Search

Background: The long-term results of surgical treatment of brachial plexus birth palsy have not been reported. We present the findings of a nationwide study, with a minimum five-year follow-up, of the outcomes of surgery for brachial plexus birth palsy in Finland.Methods: Of 1,717,057 newborns, 1706 with brachial plexus birth palsy requiring hospital treatment were registered in Finland between 1971 and 1997. Of these patients, 124 (7.3%) underwent surgery on the brachial plexus at a mean age of 2.8 months (range, 0.4 to 13.2 months). The most commonly performed surgical procedure was direct neurorrhaphy after neuroma resection. One hundred and twelve patients (90%) returned for a clinical and radiographic follow-up examination after a mean of 13.3 years. Activities of daily living were recorded on a questionnaire, and the affected limb was assessed with use of joint-specific functional measures.Results: Two-thirds (63%) of the patients were satisfied with the functional outcome, although one-third of all patients needed help in activities of daily living. One-third of the patients, including all nine with a clavicular nonunion from the surgical approach, experienced pain in the affected limb. All except four patients used the hand of the unaffected limb as the dominant hand. Shoulder function was moderate, with a mean Mallet score of 3.0. Both elbow and hand function were good, with a mean score on the Gilbert elbow scale of 3 and a mean Raimondi hand score of 4. Incongruence of the glenohumeral joint was noted in sixteen (16%) of the ninety-nine patients in whom it was assessed, and incongruence of the radiohumeral joint was noted in twenty-one (21%). The extent of the brachial plexus injury was found to be strongly associated with the final shoulder, elbow, and hand function in a multivariate analysis.Conclusions: Following surgical treatment of brachial plexus birth palsy, substantial numbers of the patients continued to need help performing activities of daily living and had pain in the affected limb, with the pain due to a clavicular nonunion in one-fourth of the patients. The strongest prognostic factor predicting outcome appears to be the extent of the primary plexus injury. [ABSTRACT FROM AUTHOR]

Many studies have explored children's acquisition of temporal adverbs. However, the extent to which children's early temporal language has discursive instead of solely temporal meanings has been largely ignored. We report two corpus-based studies that investigated temporal adverbs in Finnish child-parent interaction between the children's ages of 1;7 and 4;11. Study 1 shows that the two corpus children used temporal adverbs to construe both temporal and discursive meanings from their early adverb production and that the children's usage syntactically broadly reflected the input received. Study 2 shows that the discursive uses of adverbs appeared to be learned from contextually anchored caregiver constructions that convey discourse functions like urging and reassuring, and that the usage is related to the children's and caregivers' interactional roles. Our study adds to the literature on the acquisition of temporal adverbs by demonstrating that these items are learned also with additional discursive meanings in family interaction.

This paper describes the development of a fixed dose dry powder combination of indacaterol maleate (Inda) and glycopyrronium bromide (Glyco) in Easyhaler® inhaler for a comparative pharmacokinetic (PK) study, as well as the outcome of such a study. The development aim was to produce formulations with three different in vitro dispersibility profiles for both Inda and Glyco. This so-called 'rake' approach allows for quantitation of the candidate formulations relative to the reference product Ultibro® Breezhaler® in terms of the key PK parameters. Three formulations (A, B and C) were produced based on the mixing energy concept. For both APIs, formulation A (lowest mixing energy) displayed the highest fine particle fractions and formulation C (highest mixing energy) the lowest. GMP manufacturing confirmed the performance of the three formulations. The candidate formulations were tested against the reference product in a single dose PK study in healthy volunteers. Clear differences in Inda plasma concentration profiles were observed between the treatments when administered concomitantly with charcoal, with Easyhaler A showing the highest C max value and Easyhaler C the lowest. Easyhaler B was bioequivalent to Ultibro Breezhaler with regard to the primary PK parameters of Inda, C max and AUC 72h . For Glyco, Easyhaler formulations A, B and C provided lower peak concentrations than Ultibro Breezhaler. For AUC 72h of Glyco , Easyhaler B was bioequivalent to the reference product. Additional measures for adjustment of formulation performance can be foreseen, whose effects can be predicted based on mixing energy theory., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The current paper presents three studies that investigated the effect of exposure on the mental representations of filled pauses ( um/uh ). In Study 1, a corpus analysis identified the frequency of co-occurrence of filled pauses with words located immediately before or after them in naturalistic spoken adult British English (BNC2014). Based on the collocations identified in Study 1, in Study 2, 22 native British English-speaking adults heard sentences in which the location of filled pauses and the co-occurring words were manipulated and the participants were asked to judge the acceptability of the sentences heard. Study 3 was a sentence recall experiment in which we asked 29 native British English adults to repeat a similar set of sentences as used in Study 2. We found that frequency-based distributional patterns of filled pauses (Study 1) affected the sentence judgments (Study 2) and repetition accuracy (Study 3), in particular when the filled pause followed its collocate. Thus, the current study provides converging evidence for the account maintaining that filled pauses are linguistic items. In addition, we suggest filled pauses in certain locations could be considered as grammatical items, such as suffixes.

The current paper presents two experiments investigating the effect of presence versus absence of compulsory number marking in a native language on a speaker's ability to recall number information from photos. In Experiment 1, monolingual English and Japanese adults were shown a sequence of 110 photos after which they were asked questions about the photos. We found that the English participants showed a significantly higher accuracy rate for questions testing recall for number information when the correct answer was "2" (instead of "1") than Japanese participants. In Experiment 2, English and Japanese adults engaged in the same task as in Experiment 1 with an addition that explored reasons for the results found in Experiment 1. The results of Experiment 2 were in line with the results of Experiment 1, but also suggested that the results could not be attributed to differences in guessing patterns between the two groups or the type of linguistic constructions used in the test situations. The current study suggests that native language affects speakers' ability to recall number information from scenes and thus provides evidence for the Whorfian hypothesis., (© 2020 Cognitive Science Society, Inc.)

Background: Easyhaler ® dry powder inhaler (DPI) containing salmeterol and fluticasone propionate was developed for the treatment of asthma and chronic obstructive pulmonary disease. Three different Salmeterol/fluticasone Easyhaler test products (Orion Pharma, Finland) were compared against the reference product Seretide ® Diskus ® DPI (GlaxoSmithKline, United Kingdom) to study whether any of the test products are bioequivalent with the reference., Methods: Open and randomized pharmacokinetic four-period crossover study on 65 healthy volunteers was performed in a single center to compare the lung deposition and total systemic exposure of salmeterol and fluticasone propionate after administration of single doses (two inhalations of 50/500 μg/inhalation strength) in fasting conditions. Blood samples were drawn before dosing and at frequent time points between 2 minutes and 34 hours after dosing for determination of drug concentrations. The primary variables for total systemic exposure and lung deposition of fluticasone propionate were maximum concentration of the concentration-time curve (C max ) and area under the concentration-time curve from time zero to the last sample with quantifiable concentration (AUC t ). For salmeterol, the primary variables for total systemic exposure were C max and AUC t and for lung deposition C max and AUC up to 30 minutes after study treatment administration (AUC 30min )., Results: One of the Easyhaler test products met all the criteria for bioequivalence with the reference. The 96.7% confidence intervals (CIs) for the test/reference ratios of fluticasone propionate C max and AUC t were 0.9901-1.1336 and 0.9448-1.0542, respectively. Ninety percent CIs for salmeterol C max , AUC 30min , and AUC t ratios were 1.0567-1.2012, 1.0989-1.2255, and 1.0769-1.1829, respectively. Median salmeterol time to maximum concentration (t max ) was 4.0 minutes. Median fluticasone propionate t max was from 1.5 to 2.0 hours. Terminal elimination half-life was 11 hours for salmeterol and 9-10 hours for fluticasone propionate., Conclusions: Salmeterol/fluticasone Easyhaler was shown to be bioequivalent with the reference product.

An experimental study was conducted on children aged 2;6-3;0 and 3;6-4;0 investigating the priming effect of two WANT-constructions to establish whether constructional competition contributes to English-speaking children's infinitival to omission errors (e.g., *I want ___ jump now). In two between-participant groups, children either just heard or heard and repeated WANT-to, WANT-X, and control prime sentences after which to-infinitival constructions were elicited. We found that both age groups were primed, but in different ways. In the 2;6-3;0 year olds, WANT-to primes facilitated the provision of to in target utterances relative to the control contexts, but no significant effect was found for WANT-X primes. In the 3;6-4;0 year olds, both WANT-to and WANT-X primes showed a priming effect, namely WANT-to primes facilitated and WANT-X primes inhibited provision of to. We argue that these effects reflect developmental differences in the level of proficiency in and preference for the two constructions, and they are broadly consistent with "priming as implicit learning" accounts. The current study shows that (a) children as young as 2;6-3;0 years of age can be primed when they have only heard (not repeated) particular constructions, (b) children are acquiring at least two constructions for the matrix verb WANT, and (c) that these two WANT-constructions compete for production., (Copyright © 2016 The Authors. Cognitive Science published by Wiley Periodicals, Inc. on behalf of Cognitive Science Society.)

Context: We previously identified 2 Finnish families with dominantly inherited, low-turnover osteoporosis caused by mutations in WNT1 or PLS3., Objective, Design, and Setting: This prospective, longitudinal, uncontrolled study was undertaken to evaluate whether these patients respond to teriparatide., Patients and Intervention: We recruited 6 adults (median age, 54 years); 3 with a WNT1 missense mutation, c.652T>G, and 3 with a PLS3 splice mutation, c.73-24T>A, to receive teriparatide 20 μg daily for 24 months. Five patients had previously used bisphosphonates., Main Outcome Measures: Outcome measures included lumbar spine and hip bone mineral density (BMD) by dual-energy X-ray absorptiometry, distal radius peripheral quantitative computed tomography, spinal radiography, serum bone turnover markers, paired iliac crest biopsies., Results: All patients showed increases in formation markers procollagen type 1 amino-terminal propeptide (90% to 398%) and osteocalcin (50% to 280%) and in resorption markers cross-linked C-terminal telopeptide of type I collagen (58% to 457%) and tartrate-resistant acid phosphatase 5b (20% to 68%) in first 6 months. Lumbar spine BMD increased 5.2% to 7.9% in 5 patients and femoral neck BMD 2.6% to 7.8% in 4 patients in 24 months. Distal radius cortical volumetric BMD decreased 5.4% to 26.1%. In histomorphometric analyses, osteoid indices increased more consistently in patients with WNT1 vs PLS3 mutation. Eroded surface decreased 44% to 100% in all patients. Adipocyte number increased in 5 patients studied., Conclusions: Patients with WNT1 or PLS3 mutation-related osteoporosis responded to teriparatide treatment. Future studies are needed to evaluate whether observed changes translate to fracture resistance., (Copyright © 2017 by the Endocrine Society)

We report three studies (one corpus, two experimental) that investigated the acquisition of relative clauses (RCs) in Finnish-speaking children. Study 1 found that Finnish children's naturalistic exposure to RCs predominantly consists of non-subject relatives (i.e. oblique, object) which typically have inanimate head nouns. Study 2 tested children's comprehension of subject, object, and two types of oblique relatives. No difference was found in the children's performance on different structures, including a lack of previously widely reported asymmetry between subject and object relatives. However, children's comprehension was modulated by animacy of the head referent. Study 3 tested children's production of the same RC structures using sentence repetition. Again we found no subject-object asymmetry. The pattern of results suggested that distributional frequency patterns and the relative complexity of the relativizer contribute to the difficulty associated with particular RC structures.

Background: Easyhaler(®) device-metered dry powder inhaler containing budesonide and formoterol fumarate dihydrate (hereafter formoterol) for the treatment of asthma and chronic obstructive pulmonary disease has been developed. The current approvals of the product in Europe were based on several pharmacokinetic (PK) bioequivalence (BE) studies, and in vitro-in vivo correlation (IVIVC) modeling., Methods: Four PK studies were performed to compare the lung deposition and total systemic exposure of budesonide and formoterol after administration of budesonide/formoterol Easyhaler and the reference product, Symbicort Turbuhaler. The products were administered concomitantly with oral charcoal (lung deposition) and in two of the studies also without charcoal (total systemic exposure). Demonstration of BE for lung deposition (surrogate marker for efficacy) and non-inferiority for systemic exposure (surrogate marker for safety) were considered a proof of therapeutic equivalence. In addition, IVIVC models were constructed to predict study outcomes with different reference product fine particle doses (FPDs)., Results: In the first pivotal study, the exposure and lung dose via Easyhaler were higher compared to the reference product (mean comparison estimates between 1.07 and 1.28) as the FPDs of the reference product batch were low. In the following studies, reference product batches with higher FPDs were utilized. In the second pivotal study, non-inferiority of Easyhaler compared to Turbuhaler was shown in safety and BE in efficacy for all other parameters except the formoterol AUCt. In the fourth study where two reference batches were compared to each other and Easyhaler, budesonide/formoterol Easyhaler was bioequivalent with one reference batch but not with the other having the highest FPDs amongst the 28 reference batches studied. In the IVIVC based study outcome predictions, the test product was bioequivalent with great proportion of the reference batches. For the test product and the median FPD reference product BE was predicted., Conclusions: Equivalence regarding both safety and efficacy between budesonide/formoterol Easyhaler and Symbicort Turbuhaler was shown based on totality of evidence from the PK studies and IVIVC analyses, and therefore, therapeutic equivalence between the products can be concluded. The results of the PK studies are likely dependent on the variability of FPDs of the reference product batches.

English-speaking children make pronoun case errors producing utterances where accusative pronouns are used in nominative contexts (me do it). We investigate whether complex utterances in the input (Let me do it) might explain the origin of these errors. Longitudinal naturalistic data from seventeen English-speaking two- to four-year-olds was searched for 1psg accusative-for-nominative case errors and for all 1psg preverbal pronominal contexts. Their caregivers' data was also searched for 1psg preverbal pronominal contexts. The data show that the children's proportional use of me-for-I errors correlated with their caregivers' proportional use of me in 1psg preverbal contexts. Furthermore, the verbs that children produced in me-error utterances appeared in complex sentences containing me in the input more often than verbs that did not appear in me-for-I errors in the children's speech. These findings are discussed in the context of current explanations for children's case marking errors.

Objective: To study the effects of cervical headgear treatment of Class II division 1 malocclusion on upper airway structures in children., Materials and Methods: Forty children aged 9.1 (7.2-11.5) years with Class II division 1 malocclusion were treated using a cervical headgear as the only treatment appliance. The headgear consisted of a long outer bow bent 15 degrees upward and a large inner bow expanded 10 mm larger than the intermolar distance. Lateral cephalograms were taken before and after the treatment. Upper airway structures were estimated from the cephalograms. The results were compared to cross-sectional data of 80 age-matched controls with a Class I molar relationship., Results: A Class I molar relationship was achieved in all treated children. The mean treatment time was 1.6 (0.3-3.1) years. The Class II malocclusion was accompanied by a similar or wider nasopharyngeal space than in the controls but narrower oro- and hypopharyngeal spaces. The retropalatal area was widened by the treatment (P < .05), whereas the rest of the oropharynx and hypopharynx remained narrower than in the controls. Before the treatment, the mandibular plane was in a more horizontal position than in the controls, but during the treatment, it rotated to a position similar to that of the controls., Conclusion: Class II division 1 malocclusion is associated with a narrower upper airway structure even without retrognathia. Headgear treatment is associated with an increase in the retropalatal airway space.

Objective: To characterize the effects of early cervical headgear treatment on the facial profile of children in Class II division 1 malocclusion., Materials and Methods: Forty children aged 9.1 (7.2-11.5) years with Class II division 1 malocclusion were treated using a cervical headgear appliance. The headgear consisted of a long outer bow bent upward 15 degrees and a large expanded inner bow. Lateral cephalograms were taken before and after treatment, and the facial profile was estimated from the cephalograms. The results were compared to an age- and sex-matched normal cohort of 644 Finnish children., Results: Class I molar relationship was achieved in all treated children. The treatment time was 1.6 (0.3-3.1) years on average. Compared to the controls, the treatment restricted the forward growth of maxillary A-point, and the SNA angle decreased 1.4 degrees +/- 1.2 degrees per year (P < .00001). Decreased maxillary prognathism was associated with decreased facial convexity, g-sn-pg (P = .02), and the ANB (P < .00001) angles decreased compared to the controls. Upper lip protrusion (distance ls to sn-pg; P < .00001) was decreased, and the nasolabial angle (cm-sn-ls) widened despite the increased facial inclination of the upper incisors (P = .0005). The treatment significantly decreased the gap between the lips (P = .0009) in their relaxed position., Conclusion: Cervical headgear treatment in Class II correction is associated with a decreased facial convexity caused by the restriction of forward growth of the maxillary A-point, while the rest of the facial profile, including the mandible, continue to grow forward at a normal rate.

Aims: The aim of this study was to compare lung deposition of budesonide administered from two dry powder inhalers, Giona Easyhaler 200 microg/dose and Pulmicort Turbuhaler 200 microg/dose by utilizing a pharmacokinetic method., Methods: This was an open, randomized, crossover study in 33 healthy subjects. The study consisted of four treatment periods separated by at least 4 wash-out days. Equivalence in lung deposition was assessed after a single inhaled 1000 microg (5 x 200 microg) dose of budesonide from Giona Easyhaler and from Pulmicort Turbuhaler. Concomitant oral charcoal administration (40 g) was used to prevent gastrointestinal (GI) absorption of budesonide. The efficacy of the charcoal was studied after oral administration of a budesonide 2 mg capsule. The subjects were trained to inhale the study drugs with controlled flow rates, which resulted in an equal pressure drop (4 kPa) across both inhalers. Venous blood samples for the determination of budesonide concentrations in plasma were drawn before and at predetermined time points up to 8 h after drug administration. Budesonide concentrations in plasma were determined using liquid chromatography-tandem mass spectrometry. Several pharmacokinetic parameters were estimated, the area under the budesonide concentration in plasma vs time curve from dosing to infinity (AUC(0, infinity)) being the primary response variable. Equivalence in lung deposition was concluded if the 90% confidence interval (CI) for the Easyhaler : Turbuhaler ratio of AUC(0, infinity) fell within the limits of 0.8-1.25., Results: The mean AUC(0,infinity) value after Easyhaler treatment was 3.48 (standard deviation (SD) 0.93) ng ml(-1) h and after Turbuhaler treatment 3.46 (1.13) ng ml(-1) h. The Easyhaler : Turbuhaler AUC(0, infinity) ratio was 1.02 and the 90% CI was from 0.96 to 1.09. The mean C(max) values (SD) for budesonide in plasma after Easyhaler and Turbuhaler treatments were 1.22 (0.41) ng ml(-1) and 1.29 (0.44) ng ml(-1), respectively. There was no statistically significant difference (P = 0.39) between the median t(max) for Easyhaler (30 min) and Turbuhaler treatment (23 min). Charcoal impaired the GI absorption of budesonide by 96%. The occurrence of adverse events was similar during both treatments., Conclusions: The results show that the lung deposition of budesonide from Giona Easyhaler 200 microg/dose and Pulmicort Turbuhaler 200 microg/dose dry powder inhalers is equivalent. The charcoal block used to prevent GI absorption of swallowed budesonide was found to be effective.

The permeability characteristics of an organotypic epidermal culture model derived from rat epidermal keratinocytes, ROC, and isolated human cadaver epidermis, HEM, were compared. Rat epidermal keratinocyte (REK) cell line was grown for 3 weeks on collagen gel in the absence of feeder cells in culture inserts at an air-liquid interface. Transdermal permeabilities of 18 compounds ranging from 92 to 504 in molecular weight and from -4.3 to 3.9 in log of octanol-water partition coefficient, charged or uncharged, were measured in the culture model and isolated human epidermis. The REK organotypic culture model (ROC) provided a close estimate of human epidermal permeabilities over the whole range of the solutes used with on the average of 2-fold higher permeability coefficients (range 0.3-5.2) than those obtained from isolated human cadaver epidermis. The easily maintained and reproducible ROC model may be useful in screening transepidermal drug permeabilities together with possessing potential for research on dermal formulations, irritation, toxicity and gene therapy.

Class-II, division-1 malocclusion appears to be associated with a narrow maxilla. A Class-II malocclusion may be corrected to a Class-I relationship in children using a cervical headgear provided that the narrow maxilla is expanded. This expansion is possible using headgear by dental cast analysis, but this has not been confirmed by cephalometry. We studied the effects of orthopedic cervical headgear on dental and skeletal facial widths in 40 children aged 9.1 (7.2-11.5) who had Class-II, division-I malocclusions. The headgear consisted of a long outer bow bent 15 degrees upward and a large inner bow expanded by 10 mm. Posteroanterior cephalographs and dental casts were taken before and after treatment. The results were compared with the control values presented in the literature. The malocclusion was treated to a Class-I relationship in all children. The average treatment time was 1.6 (0.3-3.1) years. The maxilla was widened significantly (P < .0001). The upper first molar width (um-um) and maxillary width (mx-mx) increased 3.2 and 1.6 mm/y, respectively. Maxillary widening was also observed in the nasal structure as indicated by an increase in lateronasal width (lap-lap) by 1.0 mm/y (P < .005). With maxillary widening, the mandibular dental arch widened spontaneously. The lower first molar width (lm-lm) increased 0.8 mm/y, which was more than the increase in the controls (P < .0001). However, the antegonial width (ag-ag) remained unaffected. By using a widened inner bow in headgear therapy with Class-II malocclusions, a widening of maxilla and nasal cavity may be obtained.

A continuous rat epidermal cell line (rat epidermal keratinocyte; REK) formed a morphologically well-organized epidermis in the absence of feeder cells when grown for 3 weeks on a collagen gel in culture inserts at an air-liquid interface, and developed a permeability barrier resembling that of human skin. By 2 weeks, an orthokeratinized epidermis evolved with the suprabasal layers exhibiting the differentiation markers keratin 10, involucrin, and filaggrin. Granular cells with keratohyalin granules and lamellar bodies, and corneocytes with cornified envelopes and tightly packed keratin filaments were present. Morphologically, vitamin C supplementation of the culture further enhanced the normal wavy pattern of the stratum corneum, the number of keratohyalin granules present, and the quantity and organization of intercellular lipid lamellae in the interstices of the stratum corneum. The morphological enhancements observed with vitamin C correlated with improved epidermal barrier function, as indicated by reduction of the permeation rates of tritiated corticosterone and mannitol, and transepidermal water loss, with values close to those of human skin. Moreover, filaggrin mRNA was increased by vitamin C, and western blots confirmed higher levels of profilaggrin and filaggrin, suggesting that vitamin C also influences keratinocyte differentiation in aspects other than the synthesis and organization of barrier lipids. The unique REK cell line in organotypic culture thus provides an easily maintained and reproducible model for studies on epidermal differentiation and transepidermal permeation.

Forty consecutively referred children, 20 boys and 20 girls, with a Class II division I malocclusion and protrusive maxilla were treated with orthopedic cervical headgear with a 10 mm expanded inner bow and a long outer bow bent 15 degrees upwards. The mean age of the children at the beginning of treatment was 9.3 years (SD 1.3, range 6.6 to 12.4 years), and the average treatment time was 1.8 years (SD 0.6, range 0.8 to 3.1 years). In all patients Class II molar relationships were successfully corrected to Class I molar relationships. This was accompanied by a marked widening of both maxillary and mandibular dental arches. The cephalometric analysis suggested that the observed improvement of the occlusion was due to an inhibition of forward growth of the maxilla and anterior downward rotation of the palate.

Objectives: Few data exist for long-term results after the Senning operation for transposition of the great arteries. Sinus node dysfunction and systemic ventricular dysfunction have been the main problems. We evaluated risk factors for late death and the incidence of late death, sinus node dysfunction, and right ventricular dysfunction in 100 patients., Methods: The study was a retrospective analysis with a mean follow-up time of 12.8 +/- 3.1 years. No patients were lost to follow-up. Patients were divided in 2 groups according to ventricular septal defect (73 simple, 27 complex). The electrocardiogram, ambulatory electrocardiogram, echocardiogram, and chest radiograph were reviewed for each patient., Results: The overall mortality rate was 10%. The actuarial survival was 90% (simple) and 78% (complex); the probability of staying in sinus rhythm was 34% and 7%, and the probability of normal right ventricular function was 52% and 39%, respectively, 15 years after operation. The incidence of sinus node dysfunction increased gradually over time, although the incidence of right ventricular dysfunction increased rapidly after 10 years of follow-up. Late deaths, arrhythmias, and right ventricular dysfunction were significantly more frequent in the complex group. Right ventricular dysfunction and active arrhythmias were risk factors for late death., Conclusion: Long-term follow-up after the Senning operation shows increasing incidence of sinus node dysfunction and right ventricular dysfunction over time. Deteriorating right ventricular function is a major concern. Its early recognition and initiation of appropriate management to preserve cardiac function is an important follow-up goal.

Liposomes have been suggested as a vehicle for dermal and transdermal drug delivery, but the knowledge about the interaction between lipid vesicles and human skin is poor. Therefore, we visualized liposome penetration into the human skin by confocal laser scanning microscopy (CLSM) in vitro. Liposomes were prepared from phospholipids in different compositions and labeled with a fluorescent lipid bilayer marker, N-Rh-PE (L-alpha-phosphatidylethanolamine-N-lissamine rhodamine B sulfonyl). Fluorescently labelled liposomes were not able to penetrate into the granular layers of epidermis. However, the fluorescence from liposome compositions containing DOPE (dioleylphosphatidyl ethanolamine) was able to penetrate deeper into the stratum corneum than that from liposomes without DOPE. Pretreatment of skin with unlabeled liposomes containing DOPE or lyso-phosphatidyl choline (lyso-PC) enhanced the subsequent penetration of the fluorescent markers, N-Rh-PE and sulforhodamine B into the skin, suggesting possible enhancer activity, while most liposomes did not show such enhancement. Resonance energy transfer (RET) and calcein release assay between stratum corneum lipid liposomes (SCLLs) and the phospholipid vesicles suggested that the liposomes containing DOPE may fuse or mix with skin lipids in vitro and loosen the SCLL bilayers, respectively. Among the factors not affecting stratum corneum penetration were: negative charge, cholesterol inclusion and acyl chain length of the phospholipids. In conclusion, fusogenicity of the liposome composition appears to be a prerequisite for the skin penetration.