Optical path clearing and enhanced transmission through colloidal suspensions.

We utilize advanced laser fields to clear a path through a dynamic turbid medium, a concept termed "Optical path clearing (OPC)." Particles are evacuated from a volume of the medium using the gradient and/or scattering forces due to an applied laser field with a suitably tailored spatial profile. Our studies encompass both an analytical model and proof-of-principle experiments where paths are cleared in dense bulk colloidal suspensions. Based on our results we suggest that high-performance and high efficiency OPC will be achieved by multiple-step clearing using dynamic laser fields based on Airy or inverted axicon beams.

Clinical investigation of hospitalized human cases of West Nile virus infection in Houston, Texas, 2002-2004.

The objective of this study was to describe the clinical features of cases hospitalized with West Nile virus (WNV) infections and identify clinical parameters that could potentially predict poor outcome (death). Retrospective medical chart reviews were completed for 172 confirmed cases of WNV infection hospitalized in the Houston, Texas, metropolitan area between 2002 and 2004. Of the 172 patients, 113 had encephalitis which resulted in 17 deaths, 47 had meningitis, and 12 had uncomplicated fever. Risk factors associated with progression from encephalitis to death were absence of pleocytosis in the cerebrospinal fluid, renal insufficiency, requiring intubation and mechanical ventilation, presence of myoclonus or tremors, and loss of consciousness. These findings can aid physicians in evaluating their patients suspected of WNV infection and determining outcomes in their patients with confirmed WNV neuroinvasive disease.

Risk factors for encephalitis and death from West Nile virus infection.

We conducted a nested case-control study to determine potential risk factors for developing encephalitis from West Nile virus (WNV) infection. Retrospective medical chart reviews were completed for 172 confirmed WNV cases hospitalized in Houston between 2002 and 2004. Of these cases, 113 had encephalitis, including 17 deaths, 47 had meningitis, and 12 were fever cases; 67% were male. Homeless patients were more likely to be hospitalized from WNV compared to the general population. A multiple logistic regression model identified age [odds ratio (OR) 1.1, P<0.001], history of hypertension, including those cases taking hypertension-inducing drugs (OR 2.9, P=0.012), and history of cardiovascular disease (OR 3.5, P=0.061) as independent risk factors for developing encephalitis from WNV infection. After adjusting for age, race/ethnicity (being black) (OR 12.0, P<0.001), chronic renal disease (OR 10.6, P<0.001), hepatitis C virus (OR 23.1, P=0.0013), and immunosuppression (OR 3.9, P=0.033) were identified as risk factors for death from WNV infection.

Diclofenac-potassium in migraine: a review.

UNLABELLED: The NSAID diclofenac is a potent inhibitor of prostaglandin synthesis and an established antipyretic and analgesic agent. Diclofenac-potassium was developed as an immediate-release tablet with the aim of providing rapid onset of action after oral administration. This formulation has been investigated in the acute treatment of migraine. Data from available placebo-controlled clinical trials indicate that diclofenac-potassium 50 or 100mg as an immediate-release tablet is more effective than placebo and as effective as oral sumatriptan 100mg and ergotamine plus caffeine at reducing pain intensity in patients with migraine 2 hours after initial administration. Duration of pain relief is similar for the 3 drugs but onset appears to be faster with diclofenac-potassium than with oral sumatriptan or ergotamine plus caffeine. Diclofenac-potassium appears to have favourable effects on some accompanying symptoms such as nausea and vomiting. The frequency of these symptoms was significantly lower with diclofenac-potassium than with sumatriptan in 1 study, although only a few patients had vomiting at baseline. Effects on phonophobia or photophobia did not differ between diclofenac-potassium, sumatriptan and ergotamine plus caffeine. The need for rescue medication is consistently less with diclofenac-potassium than with placebo. Data are inconsistent or scarce regarding the effects of diclofenac-potassium versus placebo on other measures such as headache recurrence and working ability. Diclofenac-potassium was generally well tolerated in clinical trials in patients with migraine. Adverse events reported most frequently (abdominal pain, tiredness and fatigue and nausea) were typically mild to moderate. CONCLUSION: Diclofenac-potassium provides rapid pain relief (within 60 to 90 minutes), is well tolerated and reduces the frequency of some of the accompanying symptoms in patients with migraine. Available trials indicate that diclofenac-potassium provides similar pain relief to sumatriptan and is at least as effective as ergotamine plus caffeine, but appears to have a greater effect on nausea and vomiting than sumatriptan and a faster onset of action than both drugs. Comparisons with other NSAIDs are lacking. Diclofenac-potassium is likely to find a role as a useful first-line option in the acute treatment of migraine.

Nebivolol in the management of essential hypertension: a review.

UNLABELLED: Nebivolol is a lipophilic beta1-blocker. It is devoid of intrinsic sympathomimetic or membrane stabilising activity but appears to have nitric oxide-mediated vasodilatory effects. Nebivolol is administered as a racemic mixture of equal proportions of d- and l-enantiomers. The drug does not significantly influence glucose or plasma lipid metabolism and appears to have a protective effect on left ventricular function. At the recommended dosage (5 mg once daily) nebivolol reduces resting diastolic blood pressure as effectively as standard therapeutic dosages of atenolol, metoprolol, lisinopril and nifedipine, as shown in comparative trials. Nebivolol reduced blood pressure significantly more than enalapril 10 mg daily in the short but not the long term, although the enalapril dose may not have been optimal. Nebivolol has an additive effect in combination with hydrochlorothiazide. Standing blood pressure and/or mean 24-hour ambulatory blood pressure is significantly and similarly reduced with nebivolol, atenolol or nifedipine. Nebivolol tended to prevent increases in early morning blood pressure better than nifedipine. Overall response rates to nebivolol therapy (a decrease in sitting/supine diastolic blood pressure to < or = 90 mm Hg or a 10% or > or = 10 mm Hg fall in diastolic blood pressure) ranged from 58 to 81% after 4 to 52 weeks' treatment. In comparative studies, response rates were greater in nebivolol than in enalapril or metoprolol recipients, but not significantly different from those in atenolol or nifedipine recipients. Nebivolol 5 mg once daily is well tolerated in patients with hypertension. Adverse events are infrequent, transient and mild to moderate. Those reported most often include headache, fatigue, paraesthesias and dizziness. Several studies reported no signs of orthostatic hypotension with nebivolol. Comparative trials revealed no significant differences between the frequency and severity of adverse events in patients receiving nebivolol, atenolol, enalapril or placebo; however, the overall incidence of adverse events was greater with nifedipine or metoprolol. Some atenolol or enalapril, but not nebivolol, recipients reported impotence or decreased libido during therapy. CONCLUSION: Current evidence indicates that nebivolol 5 mg once daily is a well tolerated beta-blocker, which is as effective as once daily atenolol and other classes of antihypertensive agents. It may therefore be recommended as a useful alternative first-line treatment option for the management of patients with mild to moderate uncomplicated essential hypertension.

5-Methoxypsoralen. A review of its effects in psoriasis and vitiligo.

UNLABELLED: 5-Methoxypsoralen, a naturally occurring linear furocoumarin, has been successfully used in combination with ultraviolet (UV) A irradiation [psoralen plus UV (PUVA)] to manage psoriasis and vitiligo. In patients and volunteers, PUVA 5-methoxypsoralen causes a dose-related increase in cutaneous photosensitivity. However, mean minimum phototoxic doses (MPD) were 30 to 50% greater with 5-methoxypsoralen than with 8-methoxypsoralen within individuals; this suggests lower photoactivity with 5-methoxypsoralen. In comparative clinical trials of parallel design, psoriasis clearance rates of > 90% or > 97% were observed in similar numbers of patients (60 to 77%) receiving oral PUVA 5-methoxypsoralen (typically 1.2 mg/kg) or oral PUVA 8-methoxypsoralen (0.6 mg/kg) treatment. Generally, 5-methoxypsoralen recipients required a greater total UVA exposure than 8-methoxypsoralen recipients to achieve end-point. However, study end-point was achieved sooner with oral or topical PUVA 5-methoxypsoralen in a small number of patients with psoriasis who received both treatments simultaneously and contralaterally. Up to 56% of patients with vitiligo achieved > 75% repigmentation with 5-methoxypsoralen (oral or topical) combined with UV irradiation (lamp or sun); the face and trunk were the most responsive areas. Lack of response to PUVA 5-methoxypsoralen treatment was observed in up to 16% of patients with psoriasis and, in 1 trial, in 22% of those with vitiligo. Lesion spreading during treatment of vitiligo was also observed in 7 (19%) patients in 1 study. The incidence and severity of adverse events was generally lower in PUVA 5-methoxypsoralen 1.2 mg/kg than in PUVA 8-methoxypsoralen 0.6 mg/kg recipients. Nausea and/or vomiting, pruritus and erythema were the most commonly reported adverse events in the short term; they occurred about 2 to 11 times more frequently in 8-methoxypsoralen than 5-methoxypsoralen recipients within clinical trials. Adverse hepatic events after oral administration of the drug were uncommon. Long term tolerability data for PUVA 5-methoxypsoralen are scarce; however, carcinogenicity was not reported during a 14-year observation period of 413 patients with psoriasis. CONCLUSION: Similar lesion clearance rates were observed with oral 5- or 8-methoxypsoralen plus UVA exposure in patients with vitiligo or psoriasis, although patients given 5-methoxypsoralen often required a greater total UV exposure than 8-methoxypsoralen recipients. The incidence of short term cutaneous and gastrointestinal adverse effects is markedly less with 5-methoxypsoralen than with 8-methoxypsoralen, which is an advantage, although the long term tolerability of 5-methoxypsoralen has yet to be fully established. Nevertheless, in appropriately selected patients, PUVA 5-methoxypsoralen therapy may be recommended as an alternative first-line systemic treatment option for the management of vitiligo or psoriasis.

Orlistat.

Orlistat (tetrahydrolipstatin) is an inhibitor of pancreatic and other lipases. As a pancreatic lipase inhibitor, it acts in the gastrointestinal lumen and is indicated for use in obesity. Serum total cholesterol and low density lipoprotein-cholesterol levels were reduced in obese, but otherwise healthy, patients during < or = 2 years' orlistat treatment; serum triglyceride and high density and very low density lipoprotein-cholesterol levels were unchanged in trials of < or = 12 weeks. Obese patients who were maintained on a hypocaloric diet and who received orlistat 360 mg/day for 12 weeks lost a significantly greater percentage of bodyweight than placebo recipients (5 vs 3.5%). In 2-year studies, weight loss was significantly greater in orlistat than in placebo recipients by the end of year 1; weight was further reduced or maintained in the second year, when a eucaloric diet was allowed, in orlistat but not placebo recipients. A greater proportion of orlistat than placebo recipients lost > 5% or > 10% of their initial bodyweight in 1- and 2-year studies.

Intranasal azelastine. A review of its efficacy in the management of allergic rhinitis.

UNLABELLED: Azelastine, a phthalazinone compound, is a second generation histamine H1 receptor antagonist which has shown clinical efficacy in relieving the symptoms of allergic rhinitis when administered as either an oral or intranasal formulation. It is thought to improve both the early and late phase symptoms of rhinitis through a combination of antihistaminic, antiallergic and anti-inflammatory mechanisms. Symptom improvements are evident as early as 30 minutes, after intranasal administration of azelastine [2 puffs per nostril (0.56mg)] and are apparent for up to 12 hours in patients with seasonal allergic rhinitis (SAR). The effect on nasal blockage is variable: in some studies objective and/or subjective assessment showed a reduction in blockage, whereas in other studies there was no improvement. Intranasal azelastine 1 puff per nostril twice daily is generally as effective as standard doses of other antihistamine agents including intranasal levocabastine and oral cetirizine, ebastine, loratadine and terfenadine at reducing the overall symptoms of rhinitis. The relative efficacies of azelastine and intranasal corticosteroids (beclomethasone and budesonide) remain unclear. However, overall, the corticosteroids tended to improve rhinitis symptoms to a greater extent than the antihistamine. Azelastine was well tolerated in clinical trials and postmarketing surveys. The most frequently reported adverse events were bitter taste, application site irritation and rhinitis. The incidence of sedation did not differ significantly between azelastine and placebo recipients and preliminary report showed cardiovascular parameters were not significantly altered in patients with perennial allergic rhinitis (PAR). CONCLUSION: Twice-daily intranasal azelastine offers an effective and well tolerated alternative to other antihistamine agents currently recommended for the symptomatic relief of mild to severe SAR and PAR in adults and children (aged > or = 12 years in the US; aged > or = 6 years in some European countries including the UK). The rapid onset, confined topical activity and reduced sedation demonstrated by the intranasal formulation of azelastine may offer an advantage over other antihistamine agents, although this has yet to be confirmed.

Triflusal.

Triflusal is an antiplatelet agent structurally related to the salicylate group of compounds, but it is not derived from aspirin (acetylsalicylic acid). Platelet antiaggregant properties of triflusal and its active 3-hydroxy-4-trifluoro-methylbenzoic acid metabolite are primarily mediated by specific inhibition of platelet arachidonic acid metabolism. Triflusal, compared with placebo for 6 months, significantly reduced the incidence of nonfatal myocardial infarction in patients with unstable angina. In patients with peripheral arteriopathy, total and pain free walking distances were markedly improved in triflusal compared with placebo recipients. The cumulative event rate for stroke, ischemic cardiopathy and vascular death was lower, but not significantly different, in patients with atherothrombotic stroke who received triflusal than in aspirin recipients. Differences were significant, and favoured triflusal, in a subgroup of patients with > 70% carotid stenosis. Prophylaxis with triflusal for 6 months after aortocoronary vein grafting reduced the number of new distal anastomosis occlusions and the graft attrition rate more than aspirin or placebo. The incidence of deep vein thrombosis or pulmonary embolism in more than 500 patients undergoing hip surgery was similar for these 3 treatments. The amount of blood transfused was significantly reduced in triflusal compared with aspirin recipients who underwent hip surgery. Risk of haemorrhage was also reduced in ischemic stroke patients receiving triflusal versus aspirin.

Butenafine.

Butenafine is a new antifungal agent with primary fungicidal activity against dermatophytes such as Trichophyton mentagrophytes, Microsporum canis and Trichophyton rubrum which cause tinea infections. 14C-labelled butenafine (approximately 30 micrograms/g tissue) was found within guinea-pig dorsal skin 24 hours after topical application. Most of the drug was distributed into the epidermis including the horny layer. Small amounts were found in the dermis, probably transported via sebaceous glands and hair follicles. In vitro, the minimum concentration that completely inhibited growth of dermatophytes (MIC) and the minimum fungicidal concentrations (MFC) for butenafine against T. mentagrophytes and M. canis were similar (0.012 to 0.05 mg/L) and were 4 to 130 times lower than those for naftifine, tolnaftate, clotrimazole and bifonazole. It also has greater activity against T. rubrum, M. gypseum and Epidermophyton floccosum when compared with naftifine, tolnaftate and clotrimazole; comparisons with bifonazole against these strains were not available. Assessment after 1 week's treatment in patients with tinea pedis revealed that mycological cure rates were greater in those who received twice-daily butenafine for 1 week or once-daily butenafine for 4 weeks than in placebo recipients. Mycological and overall cure rates were either further increased or maintained up to 5 weeks after treatment cessation compared with end-of-treatment values. In patients with tinea cruris or tinea corporis who received once-daily butenafine 1% for 2 weeks, the mycological and overall cure rates continued to increase for up to 4 weeks after treatment cessation.

Sibutramine. A review of its contribution to the management of obesity.

Sibutramine is an orally administered centrally acting weight management agent apparently devoid of amphetamine-like abuse potential. Its primary (M2; BTS 54,505) and secondary (M1; BTS 54,354) amine metabolites are pharmacologically active and are thought to induce the natural processes leading to enhancement of satiety and thermogenesis by inhibiting serotonin (5-hydroxytryptamine, 5-HT) and noradrenaline (norepinephrine) reuptake. In clinical trials, once-daily sibutramine was administered at dosages of < or = 30 mg for < or = 24 weeks and 10 or 15 mg for 1 year in conjunction with reduced calorie intake, increased daily exercise and advice on eating behaviour. Dose-related bodyweight loss was greater with sibutramine than with placebo. Clinical effects were most commonly apparent at dosages > or = 10 mg/day. Weight loss of > 1% within the first month of treatment appears indicative of good long term response with sibutramine. Weight loss was maintained during therapy for 1 year; longer term data are lacking. Weight regain occurred after treatment cessation in studies of < or = 24 weeks' duration; data from longer trials are unavailable. Up to 15% of patients in < or = 6-month studies did not respond to treatment irrespective of dose. Obese patients with type 2 (non-insulin-dependent) diabetes or hypertension lost significantly more mean bodyweight with sibutramine than with placebo, although weight loss was less than that in obese patients without comorbidities. The effect of sibutramine on mean fasting blood glucose levels and plasma lipid levels was unclear. Sibutramine, compared with placebo, statistically significantly increased blood pressure and heart rate in obese patients with or without hypertension when given for up to 12 months. However, after 12 weeks' treatment in hypertensive obese patients, diastolic blood pressure was reduced by similar amounts with sibutramine or placebo. Concerns over potential pressor effects with sibutramine are reflected in the manufacturer's dosage and administration recommendations.

Occult blood versus fecal leukocytes in the diagnosis of bacterial diarrhea: a study of U.S. travelers to Mexico and Mexican children.

A study was done to test the effectiveness of fecal occult blood as a screening test for invasive bacterial pathogens and as a substitute for the fecal leukocyte examination in adult and pediatric cases of acute diarrhea. United States citizens studying in Mexico and Mexican children, both with acute diarrhea had their stools cultured, examined for fecal leukocytes, and tested for occult blood. Using culture results as the criterion standard for detection of bacterial agents, and fecal leukocytes for diarrhea associated with diffuse colonic inflammation, occult blood was tested for its sensitivity, specificity, and predictive value using 2 x 2 tables. Analysis of the data found that occult blood negative samples were reliable indicators of a lack of invasive bacteria in both adult and pediatric patients (negative predictive values of 87% and 96%, respectively). Positive results for either test were not reliably predictive as indicators of invasive bacteria among adults. A positive occult blood test result was significantly more sensitive than a positive fecal leukocyte test result (79% versus 42%) in detecting invasive bacteria in the pediatric patients; however, the positive predictive value was only 24%. The fecal occult blood test is an uncomplicated, low-cost test that was reliable when giving a negative result in detecting a lack of invasive bacteria in adult and pediatric patients with diarrhea. In children, a positive result on a fecal occult blood test is sensitive but not specific in detecting invasive bacterial enteropathogens. These data also indicate that a commercially available test for occult blood represents a suitable alternative to microscopic examination of fecal samples for leukocytes obtained from patients with acute diarrhea.