2H-enrichment of cellulose and n-alkanes in heterotrophic plants.

Hydrogen (H) isotopes of plant organic compounds are rarely employed in ecological studies. If so, these values are interpreted as being indicative of the plant source and/or leaf water. Recent observations suggest, however, that variations in hydrogen isotope fractionation that occur during the biosynthesis of plant compounds (2H-εbio) imprint valuable metabolic information into the hydrogen isotope composition (δ2H values) of plant organic compounds. Here we show a consistent 2H-enrichment of compounds in heterotrophically growing plants across a series of autotrophic/heterotrophic plant pairs. We suggest that this is due to a higher recycling of compounds in the Calvin and tricarboxylic acid cycles in heterotrophic plants that is associated with a more complete exchange of C-bound H with the surrounding 2H-enriched foliar water. Interestingly, we found that 2H-enrichment in heterotrophic plants was larger for carbohydrates than for lipids, with an average 2H-enrichment of 76 ± 9‰ in α-cellulose and 23 ± 23‰ in n-alkanes. We propose that this systematically larger 2H-enrichment for carbohydrates than for lipids is either due to different level of 2H-fractionation associated with heterotrophically produced NADPH, or to the potential uptake of lipids by heterotrophic plants. With the work we present here, we contribute to a better mechanistic understanding of what the biochemical principles are that couple the carbohydrate dynamics of plants to their δ2H values and hope to foster as such the application of H isotopes in plant sciences.

Diel variations in carbon isotopic composition and concentration of organic acids and their impact on plant dark respiration in different species.

Leaf respiration in the dark and its C isotopic composition (δ(13) CR ) contain information about internal metabolic processes and respiratory substrates. δ(13) CR is known to be less negative compared to potential respiratory substrates, in particular shortly after darkening during light enhanced dark respiration (LEDR). This phenomenon might be driven by respiration of accumulated (13) C-enriched organic acids, however, studies simultaneously measuring δ(13) CR during LEDR and potential respiratory substrates are rare. We determined δ(13) CR and respiration rates (R) during LEDR, as well as δ(13) C and concentrations of potential respiratory substrates using compound-specific isotope analyses. The measurements were conducted throughout the diel cycle in several plant species under different environmental conditions. δ(13) CR and R patterns during LEDR were strongly species-specific and showed an initial peak, which was followed by a progressive decrease in both values. The species-specific differences in δ(13) CR and R during LEDR may be partially explained by the isotopic composition of organic acids (e.g., oxalate, isocitrate, quinate, shikimate, malate), which were (13) C-enriched compared to other respiratory substrates (e.g., sugars and amino acids). However, the diel variations in both δ(13) C and concentrations of the organic acids were generally low. Thus, additional factors such as the heterogeneous isotope distribution in organic acids and the relative contribution of the organic acids to respiration are required to explain the strong (13) C enrichment in leaf dark-respired CO2 .

Thyroglobulin fluctuations in patients with iodine-refractory differentiated thyroid carcinoma on lenvatinib treatment - initial experience.

Tyrosine kinase inhibitors (TKI) have shown clinical effectiveness in iodine-refractory differentiated thyroid cancer (DTC). The corresponding role of serum thyroglobulin (Tg) in iodine-refractory DTC has not been investigated yet. 9 patients (3 female, 61 ± 8y) with progressive iodine-refractory DTC starting on lenvatinib were considered. Tumor restaging was performed every 2-3 months including contrast-enhanced computed tomography (CT, RECIST 1.1). Serum Tg was measured and compared to imaging findings. After treatment initiation, serum Tg levels dropped in all patients with a median reduction of 86.2%. During long-term follow-up (median, 25.2 months), fluctuations in Tg could be observed in 8/9 subjects. According to RECIST, 6/9 subjects achieved a partial response or stable disease with the remaining 3/9 experiencing progressive disease (2/3 with Tg levels rising above baseline). All of the patients with disease progression presented with a preceding continuous rise in serum Tg, whereas tumor marker oscillations in the subjects with controlled disease were only intermittent. Initiation of lenvatinib in iodine-refractory DTC patients is associated with a significant reduction in serum Tg levels as a marker of treatment response. In the course of treatment, transient Tg oscillations are a frequent phenomenon that may not necessarily reflect morphologic tumor progression.

Correlations between the 13C Content of Primary and Secondary Plant Products in Different Cell Compartments and That in Decomposing Basidiomycetes.

Relative carbon isotope ratio ([delta]13C values) of primary and secondary products from different compartments of annual plants, pine needles, wood, and decomposing Basidiomycetes have been determined. An enrichment in 13C was found for storage tissues of annual plants, because of the high level of the primary storage products sucrose and starch; however, the enrichment was even greater in leaf starch. All of these compounds had the same relative 13C enrichment in positions 3 and 4 of glucose. Secondary products in conifer needles (lignin, lipids) were depleted in 13C by 1 to 2 [per mille (thousand) sign] relative to carbohydrates from the same origin. Air pollution caused a small decrease in [delta]13C values; however, the relative content of plant products, especially of the soluble polar compounds, was also affected. Decomposing fungi showed a global accumulation of 13C by 4[per mille (thousand) sign] relative to their substrates in wood. Their chitin was enriched by 2[per mille (thousand) sign] relative to the cellulose of the wood. Hence, Basidiomycetes preferentially metabolize "light" molecules, whereas "heavy" molecules are preferentially polymerized. Our results are discussed on the basis of a kinetic isotope effect on the fructose-1,6-bisphosphate aldolase reaction and of metabolic branching on the level of the triose phosphates with varying substrate fluxes.

Prognostic Value of Serum Tumor Markers in Medullary Thyroid Cancer Patients Undergoing Vandetanib Treatment.

Tyrosine kinase inhibitors (TKIs) such as vandetanib have shown clinical effectiveness in advanced medullary thyroid cancer (MTC). During TKI treatment, fluctuations in the tumor markers carcinoembryonic antigen (CEA) and calcitonin (CTN) are frequently observed. Their role for treatment monitoring and the decision-making process has not been fully elucidated yet.Twenty-one patients (male, 16, female, 5; mean age, 49 ±â€Š13 years) with progressive MTC receiving vandetanib (300 mg orally per day) were considered. Tumor restaging was performed every 3 months including contrast-enhanced computed tomography (CT). Response was assessed according to recent criteria (Response Evaluation Criteria in Solid Tumors, RECIST 1.1). Additionally, CEA and CTN were measured at the day of CT imaging and alterations observed in tumor markers were compared to respective imaging findings (partial response, PR; stable disease, SD; progressive disease, PD).During long-term follow-up (510 ±â€Š350 days [range, 97-1140 days]), CTN and CEA levels initially dropped in 71.4% and 61.9% of the patients followed by fluctuations in serum marker levels. A rise in CTN ≥39.5% between 2 subsequent measurements (defined by ROC analysis) had a sensitivity of 70.6% and a specificity of 83.2% in predicting PD with an accuracy of 82.0% (area under the curve (AUC), 0.76). Oscillations in CEA levels were not predictive for PD.Whereas tumor marker fluctuations in MTC patients undergoing TKI treatment are a frequent phenomenon, a significant rise in CTN ≥40% turns out to as an early indicator of tumor progression.

The relationship between needle sugar carbon isotope ratios and tree rings of larch in Siberia.

Significant gaps still exist in our knowledge about post-photosynthetic leaf level and downstream metabolic processes and isotopic fractionations. This includes their impact on the isotopic climate signal stored in the carbon isotope composition (δ(13)C) of leaf assimilates and tree rings. For the first time, we compared the seasonal δ(13)C variability of leaf sucrose with intra-annual, high-resolution δ(13)C signature of tree rings from larch (Larix gmelinii Rupr.). The trees were growing at two sites in the continuous permafrost zone of Siberia with different growth conditions. Our results indicate very similar low-frequency intra-seasonal trends of the sucrose and tree ring δ(13)C records with little or no indication for the use of 'old' photosynthates formed during the previous year(s). The comparison of leaf sucrose δ(13)C values with that in other leaf sugars and in tree rings elucidates the cause for the reported (13)C-enrichment of sink organs compared with leaves. We observed that while the average δ(13)C of all needle sugars was 1.2‰ more negative than δ(13)C value of wood, the δ(13)C value of the transport sugar sucrose was on an average 1.0‰ more positive than that of wood. Our study shows a high potential of the combined use of compound-specific isotope analysis of sugars (leaf and phloem) with intra-annual tree ring δ(13)C measurements for deepening our understanding about the mechanisms controlling the isotope variability in tree rings under different environmental conditions.

SPECT- and PET-based patient-tailored treatment in neuroendocrine tumors: a comprehensive multidisciplinary team approach.

The overexpression of somatostatin receptors on the tumor cell surface of neuroendocrine tumors (NETs) detected by multimodal functional imaging modalities such as SPECT and PET tracers constitutes a therapeutic option using targeting radiolabeled compounds. We will introduce the theranostic concept in general, explain in more detail its development in NETs, and discuss available SPECT and PET tracers regarding their potential for diagnostic imaging, visualization of target expression, and treatment tailoring. Moreover, we will discuss the currently available peptide receptor radionuclide therapy principles and compare them to previously published studies. Finally, we will discuss which new concepts will most likely influence the theranostic treatment approach in NETs in the future.

18O pattern and biosynthesis of natural plant products.

Oxygen atoms in plant products originate from CO(2), H(2)O and O(2), precursors with quite different delta18O values. Furthermore their incorporation by different reactions implies isotope effects. On this base the resulting non-statistical 18O distributions in natural compounds are discussed. The delta18O value of cellulose is correlated to that of the leaf water, and the observed 18O enrichment (approximately +27 per thousand) is generally attributed to an equilibrium isotope effect between carbonyl groups and water. However, as soluble and heterotrophically synthesised carbohydrates show other correlations, a non-statistical 18O distribution - originating from individual biosynthetic reactions - is postulated for carbohydrates. Similarly, the delta18O values of organic acids, carbonyl compounds, alcohols and esters indicate water-correlated, but individual 18O abundances (e.g. O from acyl groups approximately +19% above water), depending upon origin and biosyntheses. Alcoholic groups introduced by monooxygenase reactions, e.g. in sterols and phenols, show delta18O values near +5 per thousand, in agreement with an assumed isotope fractionation factor of approximately 1.02 on the reaction with atmospheric oxygen (delta18O=+23.5 per thousand). Correspondingly, a "thermodynamically ordered isotope distribution" is only observed for oxygen in some functional groups correlated to an origin from CO(2) and H(2)O, not from O(2). The individual isotopic increments of functional groups permit the prediction of global delta18O values of natural compounds on the basis of their biosynthesis.

The effect of gabapentin on neuropathic pain.

OBJECTIVE: To evaluate the effects of gabapentin on pain scores and opiate use. DESIGN: Retrospective review of patients charts who received gabapentin for at least 30 days. Data were collected concerning patients' diagnosis, current drug use, concurrent drug use, gabapentin dose, pain scores, and patient-reported side effects. Patients were divided into three groups based on their pain diagnosis; low back, neuropathic, and myofascial pain. The neuropathic group was subdivided into postherpetic neuralgia, diabetic neuropathy, sympathetically maintained pain, and phantom pain. SETTING: Two tertiary referral teaching hospitals in southeastern Michigan. RESULTS: A total of 122 charts were reviewed and included in this study. A significant decrease in pain scores with gabapentin was seen in the neuropathic pain group (paired t-test, p < .0001) but not in the low back pain group. Of the neuropathic pain group, patients with postherpetic neuralgia had the greatest decrease in pain scores. Ten patients showed a > 75% decrease in pain scores, of these: nine had a direct nerve injury, and one had postherpetic neuralgia. Opiate use was unchanged in all groups. Patients who were taking opiates had significantly less benefit with gabapentin use in terms of pain score. Patient-reported side effects were similar to those reported in a nonchronic pain population. CONCLUSION: Gabapentin may be a useful adjunct for treating neuropathic pain with a minimum of side effects. Particular advantage may be gained with the use of this drug for postherpetic neuralgia and direct peripheral nerve injuries.

Effect of nitrogen fertilization upon the secondary chemistry and nutritional value of quaking aspen (Populus tremuloides Michx.) leaves for the large aspen tortrix (Choristoneura conflictana (Walker)).

We investigated the effects of nitrogen fertilization upon the concentrations of nitrogen, condensed tannin and phenolic glycosides of young quaking aspen (Populus tremuloides) leaves and the quality of these leaves as food for larvae of the large aspen tortrix (Choristoneura conflictana), a Lepidopteran that periodically defoliates quaking aspen growing in North America. Nitrogen fertilization resulted in decreased concentrations of condensed tannin and phenolic glycosides in aspen leaves and an increase in their nitrogen concentration and value as food for the large aspen tortrix. These results indicate that plant carbon/nutrient balance influences the quality of aspen leaves as food for the large aspen tortrix in two ways, by increasing the concentrations of positive factors (e.g. nitrogen) and decreasing the concentrations of negative factors (eg. carbon-based secondary metabolites) in leaves. Addition of purified aspen leaf condensed tannin and a methanol extract of young aspen leaves that contained condensed tannin and phenolic glycosides to artificial diets at high and low levels of dietary nitrogen supported this hypothesis. Increasing dietary nitrogen increased larval growth whereas increasing the concentrations of condensed tannin and phenolic glycosides decreased growth. Additionally, the methanol extract prevented pupation. These results indicate that future studies of woody plant/insect defoliator interactions must consider plant carbon/nutrient balance as a potentially important control over the nutritional value of foliage for insect herbivores.

Absence of polyneuropathy among workers previously diagnosed with solvent-induced toxic encephalopathy.

An association between polyneuropathy and occupational exposure to trichloroethylene, trichloroethane, perchloroethylene, or similar solvents alone or in combination is controversial. We sought to determine whether workers previously diagnosed with solvent-induced toxic encephalopathy had objective evidence of polyneuropathy. Thirty railroad workers previously diagnosed with toxic encephalopathy were examined in the context of litigation against their employers. All described long-term occupational solvent exposure averaging 20 years in duration (range, 10 to 29 years) and producing acute intoxication on a regular basis. The diagnosis of subclinical or clinical polyneuropathy was established using a combination of symptoms, signs, and nerve conduction study (NCS) measures, consistent with standard clinical practice. Potential confounders were identified. NCS results were compared with historical controls, including unexposed workers matched by gender, age, and body mass index. Dose-response relationships were evaluated using simple linear and stepwise regression models. Three workers fulfilled clinical polyneuropathy criteria. The only worker fulfilling NCS criteria for confirmed clinical polyneuropathy had diabetes mellitus. Mean NCS values for most measures were similar to control values, and existing differences in sensory amplitudes disappeared when compared with the matched control group. NCS measures were not significantly influenced by exposure duration or job title. Separation into groups on the basis of the presence or absence of polyneuropathy symptoms, previous diagnosis of polyneuropathy, disability status, and severity or type of encephalopathy did not demonstrate significant NCS differences. The complaints of these workers claiming neurotoxic injury from occupational solvent exposure are not explained by peripheral nervous system dysfunction.

The relationship of vitamin B6 status to median nerve function and carpal tunnel syndrome among active industrial workers.

Case reports and small case series suggest that vitamin B6 deficiency is an important etiologic factor in carpal tunnel syndrome (CTS). This hypothesis has never examined in a randomly selected study population, particularly among active workers. We examined 125 randomly selected active workers from two industrial plants. Each worker completed a self-administered symptom questionnaire and underwent electrodiagnostic testing of the median and ulnar sensory nerves. Laboratory biochemical analyses of vitamin B6 status were also performed using the erythrocyte glutamic pyruvic transaminase assay, and quantification of plasma pyridoxal-5'-phosphate. Measurements of vitamin B6 status were unrelated to self-reported symptoms potentially consistent with CTS, electrophysiologically determined median or ulnar nerve function, and CTS defined on the basis of self-reported symptoms and electrophysiologic measurements. These results suggest that CTS among active industrial workers is unrelated to vitamin B6 status. Furthermore, in our opinion, empiric prescription of vitamin B6 to patients with CTS is unwarranted and potentially hazardous.

Test-retest reliability of an upper-extremity discomfort questionnaire in an industrial population.

OBJECTIVES: Efforts to understand or to monitor upper-extremity musculoskeletal disorders among workers have usually involved the use of questionnaires. The goal of this study was to assess the test-retest reliability of an upper-extremity discomfort questionnaire among industrial workers. METHODS: Test-retest agreement among 148 workers was analyzed using the kappa coefficient for categorical outcomes. Values of kappa greater than 0.75 are considered excellent, values between 0.40 and 0.75 are fair to good, and values of less than 0.40 represent poor agreement beyond chance alone. Test-retest results of continuous measures (eg, visual analogue scale responses) were compared with paired t-tests. RESULTS: The test-retest reliability of the questionnaire used to elicit demographic information, medical history, exercise participation, and information on musculoskeletal symptoms among industrial workers appears to be good to excellent in most instances. CONCLUSIONS: These results suggest that most results of this discomfort questionnaire are reliable and suitable for use in epidemiologic studies. For reassurance of the robustness of these findings, similar studies should be carried out in other worker populations with this, and other, questionnaire instruments.

Agreement between symptom surveys, physical examination procedures and electrodiagnostic findings for the carpal tunnel syndrome.

OBJECTIVES: The goal of this study was to evaluate the concordance between various clinical screening procedures for carpal tunnel syndrome. METHODS: The subject population consisted of 824 workers from 6 facilities. The evaluated procedures included bilateral sensory nerve conduction testing, physical examinations, and symptom surveys, including hand diagrams. The agreement between the outcomes of various combinations of these procedures was assessed by determining the kappa coefficient. RESULTS: There was relatively poor overlap between the reported symptoms, the physical examination findings, and the electrodiagnostic results consistent with carpal tunnel syndrome. Overall, only 23 out of 449 subjects (5%) with at least 1 positive finding met all 3 criteria (symptoms, physical examination findings, and electrophysiological results consistent with carpal tunnel syndrome) for the dominant hand. The screening procedures showed poor or no agreement with kappa values ranging between 0.00 and 0.18 for all the case definitions evaluated for carpal tunnel syndrome. CONCLUSIONS: The poor overlap between the various screening procedures warns against the use of electrodiagnostic findings alone without the symptom presentation being considered. The results of this study also point to a need for the further development and evaluation of methods for detecting carpal tunnel syndrome.

Prevalence of carpal tunnel syndrome and median mononeuropathy among dentists.

BACKGROUND: The authors undertook a study to determine the prevalence in dentists of abnormal sensory nerve conduction and/or symptoms of carpal tunnel syndrome, or CTS, the most common nerve entrapment syndrome. METHODS: In a cross-sectional study, dentists (n = 1,079) were screened during the American Dental Association's Annual Health Screening Program in 1997 and 1998 by means of standard electrodiagnostic measures in the dominant hand and a self-reported symptom questionnaire. The authors diagnosed a median mononeuropathy from a 0.5- or 0.8-millisecond, or ms, prolongation of the median sensory-evoked peak latency compared to the ulnar latency. They diagnosed CTS if the subject also had accompanying symptoms of numbness, tingling or pain. RESULTS: Thirteen percent of screened dentists were diagnosed with a median mononeuropathy (using a 0.5-ms prolongation as the criterion), but only 32 percent of these had symptoms consistent with CTS (4.8 percent overall). When the 0.8-ms prolongation was used as the electrodiagnostic criterion, only 2.9 percent (overall) were diagnosed with CTS. People with diabetes, rheumatoid arthritis and obesity were more likely to have a median mononeuropathy. CONCLUSIONS: The prevalence of symptoms consistent with CTS in the dominant hand among dentists was higher than the prevalence in the general population. However, when electrodiagnostic confirmation is added, the prevalence of CTS was nearly the same as that among the general population. CLINICAL IMPLICATIONS: Early recognition of CTS can lead to more effective management. Education regarding ergonomic risk factors can be an effective preventive measure.

Effects of permethrin on aquatic organisms in a freshwater stream in south-central Alaska.

Permethrin (0.5%) was applied to individual Lutz spruce, Picea x lutzii Little, to protect them from attack by spruce beetles, Dendroctonus rufipennis (Kirby). Residue levels were monitored in a freshwater stream above, adjacent to, and below the treatment site at intervals before, during, and after treatment. Maximum residue levels in the stream within the treatment site ranged from 0.05 +/- 0.01 ppb 5 h after treatment to 0.14 +/- 0.03 ppb 8-11 h after treatment, with a decrease to 0.02 +/- 0.01 ppb 14 h after treatment. Levels of permethrin in standing pools near the stream within the treatment site were 0.01 +/- 0.01 ppb. Numbers of drifting aquatic invertebrates increased 2-fold during treatment and 4-fold 3 h after treatment and declined to before spray numbers within 9 h. Terrestrial insects did not appear to respond to treatments because none was found in stream drift samples. Trout fry (Dolly Varden), aquatic insect larvae, and periphyton (attached algae) within and below the treatment site during and after treatment did not show signs of mortality compared with an upstream untreated control site.

Paraplegia and quadriplegia after intrathecal chemotherapy.

Transient or permanent paraplegia after the use of intrathecal (IT) methotrexate (MTX) or cytosine arabinoside (Ara-C) for treatment or prophylaxis of patients with meningeal leukemia is an unusual complication, with an incidence of less than 3% among such patients. Only 15 cases involving IT MTX have been documented and even fewer with IT Ara-C. Three patients were studied who developed permanent or ascending myelopathy from treatment of their leukemia or rhabdomyosarcoma with IT chemotherapy. The patients' ages ranged from 7 to 62 years. Two of the three patients had electromyographic examinations. These revealed a primary motor neuron degeneration or a polyradiculopathy, superimposed on a mild axonal peripheral neuropathy associated with vincristine therapy. This is consistent with other electromyographic studies. Two of the patients showed an elevation of the cerebral spinal fluid (CSF) protein before development of paraplegia; one also showed a rise in myelin basic protein associated with his myelopathy. Neuropathologic findings suggest demyelination as the primary process leading to myelopathy. Increasing evidence has shown that total CSF protein, or more specifically, the myelin basic protein, may be elevated before development of paraplegia. Routine serial testing of the CSF for total protein could be used as a screening test during therapy.