Microbes: possible link between modern lifestyle transition and the rise of metabolic syndrome.

The rapid decrease in infectious diseases globally has coincided with an increase in the prevalence of obesity and other components of metabolic syndrome. Insulin resistance is a common feature of metabolic syndrome and can be influenced by genetic and non-genetic/environmental factors. The emergence of metabolic syndrome epidemics over only a few decades suggests a more prominent role of the latter. Changes in our environment and lifestyle have indeed paralleled the rise in metabolic syndrome. Gastrointestinal tract microbiota, the composition of which plays a significant role in host physiology, including metabolism and energy homeostasis, are distinctly different within the context of metabolic syndrome. Among humans, recent lifestyle-related changes could be linked to changes in diversity and composition of 'ancient' microbiota. Given the co-adaptation and co-evolution of microbiota with the immune system over a long period of time, it is plausible that such lifestyle-related microbiota changes could trigger aberrant immune responses, thereby predisposing an individual to a variety of diseases. Here, we review current evidence supporting a role for gut microbiota in the ongoing rise of metabolic syndrome. We conclude that population-level shifts in microbiota can play a mediatory role between lifestyle factors and pathogenesis of insulin resistance and metabolic syndrome.

Injection of botulinum toxin before pneumatic dilatation in achalasia treatment: a randomized-controlled trial.

BACKGROUND: Pneumatic dilatation is the first line therapy in achalasia, but half of patients relapse within 5 years of therapy and require further dilatations. AIM: To assess whether botulinum toxin injection before pneumatic dilatation is superior to pneumatic dilatation alone in achalasia patients. METHODS: Newly diagnosed achalasia patients were randomly assigned to receive botulinum toxin 1 month before pneumatic dilatation (botulinum toxin-pneumatic dilatation group: 27 patients with median age of 38) or to undergo pneumatic dilatation alone (pneumatic dilatation group: 27 patients with median age of 30). Response to therapy was assessed by clinical and objective methods at various intervals. RESULTS: One-year remission rate of patients in botulinum toxin-pneumatic dilatation group was 77% compared with 62% in pneumatic dilatation group (P = 0.1). In pneumatic dilatation group, the oesophageal barium volume significantly (P < 0.001) decreased at 1 month, but this reduction did not persist over 1-year follow-up. Botulinum toxin-pneumatic dilatation group showed a significant (P < 0.001) reduction in barium volume at the various times intervals post-treatment. In the botulinum toxin-pneumatic dilatation group, 10/11 (91%) patients over 40 were in remission at 1 year, comparing with only five of nine (55%) cases in pneumatic dilatation group (P = 0.07). CONCLUSION: Injection of botulinum toxin before pneumatic dilatation does not significantly enhance the efficacy of pneumatic dilatation.

Patterns of K-ras mutation in colorectal carcinomas from Iran and Italy (a Gruppo Oncologico dell'Italia Meridionale study): influence of microsatellite instability status and country of origin.

BACKGROUND: K-ras mutations are a key step in colorectal cancer progression. Such mutations have been widely studied in case series from Western countries but there are few data on the rate and spectrum of mutations in tumors from countries where the epidemiological features of the disease are different. PATIENTS AND METHODS: Tumor samples from 182 Iranian colorectal cancer patients (170 sporadic cases and 12 HNPCC cases) were screened for K-ras mutations at codons 12, 13 and 61 by sequencing analysis. The cases were also characterized for microsatellite instability at mononucleotide repeats by PCR and fragment analysis, and classified according to microsatellite instability status. The frequency and the spectrum of K-ras mutations were compared with those observed in a series of colorectal cancer patients from Italy. RESULTS: K-ras mutations were observed in 68/182 (37.4%) cases. Mutation frequencies were similar in HNPCC-associated, sporadic MSI-H and sporadic microsatellite-stable (MSS) tumors. However, the G13D substitution was more frequent in HNPCC (3/4, 75%) and sporadic MSI-H (7/11, 63.6%) tumors compared to sporadic MSS tumors (11/53, 20.4%) (P <0.01). Comparison of mutations in the two series from Iran and Italy showed a significantly higher frequency of G13D among Italian patients. CONCLUSIONS: While the frequency of K-ras mutations could be similar, the mutational spectrum could be differentially influenced by genetic and environmental factors.

Efficacy of botulinum toxin injection before pneumatic dilatation in patients with idiopathic achalasia.

Graded pneumatic dilatation (PD) is an appropriate long-term therapy and botulinum toxin injection (BT) is a relatively short-term therapy in idiopathic achalasia. Their combination has not been previously scrutinized. This study aimed to evaluate the role of BT in enhancing the efficacy of PD with 30 mm balloons. Patients who underwent PD with 30 mm balloons after botulinum toxin injections and a group of age- and sex-matched controls who were treated only with PD were enrolled in the study. Symptom scores were taken before, 1 month after and then every 3 months after PD. There were no significant differences between the two groups in gender, duration or severity of symptoms. One of the 12 patients in the case group relapsed 30 months after PD but the others were in remission for an average of 25.6 months. In the control group, all the patients relapsed after a mean of 12.6 months and needed a 35-mm PD. The cumulative remission rate was significantly higher in the case group compared with the control group (P < 0.01). The mean symptom score decreased by 76% in the case group (P < 0.001) and 53% in the controls (P < 0.01) at the end of the first month. Neither age, sex, nor duration or severity of symptoms were predictive of patients' responses to treatment. It seems that BT may be a meaningful enhancing factor in long-term efficacy of PD. PD with a 30 mm balloon after a BT session may resolve the need for the future higher grade PD.

Pneumatic balloon dilatation in achalasia: a prospective comparison of safety and efficacy with different balloon diameters.

BACKGROUND: Pneumatic dilatation is considered to be the first line therapy for achalasia, but long-term outcome studies are scarce and limited by their retrospective design. There is also no consensus on the optimal method for performing pneumatic dilation as regard to balloon diameter, amount and the rate inflation pressure. AIM: To address these questions in a large long-term prospective study. METHODS: Over a period of 10 years 262 achalasia patients referred to our centre were enrolled. All patients underwent a pre-treatment clinical evaluation and were followed every 6 months. The first 62 patients (group A) underwent dilatation with initial use of a 35 mm balloon with inflation pressure of 10 psi in 10 seconds (s). In group B (200 patients) we initially used a 30 mm balloon with inflation pressure of 10 psi in 30 s. Dilatation was repeated with incrementally larger balloons (35 and 40 mm) in case of relapse. We used rigiflex balloon and maintained pressure for 60 s after inflation in both groups. RESULTS: Three perforations occurred in group A whereas no perforation took place in Group B. The cumulative proportional remission rate with single dilatation in groups A and B decreased from 83 and 75% in 6 months to 60 and 57% after 30 months of therapy respectively, the differences did not reach statistical significance. In patients who had undergone further dilatations the probability of remaining in remission at 1 year after the first and the second dilatation was 38 and 88% in group A, 20 and 89% in group B respectively. The probability of remaining in remission for 2 years increased from 20% after the first dilatation to 70% after the second dilatation. CONCLUSION: Graded pneumatic balloon dilatation with 30 mm diameter and slower rate of balloon inflation is an effective and safe initial method of therapy for achalasia. The duration of remission can be extended by repeated dilatation with larger size balloon.