[Compromising due to additive cerclages : Can surgical treatment of humeral shaft fractures cause damage to the radial nerve?] / Kompromittierung durch additive Cerclagen : Ist der N. radialis in der operativen Versorgung der Humerusschaftfraktur in Gefahr?

BACKGROUND: In many cases the treatment of humeral shaft fractures is challenging and despite the large diversity of available approaches, no standard treatment exists. In addition to conservative treatment, intramedullary nails and plate osteosynthesis are competing methods for healing humeral shaft fractures. Furthermore, cerclage is considered to be an additive treatment for spiral fractures; however, this also increases the risk of radial nerve neuropathy and is said to compromise the perfusion of bone fragments. The goal of this study was to investigate secondary radial nerve neuropathy using additive and limited invasive cerclages for nail osteosynthesis of humeral shaft fractures. METHODS: In the present study a total of 102 patients with humeral shaft fractures were clinically and neurologically re-examined after having been treated with nail osteosynthesis and additive cerclage via a limited invasive access over the past 5 years. In total 193 cerclages with limited invasive access were inserted during this time period. RESULTS AND CONCLUSION: Of the patients four (3.9%) showed a secondary radial neuropathy during operative stabilization. Neurophysiological and neurosonographic examinations revealed that this had not been caused by compromising, embedding or severance of the radial nerve due to the cerclage. Two out of these nerve lesions recovered spontaneously within 3 and 6 months, respectively. The other two cases could not be documented over a period of 12 months due to death of the patient. With 3.9% of iatrogenic radial nerve lesions the rate of nerve lesions falls into the lower range of that which has previously been described in the literature for nerve lesions due to operative treatment of humeral shaft fractures (3-12%). We thus conclude that there is no increased risk for iatrogenic injury of the radial nerve using additive and limited invasive cerclage.

The steroid metabolome in women with premenstrual dysphoric disorder during GnRH agonist-induced ovarian suppression: effects of estradiol and progesterone addback.

Clinical evidence suggests that symptoms in premenstrual dysphoric disorder (PMDD) reflect abnormal responsivity to ovarian steroids. This differential steroid sensitivity could be underpinned by abnormal processing of the steroid signal. We used a pharmacometabolomics approach in women with prospectively confirmed PMDD (n=15) and controls without menstrual cycle-related affective symptoms (n=15). All were medication-free with normal menstrual cycle lengths. Notably, women with PMDD were required to show hormone sensitivity in an ovarian suppression protocol. Ovarian suppression was induced for 6 months with gonadotropin-releasing hormone (GnRH)-agonist (Lupron); after 3 months all were randomized to 4 weeks of estradiol (E2) or progesterone (P4). After a 2-week washout, a crossover was performed. Liquid chromatography/tandem mass spectrometry measured 49 steroid metabolites in serum. Values were excluded if >40% were below the limit of detectability (n=21). Analyses were performed with Wilcoxon rank-sum tests using false-discovery rate (q<0.2) for multiple comparisons. PMDD and controls had similar basal levels of metabolites during Lupron and P4-derived neurosteroids during Lupron or E2/P4 conditions. Both groups had significant increases in several steroid metabolites compared with the Lupron alone condition after treatment with E2 (that is, estrone-SO4 (q=0.039 and q=0.002, respectively) and estradiol-3-SO4 (q=0.166 and q=0.001, respectively)) and after treatment with P4 (that is, allopregnanolone (q=0.001 for both PMDD and controls), pregnanediol (q=0.077 and q=0.030, respectively) and cortexone (q=0.118 and q=0.157, respectively). Only sulfated steroid metabolites showed significant diagnosis-related differences. During Lupron plus E2 treatment, women with PMDD had a significantly attenuated increase in E2-3-sulfate (q=0.035) compared with control women, and during Lupron plus P4 treatment a decrease in DHEA-sulfate (q=0.07) compared with an increase in controls. Significant effects of E2 addback compared with Lupron were observed in women with PMDD who had significant decreases in DHEA-sulfate (q=0.065) and pregnenolone sulfate (q=0.076), whereas controls had nonsignificant increases (however, these differences did not meet statistical significance for a between diagnosis effect). Alterations of sulfotransferase activity could contribute to the differential steroid sensitivity in PMDD. Importantly, no differences in the formation of P4-derived neurosteroids were observed in this otherwise highly selected sample of women studied under controlled hormone exposures.

Dosimetric characteristics of the novel 2D ionization chamber array OCTAVIUS Detector 1500.

PURPOSE: The dosimetric properties of the OCTAVIUS Detector 1500 (OD1500) ionization chamber array (PTW-Freiburg, Freiburg, Germany) have been investigated. A comparative study was carried out with the OCTAVIUS Detector 729 and OCTAVIUS Detector 1000 SRS arrays. METHODS: The OD1500 array is an air vented ionization chamber array with 1405 detectors in a 27 × 27 cm(2) measurement area arranged in a checkerboard pattern with a chamber-to-chamber distance of 10 mm in each row. A sampling step width of 5 mm can be achieved by merging two measurements shifted by 5 mm, thus fulfilling the Nyquist theorem for intensity modulated dose distributions. The stability, linearity, and dose per pulse dependence were investigated using a Semiflex 31013 chamber (PTW-Freiburg, Freiburg, Germany) as a reference detector. The effective depth of measurement was determined by measuring TPR curves with the array and a Roos chamber type 31004 (PTW-Freiburg, Freiburg, Germany). Comparative output factor measurements were performed with the array, the Semiflex 31010 ionization chamber and the Diode 60012 (both PTW-Freiburg, Freiburg, Germany). The energy dependence of the OD1500 was measured by comparing the array's readings to those of a Semiflex 31010 ionization chamber for varying mean photon energies at the depth of measurement, applying to the Semiflex chamber readings the correction factor kNR for nonreference conditions. The Gaussian lateral dose response function of a single array detector was determined by searching the convolution kernel suitable to convert the slit beam profiles measured with a Diode 60012 into those measured with the array's central chamber. An intensity modulated dose distribution measured with the array was verified by comparing a OD1500 measurement to TPS calculations and film measurements. RESULTS: The stability and interchamber sensitivity variation of the OD1500 array were within ±0.2% and ±0.58%, respectively. Dose linearity was within 1% over the range from 5 to 1000 MU. The effective point of measurement of the OD1500 for dose measurements in RW3 phantoms was determined to be (8.7 ± 0.2) mm below its front surface. Output factors showed deviations below 1% for field sizes exceeding 4 × 4 cm(2). The dose per pulse dependence was smaller than 0.4% for doses per pulse from 0.2 to 1 mGy. The energy dependence of the array did not exceed ±0.9%. The parameter σ of the Gaussian lateral dose response function was determined as σ6MV = (2.07 ± 0.02) mm for 6 MV and σ15MV = (2.09 ± 0.02) mm for 15 MV. An IMRT verification showed passing rates well above 90% for a local 3 mm/3% criterion. CONCLUSIONS: The OD1500 array's dosimetric properties showed the applicability of the array for clinical dosimetry with the possibility to increase the spatial sampling frequency and the coverage of a dose distribution with the sensitive areas of ionization chambers by merging two measurements.

Nutrient and particle load estimates to Lake Tahoe (CA-NV, USA) for Total Maximum Daily Load establishment.

The Lake Tahoe Total Maximum Daily Load (TMDL) requires detailed methodologies to identify sources of flows and pollutants (particles and nutrients) for estimating time-variant loads as input data for the Lake Tahoe clarity model. Based on field data and a modeling study, the major sources of pollutant loads include streams (three subdivisions of this category are urban, nonurban, and stream channel erosion), intervening zones (IZs) (two subdivisions of this category are urban and nonurban), atmosphere (wet and dry), groundwater and shoreline erosion. As Lake Tahoe remains well oxygenated year-round, the contribution of internal loading from the bottom sediments was considered minor. A comprehensive quantitative estimate for fine particle number (< 16 µm diameter) and nutrient (nitrogen and phosphorus) loading is presented. Uncertainties in the estimation of fine particle numbers and nutrients for different sources are discussed. Biologically available phosphorus and nitrogen were also evaluated. Urban runoff accounted for 67% of the total fine particle load for all sources making it the most significant contributor although total urban runoff was only 6%. Non-urban flows accounted for 94% of total upland runoff, but the nitrogen, phosphorus and fine sediment loadings were 18%, 47% and 12%, respectively of the total loadings. Atmospheric nitrogen, phosphorus, and fine particle loadings were approximately 57%, 20%, and 16%, respectively of the total loading. Among streams and IZs, IZ 8000, Upper Truckee River, Trout Creek, Blackwood Creek, and Ward Creek are the top fine particle, nitrogen and phosphorus contributors. The relative percentage contribution of inorganic fine particles from all sources based on annual average for the period 1994-2008 on size classes 0.5-1, 1-2, 2-4, 4-8, and 8-16 µm are 73%, 19%, 5%, 2%, and 1%, respectively. These results suggest clear priorities for resource managers to establish TMDL on sources and incoming pollutants and preserving lake clarity.

Topical application of solubilized Reseda luteola extract reduces ultraviolet B-induced inflammation in vivo.

We investigated the skin tolerance and anti-inflammatory potential of a nanoparticular solubilisate of a luteolin-rich Reseda extract (s-RE) in two independent studies in vivo. Reseda luteola extract containing 40% flavonoids was solubilized with polysorbate, resulting in product micelles with a diameter of 10 (+/-1.5)nm. Standardized inflammation was induced by irradiating test areas on the back of healthy volunteers with defined doses of ultraviolet B (UVB). In the first study different concentrations of s-RE were tested in 10 volunteers to evaluate dose-dependency of anti-inflammatory effects of s-RE. In the second randomized, double-blind, placebo-controlled study a defined concentration of s-RE (2.5%w/w) was tested in 40 volunteers in comparison to the vehicle (glycerol) and hydrocortisone (1%w/w). s-RE dose-dependently reduced UVB-induced erythema when applied 30 min before irradiation. To a lesser extent, topical application of s-RE after irradiation also reduced UVB-induced erythema. s-RE was as effective as hydrocortisone, whereas the vehicle had no effect. Occlusive application of s-RE on non-irradiated test sites did not cause any skin irritation. Due to excellent skin tolerance combined with potent anti-inflammatory properties s-RE bears potential especially for the prevention but also for the treatment of inflammatory skin conditions such as UV-induced erythema.

Potential toxicity concerns from chemical coagulation treatment of stormwater in the Tahoe basin, California, USA.

Coagulant dosing of stormwater runoff with polyaluminum chlorides (PACs) is used in numerous waterbodies to improve water clarity, but the potential risks of PACs to aquatic organisms in Lake Tahoe, California are not fully understood. To assess these risks, the USEPA 3-species toxicity test and a non-standard fish test using Japanese medaka (Oryzias latipes) were used to determine the toxicity of PAC-treated and non-treated stormwater samples to aquatic species. Stormwater samples were collected from three sites representing runoff from different urbanized areas in May 2004; samples received coagulant dosing using three different coagulants (JC1720, PAX-XL9, Sumalchlor50) at levels optimized with jar testing. Raw stormwaters were toxic to algae and fathead minnows (mortality). Treatment with coagulants increased toxicity to zooplankton (reproduction) and had no consistent effects on the other toxicity metrics.

Skin tolerance of a new bath oil containing St. John's wort extract.

BACKGROUND: Dry and atopic skin requires skin care with lipid-rich emollients and moisturizing bath or shower oils. However, it has been shown recently that some bath oils may even impair the skin barrier. OBJECTIVE: To investigate the skin-irritating potential of a new bath oil containing a lipophilic St. John's wort (Hypericum perforatum) extract. METHODS: In this single-center, randomized, double-blind, prospective study, 3 bath oils together with positive and negative controls were applied under occlusion on test areas on the volar forearms of 18 volunteers (visit 1). After 24 h, the tapes were removed, and the test areas were evaluated by a visual score and the instrumental measurement of skin erythema and transepidermal water loss (TEWL) using a Mexameter and a Tewameter (visit 2). The test substances were applied a second time, and the measurements were performed after another 24 h (visit 3). RESULTS: The positive control, 1% vol/vol sodium lauryl sulfate (SLS), caused a significant increase in skin erythema and TEWL. In contrast, distilled water as a negative control did not influence these parameters. The new bath oil containing St. John's wort extract and 1 of the other 2 commercial products were not different from the water control. The third bath oil displayed a skin-irritating effect similar to SLS. CONCLUSION: The results of this study confirm the different skin-irritating potential of bath oils and demonstrate good skin tolerance of the new bath oil containing St. John's wort extract.

Investigation of the anti-inflammatory potential of Aloe vera gel (97.5%) in the ultraviolet erythema test.

BACKGROUND: Aloe vera is a natural product that is frequently used in soothing skin care products such as aftersun lotions. In the present study we aimed to explore the anti-inflammatory potential of a highly concentrated A. vera gel in the UV erythema test in vivo. METHODS: 40 volunteers with skin types II and III were included in the randomized, double-blind, placebo-controlled, phase III monocenter study. Test areas on the back were irradiated with the 1.5-fold minimal erythema dose of UVB. Subsequently, the test areas were treated occlusively on 2 subsequent days with A. vera gel (97.5%), the positive controls (0.25% prednicarbate, 1% hydrocortisone in placebo gel and 1% hydrocortisone cream) and a placebo gel. Erythema values were determined photometrically after 24 and 48 h. RESULTS: A. vera gel (97.5%) significantly reduced UV-induced erythema after 48 h, being superior to 1% hydrocortisone in placebo gel. In contrast, 1% hydrocortisone in cream was more efficient than A. vera gel. CONCLUSIONS: In this study after 48 h the A. vera gel (97.5%) displayed some anti-inflammatory effects superior to those of 1% hydrocortisone in placebo gel. The A. vera gel tested here might be useful in the topical treatment of inflammatory skin conditions such as UV-induced erythema.

Anti-inflammatory effect of pimecrolimus in the sodium lauryl sulphate test.

BACKGROUND: Pimecrolimus is a calcineurin inhibitor used for the topical treatment of inflammatory skin diseases. We have shown previously that pimecrolimus cream is not effective on intact skin in the ultraviolet erythema test. OBJECTIVE: To test the anti-inflammatory effect of pimecrolimus cream after damage of the skin barrier by sodium lauryl sulphate (SLS) in a randomised, placebo-controlled, observer-blinded study. METHODS: SLS (3% v/v) was applied under occlusion on the back of 36 healthy volunteers for 24 h. Subsequently, the test areas were treated for 24 h with pimecrolimus cream, 1% hydrocortisone in a hydrophilic ointment, and the vehicle alone over three consecutive days. One control area remained untreated. The erythema index and the transepidermal water loss (TEWL) served as readout parameters to assess the SLS-induced skin irritation. RESULTS: Pimecrolimus cream and 1% hydrocortisone cream significantly reduced the SLS-induced erythema. The two test preparations did not have a significant effect on the TEWL. CONCLUSION: After damage to the skin barrier by SLS, pimecrolimus seems to penetrate into the skin as shown by a reduction of the irritation-induced erythma. These data further support the notion that pimecrolimus is selectively effective in the treatment of skin disorders with an impaired function of the epidermal barrier.

Usnea barbata extract prevents ultraviolet-B induced prostaglandin E2 synthesis and COX-2 expression in HaCaT keratinocytes.

Usnea barbata and its major constituent usnic acid are potent antimicrobial agents. Here, we have investigated anti-inflammatory properties of an U. barbata extract (UBE) containing 4% usnic acid in an ultraviolet-B (UVB) model with HaCaT keratinocytes. UVB irradiation induced PGE(2) production and COX-2 expression in a time and dose-dependent manner. UBE inhibited PGE(2) production at a half-maximal concentration of 60 microg/ml (2.4 microg/ml usnic acid) that did not affect the UVB-induced upregulation of COX-2, suggesting an effect on enzyme activity rather than on protein expression. The inhibition of PGE(2) production by UBE was not due to cytotoxicity. Besides its known antimicrobial properties, UBE displays specific UVB protective effects that might be useful in the topical treatment of UVB-mediated inflammatory skin conditions.

[Erythema annulare centrifugum Darier. Successful therapy with topical calcitriol and 311 nm-ultraviolet B narrow band phototherapy]. / Erythema anulare centrifugum Darier. Erfolgreiche Therapie mit topischem Calcitriol und UVB-Schmalspektrumbestrahlung.

Erythema annulare centrifugum is an acute dermatosis of unclear etiology, which presents with annular erythematous lesions with marginal scale. Therapeutically, systemic and topical glucocorticosteroids are used primarily. We treated a patient with large lesions in the area of the thighs resistant to a therapy with topical glucocorticosteroids, with topical calcitriol in combination with 311 nm ultraviolet B narrow band phototherapy. After four weeks of treatment the skin lesions had cleared nearly completely without any side effects. The combination topical vitamin D3-analogue calcitriol and 311 nm ultraviolet B narrow band phototherapy was effective and can be regarded as a useful alternative to glucocorticosteroids for erythema annulare centrifugum.

Selective attention and Pavlovian conditioning.

The present results show that the common practice of using self-indexing conditioned stimuli (CSs) in research on Pavlovian conditioning is a major source of experimental bias. The typical stimulus used is either a light flash or a sound pulse in a light/sound-shielded chamber. Under these conditions the onset characteristics of the CS signal totally predominate over the durational characteristic, i.e. the pattern information. Thus a visual pattern presented as a CS in a dark chamber is confounded with a brightness change from darkness to light. In the first experiment, animals were conditioned with a brightness CS using a self-indexing signal paradigm. When tested for specificity of the conditioning, they showed complete transfer of learning to either a visual pattern or even an auditory CS. These findings indicated that the traditional conditioning paradigm is biased towards non-specific sensory learning. The second experiment showed that specific sensory conditioning is critically dependent on selective attention mechanisms. When the onset characteristics of the CS signal were de-emphasized by the use of equal energy background illumination in the intertribal interval (ITI) during conditioning, the animals were not able to feature extract either the onset or the durational component of the CS signal from the ITI background despite prolonged training. It was only by starting with conditioning that was initially anchored to the CS onset characteristics that a perceptual fade-in procedure would bias attention to feature extract the durational characteristics of the CS. Thus conditioning occurred only when the rabbit's attention was directed to detection of the gratings display without any associated changes in visual albedo. Perhaps the most important finding of the present experiments is that the use of self-indexing CS signals in Pavlovian conditioning inevitably introduces non-specific sensory processing involving multiple sensory input pathways in the conditioning. This inherent uncertainty of the sensory input pathways presents a problem for clarifying the role of sensory pathways in the neural mechanisms of NM conditioning. In addition, the use of self-indexing CSs inevitably leads to an underestimation of the role of forebrain mechanisms in Pavlovian conditioning.

Continuous renal replacement therapy in patients following traumatic injury.

In critically injured patients, the incidence of acute renal failure has been reported to occur in as many as 31% of patients. The use of CRRT modalities for patients following traumatic injuries is becoming more common, albeit slowly, and this therapy may impact upon long-term recovery of renal function and mortality. Historical studies investigating the early use of intermittent dialysis reported significant improvement in survival in patients who were dialyzed earlier and more vigorously than in control subjects. Early trauma patients also showed improved survival following war injuries when dialyzed prophylactically. Although there is a growing acceptance in favor of earlier renal replacement therapy, the published consensus and the practice in many centers has been to dialyze/filter relatively ill rather than relatively healthy patients. The R Adams Cowley Shock Trauma Center (STC) in Baltimore, Maryland, USA, admits over 8,000 trauma patients each year. Within the STC, a program of continuous renal replacement therapy was established in the early 1980's. We review both historical and current literature on the use of renal replacement therapies after traumatic injury, and suggest some future areas of investigation and indications for these modalities.

Infrequent mutation of the tumour-suppressor gene Smad4 in early-stage colorectal cancer.

Smad4 is a candidate tumour-suppressor gene identified recently on chromosome 18q21.1. Both alleles are inactivated in nearly one-half of pancreatic carcinomas, but its role in the tumorigenesis of other tumours is still unknown. The aim of this study was to investigate the potential involvement of the Smad4 locus in early-stage colorectal cancers (stages I-III) in tumour samples from a randomised multicentre trial. Of a large collection of DNA samples, 73 with a loss of one allele of the Smad4 gene were analysed for the presence of point mutations in the remaining gene. Patients, from whom biopsies were isolated, were part of a previous randomised multicentre study of the Swiss Group for Clinical Cancer Research on the benefit of adjuvant chemotherapy (SAKK study 40/81). Mutation analysis was restricted to the highly conserved C-terminal domain (exons 8, 9, 10 and 11) of Smad4, using PCR and single-strand conformational variant analysis. Two of the 73 patients (3%) with loss of one allele of Smad4 had a point mutation in the remaining allele. These results indicate that whereas Smad4 point mutations are prevalent in pancreatic carcinoma, they are infrequent in early stages (I-III) of colorectal cancer.

SMAD4 is a predictive marker for 5-fluorouracil-based chemotherapy in patients with colorectal cancer.

The gene for the transducer of transforming growth factor-beta/bone morphogenetic protein signalling SMAD4, a potential suppressor of colorectal carcinogenesis, is located at the chromosomal region 18q21. In order to evaluate the clinical relevance of SMAD4 deletion, gene copy alterations were determined by copy dosage using real-time quantitative PCR in 202 colorectal tumour biopsies from a previous randomised study of adjuvant chemotherapy. Patients with normal SMAD4 diploidy turned out to have a three-fold higher benefit of 5-fluorouracil-based adjuvant chemotherapy with a border line significance (overall survival: 3.23, P=0.056; disease-free survival: 2.89, P=0.045). These data are consistent with the previous observation that patients whose cancer had retention of the 18q21 region had a significantly higher benefit from 5-fluorouracil-based therapy. Moreover, these results may provide a refinement at the gene level of the clinical relevance of 18q21 deletion, thereby suggesting SMAD4 as a predictive marker in colorectal cancer. This data also indicate that integrity of this component of the transforming growth factor-beta/bone morphogenetic protein signalling pathway may be a critical factor for benefit of chemotherapy in patients with colorectal cancer.

Optimization of cottontail rabbit papilloma virus challenge technique.

Disease induced by Cottontail Rabbit Papilloma Virus (CRPV) scarification in domestic rabbits shares many attributes with disease induced by human papilloma virus (HPV). CRPV induces squamous papillomas in domestic rabbits, of which approximately 70% transform into invasive carcinomas. In advanced tumors, virus is often undetectable, and occasionally, some rabbits undergo spontaneous regression of papillomas. Techniques utilized to scarify rabbit skin are diverse, often labor intensive and time consuming with the possibility for significant variability. Using four unique infection techniques, resultant papilloma incidence, time to onset, and total papilloma volumes were compared to determine an optimal challenge method. Five rabbits were each infected with CRPV via a tattoo gun with and without ink, an intradermal injection, manual use of a tattoo needle, or a sterile blade followed by manual use of a tattoo needle. Papilloma formation was monitored weekly after inoculation for 6 weeks. CRPV papillomas began as pinpoint foci at 3 weeks post challenge and grew exponentially throughout the course of measurement. Individual foci coalesced rapidly to form larger papilloma aggregates. Although intradermal injection was well tolerated and easily performed, it was the worst method of papilloma production (2.2 mm(3) at 6 weeks). The best method, a sterile blade followed by manual use of a tattoo needle, produced significantly larger papillomas over all time periods (>1100 mm(3) at 6 weeks, P<0.01). Inoculation of CRPV using this method produces highly repeatable papillomas beginning 3 weeks post-infection.

Combined copy status of 18q21 genes in colorectal cancer shows frequent retention of SMAD7.

Deletions of chromosome band 18q21 appear with very high frequency in a variety of carcinomas, especially in colorectal cancer. Potent tumor suppressor genes located in this region encode transforming growth factor beta (TGF-beta) signal transducers SMAD2 and SMAD4, and inactivation of either one leads to impaired TGF-beta-mediated cell growth/apoptosis. Following the assignment of SMAD7 to 18q21, we first refined the SMAD7 gene position within this region by genetically mapping SMAD7 between SMAD2 and SMAD4. Further, to compare the respective frequencies of genetic alterations of these three SMAD genes in colorectal cancer, we undertook a large-scale evaluation of the copy status of each of these genes on DNA samples from colorectal tumor biopsy material. Among a subset of 233 DNA samples for which data were available for all four genes, SMAD4, SMAD2, and the nearby gene DCC showed high deletion rates (66%, 64%, and 59%, respectively), whereas SMAD7 was deleted in only 48% of the tumors. Unexpectedly, we found some gene duplications; SMAD7 appears to be more frequently amplified (10%) than the three other genes (4-7%). Compiled data for SMAD genes in each tumor show that the most common combination (26% of all the tumors) consists of the simultaneous deletions of SMAD2 and SMAD4 associated with normal diploidy or even duplication of SMAD7. Since SMAD7 normally counteracts SMAD2 and SMAD4 in TGF-beta signaling, we hypothesize that the tumor might not benefit from simultaneous SMAD7 inactivation, thereby exerting selective pressure to retain or even to duplicate the SMAD7 gene.

Stream phosphorus transport in the Lake Tahoe basin, 1989-1996.

Lake Tahoe is undergoing the initial stages of cultural eutrophication due to human alteration of the airshed and watershed. The lake's switch from nitrogen (N) to phosphorus (P) limitation has been attributed primarily to atmospheric N loading. This places an increased importance on controlling watershed movement of P to the lake. A stream water quality monitoring data set consisting of nine streams in the Lake Tahoe basin has been analyzed to characterize the spatiotemporal variation of P delivery to the lake. This data is from the Lake Tahoe Interagency Monitoring Program (LTIMP), which provides scientific data for planning and regulatory agencies to address environmental problems in the Lake Tahoe basin. Results indicate that P delivery (concentrations, loads) varies greatly at interannual, seasonal, and spatial scales. Annual and seasonal total P (TP) concentrations can vary up to three orders of magnitude in a given stream and are strongly associated with suspended sediment. Particulate P is the major form of P transported by Tahoe streams and was strongly correlated with percent surficial geologic deposits, which are primarily located near streams. Tahoe streams with the highest annual P concentrations often had the lowest annual P loads, and visa versa. P loading is greatest during the spring snowmelt (75% of annual average). Potential watershed parameters influencing P delivery to Lake Tahoe have been identified as precipitation, basin area, basin steepness, and road and human development coverage. Results also suggest that human development impacts on stream P loads are most prevalent during high precipitation years. Identification and quantification of stream sediment and P sources such as streambanks and impervious surface is necessary to aid in watershed restoration efforts.