Clinical differences between benign and malignant pheochromocytomas.
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Most pheochromocytomas can be cured by resection. In view of the unfavourable prognosis for surgical therapy in cases of late tumour detection and malignant tumours, the aim of the present study is to differentiate between typical signs and symptoms of malignant versus benign pheochromocytomas. We investigated the records of 133 patients retrospectively (1967-1998). In cases of benign tumours (104 of 133, mean age 42+/-15.8 years) tumour size was 5.9+/-3.4 cm, and history was 47.4+/-75.4 months. 7.7% of the tumours were extraadrenal, and 77% had paroxysmal manifestations. The other 29 patients (mean age: 39.2+/-21.9 years) had malignant lesions (tumour size: 9.4+/-5.9 cm (p=0.0022); history: 7.4+/-5.6 months (p=0.0137); extraadrenal: 24.1% (p=0.0219); paroxysmal: 37.9% (p=0.0012)). Symptoms of patients with benign tumours were hypertension (80%), headaches (42.3%), sweating (30.8%), tachycardia (26%) and pallor (24%) (Malignant: Hypertension 46%, p=0.0873; headaches 11%, p=0.0008; sweating 11%, p=0.0196; tachycardia 14%, p=0.1961 and pallor 0%, p=0.0010). Abdominal pain and dorsalgia occurred more frequently in malignant pheochromocytomas (26% versus 7%, p=0.0014). Unusually short histories and extraadrenal localization appear to be suspicious for malignancy. The "typical" clinical signs and symptoms occur more frequently in patients with benign tumours and can therefore be regarded as typical signs of benign pheochromocytomas. (+info)
Drug therapy options for patients with irritable bowel syndrome.
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Existing pharmacotherapeutic options for the treatment of patients with irritable bowel syndrome (IBS) are limited in treating the multiple symptoms associated with the disorder. There is much interest in the use of serotonin agents as new therapeutics. Acting primarily through 5-HT3 and 5-HT4 receptors, serotonin elicits changes in motor function and possibly visceral sensation. Two serotonin agents were developed specifically for IBS: tegaserod, a 5-HT4 receptor partial agonist, and alosetron, a 5-HT3 receptor antagonist (which is no longer available). Phase III clinical trial data show that during a 12-week treatment period with tegaserod, IBS patients with abdominal pain and discomfort, bloating, and constipation experienced significant global relief (i.e., improvement in overall well-being, abdominal pain, and bowel habit) compared with placebo. Improvement in bowel movement frequency and consistency was achieved and pain was relieved by 1 week. During 12 weeks of treatment, alosetron was shown to elicit significant relief of abdominal pain and discomfort compared with placebo or mebeverine in female IBS patients with diarrhea. Alosetron slowed colonic transit and treatment efficacy was apparent after a week of treatment. Another 5-HT4 receptor agonist, prucalopride, which is being developed for chronic constipation, accelerates colonic transit and increases stool frequency. Therefore, this agent may be of benefit in IBS patients with constipation. (+info)
Probable atypical cat scratch disease presenting as isolated posterior pancreatic duodenal lymphadenitis and abdominal pain.
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We report a case involving a 15-year-old girl with atypical, clinically unsuspected cat scratch disease (CSD) presenting as isolated posterior pancreatic duodenal lymphadenitis, fever, and abdominal pain. The serological, abdominal ultrasonographic, and CT findings, as well as clinical and epidemiological data, indicate that B. henselae was likely an etiologic agent of CSD in our patient. (+info)
The abdominal wall: an overlooked source of pain.
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When abdominal pain is chronic and unremitting, with minimal or no relationship to eating or bowel function but often a relationship to posture (i.e., lying, sitting, standing), the abdominal wall should be suspected as the source of pain. Frequently, a localized, tender trigger point can be identified, although the pain may radiate over a diffuse area of the abdomen. If tenderness is unchanged or increased when abdominal muscles are tensed (positive Carnett's sign), the abdominal wall is the likely origin of pain. Most commonly, abdominal wall pain is related to cutaneous nerve root irritation or myofascial irritation. The pain can also result from structural conditions, such as localized endometriosis or rectus sheath hematoma, or from incisional or other abdominal wall hernias. If hernia or structural disease is excluded, injection of a local anesthetic with or without a corticosteroid into the pain trigger point can be diagnostic and therapeutic. (+info)
A novel tachykinin NK2 receptor antagonist prevents motility-stimulating effects of neurokinin A in small intestine.
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1. MEN 11420 (nepadutant) is a potent, selective and competitive antagonist of tachykinin NK2 receptors. 2. The objective of the present study was to assess the capability of the drug to antagonize the stimulatory effects of neurokinin A (NKA) on gastrointestinal motility, as well as to change the fasting migrating motor complex (MMC). 3. Thirty-four male volunteers were randomized to treatment with either placebo or MEN 11420 in a double-blinded manner. Effects of MEN 11420 (8 mg intravenously) were evaluated as changes in phases I, II and III of MMC, as well as contraction frequency, amplitude and motility index during baseline conditions and during stimulation of motility using NKA (25 pmol kg(-1) min(-1) intravenously). 4. NKA preceded by placebo increased the fraction of time occupied by phase II, increased contraction frequency, amplitude and motility index. 5. MEN 11420 effectively antagonized the motility-stimulating effects of NKA. MEN 11420 reduced the phase II-stimulating effect of NKA. In addition, the stimulatory effect of NKA on contraction frequency and amplitude, as well as motility index were inhibited by MEN 11420. MEN 11420 did not affect the characteristics of MMC during saline infusion. 6. Plasma levels of MEN 11420 peaked during the first hour after infusion and decreased to less than half during the first 2 h. 7. In conclusion, intravenous MEN 11420 effectively inhibited NKA-stimulated, but not basal gastrointestinal motility, and was well tolerated by all subjects. (+info)
Virus-directed, enzyme prodrug therapy with nitroimidazole reductase: a phase I and pharmacokinetic study of its prodrug, CB1954.
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CB1954 [5-(aziridin-1-yl)-2,4-dinitrobenzamide] is converted by the bacterial enzyme nitroimidazole reductase (NTR) into a potent cytotoxic bifunctional alkylating agent, which can be delivered to tumors in adenoviral vectors as virus-directed, enzyme prodrug therapy. This report summarizes a Phase I and pharmacokinetic study of the prodrug, CB1954. Thirty patients, ages 23-78 years (median 62 years), with predominantly gastrointestinal malignancies were treated. CB1954 was administered by i.v. injection every 3 weeks or i.p. followed by 3-weekly i.v. injections, toward a maximum of six cycles. The dose was escalated from 3 to 37.5 mg/m2. No significant toxicity was seen until 24 mg/m2 (recommended i.v. dose). Dose-limiting toxicities (DLT) were diarrhea and hepatic toxicity, seen at 37.5 mg/m2. DLT has not been observed at the current i.p. dose of 24 mg/m2. There was no alopecia, marrow suppression, or nephrotoxicity. Clearance data suggest hepatic metabolism, and <5% of CB1954 was renally excreted. There was a nonlinear relationship between i.v. dose and area under the curve (AUC). At the recommended i.v. dose of 24 mg/m2, the AUC was 5.8 microM/h. Intraperitoneal administration (24 mg/m2) achieved an AUC of 387 microM/h, giving a considerable regional advantage. In vitro, the AUC required to achieve the IC50 for CB1954, in NTR-expressing cancer cells, ranges from 10-50 microM/h. Thus, CB1954 is well tolerated at a dose of 24 mg/m2, and sufficient serum/peritoneal levels are achieved for an enzyme-prodrug approach to be feasible. We are now conducting a Phase I trial combining adenovirus-mediated NTR and i.v. CB1954 (24 mg/m2) in patients with primary and secondary liver tumors. (+info)
Double-blind placebo-controlled multicentre studies of rebamipide, a gastroprotective drug, in the treatment of functional dyspepsia with or without Helicobacter pylori infection.
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BACKGROUND: Functional dyspepsia is a problem that is difficult to treat in clinical practice. AIM: To evaluate the efficacy and safety of rebamipide (a cytoprotective drug) in functional dyspepsia. METHODS: Patients with functional dyspepsia (n=557) were divided a priori into two studies by Helicobacter pylori status, and enrolled in a 2-week baseline evaluation period. Ninety-nine patients with Helicobacter pylori and 173 patients without Helicobacter pylori, continuing to have at least moderate upper abdominal pain or discomfort, were randomly assigned to rebamipide 100 mg, rebamipide 200 mg or placebo, three times a day, in a double-blind design for 8 weeks. RESULTS: There was significant improvement of individual symptom scores from baseline in all the treatment arms. No significant improvement of individual symptom scores was observed in either rebamipide group at the end of the studies compared to placebo, although the belching score was significantly reduced in the rebamipide 100 mg and 200 mg groups at week 2 (P=0.017 and P=0.012, respectively) in the Helicobacter pylori-positive patients. The ratio of patients who requested usage of the study medication again was greater in the rebamipide 100 mg (85%) and 200 mg (96%, P=0.020) groups compared with the placebo group (72%) among Helicobacter pylori-positive patients. There were no serious study medication related adverse events. CONCLUSIONS: Rebamipide was not superior to placebo in terms of individual symptoms at the end of treatment. (+info)
Tegaserod, a 5-HT(4) receptor partial agonist, relieves symptoms in irritable bowel syndrome patients with abdominal pain, bloating and constipation.
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AIM: To investigate the efficacy and safety of tegaserod, a novel 5-HT(4) receptor partial agonist, in a randomized, double-blind, placebo-controlled, 12-week treatment, multicentre study. METHODS: Eight hundred and eighty-one patients with irritable bowel syndrome, characterized by abdominal pain, bloating and constipation, received tegaserod, 2 mg b.d. or 6 mg b.d., or placebo for 12 weeks. RESULTS: Tegaserod, 2 mg b.d. and 6 mg b.d., showed a statistically significant relief of overall irritable bowel syndrome symptoms, measured by a weekly, self-administered questionnaire. At end-point, treatment differences from placebo were 12.7% and 11.8% for 2 mg b.d. and 6 mg b.d., respectively. The effect of tegaserod was noted as early as week 1, and was sustained over the 12-week treatment period. Individual irritable bowel syndrome symptoms assessed daily also showed a statistically significant improvement of abdominal discomfort/pain, number of bowel movements and stool consistency, and a favourable trend for reducing days with significant bloating. Adverse events were similar in all groups, with transient diarrhoea being the only adverse event seen more frequently with tegaserod than placebo. CONCLUSIONS: Based upon the results of this study, tegaserod offers rapid and sustained relief of the abdominal pain and constipation associated with irritable bowel syndrome. Tegaserod is also well tolerated. (+info)