The efficacy of balloon dilation in achalasia is the result of stretching of the lower esophageal sphincter, not muscular disruption.

Pneumatic dilation (PD) of the lower esophageal sphincter (LES) in achalasia is a major palliative treatment. It is generally believed, although never substantiated, that therapeutic efficacy of ballooning in achalasia is the result of the disruption and tearing of the muscular layers of the LES. To clarify this issue, we investigated the frequency of muscular disruption at the LES, 24 hours after PD, by employing the endoscopic ultrasound (EUS), in a group of 43 consented patients with achalasia. Between July 2009 and March2012, 51 consecutive adult patients with tentative diagnosis of achalasia, some with recurrence of symptoms after an earlier treatment with balloon dilation, were evaluated and underwent PD, using Rigiflex balloon without major adverse effect. Out of the 51 evaluated, 43 eligible and consenting patients who underwent EUS, 24 hours after PD, using Olympus GF-UE 160 echoendoscope and an Aloka Prosound probe at 7.5 MHZ, are the subjects of this study. The EUS in 43 eligible patients revealed an intact LES in 36 (83.7%), small area of muscular disruption in 5 (11.6%) and small hematoma in 2 patients (4.6%). Our data convincingly demonstrate that the clinical effectiveness of balloon dilation in achalasia is not the result of muscular disruption, but of circumferential stretching of the LES. Our findings on the mechanism of action of PD in achalasia could result in modifying the current method of dilation for a safer procedure, by slowing the rate of inflation and allowing the sphincter to slowly stretch itself to the distending balloon.

Sympathetic skin response (SSR) in Crohn disease: a pilot study.

Peripheral neuropathy is one of the most frequently reported neurological extra-intestinal manifestations of the Crohn disease. Former studies have showed sympathetic neuropathy as early manifestation of CD by physical tests. The aim of this study is to examine sympathetic neuropathy in CD by using sympathetic skin response (SSR). We performed SSR on 6 Patients (4 male, 2 female) that were diagnosed as CD. Their age was between 26 till 68 years with the mean of (43.3 +/- 17.1) years. The duration of their disease was at least 4 years (mean: 9.0 +/- 8.4) and none of the patients had any symptoms or signs related to autonomic nervous system dysfunction. Hand and foot latencies in CD patients were prolonged relative to controls and the difference of hand latencies was statistically significant. Two patients demonstrated total abnormal results. In conclusion, there is some sub-clinical sympathetic dysfunction in CD patient. This suggests that SSR can be useful in detecting early autonomic changes in these patients.

Promoter polymorphism of transforming growth factor-beta1 gene and ulcerative colitis.

AIM: To elucidate the possible difference in two promoter polymorphisms of the transforming growth factor-beta1 (TGF-beta1) gene (-800G > A, -509C > T) between ulcerative colitis (UC) patients and normal subjects. METHODS: A total of 155 patients with established ulcerative colitis and 139 normal subjects were selected as controls. Two single nucleotide polymorphisms within the promoter region of TGF-beta1 gene (-509C > T and -800G > A) were genotyped using PCR-RFLP. RESULTS: There was a statistically significant difference in genotype and allele frequency distributions between UC patients and controls for the -800G > A polymorphism of the TGF-beta1 gene (P < 0.05). The frequency of the TGF-beta1 gene polymorphism at position -800 showed that the AA genotype and the allele A frequencies significantly differed between the patients and healthy controls (P < 0.05). At position -509, there was no statically significant difference in genotype and allele frequency between the patients and control subjects. CONCLUSION: The results of our study indicate that there is a significant difference in both allele and genotype frequency at position -800G > A of TGF-beta1 gene promoter between Iranian patients with UC and normal subjects.

Management and prognostic features of intracerebral hemorrhage during anticoagulant therapy: a Swedish multicenter study.

BACKGROUND AND PURPOSE: Patients treated with oral anticoagulants (ACs) have an increased risk of intracerebral hemorrhage (ICH), which is more often fatal than spontaneous ICH. Options to reverse the AC effect include intravenous administration of vitamin K, plasma, and coagulation factor concentrate. However, the optimal management of AC-related ICH has not been determined in any randomized trial. In this study, the present management of AC-related ICH was surveyed, and determinants of survival were assessed. METHODS: We retrospectively reviewed the medical records of all AC-related ICHs at 10 Swedish hospitals during a 4-year period, 1993 to 1996. Survival status after the ICH was determined from the Swedish National population register. RESULTS: We identified 151 patients with AC-related ICH. Death rates were 53.6% at 30 days, 63.6% at 6 months, and 77.5% at follow-up (mean 3.5 years). The case fatality ratio at 30 days was 96% among patients unconscious on admission (n=27), 80% among patients who became unconscious before active treatment was started (n=15), 55% among patients in whom no special action was taken except withdrawal of AC treatment (n=42), and 28% among patients given active anti-coumarin treatment while they were still conscious (n=64). The case fatality ratio at 30 days was 11% in the group treated with plasma (n=18), 30% in the group treated with vitamin K (n=23), and 39% in the group treated with coagulation factor concentrate (n=23). Within the first 24 to 48 hours after admission, 47% of the patients deteriorated. Choice of therapy to reverse the AC effect differed substantially between the hospitals (P<0.0001), as did the time interval from symptom onset to start of treatment. Multiple logistic regression analysis showed only 2 factors (intraventricular extension of bleeding and ICH volume) that were independently related to case fatality at both 30 days and 6 months. The results were similar when the analysis was restricted to patients who were conscious on admission. CONCLUSIONS: In AC-related ICH, a progressive neurological deterioration during the first 24 to 48 hours after admission is frequent, and the mortality is high. Choice of therapy to reverse the AC effect differed considerably between the hospitals. There was no evidence that any treatment strategy was superior to the others. A randomized controlled trial is needed to determine the best choice of treatment.

Comparison of intradermal and intramuscular administration of hepatitis B vaccine in neonates.

BACKGROUND: Hepatitis B virus (HBV) infection and its complications are among the most common diseases in Iran. National mass vaccination of neonates against hepatitis B was started in 1991, but was considered a costly venture. AIM: To compare the efficacy of low-dose intradermal HBV recombinant vaccine with standard intramuscular dose in neonates. METHOD: 165 apparently healthy neonates born in Shiraz were randomized to receive either 10 microg [corrected] of recombinant vaccine intramuscularly (IM; n=82) or 2 microg [corrected] vaccine intradermally (ID; n=83) at months 0, 1, 6. Anti-HBs titers were measured at 6 and 18 months after the first dose. RESULTS: 53 and 51 neonates in the IM and ID groups, respectively, completed the study. Protective anti-HBs titers (>10 IU/L) at 18 months after the first dose were achieved in 98.1% and 96.2% of neonates in IM and ID groups, respectively (p=ns). The only side effect in the ID group was local hyperpigmentation, which was seen in 55%; no significant side effect was reported in the IM group. CONCLUSION: Intradermal vaccination with 20% of standard dose is as effective as IM vaccination when evaluated at 18 months after the first dose.

Pharmacokinetics and pharmacodynamics of melagatran, a novel synthetic LMW thrombin inhibitor, in patients with acute DVT.

Forty-eight patients with acute proximal deep vein thrombosis (DVT) were randomised to intravenous infusions for 4 to 6 days with melagatran, a novel synthetic low molecular weight thrombin inhibitor, or unfractionated heparin adjusted by the activated partial thromboplastin time (APTT). The aim of the study was to investigate the pharmacokinetics, pharmacodynamics and the safety of melagatran therapy at three different doses. Steady-state plasma concentrations were rapidly achieved and maintained throughout the infusion period. The mean plasma concentrations in the low, medium and high dose groups were 0.17, 0.31 and 0.53 micromol/l, respectively. The prolongation of APTT was stable during the melagatran infusions and correlated to the plasma concentration. Phlebographically verified regression of thrombus size measured as decrease in Marder score was seen after 4 to 6 days in 8 of 12 patients, 6 of 12 patients and 5 of 11 patients in the low, medium and high dose groups of melagatran and in 5 of the heparin-treated patients. In the low dose group with melagatran, thrombus extension was seen in one patient. At the dose levels studied, melagatran was well tolerated with no clinically significant bleeding problems, suggesting that melagatran could safely be given to patients suffering from DVT.