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PubMed2002

Tolerabilities of antiretrovirals in paediatric HIV infection.

Data on the efficacy and tolerability of antiretrovirals in children are limited as, in contrast to adult studies, large paediatric cohort studies are lacking. Thus, data pertaining to adults are often extrapolated to children despite the acknowledgement that children are not little adults. This review summarises information gathered from existing reports and focuses on the tolerabilities of antiretrovirals in children infected with HIV-1. The efficacy of antiretrovirals is not included in the scope of the discussion. Taste of antiretrovirals should be an important factor when considering the tolerability of antiretrovirals in children. However, antiretroviral options are often limited in young children as only some of the antiretrovirals are available as paediatric formulations. All antiretrovirals have been associated with toxicities in children, but in general, they are relatively well tolerated. The gastrointestinal system including hepatic system is most prone to being affected by these drugs. Skin rashes and hypersensitivity reactions are also associated with antiretroviral use, particularly with the non-nucleoside reverse transcriptase inhibitors. Mitochondrial toxicities that lead to impairment of liver function, pancreatic function and lactic acidosis are associated with most of the nucleoside analogues. Haematological toxicity is often a dose limiting adverse effect especially of the nucleoside analogues, in particular zidovudine. The protease inhibitors are associated with gastrointestinal intolerance (diarrhoea) and metabolic derangements that can lead to hypercholesterolaemia and hypertriglyceridaemia, which in turn and can lead to changes in body habitus. The renal system is also affected by several drugs, the most important of which is indinavir, which has been associated with renal stones and damage to the renal tubules. Fortunately, with lower incidence of major toxicity and with the range of drugs now available for paediatric use, toxicities are usually not a barrier to effect antiretroviral therapy in children.

Anti-HIV Agents↗

PubMed1999

A review of gastrointestinal manifestations of systemic lupus erythematosus.

In this review, we analyse critically the effects of systemic lupus erythematosus (SLE) on the gastrointestinal (GI) tract from mouth to anus, attempting to distinguish the features that are most likely to be due to therapy. GI manifestations of SLE include mouth ulcers, dysphagia, anorexia, nausea, vomiting, haemorrhage and abdominal pain. GI vasculitis is usually accompanied by evidence of active disease in other organs. Early recognition of the significance of these symptoms offers the best opportunity to improve the symptoms and to aid long-term survival.

Gastrointestinal Diseases↗

PubMed2004

Implementation of a computer-assisted monitoring system for the detection of adverse drug reactions in gastroenterology.

AIM: To investigate the effectiveness of a computer monitoring system that detects adverse drug reactions (ADRs) by laboratory signals in gastroenterology. METHODS: A prospective, 6-month, pharmaco-epidemiological survey was carried out on a gastroenterological ward at the University Hospital Erlangen-Nuremberg. Two methods were used to identify ADRs. (i) All charts were reviewed daily by physicians and clinical pharmacists. (ii) A computer monitoring system generated a daily list of automatic laboratory signals and alerts of ADRs, including patient data and dates of events. RESULTS: One hundred and nine ADRs were detected in 474 admissions (377 patients). The computer monitoring system generated 4454 automatic laboratory signals from 39 819 laboratory parameters tested, and issued 2328 alerts, 914 (39%) of which were associated with ADRs; 574 (25%) were associated with ADR-positive admissions. Of all the alerts generated, signals of hepatotoxicity (1255), followed by coagulation disorders (407) and haematological toxicity (207), were prevalent. Correspondingly, the prevailing ADRs were concerned with the metabolic and hepato-gastrointestinal system (61). The sensitivity was 91%: 69 of 76 ADR-positive patients were indicated by an alert. The specificity of alerts was increased from 23% to 76% after implementation of an automatic laboratory signal trend monitoring algorithm. CONCLUSION: This study shows that a computer monitoring system is a useful tool for the systematic and automated detection of ADRs in gastroenterological patients.

Adolescent↗

PubMed2000

Gastroprotection of DNA with a synthetic cholic acid analog.

The oral delivery of functional DNA to the gastrointestinal system would constitute a desirable, noninvasive method for potentially treating a variety of diseases. The digestive process, however, remains a formidable barrier. This dilemma may be addressed by using targeted liposomes both to protect the polynucleotide and to deliver the therapeutic DNA with high tissue specificity. The present study represents the initial steps toward developing a novel gene delivery system designed to interact with the enterohepatic receptors of the small intestine. Two cholic acid esters were synthetically modified at position C(3) to incorporate a DNA-binding domain. These novel compounds were evaluated for their ability to protect DNA from the nucleases found in gastrointestinal segments. Additionally, the compounds were screened as a component of a gene delivery vector. Formulations containing the new bile salt derivatives protected DNA from degradation for more than 2 h and were capable of transfecting cultured NIH 3T3 cells.

3T3 Cells↗

PubMedDate not supplied

Criteria to consider when assessing the mortality risk in geriatric surgery.

As the population ages, surgery is performed more frequently on geriatric patients for both elective and emergency situations. Four hundred sixty-nine patients > or = 70 years of age who underwent operations were retrospectively reviewed. Sex, American Society of Anesthesiologists (ASA) score, type of admission, main surgical diagnosis, benign or malignant nature, site of disease, concomitant disease, preoperative ASA grade, and death were assessed. The ratio of the elderly against all those who were operated on in our department during the same period was 5.9%. The mortality rate was 8.5% for men and 9.4% for women. According to ASA scoring, mortality rates were 0%, 8.8%, 29.8%, 36.8%, and 66.6%, respectively (P < 0.05). The mortality rate was 2.5% for elective and 49.2% for emergency procedures (P < 0.0001). The mortality rate was 9.7% for benign and 7.2% for malignancy. Hepatopancreatic biliary conditions were most common (39.6%), followed by colorectal (19.4%), hernia (18.8%), upper gastrointestinal (15.3%), and endocrine disease (6.9%). The highest mortality rate was for diseases of the upper gastrointestinal system (30.5%; P < 0.001). The incidence of associated disease was 13.1% in patients who died (P < 0.005). Overall mortality rate in this study was 8.9%. In emergency surgery, the presence of associated disease, an ASA score of III-V, and upper gastrointestinal surgery affected the risk of postoperative death in elderly patients.

Age Factors↗

PubMed1986

[Closure systems of the gastrointestinal tract and their surgical significance].

The closure systems of the gastro-intestinal canal are based on three major forms, constrictive sphincter, dilatory closure, and kinking closure. A constrictive sphincter is attached to the oesophageal inlet and a dilatory closure to the cardiac orifice. Reflux oesophagitis may result from failure of dilatory closure. Helical fibres in crosswise arrangement rather than isolated sphincters are recordable from the pyloric region. Their function is identical with that of dilatory closure. The principle of kinking closure applies to the Papilla Vateri and the ileocecal valve. Conclusions are suggested for therapeutic approach problems of the closure systems.

Ampulla of Vater↗

PubMed1980

An introduction to the diagnosis of parathyroid disorders.

The head and neck surgeon must be well acquainted with the embryology and anatomy of the parathyroid glands to facilitate operative localization. In dealing with diseases of this multiple unit single organ system an awareness of the variety of concomitant presentations is necessary in order to surgically manage the diseased glands. Diagnosis and preoperative localization of the parathyroid glands in their hyperfunctional state demand an appreciation of their physiologic interaction with the renal, skeletal, and gastrointestinal systems.

Diagnosis, Differential↗

PubMed1990

[Studies on orocecal transit in diabetes mellitus].

The present study investigated changes of gastrointestinal transit in diabetes mellitus by a variant of the hydrogen exhalation method, which produces reliable estimates of oro-cecal transit times of a lactulose test meal. Relation to metabolic state and small fibre neuropathy was also evaluated. The latter was indexed by Airaksinen's variability score for resting pulse frequency, Ewing's index of respiratory sinus arrhythmia, and warm and cold thresholds at the foot. 15 inpatients with verified type I diabetes (nine female, six male) and eleven healthy controls (nine female, two male) were under investigation. Ages ranged from 19 to 47 and 27 to 49 years, respectively. No clearcut signs of angiopathy or neuropathy were present in patients. HbA1c values were moderately high (means +/- s = 8.2 +/- 1.6). Diabetes patients showed prolonged transit compared to controls (means +/- s = 102.7 +/- 28.2 min, and 79.6 +/- 15.4, resp.; p = 0.02, U-test). Two patients had extremely long transit times, none showed acceleration. However, neither indices of small fibre neuropathy nor metabolic parameters were significantly correlated with transit measures. Prolonged oro-cecal transit, therefore, seems to be due to a specific visceral-autonomic or primary enteric neuropathy, which is still limited to the gastrointestinal system in this stage, and/or metabolic effects.

Adult↗

PubMed2006

The life, achievements and legacy of a great Canadian investigator: Professor Boris Petrovich Babkin (1877-1950).

The present paper reviews the life and achievements of Professor Boris Petrovich Babkin (MD DSc LLD). History is only worth writing about if it teaches us about the future; therefore, this historical review concludes by describing what today's and future gastrointestinal physiologists could learn from Dr Babkin's life. Dr Babkin was born in Russia in 1877. He graduated with an MD degree from the Military Medical Academy in St Petersburg, Russia, in 1904. Not being attracted to clinical practice, and after some hesitation concerning whether he would continue in history or basic science of medicine, he entered the laboratory of Professor Ivan Petrovich Pavlov. Although he maintained an interest in history, in Pavlov's exciting environment he became fully committed to physiology of the gastrointestinal system. He advanced quickly in Russia and was Professor of Physiology at the University of Odessa. In 1922, he was critical of the Bolshevik revolution, and after a short imprisonment, he was ordered to leave Russia. He was invited with his family by Professor EH Starling (the discoverer of secretin) to his department at University College, London, England. Two years later, he was offered a professorship in Canada at Dalhousie University, Halifax, Nova Scotia. After contributing there for four years, he joined McGill University, Montreal, Quebec, in 1928 as Research Professor. He remained there for the rest of his career. Between 1940 and 1941, he chaired the Department, and following retirement, he remained as Research Professor. At the invitation of the world-famous neurosurgeon, Wilder Penfield, Dr Babkin continued as Research Fellow in the Department of Neurosurgery until his death in 1950 at age 73. His major achievements were related to establishing the concept of brain-gut-brain interaction and the influence of this on motility, as well as on interface of multiple different cells, nerves and hormones on secretory function. He had a major role in the rediscovery of gastrin. He established a famous school of gastrointestinal physiologists at McGill University. He supported his trainees and helped them establish their careers. He received many honors: a DSc in London, England, and an LLD from Dalhousie University. Most importantly, he was the recipient of the Friedenwald Medal of the American Gastroenterological Association for lifelong contributions to the field. Dr Babkin taught us his philosophical aspect of approaching physiology, his devotion to his disciples and his overall kindness. Most importantly, he has proven that one can achieve international recognition by publishing mainly in Canadian journals. He is an example to follow.

Achievement↗

PubMed2001

New pharmacological agents under clinical investigation for treating disorders of lipoprotein regulation leading to atherosclerosis.

Coronary heart disease (CHD), whose primary aetiology is atherosclerosis, is the leading cause of mortality and a major cause of morbidity in the industrialised world [1]. Serum lipoprotein levels are aetiologically related to the risk of atherosclerosis and CHD [2]. The liver and the gastrointestinal system are the major protagonists involved in regulation of lipoprotein biochemical-physiological mechanisms and the development of hypercholesterolaemia. Furthermore, specific lipoprotein receptors are being discovered as targets for pharmacological intervention to correct lipoprotein disorders. Agents that target lipoprotein regulation in the liver, gastrointestinal-biliary and atherosclerotic tissues resulting in improved serum lipoprotein levels and/or control of primary and secondary dyslipidaemic disorders including diabetes, are currently undergoing clinical trials. The most novel promising compounds, after the greatly effective newest HMG-CoA reductase inhibitors, are drugs that affect peroxisome proliferator-activated receptors, PPARalpha and PPARgamma receptors, bile acid transport mechanisms, cholesterol absorption and cholesterol acyltransferase and other biochemical targets of lipoprotein regulation. Current knowledge and ongoing trials with these agents are described here within the boundaries of investigator confidentiality agreements.

Animals↗

PubMed2005

The role of PRAJA and ELF in TGF-beta signaling and gastric cancer.

Emerging research has shown that the transforming growth factor-beta (TGF-beta) pathway plays a key role in the suppression of gastric carcinoma. Biological signals for TGF-beta are transduced through transmembrane serine/threonine kinase receptors, which in turn signal to Smad proteins. Inactivation of the TGF-beta pathway often occurs in malignancies of the gastrointestinal system, including gastric cancer. Yet, only a fraction of sporadic gastric tumors exhibit inactivating mutations in early stages of cancer formation, suggesting that other mechanisms play a critical role in the inactivation of this pathway. Smad4, a tumor suppressor, is often mutated in human gastrointestinal cancers. The mechanism of Smad4 inactivation, however, remains uncertain and could be mediated through E3-mediated ubiquitination of Smad4/adaptor protein complexes. The regulation of the TGF-beta pathway through a PRAJA, a RING finger (RING-H2) protein, and ELF, a beta-Spectrin adaptor protein, both which were originally identified in endodermal stem/progenitor cells committed to foregut lineage, could play a pivotal role in gastric carcinogenesis. PRAJA, which functions as an E3 ligase, interacts with ELF in a TGF-beta-dependent manner in gastric cancer cell lines. PRAJA is increased five-fold in human gastric cancers, and inactivates ELF. This is particularly significant since ELF, a Smad4 adaptor protein, possesses potent anti-oncogenic activity and is frequently seen to be inactivated in carcinogenic gastric cells. Strikingly, PRAJA manifests substantial E3-dependent ubiquitination of ELF and Smad3, but not Smad4. The alteration of ELF and/or Smad4 expression and function in the TGF-beta signaling pathway may be induced by enhancement of ELF degradation, which is mediated by the high level expression of PRAJA in gastrointestinal cancers. These studies reveal a mechanism for gastric tumorigenesis whereby defects in adaptor proteins for Smads, such as ELF, can undergo degradation by PRAJA, through the ubiquitin-mediated pathway.

Ephrin-A2↗

PubMed2006

Do audible and ultrasonic sounds of intensities common in animal facilities affect the autonomic nervous system of rodents?

In animal facilities, noises, often poorly controlled, occur over a wide range of frequencies and intensities. Evidence demonstrates that audible noise and ultrasound have deleterious effects on rodent physiology, but it is not known how they affect the autonomic nervous system (ANS). This study exposed 3 unrestrained, male, Sprague-Dawley rats daily to a 15-min white noise regime (90 dB), a quiet regime, or a 15-min ultrasound regime (90 dB at 4 frequencies in the range 20 to 40 kHz)--each for several weeks--and used radiotelemetry to monitor their cardiovascular responses. Exposure to audible noise increased heart rate and mean arterial pressure. Spectral analysis of HR variability showed diminished stimulation of the parasympathetic nervous system, shifting the sympathovagal balance. However, ultrasound, at the frequencies used, did not reproducibly affect cardiovascular parameters. The preliminary data obtained from this study indicate that audible noise, but not ultrasound (delivered using the same protocol), affects the ANS. Because the cardiovascular, respiratory, renal, and gastrointestinal systems are under autonomic control, such noise could have wide-ranging effects on animal physiology.

Animals↗

PubMed1991

Cytoplasmic vacuolization of enterocytes: an unusual histopathologic finding in juvenile nutritional megaloblastic anemia.

We report a case of juvenile nutritional megaloblastic anemia with emphasis on the histologic findings in the upper gastrointestinal system, including the previously unreported feature of periodic acid-Schiff (PAS)-negative, Alcian blue-negative cytoplasmic vacuoles (CV) in duodenal enterocytes. These CV were reminiscent of those described in abetalipoproteinemia; however, the patient's lipid profile was normal. All histopathologic changes in the upper gastrointestinal tract (with the exception of mild reflux esophagitis) reverted to normal following parenteral administration of vitamin B12. This case supports the notion that CV in enterocytes are a component (albeit a rare one) of the histopathology in cobalamin deficiency.

Anemia, Megaloblastic↗

PubMed1998

Prevalence of infectious diseases and associated symptoms in wastewater treatment workers.

Wastewater treatment workers (WWTW) are potentially exposed to a variety of infectious agents and toxic materials. We conducted a retrospective epidemiological study to examine the prevalence of infectious diseases and associated symptoms in WWTW. From a possible 242 WWTW, 150 completed a questionnaire that provided data pertaining to the diagnosis of an infectious disease or the prevalence of associated symptoms over a 12-month period. Comparison data were obtained from questionnaires completed by 54 college maintenance and oil refinery workers. The WWTW exhibited a significantly higher prevalence of gastroenteritis, gastrointestinal symptoms (specifically abdominal pain), and headaches. No significant differences were found with regard to respiratory and other symptoms. Employees classified by exposure categories did not exhibit significant differences in the prevalence of symptoms. While significant differences were found with regard to the health status of WWTW and controls, it appears that these risks are confined to symptoms and infectious diseases associated with the gastrointestinal system and are not inclusive of all such symptoms or diseases.

Adult↗

PubMed2001

Orlistat: in the prevention and treatment of type 2 diabetes mellitus.

Orlistat is a nonsystemically acting gastric and pancreatic lipase inhibitor that limits the absorption of dietary fat. A retrospective pooled analysis of three 2-year, double-blind, randomised, placebo-controlled trials involving patients with obesity revealed that orlistat recipients were more likely to experience an improvement, and less likely to experience a deterioration, in glucose tolerance status than placebo recipients. In comparison with placebo, orlistat recipients had significantly greater reductions in glycosylated haemoglobin and fasting plasma glucose levels in large, double-blind, randomised, placebo-controlled studies of 24 to 52 weeks' duration involving patients with obesity and type 2 diabetes mellitus. In one such study, the dosage of concomitant sulphonylureas was able to be reduced in more orlistat than placebo recipients (43.2 vs 28.9%), with discontinuation of sulphonylurea therapy achieved in 11.7% of orlistat recipients. The most common adverse effects reported in orlistat recipients with type 2 diabetes mellitus relate to the gastrointestinal system and are similar to those reported in studies involving patients without type 2 diabetes mellitus.

Administration, Oral↗

PubMed2006

[Effect of sarpogrelate in enteral feeding of patients with gastroesophageal reflux (GER)].

AIM: Enteral feeding of patients who are unable to eat or drink because of neurological disorders finally undergo percutaneous endoscopic gastrostomy (PEG) or nasogastric tube feeding. Their most common serious complication is aspiration pneumonia. Our objectives were to evaluate the effect of sarpogrelate (a 5-HT2A receptor blocker) on gastroesophageal reflux (GER) in these patients. METHODS: This study was performed in 5 elderly patients, aged 70-87 years with neurological disorders (stroke 4, post herpes encephalitis 1), on PEG or nasogastric feeding for 5 weeks-1 year. A 48-hour esophageal pH study was performed using the Degitrapper pH400 (Medtronic Co.). The pH monitor catheter was passed into the esophagus transnasally and positioned with the pH electrode 5cm above the lower esophageal sphincter. During the first 24 hours drug no drug was given, and during the next 24 hours we gave 100mg sarpogrelate 3 times. We analyzed the frequency of acid reflux (when the pH in the esophagus become less than 4.0 for more than 5 seconds, we defined this is 1 episode of acid reflux), frequency of acid reflux and mean pH values between drug-on and drug-off periods. An upright position was maintained for two hours after each meal. RESULTS: When the results of pH monitoring during two half days (from 7 pm to 7 am: 12 hours) was compared between drug-on term and drug-off term, mean pH value was statistically elevated from 6.0 +/- 0.2 (drug-off) to 6.5 +/- 0.4 (drug-on) (mean +/- SD, p< 0.05). Frequency and the total time of acid reflex showed no difference between the two periods. CONCLUSION: Treatment with sarpogrelate might be effective in patients with GER by blocking activated serotonin receptor in the gastrointestinal system.

Aged↗

PubMed1989

Small intestinal development in growth-retarded fetal sheep.

The functional maturity of the gastrointestinal system is essential for the survival of the neonate. The effects of reducing placental size and the ensuing fetal growth retardation on the development of the small intestine (SI) of the sheep fetus were investigated. At 140 days of gestation (term is 147 days), fetal body weight, gastrointestinal weight (from the abomasum to the rectum, i.e., the gut), SI weight, and SI length in the growth-retarded fetuses (n = 6) were significantly reduced (p less than 0.05) when compared with age- and breed-matched control fetuses. The SI weight was disproportionately reduced as a fraction of the gut weight or SI length (p less than 0.01). The proximal SI showed marked reductions in the thickness of the wall, muscularis externa, mucosa, villus height, and crypt depth (p less than 0.003). Densities of villi and crypts were also reduced (p less than 0.02). The crypt-to-villus ratio was maintained. Glycogen was accumulated basally in the villus epithelial cells, and their nuclei were located apically. These characteristics are comparable to those of much younger fetuses. In the distal SI, interanimal variation was large; however, the mean thickness of the wall, the muscularis externa, the mucosa, and the villus height were all reduced (p less than 0.05). In this region, the density of villi and crypts, the pattern of glycogen accumulation, and the position of the nuclei did not markedly differ between growth-retarded and control fetuses. Villus cell density was increased (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Pneumatosis cystoides intestinalis in quadriplegia: a case report.

Pneumatosis cystoides intestinalis is an uncommon clinical entity with nonspecific symptomatology of the gastrointestinal system. Its diagnosis is made by radiologic demonstration of multiple gas-filled cysts in the submucosa or subserosa of the intestinal tract. There are two major clinical types--idiopathic and secondary. A case report of a spinal cord injured patient with this condition is presented. Since gastrointestinal disturbances are common in spinal cord injured patients, health care professionals should be aware of this condition. Identification of pneumatosis cystoides intestinalis is important since it represents a benign condition and usually requires no treatment.

Humans↗