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PubMed2001

Effects of selenium and zinc supplementation on nutritional status in patients with cancer of digestive tract.

OBJECTIVE: To evaluate the effect of oral administration of selenium and zinc tablets in patients with cancer of the digestive tract during chemotherapy. DESIGN: A case-control, randomized study. SETTING: Medical Oncology, II University of Naples, Naples, Italy. SUBJECTS: A total of 60 patients (median age 55 y, range 46-61 y) with diagnosis of gut cancer were randomized in 1999. Patients were treated for 60 days with chemotherapy. INTERVENTIONS: Trace elements were measured by atomic absorption spectroscopy. The nutritional status of the patients was assessed by biochemical and bio-impedance analysis (BIA) parameters in basal condition and after 60 days of treatment. Oral administration of selenium and zinc in oral tablet form for 50 days was Se 200 microg/day (50 microg/tablet) and Zn 21 mg/day (7 mg/tablet). RESULTS: Both in the basal condition and at 60 days all patients were malnourished. Selenium and zinc concentrations were significantly lower (P < 0.01) whereas copper concentration was significantly higher (P < 0.01) in cancer patients than in control subjects. However, 21/30 (70%) of those treated with Se and Zn did not showed a further worsening of nutritional status and experienced a significant decrease of asthenia with an increase of appetite. On the other hand, 24/30 (80%) untreated patients had a significant decline of all parameters studied after 60 days (prealbumin, cholesterol, transferrin, P < 0.05 vs 0 time; total proteins, albumin/globulin ratio, P < 0.01 vs 0 time; fat-free mass, fat mass, Na+/K+ ratio, body mass index P < 0.05 vs 0 time; fat free mass/fat mass, total body water, extra cellular/intra cellular water, basal metabolic rate: P < 0.01 vs 0 time). CONCLUSIONS: Data indicate that Se and Zn supplementation may improve the clinical course of general conditions in patients with gut cancer. These effects of Se and Zn require confirmation in an independent trial of appropriate design before new public health recommendations regarding Se and Zn supplementation can be made.

Case-Control Studies↗
PubMed2002

Dietary intakes and vitamin status of a sample of homeless people in Paris.

OBJECTIVE: To determine nutritional intake and vitamin status in a sample of homeless people who had been on the streets of Paris for more than 2 y. DESIGN: The nutritional status was evaluated by a 24 h recall questionnaire and by assay of circulating levels of vitamins A, B1, B6, B12, C and E. SETTING: The study was conducted in four accommodation centres of the SAMU Social of Paris (CHUSI units) from July 1999 to May 2000. SUBJECTS: A total of 329 homeless people were interviewed. Only 87 subjects, aged 26-76 y, were recruited based on seven selection criteria (over 18 y old, being homeless for more than 2 y, interviewed before taking a meal in the CHUSI units, good understanding of French, in a calm state, not coming from hospital or another CHUSI units, without any acute condition that might affect usual dietary habits), and completed the dietary questionnaire. Out of these 87, 71 agreed to blood sampling. RESULTS: In all 84% of the subjects declared that they drank alcoholic beverages regularly (175+/-167 g/day of alcohol), and 75.5% of the subjects also declared that they smoked. The mean total energy intake was 2111+/-1482 kcal/day for the men (8823.98+/-6194.76 kJ/day) and 1523+/-531 kcal/day for the women (6366.14+/-2219.58 kJ/day). Alcohol accounted for 44+/-30% and 19+/-17% of the total energy intakes (TEI) for the men and women, respectively. Proteins, lipids and carbohydrates accounted for 21+/-9, 23+/-14 and 57+/-16%, respectively, of the energy intake without alcohol for men, and 15+/-5, 22+/-11 and 62+/-14% EIWA for women. For all micronutrients, except for iron in the men, more than 50% of the population studied had intakes below the French recommendations for the adult population. All the women had calcium, vitamin E and vitamin B1 intakes below the recommendations for French women (900, 12 and 1.3 mg/day, respectively) in the general population. For the men, 98.7, 96.1 and 93.5% of the subjects had vitamin E, B1 and C intakes below the recommendations for French males in the general population (12, 1.5 and 80 mg/day, respectively). It is of note that subjects who ate in the CHUSI units more than once a day per week had significantly (P=0.018) higher intakes of vitamin C (27+/-38 mg/day) than did the subjects who ate in the CHUSI units less than once a day (8+/-12 mg/day). Measurement of serum vitamin levels demonstrated a deficiency in 95% of the subjects, mainly for vitamin C. The mean concentration in serum was 16+/-8 micromol/l, although 72% of the subjects had levels of 6 micromol/l. In contrast, 50.7, 42.2 and 35.2% of the subjects had high levels of vitamin B6, B12 and B1, respectively (100 nmol/l, 420 pmol/l and 40 micromol/l). CONCLUSION: Alcohol takes a high place in the diet of these homeless people. Although the total energy intake was too low, macronutrient intakes seem to be satisfactory in quality (well-balanced). However, calcium and vitamin C intakes were too low, and these deficiencies favour the development of disease (scurvy, asthenia, ecchymosis), in addition to alcohol-linked disease. Furthermore, the overexposure to vitamin B6, among the other B vitamins, is a matter of concern since it has been shown to be toxic in high doses.

Adult↗
PubMed2004

Comparison of the antihypertensive effects of the fixed dose combination enalapril 10 mg/nitrendipine 20 mg vs losartan 50 mg/hydrochlorothiazide 12.5 mg, assessed by 24-h ambulatory blood pressure monitoring, in essential hypertensive patients.

Fixed combinations of calcium channel blockers and angiotensin converting enzyme inhibitors represent an alternative to diuretic-based combination therapy. The aim of the present study was to compare the antihypertensive efficacy of the combination enalapril 10 mg/nitrendipine 20 mg (E/N) vs losartan 50 mg/hydrochlorothiazide 12.5 mg (L/H), assessed by 24-h ambulatory blood pressure monitoring. This multicentre, double-blind, parallel study included 97 hypertensive patients (office diastolic blood pressure (DBP) 90-109 mmHg and daytime DBP > 85 mmHg). After a 2- to 3-week period of single-blind placebo, they were randomized to receive double-blind treatment with E/N (n = 48) or L/H (n = 49) for a 4-week period. The primary outcome measure was the difference in 24-h DBP reduction between treatments from randomization to the end of the double-blind period. Secondary efficacy variables included differences in 24-h systolic (S) BP reduction, daytime, night-time and office SBP and DBP reduction, proportion of responders and controlled patients, trough-to-peak ratio and smoothness indexes. Safety was assessed by the proportion of patients with adverse events and the detection of laboratory abnormalities. No significant differences were observed in the primary outcome measure. The group receiving E/N tended to show greater reductions in most measures (24 h, daytime and office SBP and DBP) and higher BP control rates, but only the difference in the rate of office SBP control (< 140 mmHg) reached statistical significance (42.2 vs 22.4%; P = 0.048). The trough-to-peak ratios and smoothness indexes were similar in both groups. The incidence of adverse events related to the treatment was 27.1% (95% CI 14.5-39.6%) in E/N-treated patients and 14.3% (95% CI 4.5-45.8%) in the L/H group, but differences were not significant. The kind of event more frequently observed were flushing and headache in E/N, and dizziness and asthenia in L/H; all observed adverse events were mild. We conclude that E/N and L/H have a similar antihypertensive efficacy, assessed by office or ambulatory blood pressure monitoring. E/N achieved a significantly higher office SBP control rate, but this was accompanied by an apparently higher proportion of mild adverse events.

Antihypertensive Agents↗
PubMed2004

Once-daily eprosartan mesylate in the treatment of elderly patients with isolated systolic hypertension: data from a 13-week double-blind, placebo-controlled, parallel, multicenter study.

This was a double-blind, randomized, placebo-controlled multicenter, titration-to-effect study of eprosartan in patients > or =60 years of age with isolated systolic hypertension. The study consisted of a 3 to 5-week placebo run-in period, a 13-week double-blind treatment period (6-week titration with eprosartan 600-1200 mg/day, 3-week maintenance, 4-week combination therapy with hydrochlorothiazide/HCTZ 12.5 mg), and a follow-up period within 5-7 days of last treatment dose. Overall, 283 patients (placebo/P: 135; eprosartan /E: 148) were randomized [female patients-P: 55.6%, E:54.7%; white-P:66.7%, E:67.6%). Mean sitting systolic blood pressure (SitSBP) at baseline was comparable (P: 170+/-0.8 mmHg; E: 171+/-0.8 mm Hg). At monotherapy end point, eprosartan produced a significant reduction in SitSBP (E: 16.1 mmHg vs P: 8.4 mmHg; P<0.0001). In all, 57.4% of patients responded to eprosartan monotherapy. Among nonresponders, the addition of HCTZ resulted in a decrease in SitSBP from baseline (E: 21.7 mmHg; P: 14.4 mmHg; P<0.002). Reductions were also noted in Standing SBP (monotherapy: P<0.001; combination therapy: P=0.03). No reductions in SitDBP >4 mmHg were found during the study. Age, gender, and race did not have any impact on the results. Post hoc analysis showed a reduction in pulse pressure from 87.3 to 78.2 mmHg with placebo and from 87.6 to 70.7 mmHg with eprosartan monotherapy. Treatment with eprosartan in once-daily doses up to 1200 mg alone or in combination with HCTZ was well tolerated, with dizziness and asthenia being the most common side effects.

Acrylates↗
PubMed1999

alpha(1)-Blocker therapy in the nineties: focus on the disease.

Therapy for benign prostatic hyperplasia has evolved rapidly over the last decade, with the introduction in the early 1990s of new agents such as alpha(1)-blockers and 5alpha-reductase inhibitors. The major advantage of alpha(1)-blockers over 5alpha-reductase inhibitors is their rapid onset of action. Maximum flow rate is improved after first administration and optimal symptom relief is usually reached within 2-3 months. In addition, alpha(1)-blockers are effective regardless of prostate size and they provide a similar degree of symptom relief in patients with or without bladder outlet obstruction. The main adverse events with the alpha(1)-blockers relate to their effects on the cardiovascular system (postural hypotension) and central penetration (asthenia, somnolence). Newer uroselective alpha(1)-blockers, such as alfuzosin and tamsulosin, have a better safety profile and, as such, do not require initial dose titration. Alfuzosin has also been shown in a six-month study to significantly reduce both residual urine and the incidence of acute urinary retention (AUR) compared with placebo. In addition, alfuzosin is effective in improving the success rate of a trial without catheter in patients with AUR.

Journal Article↗
PubMed2006

Phase 2 trial of sustained-release fampridine in chronic spinal cord injury.

STUDY DESIGN: Double-blind, randomized, placebo-controlled, parallel-group clinical trial. OBJECTIVE: Assess safety and efficacy of sustained-release fampridine in subjects with chronic spinal cord injury. SETTING: A total of 11 academic rehabilitation research centers in the United States. METHODS: A total of 91 subjects with motor-incomplete spinal cord injury (SCI), randomized to three arms: fampridine, sustained release, 25 mg b.i.d. (Group I), 40 mg b.i.d. (Group II), and placebo (Group III) for 8 weeks. OUTCOME MEASURES: Patient diary questionnaire, Ashworth score, American Spinal Cord Injury Association International Standards, International Index of Erectile Function, bladder and bowel management questionnaires, and Clinician and Subject Global Impressions (Clinician Global Impression of change, Subject Global Impression (SGI)). Safety was evaluated from adverse events, physical examinations, vital signs, electrocardiograms, and laboratory tests. RESULTS: In total, 78% of the subjects completed the study. More (13/30) discontinued from Group II than Group I (4/30) and Group III (3/31). The most frequent adverse events across groups were hypertonia, generalized spasm, insomnia, dizziness, asthenia, pain, constipation, and headache. One subject in Group II experienced a seizure. SGI changed significantly in favor of Group I (P=0.02). Subgroup analysis of subjects with baseline Ashworth scores >1 showed significant improvement in spasticity in Group I versus III (P=0.02). CONCLUSIONS: Group I showed significant improvement in SGI, and potential benefit on spasticity. The drug was well tolerated. Group II showed more adverse events and discontinuations.

4-Aminopyridine↗
PubMed1999

A patient preference study comparing raltitrexed ('Tomudex') and bolus or infusional 5-fluorouracil regimens in advanced colorectal cancer: influence of side-effects and administration attributes.

Current chemotherapy regimens used in advanced colorectal cancer (ACRC) are similar in terms of efficacy, but differ importantly in terms of side-effects and administration profiles. These differences may impact significantly on patients' lives. We have evaluated patient preferences between raltitrexed ('Tomudex') and 5-fluorouracil-based chemotherapy regimens, with regard to side-effect attributes (raltitrexed and Mayo regimens) and administration attributes (raltitrexed, Mayo, De Gramont and Lokich regimens) in a study based on 82 patients with ACRC. Patients completed a series of rating tasks on how 'upsetting' these attributes were to them using a visual analogue scale (VAS) in a structured interview conducted by a research nurse. Mucositis and asthenia were the most and least upsetting side-effects, respectively. The side-effect profile of raltitrexed was clearly preferred by 78% of patients versus 14% for Mayo (P < 0.001). When side-effects and administration attributes were combined into an overall profile, 91% of patients selected raltitrexed as their clearly preferred regimen, versus 6% for Mayo (P < 0.001). The administration regimen of raltitrexed was ranked most acceptable (mean rank score 1.5 compared with Mayo 2.6, De Gramont 2.7, and Lokich 3.3). Given similar palliative effects, patients with ACRC exhibit preferences for raltitrexed over other regimens, based on administration and/or side-effect attributes. Such preferences should constitute an important part of decisions relating to the choice of chemotherapy regimen in ACRC.

Adult↗
PubMed1996

Comparisons of oral propafenone and quinidine as an initial treatment option in patients with symptomatic paroxysmal atrial fibrillation: a double-blind, randomized trial.

OBJECTIVE: The main aim of the study was to evaluate the safety and efficacy of propafenone versus quinidine as an initial choice in treatment of symptomatic paroxysmal atrial fibrillation. DESIGN: The study consisted of a 3-month treatment with oral propafenone hydrochloride or quinidine sulphate in patients with paroxysmal symptomatic atrial fibrillation, according to a double-blind randomized system. SETTING: The study was performed in the out-patient clinic of university hospital. MAIN OUTCOME MEASURES: The effects of the two drugs on attack frequency, ventricular rate and symptoms of symptomatic paroxysmal atrial fibrillation. RESULTS: In the oral propafenone group (n = 48), two patients (4%) discontinued the treatment because of dizziness. In the 46 patients who continued the treatment, the attack frequency decreased from 11 +/- 3 times per week at baseline to 1 +/- 1 times per week after treatment (P < 0.01). Forty (87%) out of the 46 patients had effective response to oral propafenone (more than 75% reduction of symptomatic arrhythmic attacks) on a mean dose of 615 +/- 10 mg day-1; the decrease in attack frequency was from 10 +/- 3 to 1 +/- 1 times per week. Twenty-three (50%) patients were free from recurrence of symptomatic paroxysmal atrial fibrillation. Comparisons of symptom scores for patients (n = 23) with attacks of paroxysmal atrial fibrillation after oral propafenone treatment showed that there was a significantly lower symptom score of palpitation, asthenia, effort dyspnea, dizziness, rest dyspnea and chest oppression in attacks of paroxysmal atrial fibrillation after propafenone treatment (11.05 +/- 3.78 versus 7.60 +/- 3.46, P < 0.01). From the oral quinidine group (n = 48), two patients (4%) discontinued treatment because of gastrointestinal discomfort. In the 46 patients who continued the treatment, the attack frequency decreased from 11 +/- 4 times per week at baseline to 3 +/- 2 times per week after treatment (P < 0.01). Twenty-one (46%) out of the 46 patients had effective response to oral quinidine on a mean dose of 1067 +/- 462 mg day-1, with a decrease in attack frequency from 12 +/- 3 to 1 +/- 1 times per week. Only 10 (22%) patients were free from recurrence of paroxysmal atrial fibrillation. Comparisons of symptom scores for patients (n = 36) with attacks of paroxysmal atrial fibrillation after quinidine treatment showed that there was no significant decrease of symptom score in attacks of atrial fibrillation (10.65 +/- 3.92 versus 10.20 +/- 3.80, P = 0.57). Furthermore, the percentage decrease of ventricular rate during atrial fibrillation was significantly greater in patients with propafenone (-25 +/- 4% versus -8 +/- 3%, P < 0.01). CONCLUSIONS: Oral propafenone appeared to be more effective than quinidine in suppressing attacks and alleviating symptoms of paroxysmal atrial fibrillation.

Administration, Oral↗
PubMed2001

Chronic fatigue and immune dysfunction syndrome associated with Staphylococcus spp. bacteraemia responsive to thiacetarsamide sodium in eight birds of prey.

Chronic fatigue and immune dysfunction syndrome (CFIDS) is a recognized human illness with zoonotic implications that is rarely described in animals. Eight birds of prey examined between 1992 and 1995 and sharing common symptoms (asthenia, inability to fly, poor appetite and emaciation) underwent laboratory tests revealing immunodeficiency, anaemia, high creatine kinase levels and low serum magnesium levels. Diagnosis of CFIDS was based upon these features. The effectiveness of an arsenic-based medication, thiacetarsamide sodium, administered intravenously for 2-3 days at low dosages (0.1 ml/kg/day) has been demonstrated by checks carried out 10, 20 and 30 days after therapy. The symptoms and the immune and haematological dysfunctions disappeared within 2-4 weeks of treatment. In all patients, micrococcus-like organisms found adhering to the outer surface of many red blood cells, had disappeared at post-treatment controls. Two of five blood cultures were positive for Staphylococcus spp. (S. intermedius and S. xilosus). Consideration is given to the pharmacological activity of an arsenic-based drug in animal illnesses resembling CFIDS.

Animals↗
PubMed2000

[Conservative treatment of renal ptosis].

BACKGROUND: Nephroptosis or floating kidney is an acquired, caudal displacement of one or both kidneys, with differing stages and etiology. It has been almost completely ignored over the past few years. The general tendency to regard nephroptosis as a urological pathology has prompted researchers to look for resolutive surgical treatment. The existence of over 150 surgical techniques is a clear demonstration of the high failure rate with the result that surgeons are unwilling to tackle this pathology, often leaving the patient alone with his problems. The numerous nephrological complications caused by nephroptosis have prompted us to look for alternative therapies to propose to nephrologists for the consecutive treatment of the floating kidney, enabling the patient to live with his pathology. METHODS: A longitudinal study was performed for 60 months in 102 patients with mono or bilateral nephroptosis. Hematuria, urinary cylindroids, asthenia, pain and the daily intake of antispastic lenitives were analysed at 6, 12, 24 and 60 months. Throughout this period all patients were treated with a water cure (31/day) and nocturnal decubitus in Trendelenburg's position (the foot of the bed is raised by 10 cm). Patients with primary or secondary kidney pathology, UTI and nephrolithiasis were excluded from the study. RESULTS: All the parameters showed a marked and steady improvement. At one year, over half the patients treated had improved, and at two years over two thirds only complained of marginal symptoms. CONCLUSIONS: Quali-quantitative and temporal values are reported in the light of which we can affirm that conservative treatment enables the patient to lead an almost normal life, as well as returning to work, with a reduced risk of complications.

Congenital Abnormalities↗
PubMed1997

The treatment of benign prostatic hyperplasia with alpha blockers in men over the age of 80 years.

OBJECTIVE: To determine the safety and efficacy of alpha blockade with doxazosin and terazosin in men over the age of 80 years with symptomatic benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: Thirty-six men (mean age 83.6 years, SD 5.6, range 80-96) received either doxazosin 4 mg (11 men) or 8 mg (10 men), or terazosin 5 mg (five men) or 10 mg (10 men), once daily at night. Twenty-eight men (78%) were on other anti-hypertensive medication; the type and dosage were not changed during the study. Efficacy and safety were assessed using measurements of peak urinary flow rate, symptom scores and the incidence of adverse events. RESULTS: Of the 36 men, 33 (92%) remained on study medication at 6 months; the remaining three (8%) discontinued because of asthenia. After 3 months of treatment, the peak urinary flow rate increased significantly (P < 0.008) for both doxazosin (+3.7 mL/s) and terazosin (+3.2 mL/s). The American Urological Association symptom score improved significantly (P < 0.01) with both alpha blocker after 3 months of treatment and efficacy was maintained at 6 months. There were small, non-significant decreases in blood pressure in patients receiving doxazosin or terazosin, but no differences between patients who were normotensive at baseline and those whose blood pressure was controlled by other anti-hypertensive drugs. CONCLUSION: These results suggest that alpha blockade with either doxazosin or terazosin is well tolerated and effective in older men with symptomatic BPH. Furthermore, patients on concomitant anti-hypertensive medication need no alteration of their therapeutic regimen before the initiation of alpha blockade for BPH.

Adrenergic alpha-Antagonists↗
PubMed1998

Cystic renal cell carcinoma: pathological features, survival and implications for treatment.

OBJECTIVES: To assess the incidence, clinicopathological features, prognosis and therapeutic options of cystic renal cell carcinoma (CRCC). PATIENTS AND METHODS: The clinical records and nephrectomy specimens from 206 patients with renal cell carcinoma (RCC) were reviewed after a minimum follow-up of 5 years. The mode of presentation, tumour size, growth pattern, nuclear grade, cytoplasmic appearance and pathological stage at presentation were compared with the outcome, as measured by disease-free and overall survival of the patients. RESULTS: From the 206 patients with RCC, 25 (12%) were classified as having CRCC; most of these cases (96%) occurred in male patients, as opposed to 64% in the remaining patients RCC (P = 0.0029). The clinical features at diagnosis were similar in both groups, although asthenia, anorexia and weight loss were uncommon in patients with CRCC (P = 0.045). Nuclear grade and pathological stage were usually lower in those with CRCC than in those with RCC (P = 0.0071 and P = 0.0033, respectively). Survival was significantly longer in patients with CRCC (P = 0.0342). CONCLUSIONS: CRCC is a type of RCC that is usually identified at earlier stages, has a slower growth rate, and is therefore associated with a better prognosis and longer survival than conventional RCC. The differential diagnosis between CRCC, cystic multilocular nephroma and cysts with a superimposed infectious or haemorrhagic process can be extremely difficult in imaging studies, and even in intra-operative frozen-section analysis. Because of this, and with the better prognosis of CRCC, a conservative surgical approach would be the treatment of choice whenever technically feasible.

Carcinoma, Renal Cell↗
PubMed1998

Zolmitriptan, a 5-HT1B/1D receptor agonist for the acute oral treatment of migraine: a multicentre, dose-range finding study.

Zolmitriptan is a selective 5-HT1B/1D receptor agonist for acute oral migraine therapy. This randomized, placebo-controlled, parallel-group study investigated the efficacy and tolerability of oral zolmitriptan (5, 10, 15 and 20 mg) in the treatment of single acute migraine attacks. Of 1181 patients randomized, 840 were evaluable for the primary efficacy analysis. Headache response rates (a reduction in headache intensity from severe or moderate at baseline to mild or no pain at 2 hours post-treatment) were similar across the zolmitriptan dose groups (66%, 71%, 69% and 77% for 5 mg, 10 mg, 15 mg and 20 mg, respectively) and were significantly higher than that for placebo (19%; all groups P < 0.001). A headache response was reported at 1 hour by 40-50% of zolmitriptan recipients (16% placebo). At 2 hours post dose, 39-47% of zolmitriptan-treated patients were pain-free, compared with 1% of placebo recipients. Headache recurrence occurred in 21-29% (upper 95% CI 37.1) of zolmitriptan-treated patients and in 65% (95% CI 38.3, 85.8) of placebo recipients. Zolmitriptan was well tolerated at each dose. The most commonly reported adverse events were asthenia, dizziness, paraesthesia and feelings of heaviness. Most adverse events were of mild or moderate intensity and were transient. The frequency of adverse events was dose-related. Although, zolmitriptan 5 mg exhibited the most favourable efficacy and tolerability profile, the dose response data suggest that lower doses would also offer significant efficacy. Copyright 1998 Lippincott Williams & Wilkins

Journal Article↗
PubMed1997

Safety, tolerability, and pharmacokinetics of sumatriptan suppositories following single and multiple doses in healthy volunteers.

A suppository formulation of the 5HT1 agonist sumatriptan could prove an important therapeutic option in migraine patients who dislike or poorly tolerate injectable therapy and where oral tablet administration is unsuitable because of severe migraine-related vomiting. Two independent double-blind, randomized clinical studies were conducted to evaluate the safety, tolerability and pharmacokinetics of sumatriptan suppositories following ascending single doses (four different dose levels) and multiple doses. In the four-period, crossover, single-dose study, 24 healthy male subjects were randomized to receive a suppository containing 12.5, 25, 50, or 100 mg on separate occasions 3-14 days apart. The suppositories were generally well tolerated; transient asthenia, drowsiness, and headache were the most frequently reported adverse events, and these were not dose-related. Peak plasma concentrations (Cmax) of sumatriptan were proportional to dose from 25 to 100 mg; area under the plasma concentration-time curve (AUC infinity) values were proportional to dose except at the highest doses, when they were greater than those predicted from lower doses. For all doses, the tmax of sumatriptan occurred within 2.5 h, and the t1/2 was approximately 2 h. In the two-period, placebo-controlled, crossover, repeat-dose study, 12 healthy adult male subjects were randomized to receive either a 50-mg sumatriptan suppository or placebo suppository, administered rectally twice a day, for 11 doses (5 1/2 days). Adverse events were no more frequent with sumatriptan than with placebo, and stool guaiac, rectal examinations, and physical examinations remained normal. No significant differences were noted between Day 1 and Day 6 values in the AUC, Cmax, time of peak serum concentration (tmax), elimination half-life (t 1/2), fraction of the dose excreted in the urine (fe), or renal clearance (Clr) of sumatriptan or its pharmacologically inactive indole acetic acid metabolite. Serum metabolite concentrations were two to three-fold higher than corresponding sumatriptan concentrations. No clinically significant accumulation of sumatriptan or its metabolite occurred. Overall, these studies show that sumatriptan administration via a suppository formulation is well tolerated, allows rapid absorption of sumatriptan, results in sumatriptan Cmax values that are proportional to dose from 25 to 100 mg, and is not associated with accumulation of sumatriptan or its metabolite.

Adolescent↗
PubMed2003

Eletriptan for the treatment of migraine in patients with previous poor response or tolerance to oral sumatriptan.

To determine the tolerability and efficacy of eletriptan in patients who had discontinued oral sumatriptan due to lack of efficacy or intolerable adverse events (AEs) during previous clinical treatment (not a controlled trial). Eletriptan is a potent, selective 5-HT1B/1D receptor agonist with beneficial pharmacokinetic properties compared with sumatriptan. In a double-blind, parallel group, placebo-controlled multicentre study, patients with and without aura (n = 446) were randomized to 40 mg eletriptan (E40, n = 188), 80 mg eletriptan (E80, n = 171) or placebo (n = 87) for treatment of up to three migraine attacks. Two-hour headache response, based on first-dose, first-attack data, was 59% for eletriptan 40 mg, 70% for eletriptan 80 mg, and 30% for placebo (P < 0.0001 for both doses of eletriptan vs. PBO; P < 0.05 for E80 vs. E40). Onset of action was rapid, with 1-h headache response rates significantly superior for E40 and E80 vs. placebo (40%, 48%, 15%; P < 0.0005). Both E40 and E80 were significantly superior to placebo, based on first-dose, first-attack data, for 2-h pain-free response (35%, 42%, and 7%; P < 0.0001). Both E40 and E80 demonstrated significant consistency of response, with headache relief rates at 2 h on at least two of three attacks in 66% and 72% vs. 15% on placebo (P < 0.001). AEs were mild to moderate in severity and dose related. The most commonly reported AEs included nausea, vomiting, asthenia, and chest symptoms. E40 and E80 produce an effective response in patients who had previously discontinued treatment with sumatriptan due to lack of efficacy or side-effects.

Administration, Oral↗
PubMed2000

Outbreak of Salmonella braenderup gastroenteritis due to contaminated meat pies: clinical and molecular epidemiology.

OBJECTIVES: To determine the epidemiologic, clinical and molecular characteristics of an outbreak of severe gastroenteritis due to the ingestion of meat pies highly contaminated with Salmonella braenderup. METHODS: In October 1993, we observed an outbreak of Salmonella braenderup gastroenteritis that occurred in the Lausanne area, Canton de Vaud, Switzerland. Cultures of suspected food products, of samples at the incriminated food factory and from workers, as well as a case-control study, were used to determine the source of the epidemics. Ribotyping of representative Salmonella braenderup strains was performed to define the molecular epidemiology. The clinical characteristics of this infection were determined by using a standardized interview performed during and 6 months after the outbreak in 156 of 215 identified patients. RESULTS: The outbreak resulted from the ingestion of pies, heavily contaminated (> 106 CFU/g) with a strain of Salmonella braenderup. The contamination was due to mishandling and recycling of jelly poured on top of the products. According to its ribotype and plasmid characteristics, this strain had not been isolated previously in Switzerland. Ten of the 24 workers of the incriminated food factory were shedding the epidemic strain in their stools, and one of them reported gastroenteritis 3 weeks before the beginning of the outbreak. The estimated attack rate in the exposed population was 7.5%. The median incubation time was 18 h. Among 127 adult patients studied, 98% had diarrhea, 95% abdominal pain, 74% fever > or = 38.5 degrees C, 69% nausea and 35% vomiting. One patient developed prosthetic valve endocarditis, and one reactive arthritis. Long-term complications were not identified, although 12 patients complained of irritable bowel syndrome and 24 of unusual asthenia lasting for more than 6 weeks after infection. Children had more severe signs and symptoms compared to adults, and six of 29 needed hospitalization. CONCLUSIONS: This study showed that ingestion of food highly contaminated with Salmonella braenderup resulted in severe but typical gastroenteritis and indicated mishandling of food during manufacture as the cause of this outbreak.

Adult↗
PubMed2003

Toxoplasmic lymphadenitis--clinical and serologic profile.

OBJECTIVE: To study the serologic profile of several types of test for toxoplasmosis, in order to contribute to the interpretation of antibody kinetics. METHODS: The clinical and serologic features of 120 cases of lymphadenopathy with known time of clinical onset were studied during 18 months postinfection. Antibody kinetics was determined by Sabin-Feldman dye test, complement fixation with light antigen, IgM immunofluorescent antibody test, and IgM immunosorbent agglutination assay (IgM-ISAGA). Cell-mediated immunity was evaluated by the toxoplasmin skin test. RESULTS: Seventy-five female patients aged 11-54 years (median 27 years) and 45 male patients aged 3-59 years (median 17 years) were studied, 85% of whom were under 30 years of age. Cervical lymph nodes were involved throughout, generally on both sides, with more than one affected ganglion group in 88%. The predominant symptom was asthenia (69%), which persisted in some cases for several months. A negative Sabin-Feldman dye test in a lymphadenopathy with more than three weeks' evolution excludes a toxoplasma etiology. A positive Sabin-Feldman dye test with negative IgM-ISAGA almost invariably excludes recent infection. The Sabin-Feldman dye test was positive in 94% of patients with titers higher than 1 : 16 000 within the first three months. The IgM-ISAGA yielded 98% of positive results, of which 94% were high titers. Titers >/= 1 : 160 in the IgM immunofluorescent antibody test and complement fixation were found to be highly indicative of recent infection, since 87% and 91%, respectively, were found within the first three months. A negative skin test plus positive serology values indicates recent infection. CONCLUSION: Our results indicate that estimation of time of infection on the basis of serologic results is improved by the simultaneous application of several tests, and correlates closely with the presence of clinical lymphadenitis.

Adolescent↗
PubMedDate not supplied

L-carnitine in dialysis patients.

Hemodialysis (HD) patients often have low serum concentrations of free L-carnitine and decreased skeletal muscle stores. As L-carnitine is an essential cofactor in fatty acid and energy metabolism, it is possible that abnormal carnitine metabolism in dialysis patients may be associated with clinical problems such as skeletal myopathies, intradialytic symptoms, reduced cardiac function, and anemia. Studies have shown that L-carnitine supplementation in HD patients improves several complications seen in dialysis patients, including cardiac complications (arrhythmias, reduced output, low cardiothoracic ratio), limitation of exercise capacity, increased intradialytic hypotension, and muscle symptoms. The most promising results have been noted in the treatment of erythropoietin-resistant anemia. Routine administration of L-carnitine to all dialysis patients is not recommended at this time; however, a therapeutic trial of L-carnitine can be useful in symptomatic patients with certain clinical features unresponsive to the usual measures. These include intradialytic muscle cramps and hypotension, asthenia, cardiomyopathy, lowered ejection fraction, muscle weakness or myopathy, reduced oxygen consumption, and anemia requiring large doses of EPO.

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