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- Gastrointestinal Dysfunction in Children With Autism Spectrum Disorders. [JOURNAL ARTICLE]
- Autism Res 2014 Apr 21.
Gastrointestinal (GI) dysfunctions are frequently reported by parents of children with autism spectrum disorders (ASD) and have been recently recognized as a comorbid condition. However, the clinical significance of these GI dysfunctions remains to be delineated. This study describes the clinical characteristics, associated comorbid disorders, and endoscopic and colonoscopic evaluation of GI dysfunction in a cohort of 164 children with ASD evaluated at a pediatric neurology practice. Symptoms of GI dysfunction were prevalent: 49% of the children reported one or more chronic GI complaints, 22% exhibited diarrhea, 26% suffered from constipation. Furthermore 13% of the parents reported their children to suffer from bloating and/or being gassy and while 10% of the parents reported vomiting or gastroesophageal reflux problems. Similar rates of GI symptoms were reported among pre-school and school-aged children. Inflammation of the gut was found in 6 of the 12 subjects who underwent endoscopic and colonoscopic evaluations, however clinical symptoms did not predict the results of the evaluation. GI dysfunction was significantly associated with sleep disorders and food intolerance, but not with irritability or aggressiveness. In summary, GI dysfunction was prevalent in this cohort of children with ASD, observations consistent with the reports of parents and other clinicians. We conclude that the GI dysfunction in ASD requires proper evaluation and treatment. Autism Res 2014, ●●: ●●-●●. © 2014 International Society for Autism Research, Wiley Periodicals, Inc.
- [Two cases of curative resection by laparoscopic surgery following preoperative chemotherapy with bevacizumab for locally advanced colon cancer]. [English Abstract, Journal Article]
- Gan To Kagaku Ryoho 2014 Apr; 41(4):503-7.
Here we report 2cases of curative resection following preoperative chemotherapy with bevacizumab for locally advanced colon cancer. Case 1 was a 62-year-old man admitted with constipation, abdominal distention, and abdominal pain. An abdominal computed tomography(CT)scan revealed an obstructive tumor of the sigmoid colon with invasion into the bladder. A diverting colostomy was performed, and chemotherapy with mFOLFOX6(infusional 5-fluorouracil/Leucovorin+ oxaliplatin)plus bevacizumab was initiated. The tumor shrunk markedly after 6 courses of this treatment. Thereafter, laparoscopy- assisted sigmoidectomy was successfully performed. Case 2was a 61-year-old woman admitted with diarrhea, abdominal pain, and fever. An abdominal CT scan revealed an obstructive tumor of the sigmoid colon with invasion into the ileum, uterus and retroperitoneum. A diverting colostomy was performed, and chemotherapy with XELOX(capecitabine+ oxaliplatin)plus bevacizumab was initiated. The tumor shrunk markedly after 6 courses of this treatment. Thereafter, laparoscopy- assisted sigmoidectomy was successfully performed. Both cases demonstrated partial clinical responses to chemotherapy; thus, curative resection surgeries were performed. There were no perioperative complications. Therefore, we conclude that oxaliplatin-based chemotherapy plus bevacizumab and laparoscopic resection could be very effective for locally advanced colon cancer.
- [Induction chemotherapy with s-1/oxaliplatin prevented colostomy in a patient with advanced rectal cancer]. [English Abstract, Journal Article]
- Gan To Kagaku Ryoho 2014 Mar; 41(3):395-7.
A 72-year-old woman was admitted to our hospital with bloody stools and constipation. She was diagnosed with advanced lower rectal cancer with multiple liver and pulmonary metastases. Because the rectal cancer was located 2 cm from the anal verge, we suggested she undergo an abdominoperineal resection(Miles operation), but she refused to undergo a colostomy. Then, 6 courses of chemotherapy with S-1/oxaliplatin(SOX)were administered, and the local tumor, liver metastases, and pulmonary metastases were all significantly decreased in size(reduction rate 60%). After chemotherapy, she chose to undergo low anterior resection(LAR), D2. Postoperative recovery was uneventful, and she currently has stable disease with adjuvant SOX chemotherapy. Induction SOX chemotherapy was considered to be useful for maintaining the quality of life(QOL) in a patient with advanced rectal cancer.
- Motor and non-motor features of Parkinson's disease that predict persistent drug-induced Parkinsonism. [JOURNAL ARTICLE]
- Parkinsonism Relat Disord 2014 Apr 1.
Drug-induced Parkinsonism is common, causes significant morbidity, and can be clinically indistinguishable from idiopathic Parkinson's disease. Additionally, drug-induced Parkinsonism may, in some cases, represent "unmasking" of incipient Parkinson's disease. Clinical features or tests that distinguish degenerative from pharmacologic Parkinsonism are needed.We performed a retrospective case-control study of 97 drug-induced Parkinsonism subjects and 97 age-matched patients with Parkinson's disease. We compared the frequency of subjective motor and non-motor complaints, objective motor findings (Unified Parkinson's Disease Rating Scale Part III) and, where available, objective olfactory tests. We also performed a nested case-control study wherein we compared these same features between drug-induced Parkinsonism patients based on whether or not they recovered after changing the offending agent.Non-motor symptoms including constipation and sexual dysfunction were more common in Parkinson's disease than in drug-induced Parkinsonism. While total motor scores were similar between groups, Postural Instability-Gait Difficulty scores were also higher in Parkinson's disease. Features that were significantly different or showed a trend towards significance in both comparisons included subjective loss of facial expression, dream-enactment behavior, autonomic complaints and Postural Instability-Gait Difficulty scores. Hyposmia was more common in Parkinson's disease and was strongly predictive of persistent drug-induced Parkinsonism after therapy change (odds ratio 30.3, 95% confidence interval: 1.5-500, p = 0.03).A constellation of motor and non-motor features may differentiate unmasked Parkinson's disease from drug-induced Parkinsonism. In particular, olfactory testing may offer a simple and inexpensive method to help predict outcomes in drug-induced Parkinsonism and, potentially, identify a cohort of pre-motor Parkinson's disease.
- Anorectal conditions: rectal prolapse. [Journal Article]
- FP Essent 2014 Apr.:28-34.
Rectal prolapse, the protrusion of the layers of the rectal wall through the anal canal, may be partial (mucosal) or complete (full thickness). Although prolapse is most common among older women, it affects individuals of all ages, including children. Associated fecal incontinence and constipation are typical. Urinary incontinence and uterovaginal/bladder prolapse also may coexist. Some patients may have rectal ulcers. Diagnosis is predominantly clinical; visualization of the prolapse may require the patient to strain while sitting or squatting. Imaging studies, including fluoroscopic or dynamic magnetic resonance defecography, can confirm the prolapse if the diagnosis is uncertain, and endoscopy can aid in detecting other colonic/extracolonic pathology. Nonsurgical management (eg, increased fiber intake, fiber supplements, biofeedback) often is therapeutic in minor (first- or second-degree) mucosal prolapse and can help alleviate constipation and incontinence before and after surgery for patients with full-thickness prolapse. However, for full-thickness prolapse, transabdominal procedures are the most effective management and are favored for healthy patients, irrespective of age. Perineal procedures (eg, rubber band ligation, mucosal excision) can be used for patients with full-thickness prolapse who are not candidates for transabdominal surgery and for those with second- and third-degree mucosal prolapse.
- Anorectal conditions: anal fissure and anorectal fistula. [Journal Article]
- FP Essent 2014 Apr.:20-7.
Anal fissures are linear splits in the anal mucosa. Acute fissures typically resolve within a few weeks; chronic fissures persist longer than 8 to 12 weeks. Most fissures are posterior and midline and are related to constipation or anal trauma. Painful defecation and rectal bleeding are common symptoms. The diagnosis typically is clinical. High-fiber diet, stool softeners, and medicated ointments relieve symptoms and speed healing of acute fissures but offer limited benefit in chronic fissures. Lateral internal sphincterotomy is the surgical management of choice for chronic and refractory acute fissures. Anorectal fistula is an abnormal tract connecting the anorectal mucosa to the exterior skin. Fistulas typically develop after rupture or drainage of a perianal abscess. Fistulas are classified as simple or complex; low or high; and intersphincteric, transsphincteric, suprasphincteric, or extrasphincteric. Inspection of the perianal area identifies the skin opening, and anoscopy visualizes internal openings. The goal of management is to obliterate the tract and openings with negligible sphincter disruption to minimize incontinence. Fistulotomy is effective for simple fistulas; patients with complex fistulas may require fistulectomy. Other procedures that are used include injection of fibrin glue or insertion of a bioprosthetic plug into the fistula opening.
- Anorectal conditions: hemorrhoids. [Journal Article]
- FP Essent 2014 Apr.:11-9.
Hemorrhoids are engorged fibrovascular cushions lining the anal canal. Constipation, increased intra-abdominal pressure, and prolonged straining predispose to hemorrhoids. Approximately 1 in 20 Americans and almost one-half of individuals older than 50 years experience symptomatic hemorrhoids. Bright red, painless rectal bleeding during defecation is the most common presentation. Even if hemorrhoids are seen on examination, patients with rectal bleeding who are at risk of colorectal cancer (eg, adults older than 50 years) should still undergo colonoscopy to exclude cancer as the etiology. Nonsurgical treatment for nonthrombosed hemorrhoids includes increased fiber intake, sitz baths, and drugs. If nonsurgical management is unsuccessful, rubber band ligation is the most effective office-based procedure for grades I, II, and III hemorrhoids. Surgical hemorrhoidectomy is indicated after failure of nonsurgical management and office-based procedures and also as initial management for grades III and IV hemorrhoids. Several different procedures can be used. For acutely thrombosed external hemorrhoids, excision and evacuation of the clot, ideally within 72 hours of symptom onset, is the optimal management. Prolapsed and strangulated hemorrhoids are best managed with stool softeners, analgesics, rest, warm soaks, and ice packs until recovery; residual hemorrhoids are banded or excised later.
- Massive pericardial effusion associated with hypotiroidism. [Journal Article]
- Rev Med Chir Soc Med Nat Iasi 2014 Jan-Mar; 118(1):87-91.
The diagnosis of hypothyroidism is difficult because hypothyroidism in adults and especially the elderly, classic, has an insidious onset with a range of nonspecific symptoms which may delay diagnosis for months or even years. Old age seems to represent trigger factor for autoimmune diseases, including hypothyroidism. Clinical features in hypothyroidism, such as weight gain, fatigue, intolerance of the cold, constipation, dry skin, edema and muscle weakness, and decreased osteo-tendinous reflexes are usually subtle and can be overlooked. Thyroid dysfunction may be associated with a negative impact on the cardiovascular system. Pericardial, pleural and peritoneal effusions are common findings in hypothyroidism. This case report represents a typical primary hypothyroidism (autoimmune) and shows the clinical features of this disease. Basically we talked about a severe myxedema with the involvement of internal organs in an elderly woman and the euthyroidism restoration, under thyroid replacement therapy, was correlated with the clinical improvement and cardiovascular and neurological status, with radiographic remission and regression to extinction of pericardial effusion at repeated echocardiographic evaluations.
- A randomized, placebo-controlled, four-period crossover, definitive QT study of the effects of APF530 exposure, high-dose intravenous granisetron, and moxifloxacin on QTc prolongation. [Journal Article]
- Cancer Manag Res 2014.:181-90.
Regulatory concern about potential QT-interval prolongation by serotonin-receptor antagonist antiemetics prompted product-label changes. The first-generation serotonin-receptor antagonist granisetron is available in oral (PO), intravenous (IV), and transdermal formulations. APF530 is a formulation that provides sustained release of granisetron when administered as a single subcutaneous (SC) injection. The Phase I study reported here evaluated effects of APF530 on electrocardiographic intervals.This single-site, double-blind, placebo-controlled, four-period crossover trial randomized healthy men and women to receive varying sequences of APF530 1 g SC, granisetron 50 μg/kg IV, moxifloxacin 400 mg PO, and placebo. Subjects were assessed for 49 hours after each treatment. The primary objective was to evaluate differences between baseline-adjusted, heart rate-corrected QT-interval change using the Fridericia rate correction (dQTcF) for APF530 1 g SC and placebo. Electrocardiograms were performed at various times throughout the assessment period. Pharmacokinetics and safety were evaluated.The upper one-sided 95% confidence interval (CI) for mean baseline-adjusted dQTcF at each post-dose time point between APF530 and placebo excluded 10 ms, indicating that APF530 1 g SC had no clinically significant effect on QTcF. Maximum observed QTcF change was 4.15 ms (90% CI, 0.94 to 7.36) at Hour 3. No clinically significant changes in other electrocardiogram intervals were observed. APF530 SC pharmacokinetics were as expected, with slow absorption (maximum plasma concentration 35.8 ng/mL, median time to maximum plasma concentration 11.1 hours) and slow elimination (mean half-life 18.6 hours; systemic clearance 20.2 L/hour) of granisetron versus the expected early peak concentration and elimination of granisetron IV. APF530 SC was well tolerated. Adverse events, most commonly constipation and SC injection-site reactions, were generally mild and quickly resolved.APF530 1 g SC did not induce clinically significant QTcF interval prolongation or changes in the other electrocardiogram intervals, and was well tolerated at twice the recommended dose.
- Cost savings of reduced constipation rates attributed to increased dietary fiber intakes: a decision-analytic model. [JOURNAL ARTICLE]
- BMC Public Health 2014 Apr 17; 14(1):374.
Nearly five percent of Americans suffer from functional constipation, many of whom may benefit from increasing dietary fiber consumption. The annual constipation-related healthcare cost savings associated with increasing intakes may be considerable but have not been examined previously. The objective of the present study was to estimate the economic impact of increased dietary fiber consumption on direct medical costs associated with constipation.Literature searches were conducted to identify nationally representative input parameters for the U.S. population, which included prevalence of functional constipation; current dietary fiber intakes; proportion of the population meeting recommended intakes; and the percentage that would be expected to respond, in terms of alleviation of constipation, to a change in dietary fiber consumption. A dose-response analysis of published data was conducted to estimate the percent reduction in constipation prevalence per 1 g/day increase in dietary fiber intake. Annual direct medical costs for constipation were derived from the literature and updated to U.S. $ 2012. Sensitivity analyses explored the impact on adult vs. pediatric populations and the robustness of the model to each input parameter.The base case direct medical cost-savings was $12.7 billion annually among adults. The base case assumed that 3% of men and 6% of women currently met recommended dietary fiber intakes; each 1 g/day increase in dietary fiber intake would lead to a reduction of 1.9% in constipation prevalence; and all adults would increase their dietary fiber intake to recommended levels (mean increase of 9 g/day). Sensitivity analyses, which explored numerous alternatives, found that even if only 50% of the adult population increased dietary fiber intake by 3 g/day, annual medical costs savings exceeded $2 billion. All plausible scenarios resulted in cost savings of at least $1 billion.Increasing dietary fiber consumption is associated with considerable cost savings, potentially exceeding $12 billion, which is a conservative estimate given the exclusion of lost productivity costs in the model. The finding that $12.7 billion in direct medical costs of constipation could be averted through simple, realistic changes in dietary practices is promising and highlights the need for strategies to increase dietary fiber intakes.