Search PubMed⌕ Search

Biomedical subjects

S M Cheer

Publications and source records attributed to S M Cheer.

10 recordsLinked to original sources
PubMed2001

Fluoxetine: a review of its therapeutic potential in the treatment of depression associated with physical illness.

UNLABELLED: Fluoxetine is a potent and selective inhibitor of neuronal serotonin (5-hydroxytryptamine) reuptake. Fluoxetine reduces food, energy and carbohydrate intake and increases resting energy expenditure, which may account for the moderate and transient bodyweight loss observed with its use. Glucose tolerance and/or hypoglycaemia in patients with type 2 diabetes mellitus improve with fluoxetine therapy. The ability of fluoxetine to inhibit cytochrome P450 (CYP) isoenzymes (CYP2D6, CYP2C and CYP3A4), is potentially important for patients with physical illness who may be taking multiple concomitant medications. Fluoxetine was more effective than placebo in 2 double-blind, randomised trials, and according to limited data appears to be equally effective compared with other SSRIs and tricyclic antidepressants (TCAs), in the treatment of depression in patients with HIV/AIDS. The efficacy of fluoxetine is also superior to that of placebo in the treatment of depression in patients with diabetes mellitus and stroke as shown in double-blind randomised trials, although its efficacy relative to that of nortriptyline in stroke is uncertain. Fluoxetine had similar efficacy to that of desipramine in patients with cancer, with improved Hamilton Depression Rating Scale and quality-of-life scores from baseline; however, the drug was not more effective than placebo in a double-blind randomised trial. Medically healthy individuals tolerate fluoxetine well. Like other SSRIs, fluoxetine lacks the anticholinergic, cardiovascular, sedative and weight-increasing properties of TCAs, and is safer in overdose than TCAs and monoamine oxidase inhibitors. Rates of sexual dysfunction and suicidal ideation with fluoxetine appear similar to those seen with other SSRIs. CONCLUSION: Fluoxetine has shown superior efficacy compared with placebo in the treatment of depression in patients with HIV/AIDS, diabetes mellitus or stroke; however, it has not significantly improved depressive symptoms versus placebo in patients with cancer. The efficacy of fluoxetine appears similar to that of desipramine in patients with stroke, cancer or HIV, and is similar to that of sertraline or paroxetine in patients with HIV/AIDS; comparisons with nortriptyline give equivocal results. The potential for drug interactions with fluoxetine use should be carefully considered because most patients with comorbid physical illness will be receiving multiple comedications. Although fluoxetine has proved effective as an antidepressant in this population in several clinical trials, its drug interaction profile and long half-life are a potential limitation, and these properties should be carefully considered in relation to the status of each patient.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Zoledronic acid.

Zoledronic acid (zoledronate) is a new generation bisphosphonate that inhibits osteoclast bone resorption. It was much more potent than other bisphosphonates at inhibiting 1,25-dihydroxyvitamin D3-induced hypercalcaemia in a rat model and calcium release in vitro. A single 5-minute intravenous infusion of zoledronic acid (4 or 8 mg) was significantly more effective than a 2-hour infusion of pamidronic acid (pamidronic acid disodium, pamidronate disodium) [90 mg] in normalising serum calcium levels in patients with hypercalcaemia of malignancy and resulted in a significantly longer median time to relapse (pooled analysis from 2 randomised, double-blind, parallel-group trials). There were no differences in tolerability between zoledronic acid and pamidronic acid in comparative trials; the most common events in pivotal trials were fever, anaemia, nausea, constipation and dyspnoea. Fever, hypophosphataemia and hypocalcaemia were the most common events in a small phase I trial.

Animals↗
PubMed2001

Parecoxib (parecoxib sodium).

Parecoxib (parecoxib sodium) is an injectable pro drug of valdecoxib, which is a potent and selective inhibitor of cyclo-oxygenase-2. Intravenous (IV) or intramuscular (IM) parecoxib >20 mg has analgesic activity superior to that of placebo and similar to that of IV or IM ketorolac 30 or 60 mg well controlled trials in patients with postoperative dental pain (n = 304 to 457). In a well controlled trial (n = 202), IV parecoxib 20 or 40mg showed analgesic activity greater than that of placebo and IV morphine 4mg and similar to that of IV ketorolac 30 mg following gynaecological surgery Following orthopaedic surgery, the analgesic activity of IV parecoxib 20 or 40mg was similar to that of IV ketorolac 30 mg and superior to that of IV morphine 4 mg or placebo in well controlled trials (n = 175 and 208). IV parecoxib (40 mg twice daily for 7 days) produced significantly fewer gastrointestinal erosions and/or ulcers than ketorolac (15 mg 4 times a day for 5 days) in healthy volunteers in a well controlled trial; effects on upper gastrointestinal mucosa were similar for parecoxib and placebo. Parecoxib is well tolerated after dental, gynaecological or orthopaedic surgery. The most common adverse events irrespective of treatment (parecoxib, ketorolac or placebo) after dental surgery were nausea, alveolar osteitis, dizziness and headache. Nausea, abdominal pain, headache, abdominal fullness, dizziness, back pain, fever, hypoactive bowel sounds, vomiting, tachycardia, somnolence, abnor mal breath sounds and pruritus occurred in > or = 10% of parecoxib recipients after gynaecological surgery. Similar results were seen in placebo recipients.

Abdominal Pain↗
PubMed2001

Perindopril/indapamide 2/0.625 mg/day: a review of its place in the management of hypertension.

The fixed low-dose combination of the ACE inhibitor perindopril and the non-thiazide diuretic indapamide has been evaluated in the management of patients with mild to moderate hypertension. Combination therapy aims to improve overall therapeutic efficacy while minimising adverse effects. In well-designed multicentre clinical trials, perindopril/indapamide at doses ranging from 2/0.625 to 8/2.5 mg/day was significantly more effective than placebo in achieving adequate blood pressure (BP) control. A similar reduction in supine BP was observed when combined perindopril/indapamide 2/0.625 mg/day was compared with losartan 50 mg/day or atenolol 50 mg/day. Similar reductions in 24-hour ambulatory BP were also seen with perindopril/indapamide 2/0.625 mg/day and irbesartan 150 mg/day. However, response and normalisation rates were significantly higher with combination therapy than with losartan or irbesartan monotherapy. Combined perindopril/indapamide 2/0.625 mg/day therapy effectively reduced BP in elderly patients aged 65 to 85 years to a significantly greater extent than either atenolol 50 mg/day or placebo. Supine BP was also normalised in approximately two-thirds of patients in a small noncomparative trial in patients with hypertension and renal impairment. Low-dose perindopril/indapamide 2/0.625 mg/day was well tolerated in clinical trials; the most common adverse events were headache and cough. Hypokalaemia, associated with the use of diuretics, occurred with a higher incidence with combined perindopril/indapamide 2/0.625 mg/day therapy than with either atenolol 50 mg/day or placebo. Perindopril/indapamide 2/0.625 mg/day has shown efficacy in well designed comparative trials with atenolol, losartan and irbesartan including elderly patients and patients with renal impairment. Studies comparing this dosage of perindopril/ indapamide with other combination therapies would be beneficial in allowing the place of perindopril/indapamide to be more accurately determined. The fixed-low dose combination of perindopril/indapamide provides a promising and well tolerated treatment option in the management of patients with mild to moderate hypertension.

Adult↗
PubMed2001

Manidipine: a review of its use in hypertension.

UNLABELLED: Manidipine is a dihydropyridine calcium antagonist, which causes systemic vasodilation by inhibiting the voltage-dependent calcium inward currents in smooth muscle cells. The resulting reduction in blood pressure (BP) in patients with hypertension is maintained over 24 hours. Manidipine 10 to 40 mg once daily for 4 weeks significantly lowered office BP from baseline and compared with placebo, and significantly reduced 24-hour BP compared with placebo in patients with essential hypertension in a well controlled trial. The decline in BP was maintained over 24 hours (trough to peak BP ratios were >50%) without disturbing the circadian BP pattern. BP reductions with therapeutic dosages of manidipine were maintained for up to 1 year in noncomparative trials. The BP-lowering capacity of manidipine 5 to 20 mg/day appears to be similar to that of other calcium antagonists with which it has been compared in randomised double-blind and nonblind trial. In a well controlled short term trial, manidipine 10 mg daily significantly decreased trough sitting BP compared with placebo in elderly patients with mild to moderate essential hypertension. Decreases in BP were maintained for up to 3 years of treatment. The drug (10 or 20 mglday) also significantly lowered sitting BP from baseline in patients with hypertension and type 2 diabetes mellitus in randomised, long term comparative trials. In general, the observed reduction in BP with manidipine was similar to that observed with amlodipine, enalapril or delapril. The effects of manidipine on urinary albumin excretion (UAE) have not been clearly demonstrated in clinical trials in this patient group. BP was also reduced with manidipine in patients with impaired glucose tolerance. Manidipine was well tolerated in clinical trials, with most adverse effects related to vasodilation. Commonly reported events included ankle oedema, headache. palpitation. flushing, dizziness, rash and fatigue. Manidipine appears to have less potential for pedal oedema than amlodipine. CONCLUSIONS: Manidipine has shown antihypertensive efficacy and appears to be well tolerated in adult and elderly patients with mild or moderate essential hypertension. The BP-lowering effects of the drug in patients with hypertension and type 2 diabetes mellitus or impaired glucose tolerance were not associated with any adverse metabolic effects. The effects of manidipine on UAE in this patient group remain unclear. Manidipine provides an additional treatment option for patients for whom dihydropyridine calcium antagonists are appropriate. Manidipine is a dihydropyridine calcium antagonist, which causes systemic vasodilation by inhibiting the voltage-dependent calcium inward currents in smooth muscle cells. The resulting reduction in blood pressure (BP) in patients with hypertension is maintained over 24 hours. Manidipine 10 to 40mg once daily for 4 weeks significantly lowered office BP from baseline and compared with placebo, and significantly reduced 24-hour BP compared with placebo in patients with essential hypertension in a well controlled trial. The decline in BP was maintained over 24 hours (trough to peak BP ratios were >50%) without disturbing the circadian BP pattern. BP reductions with therapeutic dosages of manidipine were maintained for up to 1 year in non-comparative trials. The BP-lowering capacity of manidipine 5 to 20 mg/day appears to be similar to that of other calcium antagonists with which it has been compared in randomised double-blind and nonblind trial. In a well controlled short term trial, manidipine 10 mg daily significantly decreased trough sitting BP compared with placebo in elderly patients with mild to moderate essential hypertension. Decreases in BP were maintained for up to 3 years of treatment. The drug (10 or 20 mg/day) also significantly lowered sitting BP from baseline in patients with hypertension and type 2 diabetes mellitus in randomised, long term comparative trials. In general, the observed reduction in BP with manidipine was similar to that observed with amlodipine, enalapril or delapril. The effects of manidipine on urinary albumin excretion (UAE) have not been clearly demonstrated in clinical trials in this patient group. BP was also reduced with manidipine in patients with impaired glucose tolerance. Manidipine was well tolerated in clinical trials, with most adverse effects related to vasodilation. Commonly reported events included ankle oedema, headache. palpitation. flushing, dizziness, rash and fatigue. Manidipine appears to have less potential for pedal oedema than amlodipine. CONCLUSIONS: Manidipine has shown antihypertensive efficacy and appears to be well tolerated in adult and elderly patients with mild or mo

Aged↗
PubMed2001

Tacrolimus ointment. A review of its therapeutic potential as a topical therapy in atopic dermatitis.

UNLABELLED: Tacrolimus, a macrolide immunomodulator, is believed to control atopic dermatitis by inhibiting T lymphocyte activation, altering cell surface expression on antigen-presenting dendritic cells and modulating the release of inflammatory mediators from skin mast cells and basophils. Tacrolimus ointment penetrates human skin with no systemic accumulation after repeated applications; systemic absorption is generally low, with most patients in clinical trials having blood concentrations of the drug below the limit of quantification. Moderate to severe atopic dermatitis significantly improved (measured using multiple end-points, including > or = 90% improvement in Physician's Global Evaluation of Clinical Response) with tacrolimus 0.03 and 0.1% ointment compared with vehicle in both adult (n = 304 and 328) and pediatric (n = 351) patients in three 12-week, double-blind, randomized, phase III trials. In adults, tacrolimus ointment was effective therapy for the treatment of atopic dermatitis on all skin regions, including the head and neck. The 0.1% concentration was more effective than the 0.03% concentration. Clinical improvement in moderate to severe atopic dermatitis in adult (n = 316) or pediatric (n = 255) patients was seen as early as week 1, and improvement continued and/or was maintained for up to 6 and/or 12 months in long-term studies. The 0.1% formulation was also effective and well tolerated for up to 2 years. Tacrolimus 0.03 and 0.1% ointment was associated with significant quality-of-life benefit in adults, children (aged 5 to 15 years) and toddlers (aged 2 to 4 years) with atopic dermatitis in 12-week phase III trials (n = 985). Skin burning and pruritus were the most common application site adverse events in adult and pediatric patients in short-term and long-term trials. These events were generally of short duration and mild or moderate severity. Cutaneous infections occurred with a similar incidence after treatment with tacrolimus ointment to that seen after vehicle in short-term trials. CONCLUSION: Both short- and long-term monotherapy with tacrolimus 0.03 and 0.1% ointment improves moderate to severe atopic dermatitis in adult and pediatric patients. Topical tacrolimus ointment is well tolerated, with the majority of adverse events being localized, transient in nature and of mild or moderate severity. Tacrolimus ointment provides a promising addition to the currently available treatments for atopic dermatitis; it can be used as a short- or long-term intermittent therapy for moderate to severe disease, including disease on the head or neck, in adult (0.1 and 0.03% formulations) and pediatric (0.03% formulation) patients who are not adequately responsive to or are intolerant of conventional treatments.

Administration, Topical↗
PubMed2001

Fluvoxamine: a review of its therapeutic potential in the management of anxiety disorders in children and adolescents.

Fluvoxamine is a selective serotonin reuptake inhibitor (SSRI) which may be used for the management of anxiety disorders in children and adolescents. Absorption of fluvoxamine was similar in adolescents to that in adults, which suggests that the maximum dosage of the drug for patients aged between 12 and 17 years can be as high as 300 mg/day. However, steady-state plasma fluvoxamine [corrected] concentrations were 2 to 3 times higher in children (aged between 6 and 11 years) than in adolescents; thus, the maximum fluvoxamine dosage recommended for children is 200 mg/day. Fluvoxamine (50 to 300 mg/day) for 8 to 16 weeks significantly reduced symptoms of obsessive-compulsive disorder (OCD) [measured across multiple assessment scales] compared with placebo in a well controlled trial in paediatric patients (n = 120) or from baseline in noncomparative trials in adolescent (n = 20) or paediatric (n = 16) patients. Improvements with fluvoxamine (up to 200 mg/day) were observed for up to 1 year in 98 patients with OCD in a noncomparative trial. The drug (up to 250 or 300 mg/day) also improved symptoms of anxiety compared with placebo in an 8-week well controlled trial in 128 paediatric patients with social phobia, separation anxiety disorder or generalised anxiety disorder (GAD). Fluvoxamine (50 to 300 mg/day) appears to be well tolerated in paediatric patients, with most adverse events with the drug (except abdominal discomfort, which occurred more often in patients receiving fluvoxamine) occurring with a similar incidence to those with placebo. The most common adverse events involved the central nervous system or gastrointestinal system. Most adverse events reported by paediatric patients with OCD were similar to those reported by adults. In conclusion, fluvoxamine is generally well tolerated and has demonstrated short-term efficacy compared with placebo in the treatment of OCD, and social phobia, separation anxiety disorder or GAD in well controlled trials in paediatric patients. Reductions in symptoms of anxiety with fluvoxamine have been observed for up to 1 year in children and adolescents with OCD. However, there are currently no comparative trials of fluvoxamine with other pharmacological agents. In the absence of such trials, current consensus opinion recommends that when pharmacotherapy is indicated, fluvoxamine, like other SSRIs, can be used as first-line treatment for anxiety disorders, particularly OCD, in paediatric patients. However, direct comparisons are required to assess the relative efficacy and tolerability of pharmacological agents in order to make firm recommendations for the treatment of anxiety disorders in this patient group.

Adolescent↗
PubMed2000

Lactose digestion capacity in Tokelauans: a case for the role of gene flow and genetic drift in establishing the lactose absorption allele in a Polynesian population.

Throughout the Pacific, lactose absorption occurs at rates of 0-46%. Most authors explain the current rate of lactose absorption in the Pacific in terms of gene flow with Europeans. However, researchers have not been able to determine the exact historical circumstances of the introduction of the lactose absorption gene. The availability of genealogical material, historical information, and mal/absorption frequencies for Tokelau (a Polynesian population) presents a unique opportunity to examine the role of gene flow in establishing lactose absorption in Pacific isolates. In an earlier study, Cheer and Allen ([1997] Am. J. Hum. Biol. 93:1-34) determined lactose digestion capacities for 58 Tokelauans. In the current study, we constructed pedigrees for the same 58 individuals, using the Tokelau Island Migrant Study genealogies (Wessen et al. [1992]). Results indicated that 8 of 13 lactose-absorbing individuals have European ancestors, compared with only 4 of 35 lactose malabsorbers (Chi(2) = 15.75, P < 0.01). Six lactose-absorbing individuals have either American or Portuguese ancestors dating back to the mid-1800s. Historical data were used to establish the contribution of Portuguese and American genetic material to the Tokelau population following massive depopulation after the Peruvian slave raids of 1863. This study provides clear evidence for the role of a population bottleneck followed by gene flow and genetic drift in establishing lactose absorption in the Tokelau population. Furthermore, it is the first study of a Pacific population to directly link lactose absorption with gene flow.

Absorption↗
PubMedDate not supplied

Alitretinoin.

Alitretinoin is a retinoid receptor pan-agonist, which has been investigated in the treatment of Kaposi's sarcoma (KS). Binding with high affinity to all known retinoid receptors, alitretinoin is thought to regulate proliferation, differentiation, and apoptosis of KS cells. Significantly more patients experienced complete or partial responses [according to the AIDS Clinical Trials Group (ACTG) criteria for topical treatment of cutaneous KS] with alitretinoin 0.1% gel 2 to 4 times daily than with vehicle gel in 2 phase III, multicenter, 12-week, randomized, double-blind clinical trials of patients with AIDS-related KS (35 vs 18%, p = 0.002 and 37 vs 7%, p = 0.00003, respectively). Responses were also observed in patients refractory to prior systemic or topical anti-KS therapies. In an intent-to-treat analysis in a phase II trial, 37% of patients with AIDS-related KS receiving alitretinoin capsules 60 to 100 mg/m2/day demonstrated either complete or partial responses (determined by ACTG criteria). The majority of adverse events associated with alitretinoin 0.1% gel were classified as either mild or moderate, occurred at the site of application and were reversible. In both phase III trials, rash was the most common adverse event. The most common adverse events in patients taking alitretinoin capsules included headache, dry skin, rash, alopecia, exfoliative dermatitis, and hyperlipidemia.

Alitretinoin↗