Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024523 (malabsorption)
 7,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Any infant who is jaundiced beyond two to three weeks of life should be evaluated for neonatal cholestasis. Neonatal cholestasis is defined as accumulation of bile substances in blood due to impaired excretion. These infants should always have fractionated serum bilirubin levels checked to differentiate the conjugated hyperbilirubinemia of cholestasis from unconjugated hyperbilirubinemia that is usually benign and spontaneously resolves. Conjugated hyperbilirubinemia, pale stools and dark urine are the cardinal features of neonatal cholestasis. The differential diagnosis of cholestasis is extensive and a systematic approach is helpful to quickly establish the diagnosis. Biliary atresia is a common cause of neonatal cholestasis and affected infants need surgery before 60 days of life for better prognosis. Premature infants have multifactorial cholestasis and need a modified approach to the evaluation of cholestasis. Management of cholestasis is mostly supportive, consisting of medical management of complications of chronic cholestasis like pruritus and nutritional support for malabsorption and vitamin deficiency.
 ...
PMID:Neonatal cholestasis. 1568 66

Patients with chronic cholestasis, particularly those with associated cirrhosis, are susceptible to infectious complications. A predictable consequence of cholestasis is malabsorption of fat-soluble vitamins and free radical scavengers. On the other hand, it has been postulated that cholestasis affects polymorphonuclear leukocytes function by impeding chemotaxis, phagocytosis and superoxide anion release in experimental animals. This work is aimed to evaluate the antioxidant status and phagocytic activity of neutrophils in chronic liver disease patients. 15 primary biliary cirrhosis (PBC) patients, 15 primary sclerosing cholangitis (PSC) patients, 15 chronic viral hepatitis C (HCV) patients, and 15 healthy individuals (control group) were included in this study. Levels of catalase (Cat), superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidase (GPx) and malondialdehyde (MDA) were assessed in both serum and neutrophils homogenates. Neutrophils function was estimated by nitroblue tetrazolium (NBT) reduction assay. A marked decrease in the antioxidant status was observed in serum and neutrophils' homogenate of patients with chronic liver diseases compared to healthy subjects. Significant elevation of lipid peroxides was found in all groups of liver disease patients. The majority of patients had reduced value in NBT reduction assay, which suggested a lack of response to infection by neutrophils. In conclusion, deficient antioxidant defense mechanisms may lead to excess oxygen free radicals formation that promote the pathological process in the liver. The use of free radicals scavengers by chronic liver patients may potentiate the antioxidant defense system against oxidative stress.
 ...
PMID:Study of antioxidant enzymes level and phagocytic activity in chronic liver disease patients. 1571 21

Altered bile flow physiology leads to many complications commonly seen in patients with cholestatic liver disease, regardless of the etiology. For each individual patient, a coordinated and effective treatment strategy must address the presence and the severity spectrum of malabsorption, malnutrition, vitamin and micronutrient deficiencies, pruritus, xanthomata, ascites, and liver failure, which are attributed directly or indirectly to diminished bile flow. An aggressive approach to maximizing the nutritional status of the child is vital to ensure optimal growth and development. Protein-calorie and/or fat supplementation is best discussed early. Decreasing the percentage of dietary long-chain triglycerides, providing medium-chain triglycerides, and ensuring adequate essential fatty acid and adequate protein intake may be helpful. Fat-soluble vitamin (A, D, E, and K) levels and micronutrient levels must be carefully and serially monitored and supplemented as necessary. Because the mechanisms that mediate pruritus of cholestasis remain to be determined, the use of empirical therapies continues to be standard practice. Ursodeoxycholic acid may ameliorate pruritus. Antihistamines and rifampicin may also provide temporary relief for some children. Based on the evidence that increased central opioidergic tone is present in chronic cholestasis, the use of opiate antagonists is promising but has not been evaluated in children. Selected patients with refractory pruritus that have failed maximal medical therapy have benefited from partial external biliary diversion. Ongoing dialogue with the family regarding the indications for liver transplantation is reasonable. Optimization and adherence with the pretransplant medical management enhance the chances for a successful outcome from liver transplantation. Specific to the pediatric patient, optimizing growth, development and nutrition, minimizing discomfort and disability, and aiding the child and family in coping with the stress, social, and emotional effects of chronic liver disease remain paramount.
 ...
PMID:Treatment options for chronic cholestasis in infancy and childhood. 1616 8

Malabsorption of fat-soluble vitamins is a major complication of chronic cholestatic liver disease. The most accurate way to assess vitamin A status in children who have cholestasis is unknown. The goal of this study was to assess the accuracy of noninvasive tests to detect vitamin A deficiency. Children with chronic cholestatic liver disease (n = 23) and noncholestatic liver disease (n = 10) were studied. Ten cholestatic patients were identified as vitamin A-deficient based on the relative dose response (RDR). Compared with the RDR, the sensitivity and specificity to detect vitamin A deficiency for each test was, respectively: serum retinol, 90% and 78%; retinol-binding protein (RBP), 40% and 91%; retinol/RBP molar ratio, 60% and 74%; conjunctival impression cytology, 44% and 48%; slit-lamp examination, 20% and 66%; tear film break-up time, 40% and 69%; and Schirmer's test, 20% and 78%. We developed a modified oral RDR via oral coadministration of d-alpha tocopheryl polyethylene glycol-1000 succinate and retinyl palmitate. This test had a sensitivity of 80% and a specificity of 100% to detect vitamin A deficiency. In conclusion, vitamin A deficiency is relatively common in children who have chronic cholestatic liver disease. Our data suggest that serum retinol level as an initial screen followed by confirmation with a modified oral RDR test is the most effective means of identifying vitamin A deficiency in these subjects.
 ...
PMID:Comparison of indices of vitamin A status in children with chronic liver disease. 1617 20

Feeding intolerance is a common problem in infants who have had multiple or extensive resections of their small bowel. Chronic malabsorption and diarrhea are common side effects that inhibit the advancement of enteral feedings and prolong dependence on parenteral nutrition (PN). Poor growth, recurrent central line infections, cholestasis, and osteopenia are well-known complications associated with long-term PN dependency. It has been shown that, in adults with short bowel syndrome, providing dietary fiber can improve tolerance to enteral feeding. There are no published studies that have addressed the influence of dietary fiber on feeding intolerance in infants after bowel resections. The ensuing case studies illustrate the positive outcomes of fiber use in infants with diarrhea secondary to small bowel resections.
 ...
PMID:Adding dietary green beans resolves the diarrhea associated with bowel surgery in neonates: a case study. 1630 6

Primary biliary cirrhosis is a chronic liver disease of unknown etiology, characterized by inflammation and destruction of the intrahepatic biliary ducts, resulting in chronic cholestasis and eventually cirrhosis. The main clinical manifestations consists of pruritus, jaundice, xanthomas, and the consequences of intestinal malabsorption, including vitamin deficiencies and osteodystrophy. Treatment of PBC is addressed at preventing or relieving the symptoms and clinical consequences of chronic cholestasis, and also at correcting the bile duct abnormalities by specific treatments. Pruritus is treated with cholestyramine, but in some cases other drugs, such as rifampicin or opioid antagonists are needed. Bisphosphanates are effective for increasing bone mass in osteopenic patients. Vitamin D and cAlcium supplements are also recommended, particularly in patients with severe cholestasis. Ursodeoxycholic acid (UDCA) has become the standard treatment (13-15 mg/kg/day), resulting in marked relieving of cholestasis. UDCA also prevents the histological progression of the disease, although the effects on survival are less apparent. Small trials of combination therapy using UDCA with methotrexate, colchicine, or prednisone, have been reported but have not shown any increased efficacy over UDCA therapy. Liver transplantation is the only treatment available when cholestasis progresses, with very good survival rates.
 ...
PMID:Treatment of primary biliary cirrhosis. 1649 78

Bile acids are synthesized by the liver from cholesterol through a complex series of reactions involving at least 14 enzymatic steps. A failure to perform any of these reactions will block bile acid production with failure to produce "normal bile acids" and, instead, result in the accumulation of unusual bile acids and intermediary metabolites. Failure to synthesize bile acids leads to reduced bile flow and decreased intraluminal solubilization of fat and fat-soluble vitamins. In some circumstances, the intermediates created because of blockade in the bile acid biosynthetic pathway may be toxic to hepatocytes. Nine recognized inborn errors of bile acid metabolism have been identified that lead to enzyme deficiencies and impaired bile acid synthesis in infants, children, and adults. Patients may present with neonatal cholestasis, neurologic disease, or fat and fat-soluble vitamin malabsorption. If untreated, progressive liver disease may develop or reduced intestinal bile acid concentrations may lead to serious morbidity or mortality. This review focuses on a description of the disorders of bile acid synthesis that are directly related to single defects in the metabolic pathway, their proposed pathogenesis, treatment, and prognosis.
 ...
PMID:Inborn errors of bile acid metabolism. 1768 75

Obesity is reaching epidemic proportions worldwide and it is correlated with various comorbidities, among which the most relevant are diabetes mellitus, arterial hypertension, and cardiovascular diseases. Obesity management is a modern challenge because of the rapid evolution of unfavorable lifestyles and unfortunately there are no effective treatments applicable to the large majority of obese/overweight people. The current medical attitude is to treat the complications of obesity (e.g. dyslipidemia, hypertension, diabetes, and cardiovascular diseases). However, the potential of treating obesity is enormous, bearing in mind that a volitional weight loss of 10 kg is associated with important risk factor improvement: blood pressure -10 mmHg, total cholesterol -10%, LDL cholesterol -15%, triglycerides -30%, fasting glucose -50%, HDL cholesterol +8%. Drug treatment for obesity is an evolving branch of pharmacology, burdened by severe side effects and consequences of the early drugs, withdrawn from the market, and challenged by the lack of long-term data on the effect of medications on obesity-related morbidity and mortality, first of all cardiovascular diseases. In Europe three antiobesity drugs are currently licensed: sibutramine, orlistat, and rimonabant; important trials with clinical endpoints are ongoing for sibutramine and rimonabant. While waiting for their results, it is convenient to evaluate these drugs for their effects on body weight and cardiometabolic risk factors. Sibutramine is a centrally acting serotonin/noradrenaline reuptake inhibitor that mainly increases satiety. At the level of brown adipose tissue, sibutramine can also facilitate energy expenditure by increasing thermogenesis. The long-term studies (five) documented a mean differential weight reduction of 4.45 kg for sibutramine vs placebo. Considering the principal studies, attrition rate was 43%. This drug not only reduces body weight and waist circumference, but it decreases triglycerides and uric acid as well and it increases HDL cholesterol; in diabetics it improves glycated hemoglobin. Sibutramine has conflicting effects on blood pressure: in some studies there was a minimal decrease, in some others a modest increase. In all the studies this drug increased pulse rate. Sibutramine is not recommended in patients with uncontrolled hypertension, or in case of history of cardio- and cerebrovascular disease. Orlistat is a pancreatic lipase inhibitor that reduces fat absorption by partially blocking the hydrolysis of dietary triglycerides. A recent meta-analysis evaluated 22 studies lasting for at least 12 months, in obese patients with a mean body mass index of 36.7 kg/m2, where orlistat was associated with hypocaloric diet or behavioral interventions: the net average weight loss was 2.89 kg (confidence interval 2.27-3.51 kg). Considering the principal studies, attrition rate ranged from 33 to 57%. Orlistat significantly decreases waist circumference, blood pressure, total and LDL cholesterol, but has no effect on HDL and triglycerides. This drug significantly reduced the incidence of diabetes only in subjects with impaired glucose tolerance. The major adverse effects with orlistat are mainly gastrointestinal (fatty and oily stool, fecal urgency, oily spotting, fecal incontinence) and attenuate over time. Orlistat should be avoided in patients with chronic malabsorption and cholestasis. Rimonabant is a selective antagonist of cannabinoid type 1 receptor. This drug, by inhibiting the overactivation of the endocannabinoid system, produces anorectic stimuli at the central nervous level, but also has effects on the peripheral systems involved in metabolism control, such as liver, adipose tissue, skeletal muscles, endocrine pancreas, and gastrointestinal apparatus, influencing many processes partially unknown. An ample experimental program named RIO (Rimonabant In Obesity) involved about 6600 obese or overweight patients to identify the effects of rimonabant in weight loss and associated cardiometabolic abnormalities, over and beyond a caloric restriction of 600 kcal in the treatment and placebo arms. In the four double-blind RIO trials published (Rio-North America, RIO-Europe, RIO-Lipids, RIO-Diabetes), rimonabant 20 mg significantly (p <0.001) reduced weight by 6.3-6.9 kg in the non-diabetic groups vs placebo (-1.5-1.8 kg), whereas in the diabetic subjects enrolled in RIO-Diabetes, weight loss was 5.3 vs 1.4 kg in the placebo group. Attrition rate at 1 year ranged between 40 and 50%, similar to the studies with sibutramine or orlistat. Similarly to weight loss, also waist circumference was significantly reduced by rimonabant. As for cardiometabolic parameters, rimonabant induced a significant increase in HDL cholesterol and a significant decrease in triglycerides. Even if no significant LDL reduction was achieved, the RIO-Lipids study showed a significant decrease in small dense LDL particles, more atherogenic, in rimonabant-treated subjects. Non-diabetic treated patients improved basal insulin and indirect indexes of insulin resistance, while in the RIO-Diabetes study, the only one including diabetics, glycated hemoglobin improved by 0.7% in the active treatment arm vs placebo. The effects on HDL cholesterol and glycated hemoglobin seem in a large percentage unrelated to weight loss. These effects have been confirmed by another trial, named SERENADE, evaluating the treatment in naive diabetic patients. Rimonabant is not recommended in patients with a history of depressive disorders or suicidal ideation and with uncontrolled psychiatric illness, and is contraindicated in patients with ongoing major depression or ongoing antidepressive treatment. In conclusion, despite an enormous advancement in basic research to understand the pathogenetic mechanisms at the base of obesity, the pharmacological research did not reach the therapeutic opportunities available for other chronic conditions, like hypertension and dyslipidemia. However, the few molecules available for clinical practice (sibutramine, orlistat, rimonabant) have shown, when properly used, to contribute to reduce body weight and undoubtedly improve cardiometabolic risk factors. With this preamble, according to current guidelines and pharmacoeconomic studies, patients who might benefit from antiobesity treatment are those with a body mass index > or =30 or 27-29.9 kg/m2 with major obesity-related comorbidities such as hypertension, diabetes, dyslipidemia, obstructive sleep apnea, and metabolic syndrome.
 ...
PMID:[Pharmacological therapy of obesity]. 1877 55

Wilson's disease is an infrequent, autosomic recessive pathology, resulting from a loss of function of an adenosine triphosphatase (ATP7B or WDNP), secondarily to a change (more than 60 are described currently), insertion or deletion of the ATP7B gene located on the chromosome 13q14.3-q21.1, which involves a reduction or an absence of the transport of copper in the bile and its accumulation in the body, notably the brain. Wilson's disease is transmitted by an autosomic recessive gene located on the long arm of chromosome 13. The prevalence of the heterozygote is evaluated at 1/90 and the homozygote at 1/30,000. Consanguinity, frequent in the socially geographically isolated populations, increases the prevalence of the disease. The toxic quantities of copper, which accumulate in the liver since early childhood and perhaps before, remain concentrated in the body for years. Hence, cytological and histological modifications can be detected in the biopsies, before the appearance of clinical or biological symptoms of hepatic damage. The accumulation of copper in the liver is due to a defect in the biliary excretion of metal and is accompanied invariably by a deficit in ceruloplasmin; protein synthesized from a transferred ATP7B gene, which causes retention of the copper ions in the liver. The detectable cellular anomalies are of two types: hepatic lesions resulting in acute hepatic insufficiency, acute hepatitis and finally advanced cirrhosis and lesions of the central nervous system responsible for the neurological and psychiatric disorders. In approximately 40-50% of the patients, the first manifestation of Wilson's disease affects the central nervous system. Although copper diffuses in the liver towards the blood and then towards other tissues, it has disastrous consequences only in the brain. It can therefore cause either a progressive neurological disease, or psychiatric disorders. Wilson's disease begins in the form of a hepatic, neurological, or psychiatric disease in at least 90% of the patients. In some rare cases, the first manifestations of the disease can be psychiatric which, according to the literature, accounts for only 10% of the cases. The disease can be revealed by isolated behavioral problems, an irrational syndrome, a schizophrenic syndrome, or a manic-depressive syndrome. Damage to the central nervous system can be more severe, thus, several differential diagnoses have been discussed: a psychotic disorder of late appearance; a depressive state; a mental confusion disorder. The clinical syndrome is complex. Indeed, it is the polymorphism, which dominates in the description of the psychiatric demonstrations of the disease. This can lead to prejudicial diagnostic wandering, particularly since heavy sedative treatment may be required to suppress behavioral problems. Clinically, Wilson's disease generally appears between the age of 10 and 20. It rarely remains masked until after the age of 40. The first manifestations are hepatic (40% of the cases), neurological (35%) or psychiatric (10%). The inaugural disorder can finally take on a haematological, renal, or mixed form in approximately 15% of the cases. We have detailed the principal clinical elements. In approximately 40-50% of the patients, the first manifestation of the disease affects the central nervous system, where it can cause either a progressive neurological disease, or psychiatric disorders. The ophthalmologic disorder is dominated by Kayser-Fleischer's ring, representing a green or bronze colored ring on the periphery of the cornea. It occupies the higher pole of the cornea, then the lower pole, and extends to the whole circumference. It is generally only visible under examination with a slit lamp. It disappears on average within 3-5 years following copper chelating therapy. Kayser-Fleischer's ring has been described other than in Wilson's disease, in exceptional cases of prolonged cholestasis. On haematological level, the hyperhaemolysis is due to the toxicity of the ionic copper, released massively in the plasma by hepatocellular necrosis. The other manifestations can be found in the following organs: renal, osteoarticular, cardiac, endocrine, cutaneous, and in the teguments. Until 1952, the diagnosis was evoked only on clinical symptomatology. It can henceforth be marked unambiguous, even in the absence of any symptom, by the description of a ceruloplasmin plasma concentration of less than 200 ml/l, and of a Kayser-Fleischer's ring. Hepatic copper on sample is constantly increased during the disease (from 3 to 25 micromol/g of dry weight). On the other hand, the absence of a reduction in the plasma ceruloplasmin does not make it possible to exclude the diagnosis. Conversely, a reduction in ceruloplasmin can exist other than in Wilson's disease (nephritic syndrome, malabsorption syndrome, or severe hepatic insufficiency). Kayser-Fleischer's ring is quasiconstant among patients with neuropsychiatric demonstrations (thus, its absence represents a very strong argument against the diagnosis). It can on the other hand be lacking during hepatic forms, and in this case, its absence is not an argument against the diagnosis. Magnetic resonance imaging can reveal abnormal signals of the grey cores. A genetic study is conducted by liaison analysis in the event of a family history of the disease. When it is not treated, Wilson's disease induces lesions of the tissues, the outcome of which is always fatal. Treatment relies on the regulation of copper chelation, which improves the prognosis, and zinc, which captures the copper in a nontoxic form. The severe psychiatric disorders observed during Wilson's disease may require tranquilizers, but care should be taken because of potential neurological or hepatic side effects. Lithium seems an interesting treatment and remains theoretically indicated, taking into account the scarcity of the extrapyramidal symptoms and the hepatic dysfunction among patients at the stage of cirrhosis, since it is not metabolized in the liver. Although rare, it is important to approach Wilson's disease in psychiatry because the psychiatric manifestations can precede the somatic disorders and help to pose the diagnosis. We stress the importance of the early diagnosis of the pathology, the outcome of which is fatal in the absence of specific treatment.
 ...
PMID:[The onset of psychiatric disorders and Wilson's disease]. 1878 84

Vitamin K deficiency bleeding (VKDB) is a rare and potentially life-threatening bleeding disorder of early infancy. Vitamin K stores are low at birth; thereafter breast-fed infants are at risk because of low concentrations in human milk. Classical VKDB occurs in the first week of life, is related to delayed or inadequate feeding and is readily prevented by small doses of vitamin K at birth. Late VKDB peaks at 3-8 weeks, typically presents with intracranial haemorrhage often due to undiagnosed cholestasis with resultant malabsorption of vitamin K. Diagnosis can be difficult but PIVKA-II measurements can provide confirmation even several days post-treatment. Without vitamin K prophylaxis, the incidence of late VKDB in Europe is 4-7 cases per 10(5) births; it is higher in SE Asia where in rural, low-income areas some 0.1% of affected infants may suffer intracranial bleeding. Late VKDB is largely preventable with parenteral vitamin K providing the best protection. The efficacy of oral prophylaxis is related to the dose and frequency of administration. Most multi-dose oral regimens provide protection for all except a small reservoir of infants with undetected hepatobiliary disease. Targeted surveillance of high-risk groups (e.g. biliary atresia) offers a novel approach to assess efficacy of prophylaxis.
 ...
PMID:Vitamin K deficiency bleeding (VKDB) in early infancy. 1880 3


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>