Tobacco-specific N-nitrosamines NNN and NNK levels in cigarette brands between 2000 and 2014.

The evolution of the levels of tobacco-specific N-nitrosamines (TSNA), N-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in mainstream (MS) cigarette smoke is investigated based on smoke and tobacco chemistry data of cigarette brands sold by Philip Morris International (PMI) between 2000 and 2014. A total of 315 cigarette samples representing a wide range of product and design characteristics manufactured by PMI between 2008 and 2014 were analyzed and compared to a previously published dataset of PMI brands manufactured in 2000. The data indicate that there is a substantial reduction of NNN and NNK levels in tobacco fillers and MS cigarette smoke per mg of tar and per mg of nicotine using Health Canada Intense (HCI) machine-smoking regime. This observed reduction in NNN and NNK levels in MS cigarette smoke is also supported by the downward trend observed on NNN and NNK levels in USA flue-cured Virginia and Burley tobacco lots from 2000 to 2014 crops, reflecting effectiveness of measures taken on curing and agricultural practices designed to minimize TSNA formation in tobacco.

Association between neuraxial analgesia, cancer progression, and mortality after radical prostatectomy: a large, retrospective matched cohort study.

BACKGROUND: Systemic opioids are immunosuppressive, which could promote tumour recurrence. We, therefore, test the hypothesis that supplementing general anaesthesia with neuraxial analgesia improves long-term oncological outcomes in patients having radical prostatectomy for adenocarcinoma. METHODS: Patients who had general anaesthesia with neuraxial analgesia (n=1642) were matched 1:1 based on age, surgical year, pathological stage, Gleason scores, and presence of lymph node disease with those who had general anaesthesia only. Medical records were reviewed. Outcomes of interest were systemic cancer progression, recurrence, prostate cancer mortality, and all-cause mortality. Data were analysed using stratified proportional hazards regression, the Kaplan-Meier method, and log-rank tests. The median follow-up was 9 yr. RESULTS: After adjusting for comorbidities, positive surgical margins, and adjuvant hormonal and radiation therapies within 90 postoperative days, general anaesthesia only was associated with increased risk for systemic progression [hazard ratio (HR)=2.81, 95% confidence interval (CI) 1.31-6.05; P=0.008] and higher overall mortality (HR=1.32, 95% CI 1.00-1.74; P=0.047). Although not statistically significant, similar findings were observed for the outcome of prostate cancer deaths (adjusted HR=2.2, 95% CI 0.88-5.60; P=0.091). CONCLUSIONS: This large retrospective analysis suggests a possible beneficial effect of regional anaesthetic techniques on oncological outcomes after prostate surgery for cancer; however, these findings need to be confirmed (or refuted) in randomized trials.

Obesity trends in the surgical population at a large academic center : a comparison between 1989-1991 to 2006-2008 epochs.

BACKGROUND: Changes in the prevalence of obesity of surgical patients overtime and in relation to the general population have not been well characterized. METHODS: Height, weight, age and gender data of adult patients who underwent general anesthesia at our institution were abstracted. Reliable data was available for the years 1989-1991 and 2006-2008, and comparisons were made between these epochs. Additional comparisons were made between our Minnesota surgical patients and the general Minnesota population. RESULTS: Substantial changes in patient weight occurred with a decline in normal weight patients (body mass index [BMI] < or =25.0) from 41.6% to 30.9% (P <0.001), while the prevalence of obesity (BMI 30-34.9) increased from 14.9% to 20.6% (P <0.001) and morbidly obesity (BMI > 35) from 7.1% to 14.8% (P <0.001). Minnesota surgical patients had a higher prevalence of obesity in every demographic category (P <0.001) compared to the general population. CONCLUSION: A substantial increase in the prevalence of obesity and morbid obesity among surgical patients at our institution occurred and the prevalence of obesity in our contemporary practice is higher than the general population. These observations most likely have profound implications on healthcare delivery resources, though its impact has yet to be determined.

Accumulation of toxicants in tadpoles of the common frog (Rana temporaria) in high mountains.

We analyzed the accumulation of inorganic and organic toxicants in tadpoles from nine populations of the common frog (Rana temporaria) at different altitudes of the Hohe Tauern National Park in Austria). Lead and cadmium concentrations in tadpoles increased with the acidity and metal-to-HCO3(-) ratio in the water exceeding those found in tadpoles from agricultural areas. Organochlorines (DDTs, polychlorinated biphenyls, lindane) and polyaromatic hydrocarbons were present in all of the populations, but only DDTs accumulated significantly compared with the concentrations in their diet.

Dating of ballpoint pen ink.

In this paper we describe a case in which a cash book, dated of the year 2000, was sent to the Forensic Science Division, Document Laboratory, Zurich Canton Police in March 2003. The questioned document was a list of 29 pages containing a consecutive handwritten numbering and dated entries (payments) made of blue ballpoint pen ink. By definition, a cash book has to be written by hand and the entries have to be made daily. The questioned document was suspected to have been written within a short period (e.g., a few hours) and backdated. The document lab was asked to determine the date of the entries of the questioned list. On one hand, we were asked, if the cash book had been kept on account consecutively during the period of one year, and on the other hand, the judges were interested in knowing, if the document could have been written in 2003 and back dated to 2000. To answer these questions, the document was examined for latent elements by electrostatic detection device (ESDA). The relative dating of the entries was performed by the quantification of the ballpoint pen ink dyes and their degradation products using HPLC. Results show that it is possible to determine the relative age of entries written by ballpoint pen within a relatively short time scale, if storage and supporting material of the different samples are the same or at least similar.

Anomia for people names in DAT--evidence for semantic and post-semantic impairments.

Proper name anomia is a frequent finding among patients in the early stages of Alzheimer's disease. The present study investigates naming of famous persons in a group of DAT patients, a group of persons with mild cognitive impairment (MCI) and healthy controls. The study is aimed at distinguishing the relative contributions of semantic and post-semantic factors to difficulties in proper name retrieval. As shown by a significantly lower score in answering semantic questions, DAT patients retrieve less biographical knowledge related to famous persons than healthy elderly subjects and persons with mild cognitive impairment. This finding is in line with the frequent observation of semantic deficits in early and moderate DAT. The high number of Tip-of-the-Tongue (TOT) answers in DAT found in relation to few spontaneously named items shows that post-semantic deficits are as important as semantic deficits in determining anomia for people names in DAT. Moreover, DAT patients were less sensitive to phonological cueing than healthy persons or persons with mild cognitive impairment. These findings suggest that proper name anomia in DAT is not only due to semantic deficits, but also to problems in accessing the phonological representation, as well as to a degradation of phonological representations. Thus, naming deficits in DAT differ not only quantitatively, but also qualitatively from the difficulties of healthy elderly persons. No significant differences were found between persons with mild cognitive impairment and healthy controls in proper name retrieval.

Reduction of stem growth and site dependency of leaf injury in Massachusetts black cherries exhibiting ozone symptoms.

Leaf ozone symptoms in natural ecosystems are increasingly reported but ozone effects on tree growth and the mediation of site conditions are still little documented. This study tests two hypotheses: (1) leaf injury in black cherry is associated with decline in radial growth, (2) symptoms are more prevalent on mesic sites. On sites supporting black cherry across Massachusetts, tree growth and leaf ozone injury were surveyed in 1996 using a randomized plot network established in the 1960s. Forty-seven percent of 120 trees sampled for ozone symptoms were symptomatic with generally low levels of injury. Over a 31-year period symptomatic trees had 28% lower stem growth rates than asymptomatic trees. Ozone symptom expression was enhanced in well growing stands on moister, cooler and more elevated sites. Ozone appeared to increase environmental stress and had a more pronounced effect on growth in better growing black cherry stands. This complicates management decisions as thinning increases growth and moisture availability.

Selective trapping of organochlorine compounds in mountain lakes of temperate areas.

The study of fish concentrations and sediment inventories in 19 European high mountain lakes (40-67 degrees N) shows that a fraction of organochlorine compounds (OCs), the less volatile compounds (LVC; subcooled liquid vapor pressure < or = 10(-2.5) Pa), are trapped in the higher locations. This general trend is not significantly influenced by possible local sources. Compound distribution is related to average air temperatures. The phase-change pseudoenthalpies calculated from the sediment inventories closely match the summed theoretical volatilization and dissolution enthalpies. This fractionation effect is responsible for the accumulation of high concentrations of the LVC, the more persistent and toxic according to literature data, in organisms inhabiting sites far from the locations of synthesis or use.

[Perimetry findings and driving performance. "How much visual field" does a motorist need?]. / Perimetriebefund und Fahrtauglichkeit. "Wieviel Gesichtsfeld" braucht ein Autofahrer?

OBJECTIVE: On 01-01-99 the new driving licence regulations came into force. Are the visual field criteria mentioned there sufficient for an adequate evaluation of driving fitness? METHODS: Typical (binocular) visual field defects were digitally superimposed onto photographs of traffic scenes to show the influence of such scotomata on visual perception. RESULTS: Exemplary cases clearly show that evaluation of visual field borders alone is not sufficient for evaluating driving fitness. They also prove that binocular scotomata affecting the (para-)central region of the visual field are of special importance to driving performance. The actual guidelines given by the traffic commission of the German Ophthalmological Society (DOG) and the legally defined limits will be critically discussed. CONCLUSION: From the ophthalmological point of view the actual visual field criteria of the new driving licence regulations do not seem to be sufficient for the evaluation of driving fitness: An additional consideration of (para-)central scotoma is mandatory. This publication provides recommendations for execution and interpretation of perimetric examinations for traffic ophthalmological purposes.

Photoprotection in tadpoles of the common frog, Rana temporaria.

The common frog, Rana temporaria, spawning at altitudes up to 2600 m, is potentially threatened by UVB radiation. In laboratory experiments we found a specifically UVB absorbing substance (UVAS) in the skin of tadpoles with maximum absorption between 290 and 300 nm. The production of UVAS is induced by both visible light and ultraviolet radiation. The concentrations of UVAS found in tadpoles from the field are about as high as those found in tadpoles from laboratory experiments with UVB radiation under simulated mid-summer conditions. The existence of two powerful sun screen factors (UVAS and melanin pigmentation) may explain the high resistance of R. temporaria tadpoles to the intensive UVB radiation at high altitudes.

Study of direct variable anesthesia costs in the dilatation and curettage patient.

This retrospective study was designed to compare the cost of anesthesia in three different groups of patients who received general anesthesia for a diagnostic dilatation and curettage procedure. The analysis included 194 patients, ASA physical status I, II, or III. All patients were outpatients with similar body mass index and age. The three groups were thiopental/isoflurane (n = 13), propofol/isoflurane (n = 126), and propofol/desflurane (n = 55). Anesthesia drugs, volatile agents, personnel costs, and type of providers were included in the cost comparison. The cost of supplies, inhalation agents, and drugs for the thiopental/isoflurane group were significantly different (P < .001) than the other two groups. The mean +/- SD thiopental/isoflurane combination was $7.00 +/- $2.74, whereas, the mean +/- SD cost of the propofol/isoflurane and propofol/desflurane groups was $12.73 +/- $3.57 and $14.40 +/- $5.05, respectively. The mean +/- SD cost of all three anesthetic drugs/volatile agents/endotracheal tube groups was $12.85 +/- $4.35. No statistically significant differences between the three groups were found in postanesthesia care unit (PACU) drug costs, anesthesia personnel cost, total direct anesthesia costs, or length of stay. The incidence of antiemetic administration intraoperatively and in PACU was significantly different (P < .001) between the thiopental/isoflurane group and the other groups. The thiopental/isoflurane group did not receive any antiemetics in either area, whereas the propofol groups received antiemetics 12.7% of the time. The three anesthesia providers, Certified Registered Nurse Anesthetists, student registered nurse anesthetists (SRNA), and anesthesia residents were reviewed looking at anesthesia supply cost, personnel cost, and total direct anesthesia costs. No statistically significant differences were found between the groups. We conclude that an anesthetic using thiopental/isoflurane is more cost-effective than propofol/desflurane or propofol/isoflurane anesthetics and the postoperative length of stay is no different for the three anesthetic approaches.

Origin of cadmium and lead in clear softwater lakes of high-altitude and high-latitude, and their bioavailability and toxicity to fish.

As a consequence of atmospheric deposition, effects of pollutants such as acidification and metal contamination are evident even in remote aquatic ecosystems of mountain and polar regions. Due to similar environmental characteristics (e.g., oligotrophy, low buffering capacity, long ice-cover, high precipitation rates), clearwater high altitude and high latitude lakes represent very sensitive ecosystems, which are extremely susceptible to even slight changes of the environment. Thus, the environmental relevance of Cd and Pb for both types of lakes is discussed in relation to their extraordinary sensitivity to environmental changes. The impact of Cd and Pb on fish from high altitude and high latitude lakes is reviewed and biotic and abiotic factors controlling bioavailability and toxicity of metals to fish are summarized. Apart from direct toxic effects of low pH, acidification increases the bioavailability of metals for fish. Furthermore, low concentrations of dissolved organic carbon and suspended particles take influence on the uptake and toxicity of metals in fish from clear high altitude and high latitude lakes. Since even very low concentrations of Cd and Pb may result in high metal concentrations in fish, evaluation of critical metal loads for clear high altitude and high latitude lakes is of major importance.

Analysis of immunoglobulin classes and subclasses in response to infection of Balb/cJ and C57BL/6J mice with Coxiella burnetii.

In order to establish defined immunological parameters for Q fever infection models, a microtitre enzyme-linked immunosorbent fluorescence assay (ELISA) was used for the first time to analyse the humoral immune response of Balb/cJ and C57BL/6J mice after experimental infection with Coxiella burnetii strain 'Nine Mile' in phase I. The experimental infection evoked a seroconversion in all mice within 10 days. Typically, the immune response measured against the whole-cell antigen showed an early increase of immunoglobulin (Ig) M followed by a later increase of the IgG subclasses. The IgA was low during the entire investigation period. Within the IgG subclasses only IgG2a and IgG2b gained higher values, whereby C57BL/6J mice produced high IgG2b titres and significantly lower IgG2a titres. In contrast, Balb/cJ mice developed IgG2a and IgG2b at equal levels. The use of partial antigens of C. burnetii demonstrated that the dominating IgG2b reaction of the C57BL/6J mice was directed against the lipopolysaccharide (LPS) of C. burnetii. This reaction was almost absent in Balb/cJ mice. In contrast, the SP27 protein antigen did not evoke different IgG2b reactions within the two breeds. No significant influence was observed within the two breeds in regard to sex or between hormone synchronized and non-hormone synchronized animals.

Decreased Susceptibility to Viral Disease of [beta]-1,3-Glucanase-Deficient Plants Generated by Antisense Transformation.

Antifungal class I [beta]-1,3-glucanases are believed to be part of the constitutive and induced defenses of plants against fungal infection. Unexpectedly, mutants deficient in these enzymes generated by antisense transformation showed markedly reduced lesion size, lesion number, and virus yield in the local-lesion response of Havana 425 tobacco to tobacco mosaic virus (TMV) and of Nicotiana sylvestris to tobacco necrosis virus. These mutants also showed decreased severity of mosaic disease symptoms, delayed spread of symptoms, and reduced yield of virus in the susceptible response of N. sylvestris to TMV. The symptoms of disease in the responses of both plant species were positively correlated with [beta]-1,3-glucanase content in a series of independent transformants. Taken together, these results provide direct evidence that [beta]-1,3-glucanases function in viral pathogenesis. Callose, a substrate for [beta]-1,3-glucanase, acts as a physical barrier to the spread of virus. Callose deposition in and surrounding TMV-induced lesions was increased in the [beta]-1,3-glucanase-deficient, local-lesion Havana 425 host, suggesting as a working hypothesis that decreased susceptibility to virus resulted from increased deposition of callose in response to infection. Our results suggest novel means, based on antisense transformation with host genes, for protecting plants against viral infection. These observations also raise the intriguing possibility that viruses can use a defense response of the host against fungal infection[mdash]production of [beta]-1,3-glucanases[mdash]to promote their own replication and spread.

Norepinephrine does not potentiate porcine malignant hyperthermia.

Malignant hyperthermia (MH) is a rare genetic trait characterized by potential life-threatening episodes of hypermetabolism, hyperthermia, and muscle rigidity when susceptible humans or animals are exposed to triggering drugs. The role of norepinephrine (NE) in triggering MH is controversial. The purpose of this study was to show that NE does not initiate nor speed the onset of MH in susceptible swine exposed to known triggering drugs. Three groups of MH susceptible (MHS) pigs were exposed to two times the minimum alveolar anesthetic concentrations (MAC) halothane (2%) for 60 min and monitored continuously until a PaCO2 of 70 mm Hg was obtained as an end point for fulminant MH. This dose of halothane is associated with significant hypotension which was addressed by three modalities: no treatment; NE infusion at 8 micrograms.kg-1.min-1; and intraaortic balloon pump (IABP) with 1:1 augmentation (7.0-mL balloon catheter). NE and epinephrine (Epi) plasma levels were determined at 15-min intervals and at trigger time. All animals developed signs of MH during the study. There was no difference in pHa, lactate, PaCO2, or temperature at control or trigger times between groups. Time to trigger was longer in the untreated group compared to both the NE and the IABP groups which were equal. The NE group had greater NE and Epi plasma levels at all times than either the untreated or IABP group and the levels increased at each sample time. The IABP group had increased NE levels at time of trigger compared to control time period, however, Epi levels did not increase. In the untreated group, individual animals had marked increases in NE levels, but extreme variability in response prevented achievement of a single mean change. This group showed no increase in plasma Epi levels throughout the study. There was no difference in NE levels between the untreated and IABP groups. Three animals in the untreated group died prior to trigger due to complications of hypotension. In conclusion, addition of exogenous NE in high doses did not enhance triggering of MH. The large dose NE infusion resulted in increased total catecholamines throughout the study in the NE group with no effect on time to MH trigger compared to animals where mean arterial pressure (MAP) was maintained by IABP. Animals in all three groups with times to trigger of less than 30 min had significantly higher MAPs at control, 15 min, and trigger time than those with times to trigger of greater than 30 min. We conclude that NE does not trigger MH and that severe reduction of MAP delays the the onset of MH in susceptible swine.

Metabolism of glucose, glycogen, and high-energy phosphates during transient forebrain ischemia in diabetic rats: effect of insulin treatment.

BACKGROUND: Hyperglycemia associated with diabetes mellitus will exacerbate neurologic injury after global brain ischemia. Studies in a rat model of forebrain ischemia (bilateral carotid occlusion plus hypotension for 10 min) discovered that acute restoration of normoglycemia in diabetics, using an insulin infusion, resulted in a neurologic outcome that was similar to normoglycemic rats without diabetes. The current study evaluated cerebral glucose, glycogen, lactate, and high-energy phosphate concentrations to identify metabolic correlates that might account for an alteration in postischemic outcome. METHODS: Fifty-four pentobarbital-anesthetized Sprague-Dawley rats were assigned to three groups: chronically hyperglycemic diabetic rats (D; N = 18); insulin-treated, acutely normoglycemic diabetic rats (ID; N = 18); and nondiabetic rats (ND; N = 18). These groups were further divided into groups of six rats each that received either no ischemia, forebrain ischemia of 10 min duration without reperfusion, or ischemia plus 15 min of reperfusion. Brains were excised after in situ freezing, and metabolites were measured using enzymatic fluorometric techniques. RESULTS: Before ischemia, D rats had greater concentrations of brain glucose (12.18 +/- 2.67 micromol/g) than did either ID (5.10 +/- 1.33) or ND (3.20 +/- 0.27) rats (P < 0.05). Preischemic brain glycogen was similar in all groups. At the completion of ischemia, brain lactate concentrations in D were 86% greater than in ID and 61% greater than in ND (P < 0.05), reflecting a higher intraischemic consumption of glucose plus glycogen in D (P < 0.05). High-energy phosphate concentrations, as assessed by the energy charge of the adenylate pool, were better preserved in D (energy charge = 0.60 +/- 0.28) than in either ID (0.29 +/- 0.09) or ND (0.36 +/- 0.07; P < 0.05) rats. After 15 min of reperfusion, the energy charge returned to preischemic values (i.e., 0.91-0.92) in all groups. CONCLUSIONS: These studies demonstrated greater intraischemic carbohydrate consumption and lactate production in D than in ID or ND rats. Under these conditions, intraischemic-but not postischemic-energy status was better in D rats. Acute insulin therapy in ID rats resulted in a metabolic profile that was similar to that of ND rats. These results suggest that, in this model, primary energy failure during ischemia is not the origin of greater injury in hyperglycemic diabetics, nor is energy enhancement the origin of improved outcome after acute insulin treatment.

The temporal relationship between intraocular pressure and extraocular muscle activation in cats.

The temporal relationship between intraocular pressure and extraocular muscle activation was studied in cats in response to the administration of the depolarizing muscle relaxant, succinylcholine (i.e. bolus doses of 0.1 and 1.0 mg/kg). Simultaneous changes in intraocular pressure, extraocular muscle force, extraocular electromyograms (EMGs), limb muscle EMGs and hindlimb muscle afferent activity were recorded. Increases in intraocular pressure were associated with extraocular muscle activation and had two components: (1) an initial abrupt increase (lasting seconds) which correlated with fasciculations within the extraocular and hindlimb muscles; and (2) a latter more sustained component (minutes) presumably due to tonic muscle activation which correlated with increases in hindlimb muscle afferent activity (e.g. due to sustained activation of bag 1 intrafusal fibers by succinylcholine). In a separate group of animals, in which the extraocular muscles were detached from the right eye bilateral intraocular pressures were measured: depolarization by succinylcholine caused a significant increase in intraocular pressure only for the eye with intact muscles. Thus, increases in intraocular pressure following the administration of succinylcholine are directly related to the changes in extraocular muscle tension which is dependent on both tonic and phasic muscle fiber responses.

Temperature changes of > or = 1 degree C alter functional neurologic outcome and histopathology in a canine model of complete cerebral ischemia.

BACKGROUND: Changes in basal temperature of > or = 1 degree C (e.g., fever-induced hyperthermia or anesthesia-related hypothermia) are a common occurrence in neurologically impaired patients. The current study tested the hypothesis that temperature changes as small as 1 degree C or 2 degrees C would significantly alter post-ischemic functional neurologic outcome and cerebral histopathology. The hypothesis was tested in a canine model of transient, complete cerebral ischemia. METHODS: After institutional approval, 21 dogs were randomly assigned to one of three temperature-specific groups: (1) a reference group maintained at 37.0 +/- 0.3 degree C (target temperature +/- range); (2) a 38.0 +/- 0.3 degree C group; or (3) a 39.0 +/- 0.3 degree C group (n = 7 per group). Complete cerebral ischemia 12.5 min in duration was produced using an established model of arterial hypotension plus intracranial hypertension. Right atrial and cranial (beneath the temporalis muscles) temperatures were maintained at the target value, beginning 20 min before ischemia and ceasing 1 h postischemia. Thereafter, temperatures were returned to 37.0 +/- 0.3 degree C in all dogs. After discharge from the intensive care environment, all dogs were placed in a temperature-controlled recovery area. Neurologic assessment was performed by a blinded observer at 24, 48, and 72 h postischemia using a 100-point scoring scale. After the 72 h examination (with the dogs anesthetized) or at the time of ischemia-related death, the brains were excised and preserved. The brains subsequently were histologically scored by a neuropathologist who was unaware of the treatment groups. All 21 dogs were included in the analysis of neurologic function; however, only dogs that survived for > or = 24 h postischemia were included in the histopathology analysis. RESULTS: Dogs were well matched for systemic physiologic variables throughout the study, with the exception of temperature. During the 72 h postischemic examination, dogs maintained at 37 degrees C were either normal or near normal. In contrast, dogs maintained at 39 degrees C were either comatose or died from ischemia-related causes. Dogs maintained at 38 degrees C were intermediate between 37 degrees C and 39 degrees C dogs. When compared with the reference group, both 38 degrees C and 39 degrees C dogs had significantly worse neurologic function scores (P < 0.01 and < 0.001, respectively) and histopathology scores (P < 0.01 for both). There also was a significant correlation between neurologic function and histopathology rank scores (rs = 0.96; P < 0.001). CONCLUSIONS: Small, clinically relevant changes in temperature (1 degree C or 2 degrees C) resulted in significant alterations in both postischemic neurologic function and cerebral histopathology. Assuming that our results are transferable to humans, the results suggest that, in patients at imminent risk for ischemic neurologic injury, body temperature should be closely monitored. Further, the clinician should aggressively treat all episodes of hyperthermia until the patient is no longer at risk for ischemic neurologic injury.