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PubMed1981

The acute effect of quazepam on the sleep of chronic insomniacs. A dose-response study.

The present study investigated the effects of the benzodiazepine, 7-chloro-5-(2-fluorophenyl)-1,3-dihydro-1-(2,2,2-trifluoroethyl)-2H-1,4-benzodiazeepine-2-thione (quazepam), on hypnotic efficacy and sleep staging in chronic insomniacs. We evaluated the acute withdrawal effects of several doses (0, 7.5, 30 and 45 mg) of quazepam. The effects of the different doses were assessed using both objective (polysomnographic) and subjective sleep parameters in a double blind repeated measures design (n = 15). The results indicated that daily administration of quazepam over three nights produced increased effects on sleep which suggested drug accumulation. Lower doses (7.5 and 15 mg) only had significant effects on sleep (sleep induction and maintenance and sleep architecture) with three days of administration, while 45 mg of quazepam produced significant effects on the first night of drug administration. Contrary to previous research investigating longer periods of administration, acute administration of low doses of quazepam did not produce carryover effects on withdrawal, while higher doses did. The accumulation of the parent compound or its active metabolites thus seemed to mediate these effects on sleep in a dose related fashion.

Adolescent↗

PubMed1995

Reproducibility of postoperative courses after surgical removal of symmetrically impacted wisdom teeth.

The acute postoperative courses after bilateral ¿identical¿ surgical removals of symmetrically impacted third molars on two separate occasions were investigated in a study containing two separate trials. Both trials were conducted as open interpatient crossover trials. Codeine phosphate (50 mg), with assumed analgesic effect but with no known clinical antiinflammatory effect, was given 4 times daily for 3 days starting 2 h after surgery in one trial using 20 patients (mean age 22.7 years, 12 females/8 males) and starting 3 h after surgery in the other trial using 20 patients (mean age 23.0 years, 11 females/9 males). Identical surgical procedures were carried out by the same surgeon in the same patient. The study shows the mean postoperative time courses of pain intensity, sum pain intensity, and swelling to be similar after bilateral operations. Pain intensity difference scores as measures of analgesia suggested the influence of carryover effects with respect to the second operation, irrespective of drug starting time. Mouth opening ability was not similar on each occasion after bilateral surgery. It can be concluded that the carryover design in bilateral surgery is valid and useful with respect to testing drug effects on swelling. The bilateral third molar model also offers the ability to test clinically relevant multiple dose regimens in phase 3 trials. It should, however, be recognized that the bilateral third molar model is highly dependent on the skill of the surgeon and may thus be more difficult to complete than parallel group trials.

Adult↗

PubMed2006

The effects of antimicrobial sprays and mouthrinses on supragingival plaque regrowth: a comparative study.

BACKGROUND: Due to the side effects of chlorhexidine digluconate (CHX) mouthrinsing, a spray has been proposed as an alternative method of CHX delivery to the oral cavity. The aim of this study was to investigate the plaque inhibitory effects of CHX, cetylpyridinium chloride (CPC), and triclosan (TRN) delivered by sprays and mouthrinses. METHODS: The study was an observer-masked, randomized cross-over design balanced for carryover effects, involving 15 healthy volunteers in a 4-day plaque regrowth model. Products being tested (0.2% CHX, 0.12% CHX, 0.05% CPC, and 0.03% TRN) were used both as sprays and mouthrinses. A saline solution served as a negative control. On day 1, subjects received professional prophylaxis, suspended oral hygiene measures, and commenced using their allocated products. On day 5, subjects were scored for disclosed plaque. RESULTS: CHX sprays (P<0.01) were the most effective sprays in preventing plaque regrowth, without significant differences between the two concentrations tested (P>0.05). TRN spray showed a significant inhibition of plaque regrowth in comparison to the negative control (P<0.05). CPC spray did not differ from saline spray (P>0.05). A similar trend of efficacy was detected for rinses. Although the effect on plaque regrowth observed with CHX rinses was superior to that of CHX sprays (P<0.0003), the latter did not cause side effects (P>0.2). CONCLUSIONS: These findings, together with those from clinical trials, suggest that the CHX-containing sprays may represent an effective alternative to CHX rinses when mechanical oral hygiene has to be avoided in restricted areas. On the contrary, the TRN and CPC sprays showed little or no plaque inhibitory effects.

Adult↗

PubMed1982

Influences of environment and its modification on dairy animal health and production.

Physiological state of dairy animals is a predisposing factor in environmental influences on animal health. Critical phases of life cycle include neonatal period, postpubertal reproduction, and lactation. Primary effect of environment in neonatal period is increased disease incidence associated with reduced immunoglobulin content in plasma of calves. Cold stress has little effect on reproduction; in contrast, heat stress reduces libido, fertility, and embryonic survival in cattle. Heat stress in late gestation reduces fetal growth and alters endocrine status of the dam. Carryover effects of heat stress during late gestation on postpartum lactation and reproduction also are detectable. Heat stress of lactating cattle results in dramatic reductions in roughage intake and rumination. Decreases in roughage intake contribute to decreased volatile fatty acid production and may contribute to alteration in ratio of acetate/propionate. Rumen pH also declines during thermal stress. Electrolyte concentrations, in particular sodium and potassium, also are reduced in rumen fluid of heat stressed cattle. The decrease in sodium and potassium are related to increases in loss of urinary sodium and loss of skin potassium as well as decline in plasma aldosterone and increase in plasma prolactin. Reduction in thyroxine, growth hormone, and glucocorticoid concentrations in chronically heat stressed cattle appear to be related to decreases in basal metabolism.

Adaptation, Physiological↗

PubMed1986

Quazepam and temazepam: effects of short- and intermediate-term use and withdrawal.

Two benzodiazepine hypnotics, one with an intermediate elimination t1/2 (temazepam, 15 mg) and the other with a long t1/2 (quazepam, 15 mg), were evaluated in 22- night sleep laboratory studies. The effectiveness and side effects of these benzodiazepines were assessed during short- and intermediate term use. Subjects were also assessed for the presence of rebound insomnia after abrupt withdrawal. Quazepam, 15 mg, was significantly effective in improving sleep both with short- and intermediate-term use, but the effectiveness of temazepam was considerably less. Although temazepam was effective for maintaining sleep with short-term use, there was rapid development of tolerance for this effect with intermediate-term use. Temazepam did not produce any behavioral side effects during either drug condition. The only side effect associated with quazepam was a significant degree of daytime sleepiness. After its withdrawal, temazepam was associated with some sleep and mood disturbance on the first withdrawal night, whereas quazepam had carryover effectiveness.

Adult↗

PubMed2004

A herbal remedy, Hyben Vital (stand. powder of a subspecies of Rosa canina fruits), reduces pain and improves general wellbeing in patients with osteoarthritis--a double-blind, placebo-controlled, randomised trial.

The treatment of osteoarthritis, a disease that eventually affects the majority of the older population, involves the alleviation of symptoms such as pain and stiffness, and the reduction of inflammation. The double-blind, placebo-controlled, crossover study reported here examined the effect of Hyben Vital, a herbal remedy made from a subtype of Rosa canina and recently reported to have anti-inflammatory properties, on the symptoms of osteoarthritis. One hundred and twelve patients with osteoarthritis were randomly allocated to treatment with either Hyben Vital 5 g daily or an identical placebo for 3 months, followed immediately by the alternative treatment. The patients assessed changes in joint pain and stiffness after each treatment period on a 5-point categorical scale. General wellbeing, including mood, sleep quality and energy were also assessed and recorded in a personal diary. The results in the two arms of the crossover differed markedly. Group A (placebo first) showed significantly more improvement from Hyben Vital than from placebo, p < 0.0078 for pain and < 0.0025 for stiffness. But Group B (Hyben Vital first) revealed a positive effect of the same order as for Hyben Vital in group A, not only from the active drug, but also from placebo (difference not significant). An identical pattern was observed when we evaluated general wellbeing from the diary records. When patients, on the basis of reduction in joint pain, were divided into responders and non-responders, the first 3 months of active treatment (group A) showed a response rate of 31/47 (66%) compared to that of placebo (group B) 18/50 (36%), p < 0.0185. No major side effects occurred in either group. The data indicate that Hyben Vital reduces the symptoms of osteoarthritis. We interpret the marked differences in the responses of the two groups as indicating a strong "carryover" effect of Hyben Vital.

Adult↗

PubMed1995

Effect of combing time on cat flea (Ctenocephalides felis) recovery from dogs.

Combing the haircoat to count fleas has been used to determine the efficacy of insecticides against fleas on dogs, but no standardization of method has been reported. In this study, the effect of combing time on flea recovery from dogs was examined. Six beagle dogs were infested with 100 unfed, adult Ctenocephalides felis (Bouché) on each of three consecutive days. A crossover design, balanced for carryover effects, was used to evaluate flea removal rates from each dog by comb-counting for three different time intervals; i.e. 5, 10 and 15 min. Each dog was combed once at each time interval on a different day, over three consecutive days. The results showed that the majority of fleas were recovered in the first 5 min of combing and there were no significant differences (P > or = 0.19) in the total number of fleas recovered between the 5, 10 or 15 min protocols. Moreover, the standard deviation and coefficient of variation increased with an increase in the amount of time spent combing, resulting in a decrease in precision for the longer protocols. Therefore, the comb time of 5 min provided a precise and accurate representation of the number of fleas present on an animal and could be useful as a standard measure of flea infestation levels in efficacy trials.

Animal Husbandry↗

PubMed2006

Optimal crossover designs for logistic regression models in pharmacodynamics.

Pharmacodynamics (PD) is the study of the biochemical and physiological effects of drugs. The construction of optimal designs for dose-ranging trials with multiple periods is considered in this paper, where the outcome of the trial (the effect of the drug) is considered to be a binary response: the success or failure of a drug to bring about a particular change in the subject after a given amount of time. The carryover effect of each dose from one period to the next is assumed to be proportional to the direct effect. It is shown for a logistic regression model that the efficiency of optimal parallel (single-period) or crossover (two-period) design is substantially greater than a balanced design. The optimal designs are also shown to be robust to misspecification of the value of the parameters. Finally, the parallel and crossover designs are combined to provide the experimenter with greater flexibility.

Algorithms↗

PubMed1996

Confounding and exposure trends in case-crossover and case-time-control designs.

As with ordinary studies, both case-crossover and case-time-control studies can suffer from confounding, including confounding by indication. In a case-crossover analysis, confounding by fixed (constant) characteristics is eliminated by pairing of cases to themselves, at the possible cost of introducing bias due to time trends in exposure. A case-time-control analysis can correct case-crossover results only for bias due to such time trends. If an uncontrolled confounder (such as disease severity) is present, the use of time controls can introduce new confounding, and the case-time-control results may end up either more or less confounded than the ordinary and case-crossover results. The relative confounding in the different approaches depends on details of the relations among the unmeasured confounder, the study exposure, the study disease, and any trend in these variables or their effects. Like an ordinary study, a case-time-control study must assume absence of unmeasured confounders, whether fixed or time-varying. Like a case-crossover study, it must also assume absence of carryover effects and can be more prone to misclassification bias than an ordinary study.

Bias↗

PubMed2002

Effects of larval exposure to triphenyltin on the survival, growth, and behavior of larval and juvenile Ambystoma barbouri salamanders.

We exposed 10 sibships of the streamside salamander, Ambystoma barbouri, to two concentrations of triphenyltin (TPT) (1 and 5 microg/L) and an acetone carrier control for the entirety of the larval period. We measured effects on larval feeding rates, escape behavior, growth rates, and survival to, days to, and size at metamorphosis. Postmetamorphosis, we monitored feeding rates, growth rates, and survival of juvenile A. barbouri in order to investigate carryover effects. The 5-microg/L TPT concentration resulted in 93% mortality of the larvae. Exposure to 1 microg/L TPT had no mortality effect and no effect on the escape behavior of larvae. However, larvae exposed to this TPT concentration had significantly lower feeding rates and growth rates and therefore metamorphosed later than the controls but at the same mass. We detected a direct effect of TPT on growth rates beyond the effect through depressed feeding rates. We also found significant evidence for variation among sibships in their sensitivity to TPT toxicity. Once exposure was terminated at metamorphosis. we observed no residual effects of TPT on juveniles. Survival, feeding, and growth rates of juveniles exposed to TPT as larvae were not significantly different from those exposed only to the acetone carrier.

Ambystoma↗

PubMed1988

Quazepam. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in insomnia.

Quazepam is a trifluoroethyl benzodiazepine hypnotic with a half-life of 27 to 41 hours, which has been shown to induce and maintain sleep in the short to long term (up to 4 weeks) treatment of patients with chronic or transient insomnia. Although its hypnotic efficacy has been well characterised against placebo, there are few clinical studies in comparison with established hypnotics, particularly over long term administration. However, preliminary evidence suggests that quazepam 15 to 30 mg is as effective as flurazepam and triazolam in usual therapeutic doses, and causes minimal rebound insomnia following its withdrawal, unlike rapidly eliminated benzodiazepines such as triazolam. The lack of rebound phenomena is likely to be attributable to the 'carryover' effects occurring after discontinuation of quazepam, which has pharmacologically active metabolites with half-lives of elimination similar to or longer than that of the parent drug. Probably because of the long half-lives of quazepam's metabolites, daytime sedation, fatigue and lethargy are the most frequently reported side effects. These side effects are most intense with the 30 mg dose and least with the 7.5mg dose, which has not been studied extensively. Hence, quazepam is an effective hypnotic which may be particularly suitable for short or medium term use in patients in whom withdrawal effects or rebound insomnia may be especially bothersome. Further definition of certain characteristics of its profile--such as its long term use and potential for development of tolerance or dependence, effects on psychomotor skills, efficacy of the 7.5mg dose, and suitability in elderly patients and patients with chronic organic diseases--will assist in more clearly defining its ultimate place in therapy.

Anti-Anxiety Agents↗

PubMed1994

Effect of dietary chlortetracycline during breeding and(or) farrowing and lactation on reproductive performance of sows: a cooperative study. S-145 Committee on Nutritional Systems for Swine to Increase Reproductive Efficiency.

A cooperative regional study involving 850 litters was conducted at five experiment stations (Arizona, Florida, Oklahoma, Texas, and Virginia) to assess the effects of feeding 220 mg/kg of chlortetracycline (CTC) from 1 wk before to the initiation of the breeding season to 15 d after the breeding season and(or) from 110 d of gestation through lactation on reproductive performance of sows (2 x 2 factorial). Sows were fed 1.82 kg/d (2.27 kg during December, January, and February) during the breeding period and before farrowing. Feed was consumed on an ad libitum basis during lactation. Feeding CTC during the breeding season increased litter size at birth (10.8 vs 10.3; P < .05) and decreased feed consumption (5.4 vs 5.5 kg/d; P < .05) in the subsequent lactation period. Feeding CTC during lactation reduced lactation weight loss in sows (4.3 vs 6.1 kg; P < .07). Feeding the antibiotic at breeding had no effect on conception rate; however, feeding the antibiotic during lactation improved subsequent conception rate at the first service (80 vs 73%; P < .10) and overall conception rate (89 vs 84%; P < .05). This indicates that some carryover effect of feeding CTC during lactation occurred during the subsequent breeding period. Station x treatment interactions were observed for survival rate to 21 d (P < .05) and to weaning (P < .06). Overall, survival rates were not greatly affected by antibiotic feeding. No treatment interaction was observed for any trait measured, indicating that the effects of CTC during the breeding and lactation periods were independent.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed2004

The effects of an amine fluoride/stannous fluoride and an antimicrobial host protein mouthrinse on supragingival plaque regrowth.

BACKGROUND: Chlorhexidine (CHX)-containing mouthrinses are recommended as adjuncts to mechanical oral hygiene. The problem associated with side effects, however, has stimulated the search for alternative antiplaque agents. The aim of this study was to investigate the plaque inhibitory effects of two mouthrinses containing amine fluoride/stannous fluoride (ASF) and antimicrobial host proteins (lactoperoxidase, lysozyme and lactoferrin; LLL), respectively. METHODS: The study was an observer-masked, randomized 4x4 Latin square cross-over design balanced for carryover effects, involving 12 healthy volunteers in a 4-day plaque regrowth model. A 0.12% CHX mouthrinse and a saline solution served as positive and negative controls, respectively. On day 1, subjects received professional prophylaxis, suspended oral hygiene measures, and commenced rinsing with their allocated rinses. On day 5, subjects were scored for disclosed plaque. RESULTS: The ASF rinse showed a significant inhibition of plaque regrowth in comparison to both saline and LLL solutions, but the lowest plaque indices were obtained with the CHX formulation (P<0.01). There were no significant differences between LLL rinse and saline (P>0.05). Such pattern of efficacy was the same in anterior and posterior teeth and in vestibular and lingual surfaces as well, with the exception of the lingual anterior surfaces. In these sites, differences between the CHX and ASF rinses were not significant (P>0.05). A significantly higher prevalence of side effects was found in subjects using the CHX product (P<0.0042). CONCLUSIONS: Although the effect on plaque regrowth observed with 0.12% CHX rinsing was superior to that with ASF, the ASF rinse was not associated with side effects. These findings, together with those from long-term trials, suggest that the ASF rinse may represent an effective alternative to CHX rinse as an adjunct to oral hygiene. On the contrary, the LLL rinse did not significantly inhibit plaque regrowth.

Adult↗

PubMed1998

An electropalatographic and acoustic study of temporal coarticulation for Catalan dark/l/ and German clear/l/.

Electropalatographic and F2 frequency data in /VlV/ sequences reveal more prominent C-to-V effects for Catalan dark /l/ than for German clear /l/, more so in the /i/ context than in the /a/ context, which is in agreement with the existence of high lingual requirements on the formation of two constriction places for dark /l/. German clear /l/ exerts a similar amount of F2 displacement on both vowels which may be indicative of the tongue dorsum being directed towards a target position; this is also suggested by dorsopalatal contact and formant frequency data showing less vowel-dependent variability than clear /l/ in other languages though more so than Catalan dark /l/. Salient anticipatory requirements for the implementation of /l/ in the two languages block V1-dependent carryover effects to a large extent which results in more prominent vocalic anticipation than vocalic carryover. This directionality trend in vocalic coarticulation is more obvious for Catalan dark /l/ than for German clear /l/ (in agreement with the former consonantal variety requiring more anticipation than the latter) and opposes German /l/ to clear /l/ in other languages (i.e., the less constrained /l/ variety of Spanish may favor vocalic carryover over vocalic anticipation in VCV sequences).

Humans↗

PubMed2000

Cyclical etidronate therapy for prevention of postmenopausal bone loss: a 1-year open-label follow-up study.

The objective of this study was to evaluate whether the pharmacological activity of cyclical etidronate therapy is sustained beyond the dosing period. A group of 121 postmenopausal women who had completed a 2-year, double-blind, placebo-controlled parallel study with etidronate or placebo (400 mg/day for 14 days every 3 months) and calcium agreed to participate in a 1-year open-label follow-up study to evaluate the effect of discontinuing etidronate treatment. Fifty-nine subjects in the former etidronate group and 62 in the placebo group received 500 mg/day of elemental calcium; 54/59 and 58/62 subjects, respectively, completed the study. Outcomes of the study were bone mineral density (BMD), measured by dual energy X-ray absorptiometry (DXA), and biochemical markers of bone turnover (urinary deoxypyridinoline/creatinine and serum osteocalcin). To determine whether there was a residual effect of previous therapy we compared mean percentage changes from baseline (year 0) to year 3 for both spinal and femoral neck BMD and markers of bone turnover in the former cyclical etidronate and placebo groups. To evaluate the carryover effect of treatment we compared the percent change from year 2 to year 3 for the same variables. Mean percentage change (SEM) from year 2 to year 3 for spinal BMD in the former cyclical etidronate group was -2.87% (0.48%) versus -0.99% (0.36%) in the placebo group (P = 0.0022). In the femoral neck, the BMD changes were -0.86% (0.42%) versus -1.01% (0.41%) (NS). Biochemical markers increased within 6 months toward baseline levels. Mean percentage changes from baseline (year 0) in both spinal and femoral neck BMD were significantly different between groups 1 year after treatment discontinuation. No differences between groups were maintained in deoxypyridinoline and osteocalcin. It is concluded that following withdrawal of cyclical etidronate therapy bone loss resumes at a normal and moderately accelerated rate in the proximal femur and lumbar spine, respectively. A positive effect on BMD at both cortical and trabecular sites is maintained for 1 year after treatment withdrawal.

Amino Acids↗

PubMed1999

Inhibition of CYP2D6 by quinidine and its effects on the metabolism of cilostazol.

OBJECTIVE: In vitro results are inconclusive as to whether cilostazol is metabolised by cytochrome P450 isoenzyme 2D6 (CYP2D6). The goals of this study were (1) to assure the dose of quinidine and timing relative to cilostazol used in this study were adequate to cause inhibition of CYP2D6, (2) to evaluate carryover effects of quinidine administration, and (3) to evaluate the effect of CYP2D6 deficiency and administration of quinidine (a CYP2D6 inhibitor) on the pharmacokinetics of a single 100 mg oral dose of cilostazol. DESIGN: This study was conducted as a single-centre, open-label, randomised sequence, 2-period, crossover pharmacokinetic trial. Water alone (treatment without quinidine) or two 200 mg oral doses of quinidine sulfate with water were administered 25 hours and 1 hour prior to a single 100 mg dose of cilostazol in period 1. Study participants were crossed over to opposite treatment in period 2. Metoprolol 25 mg, used as a positive control, was administered 1 hour after quinidine sulfate with water or using water alone to assess the magnitude of CYP2D6 inhibition by quinidine. STUDY PARTICIPANTS: 22 healthy nonsmoking Caucasian (14 male and 8 female) volunteers participated in the study. MAIN OUTCOME MEASURES: Serial blood and urine samples were collected at predose and after cilostazol administration to characterise cilostazol and its metabolite pharmacokinetics. Additional plasma samples were taken to assess the pharmacokinetics of quinidine. Urine samples were collected to measure metoprolol and hydroxymetoprolol. RESULTS: Administration of metoprolol with quinidine caused a significant (p < 0.001) decrease in the urinary 4-hydroxymetoprolol/metoprolol ratio compared with administration of metoprolol alone (42-fold decrease, 0.065 vs 2.707). Hence, quinidine effectively converted extensive metabolisers of CYP2D6 to poor metabolisers of CYP2D6. The 21-day washout period was adequate to have complete recovery from quinidine inhibition of CYP2D6. The analysis of variance demonstrated that the mean maximum plasma concentration (Cmax) for cilostazol, both adjusted and unadjusted for the free fraction, was higher in the control group than in the quinidine group (p = 0.023). However, the time to Cmax (p = 0.669), the area under the plasma concentration-time curve from time zero to infinity (AUC infinity; p = 0.133), and the apparent oral clearance (p = 0.135) were unchanged. The geometric mean ratios (90% confidence interval) comparing with quinidine (test) and without quinidine (reference) coadministration for Cmax and AUC infinity are 0.86 (0.77, 0.95) and 0.92 (0.84, 1.00), respectively. Similar patterns were observed for OPC-13015 and OPC-13213 with regard to Cmax, area under the plasma concentration-time curve from time zero to the last measurable concentration at time t, and AUC infinity (where determinable). The slight decrease in the systemic availability of cilostazol and its metabolites was thought to be a result of the increased gastrointestinal motility secondary to quinidine. CONCLUSIONS: Administration of quinidine sulfate 200 mg profoundly inhibited CYP2D6-mediated metabolism. The effects of quinidine inhibition of CYP2D6 metabolism were completely reversible during the 21-day washout period. Coadministration of quinidine with cilostazol had no substantial effect on cilostazol or its metabolites (OPC-13015 and OPC-13213). Hence, CYP2D6 does not have a significant contribution in the metabolic elimination of cilostazol.

Administration, Oral↗

PubMed2004

Aquatic mesocosm assessments of a neem (azadirachtin) insecticide at environmentally realistic concentrations--2: zooplankton community responses and recovery.

A neem-based insecticide, Neemix 4.5, was applied to forest pond enclosures at environmentally realistic concentrations (i.e., below the worst-case expected environmental concentration of 35 microg L(-1)). Crustacean zooplankton communities were examined by multivariate ordination (nonmetric multidimensional scaling) and time-course analyses of population trends among indicator taxa over two field seasons to determine application effects on community structure and recovery patterns. Significant effects on zooplankton community structure were detected at all main test concentrations (n = 5) of 28, 17, and 10 microg L(-1) azadirachtin. There was also evidence of adverse effects on zooplankton communities at an auxiliary test concentration (n = 2) of 5 microg L(-1) azadirachtin. Community-level effects resulted primarily from reductions in adult copepods with short-term, reciprocal increases in cladocerans. Copepod nauplii were not significantly affected. Response patterns suggested that the reductions in adult copepods resulted from growth-regulating effects of the active ingredient azadirachtin, or other neem compounds, and not from formulation ingredients. There was no evidence of recovery among adult copepods within the season of application. At the beginning of the second sampling season, there were apparent carryover effects similar to the community responses in the previous year. By the end of the second season, there was evidence indicating recovery of community structure at the two lower test concentrations of 10 and 17 microg L(-1), but not at 28 microg L(-1). The selective toxicity to adult copepods is problematic in that this group has a relatively long life cycle (1 year), contributes a major component of zooplankton biomass and respiration, and occupies critical functional guilds within zooplankton food web structures. Mitigation measures such as reductions in application rates and efforts to avoid deposition of sprayed materials on water bodies will be required to reduce the risk of harmful effects on zooplankton communities of forest ponds and other shallow, standing-water bodies.

Animals↗

PubMed2005

Observations of the "carry-over effect" following successful termination of chronic migraine in the adolescent with short-term dihydroergotamine, dexamethasone and hydroxyzine: a pilot study.

Chronic migraine management almost always requires daily oral preventative medication with potential adverse effects. Daily oral preventative therapy may also not be effective in terminating chronic migraine. Chronic central sensitisation caused by repetitive migraine attacks in a young person may lower the threshold for future migraine episodes leading to an intractable and debilitating disease course. The objective was to determine if short-term parenteral dihydroergotamine, dexamethasone and hydroxyzine can terminate chronic migraine and be followed by a continuous respite or conversion to a more benign episodic form without the need for daily oral preventative medication ("carry-over effect"). We treated ten patients, seven adolescents and three adults, with parenteral dihydroergotamine, dexamethasone and hydroxyzine given once a week for a maximum of three weeks. No oral preventative daily medication was administered. The setting was a private practice. Chronic migraine was terminated in all 7 adolescents. Their post-treatment course was converted to a more benign episodic migraine course and no adolescent required daily oral migraine preventative therapy for significantly long carry-over post-treatment observational periods. None of the three adult chronic migraine cases could be terminated satisfactorily as they all required daily oral preventative therapy. In the adolescent group only, this strategy terminated chronic migraine and resulted in a significant carry-over effect that appeared to favourably modify the long-term course without the need for daily pharmacological, potentially toxic, preventive therapy. Although this is a very small study, which requires confirmation by a larger controlled study, our data suggest a significant carryover effect in the young migraineur by administering short-term parenteral dihydroergotamine, dexamethasone and hydroxyzine.

Administration, Oral↗