Exploring the limits of semiconductor-laser-based optical frequency combs.

We report a study on the performance limits of stabilized optical frequency combs from semiconductor mode-locked diode lasers. Operating characteristics such as the number of comb lines, comb tooth linewidth, the physical parameters that affect the independent control of pulse repetition rate and offset frequency, and the potential for self-stabilization, are explored.

Chondrocyte expansion is associated with loss of primary cilia and disrupted hedgehog signalling.

Tissue engineering-based therapies targeting cartilage diseases, such as osteoarthritis, require in vitro expansion of articular chondrocytes. A major obstacle for these therapies is the dedifferentiation and loss of phenotype accompanying chondrocyte expansion. Recent studies suggest that manipulation of hedgehog signalling may be used to promote chondrocyte re-differentiation. Hedgehog signalling requires the primary cilium, a microtubule-based signalling compartment, the integrity of which is linked to the cytoskeleton. We tested the hypothesis that alterations in cilia expression occurred as consequence of chondrocyte dedifferentiation and influenced hedgehog responsiveness. In vitro chondrocyte expansion to passage 5 (P5) was associated with increased actin stress fibre formation, dedifferentiation and progressive loss of primary cilia, compared to primary (P0) cells. P5 chondrocytes exhibited ~50 % fewer cilia with a reduced mean length. Cilia loss was associated with disruption of ligand-induced hedgehog signalling, such that P5 chondrocytes did not significantly regulate the expression of hedgehog target genes (GLI1 and PTCH1). This phenomenon could be recapitulated by applying 24 h cyclic tensile strain, which reduced cilia prevalence and length in P0 cells. LiCl treatment rescued cilia loss in P5 cells, partially restoring hedgehog signalling, so that GLI1 expression was significantly increased by Indian hedgehog. This study demonstrated that monolayer expansion disrupted primary cilia structure and hedgehog signalling associated with chondrocyte dedifferentiation. This excluded the possibility to use hedgehog ligands to stimulate re-differentiation without first restoring cilia expression. Furthermore, primary cilia loss during chondrocyte expansion would likely impact other cilia pathways important for cartilage health and tissue engineering, including transforming growth factor (TGF), Wnt and mechanosignalling.

Leukocyte-subset counts in idiopathic parkinsonism provide clues to a pathogenic pathway involving small intestinal bacterial overgrowth. A surveillance study.

BACKGROUND: Following Helicobacter pylori eradication in idiopathic parkinsonism (IP), hypokinesia improved but flexor-rigidity increased. Small intestinal bacterial-overgrowth (SIBO) is a candidate driver of the rigidity: hydrogen-breath-test-positivity is common in IP and case histories suggest that Helicobacter keeps SIBO at bay. METHODS: In a surveillance study, we explore relationships of IP-facets to peripheral immune/inflammatory-activation, in light of presence/absence of Helicobacter infection (urea-breath- and/or stool-antigen-test: positivity confirmed by gastric-biopsy) and hydrogen-breath-test status for SIBO (positivity: >20 ppm increment, 2 consecutive 15-min readings, within 2h of 25G lactulose). We question whether any relationships found between facets and blood leukocyte subset counts stand in patients free from anti-parkinsonian drugs, and are robust enough to defy fluctuations in performance consequent on short t½ therapy. RESULTS: Of 51 IP-probands, 36 had current or past Helicobacter infection on entry, 25 having undergone successful eradication (median 3.4 years before). Thirty-four were hydrogen-breath-test-positive initially, 42 at sometime (343 tests) during surveillance (2.8 years). Hydrogen-breath-test-positivity was associated inversely with Helicobacter-positivity (OR 0.20 (95% CI 0.04, 0.99), p<0.05).In 38 patients (untreated (17) or on stable long-t½ IP-medication), the higher the natural-killer count, the shorter stride, slower gait and greater flexor-rigidity (by mean 49 (14, 85) mm, 54 (3, 104) mm.s-1, 89 (2, 177) Nm.10-3, per 100 cells.µl-1 increment, p=0.007, 0.04 & 0.04 respectively, adjusted for patient characteristics). T-helper count was inversely associated with flexor-rigidity before (p=0.01) and after adjustment for natural-killer count (-36(-63, -10) Nm.10-3 per 100 cells.µl-1, p=0.007). Neutrophil count was inversely associated with tremor (visual analogue scale, p=0.01). Effect-sizes were independent of IP-medication, and not masked by including 13 patients receiving levodopa (except natural-killer count on flexor-rigidity). Cellular associations held after allowing for potentially confounding effect of hydrogen-breath-test or Helicobacter status. Moreover, additional reduction in stride and speed (68 (24, 112) mm & 103 (38, 168) mm.s-1, each p=0.002) was seen with Helicobacter-positivity. Hydrogen-breath-test-positivity, itself, was associated with higher natural-killer and T-helper counts, lower neutrophils (p=0.005, 0.02 & 0.008). CONCLUSION: We propose a rigidity-associated subordinate pathway, flagged by a higher natural-killer count, tempered by a higher T-helper, against which Helicobacter protects by keeping SIBO at bay.

Differential effect of Helicobacter pylori eradication on time-trends in brady/hypokinesia and rigidity in idiopathic parkinsonism.

BACKGROUND: We examine the effect of eradicating Helicobacter in idiopathic parkinsonism (IP). Marked deterioration, where eradication-therapy failed, prompted an interim report in the first 20 probands to reach de-blinding. The null-hypothesis, "eradication has no effect on principal outcome, mean stride length at free-walking speed," was rejected. We report on study completion in all 30 who had commenced post-treatment assessments. METHODS: This is a randomized, placebo-controlled, parallel-group efficacy study of eradicating biopsy-proven (culture and/or organism on histopathology) Helicobacter pylori infection on the time course of facets of IP, in probands taking no, or stable long-t(1/2), anti-parkinsonian medication. Persistent infection at de-blinding (scheduled 1-year post-treatment) led to open active eradication-treatment. RESULTS: Stride length improved (73 (95% CI 14-131) mm/year, p = .01) in favor of "successful" blinded active over placebo, irrespective of anti-parkinsonian medication, and despite worsening upper limb flexor rigidity (237 (57-416) Nm x 10(-3)/year, p = .01). This differential effect was echoed following open active, post-placebo. Gait did not deteriorate in year 2 and 3 post-eradication. Anti-nuclear antibody was present in all four proven (two by molecular microbiology only) eradication failures. In the remainder, it marked poorer response during the year after eradication therapy, possibly indicating residual "low-density" infection. We illustrate the importance of eradicating low-density infection, detected only by molecular microbiology, in a proband not receiving anti-parkinsonian medication. Stride length improved (424 (379-468) mm for 15 months post-eradication, p = .001), correction of deficit continuing to 3.4 years. Flexor rigidity increased before hydrogen-breath-test positivity for small intestinal bacterial overgrowth (208 (28-388) Nm x 10(-3), p = .02), increased further during (171 (67-274), p = .001) (15-31 months), and decreased (136 (6-267), p = .04) after restoration of negativity (32-41 months). CONCLUSION: Helicobacter is an arbiter of progression, independent of infection-load.

Blood profile holds clues to role of infection in a premonitory state for idiopathic parkinsonism and of gastrointestinal infection in established disease.

The two-stage neuroinflammatory process, containment and progression, proposed to underlie neurodegeneration may predicate on systemic inflammation arising from the gastrointestinal tract. Helicobacter infection has been described as one switch in the pathogenic-circuitry of idiopathic parkinsonism (IP): eradication modifies disease progression and marked deterioration accompanies eradication-failure. Moreover, serum Helicobacter-antibody-profile predicts presence, severity and progression of IP. Slow gastrointestinal-transit precedes IP-diagnosis and becomes increasingly-apparent after, predisposing to small-intestinal bacterial-overgrowth (SIBO). Although IP is well-described as a systemic illness with a long prodrome, there has been no comprehensive overview of the blood profile. Here, it is examined in relation to Helicobacter status and lactulose-hydrogen-breath-testing for SIBO. A robust finding of reduced lymphocyte count in 126 IP-probands and 79 spouses (without clinically-definite IP), compared with that in 381 controls (p < 0.001 in each case), was not explained by Helicobacter-status or breath-hydrogen. This complements a previous report that spouses were 'down-the-pathway' to 'clinically-definite' disease. In 205 other controls without clinically-definite IP, there were strong associations between sporadic cardinal features and immunoglobulin class concentration, not explained by Helicobacter-status. Premonitory states for idiopathic parkinsonism associated with relative lymphopenia, higher serum immunoglobulin concentrations and evidence of enteric-nervous-system damage may prove viral in origin.Although only 8% of the above 79 spouses were urea-breath-test-positive for Helicobacter, all 8 spouses with clinically-definite IP were (p < 0.0001). Transmission of a 'primer' to a Helicobacter-colonised recipient might result in progression to the diagnostic threshold. Twenty-five percent of the 126 probands were seropositive for anti-nuclear autoantibody. In 20 probands, monitored before and serially after anti-Helicobacter therapy, seropositivity marked a severe hypokinetic response (p = 0.03). It may alert to continuing infection, even at low-density. Hyperhomocysteinemia is a risk factor for dementia and depression. Serum homocysteine exceeded the target in 43% of the 126 IP-probands. It was partially explained by serum B12 (12% variance, p < 0.001), but not by Helicobacter-status (gastric-atrophy uncommon in IP) or levodopa treatment. Immune-inflammatory activation increases homocysteine production. Since an estimated 60% of probands are hydrogen-breath-test positive, SIBO, with its increased bacterial utilisation of B12, is a likely cause. Thus, two prognostic indicators in established IP fit with involvement of Helicobacter and SIBO.

Intracavity dispersion effect on timing jitter of ultralow noise mode-locked semiconductor based external-cavity laser.

We report the generation of optical pulse trains with 380 as of residual timing jitter (1 Hz-1 MHz) from a mode-locked external-cavity semiconductor laser, through a combination of optimizing the intracavity dispersion and utilizing a high-power, low-noise InGaAsP quantum-well slab-coupled optical waveguide amplifier gain medium. This is, to our knowledge, the lowest residual timing jitter reported to date from an actively mode-locked laser.

Msx2 induces epithelial-mesenchymal transition in mouse mammary epithelial cells through upregulation of Cripto-1.

Epithelial-mesenchymal transition (EMT) is a process occurring during both embryogenesis and early stages of invasive cancer. Epithelial cells that undergo EMT become more migratory and invasive with a mesenchymal morphology. Herein we assess EMT induction in a mouse mammary epithelial cell line driven by Msx2, a homeobox-containing transcription factor important during mammary gland development. NMuMG cells, a normal mouse mammary epithelial cell line, stably transfected with a Msx2 cDNA showed downregulation of an epithelial marker E-cadherin and upregulation of the mesenchymal markers vimentin and N-cadherin. Furthermore, overexpression of Cripto-1, a member of the epidermal growth factor-CFC protein family already known to be involved in EMT, was detected in Msx2-transfected cells. The expression of Cripto-1 was accompanied by activation of the tyrosine kinase c-Src pathway and an increase in the invasive ability of the cells. Functional assays also demonstrated inhibition of the invasive behavior of the Msx2-transfected cells by a c-Src specific inhibitor. Moreover, immunohistochemistry of human infiltrating breast carcinomas showed positive staining for Msx2 only in the infiltrating tumor cells while the non-infiltrating tumor cells were negative. These results suggest that Msx2 may play a significant role in promoting EMT in epithelial cells that acquire properties involved in tumor invasion. J. Cell. Physiol. 219: 659-666, 2009. Published 2009 Wiley-Liss, Inc.

Calculating human exposure to endocrine disrupting pesticides via agricultural and non-agricultural exposure routes.

Endocrine Disrupting Chemicals (EDCs) are of increasing concern because of their potential impacts on the environment, wildlife and human health. Pesticides and some pesticide metabolites are an important group of EDC, and exposure to them is a poorly quantified source of human and environmental exposure to such chemicals generally. Models for estimating human exposure to Endocrine Disrupting (ED) pesticides are an important risk management tool. Probabilistic models are now being used in addition to deterministic ones in all areas of risk assessment. These can provide more realistic exposure estimates, because they are better able to deal with variation and uncertainty more effectively and better inform risk management decisions. Deterministic models are still used and are of great value where exposure data are scarce. Models or groups of models that provide holistic human ED pesticide exposure estimates are required if the risk posed to humans by ED pesticides is to be better assessed. Much more research is needed to quantify different exposure routes such as exposure from agricultural spray drift and the medical use of pesticides to develop such models. Most available probabilistic models of human exposure were developed in the USA and require modification for use elsewhere. In particular, datasets equivalent to those used to create and apply the American models are required. This paper examines the known routes of human pesticide exposure with particular reference to ED pesticides and their quantification as unlike pesticides generally, many ED pesticides are harmful at very low doses, especially if exposure occurs during sensitive stages of development, producing effects that may not manifest for many years or that affect descendants via epigenetic changes. It also summarises available deterministic and probabilistic models commonly used to calculate human exposure. The main requirement if such models are to be used in the UK is more quantitative data on the sources and pathways of human ED pesticide exposure.

Endocrine disrupting pesticides: implications for risk assessment.

Endocrine disrupting (ED) chemicals are compounds that alter the normal functioning of the endocrine system, potentially causing disease or deformity in organisms and their offspring. Pesticides are used widely to kill unwanted organisms in crops, public areas, homes and gardens and medicinally to kill parasites. Many are proven or suspected to be EDs. Ancient physiological similarities between different vertebrate groups suggest that disorders observed in wildlife may indicate risks to humans. This makes accurate risk assessment and effective legislation difficult. In this paper, the hazardous properties of pesticides which are known to have ED properties are reviewed in order to assess the implications for risk assessment. As well as data on sources of exposure in the United Kingdom (UK) an assessment of the evidence on the health effects of ED pesticides is also included. In total, 127 have been identified from the literature and their effects and modes of action are listed in this paper. Using the UK as a case study, the types and quantities of pesticides used, and their methods of application are assessed, along with their potential pathways to humans. In the UK reliable data are available only for agricultural use, so non-agricultural routes of pesticide exposure have been poorly quantified. The exposure of people resident in or visiting rural areas could also have been grossly under-estimated. Material links between ED pesticide use and specific illnesses or deformities are complicated by the multifactorial nature of disease, which can be affected by factors such as diet. Despite these difficulties, a large body of evidence has accumulated linking specific conditions to ED pesticides in wildlife and humans. A more precautionary approach to the use of ED pesticides, especially for non-essential purposes is proposed.

Role of chronic infection and inflammation in the gastrointestinal tract in the etiology and pathogenesis of idiopathic parkinsonism. Part 2: response of facets of clinical idiopathic parkinsonism to Helicobacter pylori eradication. A randomized, double-blind, placebo-controlled efficacy study.

BACKGROUND: Links between etiology/pathogenesis of neuropsychiatric disease and infection are increasingly recognized. AIM: Proof-of-principle that infection contributes to idiopathic parkinsonism. METHODS: Randomized, double-blind, placebo-controlled efficacy study of proven Helicobacter pylori eradication on the time course of facets of parkinsonism. Intervention was 1 week's triple eradication therapy/placebos. Routine deblinding at 1 year (those still infected received open-active), with follow-up to 5 years post-eradication. Primary outcome was mean stride length at free-walking speed, sample size 56 for a difference, active vs. placebo, of 3/4 (between-subject standard deviation). Recruitment of subjects with idiopathic parkinsonism and H. pylori infection was stopped at 31, because of marked deterioration with eradication failure. Interim analysis was made in the 20 who had reached deblinding, seven of whom were receiving antiparkinsonian medication (long-t(1/2), evenly spaced) which remained unchanged. RESULTS: Improvement in stride-length, on active (n = 9) vs. placebo (11), exceeded size of effect on which the sample size was calculated when analyzed on intention-to-treat basis (p = .02), and on protocol analysis of six weekly assessments, including (p = .02) and excluding (p = .05) those on antiparkinsonian medication. Active eradication (blind or open) failed in 4/20, in whom B-lymphocyte count was lower. Their mean time course was: for stride-length, -243 (95% CI -427, -60) vs. 45 (-10, 100) mm/year in the remainder (p = .001); for the ratio, torque to extend to flex relaxed arm, 349 (146, 718) vs. 58 (27, 96)%/ year (p < .001); and for independently rated, visual-analog scale of stance-walk videos (worst-best per individual identical with 0-100 mm), -64 vs. -3 mm from anterior and -50 vs. 11 lateral (p = .004 and .02). CONCLUSIONS: Interim analysis points to a direct or surrogate (not necessarily unique) role of a particular infection in the pathogenesis of parkinsonism. With eradication failure, bolus release of antigen from killed bacteria could aggravate an effect of ongoing infection.

Diagnosis of bacteriuria by detection of volatile organic compounds in urine using an automated headspace analyzer with multiple conducting polymer sensors.

The Osmetech Microbial Analyzer (OMA) is an automated headspace analyzer fitted with a novel detector system consisting of an array of polymer sensors, each of which responds to different volatile organic compounds. The system can be used for screening clinical urine specimens for significant bacteriuria by sampling urine headspace and subjecting the output of the multiple-detector response to principal component analysis. The OMA readily distinguished artificially infected urine samples from sterile controls. The OMA was then used to analyze 534 unselected clinical urine specimens, of which 21.5% had significant bacteriuria (containing >10(5) CFU of bacteria/ml). The sensitivity and specificity of the OMA compared with conventional culture were 83.5 and 87.6%, respectively. The OMA is a promising automated system for the rapid routine screening of urine specimens, and further clinical trials are in progress.

Dorsal hippocampal kindling produces long-lasting changes in the origin of spontaneous discharges in the piriform versus perirhinal cortex in vitro.

In an in vitro slice preparation of the amygdala-piriform-perirhinal cortex (A-P area), it was shown previously (McIntyre, D.C., Plant, J. R., 1993. Long-lasting changes in the origin of spontaneous discharges from amygdala-kindled rats: piriform vs. perirhinal cortex in vitro, Brain Res. 624, 268-276) that the infrequent spontaneous field potentials that initially originated in or near the perirhinal (PRh) cortex of slices from control rats began instead in the piriform (Pir) cortex of amygdala-kindled rats. This change in onset was only observed in the A-P area ipsilateral to the kindled amygdala. In the present experiment, we determined whether similar changes in activity were evident following kindling from a different limbic site, the dorsal hippocampus (DH). Kindling of the DH resulted in changes in the origin of the spontaneous discharges in the A-P area similar to amygdala kindling but, importantly, the changes involved both hemispheres. In addition, the origin of spontaneous discharges in slices from partial kindled rats (those that received as many hippocampal afterdischarges as the fully kindled rats but had not developed generalized convulsive responses) initially were similar to control tissue, but, during 0 Mg(2+) perfusion, changed more quickly than control tissue to mimic the profile of generalized kindled rats. The enduring changes in A-P area excitability caused by previous generalized kindling highlights the importance of the A-P area in convulsive generalization of limbic-kindled seizures.

Clinical efficacy of selamectin for the control of fleas on dogs and cats.

The topical endectocide selamectin (Revolution, Pfizer Animal Health) was evaluated in seven veterinary dermatology specialty clinics for its ability to control fleas on 75 dogs and 46 cats from single- and multiple-animal households. All animals were treated on days 0, 30, and 60 with a minimum unit dose of 6 mg/kg of selamectin(h) applied to the skin in a single spot at the base of the neck in front of the scapulae. The product was applied according to label instructions, and the use of other topical or environmental flea control products was prohibited during the study. Efficacy was assessed by percentage reductions in geometric mean flea comb counts. The reductions in flea numbers for dogs and cats combined were 90.6%, 97.0%, and 98.0% on days 30, 60, and 90, respectively, compared with day 0. This study demonstrates that selamectin, applied at 30-day intervals to dogs and cats, effectively controls flea infestations without other flea control products in single- and multiple-animal households.

Neurotrophin modulation of NMDA receptors in cultured murine and isolated rat neurons.

Neurotrophin modulation of NMDA receptors in cultured murine and isolated rat neurons. J. Neurophysiol. 78: 2363-2371, 1997. Patch-clamp and calcium imaging techniques were used to assess the acute effects of the neurotrophins, brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and nerve growth factor (NGF), on the responses of cultured and acutely isolated hippocampal and cultured striatal neurons to the glutamate receptor agonist N-methyl--aspartic acid (NMDA). The effects of BDNF on NMDA-activated currents were examined in greater detail. Currents evoked by NMDA, and the accompanying changes in intracellular calcium, were enhanced by low concentrations of the neurotrophins (1-20 ng/ml). The potentiation by the neurotrophins was rapid in onset and offset (<1 s). The neurotrophins also reduced desensitization of these currents in most cells. The enhancement of NMDA-activated currents by BDNF was observed using both perforated and whole cell patch recording techniques and could be demonstrated in outside-out patches. Furthermore, its effects were not attenuated by pretreatment with the protein kinase inhibitors genistein or 1-(5-isoquinolynesulfony)2-methylpiperazine (H7). Therefore, the actions of BDNF do not appear to be mediated by phosphorylation. Similar enhancements were observed with NT-3 and NT-4 and with NGF despite the fact that hippocampal neurons lack TrkA receptors. All together this evidence suggests that the enhancement of NMDA-evoked currents is unlikely to be mediated through the activation of growth factor receptors. Modulation of NMDA responses by BDNF was dependent on the concentration of extracellular glycine. The most pronounced potentiation by BDNF was observed at low concentrations, whereas no potentiation was observed in saturating concentrations of glycine, suggesting that BDNF may have increased the affinity of the NMDA receptor for glycine. However, the competitive glycine-site antagonist 7-chloro-kynurenic acid blocked the enhancement by BDNF without shifting the dose-inhibition relationship for this antagonist, and Mg2+ consistently depressed the potentiation of NMDA-evoked currents by BDNF, indicating that BDNF does not alter glycine affinity. BDNF also reversibly increased the probability of opening of NMDA channels recorded from outside-out patches taken from cultured hippocampal neurons. Other unrelated peptides including dynorphin and somatostatin also caused a glycine-dependent enhancement of NMDA currents and depressed the currents in saturating concentrations of glycine. In contrast, a shortened analogue dynorphin (6-17), which lacks N-terminus glycine residues, and another peptide met-enkephalin were without effects on NMDA currents recorded in low concentrations of glycine. Our results suggest that neurotrophins and other peptides can serve as glycine-like ligands for the NMDA receptor.

Excitatory amino acid receptors at a feedback pathway in the electrosensory system: implications for the searchlight hypothesis.

The electrosensory lateral line lobe (ELL) of the South American gymnotiform fish Apteronotus leptorhynchus has a laminar structure: electroreceptor afferents terminate ventrally whereas feedback input distributes to a superficial molecular layer containing the dendrites of the ELL principle (pyramidal) cells. There are two feedback pathways: a direct feedback projection that enters the ELL via a myelinated tract (stratum fibrosum, StF) and terminates in the ventral molecular layer (VML) and an indirect projection that enters as parallel fibers and terminates in the dorsal molecular layer. It has been proposed that the direct feedback pathway serves as a "searchlight" mechanism. This study characterizes StF synaptic transmission to determine whether the physiology of the direct feedback projection is consistent with this hypothesis. We used field and intracellular recordings from the ELL to investigate synaptic transmission of the StF in an in vitro slice preparation. Stimulation of the StF produced field potentials with a maximal negativity confined to a narrow band of tissue dorsal to the StF. Current source density analysis revealed two current sinks: an early sink within the StF and a later sink that corresponded to the anatomically defined VML. Field potential recordings from VML demonstrated that stimulation of the StF evoked an excitatory postsynaptic potential (EPSP) that peaked at a latency of 4-7 ms with a slow decay ( approximately 50 ms) to baseline. Intracellular recordings from pyramidal cells revealed that StF-evoked EPSPs consisted of at least two components: a fast gap junction mediated EPSP (peak 1.2-1.8 ms) and a chemical synaptic potential (peak 4-7 ms) with a slow decay phase ( approximately 50 ms). The amplitudes of the peak and decay phases of the chemical EPSP were increased by depolarizing current injection. Pharmacological studies demonstrated that the chemical EPSP was mainly due to ionotropic glutamate receptors with bothN-methyl--aspartate (NMDA) and non-NMDA components. NMDA receptors contributed substantially to both the early and late phase of the EPSP, whereas non-NMDA receptors contributed mainly to the early phase. Stimulation of the StF at physiological rates (100-200 Hz, 100 ms) produced an augmenting depolarization of the membrane potential of pyramidal cells. Temporal summation and a voltage-dependent enhancement of later EPSPs in the stimulus train permitted the compound EPSP to reach spike threshold. The nonlinear behavior of StF synaptic potentials is appropriate for the putative role of the direct feedback pathway as part of a searchlight mechanism allowing these fish to increase the electrodetectability of scanned objects.

Puerto Rican patients travel to Puerto Rico: assessing the effect on clinical care.

OBJECTIVE: To examine travel habits of Puerto Rican patients and assess the potential effect of this travel on their health care. DESIGN: Interview and survey of patients. SETTING: Urban medical clinic. PATIENTS: Two hundred consecutive, self-identified Puerto Rican patients presenting for follow-up care. INTERVENTION: Immediately prior to a follow-up office visit, patients were interviewed in either Spanish or English. MEASUREMENTS: The patients' age, sex, education level, employment status, and place of birth were recorded. The patients were asked questions concerning the principle place of residence of their family members, their ability to speak English, and their preferences in television and radio programs. Patients who had visited Puerto Rico were asked about the duration and purpose of their most recent trip and about the health care they received in Puerto Rico. Chi-square testing was applied to categorical data and t tests for continuous data; P values were calculated using the SPSS statistical analysis program. RESULTS: Of the 200 subjects, 110 (55%) had traveled to Puerto Rico in the last five years and 90 (45%) had not. The patients who traveled were more likely to have been born in Puerto Rico, less likely to speak English, and less likely to listen to English-language programs. A majority of the patients who traveled to Puerto Rico visited for a month or less (80%) and did not experience a change in health care (78%). In comparison, however, a majority (59%) of the patients who visited for longer than a month did experience a major change in their health care status (P < .00001). CONCLUSIONS: Puerto Rican patients, particularly those born in Puerto Rico with stronger cultural "ties" to the island, frequently return to Puerto Rico. Patients who visit for longer than a month often experience changes in care which are likely to have significant effect on their health. Clinicians caring for Puerto Rican patients should ask about upcoming visits to Puerto Rico and take steps to assure continuous and coordinated medical care.

Oscillatory and burst discharge across electrosensory topographic maps.

1. Three parallel maps of the distribution of tuberous electroreceptor inputs are found in the medullary electrosensory lateral line lobe (ELL) of weakly electric fish. Pyramidal cells in each map are known to respond differentially to the frequency of amplitude modulations (AMs) of external electric fields in vivo. We used an in vitro ELL slice preparation of Apteronotus leptorhynchus to compare the characteristics of spontaneously active single units across the three tuberous maps. It was our objective to determine whether spontaneous bursting activity of pyramidal cells in each map correlates with the known AM frequency selectivities of pyramidal cells in vivo. 2. Single-unit discharges were recorded from the pyramidal cell layer of the centromedial segment (CMS), centrolateral segment (CLS), and lateral segment (LS) of the ELL. Stochastic analysis of interspike intervals (ISIs) was used to identify bursting and nonbursting unit activity, and to separately analyze intra- and interburst ISIs. Four ISI patterns were identified as 1) bursting, 2) regular spiking, 3) irregular spiking, and 4) highly irregular spiking. This work focuses primarily on the characteristics of bursting units across the ELL segments. 3. Spontaneous bursting discharge was identified in all three maps (68 of 97 units), with several characteristics changing in a gradual manner across the maps. The coefficient of variation (CV) of ISIs and intraburst ISIs decreased significantly from the CMS to the LS, whereas the CV of burst periods increased significantly from the CMS to the LS. Autocorrelations and power spectral density analysis identified units discharging in an oscillatory manner with the following ratio: CMS, 75%; CLS, 4%; LS, 8%. 4. The mean period of spike bursts decreased significantly across the segments (CMS, 2.7 s; CLS, 1.2 s; LS, 1.1 s) primarily because of a shortening of mean burst duration (CMS, 1.0 s; CLS, 0.1 s; LS, 0.05 s). The average number of spikes per burst decreased significantly across the maps (CMS, 61; CLS, 8; LS, 8), whereas the average frequency of spikes per burst increased (CMS, 90 Hz; CLS, 130 Hz; LS, 178 Hz), mainly through an increase in the maximal frequencies attained by units within each map. 5. Bursts in the CMS were unstructured in that the intraburst ISIs were serially independent, whereas for many units in the CLS and especially the LS there were serial dependencies of successive spikes, with alternating short and long ISIs during the burst. 6. These data reveal that the characteristics of bursting unit activity differ between the CMS, CLS, and LS maps in vitro, implying a modulation of the factors underlying burst discharge across multiple sensory maps. Because the pattern of change in burst activity between these maps parallels that of pyramidal cell AM frequency selectivity in vivo, oscillatory and burst discharge may represent the cellular mechanism used to tune these cells to specific frequencies of afferent input during electrolocation and electrocommunication.

Factors associated with the effectiveness of antibiotic treatment for ovine virulent footrot.

Factors associated with the proportion of sheep cured of virulent footrot after antibiotic treatment were studied in a field trial under dry environmental conditions. From 2 similar flocks, 1091 Merino sheep weighing about 50 kg and infected with virulent footrot received an intramuscular injection of either 12 mL of a mixture of penicillin (250 mg/mL) and streptomycin (250 mg/mL), 6 mL of long acting oxytetracycline (200 mg/mL) or 6 mL of a mixture of lincomycin (50 mg/mL) and spectinomycin (100 mg/mL). Variables that were significantly associated with the proportion of sheep cured were: the type of antibiotic used, the number of feet infected and the flock from which the sheep came. There was an interaction between antibiotic type and number of feet infected and between antibiotic type and flock in association with the proportion of sheep cured. The extent of paring and the occurrence of blowfly strike in footrot lesions treated with diazinon had no significant association with the proportion of sheep cured.