A prospective, single arm study of intraosseous basivertebral nerve ablation for the treatment of chronic low back pain: 12-month results.

Background: The basivertebral nerve (BVN) has been a recently discovered target as a potential source for vertebrogenic chronic low back pain (CLBP). Prior randomized controlled trials have demonstrated safety and efficacy of BVN ablation for vertebrogenic CLBP, but minimal data exists regarding BVN ablation's clinical effectiveness with broader application outside of strict trial inclusion criteria. Methods: Prospective, single arm, open label effectiveness trial of 48 patients from community spine and pain practices treated with BVN ablation. Inclusion criteria required more than 6 months of CLBP and type 1 or 2 Modic changes on MRI to be enrolled. Patients were followed post procedure for 12 months using ODI, VAS, EQ-5D-5L and SF-36 patient reported outcome metrics.Results: 47 patients successfully received BVN ablation and 45 patients completed 12 months of follow up. Mean reduction in ODI at 12 months was 32.31 +/- 14.07 (p<0.001) with 88.89% (40/45) patients reporting a ≥15 point ODI decrease at 12 months. Mean VAS pain score decrease was 4.31+/-2.51 at 12 months (p<0.001) and more than 69% reported a 50% reduction in VAS pain scale. Similarly, SF-36 and EQ-5D-5L scores improved 26.27+/-17.19 and 0.22+/-0.15 (each p<0.001). Conclusions: This data supports the clinical effectiveness of BVN ablation in the community practice setting, with similar 12 month improvements in patient reported outcomes as seen in previously published randomized control trials.

Isolation of Leptospira interrogans from suburban rats in Tandil, Buenos Aires, Argentina.

The main objective of this study was to investigate the role of wild rodents as Leptospira spp. reservoirs in a suburban area of Tandil city, Buenos Aires province (Argentina), where a person had died due to pulmonary leptospirosis. The specific objectives were: to estimate the rodent density near the patient's home, to determine the serological prevalence and isolation of leptospirosis from wild rodents, and to identify the isolated strains. The area examined was a suburban neighbourhood in Tandil near the Langueyú stream, where the patient's house is located. Rattus norvegicus were trapped on the stream banks during two nights and a high capture rate (70%), was obtained. All rats (42) were examined serologically by the microscopic agglutination test (MAT), and 22 of them (52.3%) reacted with Leptospira serovars castellonis, canicola, grippotyphosa, icterohaemorrhagiae and hebdomadis at a titer of 1:50. The kidneys from 25 animals were cultured, and 24 isolates of L. interrogans (96%) were obtained. The isolated strains were identified as Icterohaemorrhagiae serogroup by MAT performed with rabbit hyperimmune reference sera. These findings showed a high density of suburban rodents highly infected with pathogenic leptospira, sharing environment in close contact with humans with evidence of leptospiral disease.

The impact of ART scale upon health workers: evidence from two South African districts.

This study explores the effects of antiretroviral treatment (ART) programmes on health-care human resources in South Africa. The study included two parts, a questionnaire-based survey of 269 health workers published earlier and a qualitative study of 21 purposively selected health practitioners involved in ART scale up. Contrary to what has been presented in literature, our survey showed that health workers in ART programmes experienced higher levels of morale, lower stress, lower sickness absenteeism and higher levels of job satisfaction. This paper uses qualitative data to provide insights into the working environment of ART workers and examines some possible explanations for our survey findings. The key factors that contribute to the different perception of working environment by ART workers identified in this study include bringing hope to patients, delaying deaths, acquiring training and the ability to better manage and monitor the disease.

Psychosocial aspects of PKU: hidden disabilities--a review.

Phenylketonuria (PKU) is an inborn error of metabolism, and its detrimental effects on neurocognitive functioning have been well studied. Early detection and treatment of PKU prevent the severe consequences of this disorder. However, even early- and well-treated patients experience hidden disabilities, including subtle deficits in executive functioning, mild reductions in mental processing speed, social difficulties, and emotional problems that may remain unnoticed for years. Poor executive function (EF) may impact treatment adherence and may lead to psychosocial deficits that are not always visible. These psychosocial aspects include social difficulties and psychosocial problems, such as forming interpersonal relationships, achieving autonomy, attaining educational goals, and having healthy emotional development. Studies report EF deficits in children and adults with early-treated PKU, which contribute significantly to the hidden disabilities in this population. In adults, hidden disabilities affect job performance and social relationships as a result of residual attention deficits, poor EF (e.g., planning, organizing), and reduced processing speed. An indirect relationship also exists between quality of life and EF impairment. In the absence of overt psychiatric symptoms, low level depressive or anxious symptom may be present. The interaction between the neurocognitive deficits and psychiatric symptoms puts this population of patients at significant risk for experiencing hidden disability. PKU is a disorder in which a less than optimal psychosocial outcome arises from the cumulative impact of relatively mild symptoms. The key to reducing risks associated with PKU is metabolic control throughout life.

20p12.3 microdeletion predisposes to Wolff-Parkinson-White syndrome with variable neurocognitive deficits.

BACKGROUND: Wolff-Parkinson-White syndrome (WPW) is a bypass re-entrant tachycardia that results from an abnormal connection between the atria and ventricles. Mutations in PRKAG2 have been described in patients with familial WPW syndrome and hypertrophic cardiomyopathy. Based on the role of bone morphogenetic protein (BMP) signalling in the development of annulus fibrosus in mice, it has been proposed that BMP signalling through the type 1a receptor and other downstream components may play a role in pre-excitation. METHODS AND RESULTS: Using the array comparative genomic hybridisation (CGH), we identified five individuals with non-recurrent deletions of 20p12.3. Four of these individuals had WPW syndrome with variable dysmorphisms and neurocognitive delay. With the exception of one maternally inherited deletion, all occurred de novo, and the smallest of these harboured a single gene, BMP2. In two individuals with additional features of Alagille syndrome, deletion of both JAG1 and BMP2 were identified. Deletion of this region has not been described as a copy number variant in the Database of Genomic Variants and has not been identified in 13 321 individuals from other cohort examined by array CGH in our laboratory. CONCLUSIONS: Our findings demonstrate a novel genomic disorder characterised by deletion of BMP2 with variable cognitive deficits and dysmorphic features and show that individuals bearing microdeletions in 20p12.3 often present with WPW syndrome.

Microdeletion/duplication at 15q13.2q13.3 among individuals with features of autism and other neuropsychiatric disorders.

BACKGROUND: Segmental duplications at breakpoints (BP4-BP5) of chromosome 15q13.2q13.3 mediate a recurrent genomic imbalance syndrome associated with mental retardation, epilepsy, and/or electroencephalogram (EEG) abnormalities. PATIENTS: DNA samples from 1445 unrelated patients submitted consecutively for clinical array comparative genomic hybridisation (CGH) testing at Children's Hospital Boston and DNA samples from 1441 individuals with autism from 751 families in the Autism Genetic Resource Exchange (AGRE) repository. RESULTS: We report the clinical features of five patients with a BP4-BP5 deletion, three with a BP4-BP5 duplication, and two with an overlapping but smaller duplication identified by whole genome high resolution oligonucleotide array CGH. These BP4-BP5 deletion cases exhibit minor dysmorphic features, significant expressive language deficits, and a spectrum of neuropsychiatric impairments that include autism spectrum disorder, attention deficit hyperactivity disorder, anxiety disorder, and mood disorder. Cognitive impairment varied from moderate mental retardation to normal IQ with learning disability. BP4-BP5 covers approximately 1.5 Mb (chr15:28.719-30.298 Mb) and includes six reference genes and 1 miRNA gene, while the smaller duplications cover approximately 500 kb (chr15:28.902-29.404 Mb) and contain three reference genes and one miRNA gene. The BP4-BP5 deletion and duplication events span CHRNA7, a candidate gene for seizures. However, none of these individuals reported here have epilepsy, although two have an abnormal EEG. CONCLUSIONS: The phenotype of chromosome 15q13.2q13.3 BP4-BP5 microdeletion/duplication syndrome may include features of autism spectrum disorder, a variety of neuropsychiatric disorders, and cognitive impairment. Recognition of this broader phenotype has implications for clinical diagnostic testing and efforts to understand the underlying aetiology of this syndrome.

Tungiasis / Tungiasis

We present a ten years' old patient immune competent, with multiple lesions of tungiasis in both feet, that consult when she returned of her vacations in Paraguay. We make a brief description of the topic.

Se presenta una paciente de 10 años de edad inmunocompetente con lesiones múltiples de tungiasis en ambos pies, que consulta al regreso de sus vacaciones en Paraguay. Se efectúa una breve revisión del tema.

Utilización de un modelo animal para entrenamiento, en oxigenación por membrana extracorporea (ECMO) / The use of an animal model for extracorporeal membrane oxygenation (ECMO) training

ECMO es un procedimiento de rescate de recién nacidos (RN) con fallo respiratorio hipoxémico severo que no responde al tratamiento convencional. Previo a la instrumentación de esta técnica en pacientes, se realizó el entrenamiento experimental en animales. Existe escasa bibliografía sobre la utilización de porcinos como modelo animal en ECMO. Se reportan, en cambio, la implementación de otros animales, tales como el cordero. Objetivo: determinar la utilidad y el comportamiento modelo animal eligido, su respuesta al procedimiento de ECMO, describir la técnica utilizada y sus resultados. Método: se utilizaron dos porcinos de la raza Landrace, de 30 y 45 días de vida. Se canularon la vena yugular interna y la arteria carótida interna derechas; se realizó el ensamblado y purgado del circuito. El bypass se inició con un flujo de bomba de 20 mL/K/min, aumentandose hasta 100-120 mL/K/min; logrado un flujo de 80 mL/K/min se disminuyeron los parámetros de Asistencia Respiratoria Mecánica (ARM) a nivel de reposo. Durante el curso de ECMO se practicaron diferentes acciones relacionadas con el manejo del sistema de perfusión y evaluación del comportamiento clínico del modelo. Finalmente se suspendió electivamente el procedimiento; luego el animal fue dacanulado y recuperado. Resultados: tiempo promedio de ECMO: 24.5 horas. Signos vitales del animal estables. No hubo complicaciones relacionadas con el circito, ni presencia de sangrado sistémico. Se lograron tasas deseadas de hemofiltración. Ambos animales sobrevivieron. Como complicación se registró hematuria en un caso. Conclusión: El modelo animal elegido, para el entrenamiento en el manejo de ECMO, fue satisfactorio.

Exercise-induced pulmonary haemorrhage during submaximal exercise.

REASONS FOR PERFORMING STUDY: Maximally exercising horses achieve mean pulmonary artery pressures (Ppa(mean)) that exceed the minimum threshold (75 mmHg) estimated for pulmonary capillary rupture and exercise-induced pulmonary haemorrhage (EIPH). EIPH is not expected to occur during moderate submaximal exercise (i.e. 40-60% VO2max) since Ppa(mean) remains well below this threshold. HYPOTHESIS: Prolonged submaximal exercise (trotting) would precipitate locomotory respiratory uncoupling and cause EIPH. This would be present as a result of the most negative intrapleural pressures (as estimated by the minimum oesophageal pressure; Poes(min)) occurring simultaneously with the most positive Ppa (Ppa(peak)) to produce estimated maximal pulmonary artery transmural pressures (PATMPmax) that surpass the EIPH threshold. METHODS: Five Thoroughbred horses trotted to fatigue (approximately 25 min) at 5 m/sec on a 10% incline. Ventilation (V(E)), Poes, and Ppa were measured at 5 min intervals, and bronchoalveolar lavage (BAL) red blood cells (RBCs) were quantified 45 min post exercise. RESULTS: BAL revealed an increased EIPH (rest: 2.0 +/- 1 x 10(5), exercise: 17 +/- 10 x 10(5) RBCs/ml BALF; P<0.05), despite the highest Ppamean reaching only mean +/- s.e. 55 +/- 3 mmHg, while V(E), tidal volume and Poes(min) approached 70-80% of the values achieved at maximal running speeds (10% incline: 12-13 m/sec) by these same horses. The resulting PATMPmax was well above the level considered causative of EIPH. CONCLUSIONS: The finding of significant EIPH during submaximal exercise broadens the spectrum of performance horses susceptible to EIPH and supports studies that suggest that extravascular factors are of primary importance in the aetiology of EIPH. POTENTIAL RELEVANCE: Consideration of strategies such as the equine nasal strip for reducing negative extravascular pressures is warranted even for exercise at moderate intensities.

Effectiveness of an experimental consensus phytase in improving dietary phytate-phosphorus utilization by weanling pigs.

Consensus phytase is a new biosynthetic, heat-stable enzyme derived from the sequences of multiple homologous phytases. Two experiments were conducted to determine its effectiveness, relative to inorganic P and a mutant enzyme of Escherichia coli phytase (Mutant-EP), in improving dietary phytate-P availability to pigs. In Exp. 1, 36 pigs (3 wk old, 7.00 +/- 0.24 kg of BW) were fed a low-P corn-soybean meal basal diet plus consensus phytase at 0, 250, 500, 750, 1,000, or 1,250 U/kg of feed for 5 wk. Plasma inorganic P concentration, plasma alkaline phosphatase activity, bone strength, and overall ADG and gain:feed ratio of pigs were improved (P < 0.05) by consensus phytase in both linear (R2 = 0.20 to 0.70) and quadratic (R2 = 0.30 to 0.70) dose-dependent fashions. In Exp. 2, 36 pigs (4 wk old, 9.61 +/- 0.52 kg BW) were fed the basal diet + inorganic P at 0.1 or 0.2%, consensus phytase at 750 or 450 U/kg of feed, Mutant-EP at 450 U/kg of feed, or 225 U consensus + 225 U Mutant-EP/kg of feed. Pigs fed 750 U of consensus phytase or 450 U of Mutant-EP/kg feed had plasma inorganic concentrations and bone strength that fell between those of pigs fed 0.1 or 0.2% inorganic P. These two measures were 16 to 29% lower (P < 0.05) in pigs fed 450 U of consensus phytase/kg of feed than those of pigs fed 0.2% inorganic P. Plasma inorganic P concentrations were 14 to 29% higher (P < 0.05) in pigs fed Mutant-EP vs. consensus phytase at 450 U/kg at wk 2 and 3. In conclusion, the experimental consensus phytase effectively releases phytate P from the corn-soy diet for weanling pigs. The inorganic P equivalent of 750 U of consensus phytase/kg of feed may fall between 0.1 and 0.2%, but this requires further determination.

Analysis of lacI mutations in Big Blue transgenic mice subjected to parasite-induced inflammation.

Parasite infections have long been associated with specific types of human cancers. Schistosoma hematobium is an inducer of urinary bladder cancer, Helicobacter pylori is a gastric carcinogen, and hepatitis B virus and Opisthorchis viverrini are causative agents of hepatocellular carcinoma. Another liver fluke, Fasciola hepatica, has also been identified as a neoplastic risk agent, primarily in animals. We used F. hepatica-induced inflammation in mice to determine if the presence of an aggressive liver fluke could induce mutagenic events in mammalian tissue. This provides a perspective on the relationship between chronic inflammation and cancer and may be a model for future studies on this complex association. In previous studies using the Big Blue transgenic mouse assay, we demonstrated an increase in lacI mutations in liver cells harvested from mice harboring F. hepatica flukes when compared to uninfected control animals. In these studies, we report on the types of mutations associated with this parasite infection. The observed mutational spectrum roughly corresponded to the spectrum of spontaneous mutations in liver cells when compared to control (uninfected) animals. However, the spectrum of mutations from parasitized animals showed a significant increase in complex changes and multiple mutations (18.2%) when compared to what would be expected from control animals (2.8%).

Ecological conceptual models: a framework and case study on ecosystem management for South Florida sustainability.

The Everglades and South Florida ecosystems are the focus of national and international attention because of their current degraded and threatened state. Ecological risk assessment, sustainability, and ecosystem and adaptive management principles and processes are being used nationally as a decision and policy framework for a variety of types of ecological assessments. The intent of this study is to demonstrate the application of these paradigms and principles at a regional scale. The effects-directed assessment approach used in this study consists of a retrospective, eco-epidemiological phase to determine the causes for the current conditions and a prospective predictive risk-based assessment using scenario analysis to evaluate future options. Embedded in these assessment phases is a process that begins with the identification of goals and societal preferences which are used to develop an integrated suite of risk-based and policy relevant conceptual models. Conceptual models are used to illustrate the linkages among management (societal) actions, environmental stressors, and societal/ecological effects, and provide the basis for developing and testing causal hypotheses. These models, developed for a variety of landscape units and their drivers, stressors, and endpoints, are used to formulate hypotheses to explain the current conditions. They are also used as the basis for structuring management scenarios and analyses to project the temporal and spatial magnitude of risk reduction and system recovery. Within the context of recovery, the conceptual models are used in the initial development of performance criteria for those stressors that are determined to be most important in shaping the landscape, and to guide the use of numerical models used to develop quantitative performance criteria in the scenario analysis. The results will be discussed within an ecosystem and adaptive management framework that provides the foundation for decision making.

Predictive indexes of nocturnal desaturation in COPD patients not treated with long term oxygen therapy.

Nocturnal oxygen desaturation during the sleep is very frequent in patients affected by chronic obstructive pulmonary disease (COPD). Hypoventilation, rather than sleeping apnea, is commonly considered as the most relevant factor in the onset of nocturnal oxygen desaturation. On this topic, the Authors have carried on a study on the nocturnal hypoxemia in 70 hospitalized COPD patients with a mean FEV1% of 40 +/- 21 and a mean PaO2 of 67.7 +/- 6.1. Anthropometric features (sex, age, body mass index) and functional respiratory parameters (FEV1, FEV1/VC, PaO2, PaCO2, SaO2, pH) were considered. Moreover all the patients were monitorized with transcutaneous pulse oxymetry, while breathing environmental air, in nighttime. Mean oxyhemoglobinic nocturnal saturation (SaO2 noct.%), minimum registered value of nocturnal SaO2 (min SaO2 noct.%) and the minutes of nighttime SaO2 < or = 90% and < or = 85% (tSaO2 < or = 90% e < or = 85%) were considered. Fiftyfour patients (77.15%) were nocturnal desaturating (NOD), whereas 16 (22.85%) were not desaturating (nNOD). A statistically significant difference was found between the two groups as to the values of FEV1 (p < 0.05), PaCO2, pH, SaO2 noct.%, minimum SaO2 noct.% and tSaO2 < or = 90% and < or = 85% (p < 0.0001). A statistically significant correlation was found between tSaO2 < 90% and BMI (r = 0.44), PaCO2 (r = 0.48) and pH (r = -0.44), as well as between tSaO2 < 85% and PaCO2 (r = 0.57) and pH (r= -0.50), between SaO2 noct.% and BMI (r = -0.45), PaCO2 (r = -0,50), FEV1 (r = 0.44) and pH (r = 0.46) and finally between minimum SaO2 noct.% and PaCO2 (r = -0.47) was found. Eighty percent of the NOD patients had PaO2 < 75 mm Hg and PaCO2 > 44 mm Hg. All the patients with PaCO2 > 50 mm Hg were NOD. In conclusion, all COPD subjects with FEV1 < 49% and daytime PaO2 > 60 mm Hg, particularly when associated to elevated PaCO2 values and high BMI, should undergo a nocturnal pulse oxymetry in order to identify possible nocturnal desaturations. In these patients reduced FEV1, high BMI and/or elevated PaCO2 appear to be predictive indexes of nocturnal desaturation. A PaCO2 > 50 mm Hg is highly indicative for a nocturnal oxygen desaturation.

Implementation and evaluation of a clinical pathway for TRAM breast reconstruction.

Among strategies recently proposed to reduce practice variation, promote quality, and control costs in health care delivery, the concept of the clinical pathway has received considerable attention. Because transverse rectus abdominis musculocutaneous (TRAM) breast reconstruction is a common and often costly intervention, this institution sought to evaluate cost and quality outcomes of a clinical pathways program for this procedure. The TRAM reconstruction clinical pathway was implemented in April of 1996 to standardize postoperative care in this patient population. Outcomes of consecutive pathway cases for the first 14 months of the program were assessed in a retrospective cohort design, by using all nonpathway TRAM cases from the 18 months immediately before pathway implementation as controls. Outcomes assessed included length of hospital stay, postoperative complications, total postoperative charges, and total postoperative costs in relative value units. Data on these dependent variables were collected from hospital charts and billing records. The effects of pathway implementation on the outcomes of interest were analyzed by using analysis of covariance to control for potential confounding by other independent variables, including surgical site (unilateral versus bilateral reconstructions), technique (pedicle versus free TRAMs), timing (immediate versus delayed reconstructions), and patient age. Finally, a comparison of variances in the outcomes of interest between the two groups was analyzed by using an Ftest. For all statistical tests, p values of < or = 0.05 were considered significant. Twenty-nine patients were treated in the TRAM pathway group, whereas the control population included 40 nonpathway patients. After implementation of the TRAM pathway, length of stay decreased from 6.0 to 5.2 days; total postoperative charges were reduced from $8587 to $7744; and total postoperative relative value unit utilization declined from 1686 to 1104. Analysis of covariance showed that the decreases in length of hospital stay and relative value units in the TRAM pathway were statistically significant (p = 0.05 and p = 0.007, respectively). By contrast, no significant increase in complications was observed after pathway implementation. Variability in the TRAM pathway group, as measured by SD, decreased significantly for both length of hospital stay (p = 0.039) and relative value units (p = 0.023). Implementation of the TRAM reconstruction clinical pathway resulted in significant declines in length of hospital stay and total costs. These decreases in resource utilization had no significant effect on postoperative complication rates. Although additional research is needed to further assess the impact of clinical pathways, this approach offers considerable promise for improving the cost-effectiveness of health care.

Ecological risk assessment: implications of hormesis.

Hormesis is a widespread phenomenon across many taxa and chemicals, and, at the single species level, issues regarding the application of hormesis to human health and ecological risk assessment are similar. For example, convincing the public of a 'beneficial' effect of environmental chemicals may be problematic, and the design and analysis of laboratory studies may require modifications to detect hormesis. However, interpreting the significance of hormesis for even a single species in an ecological risk assessment can be complicated by considerations of competition with other species, predation effects, etc. Ecological risk assessments involve more than a single species; they may involve communities of hundreds or thousands of species as well as a range of ecological processes. Applying hormetic adjustments to threshold effect levels for chemicals derived from sensitivity distributions for a large number of species is impractical. For ecological risks, chemical stressors are frequently of lessor concern than physical stressors such as habitat alteration or biological stressors such as introduced species, but the relevance of hormesis to non-chemical stressors is unclear. Although ecological theories such as the intermediate disturbance hypothesis offer some intriguing similarities between chemical hormesis and hormetic-like responses resulting from physical disturbances, mechanistic explanations are lacking. Further exploration of the relevance of hormesis to ecological risk assessment is desirable. Aspects deserving additional attention include developing a better understanding of the hormetic effects of chemical mixtures, the relevance of hormesis to physical and biological stressors and the development of criteria for determining when hormesis is likely to be relevant to ecological risk assessments.