Experimental demonstration of surface selection rules for SERS on flat metallic surfaces.

We have measured the polarization and incident angle dependence of the Surface-Enhanced Raman Scattering (SERS) signal of a nile blue monolayer adsorbed on a flat gold surface. Comparisons with predictions of electromagnetic (EM) theory indicate that the molecules are predominantly adsorbed flat on the surface. These results provide the most direct demonstration of the concept of surface selection rules in SERS, and further confirm the validity of the SERS-EM model beyond the |E|(4)-approximation.

Neurologic complications of inferior petrosal sinus sampling.

BACKGROUND AND PURPOSE: Inferior petrosal sinus sampling (IPSS) is a useful diagnostic technique in adrenocorticotropic hormone (ACTH)-dependent hypercortisolism with normal or equivocal MR imaging. The procedure is believed to be safe, with mostly minor complications. However, there are rare, but severe, neurologic complications that need to be considered. MATERIALS AND METHODS: We performed an institutional review board-approved retrospective review of our institutional IPSS experience from July 2001 to January 2007. IPSS was performed for the evaluation of Cushing disease. The end points of particular interest were the indications for IPSS and the incidence of associated complications. RESULTS: During the study period of 5(1/2) years, 44 patients underwent IPSS for evaluation of Cushing disease. There were 33 women and 11 men with a mean age of 43.1 years. Because of equivocal imaging and endocrine testing, 36 of 44 patients underwent IPSS, and 8 of 44 underwent IPSS after failed transsphenoidal exploration. The only complication was injury to the brain stem that occurred after an unremarkable procedure in a 42-year-old woman. She developed clinical evidence of pontomedullary dysfunction with MR imaging consistent with brain stem infarction. The cause of this injury is unclear, but a venous variant leading to transient venous hypertension or thrombosis is suspected. CONCLUSION: Neurologic injury is a rare but serious complication associated with IPSS. Despite this, if performed under a strict paradigm, IPSS is both accurate and safe and can be very useful in the management of Cushing disease.

Patterns and prevalence of antidepressant drug use in the German state of Baden-Wuerttemberg: a prescription-based analysis.

PURPOSE: Population-based data about patterns and prevalence of antidepressant drug use is limited in Europe and presently unavailable for Germany. Therefore, we have identified patterns and prevalence of antidepressant use among outpatients on a population-based scale in the German state of Baden-Wuerttemberg. METHODS: We conducted a historical cohort study using a computerised prescription database referring to all members of the major German public health insurance company AOK. We assessed the prevalence of antidepressant drug use over a 3-year period, calculated the number of prescription items purchased per patient and compared first-line and second-line treatments. RESULTS: The 1-year prevalence of antidepressant drug use among more than 4,000,000 health insurance members was 7.4% (male: 4.3%; female: 10.2%). Importantly, almost 40% of the patients received only a single prescription item from 2000 to 2002. Though the use of serotonin-reuptake inhibitors (SSRIs) markedly increased by about 65% within the study period, these are primarily used as second-line drugs and still much less frequently than St. John's wort or tricyclic antidepressants such as amitryptiline or doxepin. CONCLUSIONS: The prevalence of antidepressant drug use is higher than previously reported for other European countries. The preferred use of St. John's wort and tricyclics over SSRIs and other modern-type antidepressants in Germany is quite unique in Europe and different from the US. The identified drug use pattern leaves a major room for improvement in view of the numerous single prescription items purchased.

Overview of hepatotoxicity.

This overview presents some of the salient features of liver biology and physiology that form the basis for a variety of experimental tools that are used for the study of chemical histopathology. Prevalence and risk of heptatoxicity are examined among a subset of chemicals from the EPA IRIS database. The goal is to provide an objective assessment of the magnitude of the problem of chemically-induced hepatotoxicity and contextual background against which the diversity of responses of the liver to toxicants and the analytical methods available for their study can be appreciated.

EGF receptors of hepatocytes from rats treated with phenobarbital are sensitized to down-regulation by phenobarbital in culture.

Hepatocytes from Fisher 344 rats treated with the liver tumor promoter phenobarbital (PhB; 0.1% in the drinking water, 2-3 months) exhibit reduced epidermal growth factor (EGF) binding and EGF-induced mitogenesis in culture. Similar responses are induced by >1 mM PhB added to the culture medium of hepatocytes from untreated rats. In this study, we demonstrated that hepatocyte EGFr protein, as determined by immunoblotting, was unchanged by treatment of rats with PhB. However, hepatocytes from PhB-treated rats are more sensitive to PhB in culture in that decreased EGF binding occurred with 0.05 mM PhB, a concentration also attained in plasma of rats exposed to PhB. Sensitization was reversible, as is tumor promotion, since hepatocytes from rats withdrawn from PhB for 1 month were unresponsive to <3 mM PhB. EGFr down-regulation by a series of barbiturates correlated well with their known activities as tumor promoters and CYP2B1/2 inducers, with pentobarbital and PhB yielding high activities, while barbital was intermediate and barbituric acid, 5-phenylbarbituric acid, and 5-ethylbarbituric acid were ineffective. Differentiated hepatocyte function was required for PhB-induced EGFr down-regulation since HepG2 and rat liver epithelial cells were unresponsive, but involvement of CYP2B1/2 activity was discounted by the failure of metyrapone to inhibit the response in PhB-induced hepatocytes. These studies support a role for impaired EGFr function in PhB liver tumor promotion due to effects on existing EGFr protein and suggest that EGFr down-regulation by PhB in culture is independent of CYP2B1/2 activity but shares mechanistic components involved in its transcriptional activation by PhB.

Registration of three-dimensional cardiac catheter models to single-plane fluoroscopic images.

Transvenous cardiac procedures require accurate positioning of catheters within the geometrically complex cavities of the heart. Recently, nonfluoroscopic catheter tracking technologies have been developed to quantitate the (degrees-of-freedom) three-dimensional positions of intracardiac catheters. This paper presents a projection-Procrustes method to register an animated three-dimensional (3-D) model of multiple intracardiac catheters with a single-plane fluoroscopic image. Applying the computed transformation to the catheter coordinates enables the animated 3-D model of the catheters to be viewed from the same perspective as the fluoroscopic image. Mathematical simulations show that the computed transformation parameters are sensitive to both the position errors in the 3-D catheter coordinates and to the spatial distribution of the catheter-mounted transducers. Simulations with a realistic geometric model of three catheters with four transducers per catheter showed an angular error of 1.91 degrees +/- 0.27 degree for 3-D catheter position errors of 2.0 mm. An in vitro experiment demonstrated the feasibility of the method using a water tank phantom of three catheters and fluoroscopic images taken over an 80 degrees range. The mean angular error was 0.61 degree +/- 0.48 degree. The results of this study indicate that the projection-Procrustes method is a useful tool for registering 3-D catheter tracking models to single-plane fluoroscopic images.

Evidence for site-specific bioactivation of alachlor in the olfactory mucosa of the Long-Evans rat.

Alachlor (2-chloro-2',6'-diethyl-N-[methoxymethyl]-acetanilide) is a restricted-use chloracetanilide herbicide which has been shown previously to produce a dose-dependent incidence of olfactory mucosal tumors in rats following chronic dietary exposure. However, the mechanism of alachlor carcinogenicity is poorly understood. Alachlor was administered i.p. to male Long-Evans rats for up to 28 days at doses that are carcinogenic in chronic studies in order to study olfactory lesion development and alterations in cell proliferation. Neither treatment-related olfactory mucosal lesions nor regenerative cell proliferation, as assessed with BrdU labeling, was detected. In vitro genotoxicity studies using Salmonella typhimurium strain TA100 showed that alachlor was non-mutagenic in the absence of metabolic activation. When pre-incubated with an olfactory mucosal S9 activation system, alachlor induced a weak, dose-dependent mutagenic response at 500-1250 micrograms/plate, with toxicity at higher doses. In contrast, an S9 activation system derived from nasal respiratory mucosa, the tissue physically juxtaposed with the olfactory mucosa but reportedly not susceptible to alachlor-induced tumors, did not produce a mutagenic response for alachlor or the positive control. Thus, this result suggested site-specificity of alachlor activation consistent with the target site of carcinogenicity. The mutagenicity of alachlor to Salmonella, in the presence of an olfactory mucosal-activating system, was confirmed by a limited positive response in the mouse lymphoma assay. Here there were increases in small colony mutants (indicative of chromosomal effects) as well as large colony mutants (which reflect gene mutations). This study suggests that target tissue bioactivation of alachlor results in the formation of one or more mutagenic metabolite(s), which may be critical in alachlor-induced nasal tumorigenesis.

Confirmation of the distinct genotype groups within the form species Candida parapsilosis.

The DNA relatedness and restriction fragment length polymorphism patterns of whole-cell DNA and the general phenotypic properties of 14 isolates of the form species Candida parapsilosis representing three diverse genetic groups were compared. The data confirm the unrelatedness of the three groups at the species level.

High-power Lyman-alpha source generated with an ArF excimer laser.

We report high-power vacuum-ultraviolet (vuv) generation at the Lyman- alpha wavelength of 121.6nm , using a simple experimental system. vuv radiation is produced through two-photon-resonant difference-frequency mixing with a tunable ArF excimer laser and a Nd:YAG-pumped dye laser. Using phase-matched mixtures of Kr and Ar at a total pressure of 650 mbar, we produced 7-microJ energies at Lyman- alpha in approximately 5ns (1.3kW) , as measured directly with a pyroelectric energy probe. Measurements indicate that higher powers are possible with system optimization. A tuning range of 0.1nm was achieved for a fixed gas mole fraction at a total pressure of 650 mbar. Qualitative agreement is found between measured tuning profiles and theoretical predictions.

Application of sonomicrometry and multidimensional scaling to cardiac catheter tracking.

This paper describes a technique for tracking the three-dimensional (3-D) position of a cardiac catheter using sonomicrometry and the mathematical method of multidimensional scaling (MDS). Sonomicrometry is used to measure the distances between ultrasonic transceivers. MDS is then used to calculate the 3-D coordinates of the ultrasonic transceiver locations, including the catheter tip, from the measured distances. Feasibility of catheter tracking was initially studied using simulated data from a geometric model in which the actual coordinates of all transceivers were known. The method was then shown to be feasible in vivo by tracking a catheter-mounted piezoelectric transducer using seven reference crystals sewn to the epicardial surface of a sheep heart. Simulation results indicate that a catheter can be tracked with a root-mean-square (rms) error of 1.51 +/- 0.05 mm and an average-distance error of e = 1.06 +/- 0.27 mm using 12 reference points. In vivo results showed acceptable stress values (G < 0.05) for 95% of the data samples with an average-distance error of e = 0.52 +/- 0.66 mm. These simulation and experimental results show that sonomicrometry and MDS can be used to accurately localize the 3-D position and track the motion of a catheter tip within the heart.

Retropatellar contact stress in simulated patella infera.

Six fresh-frozen cadaver knee joints were used to study changes in retropatellar contact mechanics accompanying patella infera. The knees were tested on a servohydraulic testing machine under conditions simulating stair descent at 10 degrees, 30 degrees, 60 degrees, and 90 degrees of knee flexion. A slotted metallic block mechanism embedded in the region of the tibial tubercle allowed selective distal offset of the patellar tendon insertion so as to model conditions of 0, 6, 13, 19, and 25 mm of patella infera. Patellofemoral and quadriceps tendofemoral contact areas and contact stresses were recorded using Pressensor contact film and quantitated using digital image analysis. Patella infera significantly altered retropatellar contact mechanics. Contact areas migrated proximally on the patella and decreased in size with progressive severity of patella infera. However, the peak and spatial mean retropatellar contact stresses were not elevated correspondingly. Apparently, quadriceps tendofemoral contact was initiated at progressively lower angles of knee flexion as the patella infera progressed. Under conditions of extreme infera at high flexion angles, the magnitude of tendofemoral contact force approached that of retropatellar contact force. These data indicate that in patella infera, patellofemoral contact stresses are not elevated appreciably. Therefore, the disabling symptoms associated with patella infera may be due to factors other than local mechanical overload.

The full-scale PACS archive. A prerequisite for the filmless hospital.

PURPOSE: Increasing percentages of digital modalities in radiology, in particular of digital image acquisition in conventional radiography, call for digital reporting, communication, and archiving techniques. These techniques are prerequisites for the "filmless" hospital. The first 2 have been covered extensively in the literature and by vendors. However, as regards online digital image archives there are still no satisfactory concepts available in the medical field. The present paper puts forward some suggestions as to how this situation could be improved. MATERIAL AND METHODS: Analyses of radiology operations consider the prevailing PACS (picture archiving and communication system) archive concepts that use optical discs to be too small, too slow and too cumbersome to manage and therefore unable to function as comprehensive image archives for filmless hospitals. We suggest borrowing and adapting the well tested archive technologies from space research and the oil and broadcasting industries which have much higher capacities and speeds and better software interfacing possibilities. With such technologies the needs of filmless hospital operations can be met. RESULTS: A feasible concept for a transition strategy from conventional analog to digital archives is presented. Model calculations of the necessary investments and potential savings, including generous placement of viewing stations in the entire hospital, indicate amortization periods of 3.8-4.8 years. CONCLUSION: Alternative technologies for digital image archives already today make full-scale PACS for filmless hospitals technologically and conceptually feasible and financially mandatory.

Epidermal protein kinase C-beta 2 is highly sensitive to downregulation and is exclusively expressed in Langerhans cells: downregulation is associated with attenuated contact hypersensitivity.

Treatment of mice with multiple topical applications of 12-O-tetradecanoylphorbol-13-acetate (TPA) or diacylglycerol resulted in a preferential decrease in epidermal protein kinase C-beta 2 (PKC-beta 2) compared with PKC-alpha as determined by western analysis. When PKC-alpha was decreased by 40%, PKC-beta 2 could no longer be detected, suggesting that PKC-beta 2 is more sensitive to downregulation, and/or specific epidermal cell types that contain PKC-beta 2 are more sensitive to TPA/diacylglycerol. To address this issue, we isolated Langerhans cells (LCs) from epidermal cell suspensions with immunomagnetic beads and an antibody to the class II major histocompatibility complex. Northern blot analysis revealed a PKC-beta 2 signal in isolated LCs that was 40-fold greater than that observed in unfractionated epidermal cells, and no PKC-beta 2 signal was detected in epidermal cells depleted of LCs, indicating that PKC-beta 2 is expressed exclusively in LCs within the epidermis. Western blot analysis confirmed the presence of PKC-beta 2 in LCs. PKC-beta 2 was highly sensitive to downregulation, because a single application of TPA resulted in a 90% loss of PKC-beta 2 within 6 h without a decrease in the number of LCs. To determine whether the decreased level of PKC-beta 2 within LCs was associated with an alteration in contact hypersensitivity, we treated mice with only a single application of TPA, and 6 hours later mice were sensitized with 2,4-dinitrofluorobenzene on the same dorsal area. Subsequent challenge revealed a 60% decrease in contact hypersensitivity in TPA-treated mice. These data indicate that (i) within the epidermis, PKC-beta 2 is highly sensitive to downregulation and is exclusively expressed in LCs, and (ii) the downregulation of PKC-beta 2 is associated with impaired LC function with respect to contact hypersensitivity.

Simplified PCR-SSO procedure for DQA and DQB typing. Simultaneous hybridization of two probes to one membrane.

To simplify DQA and DQB oligotyping, we applied our improved PCR-SSO procedure for DR typing. We used 12 oligonucleotide probes for DQA typing and 18 for DQB typing. Oligonucleotide probes that require the same hybridization and stringent washing conditions were selected as pairs for simultaneous hybridization to a dot-blot membrane containing various DNA samples. One probe of each pair was labeled with digoxigenin and the other with biotin. After hybridization, the dot-blot membranes were incubated with a mixture of conjugates. Specific binding of the corresponding DNA probes was visualized on an X-ray film using a chemiluminescent substrate (CSPD) and by staining using a chromogenic substrate (TMB). This approach, previously employed for DR typing, is also suitable for DQA and DQB oligotyping and significantly reduces the labor inherent in PCR-SSO typing.

Midfoot sprains in collegiate football players.

We studied midfoot sprains in collegiate football players to define and document incidence, mechanisms, injury patterns, and disabilities. Twenty-three athletes with 24 injuries from 1987 through 1991, with a mean followup of 30.8 months, were identified for the study. The injuries occurred in 4% of the football players per year with offensive linemen incurring 29.2% of the injuries. The location of maximal tenderness on physical examination was an important prognostic indicator such that injuries with medial and global midfoot tenderness to palpation had the longest time loss from participation and time until full healing. Lateral midfoot sprains required short periods of disability, and players were able to return to participation with the use of an orthosis. Nineteen athletes with 20 injuries responded to a questionnaire. Four players reported residual functional problems. Only 1 of these players had to modify his recreational activities because of pain. The other players remained very active with only mild complaints of pain after high-demand activities. Midfoot sprains were associated with acute disability that required prolonged restriction from competition, but for most players the long-term residual problems were minor.

Cervical spinal stenosis and stingers in collegiate football players.

We evaluated the relationship of cervical spinal stenosis with the occurrence of "stingers" in collegiate football players who participated at our institution from 1987 through 1991. Preparticipation cervical spine radiographs of 266 players were used to measure Torg ratio. Forty players with stingers were identified: 34 had an extension-compression mechanism; 6 had a brachial plexus stretch mechanism. Time-loss neck injuries occurred in 31 players; the remaining 195 players were asymptomatic. The mean Torg ratio was significantly smaller for the stinger group (P = 0.02). The Torg ratio was less than 0.8 at 1 or more levels in 47.5% of the stinger group, 32.3% of the time-loss neck pain group, and 25.1% of the asymptomatic group. No player with a brachial plexus stretch mechanism had a mean Torg ratio less than 0.8, but 20.6% of the players with an extension-compression mechanism had a mean Torg ratio less than 0.8. Players with a Torg ratio less than 0.8 had 3 times the risk of incurring stingers. We conclude that cervical spinal stenosis increases the risk for having stingers with complicated clinical courses.

[HLA-DR typing using PCR-SSO with simultaneous hybridization of each dot blot membrane with a digoxigenin- and a biotin-marked probe]. / HLA-DR-Typisierung mittels PCR-SSO bei gleichzeitiger Hybridisierung jeder Dot-blot-Membran mit einer Digoxigenin- und einer Biotin-markierten Sonde.

Here we present a PCR-SSO procedure designed to simplify HLA-DR typing. We labelled 8 of a total of 16 oligonucleotide probes with digoxigenin, the others with biotin, and formed 8 pairs, each containing a digoxigenin- as well as a biotin-labelled probe. Each pair was hybridized simultaneously to one of eight dot blot membranes containing the DNA to be typed. Specific binding was detected by incubation with a mixture of the appropriate conjugates followed by sequential addition first of a chemiluminescent substrate to detect the digoxigenin-labelled probe and then a chromogenic substrate for detection of the biotin-labelled probe. With this procedure, the specific binding of two different probes to the same dot blot membrane could be evaluated, considerably reducing the labor inherent in PCR-SSO typing.

A polymerase chain reaction-sequence-specific oligonucleotide procedure for HLA class II typing using biotin- and digoxigenin-labeled probes simultaneously in hybridization.

To simplify PCR-SSO HLA-DRB generic typing, we labeled eight of 15 oligonucleotide probes with DIG and the others with biotin, and hybridized each dot blot with both a biotin-labeled probe and a DIG-labeled probe simultaneously. We chose oligonucleotide pairs which require the same hybridization and stringent washing conditions and do not compete with each other during hybridization. After incubation with a mixture of anti-DIG Fab fragment-alkaline phosphatase and streptavidin-peroxidase conjugates, specific binding of the DIG-labeled probe was revealed by a chemiluminescent substrate (CSPD) and specific binding of the biotin-labeled probe was subsequently visualized by a chromogenic substrate (TMB). The sensitivity of both probes was similar and gave comparable hybridization signals. Using this simplified procedure, the number of hybridizations or dot blots can be reduced to half the usual amount and the labor involved in PCR-SSO typing significantly reduced.

Synergistic interaction between the non-phorbol ester-type promoter mirex and 12-O-tetradecanoylphorbol-13-acetate in mouse skin tumor promotion.

Mirex, an organochlorine pesticide and non-genotoxic rodent hepatocarcinogen, is also a potent non-phorbol ester-type promoter of mouse skin tumors. Mirex, unlike most other skin tumor promoters, is not a significant epidermal hyperplasiogen even at a maximally promoting dose (200 nmol). Experiments described here examined whether tumor promotion by mirex and 12-O-tetradecanoylphorbol-13-acetate (TPA) are mediated through different mechanisms as indicated by their additivity when co-applied to 7,12-dimethyl-benz[a]anthracene (DMBA, 200 nmol)-initiated female CD-1 mouse skin. Instead of the additive response of 14 plus 5 tumors/mouse predicted from mice promoted for 20 weeks (2x/week) with either mirex (200 nmol) or TPA (2 nmol) respectively, their co-application yielded 35 tumors/mouse. This synergy with TPA was specific to mirex since a structurally related compound, chlordecone (Kepone) was inactive. Mirex plus TPA-promoted papillomas contained a c-Ha-ras A182-->T mutation as frequently (13/14) as those promoted by mirex or TPA alone, suggesting that these DMBA-initiated/co-promoted papillomas were not atypical in this genotypic marker. Promotional synergy with mirex was only observed with a submaximal promoting dose of 2 nmol TPA; 5 or 8 nmol TPA plus mirex gave additive or less tumor multiplicities. This synergistic multiplicity with mirex plus 2 nmol TPA (35 tumors/mouse) approximated the sum of individual responses to 200 nmol mirex (14 tumors/mouse) and the maximally promoting dose of TPA (12 nmol), 24 tumors/mouse, suggesting that mirex potentiated the promotional activity of TPA, as well as promoted through a mirex-specific mechanism. Epidermal DNA synthesis induced by 2 nmol TPA was potentiated by mirex, further supporting a role for mirex in potentiation of epidermal TPA activity. Collectively, these studies suggest that mirex affects two possibly related responses: (i) promotion through a distinct mirex-specific mechanism, and (ii) potentiation of a mechanism mediating the promotional activity of TPA.

Minimal role of enhanced cell proliferation in skin tumor promotion by mirex: a nonphorbol ester-type promoter.

Mirex, a chlorinated hydrocarbon previously used as a systemic insecticide and flame retardant, is a nongenotoxic hepatocarcinogen in both rats and mice. In liver, mirex induced biochemical responses and hyperplasia characteristic of increased cell proliferation, which is consistent with its role as a liver tumor promoter. We have recently shown that mirex is a potent nonphorbol ester-type skin tumor promoter in 7, 12-dimethylbenz[a]anthracene (DMBA)-initiated mice. However, unlike its effect in liver, a single topical application of mirex to skin does not induce the acute biochemical responses, such as increased epidermal DNA synthesis and ornithine decarboxylase activity, indicative of increased cell proliferation. Multiple topical applications of mirex over a 1 month period induced only a minimal increase in the number of epidermal nucleated cell layers, which contrasts with definitive hyperplasia induced by a comparable tumor-promoting dose of 12-O-tetradecanoylphorbol-13-acetate (TPA). Collectively, these data indicated that mirex is promoting through a novel mechanism. Further evidence that mirex promotes tumors through a mechanism distinct from that of the prototypical skin tumor promoter, TPA, was obtained by examining the effect of their simultaneous co-treatment. The co-application of mirex and TPA yielded a tumor multiplicity greater than the sum of the responses of each promoter individually. In summary, our results demonstrate that mirex, a carcinogenic and hyperplastic agent in liver, is also a very effective tumor promoter in mouse skin, but suggest that mirex operates via a novel mechanism in skin that may involve only a minimal role for enhanced cell proliferation.