Photodiode-based time zero determination for ultrafast electron microscopy.

Pump-probe experiments in ultrafast electron microscopy require temporal overlap between the pump and probe pulses. Accurate measurements of the time delay between them allows for the determination of the time zero, the moment in time where both pulses perfectly overlap. In this work, we present the use of a photodiode-based alignment method for these time zero measurements. The cheap and easy-to-use device consists of a photodiode in a sample holder and enables us to temporally align individual, single-electron pulses with femtosecond laser pulses. In a first device, a temporal resolution of 24 ps is obtained, limited by the photodiode design. Future work will utilize a smaller photodiode with a lower capacitance, which will increase the temporal resolution and add spatial resolution as well. This upgrade will bring the method toward the micrometer and picosecond spatiotemporal resolution.

A 6-month maintenance therapy with adapalene-benzoyl peroxide gel prevents relapse and continuously improves efficacy among patients with severe acne vulgaris: results of a randomized controlled trial.

BACKGROUND: Acne vulgaris is a chronic and frequently recurring disease. A fixed-dose adapalene-benzoyl peroxide (adapalene-BPO) gel is an efficacious and safe acne treatment. OBJECTIVES: To assess the long-term effect of adapalene-BPO on relapse prevention among patients with severe acne after successful initial treatments. METHODS: This is a multicentre, double-blind, randomized and controlled study. In total, 243 subjects who had severe acne vulgaris and at least 50% global improvement after a previous 12-week treatment were randomized into the present study to receive adapalene-BPO gel or its vehicle once daily for 24 weeks. RESULTS: At week 24, compared with vehicle, adapalene-BPO resulted in significantly higher lesion maintenance success rate (defined as having at least 50% improvement in lesion counts achieved in initial treatment) for all types of lesions (total lesions: 78·9% vs. 45·8%; inflammatory lesions: 78·0% vs. 48·3%; noninflammatory lesions: 78·0% vs. 43·3%; all P < 0·001). Significantly more subjects with adapalene-BPO than with vehicle had the same or better Investigator's Global Assessment score at week 24 than at baseline (70·7% vs. 34·2%; P < 0·001). The time when 25% of subjects relapsed was 175 days with adapalene-BPO and 56 days with vehicle (17 weeks earlier; P < 0·0001). Adapalene-BPO led to further decrease of lesion counts during the study and 45·7% of subjects were 'clear' or 'almost clear' at week 24. It was also safe and well tolerated in the study. CONCLUSIONS: Adapalene-BPO not only prevents the occurrence of relapse among patients with severe acne, but also continues to reduce disease symptoms during 6 months.

A randomized trial of the efficacy of a new micronized formulation versus a standard formulation of isotretinoin in patients with severe recalcitrant nodular acne.

BACKGROUND: Isotretinoin is very frequently the drug of choice for the management of severe recalcitrant nodular acne. Recently, a new micronized and more bioavailable formulation of isotretinoin has been developed that permits once-daily administration in lower doses than usually used with standard isotretinoin (Accutane), regardless of whether it is taken with or without food. OBJECTIVE: Our purpose was to determine whether micronized isotretinoin and standard isotretinoin are clinically equivalent. METHODS: In this multicenter, double-blind, double-dummy study, 600 patients with severe recalcitrant nodular acne were treated with either 0.4 mg/kg of micronized isotretinoin once daily without food (n = 300) or 1.0 mg/kg per day of standard isotretinoin in two divided doses with food (n = 300). Lesion counts were monitored over 20 weeks. RESULTS: Both treatment groups in this well-controlled clinical trial experienced an equivalent reduction in the number of total nodules (facial plus truncal). In addition, an equivalent proportion of patients achieved 90% clearance of the total number of nodules. Both formulations had similar results for other efficacy variables. CONCLUSION: Once-daily use of the micronized and more bioavailable formulation of isotretinoin under fasted conditions is clinically equivalent to the standard twice-daily formulation under fed conditions in the treatment of severe recalcitrant nodular acne.

Safety of a new micronized formulation of isotretinoin in patients with severe recalcitrant nodular acne: A randomized trial comparing micronized isotretinoin with standard isotretinoin.

BACKGROUND: Isotretinoin is a very effective drug for treating severe recalcitrant nodular acne. A new micronized formulation of isotretinoin has been shown to be clinically equivalent to standard isotretinoin with improved bioavailability and minimal food effect. The safety profile of the micronized formulation has not been described previously. OBJECTIVE: The objective of this article is to report the incidence and intensity of adverse events found in a comparative, double-blind efficacy study that showed clinical equivalence of the new micronized formulation of isotretinoin and the standard isotretinoin formulation (Accutane). METHODS: Six hundred patients with severe recalcitrant nodular acne were treated with micronized isotretinoin (n = 300) under fasted conditions or standard isotretinoin (n = 300) under fed conditions. One cohort received single daily doses of 0.4 mg/kg of micronized isotretinoin without food and the other cohort received 1.0 mg/kg per day of standard isotretinoin in two divided doses with food. Adverse events were monitored during 20 weeks of drug therapy. RESULTS: The proportion of adverse events in most body systems was generally lower in patients receiving micronized isotretinoin than in those receiving standard isotretinoin. CONCLUSION: Micronized isotretinoin appears to have a safety profile similar to that of standard isotretinoin and to carry a lower risk of mucocutaneous events and hypertriglyceridemia.

Effect of a desogestrel-containing oral contraceptive on the skin.

OBJECTIVE: This pilot study evaluated the effects of a desogestrel-containing oral contraceptive (DSG-OC) on facial seborrhea (oiliness), acne and related factors in otherwise healthy women with moderate facial acne vulgaris. METHODS: In this double-blind, placebo-controlled study, 41 women received DSG-OC (50/100/150 microg desogestrel plus 35/30/30 microg ethinylestradiol given in a 7/7/7 day regimen) and 41 received placebo for six cycles. Seborrhea and skin assessments, and hormone analyses were performed regularly. RESULTS: Analyses of sebum output (measured using Sebutape) indicated that the effect of DSG-OC on the skin varied with facial area. Compared with placebo, DSG-OC had a statistically significant effect on the cheeks (60% relative reduction in sebum output; p = 0.02), and a non-significant effect on the forehead (30% relative reduction in sebum output). Acne lesion counts did not differ significantly between groups. Both patient and investigator assessments of skin condition (visual analog scale) indicated significant improvements with DSG-OC compared with placebo. The reduced sebum output with DSG-OC is associated with a three-fold increase in sex hormone binding globulin, as well as an expected decrease in free testosterone and other androgens that were found in this group. CONCLUSION: These results suggest that DSG-OC reduces facial oiliness and may be a useful contraceptive choice for women with this problem.

An evaluation of the effect of an alpha hydroxy acid-blend skin cream in the cosmetic improvement of symptoms of moderate to severe xerosis, epidermolytic hyperkeratosis, and ichthyosis.

A number of genetic, intrinsic, and extrinsic factors can cause conditions of problem dry skin, marked by unusual dryness, rough texture, and extreme flaking and scaling, that are generally not controlled by conventional moisturizers. A study was undertaken to evaluate the safety and efficacy of two novel alpha hydroxy acid (AHA)-containing creams in reducing the appearance and symptoms of problem dry skin on subjects with a range of dry skin conditions, including xerosis, epidermolytic hyperkeratosis, and ichthyosis. Twenty subjects completed a course of treatment with either regular or extra strength AHA-blend cream on a test site, compared with a currently marketed, non-AHA moisturizing lotion on a control site. Subjects were treated for 4 weeks, with clinical evaluations performed at weeks 0, 2, and 4. The test for mulations reduced symptoms and improved cosmetic appearance following 2 weeks of use, with continued improvement following 4 weeks of use. Improvements were significant compared to baseline and compared to sites treated with the control lotion. Some patients experienced mild to moderate local adverse effects; all subjects were able to continue using the test product for the duration of the study.

Treatment of acne with a combination clindamycin/benzoyl peroxide gel compared with clindamycin gel, benzoyl peroxide gel and vehicle gel: combined results of two double-blind investigations.

BACKGROUND: It has previously been shown that a combination of erythromycin and benzoyl peroxide is superior to either ingredient when used alone in the treatment of acne. A clindamycin/benzoyl peroxide combination gel might have an advantage over erythromycin/benzoyl peroxide gel because the former does not require refrigeration after it is dispensed. OBJECTIVE: Our purpose was to determine the efficacy and safety of a combination clindamycin/benzoyl peroxide gel when compared with benzoyl peroxide, clindamycin, or vehicle gels. METHODS: In two double-blind, randomized, parallel, vehicle-controlled trials, patients were treated for 11 weeks with once-nightly application of one of the above preparations. Evaluations were performed at 2, 5, 8, and 11 weeks and included lesion counts and assessment of global responses and irritant effects. RESULTS: A total of 334 patients completed the study. All three active preparations were significantly superior to the vehicle in global improvement and in reducing inflammatory lesions and noninflammatory lesions. The combination gel was significantly superior to the two individual agents in global improvement and reduction of inflammatory lesions and also to the clindamycin gel in reducing noninflammatory lesions. There was no significant difference in tolerance to the active gels versus the vehicle gel. CONCLUSION: In the treatment of acne, topical clindamycin/benzoyl peroxide combination gel is well tolerated and superior to either individual ingredient.

Brain glucose uptake and unawareness of hypoglycemia in patients with insulin-dependent diabetes mellitus.

BACKGROUND: In patients with insulin-dependent diabetes mellitus (IDDM) whose treatment results in nearly normal mean plasma glucose concentrations, an unawareness of hypoglycemia can develop, and such patients are at increased risk for seizures and coma. We tested the hypothesis that during hypoglycemia, these patients would have normal glucose uptake in the brain and that consequently no sympathoadrenal activation would begin, resulting in an unawareness of hypoglycemia. METHODS: We measured glucose uptake in the brain at plasma glucose concentrations of 105 and 54 mg per deciliter (5.8 and 3.0 mmol per liter) in 24 patients with IDDM, stratified into three groups according to their glycosylated hemoglobin values (mean [+/- SD] values, 7.2 +/- 0.5, 8.5 +/- 0.4, and 10.2 +/- 1.3 percent) and compared the values for brain glucose uptake with those measured in 15 normal subjects at plasma glucose concentrations of 85 and 55 mg per deciliter (4.2 and 3.1 mmol per liter). We also recorded the subjects' hypoglycemic-symptom scores and measured their plasma concentrations of counterregulatory hormones. RESULTS: There was no significant change in the uptake of glucose in the brain (calculated as the uptake during hypoglycemia minus the uptake during normoglycemia) among the patients with IDDM who had the lowest glycosylated hemoglobin values (+0.6 +/- 2.0 mg [3.3 +/- 11.1 mumol] per 100 g of brain tissue per minute, P = 0.39). Conversely, glucose uptake in the brain fell in both the group with intermediate values (a decrease of 1.3 +/- 1.0 mg [7.2 +/- 5.6 mumol] per 100 g per minute, P = 0.009) and the group with the highest values (a decrease of 1.8 +/- 1.6 mg [10.0 +/- 9.0 mumol] per 100 g per minute, P = 0.01), as it did in the normal subjects (a decrease of 1.6 +/- 1.8 mg [9.0 +/- 10.1 mumol] per 100 g per minute, P = 0.003). The responses of plasma epinephrine and pancreatic polypeptide and the frequency of symptoms of hypoglycemia were lowest in the group with the lowest glycosylated hemoglobin values. CONCLUSIONS: During hypoglycemia, patients with IDDM who have nearly normal glycosylated hemoglobin values have normal glucose uptake in the brain, which preserves cerebral metabolism, reduces the responses of counterregulatory hormones, and causes an unawareness of hypoglycemia.

Adaptation in brain glucose uptake following recurrent hypoglycemia.

Brain glucose metabolism is impaired during hypoglycemia, but, if sustained, brain metabolism reverts to normal in animal models--data in man are lacking. We tested the hypothesis that adaptations occur to allow maintenance of normal rates of brain glucose uptake (BGU) following recurrent hypoglycemia in man. Twelve normal humans were studied over 4 days. On the initial day, arterial plasma glucose concentrations were decreased from 4.72 to 2.50 mmol/liter in five 0.56 mmol/liter steps. Cerebral blood flow, brain arteriovenous glucose difference, BGU, and cognitive function were quantitated at each step. BGU was initially impaired at the 3.61 mmol/liter glucose step (P = 0.04) and was antedated by increments in epinephrine that began at 4.16 mmol/liter (P = 0.03). The onset of hypoglycemic symptoms occurred during the 3.61 mmol/liter glucose step (P = 0.02), whereas tests of cognitive function generally deteriorated at the 3.05 mmol/liter step (P < 0.05). During the next 56 hr, mean glucose concentrations were kept at 2.9 +/- 0.1 mmol/liter and reached normal only during meals. The stepped clamp protocol was repeated beginning at 4.16 mmol/liter on the last day. No decrement in BGU was observed at any step; cognitive function was preserved until significantly lower glucose concentrations on the final day relative to the first (P = 0.04). Subjects remained asymptomatic of hypoglycemia until they reached a glucose concentration of 2.50 mmol/liter (P < 0.001 vs. day 1), while initial increments in all counterregulatory hormones were forestalled to lower glucose steps than on day 1. Therefore, adaptations occur that allow normal BGU and cerebral function to be maintained during recurrent systemic hypoglycemia. Counterregulatory events that should result in symptoms of hypoglycemia and increments in endogenous glucose production are prevented until extremely subnormal glucose concentrations.