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Chronic telogen effluvium: increased scalp hair shedding in middle-aged women.

BACKGROUND: Diffuse loss of scalp hair is a common problem in middle-aged women. A segment of these cases represents idiopathic chronic telogen effluvium (CTE). OBJECTIVE: The purpose was to establish distinctive clinical and pathologic criteria for the diagnosis of CTE to facilitate its differentiation from androgenetic alopecia (AGA) and systemic causes of chronic diffuse hair loss. METHODS: A group of 355 patients (346 females, 9 males) with diffuse generalized thinning of scalp hair of unknown origin were classified as having CTE and were included in the study. Characteristically they presented with a history of hair loss with both increased shedding and thinning of abrupt onset and fluctuating course and showed diffuse thinning of hair all over the scalp, frequently accompanied by bitemporal recession. Two 4 mm punch biopsy specimens were taken mostly from the mid or posterior parietal scalp of these patients. The biopsies were performed at these same areas in 412 patients with AGA (193 male, 219 female). Similar paired biopsy specimens were also taken from 22 normal control subjects (13 males, nine females). Specimens were sectioned horizontally and vertically and were examined for terminal and velluslike (miniaturized) hairs, follicular stelae, follicular units, and perifollicular inflammation and fibrosis. RESULTS: In horizontal sections of 4 mm punch biopsy specimens from patients with CTE the average number of hairs was 39, the terminal/velluslike hair ratio was 9:1, 89% of the terminal hairs were in anagen, and 11% were in telogen. In AGA these values were 35, 1.9:1, 83.2%, and 16.8%, respectively, and in normal control subjects 40, 7:1, 93.5%, and 6.5%, respectively. Significant degrees of inflammation and fibrosis were present in only 10% to 12% of cases of CTE and normal controls, but occurred in 37% of cases of AGA. CTE ran a prolonged and fluctuating course in many patients. CONCLUSION: CTE, which usually affects 30- to 60-year-old women, starts abruptly with or without a recognizable initiating factor. It may be distinguished from classic acute telogen effluvium by its long fluctuating course and from AGA by its clinical and histologic findings.

Adolescent↗

Topoisomerase II, not topoisomerase I, is the proficient relaxase of nucleosomal DNA.

Eukaryotic topoisomerases I and II efficiently remove helical tension in naked DNA molecules. However, this activity has not been examined in nucleosomal DNA, their natural substrate. Here, we obtained yeast minichromosomes holding DNA under (+) helical tension, and incubated them with topoisomerases. We show that DNA supercoiling density can rise above +0.04 without displacement of the histones and that the typical nucleosome topology is restored upon DNA relaxation. However, in contrast to what is observed in naked DNA, topoisomerase II relaxes nucleosomal DNA much faster than topoisomerase I. The same effect occurs in cell extracts containing physiological dosages of topoisomeraseI and II. Apparently, the DNA strand-rotation mechanism of topoisomerase I does not efficiently relax chromatin, which imposes barriers for DNA twist diffusion. Conversely, the DNA cross-inversion mechanism of topoisomerase II is facilitated in chromatin, which favor the juxtaposition of DNA segments. We conclude that topoisomerase II is the main modulator of DNA topology in chromatin fibers. The nonessential topoisomerase I then assists DNA relaxation where chromatin structure impairs DNA juxtaposition but allows twist diffusion.

Chromatin↗

The effect of surface agitation on ultrasound-mediated gene transfer in vitro.

This article reports the effect of surface agitation of culture medium on ultrasound-mediated gene transfection in vitro and its possible mechanisms. The possibility of active induction of bubbles without using contrast microbubbles for effective gene transfer was also demonstrated. Cultured HeLa cells mixed with green fluorescent protein plasmid were exposed to 1.0 MHz ultrasound in 24-well culture plates. Up to 26% transfection efficiency in the survival cell population was achieved in samples exposed to 0.44 MPa ultrasound pulses with the presence of surface agitation. Inertial cavitation and bubble generation were observed throughout the ultrasound exposure. When surface agitation was suppressed by covering the medium surface with a thin membrane, bubble generation and gene transfection were significantly suppressed. Interestingly, transfection efficiency could be partially resumed by adding a small amount of culture medium onto the covering membrane to rebuild the surface agitation and bubble generation. Pressure fluctuation and transient high-pressure loci were found in samples with surface agitation. Numerical simulations of bubble dynamics showed that transient high pressures above the inertial cavitation threshold could generate bubbles, which might be subsequently stabilized at lower pressures by rectified diffusion, and exert strong shear forces that might create transient pores on cell membranes to facilitate gene transfer.

Cell Survival↗

Area ablation: a new lasing concept provides significantly enhanced acute and long-term results for treatment of in-stent restenosis.

BACKGROUND AND OBJECTIVES: Debulking is still a technique of choice for in-stent restenosis (ISR). Excimer laser debulking has enabled high procedural success with very low complication rates, but has demonstrated markedly heterogeneous results owing to differences in lasing and laser technology, and selected patient populations. Since new area-ablation technique enables ablation of larger areas than its own device size, we have evaluated their effectiveness and safety in an uncontrolled study. STUDY DESIGN/MATERIALS AND METHODS: Fifty-three patients with diffuse ISR were treated by laser area ablation, followed by adjunctive balloon angioplasty. Primary endpoint was percent of binary stenosis at 6-month follow-up; secondary endpoints were procedural success; target lesion revascularization (TLR); major adverse cardiac events (MACE); diameter stenosis (DS); and minimal lumen diameter (MLD) before and after laser debulking, and at 6-month follow-up. RESULTS: Laser debulking was feasible (as defined as < or =30% residual stenosis) in 98.1% of patients. At 6-month follow-up, binary stenosis was 26.4%; angiographic TLR, 20.7%; and MACE, 3.7%. DS decreased from 87+/-17% to 20 +/- 9% after laser debulking, and to 9+/-7% after PTCA; it was 29+/-14% at follow-up (P-values in comparison to baseline: 0.0047; 0.0036; 0.0064). MLD increased from 0.6+/-0.3 to 2.4+/-0.5 mm after laser debulking, to 2.8+/- 0.6 mm after adjunctive PTCA, and to 1.9 +/- 0.4 mm at follow-up (P-values in comparison to baseline: 0.0059; 0.0031; 0.0088). CONCLUSIONS: Owing to a significantly greater MLD, area ablation facilitates significantly enhanced immediate and follow-up results for diffuse ISR, including a simpler and more effective laser-debulking procedure than former lasing techniques.

Aged↗

Specificity of diffusion channels produced by lambda phage receptor protein of Escherichia coli.

The lamB protein, the receptor for phage lambda, was purified from the outer membrane of Escherichia coli K-12 by extraction with Triton X-100 and EDTA, chromatography on DEAE-Sephacel in Triton X-100, exchange of Triton for cholate by gel filtration, and chromatography on Sephacryl S-200 in cholate, NaCl, and EDTA. The purified protein appeared to exist as several oligomeric species. In an equilibrium retention assay with reconstituted vesicles containing phospholipids and lipopolysaccharide, the lamB protein conferred permeability for disaccharides. In a liposome swelling assay designed to measure rates of diffusion, the lamB protein conferred permeability to phospholipid liposomes for a variety of substrates. The rates obtained indicate the permeation facilitated by the lamB protein is specific, discriminating among substrates by both size and configuration. For example, maltose diffused into liposomes 40 times faster than sucrose, about 8 times faster than cellobiose, and about 12 times faster than maltoheptaose. The results suggest that the lamB protein forms a transmembrane channel containing a site (or sites) that loosely interacts with the solutes.

Bacteriophage lambda↗

Observation of contrast agent response to chirp insonation with a simultaneous optical-acoustical system.

Rayleigh-Plesset analysis, ultra-high speed photography, and single bubble acoustical recordings previously were applied independently to characterize the radial oscillation and resulting echoes from a microbubble in response to an ultrasonic pulse. In addition, high-speed photography has shown that microbubbles are destroyed over a single pulse or pulse train by diffusion and fragmentation. In order to develop a single model to characterize microbubble echoes based on oscillatory and destructive characteristics, an optical-acoustical system was developed to simultaneously record the optical image and backscattered echo from each microbubble. Combined observation provides the opportunity to compare predictions for oscillation and echoes with experimental results and identify discrepancies due to diffusion or fragmentation. Optimization of agents and insonating pulse parameters may be facilitated with this system. The mean correlation of the predicted and experimental radius-time curves and echoes exceeds 0.7 for the parameters studied here. An important application of this new system is to record and analyze microbubble response to a long pulse in which diffusion is shown to occur over the pulse duration. The microbubble response to an increasing or decreasing chirp is evaluated using this new tool. For chirp insonation beginning with the lower center frequency, low-frequency modulation of the oscillation envelope was obvious. However, low-frequency modulation was not observed in the radial oscillation produced by decreasing chirp insonation. Comparison of the echoes from similar sized microbubbles following increasing and decreasing chirp insonation demonstrated that the echoes were not time-reversed replicas. Using a transmission pressure of 620 kPa, the -6 dB echo length was 0.9 and 1.1 micros for increasing and decreasing chirp insonation, respectively (P = 0.02). The mean power in the low-frequency portion of the echoes was 8 (mV)2 and 13 (mV)2 for increasing and decreasing chirp insonation, respectively (P = 0.01).

Acoustics↗

Implementing a new health management information system in Uganda.

This paper reports on research investigating the health management information system (HMIS) implementation process in Uganda, utilizing the diffusion of innovation and dynamic equilibrium organizational change models. Neither perspective guided the HMIS development process. Instead, technological issues, rather than wider organizational issues, dominated the planned change. The need to consider the organizational context when changing information systems arises because the process is more complex than some practitioners have realized, when attempting to understand the causes of information management problems and developing HMIS in low-income countries. In particular, information system developers had not acknowledged that they were promoting an informational approach to management when they promoted a change from a centralized reporting system to a HMIS supporting use of information at the level of collection. Strategies to facilitate this approach were not advocated. Organizational theory can contribute to the diffusion of innovation framework. It has yielded an integration of Rogers's diffusion of innovation framework and Leavitt's concept of organizational forces in equilibrium. The diffusion framework describes the process, but the organizational model has given the context and reason for aspects of the process. The diffusion model does not predict what needs to change within the organization when a particular innovation is introduced, or how much. The addition of the organizational model has helped. These frameworks can facilitate the introduction of future information management innovations and allow practitioners to perceive their introduction as a staged process needing to be managed. Implications for practice are identified.

Diffusion of Innovation↗

Vulvar melanoma: diffuse melanosis and metastasis to the placenta.

Mucocutaneous melanoma, including vulvar melanoma, is rare and has a worse prognosis and higher recurrence rate than traditional cutaneous melanoma. Diffuse cutaneous melanosis is another rare clinical presentation of metastatic melanoma. It is essential for dermatologists to be alerted to rare presentations of melanoma, to facilitate early detection. We present the first case to our knowledge of metastatic vulvar melanoma with diffuse cutaneous melanosis in a pregnant young woman. Despite the occurrence of placental metastasis, a healthy, unaffected baby was born. This case exemplifies the aggressiveness of vulvar melanoma. The genitalia should be included in routine total body skin examinations. Pregnant women with generalized melanosis may be at increased risk for placental metastasis of melanoma. Pregnancy does not alter the incidence or prognosis of melanoma; however, patients with a poor prognosis or high recurrence risk should be informed of potential pregnancy complications associated with melanoma recurrence or metastasis.

Adult↗

[Do immunologic markers facilitate differentiation between histologic types of stomach cancer?].

Seventeen gastric carcinomas (intestinal n = 12; diffuse n = 1; mixed type n = 4) and one Barrett's carcinoma were prospectively studied by immunohistochemistry for the expression of different keratin polypeptides and of the brush border markers villin, sucrase isomaltase and aminopeptidase N. All carcinomas expressed the keratin polypeptides 8, 18, and 19 and were stained by the broad specific keratin antibody KL1, irrespective of histologic type. Keratin 7, however, was expressed in only one carcinoma in most tumor cells and in two further carcinomas in some tumor cells. Thus, specific differentiation of the various histologic types of gastric carcinoma does not seem to be aided by the use of keratin antibodies. Villin was positive in 80% of the tumors and sucrase isomaltase and aminopeptidase N were positive in 67% respectively with no obvious histologic difference. The frequent positivity of the brush border markers, usually typical for intestinal epithelium, reflects the high degree of intestinal differentiation of gastric carcinomas, but again does not seem to be associated with a particular histologic type.

Adenocarcinoma↗

Nonequilibrium facilitated transport of carbon dioxide in bicarbonate and bovine albumin solutions.

The nonlinear diffusion-reaction equations describing the nonequilibrium transport of CO2 through flat layers of complex but homogeneous aqueous media were solved by an approximate analytical method called the "Combined Damköhler Number" (CDN) technique. Unlike other approximate analytical solutions, the CDN technique is valid for the full range of Damköhler numbers, i.e., for any layer thickness. The present theoretical treatment uses as a basis the equilibrium approach of Stroeve, Hoofd, and Kreuzer which accounts for any species in the solution except for possible carbamate formation (binding of CO2 by the protein). The nonequilibrium model developed here for CO2 transport is the most general technique currently available in the literature. Theoretical results were compared to experimental data from the literature for diffusion in bicarbonate and albumin solutions and were generally in good agreement. Results obtained from numerical calculations were also compared and were found to be in excellent agreement with the CDN results.

Albumins↗

A furosemide-sensitive cotransport of sodium plus potassium in the human red cell.

The influxes of Na(+) and K(+) into the human red cell appear to be interrelated. This relationship was investigated under conditions in which either Na(+) or K(+) concentration outside the cell was varied or one cation was replaced by Mg(2+), choline(+), or Li(+). The effects of furosemide on Na(+) and K(+) movements were studied in the presence of ouabain. When ouabain was present, Na(+) influx was higher with K(+) ions externally than with other cations externally. Furosemide inhibited this K(+)-stimulated Na(+) influx, but it had little effect when K(+) was absent. Ouabain-insensitive K(+) influx was stimulated two-fold by external Na(+) compared with other cations. Furosemide also inhibited this stimulation, but it had little effect when Mg(2+) or choline(+) replaced external Na(+). Thus it was confirmed that synergism exists between the ouabain-insensitive influxes of Na(+) and K(+) and it was demostrated that furosemide inhibits this cooperative effect. The ouabain-insensitive influx of both K(+) and Na(+) showed a hyperbolic "saturating" dependence on the external concentration of the transported cation. Furosemide therefore eliminates a saturable component of influx of each cation. The net uptake of Na(+) in the presence of ouabain was stimulated by K(+) ions. A similar effect was observed with red cells, in which Li(+) replaced nearly all the internal Na(+) plus K(+) ions. In these cells, net Na(+) uptake was stimulated by external K(+), and net K(+) uptake was stimulated by external Na(+). Furosemide inhibited this mutual stimulation of net cation entries. The inhibitory action of furosemide was not limited to inward flux and net movement of Na(+) and K(+). Furosemide also inhibited the efflux of Na(+) into Na(+)-free media and the efflux of K(+) into K(+)-free media. It appeared, therefore, that the action of furosemide was not explained by inhibition of exchange diffusion. These data are consistent with an ouabain-insensitive transport process that facilitates the inward cotransport of Na(+) plus K(+)-ions, and that can produce a net movement of both ions. Although this process under some conditions mediates an equal bidirectional flux of both Na(+) and K(+), it cannot be defined as exchange diffusion. The contransport process is inhibited by furosemide.

Biological Transport, Active↗

The expiratory film in hyaline membrane disease: preliminary observations.

The chest radiographs of 10 babies who developed an abrupt diffuse pulmonary parenchymal opacification in conjunction with pulmonary hemorrhage, pulmonary edema, or pneumonia as a complication of hyaline membrane disease were reviewed. The chest radiographs of these 10 babies were compared to five radiographs obtained with various degrees of expiration in four babies with uncomplicated hyaline membrane disease. The comparison indicates that analysis of air bronchograms facilitates discrimination of pulmonary opacification due to filming in expiration from pathologic diffuse parenchymal opacification in babies with hyaline membrane disease. Expiration produces constriction and centralization of air bronchograms. Alveolar filling processes are associated with distension and peripheral extension of air bronchograms.

Bronchography↗

Pharmacokinetic and local tissue disposition of [14C]sodium diclofenac following iontophoresis and systemic administration in rabbits.

The systemic pharmacokinetics and local drug distribution of sodium diclofenac in skin and underlying tissues was studied. Iontophoresis facilitated local and systemic delivery of diclofenac sodium compared with passive diffusion. The maximum plasma concentration of sodium diclofenac was achieved within 1 h of iontophoresis, and the delivery was proportional to applied current density (371 +/- 141 and 132 +/- 62 microg/L at 0.5 and 0.2 mA/cm(2), respectively). The in vivo delivery efficiency for diclofenac in rabbit was 0.15 mg/mA.h. The concentrations of sodium diclofenac in the skin, subcutaneous tissue, and muscle beneath the drug application site (cathode) were significantly greater than plasma concentrations and concentrations of drug in similar tissues at the untreated sites. The results thus suggest that the cutaneous microvasculature is not always a perfect "sink" and that transdermal iontophoresis facilitated the direct penetration of diclofenac sodium to deeper tissues. No skin irritation was observed up to 0.5 mA/cm(2) current density and 7 mg/mL sodium diclofenac concentration.

Animals↗

Simulations of molecular diffusion in lattices of cells: insights for NMR of red blood cells.

The pulsed field-gradient spin-echo (PGSE) nuclear magnetic resonance (NMR) experiment, conducted on a suspension of red blood cells (RBC) in a strong magnetic field yields a q-space plot consisting of a series of maxima and minima. This is mathematically analogous to a classical optical diffraction pattern. The method provides a noninvasive and novel means of characterizing cell suspensions that is sensitive to changes in cell shape and packing density. The positions of the features in a q-space plot characterize the rate of exchange across the membrane, cell dimensions, and packing density. A diffusion tensor, containing information regarding the diffusion anisotropy of the system, can also be derived from the PGSE NMR data. In this study, we carried out Monte Carlo simulations of diffusion in suspensions of "virtual" cells that had either biconcave disc (as in RBC) or oblate spheroid geometry. The simulations were performed in a PGSE NMR context thus enabling predictions of q-space and diffusion tensor data. The simulated data were compared with those from real PGSE NMR diffusion experiments on RBC suspensions that had a range of hematocrit values. Methods that facilitate the processing of q-space data were also developed.

Animals↗

Can an intracoronary Doppler wire accurately measure changes in coronary blood flow velocity?

The purpose of this study was to compare a newly developed Doppler guide wire in the measurement of coronary blood flow velocity (CBFV) and coronary flow reserve (CFR) when compared to a previously extensively validated Doppler catheter. Sequential measurements of Doppler signals from the Doppler catheter and wire were obtained in response to graded doses of intracoronary adenosine in the left circumflex of 10 anesthetized dogs. The Doppler catheter signal was recorded on a standard physiologic chart recorder; that from the Doppler wire was recorded both on the chart recorder and the commercially available spectral analysis recording system. High correlations were obtained between the change in coronary velocity and CFR which were independent of the recording system used. Peak flow reserve in response to maximum intracoronary adenosine (24 micrograms bolus) ranged from 3.7-5.6 x basal. These results are similar to those obtained in normal humans. In spite of major differences between engineering specifications of the Doppler wire and Doppler catheter, under optimal conditions these two techniques yield similar results. The Doppler wire may facilitate measurements of CFR during diagnostic angiography in small or diffusely diseased vessels.

Adenosine↗

Effect of osmotic stress on potassium accumulation around glial cells and extracellular space volume in rat spinal cord slices.

In rat brain and spinal cord slices, the local extracellular accumulation of K(+), as indicated by K(+) tail currents (I(tail)) after a depolarization step, is greater in the vicinity of oligodendrocytes than that of astrocytes. It has been suggested that this may reflect a smaller extracellular space (ECS) around oligodendrocytes compared to astrocytes [Chvátal et al. [1997] J. Neurosci. Res. 49:98-106; [1999] J. Neurosci. Res. 56:493-505). We therefore compared the effect of osmotic stress in spinal cord slices from 5-11-day-old rats on the changes in reversal potentials (V(rev)) of I(tail) measured by the whole-cell patch-clamp technique and the changes in ECS volume measured by the real-time iontophoretic method. Cell swelling induced by a 20 min perfusion of hypoosmotic solution (200 mmol/kg) decreased the ECS volume fraction from 0.21 +/- 0.01 to 0.15 +/- 0.02, i.e., by 29%. As calculated from V(rev) of I(tail) using the Nernst equation, a depolarizing prepulse increased [K(+)](e) around astrocytes from 11.0 to 44.7 mM, i.e., by 306%, and around oligodendrocytes from 26.1 to 54.9 mM, i.e., by 110%. The ECS volume fraction decrease had the same time course as the changes in V(rev) of I(tail). Cell shrinkage in hyperosmotic solution (400 mmol/kg) increased ECS volume fraction from 0.24 +/- 0.02 to 0.32 +/- 0.02, i.e., by 33%. It had no effect on [K(+)](e) evoked by a depolarizing prepulse in astrocytes, whereas in oligodendrocytes [K(+)](e) rapidly decreased from 52 to 26 mM, i.e., by 50%. The increase in ECS volume was slower than the changes in [K(+)](e). These data demonstrate that hypoosmotic solution has a larger effect on the ECS volume around astrocytes than around oligodendrocytes and that hyperosmotic solution affects the ECS volume around oligodendrocytes only. This indicates that increased K(+) accumulation in the vicinity of oligodendrocytes could be due to a restricted ECS. Oligodendrocytes in the CNS are therefore most likely surrounded by clusters of "compacted" ECS, which may selectively affect the diffusion of neuroactive substances in specific areas and directions and facilitate spatial K(+) buffering.

Animals↗

Highly crystalline WO3 thin films with ordered 3D mesoporosity and improved electrochromic performance.

WO3 thin layers with nanometer-scale periodicity were prepared by evaporation-induced self-assembly (EISA) using a novel amphiphilic block-copolymer template (poly(ethylene-co-butylene)-block-poly(ethylene oxide)). The evolution of the mesoporous ordered network and the crystallinity of the framework were monitored by 2D-SAXS, WAXS, SEM, XPS, and porosimetry. By annealing the films, the pore-wall crystallinity is adjusted between fully amorphous and highly crystalline without mesostructural degradation. Thus, the crystalline-film framework is composed of phase-pure monoclinic WO3 nanoparticles (12-14 nm in size). Furthermore, heat treatment transforms the originally spherical mesopores into ellipsoids, resulting in a unidirectionally shrunken, but still well-defined and fully accessible bcc mesopore architecture. The influence of mesoporosity and crystallinity on electrochemical/electrochromic characteristics was addressed by monitoring electrochemical features and the absorption changes during Li insertion/extraction (repetitive potentiostatic cycling). Both the amorphous and crystalline mesoporous films possess electrochromic response times on the order of only seconds, which are attributable to the facilitated insertion of guest ions due to shortening of the diffusion path lengths. Also, the insertion/extraction reversibility of crystalline WO3 layers with 3D mesoporosity is improved compared to amorphous ones and reaches values close to 100%.

Crystallization↗

Meldola blue: a new electron carrier for the histochemical demonstration of dehydrogenases (SDH, LDH, G-6-PDH).

A new electron carrier, Meldolar Blue (8-dimethylamino-2,3-benzophenoxazine; Boehringer Mannheim GmbH, Deutsche Patentschrift P 1959410) was tested for its usefulness in the histochemical demonstration of dehydrogenase activity in adrenal cortex, liver, heart muscle of guinea pig and human oviduct and compared with PMS. For demonstrating SDH activity Meldola Blue (MB) is as efficient as PMS. A decisive advantage of MB as compared with PMS is its low sensitivity to light exposure, facilitating direct visualisation of histochemical reaction processes. Generally, a high diffusion rate of reduced electron carriers (PMS and MB) from the section into the incubation medium (PVA) leads to a loss of reduction equivalents, particularly in the demonstration of NAD- or NADP-dependent dehydrogenases (LDH, G-6-PDH) with lower TNBT concentrations. However, no inhibition of SDH-, LDH- and G-6-PDH activities was observed with incubation media containing the tested concentrations of PMS and MB.

Adrenal Glands↗