David R Goldsmith | Search PubMed

PubMed2006

Neural correlates of social cooperation and non-cooperation as a function of psychopathy.

BACKGROUND: Psychopathy is a disorder involving a failure to experience many emotions that are necessary for appropriate social behavior. In this study, we probed the behavioral, emotional, and neural correlates of psychopathic traits within the context of a dyadic social interaction. METHODS: Thirty subjects were imaged with functional magnetic resonance imaging while playing an iterated Prisoner's Dilemma game with human confederates who were outside the scanner. Subjects also completed two self-report psychopathy questionnaires. RESULTS: Subjects scoring higher on psychopathy, particularly males, defected more often and were less likely to continue cooperating after establishing mutual cooperation with a partner. Further, they experienced more outcomes in which their cooperation was not reciprocated (cooperate-defect outcome). After such outcomes, subjects scoring high in psychopathy showed less amygdala activation, suggesting weaker aversive conditioning to those outcomes. Compared with low-psychopathy subjects, subjects higher in psychopathy also showed weaker activation within orbitofrontal cortex when choosing to cooperate and showed weaker activation within dorsolateral prefrontal and rostral anterior cingulate cortex when choosing to defect. CONCLUSIONS: These findings suggest that whereas subjects scoring low on psychopathy have emotional biases toward cooperation that can only be overcome with effortful cognitive control, subjects scoring high on psychopathy have an opposing bias toward defection that likewise can only be overcome with cognitive effort.

Adult↗

PubMed2006

Mammalian cell-derived somatropin : a review of its use in the management of HIV-associated wasting.

HIV-associated wasting, characterised by progressive loss of lean body mass and bodyweight, remains a significant problem in the era of highly active antiretroviral therapy (HAART). Loss of body cell mass, a component of lean body mass, is associated with decreased survival. Somatropin (recombinant human growth hormone) derived from mammalian cells (Serostim) is the only US FDA-approved treatment indicated to increase lean body mass, bodyweight and physical endurance in HIV-associated wasting. Somatropin 0.1 mg/kg/day administered subcutaneously for 12 weeks effectively increased work output, bodyweight and lean body mass and improved health-related quality of life (HR-QOL), compared with placebo, and had a generally manageable tolerability profile in a large randomised study in patients with HIV-associated wasting. Potential areas for further research include determination of longer-term efficacy and tolerability, the cost effectiveness of treatment, the optimal somatropin dosage, management of patients after 12 weeks' therapy and whether maintenance strategies might exist to maintain accrued lean body mass with lower doses of somatropin. Nevertheless, indications to date are that somatropin is likely to have an important role in the treatment of patients with HIV-associated wasting.

Body Composition↗

PubMed2006

Spotlight on mammalian cell-derived somatropin in HIV-associated wasting.

HIV-associated wasting, characterized by progressive loss of lean body mass and bodyweight, remains a significant problem in the era of highly active antiretroviral therapy. Loss of body cell mass, a component of lean body mass, is associated with decreased survival. Somatropin (recombinant human growth hormone) derived from mammalian cells (Serostim) is the only US FDA-approved treatment indicated to increase lean body mass, bodyweight, and physical endurance in HIV-associated wasting. Somatropin 0.1 mg/kg/day administered subcutaneously for 12 weeks effectively increased work output, bodyweight, and lean body mass, and improved health-related quality of life, compared with placebo, and had a generally manageable tolerability profile in a large randomized study in patients with HIV-associated wasting. Potential areas for further research include determination of longer-term efficacy and tolerability, the cost effectiveness of treatment, the optimal somatropin dosage, management of patients after 12 weeks' therapy, and whether maintenance strategies might exist to maintain accrued lean body mass with lower doses of somatropin. Nevertheless, indications to date are that somatropin is likely to have an important role in the treatment of patients with HIV-associated wasting.

Clinical Trials as Topic↗

PubMed2005

Naftidrofuryl: a review of its use in the treatment of intermittent claudication.

Naftidrofuryl (Praxilene) is a vasodilator that has been used in the treatment of intermittent claudication for >30 years in Europe to improve walking distance and provide symptomatic relief. However, earlier trials had inconsistencies in design and the clinical relevance of the treatment effect has been controversial. Recent randomised, double-blind, placebo-controlled trials, however, have generally been conducted in accordance with updated methodology guidelines. In these studies, naftidrofuryl 200mg three times daily improved pain-free and maximal walking distances and health-related quality of life by a significantly greater extent than placebo in patients with intermittent claudication. The magnitude of these effects appears to support claims that the effects of naftidrofuryl are clinically relevant in these patients.

Humans↗

PubMed2005

Doxazosin gastrointestinal therapeutic system: a review of its use in benign prostatic hyperplasia.

Doxazosin, a well established treatment in patients with bothersome lower urinary tract symptoms from benign prostatic hyperplasia (BPH), is available in a new controlled-release formulation, doxazosin gastrointestinal therapeutic system (GITS). Doxazosin GITS (Cardura XL, Cardular PP Uro, Diblocin PP Uro) has an altered pharmacokinetic profile, which allows a higher initial dosage to be used than with the standard formulation and less titration steps to reach a clinically effective dosage. In two large, double-blind, randomised studies (one was placebo-controlled) in patients with BPH, doxazosin GITS (4-8 mg once daily) was as effective as the standard formulation (2-8 mg once daily), and both were more effective than placebo, after 13 weeks' treatment in improving symptom scores, health-related quality of life (HR-QOL), and maximum urinary flow rate (Qmax). Doxazosin GITS was at least as well tolerated as the standard formulation of doxazosin in clinical studies in patients with BPH.

Adrenergic alpha-Antagonists↗

PubMed2005

Spotlight on etanercept in plaque psoriasis and psoriatic arthritis.

Etanercept (Enbrel), a tumor necrosis factor (TNF)-alpha antagonist produced by recombinant technology, is approved for use in the US as subcutaneous monotherapy in adults with moderate-to-severe psoriasis who are candidates for systemic therapy or phototherapy. The drug is also indicated in patients with psoriatic arthritis, in whom it may be used in combination with methotrexate. In well designed trials in patients with moderate-to-severe psoriasis, short-term etanercept therapy (typically 25 or 50mg twice weekly) significantly increased the proportion of patients achieving a 75% reduction in the Psoriasis Area and Severity Index score compared with placebo. Similarly, in well designed trials in patients with psoriatic arthritis, treatment with short-term etanercept 25mg twice weekly, alone or in combination with methotrexate, improved clinical features of the disease, while radiographic progression of joint damage appeared to be significantly slowed in a nonblind 1-year extension. Short-term etanercept therapy was well tolerated in patients with psoriasis or psoriatic arthritis. Etanercept is thus a valuable new option for the treatment of patients with chronic moderate-to-severe plaque psoriasis (who are candidates for systemic therapy or phototherapy or have failed other systemic therapies) or with psoriatic arthritis.

Arthritis, Psoriatic↗

PubMed2005

Etanercept: a review of its use in the management of plaque psoriasis and psoriatic arthritis.

Etanercept (Enbrel), a tumor necrosis factor-alpha antagonist produced by recombinant technology, is approved for use in the US as subcutaneous monotherapy in adults with moderate-to-severe psoriasis who are candidates for systemic therapy or phototherapy. The drug is also indicated in patients with psoriatic arthritis, in whom it may be used in combination with methotrexate. In well designed trials in patients with moderate-to-severe psoriasis, short-term etanercept therapy (typically 25 or 50 mg twice weekly) significantly increased the proportion of patients achieving a 75% reduction in the Psoriasis Area and Severity Index score compared with placebo. Similarly, in well designed trials in patients with psoriatic arthritis, treatment with short-term etanercept 25 mg twice weekly, alone or in combination with methotrexate, improved clinical features of the disease, while radiographic progression of joint damage appeared to be significantly slowed in a nonblind 1-year extension. Short-term etanercept therapy was well tolerated in patients with psoriasis or psoriatic arthritis. Etanercept is thus a valuable new option for the treatment of patients with chronic moderate-to-severe plaque psoriasis (who are candidates for systemic therapy or phototherapy or have failed other systemic therapies) or with psoriatic arthritis.

Drug Administration Schedule↗

PubMed2004

Inhaled iloprost: in primary pulmonary hypertension.

Iloprost is a stable prostacyclin analogue with a pharmacokinetic profile allowing nebulised administration in patients with primary pulmonary hypertension (PPH). Inhaled iloprost is a potent acute pulmonary vasodilator with a duration of action of about 60 minutes. It may exert additional long-term benefit through antiproliferative and antithrombotic effects. Inhaled iloprost 2.5 or 5 microg six or nine times daily for 12 weeks (n = 101) significantly (p < 0.01) improved a combined clinical endpoint of a > or =10% increase in distance walked in 6 minutes and an improvement of > or =1 class in New York Heart Association functional class without clinical deterioration or death (16.8 versus 4.9% of placebo recipients, n = 102) in patients with severe PPH or selected forms of nonprimary pulmonary hypertension. Statistical analysis of the response for the PPH subgroup (20.8 versus 5.5% with placebo; n = 51 and 51) was not reported. Improvements from baseline in exercise capacity and haemodynamic/gas exchange variables have been reported in patients with PPH with continued use of inhaled iloprost. In addition, improvement in preinhalation vascular resistance occurred after 12 weeks of inhaled iloprost (p < 0.01 versus placebo) in a large randomised trial. Increased cough, headache, flushing and an influenza-like syndrome were the most common adverse events in the largest trial of patients receiving inhaled iloprost. Headache, flushing and jaw pain occurred significantly more frequently with inhaled iloprost than with placebo.

Administration, Inhalation↗

PubMed2004

Budesonide/formoterol: a review of its use in asthma.

Budesonide and formoterol have been combined in a single dry powder device, Symbicort Turbuhaler (budesonide/formoterol 160/9-640/18 microg/day), in an effort to simplify asthma management. The efficacy of budesonide/formoterol as maintenance therapy in patients with asthma has been examined in several randomised studies.Twice-daily budesonide/formoterol was significantly more effective than an equivalent or higher daily dose of budesonide alone or high-dose fluticasone propionate alone at improving peak expiratory flow (PEF) in adults with predominantly moderate persistent asthma. Symptom control and the risk of mild exacerbations were significantly improved versus budesonide alone. Moreover, budesonide/formoterol appeared to be as effective as concurrent therapy with equivalent dosages of budesonide and formoterol administered via separate inhalers in adults with moderate persistent asthma. Budesonide/formoterol administered once daily was as effective as twice-daily administration (equivalent daily doses) and more effective than once-daily budesonide in adults with moderate persistent asthma. Twice-daily budesonide/formoterol significantly improved PEF compared with budesonide in paediatric patients with asthma. Adjustable maintenance dosing with budesonide/formoterol was associated with significantly less study drug use than fixed dosing with budesonide/formoterol in adults with predominantly mild or moderate persistent asthma. In two of three studies (all longer than 4 months' duration), the risk of exacerbations was significantly lower with adjustable than with fixed dosing, but no difference was detected in four short-term studies. Symptom severity was maintained or improved in most patients receiving either treatment regimen. In adults with moderate-to-severe persistent asthma, adjustable maintenance dosing with budesonide/formoterol reduced the rate of exacerbations and reliever medication use compared with fixed dosing with salmeterol/fluticasone propionate. Budesonide/formoterol was well tolerated in both fixed and adjustable dosing regimens. In conclusion, in patients with persistent asthma symptoms despite treatment with inhaled corticosteroids, budesonide/formoterol administered via a single dry powder Turbuhaler device is an effective, well tolerated, convenient treatment option, which may have the potential for improved compliance. It appears to be as effective as treatment with budesonide and formoterol administered via separate inhalers and is more effective than budesonide monotherapy in improving PEF, controlling symptoms and preventing mild exacerbations. Adjustable maintenance dosing with budesonide/formoterol is associated with a lower overall dosage and appears to maintain control as effectively as fixed dosing.

Animals↗

PubMed2004

Amphotericin B lipid complex: in visceral leishmaniasis.

Amphotericin B lipid complex is a lipid formulation of amphotericin B, an antifungal drug with activity against Leishmania spp. Amphotericin B lipid complex appears to enhance uptake of amphotericin B by infected macrophages in patients with visceral leishmaniasis (VL). In randomised, open-label, dose-ranging studies, short-course treatment with once-daily amphotericin B lipid complex (5-15 mg/kg total cumulative dose over 5 days), administered by intravenous infusion, produced high rates of apparent (day 19) [93-100%] and definitive (6 months) [79-100%] cures in Indian patients with antimonial-resistant VL. Amphotericin B lipid complex appeared to be as effective as liposomal amphotericin B or the conventional deoxycholate formulation in a randomised, open-label study conducted in India in a mixed population of patients with previously untreated or antimonial-resistant VL. In patients with HIV infection and VL, amphotericin B lipid complex 3 mg/kg/day for 5 or 10 days appeared to be as effective as meglumine antimonate 20 mg/kg/day for 28 days in a small randomised pilot study in southern Europe. Amphotericin B lipid complex was generally well tolerated in patients with VL. Infusion-related reactions were the most common adverse events associated with amphotericin B lipid complex.

Amphotericin B↗

PubMed2004

Spotlight on lamotrigine in bipolar disorder.

UNLABELLED: Lamotrigine (Lamictal), a phenyltriazine derivative, is a well established anticonvulsant agent that has shown efficacy in the prevention of mood episodes in adult patients with bipolar I disorder. The mechanism of action of the drug in patients with bipolar disorder may be related to the inhibition of sodium and calcium channels in presynaptic neurons and subsequent stabilisation of the neuronal membrane. Lamotrigine monotherapy significantly delayed time to intervention with additional pharmacotherapy or electroconvulsive therapy for any new mood episode (mania, hypomania, depression and mixed episodes), compared with placebo, in two large, randomised, double-blind trials of 18 months' duration. Additionally, lamotrigine was significantly superior to placebo at prolonging time to intervention for depression. These effects of lamotrigine were demonstrated in both recently manic/hypomanic and recently depressed patients. Lamotrigine showed efficacy in delaying manic/hypomanic episodes in pooled data only, although lithium was superior to lamotrigine on this measure. Two of four double-blind, short-term studies have shown lamotrigine to be more effective than placebo in the treatment of patients with treatment-refractory bipolar disorder or those with bipolar depression. Lamotrigine has not demonstrated efficacy in the treatment of acute mania. Lamotrigine was generally well tolerated in maintenance studies with the most common adverse events being headache, nausea, infection and insomnia. Incidences of diarrhoea and tremor were significantly lower in lamotrigine- than in lithium-treated patients. The incidence of serious rash with lamotrigine treatment was 0.1% in all studies of bipolar disorder and included one case of mild Stevens-Johnson syndrome. Lamotrigine did not appear to cause bodyweight gain. The dosage of lamotrigine is titrated over a 6-week period to 200 mg/day to minimise the incidence of serious rash. Adjustments to the initial and target dosages are required if coadministered with valproate semisodium or carbamazepine. CONCLUSION: Lamotrigine has been shown to be an effective maintenance therapy for patients with bipolar I disorder, significantly delaying time to intervention for any mood episode. Additionally, lamotrigine significantly delayed time to intervention for a depressive episode and showed limited efficacy in delaying time to intervention for a manic/hypomanic episode, compared with placebo. Although not approved for the short-term treatment of mood episodes, lamotrigine has shown efficacy in the acute treatment of patients with bipolar depression but has not demonstrated efficacy in the treatment of acute mania. Lamotrigine is generally well tolerated, does not appear to cause bodyweight gain and, unlike lithium, generally does not require monitoring of serum levels.

Antidepressive Agents↗

PubMed2003

Donepezil: in vascular dementia.

Vascular dementia (VaD), caused by stroke or small vessel disease, is the second most common form of dementia after Alzheimer's disease (AD). Donepezil, an acetylcholinesterase inhibitor currently indicated for use in patients with mild to moderate AD, has recently been evaluated in VaD. Donepezil 5 or 10mg once daily provided significant improvements in cognition, as determined by the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), relative to placebo, after 24 weeks in patients with VaD. Pooled data from two, randomised, double-blind, phase III trials showed that the least-squares mean change from baseline score effect size for the ADAS-cog was -1.79 for donepezil 5mg once daily (p < 0.001) and -2.28 for donepezil 10mg once daily (p < 0.001) at 24 weeks (observed cases). Significant improvement in global functioning occurred with donepezil 5mg once daily compared with placebo (p = 0.003), but not with donepezil 10mg once daily, as measured by the Clinician's Interview-Based Impression of Change-plus version score (pooled data, observed cases). Donepezil was generally well tolerated in patients with VaD. Most adverse events were mild to moderate in nature, with diarrhoea and nausea being the most common.

Administration, Oral↗

PubMed2003

Atazanavir.

Atazanavir is a novel azapeptide protease inhibitor with high specificity for, and activity against, HIV-1 protease. The resistance profile of atazanavir is distinct, with an I50 L protease substitution appearing to be the signature mutation. Atazanavir was not associated with increases in total cholesterol, low density lipoprotein-cholesterol or triglyceride levels after 108 weeks. Atazanavir has a pharmacokinetic profile that allows for once-daily oral administration. It is a moderate inhibitor of hepatic cytochrome P450 enzymes and interacts with several drugs. In combination with stavudine plus didanosine, atazanavir 200, 400 or 500 mg once daily produced a rapid and sustained reduction from baseline in viral load of 2.57, 2.42 and 2.53 log(10) copies/mL, respectively, in treatment-naive patients after 48 weeks, compared with a decrease of 2.33 log(10) copies/mL with nelfinavir 750 mg three times daily. Nausea was the most clinically relevant adverse event reported in patients receiving atazanavir-based regimens.

Administration, Oral↗

PubMed2003

Lamotrigine: a review of its use in bipolar disorder.

UNLABELLED: Lamotrigine (Lamictal), a phenyltriazine derivative, is a well established anticonvulsant agent that has shown efficacy in the prevention of mood episodes in adult patients with bipolar I disorder. The mechanism of action of the drug in patients with bipolar disorder may be related to the inhibition of sodium and calcium channels in presynaptic neurons and subsequent stabilisation of the neuronal membrane. Lamotrigine monotherapy significantly delayed time to intervention with additional pharmacotherapy or electroconvulsive therapy for any new mood episode (mania, hypomania, depression and mixed episodes), compared with placebo, in two large, randomised, double-blind trials of 18 months' duration. Additionally, lamotrigine was significantly superior to placebo at prolonging time to intervention for depression. These effects of lamotrigine were demonstrated in both recently manic/hypomanic and recently depressed patients. Lamotrigine showed efficacy in delaying manic/hypomanic episodes in pooled data only, although lithium was superior to lamotrigine on this measure. Two of four double-blind, short-term studies have shown lamotrigine to be more effective than placebo in the treatment of patients with treatment-refractory bipolar disorder or those with bipolar depression. Lamotrigine has not demonstrated efficacy in the treatment of acute mania. Lamotrigine was generally well tolerated in maintenance studies with the most common adverse events being headache, nausea, infection and insomnia. Incidences of diarrhoea and tremor were significantly lower in lamotrigine- than in lithium-treated patients. The incidence of serious rash with lamotrigine treatment was 0.1% in all studies of bipolar disorder and included one case of mild Stevens-Johnson syndrome. Lamotrigine did not appear to cause bodyweight gain. The dosage of lamotrigine is titrated over a 6-week period to 200 mg/day to minimise the incidence of serious rash. Adjustments to the initial and target dosages are required if coadministered with valproate semisodium or carbamazepine. CONCLUSION: Lamotrigine has been shown to be an effective maintenance therapy for patients with bipolar I disorder, significantly delaying time to intervention for any mood episode. Additionally, lamotrigine significantly delayed time to intervention for a depressive episode and showed limited efficacy in delaying time to intervention for a manic/hypomanic episode, compared with placebo. Although not approved for the short-term treatment of mood episodes, lamotrigine has shown efficacy in the acute treatment of patients with bipolar depression but has not demonstrated efficacy in the treatment of acute mania. Lamotrigine is generally well tolerated, does not appear to cause bodyweight gain and, unlike lithium, generally does not require monitoring of serum levels.

Antimanic Agents↗