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PubMed2001

Fluvoxamine: a review of its therapeutic potential in the management of anxiety disorders in children and adolescents.

Fluvoxamine is a selective serotonin reuptake inhibitor (SSRI) which may be used for the management of anxiety disorders in children and adolescents. Absorption of fluvoxamine was similar in adolescents to that in adults, which suggests that the maximum dosage of the drug for patients aged between 12 and 17 years can be as high as 300 mg/day. However, steady-state plasma fluvoxamine [corrected] concentrations were 2 to 3 times higher in children (aged between 6 and 11 years) than in adolescents; thus, the maximum fluvoxamine dosage recommended for children is 200 mg/day. Fluvoxamine (50 to 300 mg/day) for 8 to 16 weeks significantly reduced symptoms of obsessive-compulsive disorder (OCD) [measured across multiple assessment scales] compared with placebo in a well controlled trial in paediatric patients (n = 120) or from baseline in noncomparative trials in adolescent (n = 20) or paediatric (n = 16) patients. Improvements with fluvoxamine (up to 200 mg/day) were observed for up to 1 year in 98 patients with OCD in a noncomparative trial. The drug (up to 250 or 300 mg/day) also improved symptoms of anxiety compared with placebo in an 8-week well controlled trial in 128 paediatric patients with social phobia, separation anxiety disorder or generalised anxiety disorder (GAD). Fluvoxamine (50 to 300 mg/day) appears to be well tolerated in paediatric patients, with most adverse events with the drug (except abdominal discomfort, which occurred more often in patients receiving fluvoxamine) occurring with a similar incidence to those with placebo. The most common adverse events involved the central nervous system or gastrointestinal system. Most adverse events reported by paediatric patients with OCD were similar to those reported by adults. In conclusion, fluvoxamine is generally well tolerated and has demonstrated short-term efficacy compared with placebo in the treatment of OCD, and social phobia, separation anxiety disorder or GAD in well controlled trials in paediatric patients. Reductions in symptoms of anxiety with fluvoxamine have been observed for up to 1 year in children and adolescents with OCD. However, there are currently no comparative trials of fluvoxamine with other pharmacological agents. In the absence of such trials, current consensus opinion recommends that when pharmacotherapy is indicated, fluvoxamine, like other SSRIs, can be used as first-line treatment for anxiety disorders, particularly OCD, in paediatric patients. However, direct comparisons are required to assess the relative efficacy and tolerability of pharmacological agents in order to make firm recommendations for the treatment of anxiety disorders in this patient group.

Adolescent↗
PubMed2005

Telomere dynamics in response to chemotherapy.

The use of chemotherapy provides an essential arm in the treatment of a number of cancers. The biological feature common to all cancerous cells that sensitizes them to chemotherapeutic agents is their elevated division rate. Rapidly dividing cells, such as tumor cells, are more sensitive to chemotherapeutic agents that act to initiate pathways leading to cell death, a process enhanced in cells with compromised DNA damage responses. The toxicity accompanying chemotherapy is due to side-effects induced in normal regenerative tissues which also have relatively high replication rates, such as hair follicles, the hematopoietic system, the gastrointestinal system, the germline and skin cells. While the side-effects of chemotherapy may be tolerated by the patient, the long term impact of the cytotoxic effects of chemotherapy on healthy tissues is only now becoming apparent. Chemotherapy-induced cytotoxicity in regenerative tissues requires multiple cell divisions in order to reconstitute the affected tissues. At least in part as a consequence of these extra divisions, telomeres in individuals treated with chemotherapy are shorter than age-matched control individuals who have never been exposed to these drugs. Given the essential role of telomeres in regulating cellular aging and chromosomal stability, it is possible that the prematurely shortened telomeres that arise following chemotherapy may impact the long-term replicative potential of these tissues. This review is focused on how telomeres may be modulated, directly or indirectly, by anticancer drugs and the potential long-term consequences of accelerated telomere shortening in healthy tissue as a result of current cancer treatment protocols.

Neoplasms↗
PubMed2002

Vesicants and nerve agents in chemical warfare. Decontamination and treatment strategies for a changed world.

Vesicants and nerve agents have been used in chemical warfare for ages. They remain a threat in today's altered political climate because they are relatively simple to produce, transport, and deploy. Vesicants, such as mustard and lewisite, can affect the skin, eyes, respiratory system, and gastrointestinal system. They leave affected persons at risk for long-term effects. Nerve agents, such as tabun, sarin, soman, and VX, hyperstimulate the muscarinic and nicotinic receptors of the nervous system. Physicians need to familiarize themselves with the clinical findings of such exposures and the decontamination and treatment strategies necessary to minimize injuries and deaths.

Antidotes↗
PubMedDate not supplied

[The treatment of cytomegalovirus retinitis in human immunodeficiency virus infection].

Most of the patients with immunodeficiency virus infection (75%-85%) are coinfected with cytomegalovirus. It is estimated that cytomegalovirus disease develops in 45% of them, mainly those presenting low CD4 cell counts (< 100/mm3). Retinitis is the most common manifestation of reactivated cytomegalovirus disease (85%), followed by other extra ocular sites (central nervous system, lungs, gastrointestinal system, adrenal glands, etc.). The particularly high incidence of cytomegalovirus retinitis, the difficulties concerning its therapeutical approach and the relatively unsatisfactory results, justify this review, according to the new treatment options presented in recent literature.

AIDS-Related Opportunistic Infections↗
PubMedDate not supplied

Isolated fetal and neonatal ascites: report of two cases.

Neonatal ascites is an uncommon problem that may be caused by a number of etiologies including diseases of genitourinary system and gastrointestinal system, cardiac disease, hepatic disease, systemic infection such as TORCH or parvovirus, chylous, ovarian cause, inborn error of metabolism and idiopathic. We reported two cases of neonatal ascites, one was caused by cytomegalovirus and no obvious causes could be detected in the second one. The ascites were diagnosed by prenatal ultrasound at the gestational age of 25 weeks and 37 weeks respectively and were resolved spontaneously after birth. One-year follow-up of both cases revealed normal growth and development. No recurrent ascites could be detected by abdominal sonography except for evidence of mild hepatomegaly that was noted in case 1. Thus, isolated fetal and neonatal ascites without other concomitant abnormalities were diagnosed, a separate entity from non-immune hydrops fetalis with excellent prognosis.

Ascites↗
PubMed1975

Arsenic poisoning from anti-asthmatic herbal preparations.

Arsenic poisoning, a disease of the past, was recently found in 74 patients in Singapore over a 15-month period. Most victims (70%) had a chronic form of poisoning and 64% of the cases were caused by a local anti-asthmatic herbal preparation containing 12,000 ppm of inorganic arsenic sulphide. The other patients were poisoned by six other brands of herbal preparations used for the treatment of asthma and a variety of other illnesses. Subsequent investigations revealed another 22 other brands of Chinese herbal preparations containing high concentrations of inorganic arsenic ranging from 25 to 107,000 ppm, of which most were imported. Nearly 40% of the patients had taken the medicine for less than six months, but the others had a longer history of exposure ranging from one to 15 years. Systemic involvement was confined mainly to the skin (91%), nervous system (51%), gastrointestinal system (23%) and blood (23%). Malignancy of the skin was present in six patients, and of the visceral samples, toxicological confirmation was found in half of the cases investigated. There was no correlation between the clinical status of the patients and their tissue arsenic content. The importance of arsenic poisoning by herbal preparations is discussed, as there are no known reports of their association.

Adolescent↗
PubMed1987

The effects of caffeine on various body systems: a review.

Caffeine is the most widely consumed drug in Western society. The intake of caffeine-containing beverages in many adults and children often reaches levels that can induce pharmacological effects. Ninety-nine percent of ingested caffeine is absorbed and distributed to all tissues and organs. The effects of caffeine intake differ greatly according to acute or chronic intake, level of intake, and the development of tolerance. Caffeine administered acutely to non-users or recent abstainers can induce hypertension, arrhythmias, altered myocardial function, increased plasma catecholamine levels, plasma renin activity, serum cholesterol levels, increased production of urine, gastric acid secretion, and alterations in mood and sleep patterns. Tolerance to chronic caffeine intake develops in most individuals, with the cessation of its effects on the renal system, the cardiovascular system, the gastrointestinal system and, to some extent, the central nervous system. Moderate caffeine consumers probably need to have little concern for the effect of caffeine intake on their health if their other life-style habits are also moderate.

Adult↗
PubMed1993

The pathology of the gastrointestinal endocrine system.

Among endocrine tumors occurring in the gastrointestinal tract, midgut argentaffin EC cell carcinoids, gastric argyrophil ECL cell carcinoids, duodenal gastrin cell tumors, and rectal trabecular L cell carcinoids (in order of decreasing frequency) are those occurring more frequently. Together, they account for more than 80% of such tumors. Duodenal somatostatin cell tumors, gangliocytic paragangliomas, and differentiated neuroendocrine carcinomas are also well-defined tumor entities. The carcinoid syndrome, either classical, with intermittent flushing, hypotension, and diarrhea, or atypical, with persistent histamine-type red flushing, bronchospasm, and no diarrhea, and Zollinger-Ellison syndrome, with severe peptide ulcer disease, are the only hyperfunctional syndromes consistently found in association with these tumors. The carcinoid syndrome occurs in about 10% of gastrointestinal carcinoids, usually in their advanced, metastatic stage. The Zollinger-Ellison syndrome occurs in association with about 40% of intestinal gastrin cell tumors, including small intramural growths. Tumor prognosis depends on the mode and site of presentation, histology, cell type(s), size, level of invasion, metastases (especially distant metastases), and associated clinical syndrome or background disease. Hormones, trophic factors, inherited genetic traits, somatic mutations, and some chronic inflammatory processes are pathogenetically important in a large proportion of cases.

Animals↗
PubMed1991

Regulation of mucosal responses by CD4+ T lymphocytes: effects of anti-L3T4 treatment on the gastrointestinal immune system.

The role of CD4+ T cells in the gastrointestinal (GI) immune system in vivo was studied in mice selectively depleted of this subset by treatment with monoclonal anti-L3T4 (GK1.5) mAb. Treatment of young BALB/c mice with weekly injections of anti-L3T4 mAb resulted in a selective depletion of CD4+ T cells in both IgA effector (lamina propria regions of the intestine; LP) and inductive (Peyer's patch; PP) sites. However, levels of CD3+CD4-CD8+ and CD4-CD8- (double negative) T cells remained constant or increased. When sections of small intestine were assessed for the isotype of Ig-containing cells, normal mice contained predominantly IgA plasma cells with small numbers of IgM and IgG plasma cells while anti-L3T4 treatment dramatically reduced the numbers of IgA plasma cells. When numbers of IgA-producing cells were assessed by the isotype-specific ELISPOT assay, the LPL of anti-L3T4 mAb-treated mice showed an 80% reduction in the number of IgA spot-forming cells. The effect of anti-L3T4 mAb treatment on IgA inductive sites was also studied and this treatment reduced the overall size of PP as well as the germinal centers in this tissue. Although anti-L3T4 treatment depleted CD3+CD4+ T cells in PP, the relative frequency of surface IgA-positive (slgA+) B cells in this tissue did not change. These results show that repeated injection of anti-L3T4 mAb results in a CD4+ T cell deficiency in both IgA inductive (PP) and effector (LP) sites. The depletion of CD4+ T cells resulted in reductions in the numbers of mature IgA plasma cells present in the LP of gut-associated tissues, and reduced the overall size of PP including germinal centers, but did not affect the frequency of sIgA+ B cells in this IgA inductive site.

Animals↗
PubMed1990

Gastrointestinal immune system and its disorders.

Over the past 15 years the basic details of the mucosal immune response have been described. The challenge of the next decade is to expand these details and to relate this basic information to pathologic processes in the gastrointestinal tract. It is now clear that secretory IgA is the main immunoglobulin produced by the mucosa. Further, we know that oral rather than parenteral priming preferentially stimulates a secretory IgA response. IgA protects mainly by binding to an intraluminal microorganism or toxin and thereby interfering with its absorption across the gut epithelium. The cellular basis for the IgA response has also been elucidated to some degree. It is clear that the response is highly T cell dependent and requires both helper T cells and switch T cells. With the use of monoclonal antibodies, we have begun to learn about cell-mediated functions in the gut. Suppressor/cytotoxic lymphocytes are largely sequestered in the epithelium whereas helper/inducer lymphocytes mainly reside in the lamina propria. In diseases such as celiac disease and inflammatory bowel disease, several alterations in the gastrointestinal immune system have been described. Some, such as the finding of antibody to gliaden, may be causally related to the disease. Others, such as antibodies to luminal bacteria, likely are secondary events. The challenge of the next decade is to expand these details and to relate this basic information to pathologic processes along the gastrointestinal tract.

Digestive System↗
PubMed1977

A new electronic transducer system for gastrointestinal pressure studies.

A new electronic transducer system has been developed for intraluminal pressure studies in the gastrointestinal tract. In contrast to other devices, inductance was used for the transformation of pressure into electrical signals. High sensitivity with a frequency response of 10(4) Hz guarantees accurate recording of sphincter as well as of peristaltic pressures. Pull-throughs can be carried out manually. Studies may be performed in the sitting as well as in the supine position since no hydraulic effects are present. No measurable temperature sensitivity was found; linearity is present in the physiological pressure range required. Small size, mechanical and electrical stability and simple handling make the PI-transducer system a suitable diagnostic tool for clinical as well as for investigatory purposes. By this method functional disorders of the esophagus, as in scleroderma, achalasia or hiatus hernia, of the pylorus and of the anal sphincter may be evaluated. The results of lower esophageal sphincter measurements in 30 asymptomatic volunteers and in 19 patients with symptomatic gastroesophageal reflux agree with the data obtained by conventional methods.

Esophageal Diseases↗
PubMed1978

Gastrointestinal therapeutic system for acetazolamide. Efficacy and side effects.

Acetazolamide has been formulated in a new gastrointestinal therapeutic system that delivers the drug at an essentially constant rate of 15 mg/hr (GITS 15/125). We compared the therapeutic effect, magnitude of plasma concentration fluctuations, and incidence of side effects produced by the GITS 15/125 with conventional 250-mg acetazolamide tablets on eight glaucomatous patients randomly assigned to a different regimen each week. One or two GITS 15/125 twice a day (bid) were found as effective in reducing intraocular pressure as one 250-mg acetazolamide tablet. Plasma concentration fluctuations with the GITS 15/125 were decreased, compared with acetazolamide tablets, and, as a result, the incidence of drowsiness, tingling feet, tingling hands, and confusion was substantially reduced.

Acetazolamide↗
PubMed2004

The early systemic and gastrointestinal oxygenation effects of hemorrhagic shock resuscitation with hypertonic saline and hypertonic saline 6% dextran-70: a comparative study in dogs.

The smaller volemic state from hypertonic (7.5%) saline (HS) solution administration in hemorrhagic shock can determine lesser systemic oxygen delivery and tissue oxygenation than conventional plasma expanders. In a model of hemorrhagic shock in dogs, we studied the systemic and gastrointestinal oxygenation effects of HS and hyperoncotic (6%) dextran-70 in combination with HS (HSD) solutions in comparison with lactated Ringer's (LR) and (6%) hydroxyethyl starch (HES) solutions. Forty-eight mongrel dogs were anesthetized, mechanically ventilated, and subjected to splenectomy. A gastric air tonometer was placed in the stomach for intramucosal gastric CO(2) (Pgco(2)) determination and for the calculation of intramucosal pH (pHi): The dogs were hemorrhaged (42% of blood volume) to hold mean arterial blood pressure at 40-50 mm Hg over 30 min and were then resuscitated with LR (n = 12) in a 3:1 relation to removed blood volume; HS (n = 12), 6 mL/kg; HSD (n = 12), 6 mL/kg; and HES (mean molecular weight, 200 kDa; degree of substitution, 0.5) (n = 12) in a 1:1 relation to the removed blood volume. Hemodynamic, systemic, and gastric oxygenation variables were measured at baseline, after 30 min of hemorrhage, and 5, 60, and 120 min after intravascular fluid resuscitation. After fluid resuscitation, HS showed significantly lower arterial pH and mixed venous Po(2) and higher systemic oxygen uptake index and systemic oxygenation extraction than LR and HES (P < 0.05), whereas HSD showed significantly lower arterial pH than LR and HES (P < 0.05). Only HS and HSD did not return arterial pH and pHi to control levels (P < 0.05). In conclusion, all solutions improved systemic and gastrointestinal oxygenation after hemorrhagic shock in dogs. However, the HS solution showed the worst response in comparison to LR and HES solutions in relation to systemic oxygenation, whereas HSD showed intermediate values. HS and HSD solutions did not return regional oxygenation to control values.

Algorithms↗
PubMed1994

Comparison of nifedipine gastrointestinal therapeutic system and atenolol on antianginal efficacies and exercise hemodynamic responses in stable angina pectoris.

A gastrointestinal therapeutic system (GITS) of nifedipine has been developed to provide a once-daily dosing, and predictable, relatively constant plasma concentrations. This study compared the antianginal efficacy of nifedipine GITS with a once-a-day beta-receptor blocker, atenolol. Seventeen patients with documented coronary artery disease and stable stress-induced angina pectoris were studied during a 2-week, single-blind, placebo baseline phase and a 12-week randomized, double-blind, active drug crossover efficacy phase, using the bicycle exercise test and ambulatory electrocardiographic recordings. Patients exercised significantly longer with nifedipine GITS (883 +/- 47 seconds) and atenolol (908 +/- 44 seconds) than with placebo (794 +/- 41 seconds). Nifedipine GITS reduced systolic blood pressure at all stages of exercise compared with placebo but, because heart rate tended to increase more during nifedipine therapy, there was no difference in rate-pressure products between the placebo and nifedipine GITS periods. In contrast, atenolol reduced heart rate, systolic blood pressure and rate-pressure product during exercise compared with placebo. Whereas left ventricular ejection fractions (by radionuclide angiocardiography) increased with exercise, the maximal increase was smaller with atenolol than with placebo and nifedipine. The net increase in left ventricular ejection fraction at the end of exercise was greater with nifedipine than with placebo or atenolol. Ambulatory electrocardiograms showed only a small number of ischemic events. Neither nifedipine GITS nor atenolol reduced the number of ischemic events or total duration of ST-segment deviations significantly. It is concluded that nifedipine GITS is as effective an antianginal agent as atenolol, but the hemodynamic effects of the 2 agents differ.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Multicenter comparison of the nifedipine gastrointestinal therapeutic system and long-acting propranolol in patients with mild to moderate systemic hypertension receiving diuretics. A preliminary experience.

The efficacy and safety of nifedipine in a gastrointestinal therapeutic system (GITS) push-pull osmotic pump formulation was compared with long-acting propranolol in 49 patients with mild to moderate hypertension already receiving diuretics. Using a two-week placebo run-in, double-blind study design, patients were randomly assigned to receive nifedipine GITS (n = 24) in doses of 30 mg, 60 mg, or 90 mg once daily; or long-acting propranolol (n = 25) in doses of 80, 160, or 240 mg once daily. Previous diuretic therapy was continued. Sitting and five-minute standing blood pressure and heart rate measurements were made 24 hours after dosing. At the endpoint of treatment, both nifedipine GITS and sustained-release propranolol reduced blood pressure compared with placebo (p less than 0.001) in the sitting and standing positions. Nifedipine GITS was more effective in lowering standing systolic blood pressure than was propranolol (p less than 0.02). Propranolol caused a greater reduction in resting heart rate than did nifedipine GITS (p less than 0.003). Both drugs were well tolerated. Nifedipine GITS is an effective and safe once-daily drug for use in patients with hypertension who are already receiving diuretics, may be more effective than sustained-release propranolol, and may be better tolerated than conventional nifedipine capsules.

Adult↗
PubMed2004

Value of endoscopic ultrasonography for upper gastrointestinal stromal tumors: a single center experience.

BACKGROUND/AIMS: Gastrointestinal stromal tumors are the rarely seen tumors of the gastrointestinal tract. The aim of the present study was to review the patients diagnosed as upper gastrointestinal stromal tumor by endoscopic ultrasonography. METHODS: Twenty-five patients diagnosed as upper gastrointestinal stromal tumor, between 1999 and 2004, were reviewed retrospectively. RESULTS: The reason for performing upper gastrointestinal system endoscopy was nonspecific upper gastrointestinal system symptoms in most (76%) of the patients. The other causes were upper gastrointestinal bleeding and dysphagia in 16% and 8% of the cases, respectively. Lesions were located in the stomach in 17 (68%), in the esophagus in six (24%), and in the duodenum in two (8%) patients. Endoscopic ultrasonographic evaluation revealed that all of the lesions arose from the muscularis propria. In 18 (72%) patients, tumors were less than 3 cm in diameter, homogeneous and hypoechoic in appearance with regular borders, concordant with benign tumor. In five (20%) patients, lesions had heterogeneous echoic appearance with anechoic spaces, two of which were larger than 3 cm and also showed irregular borders, suggesting malignancy. Surgical therapy was performed in five (20%) patients because of upper gastrointestinal bleeding or suspicion of malignancy by endoscopic ultrasonographic evaluation. Histopathological examination confirmed the diagnosis in all these patients. CONCLUSIONS: Endoscopic ultrasonographic evaluation is very useful in diagnosis and for choosing the therapeutic method for patients with upper gastrointestinal stromal tumor.

Adult↗
PubMed2006

Effect of doxazosin gastrointestinal therapeutic system on patients with uncontrolled hypertension: the ASOCIA Study.

OBJECTIVE: To evaluate extended-release doxazosin gastrointestinal therapeutic system (GITS) as add-on therapy in patients with treated, but uncontrolled hypertension. METHODS: A 16-week, open, noncomparative, multicenter, prospective study of patients with hypertension (> or = 140/> or = 90 mm Hg). Doxazosin GITS 4 mg/d was added to entry medication and increased to 8 mg/d at Week 4 in cases of inadequate blood pressure (BP) control. RESULTS: A total of 3631 patients (40% women) with mean age of 62.4 +/- 0.2 years were included. Proportion of patients reaching goal (< 140/< 90 mm Hg) after 4 weeks of add-on therapy with doxazosin GITS was 39% and increased to 61% at Week 16. Systolic and diastolic BP (mean +/- SEM) decreased, respectively, from 161.6 +/- 0.2 and 95.1 +/- 0.1 mm Hg at baseline to 142.2 +/- 0.2 and 84.1 +/- 0.1 mm Hg at Week 4 (P < 0.0001) and 136.8 +/- 0.2 and 80.6 +/- 0.2 mm Hg at Week 16 (P < 0.0001). Adverse events occurred in 108 patients (3.0%), with 57 (1.6%) related to the study treatment. In 17 patients (0.5%), serious adverse events were described, but only one was related to the study drug. CONCLUSIONS: Doxazosin GITS as add-on therapy achieved target blood pressure and was well tolerated in patients with hypertension uncontrolled by previous regimens. Doxazosin GITS efficacy and tolerability was achieved in combination with all classes of antihypertensives tested.

Adrenergic alpha-1 Receptor Antagonists↗