Cutaneous side-effects of transdermal iontophoresis with and without surfactant pretreatment: a single-blinded, randomized controlled trial.

BACKGROUND: Iontophoresis, a method that facilitates drug transport across skin by an external electrical field, offers the possibility for long-term transdermal delivery of compounds in a well-controlled manner. In general, the literature supports the contention that iontophoresis is a safe procedure. However, there are important medical issues concerning the epidermal and dermal effects of iontophoresis that have not been extensively investigated. Specific and strictly controlled studies on the dermal effect of iontophoresis are scarce. OBJECTIVES: The aim of this study was to investigate the cutaneous side-effects of transdermal iontophoresis application in healthy human volunteers. METHODS: This was a single-blinded, randomized and parallel design study. In one group (n=12) subjects were treated nonocclusively with a surfactant formulation followed by iontophoresis (3-h application at a current density of 250 microA cm(-2)). In another group (n=12) iontophoresis alone was performed. No drug was included in these studies. The corresponding passive treatments served as controls. Noninvasive methods including sensation record, transepidermal water loss (TEWL), skin colour and the visual scoring were used to assess cutaneous effects. RESULTS: Tingling and itching were commonly experienced in the first 30 min of the current application. Iontophoresis in combination with the pretreatment induced significant increases in TEWL values and in skin redness, and resulted in slight to mild erythema and oedema compared with the control. Compared with the iontophoresis alone, the presence of surfactant pretreatment caused slightly more skin irritation (erythema and oedema) but did not further disturb the skin barrier function. CONCLUSIONS: The transdermal iontophoresis challenges the skin barrier function and induces transient mild skin irritation, but does not cause any permanent damage to the skin when applied for 3 h at a current density of 0.25 mA cm(-2).

Intramedullary spinal cord abscess. A case report.

STUDY DESIGN: A case of an intramedullary spinal cord abscess is presented. The literature on this subject is carefully reviewed. OBJECTIVES: To give an overview of clinical presentation, radiographic examination, pathogenesis, treatment, and outcome of intramedullary spinal cord abscesses. Cases presented in the literature are arranged and the findings summarized. SUMMARY OF BACKGROUND DATA: Intramedullary spinal cord abscesses are rare. Most frequently, single cases were reported, followed by a short discussion. All previously reported cases were reviewed. METHODS: After an extensive literature search, all cases of an intramedullary spinal cord abscess (totaling 93 patients), including ours, were reviewed. Incidence, clinical presentation, neuroradiologic investigations, treatment, and pathogenesis are discussed. RESULTS: Intramedullary spinal cord abscesses are rare. The presentation can be very confusing, mimicking thoracic or abdominal diseases. Magnetic resonance imaging is the best diagnostic technique, although the findings are not pathognomonic. Appropriate antibiotic therapy after surgical drainage is warranted. If left untreated, the outcome is bleak. Whereas most cultures remain sterile (38.7%), Staphylococcus or Streptococcus species are involved frequently (23.7% and 17.2%). CONCLUSIONS: Although intramedullary spinal cord abscess is a rare disease, every spine surgeon should have knowledge of its existence because misjudgment and deferring adequate treatment may lead to an unfavorable outcome.

['Cerebral running nose': cerebrospinal rhinorrhea]. / 'Cerebrale loopneus': rhinorrhoea cerebrospinalis.

Cerebrospinal fluid rhinorrhoea was diagnosed in two patients, a man of 19 and a woman of 45 years old. This is a relatively rare phenomenon and clinically often difficult to differentiate from nasal secretions caused by a rhinopathy. Although cerebrospinal fluid (CSF) fistulae usually are of traumatic origin as in the first patient, they can also be caused by a congenital malformation as in the second one or by a condition with chronic increased intracranial pressure. With adequate treatment the prognosis is good. CSF can be identified very specifically by beta-transferrin determination.

The lipid and protein structure of mouse stratum corneum: a wide and small angle diffraction study.

The structure of mouse stratum corneum was investigated using small and wide angle X-ray scattering. Diffraction patterns were collected as a function of temperature and hydration. The lipid lamellar structure is characterized by a repeat distance of 13.4 nm. Occasionally a second lipid lamellar phase has been found with a repeat distance of 6.1 nm. Upon hydration neither swelling of the lamellae nor lateral swelling of the lipids was found. On the basis of these facts it was concluded that the size of the crystallographic unit cell of the lipid structure is insensitive to the water content. The 13.4 nm lamellar phase disappeared upon heating to 55 degrees C. At 45 degrees C the orthorhombic lateral packing disappeared. At this temperature only an hexagonal and liquid lateral packing of the lipids was observed. The hexagonal lateral packing transformed to a liquid one between 45 degrees C and 80 degrees C. Model calculations were carried out to obtain the electron density profile of the lamellar structure. In all models three electron lucent regions were fitted between which electron dense regions are located indicating that the 13.4 nm lamellar structure consist of three bilayers.

Epitope tagging of DAB389IL-2: new insights into C-domain delivery to the cytosol of target cells.

The fusion toxin DAB389IL-2 is composed of the catalytic (C) and transmembrane (T) domains of native diphtheria toxin to which human interleukin-2 (IL-2) has been genetically fused (1,2). Following binding to the IL-2 receptor, the fusion toxin is internalized by receptor mediated endocytosis, and upon acidification of the endocytic vesicle, the T domain spontaneously inserts into the membrane, and facilitates the delivery of the C domain to the cytosol (3,4). In order to further study the process by which the C domain is delivered to the target cell cytosol, we genetically fused an eleven amino acid epitope derived from the vesicular stomatitis virus (VSV) G protein to the N-terminal end of DAB389IL-2. The epitope labelled fusion toxin, VSV-G-DAB389IL-2, was found to retain IL-2 receptor specific binding and cytotoxic activity. Target cells were incubated for various times in the presence of VSV-G-DAB389, fixed and then treated with anti-VSV G and FITC conjugated secondary antibody. Laser scanning confocal microscopy was used to determine the location of the fluorescent signal. The VSV-G epitope tagged fusion toxin was found only to be associated with small vesicles that were situated adjacent to the plasma membrane. These results suggest that the C domain of the fusion toxin is associated with an early intracellular compartment and is rapidly delivered to the cytosol. Since channel formation by the T domain is necessary for the delivery of the C domain, it follows that T domain insertion into the membrane also occurs early in the intoxication pathway.

Transcranial Doppler ultrasonography: influence on scheduling of angiography and delayed surgery for ruptured intracranial aneurysms.

The role of transcranial Doppler ultrasound (TCD) was studied retrospectively in relation to the management of 73 patients with a subarachnoid hemorrhage due to a ruptured intracranial aneurysms. TCD velocity measurements provided very valuable data to assist scheduling of angiography and delayed surgery. Angiography and surgery were planned significantly sooner in the TCD examined group of patients with TCD velocities indicative for the absence of vasospasm than in the group of patients who did not have TCD examinations. The cerebral circulatory resistance index (R), calculated as: (maximum systolic velocity--end diastolic velocity)/maximum systolic velocity, and changes in R did not predict a change in clinical grade or outcome.

Acute pancreatitis due to sulfamethoxazole-trimethoprim.

We have reported a case of sulfonamide-induced acute pancreatitis. A review of the literature showed only eight previously reported cases. Adverse reactions to sulfonamides are well known, but acute pancreatitis is a very serious complication. If evidence of pancreatic involvement occurs during sulfonamide therapy, the medication should be discontinued immediately and, if necessary, be replaced by an alternative. Other causes of pancreatitis must be excluded.

Structural investigations of human stratum corneum by small-angle X-ray scattering.

The structure of human stratum corneum was investigated with small-angle X-ray scattering (SAXS). At room temperature the scattering curve was characterized by a strong intensity at low scattering vector (Q less than 0.8 nm-1) and two complicated diffraction peaks originating from a lamellar structure of the lipids. The lamellar lipid structure in the stratum corneum transformed to a disordered structure between 65 degrees C and 75 degrees C, the same temperature region at which a thermal lipid transition occurred. After cooling down to room temperature a recrystallization of at least a part of the lipids took place, after which only one unit cell with a repeat distance of 13.4 nm could be detected. Comparison of the scattering curve of the stratum corneum after crystallization with the scattering curve of the stratum corneum before recrystallization leads to the conclusion that in the original curve the lipids are arranged in two unit cells with repeat distances of 6.4 nm and 13.4 nm. From model calculations it appears that the latter unit cell consists of more than one bilayer. The scattering curves of stratum corneum hydrated to various levels were measured. A change in the water content of stratum corneum between 6% w/w and 60% w/w (fully hydrated) did not result in swelling of the bilayers, but the scattering curve obtained with stratum corneum hydrated to 60% w/w differed from those at lower hydration levels: the scattering curve at 60% w/w showed only the diffraction peaks corresponding to a unit cell with a repeat distance of 6.4 nm. This observation implies that the ordering of a part of the lipids is reduced at very high water contents, which may explain the strong penetration-enhancing effects of water in the stratum corneum.

Symptomatic vertebral hemangiomas.

Symptomatic vertebral hemangiomas are rare. Several therapeutic modalities for vertebral hemangiomas with neurologic deficit have been described. Personal experience with laminectomy followed by radiation therapy in four patients and radiation therapy in one patient is reported. Considering our results, literature and theoretical aspects a proposal for treatment of symptomatic vertebral hemangiomas is made.

Dissection of promoter sequences involved in transcriptional activation of the Escherichia coli replication origin.

The replication frequency of oriC plasmids in vivo is positively affected by specific transcripts running into oriC. These transcripts that activate oriC are initiated at a promoter of a gene coding for a 16kD protein. Genetic evidence is presented for binding of the initiation factor dnaA to a specific sequence (dnaA box) upstream of this promoter. Binding of the dnaA protein to this dnaA box regulates transcription initiation negatively. It was also demonstrated that binding of dnaA protein to the 16kD promoter region is essential to accomplish the actual activation event within the origin. Replication and incompatibility experiments suggest that dnaA protein is present within the activating transcription complex. The function of dnaA in this replication control mechanism is discussed.

Growth of human foreskin fibroblasts in a serum-free, defined medium without platelet-derived growth factor.

The hormones which support growth, in vitro, of normal, neonatal human foreskin fibroblasts were determined. Whereas thrombin and hydrocortisone were major growth stimulants, platelet-derived growth factor was not. Human foreskin fibroblasts grew in a serum-free, biochemically defined medium consisting of epidermal growth factor (100 ng/ml), insulin (100 ng/ml), transferrin 10 micrograms/ml), thrombin (1 microgram/ml), ascorbic acid (10 micrograms/ml), and hydrocortisone (5 x 10(-5) M) in a 1:1 mixture of Dulbecco's modified Eagle's medium and Ham's F-12, supplemented with ovalbumin (1 mg/ml) and trace elements. The growth achieved was comparable to that achieved with 5% fetal bovine serum. Neither platelet-derived growth factor, fibroblast growth factor, nor somatomedin activity increased proliferation. This serum-free medium, designated Defined Medium F, provides a biochemically defined system for growth and limited subcultivation of human foreskin fibroblasts in vitro.