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At least 145 records · Page 8Linked to original sources
PubMed1976

Ultrastructural studies in epidermolysis bullosa hereditaria. IV. Recessive dystrophic types with junctional blistering. (Infantile or Herlitz-Pearson type and adult type).

Recessive dystrophic epidermolysis bullosa with junctional blisters includes both the classical epidermolysis bullosa hereditaria letalis Herlitz (Herlitz-Pearson type) and a recently separated more benign adult type. Ultrastructural examination was performed of 13 skin specimens from 3 cases of the Herlitz-Pearson-type and one case of the adult type. Principal ultrastructural changes in involved, intact and experimentally frictioned skin regions, common to all patients, are as follows: In nonseparated areas hypoplasia of the hemi-desmosomes and mild decrease of the tonofibrils are found. Hypoplasia of hemi-desmosomes consists of a marked rudimentary structure of the sub-basal dense plaque and the attachment plaque. Focal widening of the lamina lucida suggesting early blistering occurs exclusively in the areas devoid of hemidesmosomes. In separated areas cleavage always occurs in the plane of lamina lucida, viz. the mode of blistering is junctional. Fragments of basal cells are often encountered still remaining attached to the blister floor ("epidermolytic torn-off phenomenon"). These torn-off portions of basal cells are characterized by relatively rich distribution of hemidesmosomes. Basal cells forming the blister roof frequently show small gaps of basal plasma membrane and rarefaction of the basal part of the cytoplasm, which are thought to be secondary changes. Among the observed alterations, structural defects of hemidesmosomes are considered to play the most important role in the pathogenesis of junctional blisters.

Adult↗
PubMed2003

Human subcutaneous tissue distribution of fluconazole: comparison of microdialysis and suction blister techniques.

AIMS: To investigate uptake of fluconazole into the interstitial fluid of human subcutaneous tissue using the microdialysis and suction blister techniques. METHODS: A sterile microdialysis probe (CMA/60) was inserted subcutaneously into the upper arm of five healthy volunteers following an overnight fast. Blisters were induced on the lower arm using gentle suction prior to ingestion of a single oral dose of fluconazole (200 mg). Microdialysate, blister fluid and blood were sampled over 8 h. Fluconazole concentrations were determined in each sample using a validated HPLC assay. In vivo recovery of fluconazole from the microdialysis probe was determined in each subject by perfusing the probe with fluconazole solution at the end of the 8 h sampling period. Individual in vivo recovery was used to calculate fluconazole concentrations in subcutaneous interstitial fluid. A physiologically based pharmacokinetic (PBPK) model was used to predict fluconazole concentrations in human subcutaneous interstitial fluid. RESULTS: There was a lag-time (approximately 0.5 h) between detection of fluconazole in microdialysate compared with plasma in each subject. The in vivo recovery of fluconazole from the microdialysis probe ranged from 57.0 to 67.2%. The subcutaneous interstitial fluid concentrations obtained by microdialysis were very similar to the unbound concentrations of fluconazole in plasma with maximum concentration of 4.29 +/- 1.19 microg ml(-1) in subcutaneous interstitial fluid and 3.58 +/- 0.14 microg ml(-1) in plasma. Subcutaneous interstitial fluid-to-plasma partition coefficient (Kp) of fluconazole was 1.16 +/- 0.22 (95% CI 0.96, 1.35). By contrast, fluconazole concentrations in blister fluid were significantly lower (P < 0.05, paired t-test) than unbound plasma concentrations over the first 3 h and maximum concentrations in blister fluid had not been achieved at the end of the sampling period. There was good agreement between fluconazole concentrations derived from microdialysis sampling and those estimated using a blood flow-limited PBPK model. CONCLUSIONS: Microdialysis and suction blister techniques did not yield comparable results. It appears that microdialysis is a more appropriate technique for studying the rate of uptake of fluconazole into subcutaneous tissue. PBPK model simulation suggested that the distribution of fluconazole into subcutaneous interstitial fluid is dependent on tissue blood flow.

Adult↗
PubMed1978

Freeze-fracture studies of the developing cell surface. II. Particle-free membrane blisters on glutaraldehyde-fixed corneal fibroblasts are artefacts.

We describe, in sections and by freeze-fracture, four classes of intramembrane particle (IMP)-free membrane blebs or "blisters" associated with glutaraldehyde-fixed embryonic corneal fibroblasts: (a) Single blisters attached to the cell membrane; (b) free (detached) vesicles; (c) myelin figures; (d) multivesicular protrusions which resemble the "mounds" described by others on nerve growth cones. The IMP-free, membrane-bounded blisters contain no ground cytoplasm or organelles, in contrast to blebs on trypsin-isolated fibroblasts, which we show here do contain cytoplasm and IMP-rich membranes. That the IMP-free membrane blisters in embryonic corneas are artefacts of fixation is demonstrated by (a) their absence in replicas of fibroblasts frozen and fractured without prior aldehyde fixation and (b) their absence in sections of fibroblasts fixed in a combination of glutaraldehyde and osmium tetroxide. We suggest that the addition of osmium prevents postfixation movement of membrane lipids, especially the negatively charged "fluid" lipids which others have shown are capable of considerable mobility after aldehyde fixation alone. Recent literature has implicated membrane blistering in secretory processes and in growth of nerves, but before the functional significance of such IMP-free blisters is assessed, membrane mobility of the type shown here should be taken into consideration.

Cell Membrane↗
PubMed1995

Interstitial collagenase is expressed by keratinocytes that are actively involved in reepithelialization in blistering skin disease.

Migrating keratinocytes actively involved in reepithelialization in dermal wounds acquire a collagenolytic phenotype upon contact with the dermal matrix. To determine whether this phenotype is associated with repair in other forms of wounds, we assessed collagenase expression in 50 specimens representing a variety of blistering skin diseases, including subtypes of epidermolysis bullosa, porphyria cutanea tarda, bullous pemphigoid, pemphigus, transient acantholytic dermatosis, and suction blisters. Distinct from that seen in chronic ulcers or in normal healing by second intention, reepithelialization in these blistering conditions was not necessarily associated with a complete loss of basement membrane, as determined by immunostaining for type IV collagen. Collagenase mRNA was detected in the basal keratinocytes of several specimens of epidermolysis bullosa simplex (six of 10) and of pemphigus (three of seven), as well as in one quarter of transient acantholytic dermatosis samples in the presence of an intact basement membrane. In contrast, three of nine porphyria cutanea tarda, one third of epidermolysis bullosa acquisita, and one of 10 bullous pemphigoid samples had collagenase-positive basal keratinocytes with the basement membrane disrupted. The collagenase-positive lesions generally represented older blisters with evidence of epithelial regeneration. Collagenase was also expressed in suction blisters at 2 and 5 d after induction of the blister, but was shut off when the epidermis had healed. Other metalloproteinases were expressed occasionally, if at all. Our results suggest that keratinocyte migration is associated with collagenase expression and that contact of keratinocytes with the dermal matrix is not necessarily needed for collagenase induction.

Basement Membrane↗
PubMed1994

The stereoselective disposition of the enantiomers of ibuprofen in blood, blister and synovial fluid.

1. A sensitive, stereospecific assay using gas chromatography-mass spectrometry (GC/MS) was established to measure the concentrations of the enantiomers of ibuprofen in small volumes (50 microliters) of blister fluid. 2. The concentrations of the enantiomers in blister fluid, assessed in eight patients, were similar to those in synovial fluid, both fluids behaving as peripheral compartments with respect to plasma. 3. The mean rate constants of transfer of R-ibuprofen into (0.14 +/- 0.06 h-1) and out of (0.20 +/- 0.04 h-1) blister fluid were not significantly different from those for synovial fluid (0.19 +/- 0.12 h-1, 0.34 +/- 0.11 h-1, respectively). Similarly, the mean rate constants of transfer of S-ibuprofen into (0.22 +/- 0.07 h-1) and out of (0.27 +/- 0.08 h-1) blister fluid were not significantly different from those for synovial fluid (0.29 +/- 0.10, 0.36 +/- 0.11 h-1). However, the correlations were poor between the transfer constants for each of the enantiomers between plasma, and both blister and synovial fluid (P > 0.2). 4. The complex rate constant of transfer of S-ibuprofen into blister fluid (0.22 +/- 0.07 h-1) was greater than that of R-ibuprofen (0.14 +/- 0.07 h-1), which may be explained by the lesser protein binding of the S-enantiomer.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMedDate not supplied

Aortic blisters: diagnosis and evolution.

In order to evaluate the incidence, the diagnostic modalities and significance of blisters of the abdominal aortic aneurysm wall, in a retrospective review, 14 patients (2.6%) having these lesions were identified between 1983 and 1995. At preoperative examination, aortography had less accuracy (1 case = 20%) than CT scan (3 cases = 27.2%) or MRI angiography (6 cases = 85.7%) to detect blisters; others were discovered intraoperatively in the remaining four patients. Most blisters were located on the anterior or antero-lateral wall of aneurysms; its area ranged from 0.8 to 2.6 cm2. One patient with a suspected blister diagnosed at aortography, during chest physiotherapy for his COPD, presented sudden abdominal pain: at urgent laparotomy, an acute contained rupture of a large blister, without extraluminal blood loss, was found. All patients underwent aneurysm repair, with no postoperative deaths. Occurrence of rupture in one patient clearly indicates the natural course of aortic blisters. MRI angiography may accurately detect these lesions; surgical treatment is necessary for preventing imminent rupture.

Aged↗
PubMed1990

Two-stage penetration of a single oral dose of sulphadimethoxine into skin blister fluid.

The time-dependent concentration curves of sulphadimethoxine in plasma and cantharidin-induced skin blister fluid have been evaluated following a single oral dose of 1 g. In contrast to other drugs, sulphadimethoxine exhibited two-stage penetration into the blister fluid, the second peak concentration being higher than the first. The maximum plasma concentration of 94.1 mg.l-1 was observed after 4 h, and in skin blister fluid the first peak of 25.6 mg.l-1 was found after 7 h, and the second of 58.0 mg.l-1 occurred after 30 h. The penetration of sulphadimethoxine into skin blister fluid, defined as the ratio of the AUC there to that in plasma was 0.748. The results suggest that sulphadimethoxine penetrates into skin blister fluid to a great extent from plasma and achieves concentrations exceeding the MIC for susceptible pathogens, but it requires a relatively long time to do so.

Administration, Oral↗
PubMed1990

Interleukin 2, soluble interleukin 2 receptor, and interferon-gamma in the suction blister fluids from psoriatic skin.

Psoriasis represents inflammatory skin disorders characterized by significant changes in cellular immunity, particularly exhibiting alterations in T lymphocyte-related functions. Early psoriatic lesions have been reported to show an infiltration of activated helper T cells. Elevated levels of interleukin 2 (IL-2), IL-2 receptor (IL-2R), and interferon-gamma (INF-gamma) are associated with an early activation of T cells. To examine local activation of T cells in psoriatic skin, the amounts of activated T cell products, IL-2, secretory form of IL-2R (sIL-2R) and INF-gamma were measured in the fluids of suction blisters raised on psoriatic skin. sIL-2R levels were significantly elevated in the suction blister fluids raised on psoriatic involved skin compared with those on normal and psoriatic uninvolved skin. On the other hand, neither IL-2 or IFN-gamma was detected in the suction blister fluids either from normal, psoriatic uninvolved, or involved skin. However, we could detect IFN-gamma and IL-2 in the psoriatic scale extracts. Although we failed to detect IL-2 and IFN-gamma in the suction blister fluids, the increased levels of sIL-2R in the suction blister fluids from the psoriatic lesional skin indicate local activation of T cells in psoriatic lesional skin.

Adolescent↗
PubMed1983

Vitamin A transporting proteins in human epidermis and blister fluids.

In connection with studies on vitamin A transport to keratinocytes in vivo, the retinol, retinol-binding protein (RBP), and prealbumin contents of blister fluid obtained subepidermally (suction) or intraepidermally (friction) were analyzed. The median concentrations of the three components in suction blister fluid (SBF) were all about 33% of the serum concentrations. Corresponding values for alpha 2-macroglobulin and total protein, measured as controls, were 27 and 30%, respectively. The relative amounts of retinol and prealbumin in friction blister fluid (FBF) were the same as those in SBF. By contrast, FBF contained more RBP (median value 40%; P less than 0.01 vs SBF value). It is suggested that apo-RBP (RBP without retinol) is generated within the epidermis and contributes to the high RBP value in FBF. FBF constituents are probably derived from the intercellular space of the epidermis, at least during the initial phase of blister formation. Accordingly, RBP and prealbumin were identified in homogenates of pure epidermis. During the later stages of blister formation, FBF resembles an ultrafiltrate of dermal fluid, although different in this respect from SBF.

Adult↗
PubMed1992

The site of blister formation in dermatitis herpetiformis is within the lamina lucida.

BACKGROUND: Because the initial neutrophilic infiltrate in dermatitis herpetiformis is within the dermal papillae, most investigators have assumed the vesicles occur in this same area. This was supported by electron microscopy studies. In 1983 Klein et al. refuted this concept, suggesting that vesicle formation was within the lamina lucida above the lamina densa. Despite this study, current literature continues to state that blister formation is below the lamina densa. OBJECTIVE: Our purpose was to determine the ultrastructural site of blister formation in early and late vesicles of dermatitis herpetiformis. METHODS: We evaluated eight biopsy specimens from four patients by immunomapping with antibodies to bullous pemphigoid antigen, laminin, type IV collagen, and epidermolysis bullosa acquisita antigen. RESULTS: In both early and late vesicles blister formation was found to be above the lamina densa in the lamina lucida. CONCLUSION: These findings are contrary to the commonly held concept that the blister in dermatitis herpetiformis is below the lamina densa and confirm the findings of Klein et al. that the site of blister formation in dermatitis herpetiformis is above the lamina densa within the lamina lucida.

Basement Membrane↗
PubMed1983

Reduced threshold to suction-induced blister formation in insulin-dependent diabetics.

Diabetics may have an increased susceptibility to cutaneous blister formation clinically manifest as the bullous eruption of diabetes. We evaluated the mechanical force necessary to induce suction blisters in fifteen insulin-dependent diabetics and twenty age-matched normal controls. The mean suction blister threshold for the diabetics was 31.9 minutes versus 68.0 minutes for the controls, a highly significant difference (p less than 0.01). Histologic appearance of suction blisters was similar in diabetic and normal skin, under both light and electron microscopic examination, with a noninflammatory subepidermal separation in the lamina lucida between the cell membrane and the basal lamina. These results demonstrate that insulin-dependent diabetics have a marked reduction in suction blister threshold as compared to age-matched controls.

Adult↗
PubMed2000

Human beta defensin is absent in burn blister fluid.

Defensins are a family of cationic antimicrobial peptides that participate in innate host defence. Human beta defensin-2 (HBD-2) is produced by human keratinocytes, and has a potent bactericidal activity against a wide spectrum of microorganisms. We have recently shown that expression of HBD-2 is present in normal skin and lost in the full-thickness burn wound. Defensins have been found in the blister fluid of chronic wounds. Our study was designed to examine blister fluid from partial-thickness burns for defensin content. Fluid from five patients was collected from partial-thickness burn blisters, and then analysed by sandwich Enzyme-Linked Immunosorbent Assay (ELISA) with a monoclonal antibody and rabbit polyclonal antibody to HBD-2. The assay was validated against a Western blot assay for HBD-2 in samples of bronchoalveolar lavage fluid from patients with inflammatory lung disease. No HBD-2 was detectable in any of the burn blister fluids analysed. HBD-2 is lost in the full-thickness burn wound, and we have now demonstrated its absence in burn blister fluid. This finding represents evidence of a host defence defect within the burn wound and suggests a possible therapeutic role for antimicrobial peptides in the management of burn wounds.

Adolescent↗
PubMed1998

Direct assessment of peripheral pharmacokinetics in humans: comparison between cantharides blister fluid sampling, in vivo microdialysis and saliva sampling.

AIMS: Skin blister fluid sampling, in vivo microdialysis and saliva sampling are commonly employed as surrogates for the measurement of drug concentrations in peripheral compartments. Although expected to exhibit comparable results, data derived from these techniques have never been directly compared. Thus, the aim of the present study was to evaluate the comparability of these techniques. METHODS: Paracetamol, a model drug with low protein binding, was administered to seven healthy volunteers at an oral dose of 2000 mg. Subsequently, tissue kinetics were measured simultaneously in cantharides induced skin blisters, microdialysates of subcutaneous- and skeletal muscle-tissue and saliva and compared to serum concentrations. RESULTS: Mean ratio (AUCblister/AUCserum) was 0.88 (95% CI, 0.50-1.26), mean ratio (AUCmuscle/AUCserum) was 1.08 (0.67-1.49), mean ratio (AUCsubcutaneous/AUCserum) was 0.96 (0.41-1.51) and mean ratio (AUCsaliva/AUCserum) was 1.83 (1.39-2.27). In this study the concentration profiles after single oral administration differed among the three methods. The time course of the concentration (peripheral compartment)/concentration (serum)-ratios showed that cantharides blister and microdialysate concentrations closely paralleled serum levels. An equilibration period of less than 2 h had to be taken into account for blister measurements. In contrast, saliva concentrations were significantly higher than corresponding serum concentrations. CONCLUSIONS: Skin blister sampling and microdialysis closely mirrored corresponding serum concentrations and, thus, proved to be suitable techniques for the assessment of peripheral compartment pharmacokinetics. In contrast, saliva data overestimated the corresponding serum concentrations.

Acetaminophen↗
PubMed2000

Elevated levels of eotaxin and interleukin-5 in blister fluid of bullous pemphigoid: correlation with tissue eosinophilia.

BACKGROUND: Bullous pemphigoid (BP) often provokes blood and tissue eosinophilia, which suggests that some chemoattractants modulate the eosinophil infiltration in BP. Eotaxin, a CC chemokine, strongly attracts eosinophils, and interleukin (IL)-5 induces eosinophil differentiation, proliferation and colony formation in vitro. OBJECTIVES: To examine the correlation between levels of eotaxin and IL-5 and the number of lesional eosinophils, and the expression of eotaxin in BP lesions. PATIENTS/METHODS: In this study we measured eotaxin and IL-5 levels in blister fluid of BP by enzyme-linked immunosorbent assay. We also examined the expression of eotaxin in BP lesions by immunohistochemistry. RESULTS: Both eotaxin and IL-5 were detected at high levels in BP blister fluid. Blister fluid eotaxin, but not IL-5 levels, correlated significantly with the number of dermal infiltrating eosinophils. By immunohistochemistry, eotaxin was strongly expressed in epidermal keratinocytes around BP blisters. CONCLUSIONS: These findings suggest that eotaxin and IL-5 are strongly associated with the tissue eosinophilia of BP. Therapies which aim to inhibit production of eotaxin and IL-5 may improve the inflammation and blister formation in BP.

Adult↗
PubMed2003

Bullous malignant melanoma: an unusual differential diagnosis of a hemorrhagic friction blister.

BACKGROUND: A 66-year-old woman presented to our outpatient clinic with a 3 x 2.5-cm tense, hemorrhagic-appearing bulla on her forefoot. Histopathology and immunohistochemistry confirmed a transtumoral-transepidermal blister formation within an advanced acrolentiginous malignant melanoma (MM). OBJECTIVE: To study bullous malignant melanoma. METHODS: Blistering in MMs represents a rare but clinically important pitfall in clinical differential diagnosis. The blisters are typically due to the disruption of the cohesion between neoplastic cells and keratinocytes, but physical friction may also contribute. RESULTS: Hemorrhagic blistering is, in many cases, a relatively insignificant finding in which frictional forces are imposed. CONCLUSION: The case reported here underscores that in rare cases MMs, particularly if acrally located, can be complicated by hemorrhagic blistering. Because of the life-threatening consequences, one should be aware of this rare differential diagnosis.

Aged↗
PubMed1999

Microdialysis vs. suction blister technique for in vivo sampling of pharmacokinetics in the human dermis.

Our aim was to simultaneously investigate 2 techniques for in vivo sampling of peripheral compartment pharmacokinetics after systemic administration of acetylsalicylic acid. Ten volunteers were given 2 g acetylsalicylic acid orally. Blood samples and dialysates from 4 microdialysis probes inserted in the dermis of the forearm were collected for 5 h and suction blisters were raised 1-3 h after dosing. In microdialysates, both acetylsalicylic acid and the metabolite salicylic acid were measurable in the absence of hydrolysing enzymes. The mean Cmax (maximum concentration) of total, unbound salicylic acid was 9.5 microg/ml in microdialysates, 13.2 microg/ml in suction blister fluid and 56.5 microg/ml in plasma. Mean Tmax (time to Cmax) for salicylic acid was 188 and 161 min in plasma and microdialysates, respectively. The dermis-to-plasma Cmax ratio was 0.16+/-0.04 (mean +/- SD) by microdialysis sampling and 0.25+/-0.09 by the suction blister fluid method. Close correlations (p<0.01) were found between Cmax of salicylic acid in microdialysates and plasma, and between Cmax of salicylic acid in suction blister fluid and plasma. The 2 techniques were in excellent accordance with even closer correlation between maximum concentrations obtained by microdialysis and suction blister fluid sampling (p<0.001). However, comparing the tolerability of the sampling procedure, ease of analysis, and detail in chronology, microdialysis is superior for sampling in vivo pharmacokinetics in the dermis.

Adult↗
PubMed1999

Distribution to the skin of penciclovir after oral famciclovir administration in healthy volunteers: comparison of the suction blister technique and cutaneous microdialysis.

Penciclovir is a drug active against herpes simplex viruses located in the epidermis basal layer. The aim of this study was to compare the suction blister technique and microdialysis as methods to measure the penciclovir concentration in the skin after a single dose (250 mg) of its prodrug, famciclovir. Suction blister fluid, microdialysates and plasma were sampled from 11 healthy volunteers for 5 h after famciclovir administration. Both the suction blister technique and microdialysis showed that penciclovir reaches the skin in concentrations sufficient to inhibit herpes virus replication. The maximum concentration in both suction blister fluid and in microdialysate was observed later than in plasma. The microdialysis concentration was decreased by cooling of the skin surface and by adrenaline-mediated vasoconstriction. The microdialysis recovery of penciclovir was studied with respect to the flow-rate of perfusion medium through the microdialysis probe. Microdialysis and the suction blister technique can be used to study the time-concentration profile of penciclovir in the skin and microdialysis allows a continuous sampling of the drug for a prolonged time after administration.

2-Aminopurine↗
PubMedDate not supplied

Penetration of antibiotics into human leukocytes and dermal suction blisters.

Staphylococcus aureus phagocytized by leukocytes from healthy donors and from patients with chronic granulomatous disease were protected from the antibacterial effect of gentamicin. Considerable numbers of phagocytized bacteria remained viable after exposure for 20 hr to antibiotic concentrations that killed greater than 99% of extracellular bacteria in less than 4 hr. A higher proportion of intracellular bacteria were killed by rifampin; this finding indicated that rifampin penetrates better into the phagocytic vacuole than does gentamicin and/or is more active against phagocytized bacteria than is gentamicin. After oral administration of 450 mg of rifampin to three healthy volunteers, concentrations of the antibiotic in serum and skin blister fluid were measured. Concentrations in serum peaked within 3 hr of oral administration (mean peak level, 13.2 micrograms/ml). Concentrations in blister fluid peaked between 6 hr and 9 hr (mean peak concentration, 2.7 micrograms/ml). Between 9 hr and 12 hr, the concentrations of rifampin in serum and blister fluid were similar; later, levels in blister fluid were higher than those in serum. The mean elimination half-life of rifampin was 2.5 hr in serum and 6.0 hr in blister fluid.

Adult↗