Clinical Outcomes of Sequential Intrastromal Corneal Ring Segments and an Extended Range of Vision Intraocular Lens Implantation in Patients with Keratoconus and Cataract.

PURPOSE: To evaluate efficacy, safety, and predictability of sequential Ferrara-type intrastromal corneal ring segments (ICRS) and an extended range of vision intraocular lens (IOL) implantation in patients with keratoconus and cataract. METHODS: This study comprised patients with keratoconus and cataract that had ICRS implantation followed 6 months later by extended range of vision IOL implantation. The uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), and residual refractive errors, analysed using vector analysis, were recorded preoperatively, 6 months after ICRS implantation, and 6 months after IOL implantation, respectively. RESULTS: The study enrolled 17 eyes (11 patients). The mean UDVA (logMAR scale) was 1.15 ± 0.67 preoperatively, 0.88 ± 0.69 six months after ICRS implantation (P = 0.005), and 0.27 ± 0.18 six months after IOL implantation (P < 0.0001). The CDVA changed from 0.26 ± 0.15 (logMAR) before surgery to 0.17 ± 0.08 six months after Ferrara-type ICRS implantation (P = 0.002) and to 0.07 ± 0.06 six months after IOL implantation (P < 0.0001). The spherical equivalent and the refractive cylinder declined steeply after IOL implantation (P < 0.001). The magnitude of depth of focus was 2.60 ± 1.02 D. There were no statistically significant differences in visual acuity for a defocus range from +0.50 D to -0.50 D (P > 0.1). CONCLUSION: Sequential Ferrara-type ICRS and an extended range of vision IOL implantation provided good visual and refractive outcomes, being an effective, safe, and predictable procedure for the treatment of selected cases of patients with keratoconus and cataract. In addition, this approach provides an increase of tolerance to defocus.

CD38 protein deficiency induces autoimmune characteristics and its activation enhances IL-10 production by regulatory B cells.

CD38 is a transmembrane protein expressed in B lymphocytes, and is able to induce responses as proliferation, differentiation or apoptosis. Several reports propose that CD38 deficiency accelerates autoimmune processes in murine models of autoimmune diabetes, lymphoproliferation and rheumatoid arthritis. Other reports have shown elevated CD38 expression in B and T cells from patients with autoimmunity; however, the role of CD38 is still unclear in the development of autoimmunity. Recently, it has been characterized as CD1dhi CD5+ regulatory B cell subpopulation able to produce IL-10, and the loss of these cells exacerbates the autoimmunity in murine models. Here, we report that CD38-/- mice exhibited elevated titres of ANAS, anti-dsDNA autoantibodies from 12 months of age and were higher by 16 months of age and mice presented kidney damage. Interestingly, there is a reduction in the survival of CD38-/- mice compared to the WT. Furthermore, CD38 is highly expressed by CD1dhigh CD5+ regulatory B cells, and the agonistic anti-CD38 stimulus plus LPS was able to increase the percentage of this cell subset and its ability to induce IL-10 production. Together, these results suggest that CD38 could play a role in the control of autoimmune diseases through their expression on regulatory B cells.

Horizontal gaze palsy and progressive scoliosis in a patient with congenital esotropia and inability to abduct. A case report. / Parálisis de la mirada horizontal y escoliosis progresiva en un paciente con endotropia congénita y limitación de abducción. A propósito de un caso.

CASE REPORT: The case is presented on a 4- year-old child with congenital esotropia, limitation of abduction, cross-fixation, and thoracolumbar scoliosis. Genetic testing of ROBO3 gene confirmed the diagnosis of horizontal gaze palsy and scoliosis (HGPSS) DISCUSSION: HGPPS is a rare congenital disorder characterised by absence of conjugate horizontal eye movements and progressive scoliosis developed in childhood and adolescence. We highlight this motility disorder as a part of the differential diagnosis of early childhood esotropia with cross- fixation and limitation of abduction.

Atypical carcinoid tumours of the lung: prognostic factors and patterns of recurrence.

BACKGROUND: Atypical carcinoids (AC) of the lung are rare intermediate-grade neuroendocrine neoplasms. Prognostic factors for these tumours are undefined. METHODS: Our cooperative group retrieved data on 127 patients operated between 1980 and 2009 because of an AC. Several clinical and pathological features were studied. RESULTS: In a univariable analysis, T-status (p=0.005), N-status (p=0.021), preoperative M-status (previously treated) (p=0.04), and distant recurrence developed during the outcome (p<0.001) presented statistically significant differences related to survival of these patients. In a multivariable analysis, only distant recurrence was demonstrated to be an independent risk factor for survival (p<0.001; HR: 13.1). During the monitoring, 25.2% of the patients presented some kind of recurrence. When we studied recurrence factors in a univariable manner, sublobar resections presented significant relationship with locoregional recurrence (p<0.001). In the case of distant recurrence, T and N status presented significant differences. Patients with preoperative M1 status presented higher frequencies of locoregional and distant recurrence (p=0.004 and p<0.001, respectively). In a multivariable analysis, sublobar resection was an independent prognostic factor to predict locoregional recurrence (p=0.002; HR: 18.1). CONCLUSIONS: Complete standard surgical resection with radical lymphadenectomy is essential for AC. Sublobar resections are related to locoregional recurrence, so they should be avoided except for carefully selected patients. Nodal status is an important prognostic factor to predict survival and recurrence. Distant recurrence is related to poor outcome.

Neuroendocrine tumors of the lung: hystological classification, diagnosis, traditional and new therapeutic approaches.

Lung neuroendocrine tumors are neoplasms originating from bronchopulmonary neuroendocrine cells, usually Kulchitsky cells, loaded with argentaffin granules. They account for 20-25% of all primitive lung tumors, the most common being the small-cell undifferentiated carcinoma. They include different tumors, from tumors of low-grade malignancy, especially the typical carcinoids, with high survival rates after surgical therapy, to the high-grade malignancy tumors, especially small-cell undifferentiated carcinomas. The latter have very few indications for surgical treatment with a low survival rate, even after multimodal therapy. The aim of this review is to describe the present knowledge and discuss possible new developments in the management of pulmonary neuroendocrine tumors. The authors examine and discuss in particular the role that surgical techniques should have in the treatment of small-cell lung cancer in opposition to a nihilism position that has limited therapies to non-surgical approaches. The critical review of this attitude opens the door to a more aggressive approach. In the meantime the review shows that it might be possible to include the new minimally invasive percutaneous ablative techniques as cryosurgery, thermotherapy and irreversible electroporation within a modern and flexible framework. The authors also present the hypothesis that cancer stem cells (CSC) are at the basis of recurrences of small-cell lung cancer (SCLC) and therefore that the issue is of difficult solution with the conventional oncologic approach considering the chemo-resistance of CSC to drugs. For these reasons an epigenetic therapy based on differentiation factors is proposed alongside the usual surgical and chemo-radiation protocols.

Chronic inflammatory demyelinating polyradiculoneuropathy in a patient with systemic lupus erythematosus and good outcome with rituximab treatment.

A patient with chronic inflammatory demyelinating polyradiculoneuropathy and systemic lupus erythematosus arising after rubella vaccination was initially treated with plasmapheresis, corticosteroids and intravenous immunoglobulins, with partial response. After shift to rituximab, most clinical symptoms improved markedly, emphasizing the possible role of this monoclonal antibody in conventional therapy-resistant cases.

Oral health status and inequalities among ambulant older adults living in central Chile.

OBJECTIVE: To assess the oral health status and treatment needs of older adults, living in the Valparaiso Region of Chile. BASIC RESEARCH DESIGN: A random sample of 354 older adults, aged 60 years or older, living independently in the community were examined orally by calibrated examiners and underwent a structured oral health interview. Data collection extended from October 2006 to June 2007. RESULTS: This was a largely dentate population (80%) with a mean DMFT score of 21.6 (s.d. 5.7). While about 28% of the dentate sample had all their restorative needs unmet, 30.8% had all of their restorative needs met. Regarding periodontal health, 3.3% had sound periodontum; complex periodontal therapy (CPI 3-4) was needed by 43.1% of the sample. CONCLUSION: This study represents one of the largest data collections in oral health among older adults living in Chile. Participants seemed to have better oral health status than previously reported. Of particular relevance is the reduction of the decayed component and the increased number of sound teeth in the present sample. Participants also presented lower need for advance periodontal treatment. Yet, inequalities were apparent in the proportion of unmet restorative needs. Strategies to develop oral health care programmes focused on improving access to and use of preventive services for older adults are critical. Further research is indicated to get a more complete picture of the factors that shape the oral health of Chilean older adults.

Multiple primary cancer: an increasing health problem. Strategies for prevention in cancer survivors.

This study was set to look for associations between the sites of the first and subsequent tumours in patients with multiple primary cancer (MPC) diagnosed from 1975 to 2002 in the reference hospital of a Spanish northern region, and propose prevention strategies. Patient and tumour variables were measured. Crude and standardized incidence rates per 100 000 inhabitants were obtained, and the association between MPC incidence and time was analysed by means of lineal regression. Relative risks were calculated to analyse associations between tumour sites. A total of 2737 MPC cases were registered (male/female ratio = 2). The percentage of MPC with respect to the total cancer increased from 1.78% in the 1975-1979 period to 7.08% in the 2000-2002 period (R(2) = 0.92; P = 0.003). Great increase of incidence by time was found (R(2) = 0.90; P = 0.004). Breast, prostate and bladder cancers increase risk of second tumour in female genital organs [RR 4.78 (3.84-5.93)], urinary system [RR 3.69 (2.89-4.69)] and male genital organs [RR 3.76 (2.84-4.69)] respectively. The MPC incidence is increasing. Interventions for MPC prevention, according to the European Code against Cancer, should be implemented early after the first cancer principally if patients suffer breast, bladder, prostate, larynx and colon cancers.

Regional-specific regulation of BDNF and trkB correlates with nigral dopaminergic cell sprouting following unilateral nigrostriatal axotomy.

Axotomy is a powerful stimulus of axon growth and plastic changes. We investigated the potential role of BDNF/trkB signaling in the sprouting of dopaminergic nigral axons in response to axotomy of the medial forebrain bundle. Tyrosine hydroxylase immunohistochemistry revealed the existence of sprouting mechanisms in the axotomized substantia nigra (SN). Time-course changes of trkB mRNA expression demonstrated a robust increase in an area projecting from the rostral tip of the SN to the glial scar, which coincided with evidence of nigral dopaminergic sprouting. In addition, we found an early loss of this messenger in areas related to the knife cut, which recovered by 7 days postlesion. TrkB down-regulation appeared to be associated to the lesion-induced local damage, as it was restricted to an area showing Fluoro-Jade B- and TUNEL positive cells. In trkB-depleted areas, an inverse correlation between mRNA expressions of BDNF and trkB was apparent. Specific induction of BDNF mRNA was mostly seen in border of areas devoid of trkB mRNA. In contrast, in the areas exhibiting trkB mRNA expression, no BDNF mRNA was detected. We suggest that trkB levels could be a determinant element in regulating BDNF expression. Finally, the search for molecules involved in either promoting or inhibiting axonal growth, demonstrated up-regulation of GAP-43 and Nogo-A mRNA at sites close to the knife transections as early as 1 day postlesion. However, overall, Nogo-A induction was more robust than that seen for GAP-43.

Periodontitis as risk factor for acute myocardial infarction. A case control study of Spanish adults.

OBJECTIVE: The present study was designed to determine, in a case-control study of a Spanish population, whether periodontitis is a risk factor for acute myocardial infarction. BACKGROUND: Although part of cardiovascular risk could be explained by periodontal disease, available meta-analyses find significant heterogeneity and recommend the need for further observational and intervention studies. METHODS: A case-control study was conducted of 149 Spanish patients aged between 40 and 75 years, with 72 cases (acute myocardial infarction) and 77 controls (trauma patients). Periodontitis was measured as the percentage of sites with clinical attachment loss greater than 3 mm. A multivariate logistic regression model was constructed to estimate the adjusted effect of periodontitis on acute myocardial infarction, after considering the potential confounding effect of a large pool of risk factors. RESULTS: In a bivariate analysis, males, older patients, smokers, and those with hypertension, diabetes or hypercholesterolemia, showed an increased risk of acute myocardial infarction. The cases, compared to controls, showed worse results for all periodontal variables studied: gingival retraction, pocket depth, and periodontitis. The final multiple logistic model included sex, age, tobacco habit, hypertension, diabetes, hypercholesterolemia, regular exercise, and periodontitis. The association between periodontitis (dichotomized) and acute myocardial infarction was high and significant in both the unadjusted (odds ratio = 4.42, p < 0.001) and adjusted analyses (odds ratio = 3.31, p = 0.005). CONCLUSION: There is evidence of an association between periodontitis and acute myocardial infarction after adjusting for well-known risk factors for acute myocardial infarction.

Female gender and wealth are associated to overweight among adolescents in La Paz, Bolivia.

OBJECTIVE: To describe the prevalence of overweight, obesity and being thin in adolescents of La Paz City, Bolivia. DESIGN: Cross-sectional study, clustered sampling. SETTING: La Paz, Bolivia, August-September 2003. SUBJECTS: Height and weight of 525 adolescents (mean age 16 y; s.d.+/-1.3) attending public and private schools were measured; sociodemographic characteristics were assessed with a short questionnaire. RESULTS: The present study reveals that 9.3% (+/-2.5) of the sample are thin adolescents; 19.8% (+/-3.4) is the overall prevalence of overweight and 2.3% (+/-1.3) the overall prevalence of obesity. The odds of being thin were higher among those working (P=0.03) and among those of higher age (P<0.001). The odds of being overweight were higher among female subjects (P<0.001). The odds of being obese were higher among younger adolescents (P=0.046) and among the more wealthy ones (P=0.044). CONCLUSIONS: A large prevalence of 22% overweight/obesity in adolescents from La Paz City was observed. The findings support the need of enhanced nutritional surveillance and interventions particularly in female adolescents.

Validation of a questionnaire to evaluate the attitude towards primary prevention advice from the European code against cancer.

Educative interventions to promote primary prevention of cancer (PPC) should be based on psychosocial models and be tailored to attitude. Attitude is a difficult variable to measure. The aim of this study was to draw up a questionnaire to evaluate the attitude to PPC of relatives of patients affected by cancer. An interview of 48 patients, who answered open questions, allowed 67 items to be drawn up. Three hundred and fifty-five people answered the self-administered questionnaire of 67 items (69 of them did it twice, with an interval of 2 weeks). The factorial analysis revealed five factors that explain the 36% total and the 115% common estimated variance. The Cronbach's alpha oscillated between 0.80 and 0.93. The intraclass correlation coefficient was 0.7721 (95% CI (confidence interval) 0.6311-0.8592, P<0.0001). The analysis based on Samejima's model ordered the items according to their discriminating power and the difficulty/ease with which people agree with the most preventive option. The average scores obtained in both surveys of 69 people did not show significant statistical differences (P=0.195). The definitive questionnaire obtained has 63 items that measure attitude to PPC behaviour in a reliable and stable way.

[Medication errors in a neonatal unit]. / Errores en las prescripciones médicas en una unidad neonatal.

INTRODUCTION: Medication errors occur as a result of human mistakes or system flaws and could be prevented by studying and modifying the conditions that predispose to errors. In recent years, interest in medical errors has increased because of their health and economic implications. OBJECTIVES: To evaluate the frequency and types of prescribing errors in the Neonatology Unit of the Hospital 12 Octubre before and after an intervention to raise awareness of errors among the medical staff by comparing the frequency of error before and after the intervention. PATIENTS AND METHODS: We conducted a prospective pilot study in two phases. In the first phase, we studied prescribing errors by reviewing 100 prescriptions for newborns admitted to the Intensive or Intermediate Care Units. When the prescriptions were written, the neonatologists were unaware that the study would be performed. Legibility, dose, units used to express medications, route of administration, use of abbreviations, specification of dosage per kilogram of body weight and use of brand names were evaluated. The information was analyzed and an information-training intervention was performed in which the results were made known in a clinical session and recommendations for improving prescriptions were made. In the second phase, another 100 prescriptions were reviewed. The results were compared with those obtained before the intervention using the chi-squared test. RESULTS: In the first phase, 22 % of prescriptions were illegible or doubtful, 4 % contained dose errors and 28 % did not specify the route of administration. After the intervention, 8 % (p 0.005) of prescriptions were illegible, 4 % contained dose errors and 5 % (p 0.0001) did not specify the route of administration. Regarding other quality markers, the percentage of prescriptions specifying dosage per kilogram of body weight increased from 46 % to 78 %. Brand names were used in 21 %. Units were always expressed in abbreviations. All errors were severity index 0 or 1. CONCLUSIONS: The first step in prevention is recognition of mistakes. Increasing awareness among the medical staff of the consequences of errors improved the quality of prescriptions in our department. Awareness of the frequency and type of errors is the first step towards implementing strategies to reduce iatrogeny.

Cell therapy to repair injured spinal cords: olfactory ensheathing glia transplantation.

The absence of spontaneous axonal regeneration in the adult mammalian central nervous system cause devastating functional consequences in patients with spinal cord injuries. During the past decades several attempts have been made in order to find a strategy to repair injured spinal cords in experimental animals, that could provide a novel therapeutic approach in humans. Cell transplantation has been broadly used as an intervention to influence neuronal survival and axonal regeneration in the severed neuraxis. Of the cell types used for transplantation, olfactory ensheathing glia (OEG) promoted a dramatic functional improvement and anatomical repair after complete transection of the adult mammalian spinal cord. These cells can be easily obtained from adult donors opening the possibility of autologous transplantation. Grafting OEG to repair injured spinal cords offers some advantages compared to injections of other cell types. Therefore, OEG have become good candidates to bring about repair in damaged spinal cords. In this article we review OEG transplantation studies, discuss the properties that could account for their axonal growth-promoting ability, and the advantages of using OEG as a repair strategy.

Lung cancer risk in iron and steel foundry workers: a nested case control study in Asturias, Spain.

BACKGROUND: Workers of iron and steel foundries have a high lung cancer risk but the findings on specific processes associated with this risk are inconsistent. We examined the risk of lung cancer among workers in the main industrial processes of a large iron and steel foundry in Asturias, Spain. METHODS: We conducted a nested case-control study comprised of 144 male lung cancer cases and 558 controls, selected from a study base of about 24,400 workers employed in the industry between 1952 and 1995. Cases were identified through linkage of industry records with those of two cancer registries. Controls were selected through industry records using incidence density sampling, were matched to cases by age and date of birth and had to be alive and without lung cancer at the time of selection. Smoking history was obtained through company medical records. Unconditional logistic regression was applied and all ORs were adjusted for age and tobacco consumption. RESULTS: Workers were, on an average, heavy smokers and a very strong relation was observed for smoking (OR for "ever smoker" = 32.4). Workers having ever been employed in the blast furnace had an excess lung cancer risk (OR = 2.55, 95% CI 1.25-5.21) compared to a reference group of workers not employed in metal producing departments. A similar excess was observed for workers having as their longest held job employment in the blast furnace. A two-fold risk was also observed for workers in the main foundry. For subgroups of workers, tobacco smoking appeared to be an important positive or negative confounder. CONCLUSIONS: In this large Spanish foundry, a high risk was observed for workers employed in departments with high exposure to crystalline silica, PAHs, and various other carcinogenic chemicals. Although comparisons were made between workers of the same industry, smoking habits differed and adjustment by smoking modified considerably the risk estimates.

Functional recovery of paraplegic rats and motor axon regeneration in their spinal cords by olfactory ensheathing glia.

Axonal regeneration in the lesioned mammalian central nervous system is abortive, and this causes permanent disabilities in individuals with spinal cord injuries. In adult rats, olfactory ensheathing glia (OEG) transplants successfully led to functional and structural recovery after complete spinal cord transection. From 3 to 7 months post surgery, all OEG-transplanted animals recovered locomotor functions and sensorimotor reflexes. They presented voluntary hindlimb movements, they supported their body weight, and their hindlimbs responded to light skin contact and proprioceptive stimuli. In addition, relevant motor axons (corticospinal, raphespinal, and coeruleospinal) regenerated for long distances within caudal cord stumps. Therefore, OEG transplantation provides a useful repair strategy in adult mammals with traumatic spinal cord injuries. Our results with these cells could lead to new therapies for the treatment of spinal cord lesions in humans.