Constipation associated with brumation? Intestinal obstruction caused by a fecalith in a wild red diamond rattlesnake (Crotalus ruber).

This report describes the fecalith-induced intestinal obstruction of a free-ranging red diamond rattlesnake (Crotalus ruber) and the snake's subsequent history following surgical removal of the fecalith. The captured snake exhibited an abnormally distended abdomen and an extremely hard mass, detected via palpation, near its vent. Coeliotomy yielded a 2.5-cm, 5-g fecalith from the large intestine. Microscopic dissection of the fecalith revealed no evidence of gastrointestinal parasitic worms. Subsequently, we implanted a radio-transmitter that allowed us to track the snake's movements for 7 months (until the radio signal vanished), indicating normal behaviour, complete recovery and good health apart from the obstruction. This observation suggests that fecalith development and intestinal obstruction represent potential risks of long-term faecal retention, an unusual physiological trait well documented among rattlesnakes and other stout, heavy-bodied terrestrial viperid snakes. Dehydration and decreased gut motility associated with brumation (≈hibernation) may predispose temperate snakes to fecalith formation. Regional drought and a small mammal diet with indigestible hairs might have also promoted fecalith formation in this specimen.

Predictors of early secondary IOL implantation after pediatric cataract surgery.

BACKGROUND: Pediatric aphakia may be treated conservatively with aphakic contacts or spectacles. Many families and surgeons opt for a secondary intraocular lens (IOL) when the child is older. In certain situations, pediatric aphakic patients must undergo implantation earlier than planned. The purpose of this study was to investigate how often and why early implantation occurs. METHODS: We retrospectively reviewed the medical records of consecutive patients who were left aphakic after cataract surgery in infancy and were seen at our institute at ≥4 years of age. Early implantation was defined as occurring at <4 years of age. RESULTS: A total of 175 patients fit inclusion criteria. We found that 22 of 90 patients (24%) with unilateral cataracts had undergone early secondary IOL implantation before 4 years of age compared to 10 of 85 patients (12%) with bilateral cataracts, a statistically significant difference in the relative risk of early implantation (OR 2.43 [95% CI 1.07-5.49]). Of our patients undergoing early implantation, 15 of 31 (44%) had Medicaid as the primary insurance provider, which is representative of the practice overall. In patients requiring early implantation, failure with contact lens accounted for 26 of 32 cases (81%), with 7 of 26 (27%) of these failures attributed to nonmedical reasons. CONCLUSIONS: Of the factors we analyzed, only the presence of unilateral aphakia was associated with increased risk of early IOL implantation in our study cohort.

Determination of the surface corrugation amplitude from classical atom scattering.

The energy landscape of an atomic or molecular projectile interacting with a surface is often described in terms of a corrugation function that gives the classical turning point as a function of position vector parallel to the surface. It is shown here that the relative height variation of the corrugation function for scattering of atoms under classical conditions can be determined by a measurement of the maximum intensity in energy-resolved scattering spectra as a function of surface temperature. This is demonstrated by developing a semiclassical quantum theory of atomic scattering from corrugated surfaces and then extending the theory to the classical limit of large incident energies and high surface temperatures. Comparisons of calculations with available data for Ar atom scattering determine the corrugation amplitude for a molten In surface to be about 29% of the mean interparticle spacing in the bulk liquid.

Phase I dose-escalation study to determine the safety, pharmacokinetics and pharmacodynamics of brivanib alaninate in combination with full-dose cetuximab in patients with advanced gastrointestinal malignancies who have failed prior therapy.

BACKGROUND: The objectives of this phase I study were to determine the safety, pharmacokinetics (PK), pharmacodynamics and efficacy of brivanib combined with full-dose cetuximab in patients with advanced gastrointestinal malignancies. METHODS: Patients with advanced gastrointestinal malignancies who had failed prior therapies received brivanib (320, 600 or 800 mg daily) plus cetuximab (400 mg m(-2) loading dose then 250 mg m(-2) weekly). Assessments included adverse events, PK, tumour response, 2[18F]fluoro-2-deoxyglucose positron-emitting tomography and K-Ras mutation analyses. RESULTS: Toxicities observed were manageable; the most common treatment-related toxicities (>10% of patients) were fatigue, diarrhoea, anorexia, increase in aspartate aminotransferase and alanine aminotransferase, acneiform dermatitis, headache, mucosal inflammation, nausea, dry skin, vomiting, hypertension, pruritus, proteinuria and weight loss. Of 62 patients, 6 (9.7%) had objective radiographic partial responses, with an overall response rate of 10%. Median duration of response was 9.2 months; median progression-free survival was 3.9 months. CONCLUSIONS: The acceptable toxicity profile and efficacy of brivanib observed in this study were promising. These findings are being further evaluated in a phase III study of brivanib plus cetuximab vs cetuximab alone in patients previously treated with combination chemotherapy for K-Ras wild-type advanced metastatic colorectal cancer.

Scattering of Xe from graphite.

Recently a series of experimental measurements for the scattering of Xe atoms from graphite has been reported for both energy-resolved spectra and angular distributions. This system is of fundamental interest because the projectile Xe atoms are considerably more massive than the carbon atoms making up the graphite surface. These measurements were initially analyzed using the hard cubes model and molecular dynamics simulations, and both treatments indicated that the scattering process was a single collision in which the incoming Xe atom interacted strongly with a large number of carbon atoms in the outermost graphite layer. In this work we analyze the data using a single scattering theory that has been shown to explain a number of other experiments on molecular beam scattering from surfaces. These calculations confirm that the scattering process is a single collision with an effective surface mass that is substantially larger than that of the basic graphite ring.

Angular intensity distribution of a molecular oxygen beam scattered from a graphite surface.

The scattering of the oxygen molecule from a graphite surface has been studied using a molecular beam scattering technique. The angular intensity distributions of scattered oxygen molecules were measured at incident energies from 291 to 614 meV with surface temperatures from 150 to 500 K. Every observed distribution has a single peak at a larger final angle than the specular angle of 45° which indicates that the normal component of the translation energy of the oxygen molecule is lost by the collision with the graphite surface. The amount of the energy loss by the collision has been roughly estimated as about 30-41% based on the assumption of the tangential momentum conservation during the collision. The distributions have also been analyzed with two theoretical models, the hard cubes model and the smooth surface model. These results indicate that the scattering is dominated by a single collision event of the particle with a flat surface having a large effective mass. The derived effective mass of the graphite surface for the incoming oxygen is 9-12 times heavier than that of a single carbon atom, suggesting a large cooperative motion of the carbon atoms in the topmost graphene layer.

A comparison of the compressive strength of various distal locking screw options in the treatment of tibia fractures with intramedullary nails.

Treatment of distal metaphyseal tibia fractures is often challenging. Newer tibial intramedullary (IM) nails are designed with a wider variety of distal locking options to offer greater stability in treating these fractures. In this study we attempted to determine the most biomechanically stable number and configuration of distal locking screws when treating distal metaphyseal tibia fractures with IM nails. A transverse osteotomy was created 4 cm from the tibial plafond in identical composite saw bones models (Type 43A fracture) as well as in human cadaveric bones. Each specimen was nailed using a tibial nail (Stryker T2). Distal locking was performed in one of the three configurations: (a) Group I: two screws in the medial lateral (ML) direction; (b) Group II: one ML screw and one screw in the anterior posterior (AP) direction; (c) Group 111: two ML screws and one AP screw. The specimens were then mounted onto a uniaxial material testing machine (Instron) and tested in compression. Our results showed that there was no statistical difference in the load-carrying capacity of Group 1 and Group II. This suggests that the treating surgeon can choose either of these two configurations depending on the wound or other considerations without sacrificing the compressive load-carrying capacity of the IM nail fixation. The load-carrying capacity of the Group III samples with these locking screws was higher than those of Group I & II, although this difference was not statistically significant. This work is being continued to compare the load-carrying capacity of the bone samples with the cortical thickness of bone. We also plan to examine the relationship between the load-carrying capacity of these surgical constructs with the bone mineral density of the metaphysis of these tibial specimens.

Bone compressive strength: the influence of density and strain rate.

The compressive strength of bone is proportional to the square of the apparent density and to the strain rate raised to the 0.06 power. This relationship is applicable to trabecular and compact bone, and provides clinical guidelines for predicting bone strength on the basis of x-ray and densitometric examination.

Subperiosteal expansion and cortical remodeling of the human femur and tibia with aging.

Increases with aging in subperiosteal dimensions and second moments of area (measures of bending and torsional rigidity) in femoral and tibial cross sections are documented in an archeological sample from the American Southwest. Significant differences between cross-sectional sites and between sexes in the pattern of cortical remodeling with age are also present. These differences appear to be related to variations in the stress or strain levels in different regions of the femur and tibia which result from in vivo mechanical loadings of the lower limb.

Durability of botulinum toxin treatment for axillary hyperhidrosis.

OBJECTIVES: Botulinum toxin injection effectively treats axillary hyperhidrosis. Durability estimates of 3-14 months, based on self re-referral may overestimate duration. Our objective was to determine treatment durability by active follow-up of patients. DESIGN: Audit of current practice. MATERIALS AND METHODS: Patients presenting with severe primary axillary hyperhidrosis were actively followed up for 24 months after intradermal injections of Botulinum Toxin A (Dysport 120 units/axilla). A 10-point Likert Scale (1=worst imaginable symptoms, 10=absolute resolution) and the Hyperhidrosis Disease Severity Score (HDSS) were used at 1 day and 3, 6, 12 and 24 months. We offered re-treatment when symptoms returned to the pre-intervention state. RESULTS: We treated 45 patients with a mean age of 29 (15-49) years of whom 36 (78%) were women. The median pre-treatment Likert score (i.q.r.) of 3 (2-3) improved to 10 (10-10) on day 1. Scores at 3 (n=44), 6 (n=43) and 12 (n=39) months were 10 (10-10), 8 (7.5-10), and 7 (5-8) respectively. The median 24-month score was 3 (3-6) for 35 patients, including 11 patients with scores >/=6 who have not required re-treatment. HDSS scores followed a similar pattern. CONCLUSIONS: Axillary botulinum toxin treatment is durable. Patients experience gradual return of symptoms between 6 and 24 months. A minority do not require re-treatment at this time.

Muon spin relaxation study of LaTiO(3) and YTiO(3).

We report muon spin relaxation (µSR) measurements on two Ti(3+) containing perovskites, LaTiO(3) and YTiO(3), which display long-range magnetic order at low temperature. For both materials, oscillations in the time dependence of the muon polarization are observed which are consistent with three-dimensional magnetic order. From our data we identify two magnetically inequivalent muon stopping sites. The µSR results are compared with the magnetic structures of these compounds previously derived from neutron diffraction and µSR studies on structurally similar compounds.

Whole body PD-1 and PD-L1 positron emission tomography in patients with non-small-cell lung cancer.

PD-L1 immunohistochemistry correlates only moderately with patient survival and response to PD-(L)1 treatment. Heterogeneity of tumor PD-L1 expression might limit the predictive value of small biopsies. Here we show that tumor PD-L1 and PD-1 expression can be quantified non-invasively using PET-CT in patients with non-small-cell lung cancer. Whole body PD-(L)1 PET-CT reveals significant tumor tracer uptake heterogeneity both between patients, as well as within patients between different tumor lesions.

Metabolism and evolution of Haemophilus influenzae deduced from a whole-genome comparison with Escherichia coli.

BACKGROUND: The 1.83 Megabase (Mb) sequence of the Haemophilus influenzae chromosome, the first completed genome sequence of a cellular life form, has been recently reported. Approximately 75 % of the 4.7 Mb genome sequence of Escherichia coli is also available. The life styles of the two bacteria are very different - H. influenzae is an obligate parasite that lives in human upper respiratory mucosa and can be cultivated only on rich media, whereas E. coli is a saprophyte that can grow on minimal media. A detailed comparison of the protein products encoded by these two genomes is expected to provide valuable insights into bacterial cell physiology and genome evolution. RESULTS: We describe the results of computer analysis of the amino-acid sequences of 1703 putative proteins encoded by the complete genome of H. influenzae. We detected sequence similarity to proteins in current databases for 92 % of the H. influenzae protein sequences, and at least a general functional prediction was possible for 83 %. A comparison of the H. influenzae protein sequences with those of 3010 proteins encoded by the sequenced 75 % of the E. coli genome revealed 1128 pairs of apparent orthologs, with an average of 59 % identity. In contrast to the high similarity between orthologs, the genome organization and the functional repertoire of genes in the two bacteria were remarkably different. The smaller genome size of H. influenzae is explained, to a large extent, by a reduction in the number of paralogous genes. There was no long range colinearity between the E. coli and H. influenzae gene orders, but over 70 % of the orthologous genes were found in short conserved strings, only about half of which were operons in E. coli. Superposition of the H. influenzae enzyme repertoire upon the known E. coli metabolic pathways allowed us to reconstruct similar and alternative pathways in H. influenzae and provides an explanation for the known nutritional requirements. CONCLUSIONS: By comparing proteins encoded by the two bacterial genomes, we have shown that extensive gene shuffling and variation in the extent of gene paralogy are major trends in bacterial evolution; this comparison has also allowed us to deduce crucial aspects of the largely uncharacterized metabolism of H. influenzae.

Comparison of alendronate and sodium fluoride effects on cancellous and cortical bone in minipigs. A one-year study.

Fluoride stimulates trabecular bone formation, whereas bisphosphonates reduce bone resorption and turnover. Fracture prevention has not been convincingly demonstrated for either treatment so far. We compared the effects of 1-yr treatment of 9-mo-old minipigs with sodium fluoride (NaF, 2 mg/kg/d p.o.) or alendronate (ALN, 4 amino-1-hydroxybutylidene bisphosphonate monosodium, 1 mg/kg/d p.o.) on the biomechanical and histomorphometric properties of pig bones. As expected, NaF increased and ALN decreased bone turnover, but in these normal animals neither changed mean bone volume. NaF reduced the strength of cancellous bone from the L4 vertebra, relative to control animals, and the stiffness (resistance to deformation) of the femora, relative to the ALN group. In the ALN-treated animals, there was a strong positive correlation between bone strength and L5 cancellous bone volume, but no such correlation was observed in the NaF group. Furthermore, the modulus (resistance to deformation of the tissue) was inversely related to NaF content and there was a relative decrease in bone strength above 0.25 mg NaF/g bone. Moreover, within the range of changes measured in this study, there was an inverse correlation between bone turnover, estimated as the percentage of osteoid surface, and modulus. These findings have relevant implications regarding the use of these agents for osteoporosis therapy.

Bacterial start site prediction.

With the growing number of completely sequenced bacterial genes, accurate gene prediction in bacterial genomes remains an important problem. Although the existing tools predict genes in bacterial genomes with high overall accuracy, their ability to pinpoint the translation start site remains unsatisfactory. In this paper, we present a novel approach to bacterial start site prediction that takes into account multiple features of a potential start site, viz., ribosome binding site (RBS) binding energy, distance of the RBS from the start codon, distance from the beginning of the maximal ORF to the start codon, the start codon itself and the coding/non-coding potential around the start site. Mixed integer programing was used to optimize the discriminatory system. The accuracy of this approach is up to 90%, compared to 70%, using the most common tools in fully automated mode (that is, without expert human post-processing of results). The approach is evaluated using Bacillus subtilis, Escherichia coli and Pyrococcus furiosus. These three genomes cover a broad spectrum of bacterial genomes, since B.subtilis is a Gram-positive bacterium, E.coli is a Gram-negative bacterium and P. furiosus is an archaebacterium. A significant problem is generating a set of 'true' start sites for algorithm training, in the absence of experimental work. We found that sequence conservation between P. furiosus and the related Pyrococcus horikoshii clearly delimited the gene start in many cases, providing a sufficient training set.

Muon-spin relaxation study of the double perovskite insulators Sr2 BOsO6 (B = Fe, Y, ln).

We present the results of zero-field muon-spin relaxation measurements made on the double perovskite insulators Sr2 BOsO6 (B = Fe,Y, In). Spontaneous muon-spin precession indicative of quasistatic long range magnetic ordering is observed in Sr2FeOsO6 within the AF1 antiferromagnetic phase for temperatures below [Formula: see text] K. Upon cooling below T2≈67 K the oscillations cease to be resolvable owing to the coexistence of the AF1 and AF2 phases, which leads to a broader range of internal magnetic fields. Using density functional calculations we identify a candidate muon stopping site within the unit cell, which dipole field simulations show to be consistent with the proposed magnetic structure. The possibility of incommensurate magnetic ordering is discussed for temperatures below TN = 53 K and 25 K for Sr2YOsO6 and Sr2InOsO6, respectively.

A novel human opsin in the inner retina.

Here we report the identification of a novel human opsin, melanopsin, that is expressed in cells of the mammalian inner retina. The human melanopsin gene consists of 10 exons and is mapped to chromosome 10q22. This chromosomal localization and gene structure differs significantly from that of other human opsins that typically have four to seven exons. A survey of 26 anatomical sites indicates that, in humans, melanopsin is expressed only in the eye. In situ hybridization histochemistry shows that melanopsin expression is restricted to cells within the ganglion and amacrine cell layers of the primate and murine retinas. Notably, expression is not observed in retinal photoreceptor cells, the opsin-containing cells of the outer retina that initiate vision. The unique inner retinal localization of melanopsin suggests that it is not involved in image formation but rather may mediate nonvisual photoreceptive tasks, such as the regulation of circadian rhythms and the acute suppression of pineal melatonin. The anatomical distribution of melanopsin-positive retinal cells is similar to the pattern of cells known to project from the retina to the suprachiasmatic nuclei of the hypothalamus, a primary circadian pacemaker.

Neurologic, computed cranial tomographic, and magnetic resonance imaging abnormalities in patients with small-cell lung cancer: further follow-up of 6- to 13-year survivors.

To determine the subsequent evolution of neurologic, neuropsychologic, and intracranial anatomic findings in long-term survivors of small-cell cancer, we repeated an evaluation done 4 years previously in patients 6 to 13 years after treatment. Fifteen patients were reevaluated with a history and physical examination, mental status examination, neuropsychologic testing, computed cranial tomographic (CCT) scans, and magnetic resonance imaging (MRI). All but one was ambulatory and none were institutionalized. Thirteen of 15 had neurologic complaints, 10 of 15 had an abnormal neurologic examination, seven of 14 had an abnormal mental status examination, 12 of 14 had abnormal neuropsychologic testing, 12 of 15 had abnormal CCT scans, and seven of 15 had white-matter abnormalities on MRI scans. No dramatic decline in performance status, functional status, neurologic symptoms, or neurologic examination occurred in these patients with 4 years of additional follow-up. More patients showed a decline in mental status examinations and neuropsychologic testing than demonstrated improvement. Anatomic studies showed no dramatic changes in the CCT scans and MRI confirmed these findings. From these data we conclude that there is a slow decline in neuropsychologic function in some of the patients surviving more than 6 years from a diagnosis of small-cell lung cancer. The anatomic abnormalities documented by CCT scans and MRI are more frequent in patients with abnormal neuropsychologic function.

Aminophylline fails to improve the outcome of cardiopulmonary resuscitation from prolonged ventricular fibrillation: a placebo-controlled, randomized, blinded experimental study.

OBJECTIVES: The purpose of this study was to evaluate systematically the effects of the adenosine antagonist aminophylline on resuscitation outcome in a canine model of postcardioversion nonperfusing rhythm. BACKGROUND: Theoretic considerations and experimental studies indicate that myocardial adenosine accumulation during prolonged ventricular fibrillation might play a significant role in postcardioversion asystole and electromechanical dissociation. A recent uncontrolled clinical trial has suggested that the adenosine antagonist aminophylline might improve the outcome of cardiopulmonary resuscitation from refractory bradyasystolic cardiac arrest. METHODS: Two placebo-controlled, randomized, blinded experimental studies were performed. In protocol 1 (20 dogs), ventricular fibrillation was induced and maintained for 7.5 min. Sixty seconds before cardioversion, dogs received 1 mg of epinephrine followed by 250 mg of aminophylline or placebo. In protocol 2 (20 dogs), dogs were cardioverted to electromechanical dissociation after 5 min of unsupported ventricular fibrillation. Sixty seconds later, all dogs received 1 mg of epinephrine followed by 250 mg of aminophylline or placebo. In both experiments, resuscitation efforts were continued until return of spontaneous circulation, or up to 30 min. The primary end point was survival to 1 h. RESULTS: In protocol 1, 4 of 10 dogs survived in the aminophylline group, whereas 7 of 10 dogs survived in the placebo group, a nonsignificant trend toward unfavorable outcome from aminophylline. Pretreatment with aminophylline increased the number of cardioversion applications required to terminate ventricular fibrillation. In protocol 2, 5 of 10 and 6 of 10 dogs survived in the aminophylline and placebo groups, respectively. CONCLUSIONS: The results of this study suggest that aminophylline fails to improve the outcome of resuscitation from prolonged ventricular fibrillation. It does not reverse established electromechanical dissociation and may in fact increase the number of cardioversion applications required to terminate ventricular fibrillation. The rationale for conducting clinical trials with aminophylline during cardiopulmonary resuscitation is questionable.

Mechanical properties of trabecular bone within and adjacent to osseous metastases.

Despite radiographic and histologic evidence of trabecular bone density changes within and adjacent to osseous metastases, there currently exist no data to demonstrate whether these changes are important in predicting the risk of fracture. To determine if these density changes result in significant reductions in mechanical properties, trabecular bone specimens were prepared from lower thoracic and lumbar vertebrae from two cadavers with radiographic, gross, and histologic evidence of lytic and/or blastic osseous metastases. Each specimen was classified as normal, lytic, or blastic based on appearance in fine-grain radiographs of 8-9 mm thick coronal plane sections. Specimens were tested to failure in uniaxial compression, and tissue and apparent densities were measured. Mean tissue densities were within normal ranges. The mean apparent density for all specimens combined was within the normal range for human vertebrae, and the mean apparent density for radiographically normal (0.131 g/ml) and lytic (0.111 g/ml) specimens was less than the mean apparent density of blastic (0.182 g/ml) specimens (p < 0.02). The moduli of lytic and blastic specimens were less than for normal specimens (p < 0.025). The strength of lytic specimens was less than normal (p = 0.057), but the strength of blastic specimens was not (p > 0.1). Apparent density explained significant fractions of the variations in both modulus (p < 0.001) and strength (p < 0.001). The data suggest that blastic changes associated with osseous metastases to trabecular bone disrupt the normal dependence of trabecular mechanical properties on apparent density, but lytic changes do not.(ABSTRACT TRUNCATED AT 250 WORDS)