ABSTRACT
BACKGROUND: Sampling the dermal interstitial fluid (ISF) allows the pharmacokinetics and pharmacodynamics of dermatological drugs to be studied directly at their site of action. Dermal open-flow microperfusion (dOFM) is a recently developed technique that can provide minimally invasive, continuous, membrane-free (thus unfiltered) access to the dermal ISF. Herein, we evaluate the clinical applicability and reliability of novel wearable dOFM devices in a clinical setting. METHODS: Physicians inserted 141 membrane-free dOFM probes into the dermis of 17 healthy and psoriatic volunteers and sampled dermal ISF for 25 h by using wearable push-pull pumps. The tolerability, applicability, reproducibility, and reliability of multiple insertions and 25 h continuous sampling was assessed by pain scoring, physician feedback, ultrasound probe depth measurements, and 25 h-drift and variability of the sodium relative recovery. RESULTS: Insertion pain was moderate and decreased with each additional probe. Probe insertion was precise, although slightly deeper in lesional skin. The wearable push-pull pump enabled uninterrupted ISF sampling over 25 h with low variability. The relative recovery was drift-free and highly reproducible. CONCLUSION: dOFM sampling devices are tolerable and reliable for prolonged continuous dermal sampling in a multiprobe clinical setting. These devices should enable the study of a wide range of drugs and their biomarkers in the skin.
Subject(s)
Dermatologic Agents/pharmacokinetics , Dermis/metabolism , Extracellular Fluid/metabolism , Infusion Pumps , Microdialysis/instrumentation , Perfusion/instrumentation , Administration, Cutaneous , Adult , Biomarkers/metabolism , Dermatologic Agents/administration & dosage , Dermis/drug effects , Female , Humans , Male , Microdialysis/methods , Microdialysis/standards , Middle Aged , Needles , Perfusion/methods , Perfusion/standards , Reproducibility of Results , Sodium/metabolism , Young AdultABSTRACT
AIMS: To compare the accuracy of two marketed subcutaneous glucose monitoring devices (Guardian RT, GRT; GlucoDay S, GDS) and standard microdialysis (CMA60; MD) in Type 1 diabetic patients. METHODS: Seven male Type diabetic patients were investigated over a period of 26 h simulating real-life meal glucose excursions. Catheters of the three systems were inserted into subcutaneous adipose tissue of the abdominal region. For MD, interstitial fluid was sampled at 30- to 60-min intervals for offline glucose determination. Reference samples were taken at 15- to 60-min intervals. All three systems were prospectively calibrated to reference. Median differences, median absolute relative differences (MARD), median absolute differences (MAD), Bland-Altman plot and Clark Error Grid were used to determine accuracy. RESULTS: Bland-Altman analysis indicated a mean glucose difference (2 standard deviations) between reference and interstitial glucose of -10.5 (41.8) % for GRT, 20.2 (55.9) % for GDS and 6.5 (35.2) % for MD, respectively. Overall MAD (interquartile range) was 1.07 (0.39; 2.04) mmol/l for GRT, 1.59 (0.54; 3.08) mmol/l for GDS and 0.76 (0.26; 1.58) mmol/l for MD. Overall MARD was 15.0 (5.6; 23.4) % (GRT), 19.7 (6.1; 37.6) % (GDS) and 8.7 (4.1; 18.3) % (MD), respectively. Total sensor failure occurred in two subjects using GRT and one subject using GDS. CONCLUSIONS: The three investigated technologies had comparable performance. Whereas GRT underestimated actual blood glucose, GDS and MD overestimated blood glucose. Considerable deviations during daily life meal glucose excursions from reference glucose were observed for all three investigated technologies. Present technologies may require further improvement until individual data can lead to direct and automated generation of therapeutic advice in diabetes management.
Subject(s)
Biosensing Techniques/standards , Diabetes Mellitus, Type 1/metabolism , Glucose/metabolism , Microdialysis , Subcutaneous Fat/metabolism , Abdomen , Adult , Extracellular Fluid/metabolism , Humans , MaleSubject(s)
Skin Diseases/epidemiology , Adolescent , Adult , Age Factors , Child , Child, Preschool , Dermatitis, Contact/epidemiology , Dermatitis, Seborrheic/epidemiology , Eczema/epidemiology , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Neurodermatitis/epidemiology , Periodicity , Scotland , Sex Factors , Skin Diseases/classificationABSTRACT
A questionary sent to 137 women who qualified in Glasgow during 1951-4 showed that of the 106 respondents 24% of the married women were unemployed and only 31% were working full-time. The married women had fewer qualifications than a matched group of male contemporaries, and fewer of those in hospital work were consultants. The married women in full-time work had fewer children and showed some differences in their background compared with those working part-time or unemployed. Most part-time workers were satisfied with their present posts and did not wish to work more.
