Abdominal Emergency After Subcutaneous ICD Implantation.

We describe a previously unreported and potentially fatal complication of colonic perforation following the implantation of a subcutaneous implantable cardioverter-defibrillator in a young patient with nonischemic cardiomyopathy. We discuss the importance of technique and postprocedural evaluation for subdiaphragmatic complications. This description emphasizes presenting complaints, early recognition, and management strategies. (Level of Difficulty: Beginner.).

A near miss: subclinical saddle pulmonary embolism diagnosed by handheld ultrasound.

INTRODUCTION: Pulmonary embolism (PE) is a life-threatening condition characterized by occlusive disease of the pulmonary vasculature. Point-of-care ultrasound (POCUS) of right ventricular strain patterns have high specificity and low sensitivity for diagnosis. Here, we describe a patient with a saddle PE and low pre-test probability who was diagnosed primarily by handheld POCUS. CASE REPORT: An 80-year old female was admitted to the intensive care unit with hypotension and lactic acidosis. She also had mild leukocytosis and troponinemia. No other clinical or metabolic abnormalities were present. After transfer to the floor, handheld POCUS demonstrated D-sign and McConnell's sign. Computed tomography angiography showed a saddle PE involving both main pulmonary arteries. The patient was immediately initiated on anticoagulation without further complications. CONCLUSION: Handheld POCUS is inexpensive, carries a low risk of harm and is an invaluable extension of the physical exam when interpreted in the appropriate context.

Left-sided infective endocarditis in persons who inject drugs.

PURPOSE: The purpose of this study was to describe left-sided infective endocarditis (LSIE) in persons who inject drugs (PWID) and compare that group to PWID with non-LSIE and to non-PWID with LSIE. METHODS: Retrospective single-center study of adult IE patients from 2011 to 2018. RESULTS: Of the 333 patients in our cohort, 54 were PWID with LSIE, 75 were PWID with non-LSIE, and 204 were non-PWID with LSIE. When comparing LSIE vs non-LSIE in PWID, the LSIE group was older (median age 35 vs 28.5, p < 0.01), had fewer S. aureus infections (59% vs 92%, p < 0.01), was more likely to have cardiac surgery (31% vs 13%, p < 0.01), and had a higher 10-week mortality (22% vs 5%, p < 0.01). When comparing PWID with LSIE to non-PWID with LSIE, the PWID group were younger (median age 35 vs 46, p < 0.01); had more frequent multi-valve involvement (33% vs 19%, p = 0.04), Staphylococcus aureus infections (54% vs 27%, p < 0.01), and previous IE (24% vs 8%, p < 0.01); and experienced more strokes (54% vs 31%, p < 0.01). Ten-week mortality was similar for LSIE in both PWID and non-PWID (24% vs 20%, p = 0.47). CONCLUSIONS: LSIE in PWID is not uncommon. Compared to non-LSIE in PWID, valve surgery is more common and mortality is higher. For reasons that are unclear, stroke is more frequent in LSIE in PWID than in non-PWID with LSIE but mortality is no different.

The Effect of Preexisting Anticoagulation on Cerebrovascular Events in Left-Sided Infective Endocarditis.

BACKGROUND: Stroke is a frequent complication of infective endocarditis, especially infection involving left-sided valves. Management of anticoagulation in left-sided infective endocarditis is controversial as it is unclear whether anticoagulation impacts stroke and bleeding risk in patients with this condition. The objective of this study was to evaluate the effect of anticoagulation on stroke occurrence and bleeding complications in patients with left-sided infective endocarditis. METHODS: Patients admitted to a tertiary academic hospital with left-sided infective endocarditis between December 2011 and April 2018 were identified. Patients were stratified based on receipt of therapeutic anticoagulation prior to admission. The primary outcome measure was the rate of radiographically confirmed stroke at 10 weeks. RESULTS: Two-hundred and fifty-eight consecutive patients with left-sided infective endocarditis were identified. Patients receiving anticoagulation (n = 50) were older (median age 63 vs 52; P = .02), were more likely to have a history of atrial fibrillation (22% vs 8.2%; P < .01), more often had prosthetic valves (38% vs 13.9%; P < .01), and had a lower incidence of mitral valve involvement (40% vs 62%; P < .01), compared with patients not receiving anticoagulation. There was no significant difference in the rate of stroke, cerebrovascular hemorrhage, or mortality at 10 weeks between the two cohorts. CONCLUSIONS: Preexisting anticoagulation did not appear to have an effect on stroke, cerebrovascular hemorrhage, or mortality in patients with left-sided infective endocarditis at 10 weeks. Continuation of anticoagulation in patients with a definitive preexisting indication should be considered in patients with left-sided infective endocarditis in the absence of other contraindications.

Bone loss with antiepileptic drug therapy: a twin and sibling study.

Changes in areal bone mineral density (aBMD) and other predictors of bone loss were evaluated in 48 same-sex twin/age-matched sibling pairs discordant for antiepileptic drug (AED) use. AED users had reduced BMD at the hip regions. Prolonged AED users had greater aBMD loss, predicting a higher risk of bone fragility. INTRODUCTION: To investigate the longitudinal associations of bone mineral measures with antiepileptic drug (AED) use, including enzyme-inducing (EIAED) and non-enzyme-inducing (NEIAED) types, and other predictors of bone loss in a study of 48 same-sex twin/age-matched sibling pairs (40 female, 8 male) discordant for AED use. METHODS: Using dual-energy X-ray absorptiometry (DXA), areal bone mineral density (aBMD) and content (BMC) at the hip regions, forearm, lumbar spine, and whole body were measured twice, at least 2 years apart. The mean within-pair difference (MWPD), MWPD%, and mean annual rate of aBMD change were adjusted for age, weight, and height. Predictors of bone loss were evaluated. RESULTS: AED users, compared to non-users, at baseline and follow-up, respectively, had reduced aBMD at the total hip (MWPD% 3.8, 4.4%), femoral neck (4.7, 4.5%), and trochanter regions (4.1, 4.6%) (p < 0.05). For the whole cohort, the annual rate of change in all aBMD/BMC (p > 0.05) regions did not differ within pairs. Nevertheless, EIAED users had greater aBMD loss than non-users (n = 20 pairs) at the total hip (1.7 vs. 0.3%, p = 0.013) and whole body regions (0.7% loss vs. 0.1% BMD gain, p = 0.019), which was not found in NEIAED-discordant pairs (n = 16). AED use >20 years predicted higher aBMD loss at the forearm (p = 0.028), whole body (p = 0.010), and whole body BMC (p = 0.031). CONCLUSIONS: AED users had reduced aBMD at the hip regions. Prolonged users and EIAED users had greater aBMD loss, predicting a higher risk of bone fragility. Further prospective studies of AED effects on bone microarchitecture are needed.

Pulsed resources affect the timing of first breeding and lifetime reproductive success of tawny owls.

1. According to life-history theory, environmental variability and costs of reproduction account for the prevalence of delayed reproduction in many taxa. Empirical estimates of the fitness consequences of different ages at first breeding in a variable environment are few however such that the contributions of environmental and individual variability remains poorly known. 2. Our objectives were to elucidate processes that underpin variation in delayed reproduction and to assess lifetime consequences of the age of first breeding in a site-faithful predator, the tawny owl Strix aluco L. subjected to fluctuating selection linked to cyclical variation in vole density (typically 3-year cycles with low, increasing and decreasing vole densities in successive years). 3. A multistate capture-recapture model revealed that owl cohorts had strikingly different juvenile survival prospects, with estimates ranging from 0.08 to 0.33 respectively for birds born in Decrease and Increase phases of the vole cycle. This resulted in a highly skewed population structure with >75% of local recruits being reared during Increase years. In contrast, adult survival remained constant throughout a vole cycle. The probability of commencing reproduction was lower at age 1 than at older ages, and especially so for females. From age 2 onwards, pre-breeders had high probabilities of entering the breeding population. 4. Variation in lifetime reproductive success was driven by the phase of the vole cycle in which female owls started their breeding career (26-47% of variance explained, whether based on the number of local recruits or fledglings), more than by age at first breeding or by conditions experienced at birth. Females who postponed reproduction to breed for the first time at age 3 during an Increase phase, produced more recruits, even when accounting for birds that may have died before reproduction. No such effects were detected for males. 5. Sex-specific costs of early reproduction may have accounted for females being more prone to delay reproduction. Contrary to expectations from a best-of-a-bad job strategy, early-hatched, hence potentially higher-quality females were more likely to breed at age 1, but then experienced rapidly declining food resources and so seemed caught in a life-history trap set by the multiannual vole cycle.

'Street ketamine'-associated bladder dysfunction: a report of ten cases.

Ten young ketamine abusers presented with lower urinary tract symptoms to two regional hospitals in Hong Kong. Investigations demonstrated contracted bladders and other urinary tract abnormalities. These types of findings have never been reported before in ketamine abusers. The possible aetiology is also discussed.

Anti-epileptic medication and bone health.

BACKGROUND: Epilepsy is a common chronic neurological disorder, usually requiring long-term treatment with anti-epileptic drugs (AED). Many studies have reported that AED therapy is associated with metabolic bone disease and is a major iatrogenic risk factor for fractures. There remains uncertainty about the type(s) of bone disease due to AED treatment, and the pathogenesis of AED-associated fractures. RATIONALE: Deficits in bone mineral density (BMD) are widely reported in AED-treated patient populations. However, much of the research conducted to date has been limited by factors such as small sample size, potentially biased subject selection, a lack of selection of appropriate control data, and failure to take account of important confounding influences. The pathogenesis of AED-associated fractures is likely to be multifactorial, due to factors including reduced BMD, impaired bone quality (due to osteoporosis and/or osteomalacia), increased propensity to fall, and fractures associated with seizures or loss of consciousness. RECOMMENDATIONS: Patients receiving long-term AED should be monitored for indices of bone health, including BMD and vitamin D status. Lifestyle factors should be optimized, vitamin D status maintained, and fall prevention strategies introduced as appropriate. Good seizure control is important. The use of additional, specific osteoporosis therapy is not evidence-based in this setting, but would appear reasonable in patients with clinically significant decreases in BMD, applying current treatment guidelines for osteoporosis. CONCLUSION: There is a pressing need for improved understanding of the pathogenesis of AED-associated bone disease, for better definition of the risk associated with specific AED regimens, and for the development of evidence-based preventive and treatment approaches in this common but neglected disorder.

Effect of antiepileptic medication on bone mineral measures.

OBJECTIVE: Long-term antiepileptic drug (AED) use has been associated with bone disease, but many previous studies have been limited by inadequate control subjects. We used a cotwin affected sib-pair model to investigate this issue. METHODS: The authors studied 31 female twin (15 monozygous and 16 dizygous) and four sibling pairs (< 3 years age difference) aged 21 to 75 years, in which one member had > 12 months of AED treatment. Areal bone mineral density (ABMD, g/cm2) was measured at the lumbar spine (LS), total hip (TH), femoral neck (FN), and total forearm (FA). Three primary a priori defined subgroups were analyzed: a) use for > 2 years, b) use of enzyme-inducing AEDs, or c) age older than 40 years. RESULTS: For all pairs (n = 35), there were no significant within-pair differences in any ABMD measure. However, in Subgroup a (n = 27), there was a within-pair difference at the FA (0.513 vs 0.534, -3.9%, p = 0.016). In Subgroup b (n = 29), there was also a within-pair difference at the FA for AED user vs nonuser (0.508 vs 0.529, -3.8%, p = 0.010). In Subgroup c (n = 15), there were within-pair differences at the FA (0.492 vs 0.524, -6.1%, p = 0.017) and the LS (0.884 vs 0.980, -9.8%, p = 0.036). CONCLUSIONS: Patients using AEDs for > 2 years, in particular those taking enzyme-inducing AEDs and those older than 40 years, have significantly lower bone mineral density at clinically relevant fracture risk sites.

Human milk lactoferrin is a serine protease that cleaves Haemophilus surface proteins at arginine-rich sites.

Lactoferrin is a member of the lactotransferrin family of non-haem, iron-binding glycoproteins and is found at high concentrations in all human secretions, where it plays a major role in mucosal defence. In recent work, we observed that lactoferrin has proteolytic activity and attenuates the pathogenic potential of Haemophilus influenzae by cleaving and removing two putative colonization factors, namely the IgA1 protease protein and the Hap adhesin. Experiments with protease inhibitors further suggested that lactoferrin may belong to a serine protease family. In the present study we explored the mechanism of lactoferrin protease activity and discovered that mutation of either Ser259 or Lys73 results in a dramatic decrease in proteolysis. Examination of the crystal structure revealed that these two residues are located in the N-terminal lobe of the protein, adjacent to a 12-15 A cleft that separates the N-lobe and the C-lobe and that can readily accommodate large polypeptide substrates. In additional work, we found that lactoferrin cleaves IgA1 protease at an arginine-rich region defined by amino acids 1379-1386 (RRSRRSVR) and digests Hap at an arginine-rich sequence between amino acids 1016 and 1023 (VRSRRAAR). Based on our results, we conclude that lactoferrin is a serine protease capable of cleaving arginine-rich sequences. We speculate that Ser259 and Lys73 form a catalytic dyad, reminiscent of a number of bacterial serine proteases. In addition, we speculate that lactoferrin may cleave arginine-rich sequences in a variety of microbial virulence proteins, contributing to its long-recognized antimicrobial properties.

Efficient asymmetric epoxidation of alpha,beta-unsaturated ketones using a soluble triblock polyethylene glycol-polyamino acid catalyst.

[reaction: see text]. Polyethylene glycol (PEG)-bound poly-L-leucine acts as a THF-soluble catalyst for the Juliá-Colonna asymmetric epoxidation of enones. Excellent enantioselectivities may be obtained even with short chain length polyleucine. FT-IR investigations have determined that the catalytically active polyleucine components of these copolymers have an alpha-helical structure.

Pregnancy detection and the effects of age, body weight, and previous reproductive performance on pregnancy status and weaning rates of farmed fallow deer (Dama dama).

Fallow does (n = 502) of different ages (mature, 2-yr-old, and yearling) were maintained with bucks for a 60-d breeding season to determine whether previous reproductive performance and changes in BW affect doe pregnancy rates and to compare the effectiveness of ultrasonography and serum pregnancy-specific protein B (PSPB) for the detection of pregnancy in fallow does. Ultrasonography was performed, blood samples collected, and BW recorded at buck removal (d 0) and at 30 and 90 d after buck removal. Lactational status (lactating = WET; nonlactating = DRY) were determined from farm records taken at weaning prior to each breeding season (autumn 1990 through autumn 1994). Ultrasonography and PSPB for determining pregnancy were in agreement 93% of the time. Overall pregnancy rates did not differ (P>.10) relative to age of the doe; the combined pregnancy rate was 92%. We also determined that 82.9% of does conceived early in the breeding season and that the incidence of embryonal-fetal mortality during the first 90 d after buck removal was 2.8%. In general, mature and 2-yr-old DRY does were heavier and had lower pregnancy rates than WET does. The overall weaning rate for all does was 77.9%. Loss in the number of fawns from pregnancy detection to weaning was equivalent to 14.8% for mature does, 24.7% for 2 yr old does, and 42.5% for yearling does. These data indicate that even though pregnancy rates were relatively high, further study is needed to determine the causes associated with subsequent fawn losses, particularly among yearling does. As a production tool, lactational WET/ DRY status testing was found to be an acceptable means for determining the reproductive potential of individual does within the herd. In addition, serum PSPB may be used in place of ultrasonography for pregnancy diagnosis in fallow deer as early as d 30 after buck removal.

Spatial asynchrony and periodic travelling waves in cyclic populations of field voles.

We demonstrate evidence for the presence of travelling waves in a cyclic population of field voles in northern Britain by fitting simple, empirical models to spatially referenced time series data. Population cycles were broadly synchronous at all sites, but use of Mantel correlations suggested a strong spatial pattern along one axis at a projection line 72 degrees from North. We then fitted a generalized additive model to log population density assuming a fixed-form travelling wave in one spatial dimension for which the density at each site was offset in time by a constant amount from a standard density-time curve. We assumed that the magnitude of this offset would be proportional to the spatial separation between any given site and the centroid of the sampling sites, where separation is the distance between sites in a fixed direction. After fitting this model, we estimated that the wave moved at an average speed of 19 km yr-1, heading from West to East at an angle of 78 degrees from North. Nomadic avian predators which could synchronize populations over large areas are scarce and the travelling wave may be caused by density-dependent dispersal by field voles and/or predation by weasels, both of which act at a suitably small spatial scale.

Design and synthesis of benzoic acid derivatives as influenza neuraminidase inhibitors using structure-based drug design.

A series of 94 benzoic acid derivatives was synthesized and tested for its ability to inhibit influenza neuraminidase. The enzyme-inhibitor complex structure was determined by X-ray crystallographic analysis for compounds which inhibited the enzyme. The most potent compound tested in vitro, 5 (4-acetylamino)-3-guanidinobenzoic acid), had an IC50 = 2.5 x 10(-6) M against N9 neuraminidase. Compound 5 was oriented in the active site of the neuraminidase in a manner that was not predicted from the reported active site binding of GANA (4) with neuraminidase. In a mouse model of influenza, 5 did not protect the mice from weight loss due to the influenza virus when dosed intranasally.

Alpha-(1-->2)-, and alpha-(1-->3)-, and alpha-(1-->6)-linked thioglycosidic disaccharides: syntheses and anti-HIV testing of thiokojibiose octaacetate, thionigerose, and thioisomaltose.

The syntheses of several alpha-linked thioglycosidic disaccharides are described, including thiokojibiose octaacetate (1), thionigerose (2), and thioisomaltose (3). The title compounds were synthesized by coupling 2,3,4,6-tetra-O-acetyl-1.5-acetyl-1-thio-alpha-D-glucopyranose (4) with either 1,3,4,6-tetra-O-acetyl-2-O-trifluoromethylsulfonyl-beta-D-manno pyr anose (7), 1,2:5,6-di-O-isopropylidene-3-O-trifluoromethylsulfonyl-alpha-D-++ +allofuranose (15), or methyl 2,3,4-tri-O-acetyl-6-deoxy-6-iodo-alpha-D-glucopyranoside (17), respectively. Thiokojibiose octaacetate in turn was converted to 3,4,6-tri-O-acetyl-2-S-(2,3,4,6-tetra-O-acetyl-alpha-D-glucopyranosyl)-2 -thio-alpha-D-glucopyranosyl bromide (9), which was used to obtain several related disaccharides and one trisaccharide. All of the compounds, including thiomaltose and thiotrehalose, which were resynthesized by known methods, were tested for their anti-HIV activity in either CEM or MT-2 cells. Anti-HIV activity was noted only with thiokojibiose octaacetate and its 1-thio analogue (14), which had IC50 values of 51 and 48 micrograms/mL in CEM cells, respectively.

Treatment with vitamins A, D and E did not reduce weight loss in transported cattle.

Two field trials using an injectable vitamin A, D and E solution conducted in the pastoral environment of northern Australia are described. It was found that treatment of lighter (< 150 kg) or heavier (> 372 kg) weight cattle did not reduce weight loss during road transport. These findings contradict anecdotal evidence of reduced weight loss during transport with the use of vitamins A, D and E. The lack of scientific basis for their use is discussed.

Chronic posttraumatic aortic pseudoaneurysm. Recognition before rupture.

Few patients survive transection of the aorta caused by blunt trauma. However, among those who do are a small number who go on to live with an unrecognized pseudoaneurysm that may rupture at any time. Because these aneurysms may be mistaken for more common disease processes, such as hilar adenopathy, atherosclerotic aneurysm, or neoplasia, the authors describe radiographic findings that suggest the correct diagnosis.