Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pancreatic enzyme extracts have been used for several decades to decrease maldigestion of macro- and micronutrients due to pancreatic insufficiency and to alleviate various abdominal symptoms, including the pain of alcohol-induced chronic pancreatitis and distal intestinal obstruction. Decreasing nutrient maldigestion and malabsorption in pancreatic insufficiency is of additional critical importance because improvement in nutritional status reduces morbidity and mortality. For example, pancreatic sufficient patients with cystic fibrosis (CF) demonstrate a slower decline in pulmonary function. In spite of the recognized importance of pancreatic enzymes, several problems exist with current preparations, and as newer enzyme preparations are marketed, proper evaluation becomes critical. There is a clear need to optimize the constituents of enzyme preparations, improve manufacturing processes, and find better sources of enzymes. Other issues that need addressing include standardization of the ratios of enzymes (lipase, amylase, protease) in these products; the stability of the enzymes at room temperature; the shelf life of the finished product; whether there are significant batch-to-batch differences; and the need for a USP reference standard.
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PMID:Enzyme therapy for pancreatic insufficiency: present status and future needs. 810 63

In clinical practice, exogenous pancreatic enzymes are administered for the treatment of pancreatogenic steatorrhea or with the intention to relieve pain due to chronic pancreatitis. Moreover, a large number of patients take pancreatin (i.e., exogenous pancreatic enzymes) for functional dyspepsia. The effect of exogenous pancreatic enzymes on the enteropancreatic axis is a complex issue. Intraduodenal but not intrajejunal protease activity appears to exert a dose-dependent negative feedback on exocrine pancreatic secretion. Only enzymes with a proteolytic activity but not amylase and lipase exert a control on pancreatic secretion. The mechanism responsible for this feedback regulation is debated, but the cholinergic system seems to play a major role. Intraduodenal pancreatic enzymes (pancreatin) lead to an increased release of pancreatic polypeptide but do not affect the release of insulin and glucagon. In addition, pancreatic enzymes have an influence on the release of some gastrointestinal hormones (i.e., cholecystokinin, motilin, gastric inhibitory polypeptide). Neither exogenous nor endogenous pancreatic enzymes seem to play a major role in the regulation of interdigestive gastrointestinal motility. However, an adequate rate of postprandial pancreatic output is required to control gastric emptying. Current knowledge on the effect of exogenous pancreatic enzymes on the enteropancreatic axis, gut peptide release and gastrointestinal motility are updated in the present article.
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PMID:Effect of exogenous pancreatic enzymes on gastrointestinal and pancreatic hormone release and gastrointestinal motility. 822 68

Exocrine pancreatic insufficiency combined with pancreatic pain and endocrine pancreatic insufficiency are the leading symptoms of chronic pancreatitis. Due to the large functional reserve capacity of the gland, decompensation, i.e. steatorrhea, does not occur before lipase excretion is reduced to < or = 10% of normal. Pancreatic enzyme substitution is indicated when fecal fat excretion exceeds a critical value (normally > 15 g/day) and/or when weight loss is present. A number of studies have dealt with the problems of gastric acid inactivation of pancreatic enzyme preparations as well as their gastric emptying nonsimultaneously with the food. For the present, it is recommended that pancreatic enzyme substitution in patients with proven exocrine pancreatic insufficiency and normal gastric acid secretion be given in multiunit, acid-protected dosages. In patients with gastric hyposecretion and in those who underwent partial or total gastrectomy, enzyme substitution should be administered as granules to enable mixing and simultaneous transport of enzymes with the chyme. The ultimate aim of further scientific and clinical research remains the total abolishment of pancreatic steatorrhea.
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PMID:Enzyme treatment of exocrine pancreatic insufficiency in chronic pancreatitis. 822 69

In order to clarify the mechanism by which oxytocin induces the generation of prostaglandin (PG) in human myometrial smooth muscle cell, we determined the concentration of PGE2 and 6ketoPGF1 alpha in the culture supernatant of human myometrial monolayer cells stimulated by oxytocin. PGE2 and 6ketoPGF1 alpha demonstrated a biphasic increasing curve when oxytocin was added. The first increase, phase 1, was a transient phenomenon with a peak at 20 seconds whereas the second increase, phase 2, was a continuous phenomenon starting at 120 seconds. Moreover, phase 1 was significantly inhibited by the DG lipase inhibitor, RHC80267. Phase 2 was significantly inhibited by the PLA2 inhibitor, Mepacrine. Phase 1 and 2 were dose dependent in the range 10(-10) to 10(-6) M. PG production at rest during which 6ketoPGF1 alpha was higher than PGE2, was reversed by oxytocin stimulation. These results suggest that oxytocin stimulation would actuate biphasic PG production, and this mechanism would probably regulate the myometrial construction in labor-pain initiation.
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PMID:[The effect of oxytocin stimulation on PGE2, 6keto PGF1 alpha production in human myometrial monolayer culture]. 831 15

This paper describes a case of acute pancreatitis occurring in a patient immediately after delivery and in primigravida. The patient had a family case history of dyslipidemia (Type IV). The pregnancy had been complicated by preeclampsia treated at home with nifedipine tablets (one tablet three times a day) with good results on pressure values; lipidic values were high despite dietary measures taken. The baby at birth weighed 3830 g after physiologic labour and a natural delivery. Acute pancreatitis was diagnosed after observation of epigastralgia with irradiation on the left shoulder, vomiting, symptoms of acute abdomen such as sweating, increased pulse rate, hypotension, abdominal pain on palpation, and absence of peristalsis. An analysis of the blood showed high levels of amylase and hyperglycemia, an increase in XDP, and leucocytosis. Instrumental tests such as pancreatic echography revealed an increase in pancreatic volume, uneven structure of the parenchyma and higher levels of liquid in the peritoneum. The patient was moved to intensive-care, a nasal gastric probe inserted, hydroelectrolytic treatment was begun, vital functions monitored, pain kept under control by medical therapy, and antibiotics administered. Subsequent tests showed an improvement in the parameters of pancreatic functions (amylase, lipase, calcium hematic) and their gradual return to normal values. The computerized tomography of abdomen additionally revealed the presence of pancreatic pseudo-cysts and effusion of peritoneal liquid near the right kidney. The patient was discharged after two weeks in the surgical ward. There are many caused of acute abdomen during and immediately after pregnancy, and one of these is acute pancreatitis, though rare (occurring between 1:3800 and 11.467 according to Rabkin).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Acute pancreatitis in pregnancy]. 835 Oct 66

The indication for initiation of a replacement therapy with pancreatic enzymes in the course of ongoing exocrine pancreatic insufficiency is clinically given with the appearance of loss of body weight, steatorrhea with stool fat excretion of more than 15 g per day, dyspeptic symptoms with strong meteorism, diarrhoea, and subjective misbehaviour caused by chronic pancreatitis, in rare cases with the appearance of maldigestion of proteins and carbohydrates and--under certain circumstances--for the treatment of pain in chronic pancreatitis. Due to the increase of chronic pancreatitis in recent years, the number of patients who necessarily have to be treated with enzyme replacement therapy has increased, too. The adequate replacement therapy with pancreatic enzymes, especially in patients with severe exocrine pancreatic insufficiency, is still a serious problem--requiring sufficient knowledge of the individual pathophysiological circumstances of the patient as well as the various pharmacological aspects of the different types of enzyme drugs. The most important clinical aim of the replacement therapy is the necessity to achieve a sufficient lipase activity in the duodenum. Accordingly the achievement of this aim is the main problem in clinical practice, since the acid-instable lipase is predominantly inactivated by gastric acid and proteases. Furthermore, in many cases an asynchronous gastroduodenal transport of the administered enzyme drug and food is found as a result of inadequate size of the drug or drug particles. In general, the necessary doses of administered enzymes does not follow general rules, but has to be adjusted individually. Recent scientific developments, as the characterization of an acid-stable bacterial lipase, the cloning of human acid-stable lipase, the transfection of human lipase genes by virus-mediated gene transfer as well as the development of very small acid-stable mini microspheres, present interesting new perspectives to further optimize the efficacy of the therapy of exocrine pancreatic insufficiency in the near future.
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PMID:[Differential therapy of exocrine pancreatic insufficiency--current aspects and future prospects of substitution therapy with pancreatic enzymes]. 858 55

A 59-year-old man presented with painful subcutaneous nodules on the anterior surfaces of the legs. He had received oral antibiotics and supportive care for presumed cellulitis and thrombophlebitis, but had minimal improvement. Five months earlier, he had undergone pancreaticoduodenectomy for acinar pancreatic carcinoma; at that time, the serum level of amylase had been normal, but the level of lipase was elevated. The patient denied fever, rigors, arthritis/arthralgia, or pleuritic pain. His medications included aspirin, furosemide, ranitidine, and nortriptyline. He denied any allergies. Physical examination revealed numerous firm, tender, erythematous and violaceous, subcutaneous nodules on the lower extremities, with marked bilateral pitting edema (Fig. 1). Skin biopsy of a representative lesion revealed septal panniculitis, consistent with erythema nodosum (Fig. 2). None of the characteristic changes of pancreatic fat necrosis was present. The patient was treated with aspirin, 650 mg orally, q 6 h, and indomethacin, 50 mg orally, q 12 h, but he continued to develop new nodules; prednisone, 60 mg orally was begun. Although he reported improvement in symptoms, the nodules failed to respond clinically and older nodules ulcerated along the medical aspect of the right leg (Fig. 3). The complete blood count was normal, except for hemoglobin, 10.9 mg per dL. Routine serum biochemical studies were also normal, except for albumin, 3.1 mg per dL, LDH, 312 U per L, and SGOT, 51 U per L. Serum amylase was 14 U per L (normal per 30 to 115 U per L) and serum lipase was 54,160 U per L (normal 0 to 200 U per L). Chest roentgenogram and tuberculin skin test were negative. A CT scan of the abdomen revealed extensive liver metastases. A second biopsy of the skin and subcutis of a necrotic nodule revealed lobular panniculitis with the characteristic picture seen in pancreatic fat necrosis (Fig. 4). The patient was presumed to have metastatic pancreatic carcinoma and pancreatic fat necrosis. Nodules subsequently developed on the thighs, arms, hands, wrists, and fingers. He developed arthritis and arthralgias of the ankles, wrists, and hands, bilaterally, and the right knee. Aspiration of a right knee effusion revealed numerous neutrophils, but no evidence of infection. Treatment was begun with the somatostatin analog, octreotide, in increasing doses. During this therapy, the lesions did not progress and new lesions did not appear. There was no change in the lipase level. Inadvertently, octreotide was omitted at discharge, but reintroduction of octreotide was associated with lack of further progression of the nodules, according to the patient's spouse; however the patient became progressively debilitated and his abdominal pain worsened, requiring continuous sedation. His condition deteriorated and he died several weeks after hospital discharge.
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PMID:Fat necrosis with features of erythema nodosum in a patient with metastatic pancreatic carcinoma. 883 28

The aims of medical therapy in chronic pancreatitis are mainly to relieve the recurrent pain and to correct any malabsorption secondary to digestive insufficiency resulting from deficient exocrine pancreatic function. The treatment of the pain initially involves the use of dietary measures and analgesic drugs. The results of the use of pancreatic extracts and somatostatin reported in the literature are controversial, as are those of coeliac plexus block. Of unquestionable efficacy, at least in the short to medium term, are surgical decompression interventions in patients, with pain refractory to these measures and who present significant dilation of Wirsung's duct at ERCP. Endoscopic decompression constitutes an alternative to surgical decompression. In view of the transitory results of endoscopic decompression, which, in any event, should be implemented only by endoscopists possessing the necessary experience and expertise, the use of this technique may perhaps be targeted at carefully selected patients to be submitted to surgical decompression. As far as maldigestion is concerned, which occurs only when the pancreatic functional deficit reaches 90% or more, replacement therapy with pancreatic extracts must be resorted to. Multi-Unit Dose preparations are to be preferred, consisting in gastro-protected microspheres measuring not more than 2 mm in diameter and containing high doses of lipase, since at least 30,000 I.U. of lipase are required in the post-prandial phase for reasonably satisfactory correction of the steatorrhoea. Should this fail to prove effective, it is good policy to add antisecretory drugs (H2-antagonists, proton-pump inhibitors).
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PMID:[The medical therapy of chronic pancreatitis. Problems, progress and outlook]. 902 57

A patient developing acute pancreatitis with pseudocyst formation after an uncomplicated bone marrow harvest is reported. The diagnosis was confirmed by elevated serum amylase and lipase, and by CT scan. We suggest that the pancreatitis may have been precipitated by spasm of the sphincter of Oddi secondary to opiates administered as premedication and for pain relief.
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PMID:Acute pancreatitis complicating a bone marrow harvest. 905 25

A non smoking male patient 42 years old complained of pain in the calves after exercise and had a low 'high density'-lipoprotein (HDL) cholesterol serum concentration. Angiography of the leg vessels revealed no abnormalities. Treatment with simvastatin and gemfibrozil did not affect HDL cholesterol concentrations. Blood tests of relatives made familial hypo-alpha-lipoproteinaemia unlikely. It appeared that the patient had used anabolic steroids; these increase hepatic lipase activity leading to a higher metabolism of HDL and reduced HDL cholesterol levels.
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PMID:[A patient with an unexplained low level of high density lipoprotein cholesterol]. 919 May 45


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