Therapeutic Endoscopic Ultrasound for Biliary and Pancreatic Disorders

The role of endoscopic ultrasound (EUS) has greatly expanded since the first clinical examination performed nearly 30 years ago. The introduction of linear instruments allowed tissue sampling (Kulesza and Eltoum Clin Gastroenterol Hepatol 5:1248–1254, 2007; Levy and Wiersema Gastrointest Endosc 62:417–426, 2005) and therapeutic interventions applications, including celiac plexus and ganglia blockade and neurolysis (Wiersema and Wiersema Gastrointest Endosc 44:656–662, 1996; Levy and Wiersema Gastroenterol Clin North Am, 35:153–165, 2006; Levy et al. Am J Gastroenterol 103:98–103, 2008), pancreatic fluid drainage (Lopes et al. Arq Gastroenterol 45:17–21, 2008; Norton et al. Mayo Clin Proc 76:794–798, 2001; Kruger et al. Gastrointest Endosc 63:409–416, 2006; Seifert et al.: Endoscopy 32:255–259, 2000), cholecystenterostomy (Kwan et al. Gastrointest Endosc 66:582–586, 2007), and delivery of cytotoxic agents (eg, chemotherapy, radioactive seeds, and gene therapy) (Chang et al.: Cancer 88:1325–1335, 2000; Chang Endoscopy 38(Suppl 1):S88–S93, 2006). The continued need to develop less invasive alternatives to surgical and interventional radiologic therapies drove the development of EUS-guided methods for biliary and pancreatic intervention. This article reviews existing data and focuses on established and emerging EUS techniques for accessing and draining the bile and pancreatic ducts.     

Noonan syndrome and related disorders: Alterations in growth and puberty

Noonan syndrome is a relatively common multiple malformation syndrome with characteristic facies, short stature and congenital heart disease, most commonly pulmonary stenosis (Noonan, Clin Pediatr, 33:548–555, 1994). Recently, a mutation in the PTPN11 gene (Tartaglia, Mehler, Goldberg, Zampino, Brunner, Kremer et al., Nat Genet, 29:465–468, 2001) was found to be present in about 50% of individuals with Noonan syndrome. The phenotype noted in Noonan syndrome is also found in a number of other syndromes which include LEOPARD (Gorlin, Anderson, Blaw, Am J Dis Child, 17:652–662, 1969), Cardio-facio-cutaneous syndrome (Reynolds, Neri, Hermann, Blumberg, Coldwell, Miles et al., Am J Med Genet, 28:413–427, 1986) and Costello syndrome (Hennekam, Am J Med Genet, 117C(1):42–48, 2003). All three of these syndromes share similar cardiac defects and all have postnatal short stature. Very recently, HRAS mutations (Aoki, Niihori, Kawame, Kurosawa, Ohashi, Tanaka et al., Nat Genet, 37:1038–1040, 2005) have been found in the Costello syndrome and germline mutations in KRAS and BRAF genes (Rodriguez-Viciana, Tetsu, Tidyman, Estep, Conger, Santa Cruz et al., Nat Genet, 2006; Niihori, Aoki, Narumi, Neri, Cave, Verloes et al., Nat Genet, 38:294–296, 2006) in the Cardio-facio-cutaneous syndrome. Phenotypic overlap between these genetic disorders can now be explained since each is caused by germline mutations that are major components of the RAS-MAPK pathway. This pathway plays an important role in growth factor and cytokine signaling as well as cancer pathogenesis.     

A Meta-Analysis of the Efficacy of Sulfasalazine in Comparison with 5-Aminosalicylates in the Induction of Improvement and Maintenance of Remission in Patients with Ulcerative Colitis

Background Historically, sulfasalazine (SSZ) and 5-aminosalicylates (5-ASAs) have been a mainstay of mild-to-moderate ulcerative colitis (UC) remission induction and maintenance therapy. Considering the pivotal role of intestinal microbial flora in pathophysiology of UC and antimicrobial activity of sulfapyridine, we hypothesized that SSZ might be more effective than 5-ASAs in the management of UC. Aim To compare the efficacy and tolerability of SSZ with each of the 5-ASAs (mesalamine, olsalazine, and balsalazide) by a meta-analysis technique. Methods Pubmed, Embase, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials were searched for studies compared efficacy and/or tolerability of SSZ with 5-ASAs in the management of UC. The search terms were: “sulfasalazine” or “sulfasalazine” and “5-aminosalicylic acid,” “mesalazine,” “mesalamine,” “olsalazine” or “balsalazide” and “ulcerative colitis.” Data were collected from 1966 to April 2008. There was no language restriction. “Overall improvement,” “relapse rate,” “total adverse events,” and “withdrawals because of adverse events” were the key outcomes of interest. Results Twenty randomized placebo controlled trials met our criteria and were included in the meta-analysis. Comparison of SSZ with mesalamine yielded a nonsignificant relative risk (RR) of 1.04 (95% confidence interval of 0.89–1.21, P = 0.63) for overall improvement, a nonsignificant RR of 0.98 (95% CI 0.78–1.23, P = 0.85) for relapse, a nonsignificant RR of 0.76 (95% CI 0.54–1.07, P = 0.11) for any adverse events, and a nonsignificant RR of 0.78 (95% CI 0.46–1.3, P = 0.33) for withdrawals due to adverse events. Comparison of SSZ with olsalazine yielded a nonsignificant RR of 1.14 (95% CI 0.91–1.43, P = 0.25) for overall improvement, a nonsignificant RR of 0.93 (95% CI 0.77–1.12, P = 0.42) for relapse, a nonsignificant RR of 1.21 (95% CI 0.9–1.61, P = 0.20) for any adverse events, and a nonsignificant RR of 1.53 (95% CI 0.93–2.52, P = 0.09) for withdrawals due to adverse events. Comparison of SSZ with balsalazide yielded a nonsignificant RR of 1.3 (95% CI 0.93–1.81, P = 0.12) for overall improvement, and a significant RR of 0.17 (95% CI 0.06–0.49, P = 0.001) for withdrawals because of adverse events. Conclusion SSZ does not differ from mesalamine or olsalazine in terms of efficacy and tolerability in UC. Withdrawal from study due to adverse events was significantly lower for balsalazide compared with SSZ. Convincing conclusions on the comparison of effectiveness and safety of balsalazide and SSZ in UC remains to be elucidated by further clinical trials. Considering the lower cost of treatment with SSZ and the equal rate of adverse events with other 5-ASAa, it is not surprising to suggest SSZ as a first-choice treatment for UC and reserve 5-ASAs for when SSZ intolerability occurs.     

Comparison of Mesalazine and Balsalazide in Induction and Maintenance of Remission in Patients with Ulcerative Colitis: A Meta-Analysis

Background 5-Aminosalicylates are the standard treatment for induction and maintenance of remission in mild-to-moderate ulcerative colitis. In recent years, the 5-aminosalicylic acid-containing pro-drug balsalazide has been the focus of attention. Aim To compare the efficacy and tolerance of balsalazide and mesalazine by meta-analysis. Methods Pubmed, Embase, Scopus, Web of Science, and the Cochrane Central Register of Controlled Trials were searched for studies comparing the efficacy and/or tolerance of balsalazide with mesalazine in the management of UC. The search terms were: “mesalazine” or “5-aminosalicylic acid” and “balsalazide” and “ulcerative colitis.” Data were collected from 1966 to 2007 (up to February). There was no language restriction. “Symptomatic remission,” “complete remission,” “relapse rate,” “total adverse events,” and “withdrawals because of adverse events” were the key outcomes of interest. Results Six randomized placebo-controlled clinical trials met our criteria and were included in the meta-analysis. In these “symptomatic remission,” “complete remission,” “relapse rate,” “total adverse events,” and “withdrawals because of adverse events” were evaluated in three, three, two, five, and six of the trials, respectively. They included 653 patients consisting of 55.4% men and 44.6% women randomized to receive either balsalazide or mesalazine. Pooling of three trials for symptomatic remission yielded a significant relative risk (RR) of 1.23 (95% confidence interval of 1.03–1.47, P = 0.02). The summary RR for complete remission in three trials was 1.3 (95% CI of 1.002–1.68, P = 0.048). Pooling of two trials for the outcome of relapse yielded a non-significant RR of 0.77 (95% CI of 0.56–1.07, P = 0.12). Pooling five studies from which data for any adverse events were extracted, yielded a non-significant RR of 0.87 (95% CI of 0.75–1.001, P = 0.53). The summary RR for withdrawals because of adverse events in six trials was 0.69, a non-significant RR (95% CI of 0.37–1.29, P = 0.24). Conclusion Balsalazide is more effective than mesalazine in induction of remission, but balsalazide has no benefit compared with mesalazine in preventing relapse in the population selected. The number of patients with any adverse events and withdrawals because of severe adverse events is similar for mesalazine and balsalazide.     

Improving Pain Management Communication: How Patients Understand the Terms “Opioid” and “Narcotic”

Background/Objectives  Pain specialists often advocate discontinuing use of the term “narcotic,” with the negative connotations it bears for many patients, in favor of the term “opioid.” To contribute empirical data to this argument, we elicited and compared patient understandings of the terms “narcotic” and “opioid.” Design/Participants  Brief, anonymous surveys were administered to 100 outpatients. Respondents were asked to describe what a narcotic/opioid is, give example(s), explain why someone would take a narcotic/opioid and describe long term consequences of use. Results  Of the 100 outpatients, 86% responded “don’t know” to all four opioid questions. Only 12% did not know what a narcotic was (p < 001). While 50% of patients related “narcotics” to pain management, more than a third cited addiction or abuse. Of the 100 outpatients, 78% feared an adverse outcome from long-term narcotic use, with 66% of those answers citing “addiction.” Conclusion  Most patients were unfamiliar with the term opioid, while a substantial percentage identified a narcotic as an illegal drug and most reported adverse consequences as the outcome of long term use. Our findings, while preliminary, suggest that “opioid” is a more unfamiliar term, but raise questions about whether simply using different terminology would affect patient fears about this class of medications. Financial support: Dr. Crowley-Matoka’s efforts on this study were supported by a career development award through the Veterans’ Affairs Health Services Research and Development Service (MRP 03–149).     

Association between fibromyalgia and sexual dysfunction in women

The objective of the study was to review the association between fibromyalgia (FM) and sexual dysfunction in women and possible mechanisms of such association. PubMed, MEDLINE, and EMBASE databases (1950–2008) were searched for the key words “fibromyalgia”, “chronic pain”, “sexual dysfunction”, “female”, “sexuality”, “depression”, and “quality of life”. All relevant articles in English and secondary references were reviewed. All reviewed studies showed that FM is associated with sexual dysfunction in women. The major findings were as follows: decreased sexual desire and arousal, decreased experience of orgasm, and increased pain with intercourse. FM, sexual dysfunction, and depression may be interrelated with the depressive mood responsible for desire and arousal problems. On the other hand, in FM patients, the threshold at which sensory input becomes painful is lower than normal that can explain pain on intercourse. Additional studies are needed to evaluate the casual relationship and mechanism of association between FM and sexual dysfunction in women.     

Laparoscopic Ultralow Anterior Resection with Colonic J-pouch-Anal Anastomosis

Purpose  Optimal treatment of mid to distal rectal cancers includes total mesorectal excision for oncologic clearance and, where reanastomosis is feasible, a colonic J-pouch-anal anastomosis improves bowel function. There is recent interest in performing an ultralow anterior resection laparoscopically.1–3 A technique is described that includes specimen extraction through the eventual routine defunctioning colostomy or ileostomy site. Methods  Consecutive unselected patients who underwent laparoscopic ultralow anterior resection were recruited. Patients with adenocarcinoma underwent preoperative endorectal ultrasound to individualize for neoadjuvant chemoradiotherapy, based on local extent and lymph nodes seen. The operative procedures were as shown in the video. Posterior dissection along the “total mesorectal excision plane” included incision of Waldeyer’s fascia. Bowel continuity was restored by an intracoporeal double-cross stapled colonic J-pouch-anal anastomosis, but where not possible a coloplasty with pull-through handsewn coloanal anastomosis was performed. Results  Laparoscopic ultralow anterior resection was performed on 55 patients (35 men; median age, 63 (range, 33–90) years) from March 2004 to October 2006. The median body mass index was 26.3 (19–38); 14 patients (25 percent) had a body mass index >30. Ten patients (18 percent) had an American Society of Anesthesiologists’ classification of III. The indications were adenocarcinoma (n = 51), squamous-cell carcinoma of rectum (n = 1), dermoid tumor of mesorectum (n = 1), large villous adenoma (n = 1), and carcinoid with local lymph node metastases (n = 1). The adenocarcinomas were a median distance of 6 (3–12) cm from the anal verge. Neoadjuvant radiotherapy was given in 12 patients (24 percent) who had preoperative endoanal ultrasound findings of tumor extension beyond the muscularis propria and chemoradiotherapy in 7 (14 percent) of these patients where the tumor was more bulky and fixed. Laparoscopic ultralow anterior resection was completed at a median 180 (90–405) minutes, with 53.5 (2–2250) ml of blood loss, and the specimen was extracted through a 4.5 (3.5–11) cm wound. The latter included three cases (5 percent) that were converted. Significant adhesiolysis was required in 29 patients (52.7 percent) because of previous operations. The histologic grading or the adenocarcinoma patients were: Stage I, n = 14; Stage II, n = 23; Stage III, n = 11; Stage IV, n = 3. Of those who underwent curative resection (Stages I–III), the distal resection margin was 2.9 ± 0.7 cm (mean ± standard error) and the radial resection margins were at least 2 mm in all patients. The level of the coloanal anastomosis was a median 3.5 (0–4.5) cm from the anal verge; a coloanal pull-through anastomosis was required in one patient who had a distal cancer. The ileostomies functioned and patients tolerated free fluids at a median of two (1–9) days, and the median postoperative hospital stay was seven (3–22) days. At a median follow-up of 14 (2–33) months, none of the adenocarcinoma patients who had undergone curative resection had recurrences. Four patients (8 percent) had postoperative complications that required operative/invasive intervention (anatomotic leak n = 1, proximal bowel ischemia n = 1, port site hernia n = 1, pelvic collection n = 1). Four other patients had smaller pelvic collections that resolved with antibiotics; pelvic collections were associated with advanced stage of cancer (P = 0.047). Discharge was delayed by acute gastric distension in 11 patients; the latter was associated with poorer American Society of Anesthesiologists’ risk classification (P = 0.035). Erectile dysfunction occurred in ten men, and this was associated with adjuvant chemoradiotherapy (P = 0.042). One patient (2 percent) had persistent urinary retention that required catheterization at latest follow-up. The ileostomy had been closed in 50 patients, and at last follow-up, the median stool frequency was two (1–8) bowel movements per day. Conclusions  Laparoscopic ultralow anterior resection could be offered routinely and completed safely in Western populations, where obesity and adhesions from previous abdominal surgery is common. A laparoscopic technique readily allowed visual identification of the autonomic nerves in the abdomen over the aorta, which could then be followed down into the pelvis. If the pelvis was deep, inversion of the 30° laparoscope in the “upside down” position fascilited incision of Waldeyer’s fascia. This brought the rectum proximally and anteriorly, aiding with the laparoscopic stapler transection of the distal rectum, especially if the cancer was distal, the patient was obese, and the pelvis was narrow. Extraction of the specimen at the eventual defunctioning stoma site reduced the incisions required. Preoperative chemoradiotherapy may have a role in postoperative male sexual dysfunction. Further randomized, controlled studies that include assessing five-year cancer survival/recurrence, pelvic nerve dysfunction, and bowel function are needed before laparoscopic ultralow anterior resection becomes widely accepted. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

The veteran population: one at high risk for sleep-disordered breathing

Sleep complaints are very common among the general population and are usually accompanied by significant medical, psychological and social disturbances (Redline S, Strohl K, Otolaryngol Clin North Am, 132:303, 1999). A higher prevalence of sleep complaints has been described in the elderly (Vgontzas AN, Kales A, Annu Rev Med, 50:387–400, 1999). It is manifested by breathing disturbances during sleep, loud snoring, difficulties maintaining sleep, fatigue, daytime sleepiness, mood effects and impairment of daily activities (Lugaresi E, Cirignotta F, Zucconi M et al., Good and poor sleepers: an epidemiological survey of the San Marino population, Raven, New York, pp 1–12, 1983; Kales A, Soldatos CR, Kales JD, Am Fam Physician, 22:101–108, 1980). It has been associated with cardiovascular, endocrine and neurocognitive manifestations. Growing interest in early diagnosis and treatment has been noted in recent years based on emerging knowledge about the potential health consequences when the disease goes untreated (Nanen AM, Dunagan DP, Fleisher A et al., Chest, 121:1741, 2002). The veteran population in the mainland has a higher tendency for obesity, high blood pressure (HBP), sleep disorders and chronic alcohol consumption (Mustafa M, Erokwu N, Ebose I, Strohl K, Sleep Breath, 9:57–63, 2005). The Hispanic veteran population has never been studied in detail for sleep disorders and related conditions. We used previously validated screening tools for sleep disturbance breathing. Two hundred and forty-five questionnaires were administered. We found a higher prevalence of Obstructive Sleep Apnea Hypopnea Syndrome (OSAHS) in our population compared with data from the mainland (USA). The mean age was 64 years (±11). Ninety seven per cent were males. The mean body mass index was 25 kg/cm²; mean Epworth Sleepiness Scale score was 8. Thirty-four per cent met high-risk criteria for sleep apnea, 53% for insomnia, 13% for symptoms suggestive of narcolepsy and 13% for those suggestive of restless leg syndrome. There were high incidences of alcohol consumption (37.6%), diabetes (32.7%), hypercholesterolemia (31.8%), depression (31.8%), hypertension (39.6%) and post-traumatic stress disorder (PTSD) (9.8%).     

Impact of microarousal associated with increased negative esophageal pressure in sleep-disordered breathing

Purpose  

“Microarousals” during sleep have not been analyzed systematically. We investigated the importance of “microarousals” (lasting 1.5–3 s).     

Identifying Multiple Submissions in Internet Research: Preserving Data Integrity

Internet-based sexuality research with hidden populations has become increasingly popular. Respondent anonymity may encourage participation and lower social desirability, but associated disinhibition may promote multiple submissions, especially when incentives are offered. The goal of this study was to identify the usefulness of different variables for detecting multiple submissions from repeat responders and to explore incentive effects. The data included 1,900 submissions from a three-session Internet intervention with a pretest and three post-test questionnaires. Participants were men who have sex with men and incentives were offered to rural participants for completing each questionnaire. The final number of submissions included 1,273 “unique”, 132 first submissions by “repeat responders” and 495 additional submissions by the “repeat responders” (N = 1,900). Four categories of repeat responders were identified: “infrequent” (2–5 submissions), “persistent” (6–10 submissions), “very persistent” (11–30 submissions), and “hackers” (more than 30 submissions). Internet Provider (IP) addresses, user names, and passwords were the most useful for identifying “infrequent” repeat responders. “Hackers” often varied their IP address and identifying information to prevent easy identification, but investigating the data for small variations in IP, using reverse telephone look up, and patterns across usernames and passwords were helpful. Incentives appeared to play a role in stimulating multiple submissions, especially from the more sophisticated “hackers”. Finally, the web is ever evolving and it will be necessary to have good programmers and staff who evolve as fast as “hackers”.     

Spousal Intimate Partner Violence is Associated with HIV and Other STIs Among Married Rwandan Women

HIV is a health problem in Rwanda, where the adult HIV prevalence is 3.1% (WHO 2008 in Online database of HIV/AIDS epidemiological data, found at: ); the majority of those infected are women (UNAIDS 2008 in ). Prior studies indicate that intimate partner violence is frequently associated with increased HIV risk in women, often because men who abuse their wives also exhibit riskier sexual behaviors (Silverman et al. in JAMA 300:703–710 2008. Population—based data from the 2005 Rwanda Demographic and Health Survey indicate that women with few, if any, other sexual risk factors who have experienced sexual, physical, or emotional abuse within their marriages are 1.61–3.46 times as likely to test positive for HIV, and 2.14–4.11 times more likely to report another STI. These findings confirm prior clinical studies that indicate that intimate partner violence is a correlate of HIV/STIs in Rwanda. Further research is needed to determine whether Rwandan men that abuse their wives have higher baseline rates of HIV/STI infection.     

Mismatch between arterial stiffness increase and left ventricular diastolic dysfunction

Previous studies which included patients with preserved left ventricular (LV) systolic function demonstrated that arterial stiffness progressively increased as LV diastolic function decreased. However, it was unknown whether this correlation was still present in a heterogeneous study population involving patients with a wide range of LV systolic function. Seventy-five patients with depressed LV systolic function were consecutively included and 192 patients with preserved LV systolic function were randomly selected from subjects arranged for echocardiography examination. Brachial–ankle pulse wave velocity (baPWV) was measured using an ABI-form device. Of the 267 subjects (mean age 58 ± 14 years) included in the study, 105 had normal diastolic function, 74 had impaired relaxation, and 60 had pseudonormal and 28 restrictive diastolic dysfunction. BaPWV was only lower in patients with normal diastolic function than in those with abnormal diastolic function (p ≤ 0.001). It did not gradually rise as diastolic dysfunction grade increased. Multivariate analysis showed that increased age and systolic blood pressure and decreased LV ejection fraction, transmitral A velocity, and left atrial volume index (p ≤ 0.039) were correlated with increased baPWV. Our study showed that there were no positive correlation between echocardiographic LV diastolic parameters and baPWV. BaPWV did not progressively rise with increasing LV diastolic dysfunction grade. Therefore, patients with advanced LV diastolic dysfunction may not have increased arterial stiffness.     

A Surveillance Report of HIV Status and High Risk Behaviors Among Rapid Testing Participants in Tallinn,Estonia

Estonia has the second highest adult HIV prevalence in Europe of 1.3%. The primary transmission is among injecting drug users (IDU), who account for 56–90% of HIV infections (Report on the Global AIDS Epidemic: UNAIDS/WHO, July 2008 and Platt et al. AIDS 20(16):2120–2123, 2006). Of those persons newly diagnosed, 50.4% reported injecting drugs in the last 12 months, 16.3% of these reported IDU as the sole risk factor and 31.2% reported IDU among other risk factors. In this sample (n = 790) 170 persons reported a high risk behavior and 51 persons received a positive result through rapid testing. The largest proportion (35.29%) was among persons reporting high risk heterosexual intercourse and second (33.33%) among persons sharing injecting equipment. Covariates in a logistic regression model indicate that male sex (OR = 2.57, 95% CI 1.00–6.59), non-Estonian ethnicity (OR = 2.68, 95% CI 1.46–4.93), higher education (OR = 0.56, 95% CI 0.40–0.80), and high risk heterosexual intercourse (OR = 2.68, 95% CI 1.19–6.02) are statistically significant in predicting a positive HIV status.     

A Cluster Randomized Controlled Trial of an Adolescent HIV Prevention Program Among Bahamian Youth: Effect at 12?Months Post-Intervention

Behavioral interventions based on the Protection Motivation Theory (PMT) have been demonstrated to reduce HIV risk behavior among mid- and older adolescents in different settings across the globe but have not been evaluated among Caribbean nations and have received limited evaluation among pre-adolescents. To determine (1) the effectiveness among pre-adolescents in The Bahamas of a PMT-based HIV prevention program “Focus on Youth in the Caribbean” (FOYC) and (2) the role of the targeted PMT constructs in intervention effect. 1,360 sixth grade youth (10–11 years of age) from 15 urban schools in New Providence, The Bahamas were randomized by school to receive either FOYC or a control condition. Data collected at baseline, 6 and 12 months post intervention were analyzed. A five-step scheme was used to assess sexual behavior progression, ranging from “1” = “a virgin without intention to have sex” to “5” = “having sex without a condom”. Group-based trajectory analysis was utilized in assessing the program effect. Two sexual behavior progression patterns were detected: slow progressors and quick progressors. Receiving FOYC reduced the likelihood for adolescents to become quick progressors (adjusted OR = 0.77, 95% CI: 0.64–1.00). The observed effectiveness was especially impacted by a subset of the targeted PMT constructs. FOYC effectively delays sexual risk among Bahamian pre-adolescents. The group-based trajectory analysis provides an analytical approach for assessing interventions among adolescents with low rates and diverse progression patterns of sexual activity.     

Reverse chamber remodelling following adrenergic-induced advanced cardiac dilatation and pump dysfunction

As adrenergic-induced cardiac dilatation is associated with cardiomyocyte cell death, whether cessation of excessive adrenergic effects can achieve complete reverse chamber remodelling in established cardiac dilatation and pump dysfunction has been questioned. We assessed whether following the development of cardiac dilatation and pump dysfunction subsequent to 6 months of daily β-adrenergic receptor agonist administration (isoproterenol [ISO] at 0.01 mg/kg daily) to rats, withdrawal of ISO administration for a further 4 months (ISO + recovery) reverses the adverse effects on the heart. Chronic ISO administration and the withdrawal of ISO administration were associated with changes in cardiomyocyte apoptosis, but not myocardial necrosis (pathological score). After 6 months of ISO administration, left ventricular (LV) end diastolic and systolic diameters, and the volume intercept of the LV diastolic pressure–volume relationship (LV V ₀), were markedly increased and LV endocardial fractional shortening (FS_end), LV end systolic chamber (slope of the systolic pressure–volume relationship-Ees) and myocardial (slope of the systolic stress–strain relationship-En) contractility were substantially decreased. Chronic ISO administration produced a 2.5 times increase in LV V ₀ (ISO = 0.40 ± 0.04 vs. saline = 0.16 ± 0.01, P < 0.001). Following a 6-month period of ISO administration and a subsequent withdrawal period for a further 4 months, LV chamber diameters, LV V ₀ (ISO + recovery = 0.21 ± 0.02 vs. saline = 0.23 ± 0.02, P < 0.001), FS_end, LV Ees and LV En were all noted to be similar to control rats. The proportion of ISO + recovery rats with LV chamber diameters, LV V ₀, FS_end, LV Ees and LV En values above or below the 95% confidence interval for the saline + recovery rats was similar to the proportion of saline + recovery rats above or below their own 95% confidence intervals. In conclusion, even in the presence of adrenergic-induced cardiomyocyte apoptosis, marked cardiac dilatation and pump dysfunction produced by chronic β-adrenergic receptor activation can be completely reversed by withdrawal of the excessive adrenergic stimulus.     

Severe Hypophosphatemia Associated with Gallstone Pancreatitis: A Case Report and Review of the Literature

Severe hypophosphatemia (<1.0 mg/dl) is a rarely reported complication of acute pancreatitis; when it does occur, it is typically attributed to alcohol abuse rather than the pancreatitis itself (1–5). In the literature, pancreatitis is not cited as a cause of hypophosphatemia (5, 6–16). Both pancreatitis and hypophosphatemia have widespread ramifications on human physiology, affecting hematologic, neural, hepatic, endocrine, respiratory, and renal systems. Given the possible synergistic consequences of pancreatitis and low serum phosphate, we emphasize the importance of recognizing hypophosphatemia as a complication of pancreatic inflammation.Herein, we report a case of acute pancreatitis unrelated to alcohol abuse associated with severe hypophosphatemia and review the pathophysiology.     

Takotsubo Cardiomyopathy

Background  Takotsubo cardiomyopathy is a novel, yet well-described, reversible cardiomyopathy triggered by profound psychological or physical stress with a female predominance. Objective  This review is designed to increase general clinician awareness about the diagnosis, incidence, pathogenesis, and therapies of this entity. Data Sources  A complete search of multiple electronic databases (Pubmed, EMBASE, Science Citation Index) was carried out to identify all full-text, English-language articles published from 1980 to the present date and relevant to this review. Review Methods  The following search terms were used: takotsubo cardiomyopathy, stress-induced cardiomyopathy, and left ventricular apical ballooning syndrome. Citation lists from identified articles were subsequently reviewed and pertinent articles were further identified. Results  Takotsubo cardiomyopathy is typically characterized by the following: 1) acute onset of ischemic-like chest pain or dyspnea, 2) transient apical and mid-ventricular regional wall-motion abnormality, 3) minor elevation of cardiac biomarkers, 4) dynamic electrocardiographic changes, and 5) the absence of epicardial coronary artery disease. The pathogenesis of the syndrome is unknown but has mostly been associated with acute emotional or physiologic stressors. Dote, Sato, Tateishi, Uchida, Ishihara (J Cardiol. 21(2):203–214, 1991); Desmet, Adriaenssens, Dens (Heart. 89(9):1027–1031, Sep., 2003); Bybee, Kara, Prasad, et al. (Ann Intern Med. 141(11):858–865, Dec 7, 2004); Sharkey, Lesser, Zenovich, et al. (Circulation. 111(4):472–479, Feb 1, 2005) The short and long-term prognosis of these patients is overwhelmingly favorable and often only requires supportive therapy. Conclusion  Whether an emotional or physical event precedes one’s symptoms, it is apparent that takotsubo cardiomyopathy case presentations mimic ST-segment elevation myocardial infarction, and thus is an important entity to be recognized by the medical community.     

A Prospective,Randomized Study: Switch Off the Sacral Nerve Stimulator During the Night?

Purpose Sacral nerve stimulation is an effective treatment for fecal incontinence. Some have recommended to “switch off” the pacemaker during the night to extend the lifetime of the expensive pacemaker. This study was designed to investigate whether a nightly “switch off” affects the clinical results of sacral nerve stimulation. Methods Twenty patients successfully treated with sacral nerve stimulation (19 females; median age, 59 (range, 36–72) years) were randomized to: Group A, pacemaker continuously “on” for three weeks followed by three weeks with the pacemaker “off” during the night, or Group B, opposite order. Daily bowel-habit diary, Wexner, and St. Mark’s incontinence scores were obtained. Results One failed to return the daily bowel-habit diary, leaving 19 participating patients. Median Wexner incontinence score increased from 6 (range, 2–14) to 7 (range, 3–16) during the “off” period (P = 0.04), whereas St. Mark’s incontinence score increased from 10 (range, 3–16) to 11 (range, 3–18; P = 0.03). Median number of days with soiling per three weeks increased from 0 (range, 0–12) to 1 (range, 0–15) during the “off” period (P = 0.008). Seven of 19 had more days with soiling during the “off” period. Defecation frequency per three weeks increased from 26 (range, 11–71) to 34 (range, 9–70) during the “off” period (P = 0.19). Only four continued with a nightly “switch off” after the study. Conclusions It could be considered to recommend compliant patients to “switch off” the pacemaker during the night to extend the lifetime of the pacemaker. One-third experienced increased soiling, and they should turn the pacemaker on all day and night. Among the remaining, only a minor proportion will be motivated for turning the pacemaker off. Read at the meeting of the European Society of Coloproctology, Malta, September 26 to 29, 2007.