Non-pharmacologic treatment strategies in gastroesophageal reflux disease

Abstract   In the West, gastroesophageal reflux disease (GERD) is a common and well-recognized disease. Lately, it has been described as an emerging problem in the East as well. While it is not a rapidly fatal illness, it causes a myriad of disturbing symptoms that remarkably reduce the patients' quality of life (QOL). The economic impact that results from multiple consultations, diagnostic investigations, and administration of a variety of treatment regimens, including surgery, is enormous.
The operative management for GERD is fundoplication, for example Toupet (270 degree wrap of the distal esophagus) and Nissen (360 degree wrap of the distal esophagus). These surgical procedures are aimed at permanently controlling acid reflux by reconstructing the gastroesophageal junction. Currently, the ease, aesthetic advantages, and the comparable outcomes achieved by minimally invasive laparoscopic fundoplication have rekindled interest in the operative alternatives of GERD management. Fundoplication controls or diminishes considerably the severity of the symptoms associated with GERD. However, appearance of new symptoms i.e. dysphagia, 'gas–bloat syndrome', etc. as postoperative events have been reported.
Recently, several innovative endoluminal treatment modalities have been introduced, namely; endoscopic plicator/suturing devices, bulking injections, and radiofrequency treatment. They are focused on enhancing the performance of a malfunctioning lower esophageal sphincter. While results of several case series reflect substantial improvements in GERD-HRQL scores, lack of long-term durability data is a major concern when recommending these novel, relatively simple, peroral techniques to a long suffering patient. It is clear that these therapies are still evolving and long-term outcomes of properly designed comparative efficacy trials are awaited.     

Noninvasive Mapping of Human Atrial Fibrillation

Introduction: Invasive high-density mapping of atrial fibrillation (AF) has revealed different patterns of atrial activation ranging from single wavefronts to disorganized activation with multiple simultaneous wavefronts. Whether or not similar activation patterns can also be observed using body surface recordings is currently unknown, and was consequently evaluated in this study.
Methods and Results: Surface electrocardiographic mapping was performed in 14 patients (age 68 ± 14 years) with persistent AF (AF duration 12 ± 18 months). A total of 56 electrocardiographic leads were placed on the chest over the atria on the front (n = 40) and on the back (n = 16). Using 240-second recordings, wavefront propagation maps were automatically computed and visually classified as either type I (single wavefront), II (single wavefront with wave breakages and splitting), or III (multiple simultaneous wavefronts). Almost half of the patients (n = 6) presented most predominantly type III atrial activation, while six patients mostly presented type I activation. The rest of the patients (n = 2) presented mixed type I and type III activations. This classification showed to be highly reproducible over 4 minutes.
Conclusions: Using electrocardiographic body surface mapping during AF, interindividual differences of atrial fibrillatory activation can be observed. The surface activation pattern during AF shows an excellent short-term reproducibility.     

Electrocardiographic Findings,Device Therapies,and Comorbidities in Octogenarian Implantable Defibrillator Recipients

Implantable Defibrillators in Octogenarians. Background: The use of implantable cardioverter‐defibrillators (ICDs) in octogenarians is poorly defined. Objective: To assess baseline electrocardiographic (ECG) findings, arrhythmia episodes, and development of severe nonarrhythmic illness or death in patients aged ≥80 years at ICD implantation, and to compare them with younger patients. Methods: Medical records and device interrogations for 199 patients ≥70 years old who underwent ICD implantation were reviewed. Patients were divided into 3 groups based on age at the time of implant: age 70–74 (group 1; 88 patients), age 75–79 (group 2; 67 patients), and age ≥80 (group 3; 44 patients). Results: ECGs: Octogenarians were more likely to have sinus bradycardia (SB) (P = 0.047) and left bundle branch block (LBBB) (P = 0.043) compared to younger patients. There was no difference among groups in the proportion of patients with atrial fibrillation or any degree of AV block. Therapies: There was no difference between age groups in any therapy (P = 0.78), appropriate therapy (P = 0.54), or inappropriate therapy (P = 0.21) per patient‐year. There was no difference between groups in time‐to‐first therapy of any type (P = 0.71). Nonarrhythmic death/morbidity: There was no difference between groups in time to death or serious illness. Conclusion: Our study is the first to evaluate in detail the therapies received by octogenarians after ICD placement. The higher incidence of SB and LBBB might influence the number of pacing sites in octogenarian patients. Very elderly patients have similar rates of arrhythmic episodes and development of severe comorbidities as septuagenarians, and they should not be denied ICD implantation based solely on age. (J Cardiovasc Electrophysiol, Vol. 21, pp. 236–241, March 2010)     

A type‐specific study of human papillomavirus prevalence in cervicovaginal samples in three different Spanish regions

Human papillomavirus (HPV) is the most frequent sexually transmitted viral infection. It is necessary to know HPV genotype distribution to identify how many women will be protected by HPV vaccines. During a period of 18 months, we have analyzed 2362 HPV positive reporting data from a secondary demand screening program in three regions in Spain (Cantabria, Leon and Burgos). The study has been conducted using polymerase chain reaction and tube array hybridization covering the 35 HPV genotypes described as affecting anogenital mucosa. There were no significant differences between the three regions according to genotype distribution. The most frequent were HPV16 (19.18%), HPV53 (11.26%) and HPV58 (7.66%). HPV18 was the source of 4.02% of infections. High‐risk HPVs were found in 1863/2362 cases. HPV16 was present in 24.3% of high‐risk infections and HPV18 was found in 5.1%. Uncommon genotypes (<5% of the total prevalence each) were found in 17,9% of the total high‐risk infections (334/1863). Multiple infections were diagnosed in 22% of the cases. The HPV genotype distribution is different from previously published data when multiple types are included in the screening. Both HPV16/18 account for 30% of high‐risk infections in a clinical setting in Spain. The presence of multiple genotypes is very common among the population.     

The effect of maternal work on fetal growth and duration of pregnancy: a prospective study

Summary. The effect on birth outcome of work requiring different degrees of physical exertion was examined among 15 786 pregnant women who were followed through the Guatemalan Social Security Institute's hospital. Work inside and outside the home was ascertained through a questionnaire administered to each woman before delivery. Odds ratios were adjusted for household income, maternal height and age, and birthweight of previous infant. Women with three or more children and no household help were at increased risk for small-for-gestational-age (SGA) births compared with women with family (odds ratio (OR) 1.79; 95% confidence interval (CI) 1.31, 2.47) or hired help (OR 2.0; 95% CI 1-16 to 3-33). Compared with office work, manual work increased the risk for an SGA (OR 1.32 95% CI 1.12 to 1.56) and SGA/preterm birth (OR 2.56; 95% CI 1.10 to 5.96). Work in a standing compared with sitting position significantly increased the risk for a preterm birth (OR l.56; 95% CI l.04 to 2.60). There was a significant positive trend in frequency of SGA and SGA/preterm birth with an increase in the physical demands at work, as measured by an activity score. These data suggest that interventions to reduce physical exertion among pregnant women could improve birth outcome.     

THE EFFICACY OF INTRAVESICAL BACILLUS CALMETTE-GUERIN IN THE TREATMENT OF INTERSTITIAL CYSTITIS: LONG-TERM FOLLOWUP

Purpose

Interstitial cystitis is a severe debilitating bladder disease characterized by unrelenting pelvic pain and urinary frequency. A prospective, double-blind, placebo controlled study of the use of intravesical bacillus Calmette-Guerin (BCG) in the treatment of interstitial cystitis was recently completed with a mean followup of 8 months. Results demonstrated a 60% BCG response rate, compared to a 27% placebo response rate. We now report the long-term followup results of those patients who received intravesical BCG.

Materials and Methods

Subjects randomized to receive BCG were followed at routine intervals with questionnaires and voiding diaries identical to those in the blinded study. Adverse events were closely monitored in the treatment and followup phases of the study. Subject baseline values were compared to followup data.

Results

Of the BCG responders mean followup was 27 months (range 24 to 33), and 8 of 9 (89%) continue to have an excellent response in all parameters measured. The global interstitial cystitis survey improved 70%, daily voids decreased 31%, nocturia improved 54%, mean voided volume increased 61%, pelvic pain decreased 81%, vaginal pain decreased 71%, urgency decreased 71% and dysuria decreased 82%. Overall well-being improved 54% and the Rand-36 quality of life survey overall improved 64%. In 86% of the patients (6 of 7) dyspareunia resolved. Of the initial BCG nonresponders there was no significant difference in interstitial cystitis symptomatology from baseline to last followup, suggesting that BCG does not worsen interstitial cystitis symptoms. No long-term adverse events from BCG were noted.

Conclusions

Intravesical Tice^* BCG is safe, effective and durable in the treatment of interstitial cystitis. Of those patients who received only 6 weekly treatments and responded favorably 89% continue to have an excellent response with followup ranging from 24 to 33 months.     

INFLUENCE OF REGULAR ALCOHOL CONSUMPTION ON URICAEMIA IN UNSELECTED HEALTHY INDIVIDUALS

We analysed serum uric acid concentrations in a group of healthymale and female volunteers in Córdoba (Spain) possessingvarying nutritional habits, in order to correlate them withtheir usual alcohol intake as measured according to a protocolized,blind dietary questionnaire. There was no significant correlationbetween the serum uric acid and the amount of alcohol regularlydrunk by either male or female individuals. These results suggestthat a moderate alcohol intake has no effect on uricaemia inhealthy individuals.     

INVERSE EXPRESSION OF mdr 1 AND c-myc GENES IN A RHABDOMYOSARCOMA CELL LINE RESISTANT TO ACTINOMYCIN D

Cytotoxic agents used in cancer therapy may induce differentiation in tumour cells with no proliferative potential. However, chemotherapy can also induce multidrug resistance, a formidable obstacle to the successful treatment of tumours. Both events were recently shown to occur in a rhabdomyosarcoma cell line (RD-DAC) resistant to actinomycin D, a drug of choice in the treatment of these tumours. To analyse this connection, cell line RD cultures were investigated with progressive concentrations of actinomycin D and it was shown that a minimum dose (1·2×10⁻⁶ mm) of the drug was necessary to increase mdr 1 mRNA in RD-DAC. The mechanism of mdr 1 overexpression was an increase in the number of copies of the mdr 1 gene, although the mRNA levels were not correlated with mdr 1 amplification. Drug resistance mediated by mdr 1 overexpression coincided with the development of myogenic differentiation in RD-DAC and with a decrease in c- myc mRNA levels, whereas levels of N- myc mRNA showed no modulation. These findings suggest that factors implicated in cell proliferation and differentiation, such as c- myc , may be responsible for the control of genes related to the development of multidrug resistance in rhabdomyosarcomas. Modulation of these factors may determine the sensitivity of rhabdomyosarcoma cells to drugs and may play an important role in triggering the differentiation programme found in these resistant rhabdomyosarcoma cells.