Colonic gas homeostasis: Mechanisms of adaptation following HOST-G904 galactooligosaccharide use in humans.

BACKGROUND: We have shown that a galactooligosaccharide prebiotic administration (HOST-G904) initially increased intestinal gas production and this increase declined back to baseline after 2 week administration. Our aim was to determine the mechanism of microbiota adaptation; i.e., to determine whether the net reduction is due to decreased overall production or increased gas consumption. METHODS: In 10 healthy subjects, intestinal gas production and intraluminal disposal was measured before, at the beginning and after 2 week of HOST-G904 prebiotic administration. Anal gas was collected for 4 hour after a probe meal. Paired studies were performed without and with high-rate infusion of exogenous gas (24 mL/min) into the jejunum to wash-out the endogenous gas produced by bacterial fermentation. The exogenous gas infused was labeled (5% SF6 ) to calculate the proportion of endogenous gas evacuated. KEY RESULTS: The volume of intestinal gas produced i.e., endogenous gas washed-out, increased by 37% at the beginning of HOST-G904 administration (P=.049 vs preadministration) and decreased down to preadministration level after 2 week administration (P=.030 vs early administration). The proportion of gas eliminated from the lumen before reaching the anus tended to increase after 2-week administration (87±3% vs 78±5% preadministration; P=.098). CONCLUSIONS & INFERENCES: Adaptation to regular consumption of HOST-G904 prebiotic involves a shift in microbiota metabolism toward low-gas producing pathways, with a non-significant increase in gas-consuming activity. Hence, regular consumption of HOST-G904 regulates intestinal gas metabolism: less gas is produced and a somewhat larger proportion of it is consumed.

Metabolic adaptation of colonic microbiota to galactooligosaccharides: a proof-of-concept-study.

BACKGROUND: Prebiotics have been shown to reduce abdominal symptoms in patients with functional gut disorders, despite that they are fermented by colonic bacteria and may induce gas-related symptoms. AIM: To investigate changes in the metabolic activity of gut microbiota induced by a recognised prebiotic. METHODS: Healthy subjects (n = 20) were given a prebiotic (2.8 g/day HOST-G904, HOST Therabiomics, Jersey, Channel Islands) for 3 weeks. During 3-day periods immediately before, at the beginning and at the end of the administration subjects were put on a standard diet (low fibre diet supplemented with one portion of high fibre foods) and the following outcomes were measured: (i) number of daytime gas evacuations for 2 days by means of an event marker; (ii) volume of gas evacuated via a rectal tube during 4 h after a test meal; and (iii) microbiota composition by faecal Illumina MiSeq sequencing. RESULTS: At the beginning of administration, HOST-G904 significantly increased the number of daily anal gas evacuations (18 ± 2 vs. 12 ± 1 pre-administration; P < 0.001) and the volume of gas evacuated after the test meal (236 ± 23 mL vs. 160 ± 17 mL pre-administration; P = 0.006). However, after 3 weeks of administration, these effects diminished (11 ± 2 daily evacuations, 169 ± 23 mL gas evacuation). At day 21, relative abundance of butyrate producers (Lachnospiraceae) correlated inversely with the volume of gas evacuated (r = -0.52; P = 0.02). CONCLUSION: The availability of substrates induces an adaptation of the colonic microbiota activity in bacterial metabolism, which produces less gas and associated issues. Clinical trials.gov NCT02618239.

Percutaneous US-guided liver biopsy in focal lesions using a semiautomatic device allowing to perform multiple biopsies in a single-pass.

AIM: The aim of this study was to evaluate the safety and efficacy of percutaneous real-time ultra sound METHODS: One hundred and thirty-four consecutive percutaneous liver biopsies were performed in equal number of patients with focal liver lesions during a three-year period. All biopsies were performed with a single puncture, using a Tru-cat semiautomatic 18G needle (Precisa semi-automatic Tru-cut biopsy Device, HS Hospital Service, Italy) with removable inner stylet, under real-time US-guided. Two to five samples were obtained from each biopsy. In 12 cases an embolization of the biopsy track was performed. Thirty-two patients with hepatocellular carcinoma were followed for a period of 30-880 days for seeding. RESULTS: A total of 424 specimens were obtained from 134 biopsies. Evaluation of the biopsy specimens demonstrated that the 58.5% of them were >10 mm in length providing sufficient liver tissue for reliable histological diagnosis. The diagnosis was successful in 99.25% of the patients. No major complications or death occurred in our study group. Neither suspected nor confirmed tumor seeding was identified. CONCLUSION: Our results provide evidence that US-guided percutaneous liver biopsy using a semiautomatic 18G Tru-Cut needle with removable inner stylet can be performed with safety and efficacy in patients with focal liver lesions. Further-more, there are strong indications that the use of an introducer that remains in position during multiple cutting needle passes, protects normal tissue along the track and minimizes "seeding" and bleeding complications.

A double-blind, placebo-controlled, randomized human study assessing the capacity of a novel galacto-oligosaccharide mixture in reducing travellers' diarrhoea.

BACKGROUND/OBJECTIVES: Prebiotics have attracted interest for their ability to positively affect the colonic microbiota composition, thus increasing resistance to infection and diarrhoeal disease. This study assessed the effectiveness of a prebiotic galacto-oligosaccharide mixture (B-GOS) on the severity and/or incidence of travellers' diarrhoea (TD) in healthy subjects. SUBJECTS/METHODS: The study was a placebo-controlled, randomized, double blind of parallel design in 159 healthy volunteers, who travelled for minimum of 2 weeks to a country of low or high risk for TD. The investigational product was the B-GOS and the placebo was maltodextrin. Volunteers were randomized into groups with an equal probability of receiving either the prebiotic or placebo. The protocol comprised of a 1 week pre-holiday period recording bowel habit, while receiving intervention and the holiday period. Bowel habit included the number of bowel movements and average consistency of the stools as well as occurrence of abdominal discomfort, flatulence, bloating or vomiting. A clinical report was completed in the case of diarrhoeal incidence. A post-study questionnaire was also completed by all subjects on their return. RESULTS: Results showed significant differences between the B-GOS and the placebo group in the incidence (P<0.05) and duration (P<0.05) of TD. Similar findings occurred on abdominal pain (P<0.05) and the overall quality of life assessment (P<0.05). CONCLUSIONS: Consumption of the tested galacto-oligosaccharide mixture showed significant potential in preventing the incidence and symptoms of TD.

Clinical trial: the effects of a trans-galactooligosaccharide prebiotic on faecal microbiota and symptoms in irritable bowel syndrome.

BACKGROUND: Gut microflora-mucosal interactions may be involved in the pathogenesis of irritable bowel syndrome (IBS). AIM: To investigate the efficacy of a novel prebiotic trans-galactooligosaccharide in changing the colonic microflora and improve the symptoms in IBS sufferers. METHODS: In all, 44 patients with Rome II positive IBS completed a 12-week single centre parallel crossover controlled clinical trial. Patients were randomized to receive either 3.5 g/d prebiotic, 7 g/d prebiotic or 7 g/d placebo. IBS symptoms were monitored weekly and scored according to a 7-point Likert scale. Changes in faecal microflora, stool frequency and form (Bristol stool scale) subjective global assessment (SGA), anxiety and depression and QOL scores were also monitored. RESULTS: The prebiotic significantly enhanced faecal bifidobacteria (3.5 g/d P < 0.005; 7 g/d P < 0.001). Placebo was without effect on the clinical parameters monitored, while the prebiotic at 3.5 g/d significantly changed stool consistency (P < 0.05), improved flatulence (P < 0.05) bloating (P < 0.05), composite score of symptoms (P < 0.05) and SGA (P < 0.05). The prebiotic at 7 g/d significantly improved SGA (P < 0.05) and anxiety scores (P < 0.05). CONCLUSION: The galactooligosaccharide acted as a prebiotic in specifically stimulating gut bifidobacteria in IBS patients and is effective in alleviating symptoms. These findings suggest that the prebiotic has potential as a therapeutic agent in IBS.

Radiation doses to patients from digital subtraction angiography.

This investigation determined patient doses during digital subtraction angiography (DSA). Fluoroscopy time, dose-area product (DAP) and entrance surface air kerma (ESAK) were analysed from 263 DSA examinations, classified into seven categories: (1) abdominal aorta, iliac, femoral, popliteal and leg arteries; (2) abdominal aorta and superselective DSA of renal arteries; (3) combination of (1) and (2); (4) superselective DSA of common carotid and vertebral arteries, intracranial branches in face and profile projections; (5) superselective DSA of hepatic, splenic, superior and inferior mesenteric arteries; (6) combination of (1) and (4); and (7) celiac trunk and branches. Median DAP values were 67.7, 92.9, 76.6, 53.6, 105.7, 76.1 and 2.6 Gy cm2, respectively. With the exception of one examination, ESAK values were below 2 Gy: the limit for erythema. Compared with published data, DAP values were within the range reported for (1) and (4), slightly larger for (2) and (5), whereas no references were identified for the remaining three categories.

Modulation of anti-pathogenic activity in canine-derived Lactobacillus species by carbohydrate growth substrate.

AIMS: To investigate the effect of various carbon sources on the production of extracellular antagonistic compounds against two Escherichia coli strains and Salmonella enterica serotype Typhimurium by three canine-derived lactobacilli strains. METHODS AND MATERIALS: Cell-free preparations, pH neutralized, were used in antibiotic disc experiments as an initial screening. The bacteria/carbohydrate combinations that showed inhibition of the growth of those pathogens, were further investigated in batch co-culture experiments. The cell-free supernatants of the cultures, that decreased the population number of the pathogens in the co-culture experiments to log CFU ml-1

In vitro evaluation of the fermentation properties of galactooligosaccharides synthesised by alpha-galactosidase from Lactobacillus reuteri.

Stirred, pH-controlled anaerobic batch cultures were used to evaluate the in vitro utilisation by canine gut microflora of novel alpha-galactooligosaccharides synthesised with an enzyme extract from a canine Lactobacillus reuteri strain. Fructooligosaccharides (FOS), melibiose and raffinose were used as reference carbohydrates for the prebiotic properties of the synthesised oligosaccharide (galactosyl melibiose mixture-GMM). Addition of Lactobacillus acidophilus was used as control for the evaluation of the synbiotic properties of the oligosaccharide with L. reuteri. Populations of predominant gut bacterial groups were monitored over 48 h of batch culture by fluorescent in situ hybridisation, and short-chain fatty acid (SCFA) production was measured. GMM showed a higher increase in bifidobacteria and lactobacilli population number and size as well as a higher decrease in clostridia population number and size compared to the commercial prebiotics (FOS, melibiose, raffinose). This prebiotic effect was further increased by the addition of L. reuteri followed by a change in the SCFA production pattern compared to GMM alone or GMM with L. acidophilus. The observed change in SCFA production was in accordance with the fermentation properties of L. reuteri, suggesting that the novel synbiotic had a significant effect on the canine gut microflora fermentation.

Percutaneous insertion of metallic endoprostheses in the biliary tree in 66 patients: relief of the obstruction.

BACKGROUND: We evaluated the efficacy of percutaneous transhepatic insertion of metallic endoprosthesis in 66 patients with biliary obstruction. METHODS: From September 1994 through September 2002, 97 patients with obstructive jaundice attended the radiology department of our hospital; 92 had malignancy and five had benign obstruction (age range, 29-92 years; mean age, 68.3 years). In three patients, findings of percutaneous cholangiography did not indicate further access. Eighty-six metallic stents were implanted in 66 of the 94 remaining patients, and the other 27 patients were treated with percutaneous biliary drainage: external drainage in 21 patients to assist in subsequent operations and combined internal and external drainage in six patients. In one patient we performed percutaneous balloon dilatation of the stenosis of the choledochjejunal anastomosis. Hemobilia occurred in one patient and required embolization of the right hepatic artery. In nine patients (13.6%), a new procedure was used after 40 to 278 days (mean, 129 days) because of occlusion of the endoprosthesis. RESULTS: Clinical improvement and decrease in serum bilirubin level were achieved in 61 of the 66 patients (92.4%). The survival time in patients with malignancy ranged from 6 to 485 days (mean, 139 days). No intervention-related death occurred. Except for the aforementioned hemobilia, one case of biloma occurred and required immediate percutaneous drainage. CONCLUSION: Percutaneous transhepatic insertion of metallic stents was an efficient and secure method to treat biliary obstruction, particularly in malignant inoperable cases.

Synthesis of alpha-galactooligosaccharides with alpha-galactosidase from Lactobacillus reuteri of canine origin.

Crude cell-free extracts from Lactobacillus reuteri grown on cellobiose, maltose, lactose and raffinose were assayed for glycosidic activities. When raffinose was used as the carbon source, alpha-galactosidase was produced, showing the highest yield at the beginning of the stationary growth phase. A 64 kDa enzyme was purified by ultra- and gel filtration, and characterized for its hydrolytic and synthetic activity. Highest hydrolytic activity was found at pH 5.0 at 50 degrees C ( K(M) 0.55 mM, V(max) 0.80 micromol min(-1) mg(-1) of protein). The crude cell-free extract was further used in glycosyl transfer reactions to synthesize oligosaccharides from melibiose and raffinose. At a substrate concentration of 23% (w/v) oligosaccharide mixtures were formed with main products being a trisaccharide at 26% (w/w) yield from melibiose after 8 h and a tetrasaccharide at 18% (w/w) yield from raffinose after 7 h. Methylation analysis revealed the trisaccharide to be 6' alpha-galactosyl melibiose and the tetrasaccharide to be stachyose. In both cases synthesis ceased when hydrolysis of the substrate reached 50%.

Obstructive uropathy in the transplanted kidney: definitive management with percutaneous nephrostomy and prolonged ureteral stenting.

BACKGROUND AND PURPOSE: Renal transplantation is an effective treatment for end-stage renal disease. Ureteral stenosis is the most frequent urologic complication. We report our experience with percutaneous nephrostomy and antegrade ureteral stenting, which may offer a primary and definitive alternative to open surgery. PATIENTS AND METHODS: Fifteen patients with renal allograft obstructive uropathy were managed with percutaneous nephrostomy and prolonged ureteral stenting. RESULTS: Percutaneous nephrostomies were successfully performed in all 15 kidneys: In 13 patients, antegrade ureteral stenting was attempted, this being successful in 11 (85%). After prolonged ureteral stenting (mean duration 15 months), the stent was removed in eight patients, and six of them (75%) did not have recurrences. During follow-up, urea, creatinine, sodium, and potassium determinations and ultrasound scans were performed, and success was confirmed by the decline of creatinine and reduction in hydronephrosis. No major complication was observed. CONCLUSION: Percutaneous nephrostomy and ureteral stenting is a safe and effective treatment for renal allograft obstructive uropathy. Prolonged ureteral stenting may offer a definitive treatment with low morbidity.

Role of percutaneous urinary diversion in malignant and benign obstructive uropathy.

OBJECTIVES: We evaluated the feasibility and effectiveness of percutaneous urinary diversion in patients with obstructive uropathy. PATIENTS AND METHODS: A total of 206 percutaneous nephrostomies (PCNs) (right-sided in 54, left in 56, and bilateral in 48) were performed in 102 male and 57 female patients 18 to 94 years old. In 125 patients, malignancy was the underlying cause of the obstruction and in 30, benign disease. In four patients, the cause remained unknown. In most patients (N = 154), the access was guided with both ultrasound and fluoroscopy. RESULTS: Percutaneous nephrostomy was successful in 158 patients (99%). Antegrade ureteral stenting was attempted in 48 patients with a success rate of 81%. Fifteen days postprocedure, the mean urea and creatinine concentrations had declined from 160.8 mg/mL to 63 mg/mL and from 6.9 mg/dL to 2.2 mg/dL, respectively. In 66% of the patients, renal function returned to normal. In 28%, it improved with no need for hemodialysis, while in 6%, there was no improvement. Advanced age and prostate cancer were negative predictive factors for the improvement of renal function, whereas the BUN and creatinine concentrations before the procedure and performance of unilateral v bilateral nephrostomies were not. We did not have severe complications. Three patients received transfusions, and in one patient, a urinoma was drained percutaneously. Patients with malignancy had a median survival of 227 days. CONCLUSION: Percutaneous urinary diversion under radiologic guidance is a safe and effective procedure for patients with obstructive uropathy.

Long-term effects of small doses of calcitriol in hemodialysis patients with moderate secondary hyperparathyroidism.

Prevention of secondary hyperparathyroidism (SHPTH) and treatment of the moderate cases by small p.os doses of Vitamin D has not been thoroughly investigated on the long term, while large doses of Vitamin D have been successful in the short term treatment of this entity. We administered calcitriol p.os 0.5-1.0 microgram, according to iPTH levels, after each dialysis session, in 19 patients (group A) for 36 months. They were ten men and nine women, 63 years old (43-81), with iPTH levels > 4N (419 +/- 185 pg/mL). Seven adenomas were found in five of them (group A1). Serum Ca, phosphate (P) and alkaline phosphatase (AP) were measured every 15-30 days. Serum iPTH and aluminum as well as echogram or scanning of the parathyroid glands were checked every 6 months. Ten additional dialysis patients, seven men and three women, 54.5 years old (36-68), non-significantly different to group A in iPTH levels (290 +/- 225 pg/mL) with three adenomas in two of them (group B1) received no calcitriol and served as controls (group B). Calcitriol treatment significantly lowered serum iPTH levels in group A patients (from 419 +/- 185 to 173 +/- 142 pg/mL, p < 0.0001, delta iPTH: -246 +/- 161 pg/mL); iPTH remained stable in group B patients (delta iPTH: +7.9 +/- 116 pg/mL) with an intergroup significant difference at P < 0.0001. All other parameters measured did not show any significant change. No significant correlation of iPTH to Ca, P or AP was found in A. Initial iPTH levels were higher in A1 and B1 patients and decreased by calcitriol in A1 group. Adenomas in A1 patients did not change in number and size in contrast to B1 where new adenomas appeared (5 patients, 10 glands). Small doses of vitamin D lower high iPTH levels and prevent parathyroid gland hyperplasia. Existing hypertrophy is stabilized under calcitriol treatment both morphologically and biologically.

Hyperselective renal artery embolisation in the treatment of post-traumatic iatrogenic haematuria: report of two cases.

Angiography and selective renal artery embolisation were performed in two patients with post-traumatic iatrogenic kidney lesions and intractable haematuria. One patient presented after a nephrolithotomy with rupture of a segmental branch of the renal artery well demonstrated on selective angiography which showed intraparenchymal extravasion of contrast medium. The other presented after a renal biopsy with severe haematuria. Angiography performed 10 days later demonstrated an arteriovenous fistula at the site of the puncture. Hyperselective embolisation achieved immediate control of the haematuria in both patients, with maximal preservation of the renal parenchyma and maintenance of good renal function. At follow-up 12 months later, there had been no recurrence of the haematuria. These results suggest that transcatheter embolisation should be considered the method of first choice in renal trauma accompanied by intractable haematuria before any surgery is attempted.

Transcatheter arterial embolisation in nasopharyngeal angiofibroma.

Transcatheter arterial embolisation using gelfoam particles has been used in 4 young male patients with nasopharyngeal angiofibroma. The procedure proved to be extremely useful preoperatively in controlling and limiting profuse bleeding during surgery, allowing total excision of the tumor.