp or angiodysplasia. Colonoscopic and/or histopathologic abnormalities were detected in 44.5% of the 91 colonoscopy procedures. The results indicate that colonoscopy is a valuable diagnostic tool for evaluation of transplant recipients with lower gastrointestinal complaints. After an initial workup colonoscopy is important to establish an accurate diagnosis.

Adolescent↗

Gastrointestinal mucoadhesive patch system (GI-MAPS) for oral administration of G-CSF, a model protein.

A new gastrointestinal mucoadhesive patch system (GI-MAPS) has been designed for the oral delivery of protein drugs. The system consists of four layered films, 3.0 x 3.0 mm2, contained in an enteric capsule. The 40 microm backing layer is made of a water-insoluble polymer, ethyl cellulose (EC). The surface layer is made of an enteric pH-sensitive polymer such as hydroxypropylmethylcellulose phthalate (HP-55), Eudragit L100 or S100 and was coated with an adhesive layer. The middle layer, drug-containing layer. made of cellulose membrane is attached to the EC backing layer by a heating press method. Both drug and pharmaceutical additives including an organic acid, citric acid, and a non-ionic surfactant, polyoxyethylated castor oil derivative (HCO-60), were formulated in the middle layer. The surface layer was attached to the middle layer by an adhesive layer made of carboxyvinyl polymer (Hiviswako 103). Fluorescein (FL), 30mg, was first used as a model drug for oral administration of GI-MAPS having different surface layers in beagle dogs. The plasma FL concentration vs. time profiles demonstrated that the targeting of the systems was obtained, because the Tmax, the time when plasma FL concentrations reaches to its maximum lelev, was 2.33+/-0.82 h for HP-55 system, 3.33+/-0.41 h for Eudragit L100 system and 5.00+/-0.00 h for Eudragit S100 system. The same three kinds of GI-MAPSs containing 125 microg of recombinant human granulocyte colony-stimulating factor (G-CSF) were prepared and orally administered to dogs and the increase in total white blood cell (WBC) counts were measured as the pharmacological index for G-CSF. Comparison with the total increase of WBCs after iv injection of the same amount of G-CSF (125 microg) indicated the pharmacological availabilities (PA) of G-CSF were 23%, 5.5% and 6.0% for Eudragit L100, HP-55 and Eudragit S100 systems. By decreasing the amount of HCO-60 and citric acid, the PA of G-CSF decreased. These results suggest the usefulness of GI-MAPS for the oral administration of proteins.

Administration, Oral↗