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At least 793 records · Page 44Linked to original sources

PubMed2003

Comparison of sustained-release morphine with sustained-release oxycodone in advanced cancer patients.

The antinociceptive effect of morphine and oxycodone is mediated preferentially at micro and kappa receptors, respectively. The aim of this study was to evaluate the analgesic profile of the combination of morphine and oxycodone in cancer pain, compared to the standard administration of morphine alone. Controlled-release formulations of oxycodone (CRO) and morphine (CRM) were compared in 26 patients. The study started with an open-label, randomised titration phase to achieve stable pain control for 7 days, followed by a double-blind, randomised crossover phase in two periods, 14 days each. At any point, patients were allowed to use oral immediate-release morphine (IRM) as needed, in order to keep visual analogue scale < or =4. Pain, satisfaction, adverse effects and number of daily rescue morphine tablets were assessed. A total of 22 patients were evaluated. The weekly upload consumption ratio in morphine/oxycodone was 1 : 1.8 (1.80, 1.83, 1.76, 1.84). The weekly IRM consumption was higher in patients having CRM compared to patients having CRO (ratio morphine/oxycodone: 1.6, 1.6, 1.6, 1.7) (P<0.05). Patients receiving oxycodone complained of less nausea and vomiting. The rescue morphine analgesic consumption was 38% higher in patients receiving only morphine, compared to patients receiving both morphine and oxycodone. The results suggest that the combination of morphine/oxycodone (opioids with differential preferential sites of action) can be a useful alternative to morphine alone, resulting in a better analgesia profile and less emesis.

Adult↗

PubMed2003

Konjac supplement alleviated hypercholesterolemia and hyperglycemia in type 2 diabetic subjects--a randomized double-blind trial.

OBJECTIVES: The present study was designed to evaluate effects of konjac glucomannan (KGM) supplement (3.6 g/day) for 28 days on blood lipid and glucose levels in hyperlipidemic type 2 diabetic patients and the possible mechanism for the reductions in blood lipid levels. METHODS: Twenty-two diabetic subjects (age 64.2 + 8.4 years, BMI 25.5 + 3.2 kg/m(2)) with elevated blood cholesterol levels (fasting glucose between 6.7-14.4 mmol/L), but currently not taking lipid-lowering medication, were recruited to participate in a two 28-day period, randomized, double-blind, crossover clinical trial. Fasting blood samples drawn on the initial and final days of each period were determined for plasma lipids and glucose levels. Feces collected at the end of each experimental period were analyzed for neutral sterol and bile acid contents. RESULTS: Compared with placebo, KGM effectively reduced plasma cholesterol (11.1%, p = 0.0001, adjusted alpha = 0.006), LDL-cholesterol (20.7%, p = 0.0004, adjusted alpha = 0.006), total/HDL cholesterol ratio (15.6%, p = 0.0005, adjusted alpha = 0.007), ApoB (12.9%, p = 0.0001, adjusted alpha = 0.006) and fasting glucose (23.2%, p = 0.002, adjusted alpha = 0.008). Plasma triglyceride, HDL-cholesterol, LDL/HDL cholesterol, postprandial glucose and body weight were not significant after adjustment by the Bonferroni-Hochberg procedure. Fecal neutral sterol and bile acid concentrations were increased by 18.0% (p = 0.004) and 75.4% (p < 0.001), respectively, with KGM supplement. CONCLUSIONS: The KGM supplement improved blood lipid levels by enhancing fecal excretion of neutral sterol and bile acid and alleviated the elevated glucose levels in diabetic subjects. KGM could be an adjunct for the treatment of hyperlipidemic diabetic subjects.

Amorphophallus↗

PubMed1981

Photoperiodic control of reproduction in olfactory-bulbectomized rats.

30-day-old male rats were (1) sham-operated or subjected to (2) removal of the olfactory bulbs, (3) olfactory bulbectomy and blinding (4) olfactory bulbectomy and pinealectomy or (5) olfactory bulbectomy, blinding and pinealectomy. Animals were exposed from 30 to 110 days of age to long-day (14 h of light per day) or short-day (8 h of light per day) photoperiods. The reproductive system of neurologically-intact rats was not affected by exposure to short days. Nor did bulbectomy affect the reproductive system of rats exposed to long days. However, bulbectomized, short-day rats had significantly lower body weights, reduced testicular and seminal vesicle weights and lower plasma testosterone levels than did bulbectomized, long-day rats. The effects of short-day exposure on bulbectomized rats were prevented by pinealectomy. Short-day exposure and blinding exerted similar effects in bulbectomized rats. The testes of rats from all groups contained elongated spermatids; blinding and short-day treatment had no effect on spermatogenesis. Neither mating behavior nor the number of young sired was influenced by photoperiod in bulbectomized or intact rats. Removal of the olfactory bulbs unmasks photoperiodic responsiveness in rats; the antigonadal effects of short-day exposure are mediated by the pineal gland in bulbectomized rats as in species traditionally designated photoperiodic. The mechanisms by which bulbectomy renders rats responsive to short days are considered.

Animals↗

PubMedDate not supplied

Sodium cromoglycate and carbachol-induced bronchoprovocation in asthmatic children.

Ten children with mild bronchial asthma underwent bronchial challenge with carbachol on three consecutive days; using a double-blind technique, they were given inhaled saline placebo on the first day and placebo or sodium cromoglycate (SCG) on the second and third days 15 min prior to the bronchial provocation test with carbachol. We did not find any significant difference between the baseline and placebo values, but we did obtain a statistically significant difference when comparing baseline with post-SCG and placebo with post-SCG values. These results demonstrate a protective effect of SCG on carbachol-induced bronchospasm in asthmatic children.

Adolescent↗

PubMedDate not supplied

Effect of prolonged administration of the serotonin4 (5-HT4) receptor agonist cisapride on aldosterone secretion in healthy volunteers.

In man, serotonin (5-HT) has been shown to stimulate aldosterone secretion through activation of 5-HT4 receptors, In particular, we have observed that oral administration of a single dose of the 5-HT4 receptor agonist cisapride (10 mg) induces a 5-fold increase in plasma aldosterone levels in healthy volunteers. Surprisingly, the usual disorders associated with hyperaldosteronism, i.e. hypertension and hypokalemia, have never been reported during chronic treatment with cisapride. In the present study, we have investigated the effect of prolonged oral administration of cisapride (10 mg, 3 times/day during 7 days) on aldosterone secretion in 12 healthy volunteers, in a simple blind fashion versus placebo. On day 1 of the treatment, cisapride induced a significant increase in plasma aldosterone levels (PAL) which returned to the values observed after placebo treatment within 10 hrs. On days 2 and 3, PAL were similar in cisapride- and placebo-treated subjects. Urinary aldosterone, kalemia and reninemia were not influenced by cisapride during the 7 days of the treatment. The present study shows that cisapride only exerts a transient stimulatory effect on aldosterone secretion in healthy volunteers. These data explain why long-term administration of 5-HT4 agonists does not affect blood pressure in man. They also indicate that prolonged stimulation of adrenal 5-HT4 receptors in vivo yields to a rapid desensitization phenomenon, as previously observed in vitro.

Aldosterone↗

PubMed1987

[Double-blind evaluation of slow-release nicardipine using different methods of blood pressure measurement. Predictive value of the acute response to intravenous nicardipine].

Forty hypertensive patients (diastolic greater than 95 mmHg) were included after 15 days of a single blind placebo period in a randomized placebo controlled double-blind study to assess the antihypertensive effect of a new galenic form of nicardipine (N) administered 50 mg b.i.d. for 3 weeks. They comprised 27 men and 13 women aged from 27 to 72 years (mean: 53 +/- 10). Blood pressure (BP) was measured in hospital before morning drug intake by an automatic recorder (Sentron) in supine position for 30 minutes (min) and by a mercury sphygmomanometer. Ambulatory BP was assessed by a portable patient activated recorder (Remler 2000). Mercury sphygmomanometer supine BP under N fell from 160 +/- 21/104 +/- 6 mmHg to 151 +/- 14/98 +/- 8 mmHg (n = 20; p less than 0.01/p less than 0.01) whereas BP under placebo (P) was respectively 158 +/- 14/103 +/- 6 mmHg and 156 +/- 20/102 +/- 9 mmHg (NS). Sentron BP under N fell from 158 +/- 17/96 +/- 8 mmHg to 148 +/- 13/90 +/- 7 mmHg (p less than 0.001/p less than 0.01) with no BP change under P (152 +/- 12/93 +/- 7 mmHg to 151 +/- 14/93 +/- 8 mmHg NS). BP recorder every 30 min for 12 hours revealed a decrease under N (160 +/- 18/105 +/- 10 mmHg to 142 +/- 16/94 +/- 10 mmHg; p less than 0.001/p less than 0.001) with a placebo effect in the control group on the diastolic BP (160 +/- 15/103 +/- 7 mmHg to 156 +/- 16/100 +/- 8 mmHg/NS/p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed2002

Histologic and radiographic assessment of caries-like lesions localized at the crown margin.

STATEMENT OF PROBLEMS: Little is known about the impact of crown margins on the demineralization and remineralization process or on the interpretation of radiographs for the detection of early secondary caries. PURPOSE: The aim of this study was to correlate the findings from 2 different radiographic techniques with the results of a histologic assessment of carieslike lesions at the crown margin. MATERIAL AND METHODS: Ten fully impacted third molars were extracted and restored with complete metal crowns with chamfer preparations. For each tooth, the prepared margin ended in enamel on one side and extended into cementum/dentin on the other. After being thoroughly cleaned, the teeth were covered with wax except for a 2- x 3-mm window at the crown margin in each of 2 test areas localized at the interproximal enamel and cementum/dentin junction. During demineralization with 6% hydroxyethyl cellulose gel at pH 4.9, direct digital radiographs or conventional radiographs were made at baseline and after 7, 14, 21, and 28 days. Each radiograph was blinded and examined for the presence/absence of lesions by 3 calibrated observers who used predetermined criteria required for receiver operating characteristic (ROC) analysis. After 28 days, the teeth were imbibed with methyl methacrylate and serially ground sectioned for assessment of the lesions in polarized light. Morphometric analysis of lesion extension included the calculation of mean values and standard deviations. Kappa and ROC analysis were applied to assess radiographs made at different demineralization time periods, localization of the crown margins in enamel or cementum/dentin, and direct digital and conventional radiographs. Data were tested for normal distribution (QQ plot), and statistical differences were calculated with Tukey's honestly significant difference post hoc test. RESULTS: Radiographic evaluation revealed only slight interexaminer agreement (Kappa) for enamel lesions (direct digital 0.19, conventional radiographs 0.2) and a fair interexaminer agreement for cementum/dentin lesions (direct digital 0.35, conventional radiographs 0.33). ROC analysis revealed no differences between the radiographic techniques. Lesions localized in cementum/dentin (direct digital 0.86 +/- 0.14, conventional radiographs 0.86 +/- 0.09) were diagnosed more reliably than those in enamel (direct digital 0.79 +/- 0.05, conventional radiographs 0.72 +/- 0.10). As microscopically assessed, the depth of lesions in enamel was less than that of lesions in cementum/dentin (49.3 +/- 7.3 microm vs 89.5 +/- 13.2 microm). Erosions were found in cementum/dentin (depth 25.2 +/- 5.3 microm). CONCLUSION: Within the limitations of this study, small artificial lesions were detected equally well by conventional and direct digital radiography. However, because of low interexaminer agreement, the radiographic assessment did not reproduce true histopathologic lesion characteristics documented by morphometry of serial ground sections.

Adolescent↗

PubMed1989

Treatment of neuroleptic-induced akathisia with propranolol: a controlled replication study.

Twelve DSM-IIIR diagnosed schizophrenics, with neuroleptic-induced akathisia (NIA), were treated with either propranolol or matched placebo for two days, followed by a treatment crossover phase for five more days. Raters and patients were "blind" to treatment. This study shows that 120 mg of propranolol a day is more effective than placebo in reducing akathisia, and that propranolol's antiakathisic effect may require several days of treatment.

Akathisia, Drug-Induced↗

PubMed1998

Sphere spectrophotometer versus human evaluation of tooth shade.

The purpose of this study was to compare an objective to a subjective method of tooth shade evaluation using the SP78 sphere spectrophotometer and human visual analysis. Twenty extracted fully developed human maxillary teeth had their L* values (lightness) read by the SP78 on day 1 and then again on day 14. Using a blind method, five human evaluators then attempted to match shade tabs from a six-tab experimental Vita shade guide to the same teeth on days 1 and 14. The SP78 L* values read for each tooth were evaluated for a match between those obtained on day 1 and those read on day 14. The results of human evaluation of tooth shade were compared among the evaluators and then between themselves over time. Finally, the ability of human evaluators to match tooth shade was compared with the results obtained with the SP78. The SP78 reproduced L* readings within the standard error of the machine (< or = 1.0) in 16 of 20 (80%) teeth. In contrast, interevaluator agreement expressed as majority agreement (3, 4, or 5 of 5 evaluators agreeing) was only 10 of 20 (50%) teeth on day 1 and 13 of 20 (65%) teeth on day 14. Intraevaluator agreement over the experimental period ranged from 20 to 60%. The results of this study confirm that human evaluation of tooth shade is unreliable and that the SP78 sphere spectrophotometer can provide a more predictable and accurate method of evaluating tooth shade in vitro. This finding opens up a new avenue of investigation for testing the effectiveness of materials and techniques in bleaching discolored teeth.

Color↗

PubMed2000

Valproate as an adjunct to neuroleptic medication for the treatment of acute episodes of mania: a prospective, randomized, double-blind, placebo-controlled, multicenter study. European Valproate Mania Study Group.

To compare the efficacy of sodium valproate administered as adjunct to neuroleptic medication for patients with acute mania with the efficacy of neuroleptics alone, the authors conducted a 21-day, randomized, double-blind, parallel-group, placebo-controlled trial. The study design closely reflected a clinical psychiatric setting in Europe where patients with acute mania commonly receive neuroleptic medication. In this trial, 136 hospitalized patients met the ICD-10 criteria for acute manic episodes; these patients received a fixed dose of 20 mg/kg of body weight of sodium valproate (Orfiril, Desitin Arzneimittel GmbH, Hamburg, Germany) orally, in addition to basic neuroleptic medication, preferably haloperidol and/or perazine. The primary outcome measure was the mean dose of neuroleptic medication (after conversion into haloperidol-equivalents) for the 21-day study period. Severity of symptoms was measured using the Young Mania Rating Scale (YMRS), the Global Assessment Scale, and the Clinical Global Impression Scale. Intent-to-treat analysis was based on 69 patients treated with valproate and 67 patients who received placebo. Groups were comparable with regard to demographic and clinical baseline data. Premature discontinuations occurred in only 13% of the patients. The mean neuroleptic dose declined continuously in the valproate group, whereas only slight variations were observed in the placebo group; the difference was statistically significant (p = 0.0007) for study weeks 2 and 3. The combination of neuroleptic and valproate proved superior to neuroleptics in attempts to alleviate manic symptoms. The proportion of responders (a 50% improvement rate shown on the YMRS) was higher for the combination with valproate than for the group receiving only neuroleptics (70% vs. 46%; p = 0.005). Adverse events consisted of those known for valproate or neuroleptics; the only adverse event was asthenia, which occurred more frequently with the combination therapy. Valproate represents a useful adjunct medication for the treatment of acute manic symptoms. Valproate is beneficial because it allows the administration of fewer neuroleptic medications and produces improved and quicker remission of manic symptoms.

Acute Disease↗

PubMed2000

Oral treatment of fibromyalgia with tropisetron given over 28 days: influence on functional and vegetative symptoms, psychometric parameters and pain.

The 5-HT3 receptor antagonists are a novel therapy for patients suffering from fibromyalgia, although the optimal duration of treatment is still unclear. The objective of this phase II study was to evaluate whether prolonging treatment with tropisetron to 4 weeks is tolerable and correlated with an improved clinical benefit. Thirty female patients with fibromyalgia received oral tropisetron (5 mg) daily for 28 days in an open-label fashion. Treatment resulted in significantly decreased pain as measured by visual analog scale (VAS), with a mean reduction of 59.7% and an absolute median change of -25.0 from baseline to day 28 (p<0.0001). A similar, significant reduction of 55.7% and absolute median change of -31.0 was observed in the painscore (p<0.0001). The response rate with patients showing a > or = 35% reduction in individual pain scores was 72.4% at day 28. The pressure tolerance of tender-points was slightly increased at the end of the treatment period. In addition, significant improvements were observed in the State-Trait-Anxiety-Inventory (STAI), scales of von Zerssen (Bf-S) and Beck Depression Index (BDI). Functional symptoms were compared with the results from a 10-day, randomized, double-blind phase III study of tropisetron in 418 fibromyalgia patients. In both studies several functional symptoms such as sleep disturbances and dizziness improved significantly (p<0.05). In the 28 days study, the number and extent of improvement in functional symptoms was increased compared with the shorter trial. Tolerability and safety of tropisetron was good, and typically for 5-HT3-receptor antagonists, gastrointestinal symptoms and headache were the most frequently reported events. In conclusion, 28 days treatment of fibromyalgia patients with 5 mg tropisetron resulted in significant pain reduction, which was most pronounced after 10 days with a further reduction up to day 28. Psychometric tests showed significant improvements in depression and anxiety state scores, while functional symptoms improved with extended tropisetron treatment.

Administration, Oral↗

PubMedDate not supplied

A randomized, double-blind study on the efficacy and safety of a practical three-day regimen with artesunate and mefloquine for the treatment of uncomplicated Plasmodium falciparum malaria in Africa.

A randomized, double-blind, parallel-group study in 104 hospitalized patients with acute, uncomplicated Plasmodium falciparum malaria was performed in West and Central Africa from March to July 2001. Patients were randomized to receive simultaneous dosing (artesunate 200 mg/d plus mefloquine 250 mg/d from the first to the third day [investigational group]) or sequential dosing (artesunate 200 mg/d for 3 d plus mefloquine 250 mg on the second and 500 mg on the third day [reference group]). Patients were followed-up for 28 d, and clinical and parasitological outcomes were assessed. The 14-d cure rate was 100% in the investigational group and 98% in the reference group with no recrudescence until day 28. Mean times to fever and parasite clearance were similar between the 2 groups (32 h vs. 26 h and 45 h vs. 48 h) and tolerability was good in both groups. The number of patients with vomiting was statistically significantly lower in the investigational group compared to the reference group (3.8% vs. 19.2%, P = 0.014). A 3-d once-daily co-administration of artesunate and mefloquine starting on day one offers a practical dosing regimen, which is highly effective and well tolerated in patients with uncomplicated P. falciparum malaria.

Adolescent↗

PubMed1999

Combined CO2/erbium:YAG laser resurfacing of peri-oral rhytides and side-by-side comparison with carbon dioxide laser alone.

BACKGROUND: Laser resurfacing of facial rhytids has become a popular treatment option for many patients with wrinkles, photoaging, and acne scarring. Laser wavelength options and optimization of techniques continue to evolve in an attempt to shorten the healing phase associated with laser skin resurfacing. OBJECTIVE: To prospectively study the clinical effects of pulsed carbon dioxide (CO2) laser resurfacing of facial rhytids used alone, compared with a combination of CO2 and the pulsed Erbium:YAG (Er:YAG) laser. METHODS: Forty treatment sites on 20 patients were randomized and evaluated following treatment of the upper lip region with a combination of CO2 laser resurfacing alone or with the same CO2 laser treatment followed by 3 passes with the Er:YAG laser. Patient diaries were maintained to assess erythema, crusting, pain, itching, swelling, pigmentary changes, and the day of first make-up application. Blinded objective grading of improvement was independently assessed by 4 blinded observers at time intervals 3, 6, and 10 days, and 1, 2, and 4 months. Chromometer measurements of erythema were also analyzed and percentage moisture recorded. RESULTS: Subjectively, all patients reported, on average, 10 days of redness and 2.4 days of pain, with no significant difference noted between the two procedures. On average, patients were able to apply make-up 5.5 days postoperatively, regardless of which procedure used. However, the combined CO2/Er:YAG laser treatment patients experienced reduced duration of crusting, compared to the patients treated with CO2 alone. The duration of crusting was reduced on average from 7.4 to 6.5 days, and also the duration of itching was reduced in patients receiving combined treatment from 5.5 to 4.8 days. Chromometer measurements noted no significant difference between techniques in the rate of resolution of erythema. Blinded objective grading revealed that crusting was reduced on average from 7.2 to 6.0 days, and swelling was reduced from 6.3 to 6.0 days in patients receiving the combined procedure. No cases of permanent hyperpigmentation, hypopigmentation, or scarring occurred in any patients. CONCLUSION: The addition of the Er:YAG laser following CO2 laser resurfacing reduces the duration of crusting, swelling, and itching postoperatively. Medium to deep (Grade III) facial rhytids were improved by 70% with both procedures with no significant difference noted between techniques.

Adult↗

PubMed2004

A pilot randomized, double-blind, placebo-controlled study of granisetron in the treatment of sexual dysfunction in women associated with antidepressant use.

A pilot study was conducted to evaluate the usefulness of granisetron for the treatment of antidepressant induced sexual dysfunction in women. Twelve women with antidepressant induced sexual dysfunction (AISD) were assigned granisetron (n=5) or placebo (n=7) in a 14-day randomized, double-blind, placebo-controlled study. One participant in the granisetron group did not complete the study. Participants were assessed at baseline, day 7 and day 14 using the Feiger Sexual Function and Satisfaction Questionnaire and the Arizona Sexual Experience Scale. No statistical differences were measured at baseline or at endpoint between the granisetron or placebo group. This study did not produce evidence supporting the usefulness of granisetron in AISD.

Adult↗

PubMed1988

Long day photoperiods and temperature of 20 degrees C induce spermatogenesis in blinded and non-blinded marbled newts during the period of testicular quiescence.

Adult male marbled newts (Triturus marmoratus) were collected at the end of the spermatogenesis period and exposed to different photoperiods (natural-daylength-simulated photoperiod, total darkness, 8L:16D, 12L:12D, 16L:8D, and continuous light) for 3 mo. Temperature was maintained at 20 degrees C. Two additional groups of newts were blinded and exposed to either the natural-simulated photoperiod and to 16 h of light per day respectively. Quantitative histologic studies on testicular development and germ cell volume per testis were performed. The newts captured in the field at the beginning (initial controls) or at the end of the experiments (final controls) were in the period of testicular quiescence. Newts kept in total darkness or exposed to a short photoperiod (8L:16D) showed germ cell development up to primary spermatocytes, whereas germ cell development in the newts exposed to long photoperiods (12L:12D or 16L:8D) progressed to elongated spermatids. The newts exposed either to intermediate photoperiods (natural-simulated photoperiod) or to constant light showed an intermediate degree of germ cell development (up to round spermatids). No significant differences between non-blinded and blinded animals were found. These results suggest that (1) mild temperature initiates testicular development in the period of testicular quiescence, (2) long photoperiods associated with mild temperatures produce spermatogenesis in this period, (3) complete darkness or constant light are less effective than some intermediate photoperiod, and (4) the effect of photoperiod on testicular function in newts is not related to ocular photoreception.

Animals↗

PubMed1994

Serum biopterin--a novel marker for immune activation during pre-diabetes in the BB rat.

Tetrahydrobiopterin (BH4) is a pteridine product which is released by rodent macrophages on activation by cytokines. We have used serial pancreatic biopsy, and measurement of serum biopterin at 30, 60, 90 and 120 days in the BB/S rat to relate histological change to macrophage activation during the course of pre-diabetes. Using immunohistochemistry, and an arbitrary scoring system read blind and standardised against day 30, we found that pancreatic MHC class I, MHC class II and infiltrating macrophage staining were up-regulated in the BB/S diabetes-prone rats (n = 17) at day 60, markedly so at day 90, and less so at day 120. Staining for resident pancreatic macrophages remained unchanged throughout in diabetes prone, diabetes resistant and Wistar (n = 28) control animals. Serum biopterin fell progressively and identically with age in BB diabetes resistant rats (n = 11) and Wistar controls. No change in weight gain or biopterin levels was observed in the biopsied animals. Mean serum biopterin levels in diabetes prone rats (of which 13 of 17 became diabetic at median 85 days) were the same as in diabetes resistant and Wistar rats at days 30, 60 and 120, but showed a striking and highly significant elevation (p < 0.001) at day 90. Although macrophages infiltrate the islet early in pre-diabetes, the timing of their activation is unknown. The rise in biopterin we observed is a potentially important immunological event which occurred late in the progression of pre-diabetes. This acute terminal event has not been reported previously, and may modify current concepts concerning the tempo of cell destruction during pre-diabetes.

Aging↗

PubMed2005

Effects of isradipine, a dihydropyridine-class calcium-channel antagonist, on d-methamphetamine's subjective and reinforcing effects.

In healthy human volunteers, we have previously shown that isradipine, a dihydropyridine-class calcium-channel antagonist, reduces some methamphetamine-induced positive subjective effects associated with its abuse liability, presumably by antagonizing cortico-mesolimbic dopamine pathways. In the present study, we combined acute immediate-release (IR) isradipine with repeated sustained-release (SR) isradipine pretreatment to determine whether isradipine could antagonize methamphetamine's positive subjective and reinforcing effects in methamphetamine-dependent research subjects. We included 18 non-treatment-seeking, methamphetamine-dependent subjects aged between 18 and 51 years in this double-blind, within-subject, cross-over study, which was done in a human laboratory. Intravenous methamphetamine (0, 15 and 30 mg) was administered on three different days after 5 days of double-blind cross-over treatment with either isradipine or matching placebo. Subjects received oral isradipine 30 mg SR at bedtime, plus 15 mg IR administered 2 h before methamphetamine infusion. Self-report questionnaires measured drug liking, euphoria, craving, stimulation, and methamphetamine preference. Methamphetamine reinforcement was measured by a behavioural procedure involving choices between methamphetamine and money. For those who received isradipine second and placebo first as the pretreatment paradigm but not vice versa, methamphetamine-induced drug liking, elation, and preference were reduced significantly by isradipine. Depending upon conditioning status, isradipine can reduce some methamphetamine-induced positive subjective and reinforcing effects associated with its abuse liability in methamphetamine addicts.

Adolescent↗

PubMed1983

Abnormalities in gastrointestinal motor activity in patients with short bowels: effect of a synthetic opiate.

We have investigated the fasting and postprandial patterns of gastrointestinal pressure activity in a group of patients with extensive (greater than 100 cm) resections of the distal small bowel. Each short bowel patient was studied on 2 consecutive days with random single blind administration of either loperamide (6 mg at 5 h and at 30 min before the meal) or placebo, and 20 healthy controls were studied on single days (13 basal fasting, 7 placebo). During fasting, the duration of the interdigestive motor complex was significantly shorter in patients with short bowel syndrome (71.1 +/- 15.6 min vs. 109 +/- 7.8 min for controls, p less than 0.03); hence, the frequency of complexes was increased. The duration of phase 2 was strikingly shorter in patients (18.7 +/- 7.0 min vs. 52.9 +/- 8.5 min for controls, p less than 0.03). Gastric emptying and postprandial motor activity were identical in patients and controls. During fasting, loperamide prolonged phase 3 (7.6 +/- 2.2 min vs. 4.3 +/- 1.1 min for placebo, p less than 0.03). Postprandially, loperamide shortened the time from meal ingestion to the first phase 3 by 50% (p less than 0.003), and increased motility index and frequency of contraction in the gut (p less than 0.01). Thus, gut motor activity in the short bowel syndrome is characterized by more frequent interdigestive motor complexes, marked reduction in phase 2 activity, and a normal feeding pattern. Loperamide therapy increases feeding activity while at the same time shortening its duration.

Adult↗