Genomic data reveal ancient microendemism in forest scorpions across the California Floristic Province.

The California Floristic Province (CFP) in western North America is a globally significant biodiversity hotspot. Elucidating patterns of endemism and the historical drivers of this diversity has been an important challenge of comparative phylogeography for over two decades. We generated phylogenomic data using ddRADseq to examine genetic structure in Uroctonus forest scorpions, an ecologically restricted and dispersal-limited organism widely distributed across the CFP north to the Columbia River. We coupled our genetic data with species distribution models (SDMs) to determine climatically suitable areas for Uroctonus both now and during the Last Glacial Maximum. Based on our analyses, Uroctonus is composed of two major genetic groups that likely diverged over 2 million years ago. Each of these groups itself contains numerous genetic groups that reveal a pattern of vicariance and microendemism across the CFP. Migration rates among these populations are low. SDMs suggest forest scorpion habitat has remained relatively stable over the last 21 000 years, consistent with the genetic data. Our results suggest tectonic plate rafting, mountain uplift, river drainage formation and climate-induced habitat fragmentation have all likely played a role in the diversification of Uroctonus. The intricate pattern of genetic fragmentation revealed across a temporal continuum highlights the potential of low-dispersing species to shed light on small-scale patterns of biodiversity and the underlying processes that have generated this diversity in biodiversity hotspots.

The safe practice of CT coronary angiography in adult patients in UK imaging departments.

Computed tomography coronary angiography is increasingly used in imaging departments in the investigation of patients with chest pain and suspected coronary artery disease. Due to the routine use of heart rate controlling medication and the potential for very high radiation doses during these scans, there is a need for guidance on best practice for departments performing this examination, so the patient can be assured of a good quality scan and outcome in a safe environment. This article is a summary of the document on 'Standards of practice of computed tomography coronary angiography (CTCA) in adult patients' published by the Royal College of Radiologists (RCR) in December 2014.

Using multilevel spatial models to understand salamander site occupancy patterns after wildfire.

Studies of the distribution of elusive forest wildlife have suffered from the confounding of true presence with the uncertainty of detection. Occupancy modeling, which incorporates probabilities of species detection conditional on presence, is an emerging approach for reducing observation bias. However, the current likelihood modeling framework is restrictive for handling unexplained sources of variation in the response that may occur when there are dependence structures such as smaller sampling units that are nested within larger sampling units. We used multilevel Bayesian occupancy modeling to handle dependence structures and to partition sources of variation in occupancy of sites by terrestrial salamanders (family Plethodontidae) within and surrounding an earlier wildfire in western Oregon, USA. Comparison of model fit favored a spatial N-mixture model that accounted for variation in salamander abundance over models that were based on binary detection/non-detection data. Though catch per unit effort was higher in burned areas than unburned, there was strong support that this pattern was due to a higher probability of capture for individuals in burned plots. Within the burn, the odds of capturing an individual given it was present were 2.06 times the odds outside the burn, reflecting reduced complexity of ground cover in the burn. Ther was weak support that true occupancy was lower within the burned area. While the odds of occupancy in the burn were 0.49 times the odds outside the burn among the five species, the magnitude of variation attributed to the burn was small in comparison to variation attributed to other landscape variables and to unexplained, spatially autocorrelated random variation. While ordinary occupancy models may separate the biological pattern of interest from variation in detection probability when all sources of variation are known, the addition of random effects structures for unexplained sources of variation in occupancy and detection probability may often more appropriately represent levels of uncertainty.

[Malignant hypertension and pheochromocytoma: a case report]. / Hipertensión maligna y feocromocitoma: reporte de un caso.

Malignant arterial hypertension is defined by extremely high levels of pressure associated with organ damage. It is a cause of hypertensive emergency and is defined by the coexistence of high blood pressure and bilateral retinal haemorrhage or exudates (grade III hypertensive retinopathy), with or without papilloedema (grade IV hypertensive retinopathy) currently associated with organ damage such as renal or cardiac failure. Around 1% of malignant arterial hypertension is secondary to endocrinological causes, including the most common: pheochromocytoma, which is classically characterized by the triad: headache, sweating and palpitations. However, there is no single clinical finding that is of significant value in its diagnosis. We now present the case of a 23-year-old patient with a hypertensive emergency, an adrenal mass associated with grade IV hypertensive retinopathy.

Saprolegniaceae identified on amphibian eggs throughout the Pacific Northwest, USA, by internal transcribed spacer sequences and phylogenetic analysis.

We assessed the diversity and phylogeny of Saprolegniaceae on amphibian eggs from the Pacific Northwest, with particular focus on Saprolegnia ferax, a species implicated in high egg mortality. We identified isolates from eggs of six amphibians with the internal transcribed spacer (ITS) and 5.8S gene regions and BLAST of the GenBank database. We identified 68 sequences as Saprolegniaceae and 43 sequences as true fungi from at least nine genera. Our phylogenetic analysis of the Saprolegniaceae included isolates within the genera Saprolegnia, Achlya and Leptolegnia. Our phylogeny grouped S. semihypogyna with Achlya rather than with the Saprolegnia reference sequences. We found only one isolate that grouped closely with S. ferax, and this came from a hatchery-raised salmon (Idaho) that we sampled opportunistically. We had representatives of 7-12 species and three genera of Saprolegniaceae on our amphibian eggs. Further work on the ecological roles of different species of Saprolegniaceae is needed to clarify their potential importance in amphibian egg mortality and potential links to population declines.

Elimination of enoxacin in renal disease.

The elimination of enoxacin was investigated in 15 subjects, 10 of whom were hospital outpatients with renal disease and varying degrees of renal impairment. Each was given enoxacin orally (200 mg b.i.d.) for 7 days. Blood specimens collected over 24 hours after the final dose of enoxacin and urine collected during the 12-hour dose interval after the final dose were assayed for enoxacin by HPLC. The elimination half-life of enoxacin increased with worsening renal function. In general, patients with diminished renal function had lower plasma enoxacin clearance values than had normal subjects, and a statistically significant correlation between apparent oral clearance and creatinine clearance was observed. Excretion of enoxacin by the kidney accounted for 26% to 72% of the apparent plasma clearance in normal subjects. This was markedly reduced in patients with severe renal failure.

Disposition of intravenous glycofurol: effect of hepatic cirrhosis.

The disposition of intravenous glycofurol, a solvent for some drugs, was followed in nine male patients with hepatic cirrhosis. In comparison with age-matched controls, glycofurol clearance in the patients with cirrhosis was reduced 43% and terminal t 1/2 was prolonged 103%. There was no significant difference between the cirrhotic and control groups in volume of distribution.

Elimination of amphotericin B in impaired renal function.

The influence of impaired renal function on the steady-state plasma clearance of amphotericin B was determined in seven patients with creatinine clearances ranging from zero to normal. Contrary to previous reports, steady-state plasma concentrations of total drug were lower in uremic patients than in patients with normal renal function. Total plasma clearance of amphotericin B ranged from 16.7 to 39.9 ml/min, correlated directly with the plasma creatinine concentration, and correlated inversely with the creatinine clearance. Urinary excretion of unchanged drug accounted for less than 10% of the dose. In 10 healthy subjects, mean percent of amphotericin B unbound in plasma was 3.55 +/- 0.32 (SD). Binding was determined in a further group of 10 uremic patients. Mean unbound percent (4.15 +/- 0.73, SD) was higher than in the healthy subjects, and the binding ratio (molar concentration of bound to unbound drug) correlated weakly with the creatinine clearance. This suggests that plasma clearance of unbound amphotericin B and, therefore, steady-state plasma concentrations of unbound drug are not affected by renal impairment, and that dosage requirements will be overestimated if based on measurements of total drug plasma concentration.

Effects of cimetidine and ranitidine on hepatic drug metabolism.

Cimetidine has been shown to impair elimination of a number of drugs metabolized by the hepatic mixed-function oxidase enzymes. It is uncertain whether this is related to its histamine H2-receptor antagonism or to its intrinsic structure. Ranitidine is a more potent H2-receptor antagonist and has a completely different structure. Cimetidine (1 gm/day for 7 days) induced a 23% and 35% fall in mean systemic clearance of antipyrine and theophylline, whereas ranitidine (300 mg/day 7 days) had no significant effect on the clearance of either drug. Our data suggest that the inhibition of drug metabolism by cimetidine is not related to histamine H2-receptor antagonism.

The effects of dose and route of administration on the pharmacokinetics of granulocyte-macrophage colony-stimulating factor.

The pharmacokinetics of granulocyte-macrophage colony stimulating factor (GM-CSF) (0.3-30 micrograms/kg) were studied after subcutaneous bolus (n = 16) or intravenous bolus (n = 5) injection or 2 h intravenous infusion (n = 12). Each method of administration gave a different GM-CSF concentration-time profile. Highest peak serum concentrations (Cmax) followed the intravenous bolus, and the time GM-CSF persisted at a concentration greater than 1 ng/ml (t greater than 1 ng/ml) was longer after a subcutaneous than after an intravenous injection. Area under the concentration-time curve (AUC), Cmax and t greater than 1 ng/ml all increased with dose for each method of administration. After intravenous administration, there was a two-phase decline in concentration. The half-life (t1/2) of the terminal phase following an intravenous bolus ranged from 0.24 to 1.18 h and, following intravenous infusion, from 0.62 to 9.07 h and appeared to increase with dose. The apparent clearance was greatest following subcutaneous injection at doses below 3 micrograms/kg, suggesting a saturable mechanism or different bioavailability. Only 0.001%-0.2% of the injected dose appeared in the urine as immunoreactive GM-CSF.

Biological activity of C-terminal partial sequences of substance P.

Substance P (Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2) and the C-terminal partial sequences down to the tripeptide were synthesized by a solid-phase method. These peptides were assayed for vasodilator, spasmogenic, and venoconstrictor properties using three preparations, viz. the hind limb blood flow of the dog, isolated guinea pig ileum, and the isolated rabbit ear vein. The tripeptide and tetrapeptide possessed weak vasodilator properties only but no activity was detected on the other less sensitive preparations. The pentapeptide produced appreciable spasmogenic and vasoactive effects. Sequences of six or more C-terminal amino acids were able to elicity activity at comparable doses to that of the parent endecapeptide; however, the activity did not increase regularly with the chain length. In each assay preparation the octapeptide was the most potent peptide. It was twice as potent as substance P on a molar basis in the guinea pig ileum but the enhancement of activity beyond that of substance P was less pronounced in the vascular preparations.

The stability of synthetic substance P in blood.

Experiments with synthetic substance P incubated in whole blood show that apart from a moderate loss of activity immediately on exposure of the peptide to whole blood, it is inactivated slowly in this tissue, approximately 25% of control activity remaining after 30 min incubation. Incubation with plasma did not result in the degradation of substance P. The attenuation of substance P activity in blood may be due to enzymatic destruction within erythrocytes.

Cardiovascular effects of synthetic substance P in several species.

In dogs anaesthetised with chloralose, infusion of synthetic substance P into the femoral artery caused marked elevation of femoral arterial blood flow which was well sustained during the infusion period. Doses less than 59 fmol/kg/min increased femoral arterial flow only, but larger doses caused transient hypotension accompanied by tachycardia. The administration of substance P by i.v. and intravertebral (i.vert.) arterial routes caused hypotension and tachycardia of similar pattern and magnitude to those produced by intrafemoral (i.f.) arterial infusion of equivalent doses. I.v. injection of substance P into rats and rabbits caused qualitatively similar cardiovascular effects to those in dogs, but higher doses were required for threshold responses. Substance P had little effect on the spontaneously beating isolated guinea-pig heart. Like many other vasodilator substances in vivo, substance P caused constriction of the isolated perfused ear vein from the rabbit. The results suggest that the major cardiovascular effect of synthetic substance P is vasodilatation and that a direct action on vascular smooth muscle is involved.

Adhesion prevention by solutions of sodium carboxymethylcellulose in the rat. I.

Solutions of sodium carboxymethylcellulose (SCMC) were studied in rats to determine their longevity within the peritoneal cavity and their potential for prevention of postoperative intraperitoneal adhesions. In 18 rats, test solutions of SCMC and 10% dextran 40 were instilled at laparotomy. At 48 hours copious amounts of SCMC remained, whereas no 10% dextran 40 could be detected. In addition, standardized surgical injury was produced on the ceca of 100 rats at laparotomy. All control animals had significant adhesions at 2 weeks. Eighty-two percent of the 10% dextran 40 group had significant adhesions, while only 16% of the 0.9 wt% SCMC and 17% of the 1.0 wt% SCMC groups had significant adhesions. Solutions of SCMC were significantly more effective than 10% dextran 40 in the prevention of adhesions (P less than 0.001). Properties of SCMC and a possible mechanism for its striking effectiveness in adhesion prevention in this study are discussed.

Threshold contrast detail detectability measurement of the fluoroscopic image quality of a dynamic solid-state digital x-ray image detector.

Solid-state digital x-ray imaging detectors of flat-panel construction will play an increasingly important role in future medical imaging facilities. Solid-state detectors that will support both dynamic (including fluoroscopic) and radiographic image recording are under active development. The image quality of an experimental solid-state digital x-ray image detector operating in a continuous fluoroscopy mode has been investigated. The threshold contrast detail detectability (TCDD) technique was used to compare the fluoroscopic imaging performance of an experimental dynamic solid-state digital x-ray image detector with that of a reference image intensifier television (IITV) fluoroscopy system. The reference system incorporated Plumbicon TV. Results were presented as a threshold detection index, or H(T)(A), curves. Measurements were made over a range of mean entrance air kerma (EAK) rates typically used in conventional IITV fluoroscopy. At the upper and mid EAK rate range (440 and 220 nGy/s) the solid-state detector outperformed the reference IITV fluoroscopy system as measured by TCDD performance. At the lowest measured EAK rate (104 nGy/s), the solid-state detector produces slightly inferior TCDD performance compared with the reference system. Although not statistically significant at this EAK rate, the difference will increase as EAK is lowered further. Overall the TCDD results and early clinical experiences support the proposition that a current design of dynamic solid-state detector produces image quality competitive with that of modern IITV fluoroscopy systems. These findings encourage the development of compact and versatile universal x-ray imaging systems based upon solid-state detector technology to support R & F and vascular/interventional applications.

Enteral antibiotics for preventing necrotising enterocolitis in low birthweight or preterm infants.

BACKGROUND: Necrotising enterocolitis continues to be a problem, particularly in preterm neonates. There have been reports published suggesting that the use of enteral antibiotics may be effective as prophylaxis. This systematic review was undertaken to clarify the issue. OBJECTIVES: To evaluate the benefits and harms of enteral antibiotic prophylaxis for necrotising enterocolitis in low birth weight and preterm infants. SEARCH STRATEGY: Searches were made of the Oxford Database of Perinatal trials, MEDLINE (search terms: necrotizing enterocolitis, antibiotics; LIMITS: newborn infant), previous reviews with cross references, abstracts, conference and symposia proceedings, expert informants and journal handsearching in the fields of Neonatal Pediatrics and Microbiology. SELECTION CRITERIA: All randomized or quasi-randomized controlled trials where enteral antibiotics were used as prophylaxis against NEC in LBW (<2500g) and/or preterm (<37 weeks gestation) infants. DATA COLLECTION AND ANALYSIS: The standard method of the Cochrane Collaboration and its Neonatal Review Group was used. The methodological quality of each trial was reviewed by the second author who was blinded to the trial authors and institutions. Each author extracted data separately before comparison and resolution of differences. Relative risk (RR), risk difference (RD), and number needed to treat were used in the analysis. MAIN RESULTS: The administration of prophylactic enteral antibiotics resulted in a statistically significant reduction in NEC [RR 0.47 (0.23, 0.98); RD -0.072 (-0.136, -0.008); NNT 13.9 (7.4, 125)]. There was a reduction in NEC-related deaths which was of borderline statistical significance [RR 0.16 (0.02, 1.26); RD -0.097 (-0.183, -0.010); NNT 10.3 (5.46, 100)]. There were no significant differences in all deaths (one trial only) or in NEC-like enteropathies (one trial only). There was a statistically significant increase in the incidence of colonisation with resistant bacteria [RR 1.73 (1.00, 2. 97); RD 0.123 (0.008, 0.238); NNT 8.1 (4.2, 125)]. REVIEWER'S CONCLUSIONS: There is insufficient evidence to support the use of enteral antibiotic prophylaxis for NEC in clinical practice. To address this question further, a large trial would be required with a sample size sufficient to examine all the important benefits and harms. Adverse outcomes associated with infection, particularly with resistant bacteria, should be evaluated.

Enteral antibiotics for preventing necrotizing enterocolitis in low birthweight or preterm infants.

BACKGROUND: Necrotizing enterocolitis continues to be a problem, particularly in preterm neonates. There have been reports published suggesting that the use of enteral antibiotics may be effective as prophylaxis. This systematic review was undertaken to clarify the issue. OBJECTIVES: To evaluate the benefits and harms of enteral antibiotic prophylaxis for necrotizing enterocolitis in low birth weight and preterm infants. SEARCH STRATEGY: Searches were made of the Oxford Database of Perinatal trials, MEDLINE (1966 - June 2000; search terms: necrotizing enterocolitis, antibiotics; limits: newborn infant), previous reviews with cross references, abstracts, conference and symposia proceedings, expert informants and journal hand searching in the fields of neonatal pediatrics and microbiology. SELECTION CRITERIA: All randomized or quasi-randomized controlled trials where enteral antibiotics were used as prophylaxis against NEC in LBW (<2500g) and/or preterm (<37 weeks gestation) infants. DATA COLLECTION AND ANALYSIS: The standard method of the Cochrane Collaboration and its Neonatal Review Group was used. The methodological quality of each trial was reviewed by the second author who was blinded to the trial authors and institutions. Each author extracted data separately before comparison and resolution of differences. Relative risk (RR), risk difference (RD), and number needed to treat were used in the analysis. MAIN RESULTS: Five eligible trials involving 456 infants were included. The administration of prophylactic enteral antibiotics resulted in a statistically significant reduction in NEC [RR 0.47 (0.28, 0.78); RD -0.10 (-0.16, -0.04); NNT 10 (6, 25)]. There was a statistically significant reduction in NEC-related deaths [RR 0.32 (0.10, 0.96); RD -0.07 (-0.13, 0.01); NNT 14 (8, 100)]. There was a trend towards a reduction in all deaths which was not significant [RR 0.67(0.34, 1.32)]. There were no significant differences in NEC-like enteropathies (one trial only). One study found a statistically significant increase in the incidence of colonization with resistant bacteria and the summary analysis of three trials gave an increase which was just significant [RR 1.73 (1.00, 2.97); RD 0.07 (0.00, 0.13)]. REVIEWER'S CONCLUSIONS: Evidence suggests that oral antibiotics reduce the incidence of NEC in low birth weight infants. However concerns about adverse outcomes persist, particularly related to the development of resistant bacteria. To address this question further, a large trial would be required with a sample size sufficient to examine all the important benefits and harms. Adverse outcomes associated with infection should be evaluated, and microbiological studies looking for the development of resistant bacteria should be undertaken