A clinicopathological study of the effects of topical retinyl propionate cream in skin photoageing

To study the influence exerted by cutaneous ligands in nickel reactions we have evaluated the patch tests responses to 4 aqueous nickel salts (sulfate, chloride, nitrate, acetate) able to form different complexes with different geometry. Two groups of respectively 71 subjects who previously reacted only to nickel sulfate 5% petrolatum (pet) and of 30 subjects who previously reacted to nickel sulfate 5% pet and to at least 1 other transition metal, were simultaneously repatch-tested to 200 microg of Ni++ contained in nickel sulfate in pet and to 47 microg of Ni++ contained in 4 different aqueous nickel salts. Another 2 groups of 25 subjects with the same characteristics were simultaneously repatch tested to 200 microg of Ni++ in pet and to 12 microg of aq Ni++ as in the first 2 groups. Visual score, total score, and mean value of the reactions were utilized in evaluating the degree of the responses. On testing to 200 microg of Ni++ in pet all the subjects were able to give positive responses. Whilst a higher percentage of the responses of 2+ degrees was found in subjects reacting to nickel sulfate 5% pet alone, a higher percentage of responses of 3+ degrees was observed in subjects reacting to more transition metals. On testing to 47 and 12 microg of aqueous Ni++ a large variability of responses to the single salts was observed in all the subjects. However, in subjects reacting to more metals there were either a greater number of multiple responses to 3 or 4 salts or responses stronger than those found in subjects reacting to nickel sulfate alone. Although patch testing cannot give us complete information about the degree of previous exposure, the results arising from the tests seem to demonstrate that the subjects allergic to nickel and other transition metals are more reactive than the subjects allergic only to nickel to the application of the same amounts of Ni++ contained in different salts. When considering the QSAR model, the difference in the sensitizing potential of the metal at the same penetration properties can depend on the possibility of combining with specific ligands. Therefore, it is likely that in subjects reacting to more metals there is a more uniform availability of cutaneous ligands which conditions the formation of complexes more immunogenic. The arising inflammatory reaction in these cases leads to a stronger but less specific response.     

Quantitative bacteriological evaluation of a method for skin disinfection in blood donors

Skin disinfection at the site of venipuncture is a critical point in every blood transfusion collection procedure, as it contributes to ensure the bacterial safety of transfusion. Quantitative and qualitative analysis of bacteria present in the antecubital fossae before and after skin disinfection may be one method of assessing the anti-bacterial efficiency of disinfection. Swab culture systems and contact plates are the two techniques usually employed for this purpose. A washing and swabbing technique was used to quantify bacteria before and skin disinfection of the antecubital fossae in blood donors. This contra-placebo study was carried out on 32 donors, each of whom served as his own control, with a random choice of test arm and opposing control arm. Bacterial counts were determined in the antecubital fossae without skin disinfection (control, n = 32) and after a 3 step skin preparation procedure (cleaning, wiping, disinfection) using placebo (distilled water, n = 16) or an antiseptic product (mixture of chlorexidine, benzalkonium chloride and benzylic alcohol, n = 16). The absence of a statistical difference in bacterial counts between the right and left antecubital fossae without disinfection was controlled in a preliminary study of 20 subjects. Mean bacterial counts were 25,000/cm2 and 27,400/cm2 respectively for aerobic and anaerobic bacteria before disinfection, with a wide variation in results between individuals. When using placebo, preparation of the venipuncture site by the 3 step method (cleaning, wiping, disinfection) resulted in a non significant mean reduction of 0.56 log in aerobic and anaerobic bacteria. Using the antiseptic product, the same method resulted in a significant mean reduction of 1.8 and 1.7 log respectively in aerobic (p = 0.015) and anaerobic flora (p = 0.005). On an average, 2,750 aerobic bacteria/cm2 and 2,910 anaerobic bacteria/cm2 remained after disinfection, while qualitative analysis showed that disinfection suppressed the transitory flora in all cases but left part of the resident flora in 12/16 cases. These findings are comparable to those of other studies carried out to evaluate this kind of technique for the disinfection of operation sites. In comparison with other techniques classically employed for this type of evaluation (swab systems or contact plates), the method used in this study was the advantage of allowing the quantification of the reduction in bacteria. Hence this method could be employed for comparative assessment of skin disinfection techniques with the aim of improving their anti-bacterial efficiency and could also make possible the definition of a minimum bacterial count (resident flora) to be obtained in all cases after disinfection.     

Quantitative 1H MRS in the evaluation of mesial temporal lobe epilepsy in vivo

Hippocampal metabolite concentrations were determined by localized in vivo proton magnetic resonance spectroscopy (1H MRS) in eleven patients suffering from refractory mesial temporal lobe epilepsy (MTLE), as well as in eleven age-matched healthy volunteers, and compared with patient history, postoperative outcome and histopathology. Main results are: 1) In patients, the decrease in N-acetylaspartate (NAA) concentrations was highly significant ipsilateral, and less but still significant contralateral to the electroencephalogram-defined focus, as compared to controls. 2) The decrease in ipsilateral NAA measured preoperatively correlates with the degree of hippocampal sclerosis but 3) does not reliably predict postoperative outcome, although there is a trend toward better outcome in patients with a marked decrease of NAA. 4) Hippocampal NAA decrease (ipsi- and contralateral) is highly correlated with early onset age of epileptic seizures. 5) Among patients with similar onset age in early childhood, there is a strong association between duration of the disease and contralateral (and, though less clear-cut, ipsilateral) NAA loss. These results are concordant with the notion of a generally progressive worsening and complicating course of symptoms in poorly controlled MTLE.     

Reproducibility of in vivo carotid intima-media thickness measurements: a review

The gyrA gene of Campylobacter fetus subsp. fetus, which encodes the A subunit of DNA gyrase, was cloned, and its nucleotide sequence was determined. An open reading frame of 2,586 nucleotides which encodes a polypeptide of 862 amino acids with an Mr of 96,782 was identified. C. fetus subsp. fetus GyrA is most closely related to Campylobacter jejuni GyrA, with 73% homology at the nucleotide level and 78% identity between polypeptides. The next most closely related GyrA was that from Helicobacter pylori, with both DNA homology and amino acid identity of 63%. The gyrA and gyrB (DNA gyrase B subunit) genes were located on the genomic map of C. fetus subsp. fetus ATCC 27374 and shown to be separate. A clinical isolate of C. fetus subsp. fetus and a laboratory-derived mutant of ATCC 27374, both resistant to ciprofloxacin, had identical mutations within the quinolone resistance determining region. In both mutants a G-->T transversion, corresponding to a substitution of Asp-91 to Tyr in GyrA, was linked to ciprofloxacin resistance, giving MICs of 8 to 16 micrograms/ml.     

Bystander activation of cytotoxic T cells: studies on the mechanism and evaluation of in vivo significance in a transgenic mouse model

Bystander activation, i.e., activation of T cells specific for an antigen X during an immune response against antigen Y may occur during viral infections. However, the low frequency of bystander-activated T cells has rendered it difficult to define the mechanisms and possible in vivo relevance of this nonspecific activation. This study uses transgenic mice expressing a major histocompatibility complex class I-restricted TCR specific for glycoprotein peptide 33-41 of lymphocytic choriomeningitis virus (LCMV) to overcome this limitation. CD8+ T cells from specific pathogen-free maintained, unimmunized "naive" TCR transgenic mice can differentiate into LCMV-specific cytolytic effector CTL during infections with vaccinia virus or Listeria monocytogenes in vivo or mixed lymphocyte culture in vitro. We show that in these model situations (a) nonspecifically activated CTL are able to confer antiviral protection in vivo, (b) bystander activation is largely independent of the expression of a second T cell receptor of different specificity, (c) bystander activation is not mediated by a broadly cross-reactive TCR, but rather by cytokines, (d) bystander activation can be mediated by cytokines such as IL-2, but not alpha/beta-IFN in vitro; (e) bystander activation is, overall, a rare event, occuring in vivo in roughly 1 in 200 of the LCMV-specific CTL during infection of TCR transgenic mice with vaccinia virus; (f) bystander activation does not have a significant functional impact on nontransgenic CTL memory under the conditions tested; and (g) even in the TCR transgenic situation, where unphysiologically high numbers of T cells of a single specificity are present, bystander activation is not sufficient to cause clinically manifest autoimmune disease in a transgenic mouse model of diabetes. We conclude that although bystander activation via cytokines may generate cytolytically active CTL from naive precursors, quantitative considerations suggest that this is usually not of major biological consequence.     

Postovulatory ageing of mouse oocytes in vivo and premature centromere separation and aneuploidy

Two paramount observations exist regarding aneuploidy in human oocytes: its association with maternal age and its more frequent occurrence during meiosis I. Numerous experimental studies have shown that fertilization of postovulatory aged oocytes is coupled with reproductive failure and cytogenetic aberrations in embryos. However, the basic cytogenetic defect(s) of aged oocytes that causes these abnormalities has not been adequately described. The objective of this study was to test the hypothesis that postovulatory oocyte ageing results in increased frequencies of premature centromere separation (PCS) in metaphase II (MII) oocytes and aneuploidy in zygotes. MII oocytes and one-cell zygotes were collected from superovulated mice at different times after ovulation and fertilization. Chromosomes were C-banded and analyzed for structural and numerical aberrations. The frequencies of PCS in oocytes significantly (p < 0.01) increased with time postovulation: 15 h (15 of 529, 2.8%), 20 h (82 of 627, 13.1%), and 25 h (118 of 502, 23.5%). In zygotes, the frequencies of hyperploidy significantly (p < 0.01) increased with time post-fertilization: 0-4 h (0 of 260), 4-8 h (5 of 212, 2.4%), and 8-12 h (8 of 262, 3.1%). These data support the hypothesis that postovulatory ageing results in elevated levels of PCS in oocytes and of aneuploidy in zygotes. The link between PCS and aneuploidy may be random segregation of sister chromatids during anaphase II.     

Joint hospitalization of mother and child: evaluation in vivo

The impact of community mental health centers on the utilization of psychiatric services in Monroe County, New York, was evaluated by means of data from the Monroe County Psychiatric Case Register. The catchment areas that received centers served as their own controls. In addition, yearly utilization rates were compared for areas that obtained centers with those remaining centerless. Utilization rates increased markedly in catchment areas with centers, while the percentage of patients seen at the Rochester Psychiatric Center decreased from all catchment areas. Community mental health centers increased the utilization rates of the poor, children, and young adults, while the treatment needs of patient subgroups such as alcoholics, drug addicts, and the elderly were last to be addressed. The data do not evaluate issues such as the character, quality, and effectiveness of care.     

The effect of prednisolone on canine neutrophil function: in vivo and in vitro studies

It is generally accepted that growth of muscle tissue depends in part on biomechanical factors. However, the precise relationships that govern mechanically induced growth are not known. This paper uses available data to propose a set of biomechanical growth laws for striated and smooth muscle. For striated muscle fibers, transverse and longitudinal growth are hypothesized to depend on the active and passive fiber stress, respectively. For smooth muscle fibers in arteries, transverse growth is assumed to depend on the fiber stress (active behavior is ignored), with longitudinal growth depending on both fiber stress and the shear stress on the endothelium due to blood flow. In both types of muscle, the rate of growth is assumed to depend linearly on the stresses. Relatively simple models for skeletal muscle, the heart, and arteries are used to show that the proposed growth laws can predict many of the known characteristics of muscle growth during development and following load perturbations in the mature animal.     

The electrical characteristics of human skin in vivo

PURPOSE: The objectives of this study were to investigate the impedance properties of human skin in vivo and to examine the effect of iontophoresis upon them. METHODS: Having established the intra- and inter-individual variation in basal values of skin impedance, the effect of varying iontophoretic current density, ionic strength and counter-ion on the rate of recovery of skin impedance after iontophoresis was investigated. RESULTS: Passage of an iontophoretic current caused a significant reduction in the magnitude of the skin impedance. Increasing the current density caused an even greater reduction in the value of the skin impedance and slowed the rate of recovery. Reduction of the ionic strength resulted in an increase in the rate of recovery following iontophoresis. A significant increase in the rate of recovery was observed when CaCl2 replaced NaCl as the electrolyte. Although visual inspection revealed the presence of greater erythema when CaCl2 was used, there was an absence of the mild sensation experienced by volunteers when using NaCl. The last part of the study established a correlation between transepidermal water loss and impedance analysis as complementary methods for probing skin barrier function in vivo. The data were fitted to an equivalent circuit consisting of a resistor in parallel with a constant-phase element and a mechanistic model proposed to explain the electrical properties of the skin. CONCLUSIONS: The first comprehensive investigation of the effect of iontophoresis on the electrical properties of human skin in vivo has been described. It would appear from the results, and from their interpretation, that impedance spectroscopy may be an effective method to quantify the impact of iontophoresis on the skin, and to determine the extent to which proposed drug delivery regimens will perturb skin barrier function.     

Quantitative evaluation of papilledema in pseudotumor cerebri

PURPOSE: To determine the feasibility of adapting confocal scanning laser (CSL) tomography of the optic disc for quantitative evaluation of papilledema in pseudotumor cerebri (PTC). METHODS: Confocal scanning laser tomography of the optic disc was performed in 11 patients with diagnosed PTC and 12 visually normal control subjects of similar age. In five patients with active papilledema, CSL tomography was performed serially over several months. To quantify optic disc characteristics, surface topography was measured in 0.1-mm steps along the horizontal and vertical meridians and four oblique meridians. Best fit polynomial functions, describing surface topography along each meridian, were derived using linear regression analysis. RESULTS: Third-order polynomials provided excellent fits (significantly better than the second-order functions) to the surface topography for all meridians in the control subjects and patients with PTC. In control subjects and PTC patients an asymmetry in the slope of the optic disc contours was evident along the horizontal but not the vertical meridian. In patients with active papilledema a significant elevation of the center of the disc was accompanied by a change in overall surface topography. Each of the PTC patients followed up serially had a pronounced posterior deformation of the disc (i.e., a reduction in papilledema) that was initially apparent in the temporal meridian and did not proceed uniformly across all meridians. CONCLUSIONS: Confocal scanning laser tomography can quantify the magnitude and monitor the resolution of papilledema in PTC. Studies of optic nerve head topography may provide further insight into optic nerve compliance with elevated intracranial pressure.     

Glomerular permeability: in vivo tracer studies with polyanionic and polycationic ferritins

The influence of molecular charge on glomerular permeability to the globular ferritin molecule in vivo was investigated. Mice (Charles River CD strain) and rats (Munich-Wistar strain) were injected intravenously either with native anionic ferritin or various cationized derivatives with different isoelectric points (pI) and the kidneys were examined by electron microscopy. Native anionic ferritin was almost completely restricted from entry into the glomerular filter at the level of the endothelium and subendothelial layer of the glomerular basement membrane (GBM). Cationized derivatives penetrated the filter in increasing amounts depending on the pI of the tracer. Regardless of charge, all molecules that filtered through the lamina densa of the GBM and reached the subepithelial layer were completely restricted from entry into the urinary space at the level of filtration slits and appeared in phagosomes present in podocytes. Reduction of arterial pressure of cessation of renal blood flow did not influence the movement of ferritin molecules into the GBM. The results are consonant with physiological studies indicating charge dependent restriction of polyanion transport by the mammalian glomerulus. These tracer studies, in conjunction with cytochemical and biochemical evidence for the presence of polyanionic glycoproteins in the glomerular filter, suggest that glomerular restriction of plasma proteins occurs in part by a process similar to that which exludes negatively charged macromolecules in polyanionic gel systems.     

Factors determining drug residence in skin during transdermal absorption: studies on beta-blocking agents

A high rate of induction (9 of 10 cases) of human autologous cytotoxic T lymphocytes (CTL) was achieved in vitro from peripheral blood mononuclear cells of renal carcinoma patients by applying an interleukin (IL)-cocktail consisting of IL-1, -2, -4, and -6. The CTL specifically lysed their own target carcinoma cells within 24 h but did not kill neighboring autologous normal kidney cells or allogeneic renal cancer cell lines. In the case of TUHR4TKB, for which autologous CTL were not induced, no expression of MHC class-I molecules was observed on the surface of these carcinoma cells, although they were sensitive to autologous natural killer cells. The results imply that adoptive immunotherapy for metastasized renal carcinoma will be feasible with autologous CTL in combination with natural killer cells.     

Aspects on the physiology of human skin: studies using particle probe analysis

Near-infrared (NIR) spectroscopy is an inexpensive and noninvasive optical method to characterize biologic and physiologic systems. Measurements of oxygen saturation in various organs, cytochrome oxidase concentration, and glucose concentration in tissue are examples of NIR spectroscopy applications. This instrument also has potential for diagnostic imaging by comparing the optical properties of a given point in tissue with those of the surrounding areas, e.g., tumor localization, hematoma detection, or deep vein thrombosis detection. Currently, NIR spectroscopy is available in three modalities: time-resolved spectroscopy (TRS), continuous-wave spectroscopy (CWS), and a phase-modulation device. This paper describes a single-source phase-modulation device and a multiple-source (in- and anti-phased) device and their application to system identification. The phase and intensity information for homogeneous systems is correlated with system and instrumental parameters. Phase and intensity changes resulting from the presence of one and two absorbers are illustrated. The sensitivity of in- and anti-phased phase-modulation devices (phased arrays) is demonstrated. The use of amplitude-modulated phased array for heterogeneity detection is described.     

In vivo study of trace elements in leprous skin

The skin of leprous patients at various stages of the disease was investigated by diagnostic x-ray spectrometry, In the active stage raised iron and slightly raised zinc levels were found. The usefulness of the method in skin investigation is foreseen.