Proteomic Analysis of Protein Plugs: Causative Agent of Symptoms in Patients with Choledochal Cyst

Symptoms of choledochal cysts are caused by protein plugs. We performed proteomic analysis of protein plugs to elucidate formation mechanism. Protein plugs were obtained from three pediatric patients with choledochal cyst. Proteins were separated using sodium dodecyl sulfate–polyacrylamide gel electrophoresis. Gel bands common to the samples were excised for mass spectrometry. Mass spectra were compared with the NCBI database for protein identification. Gel bands of protein plug samples were predominant at 14 kilodaltons (kDa), followed by 29 kDa. Four other thin bands were common to the plug samples. Four bands (including 14 and 29 kDa) were identified as lithostathine, and one band as serum albumin. Plugs consisted mostly of lithostathine, a protein secreted by pancreatic acinar cells into pancreatic juice. The mechanism involves trypsinogen and lithostathine regurgitating into the cyst through an aberrant union of pancreaticobiliary ducts. Activated trypsin cleaves soluble lithostathine into insoluble forms that aggregate to form plugs.     

A new method for quantitation of ion fluxes across in vivo human gastric mucosa: effect of aspirin, acetaminophen, ethanol, and hyperosmolar solutions

A new, sensitive, and reproducible method for measuring hydrogen and sodium ion fluxes across the human gastric mucosa was developed and validated. By the use of a double-balloon tube that obstructed the pylorus, the stomach was converted into an in vivo Pavlov-type pouch. Duodenogastric reflux was prevented, and emptying of gastric contents into the duodenum was, on the average, 6%, thereby eliminating two important sources of error in quantitative gastric ion fluxes in humans. Transmucosal potential difference and endoscopic appearance of the gastric mucosa were also evaluated during each experiment. The mean percentage variation between duplicate tests for hydrogen ion was 3.2%, for sodium 17.5%, and the potential difference was 2.5%. Instillation of acetylsalicylic acid (36 mM, 1300 mg) in 200 ml of 100 mM hydrochloric acid for just 15 min resulted in a mean net hydrogen ion loss of 3.4 mmol/15 min, a net sodium ion gain of 1.9 mmol/15 min, a decrease in the potential difference of 23 mV, and marked gastric mucosal changes. Furthermore, exposure for 15 min to 20% ethanol (vol/vol, in 200 ml of 100 mM hydrochloric acid) and two separate hyperosmolar solutions (3600 mosmol/kg and 1800 mosmol/kg, both in 200 ml of 100 mM hydrochloric acid) also resulted in marked changes of net hydrogen ion loss (3.1, 4.8, 5.2 mmol/15 min, respectively), net sodium ion gain (2.4, 3.3, 2.4 mmol/15 min, respectively), decrease in potential difference (32, 30, 36 mV, respectively), and gross damage to the gastric mucosa. Each parameter was significantly different from the control test. Acetaminophen (86 mM, 2600 mg) or 10% ethanol (vol/vol) in 200 ml of 100 mM hydrochloric acid did not significantly alter ion fluxes or potential difference. Acetaminophen also did not significantly alter the endoscopic appearance of the gastric mucosa, whereas 10% ethanol had only a modest effect. In the control, aspirin, and acetaminophen experiments, maximal changes in the four parameters (i.e., hydrogen and sodium ion fluxes, potential difference, and endoscopic score) were significantly correlated with one another.     

Contact solvents for common bile duct stones. Study in an in vitro system

Abstract: Cholesterol and brown pigment stones found in the common bile duct are often radiolucent and therefore indistinguishable. The purpose of this study was to define contact solvent systems able to dissolve both stone types. The influence of mucolytic agents on in vitro pigment stone dissolution was first determined. It was shown that dithioerythritol induced more rapid dissolution than N-acetylcysteine. Alternating treatment with an aqueous alkaline solvent (pH=9.5), composed of sodium deoxycholate 50 mM, ethylenediaminetetraacetate 26 mM and dithioerythritol 50 mM, for 45 min, and an organic solvent methyl tert-butyl ether/dimethyl sulfoxide (90/10) for 15 min, was more effective for bilirubin, cholesterol, and fatty acid solubilization (p<0.01) than using these solvents separately. The dissolution of brown stones was nearly completed within 9 h and that of mixed cholesterol stones was obtained within 3 h. We conclude that the alternating treatment described is very effective for the rapid in vitro dissolution of the two major stone types present in the bile ducts, and deserves further assessment in vivo.     

Endoscopic biliary drainage for children with persistent or exacerbated symptoms of choledochal cysts

Background

Symptoms of choledochal cysts sometimes persist or become exacerbated. As preoperative management for patients with these cysts, we prospectively employed endoscopic drainage, based on the theory that protein plugs cause symptoms by obstructing the pancreatobiliary ducts.

Methods

Children with choledochal cysts underwent endoscopic retrograde cholangiopancreatography (ERCP). When ERCP showed compaction with filling defects in patients with persistent or worsening symptoms (study patients), the placement of a short biliary stent tube was attempted for drainage. The clinical and ERCP findings of the study patients were compared with those of patients who were asymptomatic at ERCP (asymptomatic patients).

Results

There were 13 study patients (median age 2.9 years) and 41 asymptomatic patients (4.7 years) enrolled in the study between August 2005 and February 2011. Study patients more frequently had jaundice and elevated transaminase levels. ERCP showed that all study patients had obstruction or compacted filling defects in the common channel or the narrow segment distal to the cyst. Insertion of a stent tube was successful in 11 patients. Symptoms were relieved soon after biliary drainage. Surgery revealed that the obstructing materials were protein plugs, except in one case, which involved fatty acid calcium stones.

Conclusions

These results support the protein plug theory. Endoscopic short-tube stenting is adequate and effective as preoperative management.     

Extrahepatic cyst excision and partial hepatectomy for Todani type IV-A cysts

Background

Extrahepatic cyst excision and Roux-en-Y hepaticojejunostomy is not satisfactory in many patients with complex Todani type IV-A choledochal cysts.

Aims

To report the results of combined extrahepatic cyst excision, partial hepatectomy, and Roux-en-Y hepaticojejunostomy for type IV-A choledochal cysts.

Methods

The records of patients who received extrahepatic cyst excision, partial hepatectomy, and Roux-en-Y hepaticojejunostomy for type IV-A choledochal cysts from January 2002 to December 2011 were retrospectively reviewed, and surgical outcomes analysed.

Results

59 patients (30.5% males; mean age, 43.2 ± 18.4 years) were included. Radical excision of cystically dilated bile ducts was achieved in 53 patients (89.8%). Bile leakage, delayed wound healing, and abdominal infection occurred in 5 (8.47%), 7 (11.86%), and 3 (5.08%) patients, respectively. Forty-nine patients (83.1%) were followed for an average of 42.6 ± 15.3 months. During the follow-up, 6 patients (12.2%) experienced recurrent cholangitis. Long-term biliary function was excellent in 33 (67.4%), good in 9 (18.4%), fair in 5 (10.2%), and poor in 2 (4.1%) patients.

Conclusion

Combined extra-hepatic cyst excision, partial hepatectomy, and Roux-en-Y hepaticojejunostomy is effective for the treatment of complex Todani type IV-A choledochal cysts with substantial intrahepatic bile duct involvement and hilar bile duct stenosis.     

A physiological solvent for crystalline insulin

Summary Insulin is insoluble in water at physiological pH, but dissolves relatively rapidly in plasma. To quantify the ability of various solutions to dissolve crystalline insulin, a simple assay measuring dissolution time was developed. At pH 7.5 and room temperature, distilled water, 0.154 mol/l NaCl, Ringer's lactate solution, and 5% albumin in 0.154 mol/l NaCl did not dissolve insulin crystals within 30 min. Normal postprandial human plasma and a protein-free cell culture medium dissolved insulin crystals within 3 to 8 min. This ability was inhibited by acid titration of the fluids to a stable pH of 6.30, at which point bicarbonate depletion could be implied. Repletion of bicarbonate did restore the ability of these solutions to dissolve insulin crystals, but back-titration to the initial pH with NaOH did not. The effect of sodium bicarbonate alone was strongly concentration dependent above 23 mmol/l. We suggest that the ability of physiological fluids to dissolve insulin crystals at normal pH depends on their bicarbonate content. The ability to dissolve insulin with a physiological solvent which prevents its raggregation promises to facilitate its use in portable pumping systems.     

Phenotype-dependent susceptibility of cholinergic neuroblastoma cells to neurotoxic inputs

A preferential loss of brain cholinergic neurons in the course of Alzheimer's disease and other encephalopathies is accompanied by a proportional impairment of acetyl-CoA synthesizing capacity in affected brains. Particular susceptibility of cholinergic neurons to neurodegeneration might results from insufficient supply of acetyl-CoA for energy production and acetylcholine synthesis in these conditions. Exposure of SN56 cholinergic neuroblastoma cells to dibutyryl cAMP and retinoic acid for 3 days caused their morphologic differentiation along with the increase in choline acetyltransferase activity, acetylcholine content and release, calcium content, and the expression of p75 neurotrophin receptors. Acetyl-CoA content correlated inversely with choline acetyltransferase activity in different lines of SN56 cells. In differentiated cells, aluminum (1 mM), amyloid β_25–35 (0.001 mM), and sodium nitroprusside (1 mM), caused much greater decrease of pyruvate dehydrogenase and choline acetyltransferase activities and cell viability than in nondifferentiated ones. Aluminum (1 mM) aggravated suppressory effects of amyloid β on choline acetyltransferase and pyruvate dehydrogenase activities and viability of differentiated cells. Similar additive inhibitory effects were observed upon combined exposure of differentiated cells to sodium nitroprusside and amyloid β_25–35. None or much smaller suppressory effects of these neurotoxins were observed in nondifferentiated cells. Increase in the fraction of nonviable differentiated cells positively correlated with losses of choline acetyltransferase, pyruvate dehydrogenase activities, and cytoplasmic cytochrome c content in different neurotoxic conditions. These data indicate that highly differentiated cholinergic neurons may be more susceptible to aluminum and other neurotoxins than the nondifferentiated ones due to relative shortage of acetyl-CoA, increased content of Ca²⁺, and expression of p75 receptors, yielding increase in cytoplasmic cytochrome c and subsequently grater rate of death of the former ones.     

The risk of carcinogenesis in congenital choledochal cyst patients: an analysis of 214 cases

Background. Choledochal cysts are most common in Asian populations. In addition, the incidence of biliary tract malignancies from choledochal cysts is increasing, but the risk of carcinogenesis is still unclear.Material and methods. Clinical data from 214 congenital choledochal cyst cases from 1968 to 2013 were retrospectively analyzed.Results. Todani type I was more common (139, 65.0%) than type IVa (53, 24.8%) or type V (17, 7.9%) in these choledochal cyst patients. Biliary tract malignant tumors occurred in the gallbladder (2, 13.3%), common bile duct (10, 66.7%), and intrahepatic bile duct (3, 20%) in 15 patients (7.0%), including one patient in whom malignant transformation occurred in the intrahepatic bile duct in a type IVa patient 15 years after extrahepatic cyst resection. An age at symptom onset ≥ 60 years was a risk factor (p < 0.001), while an initial complete surgery was a protective factor for carcinogenesis (p = 0.001).Conclusions. Choledochal cysts should be removed once diagnosed because of an increased risk of malignant transformation with increasing age. Complete cyst removal is necessary for the first surgical treatment. Additional hepatectomy should be considered for type IVa choledochal cysts because cholangiocarcinoma can arise from the intrahepatic bile duct years after the extrahepatic cyst excision.     

Course of choledochal cysts according to the type of treatment

Abstract

Objective. To compare natural course and treatment results of various types of choledochal cysts. Material and methods. Complication rate in treated (T) and natural course in not treated (NT) patients with choledochal cysts were compared. The level of bilioenteric anastomosis after cyst resection was categorized and their post-procedure courses were analyzed. Results. A total of 204 patients (T, 174; NT, 30) were included. Patients with initial malignancies were excluded from the outcome analysis (n = 13). Of the remaining 191 patients, the mean follow-up time was 35.9 months (range 6?310.7 months). Biliary stricture was the most troublesome post-operative complication, and occurred in 10 patients (6.1%). It occurred significantly more frequently in the above hilar anastomosis group than in at or below (p-trend = 0.017), and also with older age (p-trend = 0.019). Common bile duct stone was the most frequent adverse event among NT (42.9%). Overall, there were fewer complications among treated patients (T, 17.2%; NT, 67.9%; p < 0.001). Anomalous pancreaticobiliary union (APBU) was present in 69 patients (37.5%), which was associated with higher prevalence of carcinoma (APBU-present, 13%; APBU-absent, 3.5%; p = 0.019). No malignancy developed in both T and NT groups during follow-up. Conclusions. This study suggests, that even asymptomatic choledochal cysts should be treated, not only for prevention of malignancies, but also to lower the future adverse events. Bilioenteric anastomosis at larger caliber duct is recommended for prevention of post-operative biliary strictures.     

Baker’s cysts in knees with chronic osteoarthritic pain: a clinical,ultrasonographic, radiographic and scintigraphic evaluation

This study aimed to determine the ultrasonographic prevalence of Baker’s cysts in knees with chronic osteoarthritic pain and investigate for cysts correlates and relationships with scintigraphically established synovitis. Consecutive patients with chronic osteoarthritic knee pain underwent clinical examination, X-rays, ultrasonography and early-phase bone scintigraphy. Eighty-nine Baker’s cysts were detected in 328 knees with chronic osteoarthritic pain (27%), whereas one cyst was identified among the 54 non-osteoarthritic knees (2%, P < 0.001). Baker’s cysts were detected in 72/195 (37%) patients with knee osteoarthritis. Abnormal and intense tracer accumulation in early-phase bone scintigraphy were significantly more frequent in osteoarthritic knees with Baker’s cysts (97 and 56%, respectively), than in those without (89 and 40%, respectively, P < 0.05 for both). Clinical and radiographic variables could not predict the presence of those cysts. Baker’s cysts are a common ultrasonographic finding in knees with chronic osteoarthritic pain and are associated with synovial inflammation and its grade.     

Role of reactive oxygen species (ROS) in angiotensin II-induced stimulation of the cardiac Na/HCO3 cotransport

The sarcolemmal Na⁺/HCO₃⁻ cotransporter (NBC) plays an important role in intracellular pH (pH_i) regulation in the heart. In the present work we studied, in isolated cat ventricular myocytes, the role of Angiotensin II (Ang II) and reactive oxygen species (ROS) production as potential activators of the NBC. pH_i was measured in single cells in a medium with HCO₃⁻ using the fluorescent pH indicator BCECF. The NH₄⁺ pulse method was used to induce an intracellular acid load and the acid efflux (J_H) in the presence of the Na⁺/H⁺ exchanger blocker HOE642 (10 μM) was calculated as indicator of NBC activity. The following J_H data are presented at pH_i of 6.8 ( and ^# indicate p < 0.05 after ANOVA vs. control and Ang II, respectively). The basal J_H (1.03 ± 0.12 mM/min, n = 11) was significantly increased in the presence of 100 nM Ang II (1.70 ± 0.15 mM/min, n = 8). This effect of Ang II was abolished when we added to the extracellular solution 2 mM MPG (ROS scavenger; 0.80 ± 0.08 mM/min, n = 11^#), 300 μM apocynin (NADPH oxidase blocker; 0.80 ± 0.13 mM/min, n = 6^#), 500 μM 5-hydroxidecanoate (mitochondrial ATP dependent K⁺ channel, mK_ATP, blocker; 0.97 ± 0.21 mM/min, n = 9^#), or the inhibitor of the MAP kinase ERK pathway U0126 (10 μM; 0.56 ± 0.18 mM/min, n = 6^#). We also determined the phosphorylation of ERK during the first min of acidosis and we detected that Ang II significantly enhanced the ERK phosphorylation levels, an effect that was cancelled by scavenging ROS with MPG. In conclusion, we propose that Ang II enhances the production of ROS through the activation of the NADPH oxidase, which in turn triggers mK_ATP opening and mitochondrial ROS production (“ROS-induced ROS-release mechanism”). Finally, these mitochondrial ROS stimulate the ERK pathway, leading to the activation of the NBC.     

A follow-up study of pulmonary function in patients with primary Sjögren's syndrome

Summary Twenty-seven patients (25 women, 2 men) with primary Sjögren's syndrome, previously reported to have reduced pulmonary diffusing capacities were reexamined in a 7-year follow-up in order to evaluate longitudinal alterations in pulmonary function. Primary Sjögren's syndrome was diagnosed according to the Copenhagen criteria. The present examination revealed normal and unchanged values for vital capacity, forced expiratory volume in 1 s, maximal expiratory flow at 50% of expired vital capacity (MEF50), and diffusing capacity per liter alveolar volume. Total diffusing capacity (P<0.01) and MEF75 (P<0.05), were, however, significantly reduced compared with the predicted values, indicating pulmonary involvement primarily affecting the small airways. The longitudinal examination, furthermore, showed increasing values for total diffusing capacity (P<0.02), diffusing capacity per liter alveolar volume (P<0.001), and MEF75 (P<0.02), suggesting an improvement in lung status in the course of time. No correlation was found between MEF75 and diffusing capacities, nor between alterations in pulmonary function and complaints of dyspnoea, tiredness, cough, expectoration, tobacco smoking, or medical treatment with bromhexine, glucocorticosteroids, essential fatty acids, or nonsteroid antiinflammatory drugs.     

Cough Receptor Sensitivity to Capsaicin and Tartaric Acid in Patients with Mycoplasma Pneumonia

There has been no detailed study of cough sensitivity during acute lower respiratory infection. The aim of this study was to clarify cough sensitivity in Mycoplasma pneumonia, which is a well known acute lower respiratory infection with persistent nonproductive cough. We examined cough sensitivity to inhaled capsaicin and tartaric acid in both the acute and the convalescent phases of Mycoplasma pneumonia, cell differentials in bronchoalveolar lavage fluid, and pathologic findings of transbronchoscopic bronchial biopsy specimens. Although dry cough was observed in all patients during Mycoplasma pneumonia, cough sensitivity in the acute phase [capsaicin: 19.8 (GSEM, 0.214) μM, tartaric acid: 0.26 (GSEM, 0.356) M] were not enhanced compared with those in both control subjects [capsaicin: 27.9 (GSEM, 1.24) μM, tartaric acid: 0.316 (GSEM, 0.079) M] and patients in the convalescent phase [capsaicin: 15.7 (GSEM, 0.219) μM, tartaric acid: 0.50 (GSEM, 0.326) M] when all symptoms including cough had disappeared. The percentage of lymphocytes and neutrophils in bronchoalveolar lavage fluid BALF was significantly greater than in the control subjects, and lymphocyte-dominant bronchitis was observed in biopsied specimens. We conclude that cough threshold to inhaled capsaicin or tartaric acid was not enhanced during acute Mycoplasma pneumonia with lymphocyte-predominant bronchitis. This is the first report examining cough sensitivity in patients with acute lower respiratory infection with pneumonia. Accepted for publication: 4 December 1997     

Comparative Gravimetric Studies on Carbon Steel Corrosion in Selected Fruit Juices and Acidic Chloride Media (HCl) at Different pH

Food contamination due to metal corrosion and the consequent leakage of metals into foods is a problem. Understanding the mechanism(s) of metal corrosion in food media is vital to evaluating, mitigating, and predicting contamination levels. Fruit juices have been employed as model corrosive media to study the corrosion behaviour of metallic material in food media. Carbon steel corrosion in fresh juices of tomato, orange, pineapple, and lemon, as well as dilute hydrochloric acid solutions at varied pH, was studied using scanning electron microscopy, gravimetric and spectrophotometric techniques, and comparisons made between the corrosivity of these juices and mineral acids of comparable pH. The corrosion of carbon steel in fruit juices and HCl solutions manifests as a combination of uniform and pitting corrosion. Gravimetric data acquired after one hour of immersion at ambient temperature (22 °C) indicated corrosion rates of 0.86 mm yr⁻¹ in tomato juice (pH ≈ 4.24), 1.81 mm yr⁻¹ in pineapple juice (pH ≈ 3.94), 1.52 mm yr⁻¹ in orange juice (pH ≈ 3.58), and 2.89 mm yr⁻¹ in lemon juice (pH ≈ 2.22), compared to 2.19 mm yr⁻¹ in 10⁻² M HCl (pH ≈ 2.04), 0.38 mm yr⁻¹ in 10⁻³ M HCl (pH ≈ 2.95), 0.17 mm yr⁻¹ in 10⁻⁴ M HCl (pH ≈ 3.95), and 0.04 mm yr⁻¹ in 10⁻⁵ M HCl (pH ≈ 4.98). The correlation of gravimetrically acquired corrosion data with post-exposure spectrophotometric analysis of fruit juices enabled de-convolution of iron contamination rates from carbon steel corrosion rates in fruit juices. Elemental iron contamination after 50 h of exposure to steel samples was much less than the values predicted from corrosion data (≈40%, 4.02%, 8.37%, and 9.55% for tomato, pineapple, orange, and lemon juices, respectively, relative to expected values from corrosion (weight loss) data). Tomato juice (pH ≈ 4.24) was the least corrosive to carbon steel compared to orange juice (pH ≈ 3.58) and pineapple juice (pH ≈ 3.94). The results confirm that though the fruit juices are acidic, they are generally much less corrosive to carbon steel compared to hydrochloric acid solutions of comparable pH. Differences in the corrosion behaviour of carbon steel in the juices and in the different mineral acid solutions are attributed to differences in the compositions and pH of the test media, the nature of the corrosion products formed, and their dissolution kinetics in the respective media. The observation of corrosion products (iron oxide/hydroxide) in some of the fruit juices (tomato, pineapple, and lemon juices) in the form of apparently hollow microspheres indicates the feasibility of using fruit juices and related wastes as “green solutions” for the room-temperature and hydrothermal synthesis of metal oxide/hydroxide particles.     

Effect of sialic acid on glycation-induced fluorescence of albumin

The aims of this study were to determine whether in vitro nonenzymatic glycation of proteins by sialic acid (sialylation) induces the generation of fluorescence, and whether the presence of this keto sugar may affect the generation of fluorescence induced by other sugars. Incubation of bovine serum albumin (BSA; 1.5 mM) with sugars (50 mM in 0.2 M phosphate buffer, pH 7.4, at 37°C) resulted in a time-dependent increase of formaldehyde release (moles/moles of protein). On the 17th day of incubation, the value was 0.53±0.06, 0.78±0.15 and 1.23±0.18 for sialic acid, fructose and glucose respectively, compared with 0.37±0.05 for BSA. The fluorescence intensity (arbitrary units/mg protein) was higher after 17 days of incubation with fructose (16.9±1.8) than with glucose (12.7±1.3), while no significant increase was noted with sialic acid compared with BSA (3.8±0.4). Fluorescence intensity increase by incubation with glucose (50 mM) was significantly reduced by sialic acid (20 mM) after both 10 (P<0.001) and 14 (P<0.001) days of incubation, while inhibition was weaker after 14 (P<0.05) than after 10 (P<0.001) days when fructose (50 mM) was used as the glycating agent. This indicates that sialic acid can be potentially used to limit the damage from adverse glycation-induced processes.     

Choledochal cysts in adults and their complications

BackgroundDespite refinements in the management of choledochal cysts in children, an increasing number of patients present with ongoing symptoms in adult life. The aim of this study was to review the management of adult patients with choledochal cysts in a tertiary referral centre.MethodA retrospective review was carried out of all adult patients presenting with choledochal cysts to this department between 1992 and 2000. Patient records were reviewed and detailed analyses were made of the clinical presentation, radiological and biochemical findings, anatomical anomalies, management, complications and outcomes.ResultsOf 16 patients (12 women and 4 men; median age 23 years), 8 had undergone previous upper gastrointestinal operations before referral, including 5 who had had previous cyst drainage procedures. All patients underwent elective complete cyst excision with Roux-en-Y hepaticojejunostomy. There were no operative deaths and there was a low early postoperative morbidity rate (25%). There was no evidence of biliary malignancy in any cyst. During a median postoperative follow-up of 44 months, five patients (31%) continued to experience cholangitis and two of these required additional revisional procedures, but are now symptom-free.ConclusionPatients with choledochal cysts should be referred to specialised tertiary surgical units. Total choledochal cyst excision with Roux-en-Y hepaticojejunostomy is the treatment of choice. Patients with previous inadequate cyst excisional procedures should undergo revisional surgery, to reduce recurrent symptoms and the risk of developing cholangiocarcinoma.     

Deep Inspiration-Provoked Cough: A Sign of Cough Reflex Arc Hypersensitivity

Deep inspiration-provoked cough (DIPC) is a form of allotussia. Allotussia is thought to be a manifestation of cough reflex arc hypersensitivity but objective evidence about this is lacking. 36 subjects with chronic cough and 25 healthy subjects underwent mannitol and citric acid cough provocation tests. DIPC was defined as two or more coughs after deep inhalation of an empty mannitol capsule. Citric acid was administered utilizing a dosimetric nebulizer during controlled tidal breathing. Nine subjects demonstrated DIPC, 8/36 subjects with chronic cough and 1/25 healthy subjects (p = 0.048). The concentration of citric acid to provoke five or more coughs (C5) was 23.4 (63.8) mM among subjects with DIPC and 750 (2941) mM among the subjects without it (p = 0.006). The number of deep inspiration-provoked coughs correlated with the citric acid C5 (Rs -0.38, p = 0.002). In conclusion, DIPC, a form of allotussia, is associated with cough reflex arc hypersensitivity.

Trial Registration Number.

ClinicalTrials.gov database KUH5801136.

     

Multiple forms of acid phosphatase activity in Gaucher's disease.

Although the primary genetic defect in all individuals with Gaucher's disease is a deficiency in glucocerebrosidase activity, the finding of marked elevations in splenic and serum acid phosphatase activity is almost as consistent a finding. Gaucher spleen and serum contain at least two forms of acid phosphatase that can be readily separated by chromatography on columns containing the cation exchange resin Sulphopropyl Sephadex. The major species of acid phosphatase (designated SP-I) contained in Triton X-100 (1% v/v) extracts of Gaucher spleen accounts for 65%--95% of the total activity and has the following properties: (1) it does not bind to the cation exchange column; (2) it exhibitis a pH optimum of 4.5--5.0; (3) it is inhibited by sodium fluoride (15 mM), L(+)-tartaric acid (20 mM), and beta-mercaptoethanol (2.1 M), and (4) it is resistant to inhibition by sodium dithionite (10 mM). The minor acid phosphatase activity (designated SP-II) present in extracts of Gaucher spleen has properties similar to those of the major species of acid phosphatase activity contained in serum from patients with Gaucher's disease: (1) it binds firmly to cation exchange columns (eluted by 0.5 M sodium chloride); (2) it exhibits a pH optimum of 5.0--6.0; (3) it is inhibited by sodium fluoride and sodium dithionite; and (4) it is resistant to inhibition by beta-mercaptoethanol (2.1 M) and L(+)-tartaric acid (20 mM). In addition, a second form of acid phosphatase that is tartrate resistant was found to be elevated in Gaucher serum. This form of serum acid phosphatase did not bind to Sulphopropyl Sephadex, was found to be significantly resistant to beta-mercaptoethanol (2.1 M), and was only partially inhibited by sodium dithionite (10 mM). The findings reported here indicate that at least three distinct forms of acid phosphatase activity are elevated in Gaucher's disease. Furthermore, the minor acid phosphatase activity contained in spleen homogenates has properties very similar to those of the major acid phosphatase activity observed to be present in serum of patients with Gaucher's disease. These data indicate that simple spleen spillage cannot account for the increased levels of serum acid phosphatase in patients with Gaucher's disease.     

Randomized Study Comparing Two Regimens of Oral Sodium Phosphates Solution Versus Low-Dose Polyethylene Glycol and Bisacodyl

Purpose Low-volume bowel preparation regimens for colonoscopy are reported to improve patient acceptance and compliance. We sought to compare the bowel cleansing efficacy, tolerability, and acceptability of three low-volume regimens: an oral sodium phosphates solution 45/45 ml (NaP-45/45), a reduced-dose oral sodium phosphates solution 45/30 ml (NaP-45/30), and polyethylene glycol plus bisacodyl (PEG-2L). Results A total of 121 patients were evaluated (mean age 55.2 ± 8.9 years). Bowel cleansings rated as excellent and good were significantly different among the groups: NaP-45/45 = 98%, NaP-45/30 = 88%, and PEG-2L = 76% (P < 0.04). Side effects were not significantly different except for greater thirst in the NaP-45/45 group (P = 0.001) and increased vomiting in females using PEG-2L (two-tailed interaction, P < 0.10). Willingness to retake the preparation was higher among the sodium phosphates regimens (88, 95, and 73%, respectively; P = 0.019). Conclusions Better cleansing and willingness to retake the regimen was achieved with the oral sodium phosphates solutions than with polyethylene glycol plus bisacodyl.