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PubMed1990

Gastrointestinal manifestations of mixed connective tissue disease.

We examined the gastrointestinal tract abnormalities in 61 patients with mixed connective tissue disease. The first 34 were part of a prospective longitudinal study that included manometric and radiographic evaluation of the esophagus. Heartburn (48%) and dysphagia (38%) were by far the most common gastrointestinal symptoms. Seventeen percent of patients undergoing manometry had distal esophageal aperistalsis, and 43% low-amplitude peristalsis (less than 30 mmHg). Studies in 10 patients before and after treatment suggested that esophageal dysfunction in mixed connective tissue disease may be responsive to corticosteroids. Upper esophageal sphincter hypotension was also common. One patient had marked upper esophageal sphincter hypotension and recurrent aspiration, which resolved with corticosteroid therapy. Findings on radiographic studies of the stomach and small bowel in 54 patients and barium enemas in 16 patients were reviewed. Our series included one case each of malabsorption, colonic and small bowel perforations due to vasculitis, chronic active hepatitis, and acute pancreatitis. In conclusion, any area of the gastrointestinal tract may be affected by mixed connective tissue disease, although the esophagus is the most common location. The gastrointestinal aspects of mixed connective tissue disease overlap with those of progressive systemic sclerosis, polymyositis, and systemic lupus erythematosus.

Adolescent↗
PubMed1999

Sexual dysfunction associated with the treatment of depression: a placebo-controlled comparison of bupropion sustained release and sertraline treatment.

This study compared the sexual functioning effects as well as the safety and efficacy of bupropion sustained release (bupropion SR) and sertraline. Three hundred sixty-four patients with normal sexual functioning and recurrent major depression were treated with bupropion SR (150-400 mg/day), sertraline (50-200 mg/day), or placebo for 8 weeks in this randomized, double-blind, multicenter study. Patients' depression, sexual functioning, and overall safety were assessed at regular clinic visits. Significantly (P < 0.05) more patients treated with sertraline experienced orgasm dysfunction compared with patients treated with bupropion SR or placebo. Bupropion SR, but not sertraline, was statistically significantly superior to placebo in improving scores on all depression scales by the end of the study. Headache occurred with similar frequency in all groups. Gastrointestinal disturbances occurred more frequently with sertraline; insomnia and agitation occurred more frequently with bupropion SR. Small decreases in mean weight were seen with both active treatments; the placebo group experienced a minor increase in mean weight. Both bupropion SR and sertraline were generally well tolerated, although sertraline was more often associated with sexual dysfunction. Bupropion SR, but not sertraline, was statistically superior to placebo in relieving depression by the end of the study. Bupropion SR may offer advantages over sertraline in treating depressed patients concerned with sexual functioning.

Adult↗
PubMed2004

New insights into the pathogenesis of cystic fibrosis: pivotal role of glutathione system dysfunction and implications for therapy.

The cystic fibrosis transmembrane regulator (CFTR) should no longer be viewed primarily as a 'chloride channel' but recognized as a channel that also controls the efflux of other physiologically important anions, such as glutathione (GSH) and bicarbonate. More effective approaches to cystic fibrosis treatment may result from this reconceptualization of the CFTR by researchers and clinicians. For example, oxidant damage in cystic fibrosis has been assumed to be a significant part of the pathophysiology of the disease. Generally speaking, antioxidant status in cystic fibrosis is compromised. However, until recently this was seen as secondary to the excessive chemoattraction of neutrophils in this disease caused by mutation of the CFTR protein, leading to a high oxidant burden. New findings suggest that the cystic fibrosis mutations in fact cause a primary dysfunction in the system of one of the body's most important antioxidant and immune-signaling substances: the reduced GSH system. Cystic fibrosis mutations significantly decrease GSH efflux from cells without redundant channels to the CFTR; this leads to deficiency of GSH in the epithelial lining fluid of the lung, as well as in other compartments, including immune system cells and the gastrointestinal tract. This deficiency is exaggerated over time as the higher-than-normal oxidant burden of cystic fibrosis leads to successively larger decrements in GSH without the normal opportunity to fully recover physiologic levels. This GSH system dysfunction may be the trigger for initial depletion of other antioxidants and may also play a role in initiating the over-inflammation characteristic of cystic fibrosis. Proper GSH system functioning also affects immune system competence and mucus viscosity, both of relevance to cystic fibrosis pathophysiology. In a way, cystic fibrosis may be thought of as the first identified disease with GSH system dysfunction.This overview provides a review of the most pertinent recent research findings in this area. Exogenous augmentation of GSH in the lung epithelial lining fluid is possible, and therapeutic approaches include administration of aerosolized buffered GSH, intravenous GSH, and oral GSH. However, it is important to remember that the pathophysiology of cystic fibrosis is multifactorial, and rectification of GSH system dysfunction in patients with cystic fibrosis will not eliminate all harmful effects of the disease. The promising results of two clinical trials of aerosolized buffered GSH in cystic fibrosis patients have been published or accepted for publication at the time of this writing. GSH depletion in lung epithelial lining fluid has also been noted in other respiratory diseases such as COPD, idiopathic pulmonary fibrosis, and adult respiratory distress syndrome, and therapies to augment GSH may also be contemplated in these diseases.

Cystic Fibrosis↗
PubMed1999

Front and rear: the pelvic floor is an integrated functional structure.

The pelvic floor is a muscular structure, pierced by the urologic, genital and distal intestinal tract. This structure is not a frozen but a functional unit. Normal function can thus be replaced by dysfunctions of several kinds, overlapping voiding, sexual, genital and defecatory behaviour. For instance, vaginismus is akin to anismus and vesicourethral dyssynergia. Recent recognition of the medicosurgical consequences of sexual abuse has shown that many urologic, genital and digestive dysfunctions are sort of a body signature of the trauma, which must be dealt with if the symptom is to disappear. If the pelvic floor is integrated, unsuspected pathology will lie outside of the spectrum of activities of a given specialty, and thus urologists, gynecologists, gastroenterologists and colorectal surgeons should not only exchange, but should also be aware of the pathologies of neighbouring specialties. This paper elaborates on a more holistic vision of pelvic floor function including sexuality. Out of this, a number of different hypotheses are elaborated in the different spheres of activities, about different pathologies, their basic cause, and how they could be dealt with.

Biofeedback, Psychology↗
PubMed2001

Incidence, prevalence, and management of opioid bowel dysfunction.

Opioid bowel dysfunction (OBD) is a common adverse effect associated with opioid therapy. OBD is commonly described as constipation; however, it is a constellation of adverse gastrointestinal (GI) effects, which also includes abdominal cramping, bloating, and gastroesophageal reflux. The mechanism for these effects is mediated primarily by stimulation of opioid receptors in the GI tract. In patients with pain, uncontrolled symptoms of OBD can add to their discomfort and may serve as a barrier to effective pain management, limiting therapy, or prompting discontinuation. Patients with cancer may have disease-related constipation, which is usually worsened by opioid therapy. However, OBD is not limited to cancer patients. A recent survey of patients taking opioid therapy for pain of noncancer origin found that approximately 40% of patients experienced constipation related to opioid therapy (<3 complete bowel movements per week) compared with 7.6% in a control group. Of subjects who required laxative therapy, only 46% of opioid-treated patients (control subjects, 84%) reported achieving the desired treatment results >50% of the time. Laxatives prescribed prophylactically and throughout opioid therapy may improve bowel movements in many patients. Nevertheless, a substantial number of patients will not obtain adequate relief of OBD because of its refractory nature. Naloxone and other tertiary opioid receptor antagonists effectively reduce the symptoms of constipation in opioid-treated patients. However, because they also act centrally, they may provoke opioid withdrawal symptoms or reverse analgesia in some patients. There are 2 peripherally selective opioid receptor antagonists, methylnaltrexone and ADL 8-2698 (Adolor Corporation, Exton, PA, USA), that are currently under investigation for their use in treating OBD. Early studies confirm that they are effective at normalizing bowel function in opioid-treated patients without entering the central nervous system and affecting analgesia. With a better understanding of the prevalence of OBD and its pathophysiology, a more aggressive approach to preventing and treating OBD is possible and will likely improve the quality of life of patients with pain.

Analgesics, Opioid↗
PubMed2002

Colon atresia, facial hemiaplasia, and anophthalmia: a case report.

A case of a newborn with atresia of the transverse colon and right facial hemiaplasia, anophthalmia, and cerebral dysfunction is reported. Colon atresia is a rare cause of congenital bowel obstruction and often associated with other malformations such as abdominal wall defects, gastrointestinal, cardiac, urogenital, and musculosceletal lesions. Facial hemiaplasia may arise in frame of chromosomal defects or as a result of neurovascular compromise caused by congenital amniotic bands. However, the combination of colon atresia and facial hemiaplasia has not been reported before.

Abnormalities, Multiple↗
PubMed2004

Exploring the potential of variola virus infection of cynomolgus macaques as a model for human smallpox.

Smallpox virus (variola) poses a significant threat as an agent of bioterrorism. To mitigate this risk, antiviral drugs and an improved vaccine are urgently needed. Satisfactory demonstration of protective efficacy against authentic variola will require development of an animal model in which variola produces a disease course with features consistent with human smallpox. Toward this end, cynomolgus macaques were exposed to several variola strains through aerosol and/or i.v. routes. Two strains, Harper and India 7124, produced uniform acute lethality when inoculated i.v. in high doses (10(9) plaque-forming units). Lower doses resulted in less fulminant, systemic disease and lower mortality. Animals that died had profound leukocytosis, thrombocytopenia, and elevated serum creatinine levels. After inoculation, variola was disseminated by means of a monocytic cell-associated viremia. Distribution of viral antigens by immunohistochemistry correlated with the presence of replicating viral particles demonstrated by electron microscopy and pathology in the lymphoid tissues, skin, oral mucosa, gastrointestinal tract, reproductive system, and liver. These particles resembled those seen in human smallpox. High viral burdens in target tissues were associated with organ dysfunction and multisystem failure. Evidence of coagulation cascade activation (D dimers) corroborated histologic evidence of hemorrhagic diathesis. Depletion of T cell-dependent areas of lymphoid tissues occurred, probably as a consequence of bystander apoptotic mechanisms initiated by infected macrophages. Elaboration of cytokines, including IL-6 and IFN-gamma, contribute to a cytokine storm formerly known as "toxemia." A more precise understanding of disease pathogenesis should provide targets for therapeutic intervention, to be used alone or in combination with inhibitors of variola virus replication.

Animals↗
PubMed1983

Gastric manometric abnormalities in patients with dyspeptic symptoms after fundoplication.

We describe six patients in whom severe dyspeptic symptoms developed after fundoplication. The symptoms began immediately after operation (three patients) or shortly thereafter (three and eight months). There were no other known predisposing factors to gastroparesis. Seven, age-matched, healthy volunteers served as controls. Pressure activity from antrum (two sites), duodenum (two sites), and jejunum (one site) was recorded by a low compliance perfusion system connected to external strain gauge transducers. Activity was recorded for three hours during fasting and for two hours after the ingestion of a solid and a liquid meal. To determine whether an inadvertent vagotomy had been performed, basal acid output and the response to insulin (Hollander's test) were measured on a separate day. Manometric studies revealed postprandial hypomotility in these patients, whereas fasting antral and intestinal activities were normal. Acid output increased in all patients during insulin induced hypoglycaemia. In three patients, an antrectomy was subsequently performed, and they were relieved of their symptoms. We conclude that, after fundoplication, symptoms associated with postprandial antral hypomotility may develop in some patients. The pathophysiologic mechanism is unknown, but a positive acid response to insulin induced hypoglycaemia does not support the occurrence of incidental vagotomy. We do not know the prevalence of this motor abnormality among asymptomatic patients with prior fundoplication. A favourable symptomatic response to antrectomy in several of our patients, however, suggests that the symptoms were related to antral motor dysfunction.

Adult↗
PubMed1992

Gastroparesis: diagnostic and therapeutic strategies.

Impairment of gastrointestinal motility is common among patients with chronic dyspepsia. Gastroparesis can lead to devastating clinical consequences including malnutrition, weight loss, metabolic acidosis and psychological dysfunction. In this article, the current concepts of gastric motor function are reviewed and the diagnostic and treatment modalities of gastroparesis are discussed in detail.

Gastric Emptying↗
PubMed1991

Marked increases of plasma gamma-aminobutyric acid concentrations in cirrhotic patients with portacaval shunts are not associated with alterations of cerebral functions.

Several previous studies have shown that the plasma concentration of gamma-amino-butyric acid (GABA) is markedly increased in patients with hepatic encephalopathy, and it has been suggested that decreased metabolism of peripheral GABA might contribute to the cerebral dysfunctions observed. In the present study, plasma GABA-like activity was determined by a radioreceptor assay in 21 cirrhotic patients in whom, at least 2 months prior to the study, portocaval shunt surgery had been performed for treatment of recurrent variceal bleeding. Compared to 10 healthy volunteers, plasma GABA concentrations were increased in all cirrhotic patients, whereas most other amino acids, including those known to interfere with the GABA radioreceptor assay at elevated concentrations, were within the normal range. Despite an about 3- to 16-fold increase in individual GABA concentration, none of the patients showed clinical signs of overt hepatic encephalopathy on conventional neurologic (including EEG) and mental status examination. Furthermore, when a psychometric test system was used for evaluation of intellectual and psychomotor functions, all patients performed within the normal range and could not be distinguished from healthy volunteers. The data indicate that, at least in chronic liver disease, impaired metabolism of peripheral GABA does not lead to cerebral dysfunctions.

Electroencephalography↗
PubMed2002

Antidepressant side effects in depression patients treated in a naturalistic setting: a study of bupropion, moclobemide, paroxetine, sertraline, and venlafaxine.

OBJECTIVE: There is no commonly accepted standard for comparing antidepressant-induced side effects. This study evaluates a clinician-administered scale, the Toronto Side Effect Scale (TSES), in a natural practice clinic. METHOD: We used the TSES to assess side effects in 193 depression patients who completed 8 weeks of treatment with either bupropion, moclobemide, paroxetine, sertraline, or venlafaxine. RESULTS: Rates of remission (Hamilton Rating Scale for Depression [HRSD] < 7) did not differ across drugs after 8 weeks of treatment. Paired drug comparisons yielded significant differences in 16 of the 32 side effects. We present differences between pairs of the 5 antidepressants in Central Nervous System (CNS), gastrointestinal (GI), and sexual side effects. A measure of side-effect intensity distinguished paroxetine from the other antidepressants on a measure of sexual dysfunction. CONCLUSIONS: These results confirm the clinical utility of the TSES as a simple, clinician-administered antidepressant side-effect scale.

Adult↗
PubMed1990

Zolpidem. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential.

Zolpidem is an imidazopyridine, a chemically novel nonbenzodiazepine hypnotic agent which acts at the benzodiazepine omega 1-receptor subtype in the brain. With a rapid onset of action and short elimination half-life, it reduces the latency to and prolongs the duration of sleep in patients with insomnia, yet has no major effects on sleep stages when given in dosages of 5 to 20 mg nightly. Rebound effects on withdrawal of the drug have not been observed. Unlike benzodiazepines, zolpidem has no myorelaxant or anticonvulsant effects and its effects on anxiety appear to be minor. While zolpidem aids sedation, and may reduce memory or psychomotor function within the first 2 hours after administration of single oral doses, its use as a surgical premedicant remains to be established. Adverse effects are predominantly CNS and gastrointestinal in nature. Altered pharmacokinetics may lead to an increase in dose-proportionate adverse effects in the elderly and in patients with renal dysfunction. Limited evidence to date suggests that the dependence liability of zolpidem is minimal. Thus, zolpidem is an interesting alternative to benzodiazepines in the treatment of insomnia, with properties that potentially offer worthwhile advantages in this therapeutic area if they are confirmed with wider clinical experience.

Drug Interactions↗
PubMed2025

Radiation Without Borders: Unraveling Bystander and Non-Targeted Effects in Oncology.

Radiotherapy (RT) remains a cornerstone of cancer treatment, offering spatially precise cytotoxicity against malignant cells. However, emerging evidence reveals that ionizing radiation (IR) exerts biological effects beyond the targeted tumor volume, manifesting as radiation bystander effects (BEs) and other non-targeted effects (NTEs). These phenomena challenge the traditional paradigm of RT as a localized intervention, highlighting systemic and long-term consequences in non-irradiated tissues. This comprehensive review synthesizes molecular, cellular, and clinical insights about BEs, elucidating the complex intercellular signaling networks gap junctions, cytokines, extracellular vesicles, and oxidative stress that propagate damage, genomic instability, and inflammation. We explore the role of mitochondrial dysfunction, epigenetic reprogramming, immune modulation, and stem cell niche disruption in shaping BEs outcomes. Clinically, BEs contribute to neurocognitive decline, cardiovascular disease, pulmonary fibrosis, gastrointestinal toxicity, and secondary malignancies, particularly in pediatric and long-term cancer survivors. The review also evaluates countermeasures including antioxidants, COX-2 inhibitors, exosome blockers, and FLASH RT, alongside emerging strategies targeting cfCh, inflammasomes, and senescence-associated secretory phenotypes. We discuss the dual nature of BEs: their potential to both harm and heal, underscoring adaptive responses and immune priming in specific contexts. By integrating mechanistic depth with translational relevance, this work posits that radiation BEs are a modifiable axis of RT biology. Recognizing and mitigating BEs is imperative for optimizing therapeutic efficacy, minimizing collateral damage, and enhancing survivorship outcomes. This review advocates for a paradigm shift in RT planning and post-treatment care, emphasizing precision, personalization, and systemic awareness in modern oncology.

Humans↗
PubMedDate not supplied

Bowel care in older people.

Bowel dysfunction not only causes considerable hardship for many older people and their carers, it is also financially costly to the health service and to the individuals affected. Despite the prevalence of constipation and faecal incontinence amongst, for example, older people in institutionalised settings, both conditions are often iatrogenic and entirely preventable. One reason why these conditions are generally not well managed is that the research base is poor: there are few robust data because of methodological weaknesses in existing studies, so clinicians and care staff are left to rely on anecdote and personal experience. Secondly, the costs to the NHS involved in providing proper bowel care for the elderly would be considerable, although recent government documents have set out a specific commitment to improve standards of care in this area. In order to address some of these issues, the College has recently published a book which gathers together and assesses research on faecal incontinence and constipation, and provides informed guidance on current best practice. The contents of the publication, including comments from older people suffering from bowel dysfunction, are outlined in this article.

Adult↗
PubMed1992

[Direct ileum pouch-anal anastomosis in ulcerative colitis. Technique and complications].

Fourty-nine patients (21 female, 28 male) with ulcerative colitis underwent formation of an J-ileal pouch and construction of a direct stapled pouch-anal anastomosis (IPAA) without rectal cuff. 16 patients had previously undergone surgical interventions. Overall after IPAA 7 patients (14%) experienced 11 major complications. Gastrointestinal complications included hemorrhage in 1 patient, pelvic sepsis and ileus in 3 patients, respectively. Pancreatitis and urinary infection occurred in 2 patients, sexual dysfunction in 3 patients. After closure of the ileostomy 3 patients developed late pouch-vaginal or pouch-vesical fistulas, leading to excision of the pouch. During the long-term follow-up small bowel obstruction developed in 3 patients, pouchitis in another 6 patients. After 3 months 84% of our patients were continent during daytime, 67% during nighttime. 24 months postoperatively these data concerning continence increased to 92% and 83%, respectively. We conclude that direct IPAA is a reliable procedure achieving its purpose in 96%.

Adenomatous Polyposis Coli↗