Human asthma due to a dog's drugs.

A woman had a recurrence of asthma due to sensitization to her dog's pancreatic enzyme powder. The cause of her asthma was confirmed by bronchial inhalation challenge, and specific IgE antibodies against the enzymes were found in her serum but not in that of control subjects.

The association of nephrolithiasis with cystic fibrosis.

BACKGROUND: There is a growing body of evidence regarding the association between cystic fibrosis (CF) and nephrolithiasis and the role that Oxalobacter formigenes may have in that association. METHODS: We performed a MEDLINE search of "cystic fibrosis and nephrolithiasis" and "Oxalobacter formigenes." Epidemiological and experimental evidence and possible mechanisms explaining the association were critically reviewed. RESULTS: Of patients with CF, 3.0% to 6.3% are affected with nephrolithiasis, a percentage greater than that of age-matched controls without CF, in whom the rate is 1% to 2%. Studies have suggested possible mechanisms for the association, including hyperuricosuria, hyperoxaluria, primary defects in calcium handling caused by mutation of the CF transmembrane regulator (CFTR), hypocitraturia, and lack of colonization with O formigenes, an enteric oxalate-degrading bacterium. The absence of colonization could be related to frequent courses of antibiotics. CONCLUSION: Although the incidence of stones in patients with CF may be increased compared with controls without CF, many possible mechanisms are implicated. The relative contributions of these mechanisms remain uncertain. Future directions may include specific identification of lithogenic risks and therapy aimed at stone prevention in this population.

Pulmonary function and concentrations of alpha 1-antitrypsin and immunoglobulin E in workers exposed to pancreatic enzymes.

Fourteen workers exposed to pancreatic enzymes in tanneries were studied by interview, spirometry, and the single-breath nitrogen washout technique. Blood concentrations of alpha 1-antitrypsin and immunoglobulin E (IgE) were determined. For each exposed subject a nonexposed referent was selected, matched by sex, age, height and smoking habits. Symptoms in the airways were reported by four of the 14 subjects when weighing pancreatic enzymes. The exposed group did not show any deterioration in pulmonary volumes, forced expiratory flow, airway closure, or gas distribution when compared to the referents. The exposed group had significantly higher plasma levels of alpha 1-antitrypsin than the referents. This elevation might be a compensatory response to increased levels of proteases within the lungs. The serum levels of IgE did not differ between the groups.

Neuropathy and vasculopathy in colonic strictures from children with cystic fibrosis.

Colonic strictures are rare in patients who have cystic fibrosis, but recently have developed in those who have been treated with delayed-release high-dose pancreatic enzyme supplements. Colonic strictures from eight such pediatric patients showed neural abnormalities consisting of ganglion cell hyperplasia and ectopia, and intermyenteric plexus hyperplasia. Cholinergic and adrenergic stains of mucosal nerve fibers were more prominent in histological sections of the cystic fibrosis strictures than in sections from colons of children without cystic fibrosis. The mean grade of staining with acetylcholinesterase in the lamina propria of the strictured cystic fibrosis colons was 2.38 +/- 1.25, compared with .93 +/- .93 (P < .055) in bowels from children without cystic fibrosis. The mean grade for tyrosine hydroxylase staining in the lamina propria was 2 +/- .97 in the strictures and was .79 +/- .81 (P < .05) in the bowels of children who did not have cystic fibrosis. Vasoactive intestinal peptide staining in bowels from children with cystic fibrosis with and without stricture did not differ significantly from that of children without cystic fibrosis. Vasculopathy consisting of fibrointimal hyperplasia in submucosal veins and mesenteric arteries was found only in colonic strictures owing to cystic fibrosis. Colonic strictures in patients with cystic fibrosis who received high-dose pancreatic enzyme supplements contain ganglion cell abnormalities, and mucosal cholinergic and adrenergic activity may be increased in these strictures. The stricture vasculopathy may be drug-related and/or related to increased catecholamine activity.

A case of occupational rhinitis caused by porcine pancreatic extract developing into occupational asthma.

Porcine pancreatic extracts (PPE), which are widely used as a digestive drug in Korea, are composed of alpha-amylase and lipase. Such enzymes are commonly described as occupational allergens. This is the first report of occupational rhinitis caused by PPE developing into occupational asthma in a hospital nurse. She showed strong positive response in the skin prick test (SPT) (5+, wheal ratio of allergen to histamine) and had a high serum-specific IgE level to PPE, but showed a negative response in the methacholine bronchial challenge test (MBT). She had been exposed to PPE intermittently with intermittent medications for rhinitis. Two years later, she presented with rhinitis and additional asthmatic symptoms. In contrast to her first visit, she showed a positive response in the MBT, and developed bronchoconstriction in the PPE-bronchial provocation test (BPT). These findings suggest that inhalation of PPE powder can induce IgE-mediated occupational rhinitis in a hospital setting, which will develop into occupational asthma if avoidance is not complete.

Management of chronic pancreatitis. Focus on enzyme replacement therapy.

The goals of treatment with pancreatic extracts in patients with chronic relapsing pancreatitis are twofold: pain relief and control of maldigestion caused by exocrine pancreatic insufficiency. Experience with the use of pancreatic enzymes for analgesic purposes suggests that the less severe the pain, the greater the analgesic effect of these enzymes. However, the number of trials, as well as the number of patients treated, is fairly small and more studies in larger patient populations are needed. The use of pancreatic enzymes for maldigestion owing to exocrine pancreatic insufficiency which is secondary to chronic pancreatitis, pancreatectomy, cystic fibrosis, or GI bypass surgery incurs several problems. These problems are primarily caused by gastric inactivation of the enzymes, low enzyme activity of many commercial preparations and/or poor patient compliance. Treatment with conventional enzyme products (powdered extracts, enteric-coated tablets or capsules) has been disappointing. At best, results were inconsistent, showing a high degree of individual variation. The introduction of enzyme preparations in the form of pH-sensitive enteric-coated microspheres in hard gelatin capsules represents a significant advance. These microspheres are superior to conventional enzyme preparations in improving the symptoms of pancreatic insufficiency, particularly steatorrhea, where low doses of microspheres are as effective as large doses of conventional enzyme preparations. Steatorrhea, however, is rarely completely resolved. In cases refractory to therapy, treatment with the combination of pH-sensitive enteric-coated microspheres and H2-antagonists or prostaglandins has met with some success.

Effect of pancreatic enzyme supplements on iron absorption.

Iron deficiency has been reported in one third of patients with cystic fibrosis. There are data that suggest that iron absorption is increased with exocrine pancreatic deficiency and that administration of pancreatic enzymes may impair oral iron absorption. We compared oral iron absorption over a 3-hour period in the presence and absence of exogenous pancreatic enzymes in 13 stable young-adult patients with cystic fibrosis and 9 age-matched control patients. Although none of the patients with cystic fibrosis had a hemoglobin level less than 119 g/L, serum ferritin levels were less than 25 micrograms/L in 5 of the 13 patients, and the mean corpuscular volume was significantly lower in the patient group (86.1 +/- 2.7 vs 90.9 +/- 5 fL). Baseline mean serum iron levels were higher in controls (18.9 +/- 5.9 mumol/L) than in patients (11.9 +/- 6.3 mumol/L). There was no difference in iron absorption in the absence of exogenous pancreatic enzymes. Significant impairment of iron absorption was detected in both patients with cystic fibrosis and controls after administration of a preparation of pancreatic enzymes. There was an inverse relationship between iron stores, as measured by serum ferritin, and iron absorption. These findings suggest that long-term consumption of pancreatic enzymes by patients with cystic fibrosis may contribute to iron deficiency.

[Differential therapy of exocrine pancreatic insufficiency--current aspects and future prospects of substitution therapy with pancreatic enzymes]. / Differentialtherapie der exokrinen Pankreasinsuffizienz--Aktuelle Aspekte und zukünftige Perspektiven der Substitutionstherapie mit Pankreasenzymen.

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.

Pancreatic extract lung sensitivity.

Seven patients with respiratory tract sensitivity to powdered pig pancreatic extract were studied with regard to their atropic status and the immunological nature of this sensitivity. The results confirmed the role of allergen specific antibodies to pig pancreatic extract in this sensitization and underlined susceptibility of atopic subjects to develop respiratory sensitivity to allergens to which they are exposed.

IgE mediated hypersensitivity to pancreatic extract (PE) in parents of cystic fibrosis (CF) children.

On exposure to pancreatic extract (PE), four parents of cystic fibrosis (CF) children developed immediate hypersensitivity-like symptoms: i.e. rhinoconjunctivitis, asthma, and/or anaphylaxis. IgE to PE was demonstrated in the subjects by skin testing, leucocyte histamine release and radioallergosorbent test (RAST). No serum precipitating antibodies were found. Bronchial challenge caused an immediate asthmatic response. No delayed asthmatic response or hypersensitivity pneumonitis-like reaction occurred. The responsible antigen for PE induced asthma is unknown; trypsin failed to inhibit PE-RAST and is therefore not responsible in these subjects. Caution should be exercised in using PE for skin testing and bronchial challenge in subjects with suspected hypersensitivity to PE. Certain measures were found useful in preventing the occurrence of symptoms in the four subjects.

Medication-induced esophageal injury: report of 17 cases with endoscopic documentation.

We report on medication-induced esophageal injury (MIEI) in 17 patients (six male, 11 female) seen from October 1986 to May 1990. The mean age of patients was 27.3 (SD = 5.7) yr; mean duration of drug ingestion prior to the occurrence of symptoms 10.2 (SD = 11.5) days, and mean duration of symptoms before seeking medical attention 4.6 (SD = 3.8) days. Symptoms subsided after treatment, with a mean of 6 (SD = 2.5) days. Symptoms included odynophagia (in 17), chest pain (six), epigastric pain (three), and retrosternal pain (one). Symptoms occurred after the drug was stopped in three. MIEI was caused by doxycycline (seven), minocycline (five), Pantozyme (one), cloxacillin (one), unknown (two), and dicloxacillin + Danzen (one). Reclining after drug ingestion was the predominant risk factor. Endoscopy showed most ulcers to be multiple and at midesophagus. Barium swallows done in two patients were negative. There is no previous report of Pantozyme (pancreatic enzyme), Danzen (serratio-peptidase), cloxacillin, and dicloxacillin causing MIEI.