Oral Lactulose Research Articles

Novel regimen for colonoscopy bowel preparation with oral lactulose: a prospective comparative study.

Polyethylene glycol (PEG) is considered the gold standard regimen for bowel preparation; however, due to the necessity of a large volume, patient tolerance is impaired. Therefore, lactulose is a novel alternative for colonoscopy preparation. This study aimed to investigate the efficacy and safety of lactulose-based bowel preparations in comparison with PEG for colonoscopy. This is a prospective, non-blinded, comparative study. Outpatients were randomly divided into two groups: group 1 (111 patients), PEG; and group 2 (111 patients), lactulose. The following clinical outcomes were assessed in each group: degree of bowel clearance using the Boston bowel preparation score, colorectal polyp detection rate, adenoma detection rate, tolerability, and side effects. The rate of inadequate bowel preparation was 8.1% and 1.8% for the PEG and lactulose groups, respectively (p=0.030). The Boston bowel preparation score for the entire colon was 7.34±1.17 and 8.36±1.09 for the PEG and lactulose groups, respectively (p<0.001). The satisfactory overall experience rates were 27.9% and 62.2% for the PEG and lactulose groups, respectively (p<0.001). The novel bowel preparation with oral lactulose was superior to that with PEG in terms of colon cleansing, adenoma detection rate, tolerance, and patient experience.

Clinical Effects of Implantable Sacral Neuromodulation Combined with Floating Needle Reperfusion in the Treatment of Patients with Functional Defecation Disorders

Objective: To investigate the clinical effect of implantable sacral neuromodulation combined with floating needle reperfusion in treating patients with functional defecation disorder. Methods: 40 eligible constipated patients with defecation disorder were screened according to the criteria of Rome IV for chronic constipation, and were divided into 20 cases each in the control group and the study group according to the random number table method. The control group was given oral lactulose combined with mosapride treatment, and the study group was given implantation of sacral nerve stimulation electrodes and floating needle reperfusion treatment. The clinical symptoms, visual analog scale (VAS) score, Wexner score for constipation, quality of life score, anorectal manometry, adverse reactions, and complications were observed in both groups. Results: After treatment, the median number of voluntary feces per week and the median number of days of voluntary feces per week in the study group were higher than those in the control group, and the median duration of defecation was lower than that in the control group (P &lt; 0.05); the median VAS score of the study group was significantly higher than that of the control group (P &lt; 0.05); the constipation Wexner score of the study group was significantly lower than that of the control group (P &lt; 0.001); the quality of life scores of the study group were overall better than those of the control group (P &lt; 0.05); the anal resting pressure, anal residual pressure, and rectal propulsion of the study group were significantly better than those of the control group (P &lt; 0.05); liquefaction of the incision occurred in only one patient during treatment in the study group, which was healed after changing the medication and did not have any serious complications, and two patients in the control group had abdominal pain, and there was no significant difference between the two groups (P &gt; 0.05). Conclusion: In the treatment of patients with functional defecation disorder, implantable sacral neuromodulation combined with floating needle reperfusion therapy can effectively improve the clinical symptoms and quality of life of patients.

Polyethylene glycol compared to lactulose for constipation in pregnancy: A randomized controlled trial.

To compare polyethylene glycol 4000 versus lactulose in chronic constipation during pregnancy. Women at 28-32 weeks' gestation attending antenatal clinic for routine care were screened using the Rome IV chronic constipation criterion. Eligible women were approached and consented. Participants were randomized to oral polyethylene glycol (10 g/day) or lactulose (10 g/day) for 4 weeks. A bowel movement diary was kept and outcomes using the Patient Assessment of Constipation Symptoms questionnaire (PAC-SYM), Patient Assessment of Constipation Quality of Life questionnaire (PAC-QoL) and Bristol Stool Form Scale (BSFS), which were evaluated at the start and end of the four-week period. Relative risks (RR) were determined for the coprimary outcomes of complete spontaneous bowel movement (CSBM) and PAC-SYM mean score improvement (decrease in score of >1 from the baseline). A total of 4323 women underwent screening, of which 780 fulfilled the Rome IV criterion, and 360 consented to participate (180 randomized to PEG and lactulose, respectively). Data from 247 women who completed the study were analyzed. CSBM was achieved in 107/124 (86.3%) versus 102/123 (82.9%) (RR 1.04, 95% CI: 0.93-1.16, P = 0.464) for PEG and lactulose trial arms, respectively. PAC-SYM mean score improvement was 62/118 (52.5%) in the PEG arm versus 44/118 (37.3%) in the lactulose arm (RR 1.40, 95% CI: 1.05-1.88). Of secondary outcomes, a significant difference was found in favor of PEG, with respect to PAC-SYM abdominal symptoms subscale, normal stool versus loose stool consistency and side effects of vomiting and diarrhea. After controlling for parity, baseline PAC-SYM, PAC-QoL scores, characteristics different at baseline, only diarrhea and loose stools remained significant. Both PEG 4000 and lactulose are effective laxatives in pregnancy with similar performance after adjusted analysis. Diarrhea and loose stools are less frequently reported with PEG.

Intestinal permeability in patients undergoing stem cell transplantation correlates with systemic acute phase responses and dysbiosis.

Intestinal permeability may correlate with adverse outcomes during hematopoietic stem cell transplantation (HSCT), but longitudinal quantification with traditional oral mannitol and lactulose is not feasible in HSCT recipients because of mucositis and diarrhea. A modified lactulose:rhamnose (LR) assay is validated in children with environmental enteritis. Our study objective was to quantify peri-HSCT intestinal permeability changes using the modified LR assay. The LR assay was administered before transplant, at day+7 and+30 to 80 pediatric and young adult patients who received allogeneic HSCT. Lactulose and rhamnose were detected using urine mass spectrometry and expressed as an L:R ratio. Metagenomic shotgun sequencing of stool for microbiome analyses and enzyme-linked immunosorbent assay analyses of plasma lipopolysaccharide binding protein (LBP), ST2, REG3α, claudin1, occludin, and intestinal alkaline phosphatase were performed at the same timepoints. L:R ratios were increased at day+7 but returned to baseline at day+30 in most patients (P= .014). Conditioning regimen intensity did not affect the trajectory of L:R (P= .39). Baseline L:R ratios did not vary with diagnosis. L:R correlated with LBP levels (r2= 0.208; P= .0014). High L:R ratios were associated with lower microbiome diversity (P= .035), loss of anaerobic organisms (P= .020), and higher plasma LBP (P= .0014). No adverse gastrointestinal effects occurred because of LR. Intestinal permeability as measured through L:R ratios after allogeneic HSCT correlates with intestinal dysbiosis and elevated plasma LBP. The LR assay is well-tolerated and may identify transplant recipients who are more likely to experience adverse outcomes.

Intestinal flora in the constipation patients before versus after lactulose intervention.

This study aimed to investigate the characteristics of intestinal flora in patients with chronic functional constipation before and after lactulose intervention. Twenty-nine patients with constipation in the treatment group received oral lactulose (15 mL/d) for a month. Twenty healthy subjects served as controls. Stool specimens were collected before and after lactulose treatment. Fecal bacteria were examined by 16SrRNA gene sequencing and bioinformatics analysis. After lactulose treatment, most bacteria in the constipation group, including Bifidobacteria, Bacillus cereus, Prevotella, Bacillus, Anaerostipes, Oribacterium, and Mogibacterium increased as compared to those in the healthy control group. Anaerotruncus declined in the healthy control group after lactulose treatment. Our study shows lactulose can increase the abundance of probiotics, optimize the intestinal microenvironment, and alleviate constipation.

Aluminum phosphate gel reduces early rebleeding in cirrhotic patients with gastric variceal bleeding treated with histoacryl injection therapy.

Esophageal-gastro varices bleeding (EGVB) is the most widely known cause of mortality in individuals with cirrhosis, with an occurrence rate of 5% to 15%. Among them, gastric varices bleeding (GVB) is less frequent than esophageal varices bleeding (EVB), but the former is a more critical illness and has a higher mortality rate. At present, endoscopic variceal histoacryl injection therapy (EVHT) is safe and effective, and it has been recommended by relevant guidelines as the primary method for the treatment of GVB. However, gastric varices after endoscopic treatment still have a high rate of early rebleeding, which is mainly related to complications of its treatment, such as bleeding from drained ulcers, rebleeding of varices etc. Therefore, preventing early postoperative rebleeding is very important to improve the quality of patient survival and outcomes. To assess the efficacy of aluminium phosphate gel (APG) combined with proton pump inhibitor (PPI) in preventing early rebleeding after EVHT in individuals with GVB. Medical history of 196 individuals with GVB was obtained who were diagnosed using endoscopy and treated with EVHT in Shenzhen People's Hospital from January 2016 to December 2021. Based on the selection criteria, 101 patients were sorted into the PPI alone treatment group, and 95 patients were sorted into the PPI combined with the APG treatment group. The incidences of early rebleeding and corresponding complications within 6 wk after treatment were compared between both groups. Statistical methods were performed by two-sample t-test, Wilcoxon rank sum test and χ 2 test. No major variations were noted between the individuals of the two groups in terms of age, gender, Model for End-Stage Liver Disease score, coagulation function, serum albumin, hemoglobin, type of gastric varices, the dose of tissue glue injection and EV that needed to be treated simultaneously. The early rebleeding rate in PPI + APG group was 3.16% (3/95), which was much lower than that in the PPI group (12.87%, 13/101) (P = 0.013). Causes of early rebleeding: the incidence of gastric ulcer bleeding in the PPI + APG group was 2.11% (2/95), which was reduced in comparison to that in the PPI group (11.88%, 12/101) (P = 0.008); the incidence of venous bleeding in PPI + APG group and PPI group was 1. 05% (1/95) and 0.99% (1/101), respectively, and there was no significant difference between them (0.999). The early mortality rate was 0 in both groups within 6 wk after the operation, and the low mortality rate was related to the timely hospitalization and active treatment of all patients with rebleeding. The overall incidence of complications in the PPI + APG group was 12.63% (12/95), which was not significantly different from 13.86% (14/101) in the PPI group (P = 0.800). of abdominal pain in the PPI + APG group was 3.16% (3/95), which was lower than that in the PPI group (11.88%, 12/101) (P = 0.022). However, due to aluminum phosphate gel usage, the incidence of constipation in the PPI + APG group was 9.47% (9/95), which was higher than that in the PPI group (1.98%, 2/101) (P = 0.023), but the health of the patients could be improved by increasing drinking water or oral lactulose. No patients in either group developed spontaneous peritonitis after taking PPI, and none developed hepatic encephalopathy and ectopic embolism within 6 wk of EVHT treatment. PPI combined with APG can significantly reduce the incidence of early rebleeding and postoperative abdominal pain in cirrhotic patients with GVB after taking EVHT.

Oral Lactulose – A Safe and Effective Strategy for the Management of Constipation in Individuals with Impaired Glucose Tolerance and Diabetes

Lactulose, either as crystals or liquid syrup, is a frequently prescribed osmotic laxative agent in patients with diabetes mellitus (DM). During the manufacturing process, carbohydrate impurities can arise which could increase blood glucose levels with a possible impact on glycemic control. This important issue has now been addressed for the first time in individuals with type 2 DM. A recent RCT confirmed that there is no need to consider carbohydrate impurities in oral lactulose products administered at the recommended doses of 20 g/day and 30 g/day for blood glucose management.

The added value of MDCT enterography using oral lactulose solution in detection, characterization, and guiding management of small bowel disorders

BackgroundSmall bowel variable symptoms present a diagnostic challenge for both gastroenterologists and radiologists due to SI length, overlapping serpentine course and continuous motility. CT enterography was introduced in the last two decades as the cornerstone imaging modality in diagnosing small bowel disorders using a mixture of an oral solution containing water and a gastrointestinal diluting agent. This study aims to demonstrate the added value of MDCTE in evaluating and guiding the management of small bowel disorders in order to reduce SI-related morbidity and mortality.ResultsData analysis of 80 patient records involved in this study demonstrated the high accuracy of MDCTE in detecting different small bowel disorders and their related pathologies, confirmed by laboratory and histopathological analyses.ConclusionsMDCT enterography with oral lactulose solution is now the mainstay of imaging in the detection, characterization, and guiding management of small bowel disorders with great value of low-dose techniques in CD patient’s follow-up in order to reduce ionizing radiation exposure.

S3415 Gastroenterological Manifestations in a Patient With Common Variable Immunodeficiency

Introduction: Gastrointestinal manifestation of common variable immunodeficiency (CVID) can present with protein-losing enteropathy (PLE). A wide spectrum of liver injuries can occur with CVID, including nodular regenerative hyperplasia (NRH). Case Description/Methods: 41 y.o. female with PMH of CVID on IgG, chronically elevated LFTs, and nutritional deficiencies. Patient presented with 8-year history of diarrhea, bloating, weight loss, abdominal pain, hepatic encephalopathy (HE), new ascites, and shock. Previously was diagnosed with celiac disease and has strictly followed a gluten-free diet with no improvement. EGD on the current presentation showed visible changes in duodenal mucosa including villous flattening. Biopsies this time revealed villous flattening and absence of plasma cells consistent with CVID enteropathy. Liver biopsy 5 years prior to admission showed no liver disease. Serologic workups, including anti-gp210 and anti-sp100, were negative. Biopsy showed nodular regenerative hyperplasia and non-cirrhotic portal hypertension, which was confirmed by reticulin stain. Patient was started on budesonide 9 mg daily for treatment of PLE, and marked improvement of diarrhea was noted. Non-cirrhotic portal hypertension was managed with furosemide and spironolactone. HE was managed with oral lactulose. The patient was started on enteral and parenteral supplements. Discussion: Duodenal villous atrophy which is a diagnostic criterion for celiac disease can be seen in multiple other conditions including immune disorders such as CVID. In CVID patients with gastrointestinal symptoms, up to 80% of biopsies from different sites in the GI tract will show histological abnormalities. Given their common presentation, celiac disease can be initially diagnosed. The absence of plasma cells and apoptosis presence in duodenal biopsy can suggest PLE diagnosis. Serological studies are not reliable for celiac disease diagnosis due to deficiency of immunoglobulin production in CVID. Steroids can be used for the treatment of PLE in CVID. Hepatic manifestations in CVID are extremely varied and often misdiagnosed given they can mimic other diseases. NRH is a potentially fatal complication of CVID. Recognition of this complication allowed for symptom resolution within two days of starting lactulose therapy. NRH in CVID represents an autoimmune-like liver disease that might be driven by a local vasculopathy, and thus severe cases can warrant a trial of immunosuppression.

S3336 An Unusual Cause of Encephalopathy

Introduction: Hepatic encephalopathy, while common among cirrhosis patients, can occur without cirrhosis. In adults, 90% cases of hyperammonemia are due to cirrhosis. Ammonia is central to its pathophysiology produced by bacterial degradation in the gut from protein, urea, and glutamine. Ammonia acts as a neurotoxin which is metabolized by hepatocytes to urea for excretion via kidney and colon. Type B hepatic encephalopathy is due to portosystemic shunting without parenchymal liver disease. Case Description/Methods: A 69-year-old female with history of hepatoma with resection and chemoembolization in 1997, mucosa-associated lymphoid tissue, perforated diverticulitis status post colostomy and reversal in 2015 was in her usual state of health a day prior to admission when she presented with lethargy after episodes of nausea and vomiting. She was arousable and not able to follow commands. Her CT (computed tomography) of the brain with no acute changes followed by CT of abdomen showing dilated small intestine extending into ventral hernia with concern for obstruction. Blood tests revealed ammonia 141 umol/L, total bilirubin 4.1 mg/dL, direct bilirubin 1.5 mg/dL, international normalized ratio 1.2 and platelet 130 k/ul. Alkaline phosphatase, alanine and aspartate transaminases were within normal limits. Obstruction resolved with conservative management and she was started on rectal and oral lactulose with rifaximin via nasogastric tube. Her mentation improved significantly although the cause of her hepatic encephalopathy remained unclear. Then she underwent magnetic resonance imaging of the abdomen with contrast showing portal to hepatic vein shunt with stable postoperative changes. Shunt closure option was discussed and patient opted outpatient follow up. Discussion: Prompt diagnosis and treatment of hepatic encephalopathy is important to prevent cerebral edema. In patients with encephalopathy and elevated ammonia in absence of liver parenchymal disease, work-up for shunt and urea cycle enzyme deficiency should be done. In the absence of cirrhosis most portosystemic shunts are congenital or traumatic. This case brings a rare cause due to remote liver surgery and chemoembolization. The treatment of portosystemic shunts is evolving, balloon-occlusion retrograde transvenous obliteration is one such technique. In the absence of varices, bland embolization with ectopic coils and vascular plugs can be utilized. Endovascular treatment carries an improvement of hepatic encephalopathy by 50 to 80% at 18 to 24 months.

Kratom Associated Withdrawal Symptoms and Naltrexone: A Case Report

Kratom (Mitragyna speciosa Korth), an indigenous herb of Southeast Asia, is popularly used to treat withdrawal symptoms associated with opiate addiction and a myriad of ailments including chronic pain, anxiety and hypertension. Its use has significantly increased in western countries because of its widespread advertisement on the internet as a safe, nonaddictive alternative treatment of pain and opioid dependent disorders. This report describes the first emergency case of toxic encephalopathy, rhabdomyolysis, and liver injury in relation to kratom withdrawal syndrome induced by naltrexone in a 49-year old male. The symptoms were resolved with a regimen of dexmedetomidine, lorazepam, oral lactulose, and a bicarbonate drip. Outpatient treatment with lorazepam and tramadol was recommended for further withdrawal symptoms.

Altered Intestinal Production of Volatile Fatty Acids in Dogs Triggered by Lactulose and Psyllium Treatment.

The intestinal microbiome of dogs can be influenced by a number of factors such as non-starch polysaccharides as well as some non-digestible oligo- and disaccharides. These molecules are only decomposed by intestinal anaerobic microbial fermentation, resulting in the formation of volatile fatty acids (VFAs), which play a central role in maintaining the balance of the intestinal flora and affecting the health status of the host organism. In the present study, the effects of lactulose and psyllium husk (Plantago ovata) were investigated regarding their influence on concentrations of various VFAs produced by the canine intestinal microbiome. Thirty dogs were kept on a standard diet for 15 days, during which time half of the animals received oral lactulose once a day, while the other group was given a psyllium-supplemented diet (in 0.67 and in 0.2 g/kg body weight concentrations, respectively). On days 0, 5, 10 and 15 of the experiment, feces were sampled from the rectum, and the concentration of each VFA was determined by GC-MS (gas chromatography–mass spectrometry). Lactulose administration caused a significant increase in the total VFA concentration of the feces on days 10 and 15 of the experiment (p = 0.035 and p < 0.001, respectively); however, in the case of psyllium supplementation, the concentration of VFAs showed a significant elevation only on day 15 (p = 0.003). Concentrations of acetate and propionate increased significantly on days 5, 10 and 15 after lactulose treatment (p = 0.044, p = 0.048 and p < 0.001, respectively). Following psyllium administration, intestinal acetate, propionate and n-butyrate production were stimulated on day 15, as indicated by the fecal VFA levels (p = 0.002, p = 0.035 and p = 0.02, respectively). It can be concluded that both lactulose and psyllium are suitable for enhancing the synthesis of VFAs in the intestines of dogs. Increased acetate and propionate concentrations were observed following the administration of both supplements; however, elevated n-butyrate production was found only after psyllium treatment, suggesting that the applied prebiotics may exert slightly different effects in the hindgut of dogs. These findings can be also of great importance regarding the treatment and management of patients suffering from intestinal disorders as well as hepatic encephalopathy due to portosystemic shunt.

Saudi Experts Consensus on Diagnosis and Management of Pediatric Functional Constipation.

Although functional gastrointestinal disorders (FGIDs) are very common in pediatric patients, there is a scarcity of published epidemiologic data, characteristics, and management patterns from Saudi Arabia, which is the 2nd largest Arabic country in terms of area and the 6th largest Arabic country in terms of population, with 10% of its population aged <5 years. Functional constipation (FC) is an FGID that has shown a rising prevalence among Saudi infants and children in the last few years, which urges us to update our clinical practices. Nine pediatric consultants attended two advisory board meetings to discuss and address current challenges, provide solutions, and reach a Saudi national consensus for the management of pediatric constipation. The pediatric consultants agreed that pediatricians should pay attention to any alarming signs (red flags) found during history taking or physical examinations. They also agreed that the Rome IV criteria are the gold standard for the diagnosis of pediatric FC. Different therapeutic options are available for pediatric patients with FC. Dietary treatment is recommended for infants with constipation for up to six months of age. When non-pharmacological interventions fail to improve FC symptoms, pharmacological treatment with laxatives is indicated. First, the treatment is aimed at disimpaction to remove fecal masses. This is achieved by administering a high dose of oral polyethylene glycol (PEG) or lactulose for a few days. Subsequently, maintenance therapy with PEG should be initiated to prevent the re-accumulation of feces. In addition to PEG, several other options may be used, such as Mg-rich formulas or stimulant laxatives. However, rectal enemas and suppositories are usually reserved for cases that require acute pain relief. In contrast, infant formulas that contain prebiotics or probiotics have not been shown to be effective in infant constipation, while the use of partially hydrolyzed formula is inconclusive. These clinical practice recommendations are intended to be adopted by pediatricians and primary care physicians across Saudi Arabia.

Treatment Experience of 210 Pediatric Patients With Extraordinary Daytime Urinary Frequency: A Prospective Study.

Background: Lactulose can be used to manage chronic constipation and children who are withholding their bowel movements, but no studies are available regarding lactulose to treat pediatric extraordinary daytime urinary frequency (PEDUF). To explore the benefits of different therapeutic regimens (non-drug treatment vs. oral lactulose) in patients with PEDUF.Methods: This prospective study included PEDUF patients admitted to the Pediatric Center of Qilu Hospital of Shandong University (Qingdao) from January 2015 to December 2019. The patients randomized received non-drug treatment (counseling), drug treatment (lactulose), or combination therapy. A therapeutic effect was defined by a decrease of>10% of the urination frequency.Results: A total of 210 patients were included. They were 5.9 ± 0.4 years. There were 98 boys and 112 girls. Among the 210 patients, 82.4% (173/210) of their family members reported symptoms of constipation. Among the three groups, the response rate was 61.4% (43/70) in the non-drug treatment group, 90.0% (63/70) in the drug treatment group, and 91.4% (64/70) in the combination therapy group (P < 0.0001).Conclusion: The frequency of constipation in children with PEDUF is high. The use of a laxative, like lactulose, might achieve a high therapeutic response rate in children with PEDUF, higher than counseling alone. That might represent a valuable therapeutic strategy for PEDUF.

Blood glucose response after oral lactulose intake in type 2 diabetic individuals.

BACKGROUNDLactulose is approved for the symptomatic treatment of constipation, a gastrointestinal (GI) complication common in individuals with diabetes. Lactulose products contain carbohydrate impurities (e.g., lactose, fructose, galactose), which occur during the lactulose manufacturing process. These impurities may affect the blood glucose levels of individuals with type 2 diabetes mellitus (T2DM) using lactulose for the treatment of mild constipation. A previous study in healthy subjects revealed no increase in blood glucose levels after oral lactulose intake. However, it is still unclear whether the intake of lactulose increases blood glucose levels in individuals with diabetes.AIMTo evaluate the blood glucose profile after oral lactulose intake in mildly constipated, non-insulin-dependent subjects with T2DM in an outpatient setting.METHODSThis prospective, double-blind, randomized, controlled, single-center trial was conducted at the Clinical Research Center at the Medical University of Graz, Austria, in 24 adult Caucasian mildly constipated, non-insulin-dependent subjects with T2DM. Eligible subjects were randomized and assigned to one of six treatment sequences, each consisting of four treatments stratified by sex using an incomplete block design. Subjects received a single dose of 20 g or 30 g lactulose (crystal and liquid formulation), water as negative control or 30 g glucose as positive control. Capillary blood glucose concentrations were measured over a period of 180 min post dose. The primary endpoint was the baseline-corrected area under the curve of blood glucose concentrations over the complete assessment period [AUCbaseline_c (0-180 min)]. Quantitative comparisons were performed for both lactulose doses and formulations vs water for the equal lactulose dose vs glucose, as well as for liquid lactulose vs crystal lactulose. Safety parameters included GI tolerability, which was assessed at 180 min and 24 h post dose, and adverse events occurring up to 24 h post dose.RESULTSIn 24 randomized and analyzed subjects blood glucose concentration-time curves after intake of 20 g and 30 g lactulose were almost identical to those after water intake for both lactulose formulations despite the different amounts of carbohydrate impurities (≤ 3.0% for crystals and approx. 30% for liquid). The primary endpoint [AUCbaseline_c (0-180 min)] was not significantly different between lactulose and water regardless of lactulose dose and formulation. Also with regard to all secondary endpoints lactulose formulations showed comparable results to water with one exception concerning maximum glucose level. A minor increase in maximum blood glucose was observed after the 30 g dose, liquid lactulose, in comparison to water with a mean treatment difference of 0.63 mmol/L (95% confidence intervals: 0.19, 1.07). Intake of 30 g glucose significantly increased all blood glucose endpoints vs 30 g liquid and crystal lactulose, respectively (all P < 0.0001). No differences in blood glucose response were observed between the different lactulose formulations. As expected, lactulose increased the number of bowel movements and was generally well tolerated. Subjects experienced only mild to moderate GI symptoms due to the laxative action of lactulose.CONCLUSIONBlood glucose AUCbaseline_c (0-180 min) levels in mildly constipated, non-insulin dependent subjects with T2DM are not affected by the carbohydrate impurities contained in 20 g and 30 g crystal or liquid lactulose formulations.

Type 4 Renal Tubular Acidosis (RTA) Induced by Spironolactone Use in Secondary Adrenal Insufficiency

Type 4 RTA is caused by either decreased aldosterone production or resistance. Primary adrenal insufficiency results in decreased aldosterone whereas spironolactone can cause aldosterone resistance1. We present a case of spironolactone-induced type 4 RTA in a patient with suspected primary adrenal insufficiency.A 70-year-old female with liver cirrhosis on spironolactone and chronic bronchitis on inhaled steroids (ICS) presented for altered mental status. Laboratories showed hyponatremia 131 mmol/L (135–145 mmol/L) and hyperammonemia 113 µmol/L (11–51 µmol/L). She was successfully treated with oral lactulose for hepatic encephalopathy. However, on day 3, she developed worsening hyponatremia (126 mmol/L) and hyperkalemia 5.8 mmol/L (3.5–5.4 mmol/L). Spironolactone was discontinued, and hyperkalemia improved after medical treatment. Nonetheless, hyperkalemia recurred with worsening hyponatremia (125 mmol/L), hypoglycemia (57 mg/dL), and mild non-anion gap metabolic acidosis without other signs or symptoms of adrenal insufficiency. On day 5, her morning cortisol was 1.5 µg/dL (5–20 µg/dL), with ACTH 11 pg/mL (6–70 pg/mL). Her hyperkalemia persisted (6.3–6.8 mmol/L), and she was started on oral patiromer. Due to suspected adrenal insufficiency, she received dexamethasone 10 mg daily, and endocrinology was consulted. On day 7, an ACTH stimulation test (250 µg IV) showed a baseline ACTH <3 pg/mL, baseline cortisol 0.7 µg/dL (3–15 µg/dL), cortisol 30 minutes 9.9 µg/dL, and 60 minutes 12.2 µg/dL, consistent with incomplete response attributed to the supraphysiologic dexamethasone versus chronic ICS. On day 8, endocrinology discontinued dexamethasone and enoxaparin, and started hydrocortisone 10 mg orally in AM and 5 mg in PM. Aldosterone (measured at day 6) was 7.2 ng/dL (<= 31.0 ng/dL), renin activity 3.1 ng/mL/hr (0.5–4.0 ng/mL/hr), and aldosterone/renin ratio 2.3 (<= 25) consistent with hyporeninemic hypoaldosteronism since aldosterone and renin were inappropriately normal for the hyperkalemia. Repeat cosyntropin test on day 11 showed low ACTH (3 pg/mL), low baseline cortisol 1.1 µg/dL, cortisol 30 minutes 7.9 µg/dL, and 60 minutes 11.2 µg/dL, consistent with secondary adrenal insufficiency, ascribed to chronic ICS. Potassium level normalized seven days after spironolactone discontinuation, related to its approximate duration of action1. The patient was discharged with hydrocortisone 10 mg daily, and spironolactone was permanently discontinued.Spironolactone use can result in type 4 RTA due to aldosterone resistance and mimic mineralocorticoid deficits characteristic of primary adrenal insufficiency.1. O’Connell JE, Colledge NR. Type IV renal tubular acidosis and spironolactone therapy in the elderly. Postgrad Med J. 1993;69(817):887–889.

Development and Validation of Test for “Leaky Gut” Small Intestinal and Colonic Permeability Using Sugars in Healthy Adults

Oral monosaccharides and disaccharides are used to measure invivo human gut permeability through urinary excretion. The aims were as follows: (1) to obtain normative data on small intestinal and colonic permeability; (2) to assess variance on standard 16 g fiber diet performed twice; (3) to determine whether dietary fiber influences gut permeability measurements; and (4) to present pilot data using 2 selected probes in patients with diarrhea-predominant irritable bowel syndrome (IBS-D). Sixty healthy female and male adults, age 18-70 years, participated in 3 randomized studies (2 studies on 16.25 g and 1 study on 32.5 g fiber) in otherwise standardized diets. At each test, the following sugars were ingested: 12C-mannitol, 13C-mannitol, rhamnose (monosaccharides), sucralose, and lactulose (disaccharides). Standardized meals were administered from 24 hours before and during 24 hours post-sugars with 3 urine collections: 0-2, 2-8, and 8-24 hours. Sugars were measured using high-performance liquid chromatography-tandem mass spectrometry. Eighteen patients with IBS-D underwent 24-hour excretion studies after oral 13C-mannitol and lactulose. Baseline sugars (>3-fold above lower limits of quantitation) were identified in the 3 studies: 12C-mannitol in all participants; sucralose in 4-8, and rhamnose in 1-3. Median excretions/24 h (percentage of administered dose) for 13C-mannitol, rhamnose, lactulose, and sucralose were ∼30%, ∼15%, 0.32%, and 2.3%, respectively. 13C-mannitol and rhamnose reflected mainly small intestinal permeability. Intraindividual saccharide excretions were consistent, with minor differences with 16.25 g vs 32.5 g fiber diets. Median interindividual coefficient of variation was 76.5% (10-90 percentile: 34.6-111.0). There were no significant effects of sex, age, or body mass index on permeability measurements in health. 13C-mannitol measurements are feasible in IBS-D. Baseline 12C-mannitol excretion precludes its use; 13C-mannitol is the preferred probe for small intestinal permeability.

Oral Lactulose vs. Polyethylene Glycol for Bowel Preparation in Colonoscopy: A Randomized Controlled Study.

BackgroundColonoscopy is the method of choice to evaluate colonic mucosa and the distal ileum, allowing the diagnosis and treatment of many diseases. Appropriate bowel preparation necessitates the use of laxative medications, preferentially by oral administration. These include polyethylene glycol (PEG), sodium picosulfate, and sodium phosphate (NaP). Lactulose, a semi-synthetic derivative of lactose, undergoes fermentation, acidifying the gut environment, stimulates intestinal motility, and increases osmotic pressure within the lumen of the colon.MethodsIn this prospective randomized controlled study, we analyzed 40 patients who presented with symptomatic bleeding per rectum and underwent bowel preparation either with lactulose or polyethylene glycol for colonoscopy. The quality of bowel preparation and other variables like palatability, discomfort, and electrolyte levels were analyzed.ResultsThe majority of the patients (90%) were comfortable with the taste of lactulose solution, whereas the PEG group patients (55%) were equally divided on its palatability. On lactulose consumption, 40% of patients reported nausea/vomiting and around 10% of patients complained of abdominal discomfort. Serum sodium levels showed insignificant changes from 4.33 ± 0.07 mEq/L to 4.21 ± 0.18 mEq/L while potassium also remained similar from 4.26 ± 0.03 mEq/L to 4.22 ± 0.17 mEq/L. The mean Boston Bowel Preparation Score (BBPS) in patients who received lactulose solution was 6.25 ± 0.786 and in those who received PEG solution, it was 6.35 ± 0.813 (P-value = 0.59).ConclusionsLactulose is a significantly more palatable form of bowel preparation and causes minor discomfort. It has a good bowel cleansing action comparable to PEG without causing any hemodynamic changes. It can be considered a cheaper and safe alternative for bowel preparation in colonoscopy in low-resource settings.

Clinical investigation in non-liver cirrhosis portosystemic shunt encephalopathy-four case series.

We reported here four cases presenting with disturbance of consciousness over long periods of time and hyperammonemia. Two patients were on maintenance hemodialysis. Contrast-enhanced computed tomography (CT) of abdomen and balloon-occluded retrograde contrast venography revealed existence of a non-cirrhotic portosystemic shunt. Conservative treatment such as intravenous branched-chain amino acid administration and oral lactulose administration had only a modest effect in all patients. Improvements in symptoms were observed following the occlusion of the shunt path in three patients. Measurements of ammonia values would be the most important test for screening, but changes in Fischer’s ratio or indocyanine green (ICG) test values were also correlated with clinical symptoms. Neurologists should keep in mind the possibility of non-cirrhotic portosystemic shunts when they encounter patients with disturbance of consciousness. They should also remember that occlusion of the shunt pathway is an effective treatment.

Effect of dietary fiber and threonine content on intestinal barrier function in pigs challenged with either systemic E. coli lipopolysaccharide or enteric Salmonella Typhimurium

BackgroundThe independent and interactive effects of dietary fiber (DF) and threonine (Thr) were investigated in growing pigs challenged with either systemic E. coli lipopolysaccharide (LPS) or enteric Salmonella Typhimurium (ST) to characterise their effect on intestinal barrier function.ResultsIn experiment 1, intestinal barrier function was assessed via oral lactulose and mannitol (L:M) gavage and fecal mucin analysis in pigs challenged with E. coli LPS and fed low fiber (LF) or high fiber (HF) diets with graded dietary Thr. Urinary lactulose recovery and L:M ratio increased (P < 0.05) during the LPS inoculation period in LF fed pigs but not in HF fed pigs. Fecal mucin output was increased (P < 0.05) in pigs fed HF compared to LF fed pigs. In experiment 2, RT-qPCR, ileal morphology, digesta volatile fatty acid (VFA) content, and fecal mucin output were measured in Salmonella Typhimurium challenged pigs, fed LF or HF diets with standard or supplemented dietary Thr. Salmonella inoculation increased (P < 0.05) fecal mucin output compared to the unchallenged period. Supplemental Thr increased fecal mucin output in the HF-fed pigs (Fib × Thr; P < 0.05). Feeding HF increased (P < 0.05) VFA concentration in cecum and colon. No effect of either Thr or fiber on expression of gene markers was observed except a tendency (P = 0.06) for increased MUC2 expression with the HF diet. Feeding HF increased goblet cell numbers (P < 0.05).ConclusionDietary fiber appears to improve barrier function through increased mucin production capacity (i.e., goblet cell numbers, MUC2 gene expression) and secretion (i.e., fecal mucin output). The lack of effect of dietary Thr in Salmonella-challenged pigs provides further evidence that mucin secretion in the gut is conserved and, therefore, Thr may be limiting for growth under conditions of increased mucin production.