Discriminant ability of the Eating Assessment Tool-10 to detect aspiration in individuals with amyotrophic lateral sclerosis.

BACKGROUND: Oropharyngeal dysphagia is prevalent in individuals with amyotrophic lateral sclerosis (ALS) leading to malnutrition, aspiration pneumonia, and death. These factors necessitate early detection of at-risk patients to prolong maintenance of safe oral intake and pulmonary function. This study aimed to evaluate the discriminant ability of the Eating Assessment Tool (EAT-10) to identify ALS patients with unsafe airway protection during swallowing. METHODS: Seventy ALS patients completed the EAT-10 survey and underwent a standardized videofluoroscopic evaluation of swallowing. Two blinded raters determined airway safety using the Penetration Aspiration Scale (PAS). A between groups anova (safe vs penetrators vs aspirators) was conducted and sensitivity, specificity, area under the curve (AUC), and likelihood ratios calculated. KEY RESULTS: Mean EAT-10 scores for safe swallowers, penetrators, and aspirators (SEM) were: 4.28 (0.79) vs 7.10 (1.79) vs 20.50 (3.19), respectively, with significant differences noted for aspirators vs safe swallowers and aspirators vs penetrators (p < 0.001). The EAT-10 demonstrated good discriminant ability to accurately identify ALS penetrator/aspirators (PAS ≥3) with a cut off score of 3 (AUC: 0.77, sensitivity: 88%, specificity: 57%). The EAT-10 demonstrated excellent accuracy at identifying aspirators (PAS ≥6) utilizing a cut off score of 8 (AUC: 0.88, sensitivity: 86%, specificity: 72%, likelihood ratio: 3.1, negative predictive value: 95.5%). CONCLUSIONS & INFERENCES: The EAT-10 differentiated safe vs unsafe swallowing in ALS patients. This patient self-report scale could represent a quick and meaningful aide to dysphagia screening in busy ALS clinics for the identification and referral of dysphagic patients for further instrumental evaluation.

Modelling for conflict: the legacy of ballistic research and current extremity in vivo modelling.

Extremity ballistic injury is unique and the literature intended to guide its management is commonly misinterpreted. In order to care for those injured in conflict and conduct appropriate research, clinicians must be able to identify key in vivo studies, understand their weaknesses and desist the propagation of miscited and misunderstood ballistic dogma. This review provides the only inclusive critical overview of key studies of relevance to military extremity injury. In addition, the non-ballistic studies of limb injury, stabilisation and contamination that will form the basis from which future small animal extremity studies are constructed are presented. With an awareness of the legacy of military wound models and an insight into available generic models of extremity injury and contamination, research teams are well placed to optimise future military extremity injury management.

Growth rates are related to production efficiencies in juveniles of the sea urchin Lytechinus variegatus.

Growth rates of newly-metamorphosed urchins from a single spawning event (three males and three females) were highly variable, despite being held en masse under identical environmental and nutritional conditions. As individuals reached ~5 mm diameter (0.07-0.10 g wet weight), they were placed in growth trials (23 dietary treatments containing various nutrient profiles). Elapsed time from the first individual entering the growth trials to the last individual entering was 121 days (N = 170 individuals). During the five-week growth trials, urchins were held individually and proffered a limiting ration to evaluate growth rate and production efficiency. Growth rates among individuals within each dietary treatment remained highly variable. Across all dietary treatments, individuals with an initially high growth rate (entering the study first) continued to grow at a faster rate than those with an initially low growth rate (entering the study at a later date), regardless of feed intake. Wet weight gain (ranging from 0.13 -3.19 g, P < 0.0001, R2 = 0.5801) and dry matter production efficiency (ranging from 25.2-180.5%, P = 0.0003, R2 = 0.6162) were negatively correlated with stocking date, regardless of dietary treatment. Although canalization of growth rate during en masse early post-metamorphic growth is possible, we hypothesize that intrinsic differences in growth rates are, in part, the result of differences (possibly genetic) in production efficiencies of individual Lytechinus variegatus. That is, some sea urchins are more efficient in converting feed to biomass. We further hypothesize that this variation may have evolved as an adaptive response to selective pressure related to food availability.

Anaesthesia trainees' exposure to regional anaesthesia in an Australian tertiary adult teaching hospital.

The purpose of this study was to quantify the exposure of anaesthetic trainees to regional anaesthesia in an Australian tertiary adult teaching hospital. We reviewed data collected on all regional blocks performed by the anaesthetic department over a two-year period. The data was then broken down to give an estimate of the number of each block performed by each training year group. There was an average of 27.7 full-time equivalent trainees attached to the department. Trainees performed a total of 1374 blocks over this period. The average number of blocks performed by basic training year one trainees each year was 6.5, basic training year two trainees 13.5, advanced training year one trainees 14.9, advanced training year two trainees 19.1, advanced training year three trainees 23.1 and regional fellows 144.0. The number of total blocks and the proportion of advanced blocks increased with increasing level of training while supervision declined. Trainees in the two regional fellowship positions (7% of the trainee pool) performed 42% of the 1374 blocks. Factors that may influence the exposure of trainees to regional anaesthesia and the assessment of competency are considered.

Combined effects of formalin fixation and tissue processing on immunorecognition.

It is accepted that aldehyde-based fixation of cells can affect immunodetection of antigens; however, the effects of tissue processing on immunodetection have not been analyzed systematically. We investigated the effects of aldehyde-based fixation and the various cumulative steps of tissue processing on immunohistochemical detection of specific antigens. DU145 (prostate) and SKOV3 (ovarian) cancer cell lines were cultured as monolayers on microscope slides. Immunohistochemical detection of Ki67/MIB-1 and proliferating cell nuclear antigen (PCNA) was evaluated after various fixation times in 10% neutral buffered formalin and after each of the several cumulative steps of tissue processing. The effect of antigen retrieval (AR) was evaluated concomitantly as an additional variable. Our results indicate that in addition to fixation, each of the tissue processing steps has effects on immunorecognition of the epitopes recognized by these antibodies. Extensive dehydration through ethanols to absolute ethanol had only modest effects, except for the detection of Ki67/MIB-1 in SKOV-3 cells where the effect was stronger. In general, however, establishment of a hydrophobic environment by xylene resulted in the greatest decrease in immunorecognition. AR compensated for most, but not all, of the losses in staining following fixation and exposure to xylene; however, AR gave consistent results for most steps of tissue processing, which suggests that AR also should be used for staining PCNA. The cellular variations that were observed indicate that the effects of fixation and other steps of tissue processing may depend on how antigens are packaged by specific cells.

Long-term neurological complications associated with surgery and peripheral nerve blockade: outcomes after 1065 consecutive blocks.

Peripheral nerve blockade is gaining popularity as an analgesic option for both upper or lower limb surgery. Published evidence supports the improved efficacy of regional techniques when compared to conventional opioid analgesia. The incidence of neurological deficit after surgery associated with peripheral nerve block is unclear. This paper reports on neurological outcomes occurring after 1065 consecutive peripheral nerve blocks over a one-year period from a single institution. All patients receiving peripheral nerve blocks for surgery were prospectively followed for up to 12 months to determine the incidence and probable cause of any persistent neurological deficit. Formal independent neurological review and testing was undertaken as indicated. Thirteen patients reported symptoms that warranted further investigation. A variety of probable causes were identified, with peripheral nerve block being implicated in two cases (one resolved at nine months and one remaining persistent). Overall incidence of block-related neuropathy was 0.22%. Persistent postoperative neuropathy is a rare but serious complication of surgery associated with peripheral nerve block. Formal follow-up of all such blocks is recommended to assess causality and allow for early intervention.

Outpatient management of the chronically anticoagulated patient for elective surgery.

With the appropriate use of preadmission clinics, "hospital in the home" programs, and alternatives to intravenous heparin, the majority of chronically anticoagulated patients can be managed as outpatients prior to elective surgery. The preoperative management depends on the original indication for long-term anticoagulation, the interval since the last thromboembolic event, and the extent and type of surgery planned. Only patients who are undergoing major surgery, and who have a high risk of recurrent thrombosis or embolism, require preoperative admission to hospital and conversion to an intravenous heparin regimen. Patients undergoing minor surgery may require no change to their oral anticoagulation. The remainder require cessation of oral anticoagulation and alternative thromboprophylaxis preoperatively, which can be achieved on an outpatient basis using low molecular weight heparin. Outpatient anticoagulation management requires a clear protocol that is understood and agreed to by all parties involved in the care of surgical patients perioperatively.

Early carbonic anhydrase induction in the gills of the blue crab, Callinectes sapidus, during low salinity acclimation is independent of ornithine decarboxylase activity.

Carbonic anhydrase (CA) induction in the gills of the euryhaline blue crab, Callinectes sapidus, was measured in response to lowered environmental salinity. Simultaneous measurements of ornithine decarboxylase (ODC) activity were made in gills and nonbranchial tissues to determine whether ODC activity and the resultant synthesis of polyamines played a role in the initiation and regulation of CA induction. CA induction in the seventh gill pair (G7) was proportional to the decrease in ambient salinity, but activity in the third gill pair (G3) remained unchanged. Induction began by 24 hr after low salinity transfer, much earlier than previously reported, and peaked after 4 days. The magnitude of salinity change affected the magnitude of CA induction only, not the time course. A general cell volume regulatory response, as measured by the appearance of total ninhydrin-positive substances (TNPS) in the hemolymph, was initiated within 4 hr of low salinity transfer and was complete by 24 hr post-transfer. General cell swelling may be the initial signal in the pathway of CA induction. ODC activity in the gills of acclimated animals was not influenced by salinity. For crabs transferred from 35 to 25 ppt, ODC activity did not change significantly over the time course of acclimation. There was an early but transient increase in ODC activity in all tissues for crabs acclimated to 28 ppt and transferred to 15 ppt. Induction of ODC activity does not appear to be a precursor for CA induction; therefore, it does not appear that polyamines are substantially involved in the up-regulation of transport enzyme activity in low salinity. ODC, and resultant polyamine synthesis, may, however, have a role in cell volume regulation.

The effect of age, gender, risk level and glycosylated hemoglobin in predicting foot amputation in HMO patients with diabetes.

PURPOSE: To determine if age, gender, risk level and glucosylated hemoglobin could predict foot amputations in HMO patients with diabetes. DATA SOURCES: A retrospective chart review of a non-random sample of 27 patients with amputation and 110 randomly selected patients without amputation during the same time period. Chi-square, t-tests and logistic regression were used to analyze the data. CONCLUSIONS: There was no significant difference between the group with amputation and those without amputation in age or gender. However, there was a significant difference between the two groups in the risk stratification (p = .005) and glycosylated hemoglobin levels (p = .058). IMPLICATIONS FOR PRACTICE: Nurse practitioners can effectively screen for amputation risk factors and closely monitor glycosylated hemoglobin levels of diabetic patients to reduce the incidence of vascular complications and related lower extremity amputation.

Levels of progesterone, testosterone, and estradiol, and androstenedione metabolism in the gonads of Lytechinus variegatus (Echinodermata:echinoidea).

Levels of progesterone (P4), testosterone (T) and estradiol (E2) indicated significant variation among individual echinoids during the annual cycle, reflecting generally the variation in gamete development that can be observed among individuals. Testosterone and E2 levels in both the ovaries and testes were higher during the period of gonadal growth. Levels of all steroids were greatly reduced compared to those levels reported for asteroids. Differences in the levels of P4, T, and estrogens between asteroids and Lytechinus variegatus may be related to differences in gonad morphology and nutrient storage capacity between asteroids and echinoids. It was hypothesized that the low levels of steroids detected in L. variegatus reflect paracrine-like mechanisms in cell signaling as compared to endocrine-like mechanisms proposed to be involved in regulating gonad function in asteroids. Both the ovaries and testes of L. variegatus had the capacity to synthesize T and a variety of 5alpha-reduced androgens including 5alpha-androstane-3beta,17beta-diol and 5alpha-androstane-3alpha,17beta-diol (5alpha-adiols) from androstenedione (AD) in 8 h. Estrogen synthesis was not detected. The sex-specific pattern of accumulation of 5alpha-adiols in the ovaries and testes suggests that the 5alpha-adiols may affect processes related to reproduction in L. variegatus.

Progesterone metabolism in the ovaries and testes of the echinoid Lytechinus variegatus Lamarck (Echinodermata).

In the present study we examined the metabolic fate of progesterone (P4) in homogenate and tissue minces of the ovaries and testes of Lytechinus variegatus. P4 was metabolized primarily into 5alpha-reduced metabolites including, 5alpha-pregnane-3,20-dione (DHP), 3beta-hydroxy-5alpha-pregnan-20-one (3beta,20-one), 5alpha-pregnane-3beta,20alpha-diol (3beta,20alpha-diol), 5alpha-pregnane-3beta,20beta-diol (3beta,20beta-diol), and 5alpha-pregnane-3alpha,20alpha-diol (3alpha,20alpha-diol) by both the ovaries and testes. The capacity to metabolize P4 did not differ between the ovaries and testes. However, the relative quantity of Salpha-pregnane-3beta,20zeta-diol synthesized from ovary and testis tissue minces was about 3.3-fold higher than from homogenate preparations. Differences in the synthesis of 3beta,20-one and 3alpha,20alpha-diol in both ovary and testis minces were dependent on reproductive state. This study demonstrates the pathway of P4 conversion in the ovaries and testes of L. variegatus and indicates the rapid conversion of P4 into 5alpha-reduced metabolites in these tissues. Although P4 metabolism is not sex specific, sex-specific responses to P4 metabolites have been demonstrated previously. We hypothesize that the sex-specific responses of the ovaries and the testes to P4 may be associated with receptor-level regulatory processes.

Steroid levels and steroid metabolism in relation to early gonadal development in the tilapia Oreochromis niloticus (Teleostei: cyprinoidei).

Sex steroid levels and steroid metabolism were investigated in relation to early gonadal development in a mixed sex population of the tilapia Oreochromis niloticus. Androstenedione (AD), testosterone (T), 11-ketotestosterone (KT), and estradiol (E2) were quantified by radioimmunoassay (RIA) of whole body extracts. Androstenedione metabolism was assessed by incubations in vitro with 3H-AD and metabolites were identified by thin-layer chromatography coupled with radioisotope image analysis. Histology revealed the presence of gonadal structures at 15 days postfertilization (dpf) and ovaries at 36 dpf, with other individuals exhibiting undifferentiated gonads containing germinal cells, presumably eventual testes. Androgen levels were initially high in eggs then decreased severalfold prior to the emergence of gonads. A transient increase in the levels of T and KT occurred at 22 dpf. Levels of E2 were either low or undetectable except for a transient increase (43 dpf) after ovaries were present. Levels of T approached bimodality from 57 to 64 dpf. Steroid metabolism generally increased throughout development. Metabolites were generally similar, consisting of T predominantly as well as 5beta-reduced androgen derivatives and 11-oyxgenated derivatives. Estriol was tentatively identified. Conjugated steroids were not formed. Two types of steroid metabolic profiles occurred at 50 dpf. These results demonstrate that changes in the steroidogenic profile occur during early transitions of gonadal development. Notably, (1) steroid biosynthetic capacity preceeds gonadal differentiation, (2) evidence for estrogens occurs after ovarian development has begun, and (3) bimodality of levels of T and differential steroid metabolism later in development may reflect the onset of sexual divergence.

Proscar (Finasteride) inhibits 5 alpha-reductase activity in the ovaries and testes of Lytechinus variegatus Lamarck (Echinodermata: Echinoidea).

Recent investigations into the steroid metabolic pathway in the echinoid Lytechinus variegatus demonstrated the capacity of the gonads to convert androstenedione, the classical mammalian precursor to bioactive androgens, into testosterone and a variety of 5 alpha-reduced androgens including 5 alpha-androstane-3 beta, 17 beta-diol and 5 alpha-androstane-3 alpha, 17 beta-diol. The synthesis of these steroids, which requires 5 alpha-reductase activity, varies with sex and reproductive state in L. variegatus, suggesting that these steroids may be involved in reproductive processes. The classical method of castration followed by steroid replacement therapy to determine the biological role of steroids in the gonads of higher vertebrates is not possible in echinoids. Therefore, this study was designed to determine the efficacy of finasteride, a selective 5 alpha-reductase inhibitor in the mammalian prostate gland, on 5 alpha-reductase activity in the gonads of L. variegatus. Finasteride inhibits echinoid 5 alpha-reductase in a dose-dependent manner with IC50 approximately 2.7 microM for both ovaries and testes. These echinoid IC50s are significantly higher than those reported for humans and rats. In addition, oral administration of finasteride to the echinoids appeared to inhibit 5 alpha-reductase with no apparent stress (no spine loss) to the animals. These data suggest that finasteride may be used to selectively and chemically ablate 5 alpha-reduced androgen synthesis in the gonads of L. variegatus.

Synthesis of testosterone and 5alpha-androstanediols during nutritionally stimulated gonadal growth in Lytechinus variegatus lamarck (Echinodermata:Echinoidea).

Although sex steroids and steroid converting enzymes have been found in echinoids, the relationship between steroids and reproduction has not been demonstrated. On days 0, 4, 8, 16, 32, and 48 of feeding, the gonads of previously starved Lytechinus variegatus were excised and incubated with [3H]androstenedione for 0.5 h to determine if changes in steroidogenic capacity are correlated with gonadal growth. Total rates of androstenedione conversion in the testes and ovaries increased significantly during feeding. In addition, the types and relative quantities of metabolites synthesized varied, suggesting that androstenedione metabolism is influenced by nutritional status. Both testes and ovaries synthesized testosterone, 5alpha-androstane-3alpha,17beta-diol, and 5alpha-androstane-3beta, 17beta-diol (5alpha-adiols), 5alpha-androstanedione, epiandrosterone, and androsterone on all days of feeding. In the testes, the relative quantities of testosterone and 5alpha-adiols increased greatly on day 4 of feeding. In contrast, in the ovaries testosterone synthesis was not detectable on day 4, although the relative quantities of 5alpha-adiols increased threefold. The sex-specific changes in the synthesis of these metabolites reflect a shift in the metabolic pathway indicated by changes in the relative enzyme activity indices for 5alpha-reductase (5alpha-R) (necessary for the synthesis of 5alpha-reduced androgens) and 3alpha/beta-hydroxysteroid dehydrogenase (3alpha/beta-HSDs, necessary for the synthesis of 3alpha- or 3beta-hydroxylated androgens). In both testes and ovaries the relative activities of 5alpha-R and 3alpha/beta-HSD increased on day 4 of feeding. The physiological significance of changes in androstenedione metabolism may be associated with the initiation of biosynthetic processes associated with gametogenesis.

A randomized double-blinded comparison of metoclopramide, ondansetron and cyclizine in day-case laparoscopy.

This study determined the overall incidence of postoperative nausea and vomiting (PONV) in 38 patients undergoing laparoscopic gynaecological procedures who received a standardized propofol/isoflurane anaesthetic but no preoperative antiemetic. A further 166 patients similarly anaesthetized were then randomly allocated to receive either metoclopramide 10 mg. ondansetron 4 mg, or cyclizine 50 mg as an intravenous antiemetic immediately preinduction. Overall incidence of PONV was determined for all groups and the relative efficacy of the three antiemetic agents assessed. Fifty per cent of patients in the initial group (no antiemetic) reported significant nausea and/or vomiting up to 24 hours postoperatively. The incidence of PONV in the metoclopramide group was 24%, in the ondansetron group 20%, and in the cyclizine group 51%. There was no detectable difference in relative efficacy between ondansetron 4 mg and metoclopramide 10 mg. The incidence of PONV in the group who received cyclizine was similar to that found in the pilot group who received no PONV prophylaxis. Both metoclopramide and ondansetron may potentially decrease the incidence of PONV following gynaecologic laparoscopy by up to 50% when administered intravenously prior to a propofol/isoflurane anaesthetic.

Molecular cloning of a cDNA encoding putative molt-inhibiting hormone from the blue crab, Callinectes sapidus.

A cDNA library was constructed using poly(A+) RNA isolated from eyestalk neural ganglia of the blue crab, Callinectes sapidus. The library was screened using a probe generated by PCR based on the published amino acid sequence of molt-inhibiting hormone from the shore crab, Carcinus maenas. DNA sequence analysis of one positive clone revealed a 339 bp open reading frame encoding a 78-residue putative molt-inhibiting hormone and a 35-residue signal peptide. The deduced amino acid sequence of C. sapidus molt-inhibiting hormone is 79% homologous with that of C. maenas. Northern blot analysis, using a fragment of the cloned molt-inhibiting hormone cDNA as probe, revealed specific hybridization to a single band (approximately 1.4 kb) in RNA extracted from eyestalk but not control tissues.

Sex steroid levels in the testes, ovaries, and pyloric caeca during gametogenesis in the sea star Asterias vulgaris.

The concentrations of progesterone, testosterone, and estradiol were determined via radioimmunoassay in testes, ovaries, and pyloric caeca of the sea star Asterias vulgaris during one complete and two partial gametogenic cycles. These compounds were found in all tissues examined and were present in quantities similar to those reported previously in other echinoderms and in vertebrates. Testes and ovaries exhibited annual growth cycles during which testicular and ovarian mass increased up to 100-fold as gametes were produced and stored until spawning. Pyloric caecal mass varied during the annual reproductive season; however, no seasonal trends were apparent. In the testes, sex steroid levels were highest at the onset of spermatogenesis. Transient increases in the levels of estradiol coincided with spermatogonial mitotic proliferation. Transient increases in the levels of testosterone and progesterone in the testes coincided with spermatogenic column formation and with spermiogenesis, respectively. In the ovaries, estradiol and testosterone levels were highest at the onset of oogenesis while progesterone levels did not change significantly throughout the annual gametogenic cycle. Male and female pyloric caeca exhibited similar seasonal variations in levels of sex steroids as compared with the gonads. It is hypothesized that transient increases in the levels of sex steroids during gametogenesis may serve as endogenous modulators of reproduction.