GUT MICROBIOTA AND THE USE OF PROBIOTICS IN CONSTIPATION IN CHILDREN AND ADOLESCENTS: SYSTEMATIC REVIEW.

OBJECTIVE: To perform a systematic review of literature data on gut microbiota and the efficacy of probiotics for the treatment of constipation in children and adolescents. DATA SOURCE: The research was performed in the PubMed, the Scientific Electronic Library Online (SciELO) and the Latin American and Caribbean Health Sciences Literature (LILACS) databases in English, Portuguese and Spanish. All original articles that mentioned the evaluation of the gut microbiota or the use of probiotics in children with constipation in their title and abstract were selected. DATA SYNTHESIS: 559 articles were found, 47 of which were selected for reading. From these, 12 articles were included; they studied children and adolescents divided into two categories: a gut microbiota evaluation (n=4) and an evaluation of the use of probiotics in constipation therapy (n=8). The four papers that analyzed fecal microbiota used different laboratory methodologies. No typical pattern of gut microbiota was found. Regarding treatment, eight clinical trials with heterogeneous methodologies were found. Fifteen strains of probiotics were evaluated and only one was analyzed in more than one article. Irregular beneficial effects of probiotics have been demonstrated in some manifestations of constipation (bowel frequency or consistency of stool or abdominal pain or pain during a bowel movement or flatulence). In one clinical trial, a complete control of constipation without the use of laxatives was obtained. CONCLUSIONS: There is no specific pattern of fecal microbiota abnormalities in constipation. Despite the probiotics' positive effects on certain characteristics of the intestinal habitat, there is still no evidence to recommend it in the treatment of constipation in pediatrics.

Gut microbiota and the use of probiotics in constipation in children and adolescents: systematic review / Microbiota intestinal e emprego dos probióticos na constipação intestinal em crianças e adolescentes: revisão sistemática

ABSTRACT Objective: To perform a systematic review of literature data on gut microbiota and the efficacy of probiotics for the treatment of constipation in children and adolescents. Data source: The research was performed in the PubMed, the Scientific Electronic Library Online (SciELO) and the Latin American and Caribbean Health Sciences Literature (LILACS) databases in English, Portuguese and Spanish. All original articles that mentioned the evaluation of the gut microbiota or the use of probiotics in children with constipation in their title and abstract were selected. Data synthesis: 559 articles were found, 47 of which were selected for reading. From these, 12 articles were included; they studied children and adolescents divided into two categories: a gut microbiota evaluation (n=4) and an evaluation of the use of probiotics in constipation therapy (n=8). The four papers that analyzed fecal microbiota used different laboratory methodologies. No typical pattern of gut microbiota was found. Regarding treatment, eight clinical trials with heterogeneous methodologies were found. Fifteen strains of probiotics were evaluated and only one was analyzed in more than one article. Irregular beneficial effects of probiotics have been demonstrated in some manifestations of constipation (bowel frequency or consistency of stool or abdominal pain or pain during a bowel movement or flatulence). In one clinical trial, a complete control of constipation without the use of laxatives was obtained. Conclusions: There is no specific pattern of fecal microbiota abnormalities in constipation. Despite the probiotics' positive effects on certain characteristics of the intestinal habitat, there is still no evidence to recommend it in the treatment of constipation in pediatrics.

RESUMO Objetivo: Realizar revisão sistemática dos dados da literatura sobre a microbiota intestinal e a eficácia dos probióticos para o tratamento da constipação intestinal em crianças e adolescentes. Fonte de dados: Foi realizada busca nas bases de dados PubMed, Scientific Electronic Library Online (SciELO) e Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), em inglês, português e espanhol. Foram selecionados, pelo título e pelo resumo, todos os artigos originais que avaliaram a microbiota intestinal ou o emprego de probióticos em crianças com constipação intestinal. Síntese dos dados: Foram encontrados 559 artigos, dos quais 47 foram selecionados para leitura. Destes, foram incluídos 12 artigos que estudaram crianças e adolescentes distribuídos em duas categorias: avaliação da microbiota intestinal (n=4) e avaliação do emprego dos probióticos na terapêutica da constipação intestinal (n=8). Os quatro artigos que analisaram a microbiota fecal utilizaram metodologias laboratoriais diferentes. Não foi observado um padrão típico de microbiota intestinal. Quanto ao tratamento, foram encontrados oito ensaios clínicos com metodologias heterogêneas. Foram avaliadas 15 cepas de probióticos e apenas uma foi avaliada em mais de um artigo. Foram evidenciados efeitos benéficos não uniformes dos probióticos em algumas manifestações da constipação intestinal (frequência evacuatória, consistência das fezes, dor abdominal, dor ao evacuar ou flatulência). Em apenas um ensaio clínico foi obtido completo controle da constipação intestinal sem o emprego concomitante de laxantes. Conclusões: Não existe um padrão específico de anormalidades da microbiota fecal na constipação intestinal. Apesar dos efeitos positivos dos probióticos em determinadas características do hábito intestinal, ainda não existem evidências que permitam sua recomendação no tratamento da constipação intestinal em pediatria.

Potential risk of alpha-glucosidase inhibitor administration in prostate cancer external radiotherapy by exceptional rectal gas production: a case report.

INTRODUCTION: Radiotherapy is a standard treatment for prostate cancer, and image-guided radiotherapy is increasingly being used to aid precision of dose delivery to targeted tissues. However, precision during radiotherapy cannot be maintained when unexpected intrafraction organ motion occurs. CASE PRESENTATION: We report our experience of internal organ motion caused by persistent gas production in a patient taking an alpha-glucosidase inhibitor. A 68-year-old Japanese man with prostate cancer visited our institution for treatment with helical tomotherapy. He suffered from diabetes mellitus and took an alpha-glucosidase inhibitor. Routine treatment planning computed tomography showed a large volume of rectal gas; an enema was given to void the rectum. Subsequent treatment planning computed tomography again showed a large volume of gas. After exercise (walking) to remove the intestinal gas, a third scan was performed as a test scan without tight fixation, which showed a sufficiently empty rectum for planning. However, after only a few minutes, treatment planning computed tomography again showed extreme accumulation of gas. Therefore, we postponed treatment planning computed tomography and consulted his doctor to suspend the alpha-glucosidase inhibitor, which was the expected cause of his persistent gas. Four days after the alpha-glucosidase inhibitor regimen was suspended, we took a fourth treatment planning computed tomography and made a treatment plan without gas accumulation. Thereafter, the absence of rectal gas accumulation was confirmed using daily megavolt computed tomography before treatment, and the patient received 37 fractions of intensity-modified radiotherapy at 74 Gy without rectal gas complications. In this case study, the alpha-glucosidase inhibitor induced the accumulation of intestinal gas, which may have caused unexpected organ motion, untoward reactions, and insufficient doses to clinical targets. CONCLUSIONS: We suggest that patients who are taking an alpha-glucosidase inhibitor for diabetes should discontinue use of that particular medicine prior to beginning radiotherapy.

Effects of wheat bran extract containing arabinoxylan oligosaccharides on gastrointestinal parameters in healthy preadolescent children.

OBJECTIVES: We assessed whether wheat bran extract (WBE) containing arabinoxylan-oligosaccharides (AXOS) elicited a prebiotic effect and modulated gastrointestinal (GI) parameters in healthy preadolescent children upon consumption in a beverage. METHODS: This double-blind randomized placebo-controlled crossover trial evaluated the effects of consuming WBE at 0 (control) or 5.0 g/day for 3 weeks in 29 healthy children (8-12 years). Fecal levels of microbiota, short-chain fatty acids, branched-chain fatty acids, ammonia, moisture, and fecal pH were assessed at the end of each treatment and at the end of a 1-week run-in (RI) period. In addition, the subjects completed questionnaires scoring distress severity of 3 surveyed GI symptoms. Finally, subjects recorded defecation frequency and stool consistency. RESULTS: Nominal fecal bifidobacteria levels tended to increase after 5 g/day WBE consumption (P = 0.069), whereas bifidobacteria expressed as percentage of total fecal microbiota was significantly higher upon 5 g/day WBE intake (P = 0.002). Additionally, 5 g/day WBE intake induced a significant decrease in fecal content of isobutyric acid and isovaleric acid (P < 0.01), markers of protein fermentation. WBE intake did not cause a change in distress severity of the 3 surveyed GI symptoms (flatulence, abdominal pain/cramps, and urge to vomit) (P > 0.1). CONCLUSIONS: WBE is well tolerated at doses up to 5 g/day in healthy preadolescent children. In addition, the intake of 5 g/day exerts beneficial effects on gut parameters, in particular an increase in fecal bifidobacteria levels relative to total fecal microbiota, and reduction of colonic protein fermentation.

Safety of a dual potential prebiotic system from Mexican agave "Metlin® and Metlos®", incorporated to an infant formula for term newborn babies: a randomized controlled trial.

RATIONALE: Infant formulae are being supplemented with probiotics, prebiotics, or symbiotic despite uncertainties regarding their efficacy. Mexican agave is an interesting source of fructans with particular features and with potential prebiotic effects. MATERIAL AND METHODS: RCT in 600 healthy term babies (20 ± 7 days), allocated to receive standard infant formula (control) or infant formula added with a dual prebiotic system "Metlin® and Metlos®", from Mexican agave. Primary outcomes include stools frequency, stools consistency, gastrointestinal intolerance (frequency of abdominal distension, flatulency, regurgitations, vomiting). Secondary outcomes include changes on weight and height along the study and frequency of dermatologic problems (eczema). RESULTS: In 66,120 days of total follow-up, there were no differences on the frequency of stools passage (Human Milk: 3.8 ± 2.4 evacuations per day; Pro + Metlin + Metlos 3.6 ± 2.0; Pro + Metlin 3.6 ± 2; only Pro 3.4 ± 2.3¸ only formula 3.4 ± 2.0; p NS). Consistency of stools was similar between human milk and prebiotics supplemented groups. Also the frequency of gastrointestinal symptoms was significantly low between these groups. CONCLUSIONS: Fructans derivate from agave and added to infant formula are safe and well tolerated by Mexican healthy term babies.

Chicory inulin does not increase stool weight or speed up intestinal transit time in healthy male subjects.

Inulin is a non-digestible oligosaccharide classified as a prebiotic, a substrate that promotes the growth of certain beneficial microorganisms in the gut. We examined the effect of a 20 g day(-1) supplement of chicory inulin on stool weight, intestinal transit time, stool frequency and consistency, selected intestinal microorganisms and enzymes, fecal pH, short chain fatty acids and ammonia produced as by-products of bacterial fermentation. Twelve healthy male volunteers consumed a well-defined, controlled diet with and without a 20 g day(-1) supplement of chicory inulin (degree of polymerization (DP) ranging for 2-60), with each treatment lasting for 3 weeks in a randomized, double-blind crossover trial. Inulin was consumed in a low fat ice cream. No differences were found in flavor or appeal between the control and inulin-containing ice creams. Inulin consumption resulted in a significant increase in total anaerobes and Lactobacillus species and a significant decrease in ammonia levels and ß-glucuronidase activity. Flatulence increased significantly with the inulin treatment. No other significant differences were found in bowel function with the addition of inulin to the diet. Thus, inulin is easily incorporated into a food product and has no negative effects on food acceptability. Twenty grams of inulin was well tolerated, but had minimal effects on measures of laxation in healthy, human subjects.

Gastrointestinal tolerance to an inulin-rich soluble roasted chicory extract after consumption in healthy subjects.

OBJECTIVES: We aimed to assess in healthy subjects 1) the effect of two doses of a new naturally inulin-rich soluble chicory extract (IRSCE) on overall gastrointestinal discomfort after short-term ingestion and 2) the effect on gastrointestinal symptoms of long-term consumption of IRSCE administered at a dose compatible with its future commercial use. METHODS: First, the effect of IRSCE was assessed on overall gastrointestinal discomfort in a double-blind, crossover study where 18 subjects received in a randomized order a morning coffee drink including 10 g of sucrose alone (control period) or with IRSCE at two doses (8.9 and 14.0 g containing 5.0 and 7.8 g of inulin, respectively) during three consecutive 6-d periods. Second, 35 subjects were followed during a randomized, double-blind protocol where they were asked to take twice a day an instant coffee drink containing IRSCE (8.1 g/d containing inulin 5.0 g/d) or sucrose 8.1 g/d during 4 wk. The effects of the treatment on flatulence, bloating, abdominal pain, stool consistency, and number were recorded. RESULTS: In the first study a significant slight increase (P = 0.05) in overall abdominal discomfort was observed with the morning coffee drink containing 7.8 g of inulin after 1 wk of consumption. In the second study, no significant differences between the IRSCE and placebo groups were evidenced with respect to gastrointestinal symptoms during the consumption period. CONCLUSION: Short- and long-term consumptions of IRSCE, given at a daily dose containing 5 g of inulin, are well tolerated by healthy subjects.

Cholesterol reduction using psyllium husks - do gastrointestinal adverse effects limit compliance? Results of a specific observational study.

PURPOSE: Despite known cholesterol lowering effects the use of psyllium husk (Plantaginis ovatae testa) in Germany for hypercholesterolemia is limited compared to their use as a laxative. To investigate whether use in hypercholesterolemia is limited due to adverse effects on the gastrointestinal system, a prospective observational study was conducted. METHODS: Sixty-two outpatients with documented hypercholesterolemia and complaints of constipation were identified from an academic clinical center. Treatment with 3.5g psyllium husk preparation administered three times daily was initiated and patients were monitored at weekly intervals. Gastrointestinal symptoms were quantified using a validated Nepean Dyspepsia Index modified to identify both upper and lower abdominal symptoms. Diaries and study medication records were used to evaluate compliance. RESULTS: Fifty-four of 62 patients enrolled in the study completed the study protocol with 4 subjects discontinuing due to adverse reactions associated with psyllium husks. Total cholesterol was significantly decreased from 252+/-39mg/dl before treatment to 239+/-37mg/dl after 3 weeks of treatment. Similarly, low density lipoprotein (LDL)-cholesterol decreased from 174+/-34 to 162+/-31mg/dl during the study. Triglycerides and high density lipoprotein (HDL) were unchanged. Gastrointestinal symptoms were rated lower at the end than at the beginning of the study. In week 1 most of the patients reported gastrointestinal symptoms and also gastrointestinal adverse reactions, which however, showed a decrease from week 1 to weeks 2 and 3 in the diaries. Patient response to study medication was positive for patients completing the study. CONCLUSIONS: Psyllium husk preparations may be a therapeutic option for patients with mild to moderately elevated cholesterol levels. Adverse gastrointestinal symptoms associated with the preparation appear to be transient in some of the patients. Compliance may be optimized with adequate patient counseling.

Acarbose in the treatment of elderly patients with type 2 diabetes.

AIMS: To study the effect of acarbose, an alpha-glucosidase inhibitor, on glycemic control in elderly patients with type 2 diabetes. METHODS: Elderly patients with type 2 diabetes treated with diet alone were randomly treated in a double-blind fashion with placebo (n=99) or acarbose (n=93) for 12 months. RESULTS: After 12 months of therapy, there was a statistically significant difference in the change in glycated haemoglobin (HbA(1c)) (-0.6%) in the acarbose group versus placebo, as well as in the incremental post-prandial glucose values (-2.1 mmol h/l) and mean fasting plasma glucose (-0.7 mmol/l). Although there was no effect of acarbose on insulin release, there was a clear effect of acarbose to decrease relative insulin resistance (-0.8) (HOMA method). In addition, acarbose was generally well tolerated and safe in the elderly; most discontinuations were due to gastrointestinal side effects such as flatulence and diarrhea. There were no cases of hypoglycemia reported, and no clinically relevant changes in laboratory abnormalities or vital signs during the study. CONCLUSIONS: Acarbose improves the glycemic profile and insulin sensitivity in elderly patients with type 2 diabetes who are inadequately controlled on diet alone.

The efficacy of acarbose in type 2 diabetes mellitus in Jamaica

The efficacy and tolerability of acarbose was studied in type 2 diabetic patients eating a typical Jamaican diet. The study was an open label parallel group study without placebo control. Of the 51 subjects recruited, five (9.8 percent) did not complete the study and were excluded from further analysis. Six (13 percent) of the remaining 46 had adverse side effects and did not complete the protocol. Of the remaining 40 (Gp A), acarbose was added to their previous regime of diet alone (n=15), [Gp B], oral hypoglycaemic agents, OHAs (n=17), [Gp C], or insulin (n=8), Gp D]. In addition, during the run in period all subjects had one session each with a dietitian and a diabetes educator. Over a 3 month period, significant reductions in average glucose (mmol) were observed in Gp B 10.5 ñ 1.1 to 8.4 ñ 0.9 (p<0.027) and, from 11.0 ñ 1.0 to 8.7 ñ 0.7 (p<0.01) in Gp C. Similarly, total glycosylated haemoglobin fell from 14.8 ñ 1.1 percent to 12.2 ñ 1.0 percent (p<0.016) in Gp B, from 14.8 ñ 1.1 to 11.9 ñ 1.1 percent (p<0.002) in Gp C, and from 14.1 ñ 1.4 to 11.8 ñ 1.4 (p<0.02) in Gp D. Twenty-three per cent (23 percent) of the patients experienced flatulence; 7.5 percent changes in bowel habits and 5 percent, abdominal cramps and discomfort. Acarbose is effective as monotherapy and as combination therapy with oral hypoglycaemic agents or insulin. Side effects were common, but tolerable.(Au)

The efficacy of acarbose in type 2 diabetes mellitus in Jamaica.

The efficacy and tolerability of acarbose was studied in type 2 diabetic patients eating a typical Jamaican diet. The study was an open label parallel group study without placebo control. Of the 51 subjects recruited, five (9.8%) did not complete the study and were excluded from further analysis. Six (13%) of the remaining 46 had adverse side effects and did not complete the protocol. Of the remaining 40 (Gp A), acarbose was added to their previous regime of diet alone (n = 15), [Gp B], oral hypoglycaemic agents, OHAs (n = 17), [Gp C], or insulin (n = 8), Gp D]. In addition, during the run-in period all subjects had one session each with a dietitian and a diabetes educator. Over a 3-month period, significant reductions in average glucose (mmol) were observed in Gp B 10.5 +/- 1.1 to 8.4 +/- 0.9 (p < 0.027) and, from 11.0 +/- 1.0 to 8.7 +/- 0.7 (p < 0.01) in Gp C. Similarly, total glycosylated haemoglobin fell from 14.8 +/- 1.1% to 12.2 +/- 1.0% (p < 0.016) in Gp B, from 14.9 +/- 1.1 to 11.9 +/- 1.1% (p < 0.002) in Gp C, and from 14.1 +/- 1.4 to 11.8 +/- 1.4 (p < 0.02) in Gp D. Twenty-three per cent (23%) of the patients experienced flatulence; 7.5%, changes in bowel habits and 5%, abdominal cramps and discomfort. Acarbose is effective as monotherapy and as combination therapy with oral hypoglycaemic agents or insulin. Side effects were common, but tolerable.

Beneficial effects of acarbose on familiar hypertriglyceridemias.

Elevated serum triglyceride levels may be related to the following clinical features: increased blood coagulation and viscosity, increased serum fibrinogen levels, decreased fibrinolysis, and for serum levels over 1000 mg/dl, a strong increase of acute pancreatitis rate. Pharmacological choice among the numerous drugs to treat hypertriglyceridemias is currently debated. Our study was aimed to assess the therapeutic efficacy of acarbose in the treatment of non-diabetic subjects, affected by familiar hypertriglyceridemia (FH). We studied 18 non-diabetic patients (10 males, 8 females; mean age 57.61+/-6.85 years) without family history of diabetes mellitus affected by familiar hypertriglyceridemia. The study protocol planned a treatment period of 20 weeks, divided into five 4-week courses and made up as follows: diet plus acarbose therapy (4 weeks); diet therapy alone (4 weeks) alternatively. In the second and fourth 4-week courses diet plus acarbose were administered, while diet therapy alone was administered in the first, third, and fifth 4-week courses. Acarbose doses consisted of 50 mg (1/2 pill) twice daily. Mean serum triglyceride levels, after first month of dietary treatment, underwent a significant reduction from 481.5 +/- 67.1 mg/dl to 389.5 +/- 62.7 mg/dl, even if they did not reach the optimal levels to keep on the dietary therapy alone. After the first month of treatment with acarbose associated to diet, we observed a further reduction of serum triglycerides levels (p = 0.02). When diet alone was administered, mean triglyceride serum levels underwent a significant enhancement (p = 0.003). Restarting for the second time the association treatment, we observed a noteworthy reduction of mean serum triglyceride levels (p = 0.0001). Acarbose acts on the pathogenesis of FH, lowering the production of endogenous triglycerides. Our data suggested that acarbose can be considered a valid therapeutic tool in the treatment of familiar hypertriglyceridemias, also in non-diabetic patients.

An Asian multicenter clinical trial to assess the efficacy and tolerability of acarbose compared with placebo in type 2 diabetic patients previously treated with diet. Asian Acarbose Study Group.

OBJECTIVE: To assess the efficacy, safety, and tolerability of acarbose versus placebo during a 24-week treatment period in Asian type 2 diabetic patients with dietary failure. RESEARCH DESIGN AND METHODS: After a 6-week screening period, 126 multiethnic Asian type 2 diabetic patients (64 men, 62 women; mean age +/- SD, 53.4 +/- 10 years) were randomized to receive acarbose (n = 63) or placebo (n = 63). The dosage was increased from 50 mg t.i.d. at week 0 to 100 mg t.i.d. at week 4. Patients were then followed up at weeks 10, 16, and 24. At each visit, body weight, blood pressure, and metabolic indexes were measured. At weeks 0 and 24, fasting plasma glucose and insulin were measured before and 1 h after the administration of an individually tailored breakfast. RESULTS: Using the intention-to-treat analysis, there were greater reductions in (mean [95% CI]) HbA1c (-0.70 [-1.00 to -0.39] vs. -0.27% [-0.54 to 0]; P = 0.04), fasting plasma glucose (-0.37 [-0.75 to 0.02] vs. 0.41 mmol/l [-0.08 to 0.90]; P = 0.017) and 1-h plasma glucose (-0.77 [-1.44 to -0.10] vs. 0.65 mmol/l [-0.07 to 1.36]; P = 0.05) in the acarbose group compared with the placebo group. With acarbose treatment, 78% of patients achieved an HbAlc < 8% compared with 56% in the placebo group (P = 0.003). There was a greater reduction in body weight (-1.31 [-2.46 to -0.15] vs. 0.16 kg [-3.36 to 0.10]; P = 0.02) and higher incidence of flatulence (56 vs. 37%; P = 0.032) in the acarbose than in the placebo group. Using baseline HbA1c and race as covariates, there were no significant interethnic differences in treatment responses (P = 0.232 for treatment-race interaction; P < 0.001 for treatment effect). The dropout rates were similar between the two groups (acarbose, 11 of 63; placebo, 6 of 63). There were no significant laboratory adverse events in either group. CONCLUSIONS: In this multicenter study involving six ethnic groups, acarbose 100 mg t.i.d. was an effective, safe, and generally well-tolerated therapy in Asian type 2 diabetic patients with dietary failure. In some patients with troublesome gastrointestinal symptoms, a lower dosage may be necessary.

Acarbose in NIDDM patients with poor control on conventional oral agents. A 24-week placebo-controlled study.

OBJECTIVE: To determine the efficacy of acarbose, compared with placebo, on the metabolic control of NIDDM patients inadequately controlled on maximal doses of conventional oral agents. RESEARCH DESIGN AND METHODS: In this three-center double-blind study, 90 Chinese NIDDM patients with persistent poor glycemic control despite maximal doses of sulfonylurea and metformin were randomly assigned to receive additional treatment with acarbose 100 mg thrice daily or placebo for 24 weeks, after 6 weeks of dietary reinforcement. Efficacy was assessed by changes in HbA1c, fasting and 1-h postprandial plasma glucose and insulin levels, and fasting lipid levels. RESULTS: Acarbose treatment was associated with significantly greater reductions in HbA1c (-0.5 +/- 0.2% vs. placebo 0.1 +/- 0.2% [means +/- SEM], P = 0.038), 1-h postprandial glucose (-2.3 +/- 0.4 mmol/l vs. placebo 0.7 +/- 0.4 mmol/l, P < 0.001) and body weight (-0.54 +/- 0.32 kg vs. placebo 0.42 +/- 0.29 kg, P < 0.05). There was no significant difference between the two groups regarding changes in fasting plasma glucose and lipids or fasting and postprandial insulin levels. Flatulence was the most common side effect (acarbose vs. placebo: 28/45 vs. 11/44, P < 0.05). One patient on acarbose had asymptomatic elevations in serum transaminases that normalized in 4 weeks after acarbose withdrawal. Another patient on acarbose developed severe hypoglycemia; glycemic control was subsequently maintained on half the baseline dosage of sulfonylurea. CONCLUSIONS: In NIDDM patients inadequately controlled on conventional oral agents, acarbose in moderate doses resulted in beneficial effects on glycemic control, especially postprandial glycemia, and mean body weight. Additional use of acarbose can be considered as a useful alternative in such patients if they are reluctant to accept insulin therapy.

High dose gabapentin in refractory partial epilepsy: clinical observations in 50 patients.

Fifty patients with refractory partial seizures took part in a prospective, observational study of adjuvant gabapentin (GBP) in increasing doses. Thirty-three were started on 400 mg GBP daily with further weekly increments of 400 mg until seizures came under control for at least 6 months or to the limit of tolerability. A further 17 patients, not fully controlled on low dose GBP, followed the same regimen. All patients took the drug three times daily. Comparisons were made with seizure numbers during a 3-month baseline during which antiepileptic medication remained unchanged. Overall, 24 of the 50 patients documented a seizure reduction of 50% or more. Fifteen did so at or below 2400 mg GBP daily. Three of these patients became seizure-free. The remaining nine appeared to respond to higher daily doses of GBP (1:2800 mg; 3:3600 mg; 1:4000 mg; 1:4800 mg; 3:6000 mg), with two becoming seizure-free. Side-effects most commonly reported included tiredness, dizziness, headache and diplopia. On GBP doses exceeding 3600 mg daily, three patients developed flatulence and diarrhoea and two more had myoclonic jerks. Mean circulating GBP concentrations (mg/l) at each 1200 mg dose level were as follows: 1200 mg-4.1; 2400 mg-8.6; 3600 mg 13.2; 4800 mg 15.5; 6000 mg-17.2. In six patients, including three taking 6000 mg daily, GBP concentrations continued to rise linearly at each dosage increment. Although limited, our results do not support the suggestion that GBP absorption is saturable. High dose GBP may be effective in controlling seizures in patients with refractory partial epilepsy.

The influence of ispaghula husk on bowel habit.

Frequency of defaecation, faecal form, straining at the start and end of defaecation, feelings of incomplete evacuation of faeces and urgency of defaecation were recorded in 69 healthy volunteers during three distinct 28-day study phases: pre-treatment, treatment with ispaghula husk and post-treatment. During treatment there was a significant increase (P < 0.001) in stool frequency and significant decreases in straining at the start (P < 0.001) and end (P < 0.001) of defaecation and in feelings of incomplete evacuation (P < 0.001). There was evidence of a beneficial residual effect after treatment had stopped. There are indications that ispaghula husk (Fybogel Orange) is of benefit in relieving constipation symptoms in apparently healthy people.

The efficacy and safety of miglitol therapy compared with glibenclamide in patients with NIDDM inadequately controlled by diet alone.

OBJECTIVE: To compare the therapeutic effects of the alpha-glucosidase inhibitor miglitol (BAY m 1099), the sulfonylurea glibenclamide, and placebo on parameters of metabolic control and safety in patients with NIDDM that is inadequately controlled by diet alone. RESEARCH DESIGN AND METHODS: After a 4-week placebo run-in period, 201 patients in 18 centers in 4 countries were randomized in a double-blind manner to miglitol (50 mg t.i.d., followed by 100 mg t.i.d.), glibenclamide (3.5 mg q.d/b.i.d.), or placebo for 24 weeks. Efficacy criteria were changes from baseline of HbA1c, fasting and postprandial blood glucose and insulin levels, body weight, and serum triglycerides. RESULTS: Efficacy was assessed in 119 patients who completed the full protocol, and the results were similar to those obtained in 186 patients who fulfilled the validity criteria for analysis. Compared with placebo, mean baseline-adjusted HbA1c decreased by 0.75% (P = 0.0021) and 1.01% (P = 0.0001) in the miglitol and glibenclamide treatment groups, respectively. Blood glucose decreased slightly in the fasting state and considerably in the postprandial state in both treatment groups but not in the placebo group. Fasting insulin levels increased slightly (NS) in all treatment groups; however, postprandial insulin levels decreased with miglitol, while increasing markedly with glibenclamide (P = 0.0001 between all treatment groups). Gastrointestinal side effects (flatulence and diarrhea) occurred mostly in the miglitol-treated patients, while some glibenclamide-treated patients had symptoms suggestive of hypoglycemia. CONCLUSIONS: Miglitol monotherapy is effective and safe in NIDDM patients. Compared with glibenclamide, it reduced HbA1c less effectively and caused more gastrointestinal side effects. On the other hand, glibenclamide, unlike miglitol, tended to cause hypoglycemia, hyperinsulinemia, and weight gain, which are not desirable in patients with NIDDM.

Effect of processing on flatus producing oligosaccharides in cowpea (Vigna unguiculata) and the tropical African yam bean (Sphenostylis stenocarpa).

The effect of dehulling, soaking and soaking/cooking on sucrose, raffinose and stachyose in mature dry seeds of nine varieties of cowpea (Vigna unguiculata) and one variety of tropical African yam bean (Sphenostylis stenocarpa) were investigated. The results showed a progressive decrease in sucrose, raffinose, and stachyose contents. Soaking for 12 hours and cooking for 30 min eliminated most of the sucrose, raffinose and stachyose. The sugar contents in whole raw cowpea were sucrose 0.73-4.58%, raffinose 0.71-6.86% and stachyose 2.38-3.87%, and for tropical African yam bean sucrose 4.08%, raffinose 1.08% and stachyose 4.14% while the seeds soaked for 12 hours and cooked for 30 min had for cowpea sucrose 0.03-0.81%, raffinose 0.04-0.20% and stachyose 0.12-0.72%, and tropical African yam bean sucrose 0.70%, raffinose 0.40% and stachyose 0.41%.