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Biomedical subjects

C Surber

Publications and source records attributed to C Surber.

At least 19 recordsLinked to original sources

Capillary blood cell velocity in finger nailfold: effect of enalapril and mibefradil in patients with mild to moderate hypertension.

Outpatients with essential hypertension were randomized to receive antihypertensive treatment with either mibefradil or enalapril. Ambulatory blood pressure measurement (ABPM) and video capillary microscopy of the finger nailfold were performed at baseline and after 12 weeks of treatment. In the enalapril group (n = 21) baseline ABP was 156 +/- 12/100 +/- 9 mm Hg and decreased to 140 +/- 17/89 +/- 10 mm Hg after 12 weeks. In the mibefradil group (n = 22) mean 24-h ABP decreased from 159 +/- 14/102 +/- 7 to 140 +/- 10/89 +/- 7 mm Hg. Capillary blood cell velocity (CBV) without treatment was 0.90 +/- 0.58 mm/s (mean +/- SD) and 0.83 +/- 0.46 mm/s at rest and 0.30 +/- 0.22 and 0.21 +/- 0.20 mm/s immediately after local finger cooling in the mibefradil and the enalapril group, respectively. In the Enalapril group CBV at week 12 was 0.99 +/- 0. 60 mm/s (n.s.) at rest and 0.40 +/- 0.28 mm/s immediately after local cooling (P = 0.005 compared to 0.21 +/- 0.20 mm/s without treatment). Twelve weeks after initiation of treatment CBV was 0.76 +/- 0.48 mm/s (n.s.) at rest and 0.31 +/- 0.28 mm/s (n.s.) immediately after local cooling in the mibefradil group. Finger nailfold CBV immediately after local finger cooling was increased by enalapril compared to baseline. The T-channel-inhibiting calcium antagonist mibefradil did not change CBV in finger nailfold capillaries.

Adult

Percutaneous absorption of salicylic acid in man after topical administration of three different formulations.

OBJECTIVE: To determine the amount of drug which is absorbed during 1 day following topical application of three different preparations containing salicylic acid. METHODS: Ten grams of the formulations, either (a) Kerasaltrade mark 5% ointment, (b) salicylic acid 5% or (c) 10% in petrolatum, were administered consecutively to a 600-cm2 area on alternating sides of the back of healthy volunteers (n = 9). Thirty minutes after application, a skin area of 2.54 cm2 was stripped with D-Squametrade mark adhesive disks to determine the amount of salicylic acid in the stratum corneum. The entire application site was then covered by a thin gauze bandage and was not washed for the next 24 h. Urine was collected for 26 h following administration, hydrolyzed and assayed by HPLC analysis. RESULTS: The absolute amounts absorbed and excreted were 52.6 +/- 29.4 mg (mean +/- SD), 127.1 +/- 43.9 mg and 208.0 +/- 81.7 mg, and the doses absorbed in relation to the doses applied (500 mg salicylic acid in case of formulations a and b and 1,000 mg for formulation c) were 9.3 +/- 3.8, 25.1 +/- 8.5 and 20.2 +/- 7.7%, respectively. The amounts of salicylic acid in the skin 30 min after application were 36.3 +/- 16.5, 18.2 +/- 11.9 and 31.3 +/- 15.4 microg/ cm2 as determined by the tape stripping procedure. CONCLUSIONS: Significant differences in the doses absorbed were detected between the two formulations a and b (same concentration) with different vehicles (p value < 0.001) as well as between b and c (same vehicle) with different concentrations (p value = 0.018) using Student's paired t test. These results demonstrate that salicylic acid is well absorbed by healthy skin.

Administration, Cutaneous

Cutaneous manifestations of Paecilomyces lilacinus infection induced by a contaminated skin lotion in patients who are severely immunosuppressed.

BACKGROUND: New opportunistic fungal infections cause significant morbidity and death in patients who are severely immunocompromised. Cutaneous lesions may be the first clinical manifestation and give the clue to early diagnosis. OBJECTIVE: The purpose of this study was to describe the clinical and histologic manifestations of Paecilomyces lilacinus infection in patients who are severely immunosuppressed. METHODS: Within a 3-month period, we observed 5 patients with allogenic bone marrow transplantation and 4 patients with aplasia after chemotherapy for hematologic malignancies who developed skin eruptions caused by invasive P lilacinus. RESULTS: The skin lesions began in 7 cases during or shortly after recovery of pancytopenia. Most of the skin lesions were located on the lower extremities. The cutaneous manifestations were highly variable including erythematous macules, nodules, pustules, vesicular lesions, and necrotic crusts. In 3 biopsy specimens, histologic examination revealed hyphae in periodic acid-Schiff-stained sections. In all patients P lilacinus was isolated from skin tissue samples. P lilacinus was identified from all lesions either by skin biopsy or needle aspiration from clinically evident lesions. In 3 additional cases, the patient's hands were colonized without skin lesions. The source of the epidemic outbreak was finally traced down to several contaminated lots of a topical moisturizing agent. Two patients died; one patient had septic lesions in the eye and kidney as the result of P lilacinus. CONCLUSION: Clinical and histologic findings of P lilacinus infection with cutaneous manifestations in patients who are severely immunosuppressed are summarized. P lilacinus is resistant to all systemic antimycotics available, and in general, recovery of immunosuppression is necessary to eradicate the mold. Contaminated topical dermatologic agents should be included in the differential diagnosis as a source for severe epidemic cutaneous manifestations of fungal infection in patients who are severely immunosuppressed. This fact implies that additional safety guidelines are necessary for topical dermatologic agents used for patients who are severely immunosuppressed.

Adolescent

Effect of moxonidine and cilazapril on microcirculation as assessed by finger nailfold capillaroscopy in mild-to-moderate hypertension.

Disorders in peripheral microcirculation are observed in arterial hypertension and may be improved by antihypertensive treatment. In this pilot study the authors measured capillary blood cell velocity in the finger nailfold in 14 patients (mean age 50 +/- 14 years, range 30-71 years; 9 men, 5 women) with mild-to-moderate essential hypertension. After a 3-week placebo period, patients received double-blind randomized treatment with either 0.2- to 0.4-mg moxonidine (n=7) or 2.5- to 5.0-mg cilazapril (n=7). Finger nailfold video capillaroscopy was performed at baseline and after 8 weeks of treatment. Blood pressure was measured by conventional office technique. Capillary blood cell velocity, 1 minute after local finger cooling, increased in the Moxonidine group (0.65 +/- 0.53 mm/sec to 1.13 +/- 0.77 mm/sec; p<0.05) after 8 weeks treatment compared to the baseline. The increase in the Cilazapril group from 0.79 +/- 0.45 mm/sec to 0.93 +/- 1.03 mm/sec did not reach a level of statistical significance. Blood pressure decreased from 151 +/- 8/101 +/- 5 to 147 +/- 6/98 +/- 7 mmHg in the Moxonidine group and from 164 +/- 12/102 +/- 6 to 140 +/- 9/93 +/- 9 mmHg in the cilazapril group. Moxonidine increased nailfold capillary blood cell velocity 1 minute after local finger cooling in patients with mild-to-moderate hypertension. This improvement of the peripheral microcirculation may be associated with reversal of vascular dysfunction in hypertension.

Adult

Absorption of topical tacrolimus (FK506) in vitro through human skin: comparison with cyclosporin A.

Cyclosporin A (CsA) is efficacious in many dermatoses as an oral but not as a topical form, while tacrolimus (FK506) has been shown to be effective in both forms. As inadequate skin absorption has been proposed as the reason for inefficacy of topical CsA, factors contributing to percutaneous absorption of FK506 and CsA were studied. Partitioning of FK506 and CsA between octanol and water, stratum corneum and water, and stratum corneum and isopropyl myristate was determined. Absorption of FK506 and CsA through dermatomed human cadaver skin was determined with in vitro flow-through cells. In partitioning experiments, CsA was more lipophilic than FK506. Both drugs were seen in comparable amounts in skin layers, but FK506 permeated the skin to a greater extent than CsA.

Administration, Topical

Delayed-type hypersensitivity to subcutaneous lidocaine with tolerance to articaine: confirmation by in vivo and in vitro tests.

A 43-year-old woman suffered from recurrent localized swellings and an eczematous dermatitis starting 1 day after an injection of lidocaine. Intradermal patch and lymphocyte transformation tests revealed sensitization to lidocaine and cross-reactivity to the other aminoacylamide local anesthetics bupivacaine, mepivacaine and prilocaine, but not to articane. Contact allergy to the ester local anesthetics benzocaine, procaine and tetracaine, the quinoline or aminoacylamide cinchocaine, and the preservatives methylparaben and metabisulfite, was excluded. A subcutaneous challenge with articaine was well tolerated.

Adult

[Lindane].

In Europe and in the US ectoparasitic diseases are increasingly diagnosed in all classes of society. Modern means of transportation promote the spreading from endemic areas into new regions and therefore questions of therapy are becoming increasingly important. A series of preparations in various galenic formulations and in various concentrations are available to treat the ectoparasitic diseases. Due to reports on Lindane poisonings the clinical use of Lindane preparations for the treatment of scabies and pediculosis has become somewhat controversial. In this article we review older and more recent data on pharmacology, pharmacokinetics and toxicology of gamma-1,2,3,4,5,6-Hexachlorcyclohexan [Lindane]. It is pointed out that in the USA Lindane is offered in 1% preparations whereas in the German speaking Europe only 0.3% preparations are available. This latter concentration is considered as sufficient to treat the ectoparasitosis. Furthermore the use of this remedy and aspects of Lindane resistance are discussed. It is concluded that only through additional in depth education of the patients and their folks successful treatment is possible and intoxication can be prevented.

Dose-Response Relationship, Drug

Delayed hypersensitivity to one low-molecular-weight heparin with tolerance of other low-molecular-weight heparins.

We report a patient who developed infiltrated plaques at the sites of subcutaneous injection of a low-molecular-weight heparin. Skin tests and a lymphocyte transformation test revealed hypersensitivity to sandoparin and heparin sodium. The low-molecular-weight heparins nadroparin and dalteparin were subsequently tolerated without adverse effects. Possible risk factors for sensitization are discussed.

Drug Hypersensitivity

Determination of acitretin in the skin, in the suction blister, and in plasma of human volunteers after multiple oral dosing.

Several HPLC methods for quantification of acitretin and its 13-cis isomer in biological fluids have been described. Only limited data are available on determination of this drug in skin samples. Our objective was to improve the sensitivity and selectivity of existing methods to measure drug in small skin samples from humans treated with acitretin. With a new optimized mobile phase [methanol: acetonitrile (7:3, v/v), purified water with 1.5% (v/v) acetic acid, mixed in a 85:15 ratio (v/v)] and a new internal standard (arotinoid ethyl sulfone), a limit of quantification of 1 ng/g tissue was reached. Nine male volunteers were given an oral daily dose of 50 mg acitretin for up to 28 days. Blood and skin samples (punch and shave biopsies, suction blister skin, and fluid) were taken at various time points during and after treatment. Drug concentration and metabolism in plasma and skin samples appeared to be linked in that the trans-isomer concentration was always higher than the cis-isomer concentration during dosing and 3 h after the last dose. However, 7 and 14 days after the last dose in plasma and in all tissue samples (except the shave biopsy), the all-trans-acitretin concentration rapidly decreased and approached the detection limit. In the shave biopsy, the all-trans-acitretin concentration remained higher than the 13-cis-acitretin concentration. Furthermore, the elimination of two isomers from the shave biopsy was delayed.(ABSTRACT TRUNCATED AT 250 WORDS)

Acitretin

Pastes: what do they contain? How do they work?

BACKGROUND: Pastes are semisolid stiff preparations containing a high proportion of finely powdered material. Powders such as zinc oxide, titanium dioxide, starch, kaolin or talc are incorporated in high concentrations into a preferably lipophilic, greasy vehicle. A clinically distinctive feature which is generally attributed to pastes is the quality to absorb exudates by nature of the powder or other absorptive components. Reviewing the various pharmacopoeias serious doubts arise from the various formulas of pastes and their absorptive features. The zinc oxide pastes of the USP XXII, the DAB 10 and BP 88 (US, German and British pharmacopoeias). are composed of petrolatum, zinc oxide and starch. Petrolatum, a highly lipophilic, water-immiscible vehicle surrounds the powder particles preventing any absorption of water or exudates. OBJECTIVE: The goal of our investigation was to test a simple experimental setting to characterize the clinically important absorptive feature of powders and pastes. METHODS: The absorptive features of the powders were determined by the method of Enslin. The absorptive features of the paste preparations were calculated from the weight difference between the paste preparation before and after incubation with water using a simple standardized procedure. RESULTS: The absorptive features of titanium dioxide, zinc oxide, kaolin, corn starch and methylcellulose powder in pharmacopoeia quality were determined. Zinc oxide and kaolin powder showed the highest absorption of 1,000 mg water/g powder (100%). The water absorption of corn starch and titanium dioxide was 700 and 450 mg/g powder, respectively. The absorptive features of a series of paste preparations were studied in a simple experimental setting. The data show that two-phase pastes consisting of two immiscible components, one (the dispersed or inner phase; powder) being suspended in the other (the continuous or outer phase; lipophilic vehicle), have no absorptive features. In contrast, three-phase pastes consisting of a hydrophilic two-phase emulsion with high concentrations of incorporated powder (cream pastes) show considerable water uptake. CONCLUSIONS: We conclude that the classical two-phase pastes such as the zinc oxide pastes have no absorptive features. On the contrary, these formulations are highly occlusive. Therefore lipophilic pastes are only indicated when protection of intact skin against aggressive body exudates and humidity is required. The hydrophilic three-phase pastes or cream pastes show considerable water uptake and fulfil common expectations of pastes to dry the skin.

Absorption

Acitretin biotransformation into etretinate: role of ethanol on in vitro hepatic metabolism.

The aim of this study was to investigate the possible esterification of acitretin into etretinate by using hepatocytes in primary culture from the rat, monkey, dog and man. With rat and human hepatocytes, etretinate was detectable only when ethanol was co-administered with acitretin. With monkey and dog cells, traces of etretinate were found without ethanol addition, but the esterification of acitretin was highly enhanced by ethanol. The metabolic profile was not changed when cells were pre-incubated with ethanol. Therefore acitretin seems to act rather as a substrate than an enzymatic inducer.

Acitretin

Pain assessment after intramuscular injection.

Several parameters (pH, osmotic pressure) influencing the local tolerance of injectable drugs have been well-documented; however, little attention has been paid to pain following an injection--a common problem in clinical practice. A pain questionnaire was used to record pain up to 24 h after a deep ventrogluteal injection. Two groups of healthy volunteers were recruited: the first group (n = 6) received 3 different cotrimoxazole preparations and placebo and the second group (n = 10) received 4 different multivitamin preparations and placebo (double-blind, cross-over). Parameters monitored during and after injection included pain localization (line drawing), pain intensity (visual-analog scale: VAS) and verbal description of pain (pain rating index: PRI). In both groups, the equality of pain (VAS, PRI) induced by the preparations was rejected in all cases (Friedman's test, p < or = 1%). The pairwise comparisons of the groups showed significant differences (p < or = 5%) between various preparations. The correlation (Spearman's rank correlation) between pain parameters VAS and PRI was high. The present investigations have shown that the pain questionnaire is a valuable tool to investigate the subjective pain symptoms during and after the injection of different preparations.

Adult

In vivo skin penetration of acitretin in volunteers using three sampling techniques.

Etretinate and acitretin are given orally to treat psoriasis and various keratinization disorders. Acitretin, the main active metabolite of etretinate, has the pharmacokinetic advantage of being rapidly eliminated, but it shares etretinate's toxicologic profile. Thus a topical delivery of acitretin with no or reduced systemic adverse effects is desirable. To characterize the therapeutic potential of topically delivered acitretin, we quantitatively assessed its percutaneous penetration in healthy human volunteers. Additionally, three skin sampling techniques, the punch biopsy, the shave biopsy, and the suction blister technique, were validated to quantitate acitretin in the skin. The results suggest that topical delivery of acitretin renders skin concentrations which exceed those reported after oral administration of etretinate or acitretin. However, because of possible interlaminate drug contamination, drug localization within a particular skin compartment cannot be determined.

Acitretin

In vivo percutaneous absorption of [14C]acitretin in the hairless guinea pig and in the rhesus monkey.

The oral administration of retinoids such as etretinate and acitretin (Ro 10-1670, CAS 55079-83-9), provides a successful therapeutic approach in various cutaneous diseases characterized by disturbed keratinization, e.g. psoriasis. Nevertheless oral therapy is often associated with systemic adverse effects. This makes a topical form with no or reduced systemic side effects desirable. Direct application of a topical acitretin formulation to the skin might result in therapeutic skin concentrations while minimizing systemic exposure. In the hairless guinea pig and in the rhesus monkey the percutaneous absorption of [14C]acitretin from an isopropylmyristate formulation (160 micrograms acitretin/2.5 cm2/animal) were investigated in vivo. After a 24 h exposure drug concentration in the skin was higher in the hairless guinea pig (620 ng-eq/g wet tissue) than in the rhesus monkey (380 ng-eq/g wet tissue). A similar observation was made comparing the 24 h absorption data determined as amount of drug excreted. The results are compared with in vitro absorption data using skin from the same species.

Acitretin