El proceso en España de la adopción de una legislación eficaz para la prevención del tabaquismo

The prevention movement has been the key agent involved in smoking control policies. This study describes the context and the process in which Law 28/2005 was passed in Spain with a synthesis of its substance. It provides the background of the events leading up to Spain's current smoking control law in addition to an analysis of the role played by the different social actors in the process and the arguments and strategies employed in opposition by the tobacco industry. A review is also provided of the political agents, highlighting that decentralized countries have further problems in enforcing regulations. This case offers lessons for the future.

A PRKAR1A Mutation Associated with Primary Pigmented Nodular Adrenocortical Disease in 12 Kindreds

CONTEXT: Primary pigmented nodular adrenocortical disease (PPNAD), a rare cause of corticotropin-independent Cushing syndrome, can be part of Carney complex (CNC), an autosomal dominant multiple neoplasia syndrome characterized by spotty skin pigmentation, cardiac myxomas, and endocrine tumors or be isolated (i). Germline PRKAR1A-inactivating mutations have been observed in both CNC and iPPNAD, but with no apparent genotype-phenotype correlation. OBJECTIVE:The objectives of the study were a detailed phenotyping for CNC manifestations in 12 kindreds bearing the same PRKAR1A mutation and a study of the consequences of the mutation and a potential founder effect. DESIGN: The study consisted of descriptive case reports. SETTING: The study was conducted at two referral centers. PATIENTS: The patients described in this study were referred for PRKAR1A gene mutation analysis because of a diagnosis of apparently iPPNAD. RESULTS: We describe a 6-bp polypyrimidine tract deletion [exon 7 IVS del (-7-->-2)] in 12 unrelated kindreds that were referred for Cushing syndrome due to PPNAD. Nine of the patients had no family history; in two, there was a family history of iPPNAD. Only one patient met the criteria for CNC. Relatives carrying the same mutation had no manifestations of CNC or PPNAD, suggesting a low penetrance of this PRKAR1A defect. A founder effect was excluded by extensive genotyping of chromosome 17 markers. CONCLUSIONS: In conclusion, a small intronic deletion of the PRKAR1A gene is a low-penetrance cause of mainly iPPNAD; it is the first PRKAR1A genetic defect to have an association with a specific phenotype.

Plasmid-mediated quinolone resistance in Australia

The aim of this study was to search for plasmid-encoded quinolone resistance determinants QnrA and QnrS in fluoroquinolone-resistant and extended-spectrum beta-lactamase (ESBL)-producing enterobacterial isolates recovered in Sydney, Australia, in 2002. Twenty-three fluoroquinolone-resistant, of which 16 were also ESBL-positive, enterobacterial and nonrelated isolates were studied. PCR with primers specific for qnrA and qnrS genes and primers specific for a series of ESBL genes were used. A qnrA gene was identified in two ESBL-positive isolates, whereas no qnrS-positive strain was found. The QnrA1 determinant was identified in an Enterobacter cloacae isolate and in a carbapenem-resistant Klebsiella pneumoniae isolate, both of which expressed the same ESBL SHV- 12. Whereas no plasmid was identified in the E. cloacae isolate, K. pneumoniae K149 possessed two conjugative plasmids, one that harbored the qnrA and bla (SHV)-12 genes whereas the other expressed the carbapenemase gene bla (IMP-4). The qnrA gene, was located in both cases downstream of the orf513 recombinase gene and upstream of the qnrA1 gene, a structure identical to that found in sul1-type integron In36 and qnrA-positive strains from Shanghai, China. However, the gene cassettes of the sul1-type integrons were different. This study identified the first plasmid-mediated quinolone resistance determinant in Enterobacteriaceae in Australia.

Naevus Lentiginosus Linearis: A Distinct Skin Disorder

Congenital naevi of the melanocytic system include numerous types, which differ in their clinical appearance, pattern of distribution, and histopathological features (1). Examples are large congenital melanocytic naevus, macular naevus spilus, papular naevus spilus, café-au-lait macules of neurofibromatosis 1, café-au-lait macules arranged in broad bands as noted in McCune-Albright syndrome, partial unilateral lentiginosis, naevus achromicus (naevus depigmentosus), phylloid hypermelanosis, and phylloid hypomelanosis (1–3). We describe here two patients with a systematized pigmentary naevus that differed from all naevi reported so far.

Outcome after relapse of acute lymphoblastic leukemia in adult patients included in four consecutive risk-adapted trials by the PETHEMA Study Group

BACKGROUND About one half of adults with acute lymphoblastic leukemia are not cured of the disease and ultimately die. The objective of this study was to explore the factors influencing the outcome of adult patients with relapsed acute lymphoblastic leukemia. DESIGN AND METHODS. We analyzed the characteristics, the outcome and the prognostic factors for survival after first relapse in a series of 263 adult patients with acute lymphoblastic leukemia (excluding those with mature B-cell acute lymphoblastic leukemia) prospectively enrolled in four consecutive risk-adapted PETHEMA trials. RESULTS. The median overall survival after relapse was 4.5 months (95% CI, 4-5 months) with a 5-year overall survival of 10% (95% CI, 8%-12%); 45% of patients receiving intensive second-line treatment achieved a second complete remission and 22% (95% CI, 14%-30%) of them remained disease free at 5 years. Factors predicting a good outcome after rescue therapy were age less than 30 years (2-year overall survival of 21% versus 10% for those over 30 years old; P<0.022) and a first remission lasting more than 2 years (2-year overall survival of 36% versus 17% among those with a shorter first remission; P<0.001). Patients under 30 years old whose first complete remission lasted longer than 2 years had a 5-year overall survival of 38% (95% CI, 23%-53%) and a 5-year disease-free survival of 53% (95% CI, 34%-72%). CONCLUSIONS The prognosis of adult patients with acute lymphoblastic leukemia who relapse is poor. Those aged less than 30 years with a first complete remission lasting longer than 2 years have reasonable possibilities of becoming long-term survivors while patients over this age or those who relapse early cannot be successfully rescued using the therapies currently available.

Multiple sclerosis risk variant HLA-DRB1*1501 associates with high expression of DRB1 gene in different human populations.

The human leukocyte antigen (HLA) DRB1*1501 has been consistently associated with multiple sclerosis (MS) in nearly all populations tested. This points to a specific antigen presentation as the pathogenic mechanism though this does not fully explain the disease association. The identification of expression quantitative trait loci (eQTL) for genes in the HLA locus poses the question of the role of gene expression in MS susceptibility. We analyzed the eQTLs in the HLA region with respect to MS-associated HLA-variants obtained from genome-wide association studies (GWAS). We found that the Tag of DRB1*1501, rs3135388 A allele, correlated with high expression of DRB1, DRB5 and DQB1 genes in a Caucasian population. In quantitative terms, the MS-risk AA genotype carriers of rs3135388 were associated with 15.7-, 5.2- and 8.3-fold higher expression of DQB1, DRB5 and DRB1, respectively, than the non-risk GG carriers. The haplotype analysis of expression-associated variants in a Spanish MS cohort revealed that high expression of DRB1 and DQB1 alone did not contribute to the disease. However, in Caucasian, Asian and African American populations, the DRB1*1501 allele was always highly expressed. In other immune related diseases such as type 1 diabetes, inflammatory bowel disease, ulcerative colitis, asthma and IgA deficiency, the best GWAS-associated HLA SNPs were also eQTLs for different HLA Class II genes. Our data suggest that the DR/DQ expression levels, together with specific structural properties of alleles, seem to be the causal effect in MS and in other immunopathologies rather than specific antigen presentation alone.

Giant proliferating trichilemmal malignant tumor

Proliferating trichilemmal cyst is a benign tumor that originates in the outer root sheath of hair follicle. Usually, it is located on the scalp in older women, but also have been reported in other sites such as back, chest, axilla, groin, gluteal region, thigh, vulva, and face. Malignant transformation of proliferating trichilemmal cyst is confirmed only on histological findings. This tumor has a variable biologic behavior with local recurrence and lymph node metastasis.

Citrulina plasmática como marcador de pérdida de masa enterocitaria en la enfermedad celíaca en la infancia

Introduction: Plasma citrulline is not incorporated in endogenous or exogenous proteins so it is a theoretical marker of villous atrophy. Our aim was to correlate plasma citrulline levels with severity of villous atrophy inceliac patients. Methods: Observational case-control study longitudinal in children 16 month-old to 14 year-old: 48 with untreated celiac disease, 9 celiac children under gluten free diet and 35 non-celiac healthy children. Plasma amino acids concentration is determined, expressed in μmol/L, and so are other clinical and analytical data. Results: No statistically significative difference found in the referring to BMI, age or renal function. Small increase in fecal fat in celiac children. Citrulline, arginine and glutamine are significantly lower in cases (17.7 μmol/l, 38.7 μmol/l, 479.6 μmol/l respectively) than in controls (28.9 μmol/l, 56.2 μmol/l, 563.7 μmol/l). Citrulline levels are significantly lower in the severe degrees of atrophy than in mild ones (13.8 μmol/l vs. 19.7 μmol/l, p < 0.05), not happening so with rest of amminoacids. Summary: Postabsortive mean of plasma citrulline is a good marker of reduction in enterocyte mass in celiac patients with villous atrophy; secondary reduction in plasma arginine too. Just a small histological alteration in intestinal biopsy is enough to differentiate citrulline in cases and controls and besides it can be seen that high levels of atrophy present with lower plasma citrulline.

Acute retroperitoneal bleeding due to inferior mesenteric artery aneurysm: case report

Background: Visceral artery aneurysms (VAA), although uncommon, are increasingly being detected. We describe a case of spontaneous retroperitoneal hemorrhage from a ruptured IMA aneurysm associated with stenosis of the superior mesenteric artery (SMA) and celiac trunk, successfully treated with surgery. Methods: A 65-year-old man presented with abdominal pain and hypovolemic shock. Abdominal CT scan showed an aneurysm of the inferior mesenteric artery with retroperitoneal hematoma. In addition, an obstructive disease of the superior mesenteric artery and celiac axis was observed. Results: Upon emergency laparotomy a ruptured inferior mesenteric artery aneurysm was detected. The aneurysm was excised and the artery reconstructed by end-to-end anastomosis. Conclusions This report discusses the etiology, presentation, diagnosis and case management of inferior mesenteric artery aneurysms

Deep-brain stimulation for Parkinson's disease

Comment on N Engl J Med. 2010 Jun 3;362(22):2077-91 author reply 988.

Diarrea crónica refractaria y malabsorción secundaria a hipogammaglobulinemia común variable, infestación crónica por giardia lambila y gastrectomía total por adenocarcinoma gástrico: un manejo nutricional complejo

Gastric cancer is a frequent cause of cancer-related mortality in the world. Surgery is the only potentially curative therapy, although the adverse effects of surgery are common and considerable. Common variable immunodeficiency is in many cases cause of gastrointestinal system problems such as chronic diarrhea caused by infestation with giardia lamblia, nodular lymphoid hiperplasia ad loss of villi leading frequently to malapsortion and malnutrition. Nutritional deficiencies due to malapsorption (postgastrectomy and secondary to loss of villi, giardiasis and common variable inmunodeficiency) are common. We present the case of a patient with gastric cancer who underwent a gastrectomy with common variable hipogammaglobulinemia and chronic infestation by giardia lamblia, with serious diarrhea resistant to treatment and malabsorption.

The value of metabolic imaging to predict tumour response after chemoradiation in locally advanced rectal cancer

Background: We aim to investigate the possibility of using 18F-positron emission tomography/computer tomography (PET-CT) to predict the histopathologic response in locally advanced rectal cancer (LARC) treated with preoperative chemoradiation (CRT). Methods: The study included 50 patients with LARC treated with preoperative CRT. All patients were evaluated by PET-CT before and after CRT, and results were compared to histopathologic response quantified by tumour regression grade (patients with TRG 1-2 being defined as responders and patients with grade 3-5 as non-responders). Furthermore, the predictive value of metabolic imaging for pathologic complete response (ypCR) was investigated. Results: Responders and non-responders showed statistically significant differences according to Mandard's criteria for maximum standardized uptake value (SUVmax) before and after CRT with a specificity of 76,6% and a positive predictive value of 66,7%. Furthermore, SUVmax values after CRT were able to differentiate patients with ypCR with a sensitivity of 63% and a specificity of 74,4% (positive predictive value 41,2% and negative predictive value 87,9%); This rather low sensitivity and specificity determined that PET-CT was only able to distinguish 7 cases of ypCR from a total of 11 patients. Conclusions: We conclude that 18-F PET-CT performed five to seven weeks after the end of CRT can visualise functional tumour response in LARC. In contrast, metabolic imaging with 18-F PET-CT is not able to predict patients with ypCR accurately

Extranodal NK/T-Cell Lymphoma without Nasal Cavity Involvement Associated with Epstein-Barr Virus:AMultimodality-Based Diagnosis of Two Cases

We report two cases of extranodal NK/T-cell lymphoma, nasal type, in immunocompetent patients without nasal cavity involvement. In the two cases, the initial presumptive diagnosis was tuberculosis and there was a rapid dissemination of the tumor with short survival after the hospital admittance. An autopsy was performed showing infiltration in several organs including lymph nodes and mesenteric and retroperitoneal fat. Histological sections showed an angiocentric and angiodestructive growth pattern and the immunophenotype was CD45+, CD3+ (cytoplasmic), as well as Granzyme B+ and EBV+. However, CD56 expression was only positive in a case in which the molecular study showed T-cell gene rearrangement with monoclonal appearance and associated with hemophagocytic syndrome. These cases represent rare examples of NK/T-cell lymphoma disseminated outside the nasal cavity highly aggressive that lead to the rapid death of the patients.

Psychometric characteristics of the Spanish version of instruments to measure neck pain disability

BACKGROUND. The NDI, COM and NPQ are evaluation instruments for disability due to NP. There was no Spanish version of NDI or COM for which psychometric characteristics were known. The objectives of this study were to translate and culturally adapt the Spanish version of the Neck Disability Index Questionnaire (NDI), and the Core Outcome Measure (COM), to validate its use in Spanish speaking patients with non-specific neck pain (NP), and to compare their psychometric characteristics with those of the Spanish version of the Northwick Pain Questionnaire (NPQ). METHODS. Translation/re-translation of the English versions of the NDI and the COM was done blindly and independently by a multidisciplinary team. The study was done in 9 primary care Centers and 12 specialty services from 9 regions in Spain, with 221 acute, subacute and chronic patients who visited their physician for NP: 54 in the pilot phase and 167 in the validation phase. Neck pain (VAS), referred pain (VAS), disability (NDI, COM and NPQ), catastrophizing (CSQ) and quality of life (SF-12) were measured on their first visit and 14 days later. Patients' self-assessment was used as the external criterion for pain and disability. In the pilot phase, patients' understanding of each item in the NDI and COM was assessed, and on day 1 test-retest reliability was estimated by giving a second NDI and COM in which the name of the questionnaires and the order of the items had been changed. RESULTS. Comprehensibility of NDI and COM were good. Minutes needed to fill out the questionnaires [median, (P25, P75)]: NDI. 4 (2.2, 10.0), COM: 2.1 (1.0, 4.9). Reliability: [ICC, (95%CI)]: NDI: 0.88 (0.80, 0.93). COM: 0.85 (0.75,0.91). Sensitivity to change: Effect size for patients having worsened, not changed and improved between days 1 and 15, according to the external criterion for disability: NDI: -0.24, 0.15, 0.66; NPQ: -0.14, 0.06, 0.67; COM: 0.05, 0.19, 0.92. Validity: Results of NDI, NPQ and COM were consistent with the external criterion for disability, whereas only those from NDI were consistent with the one for pain. Correlations with VAS, CSQ and SF-12 were similar for NDI and NPQ (absolute values between 0.36 and 0.50 on day 1, between 0.38 and 0.70 on day 15), and slightly lower for COM (between 0.36 and 0.48 on day 1, and between 0.33 and 0.61 on day 15). Correlation between NDI and NPQ: r = 0.84 on day 1, r = 0.91 on day 15. Correlation between COM and NPQ: r = 0.63 on day 1, r = 0.71 on day 15. CONCLUSION. Although most psychometric characteristics of NDI, NPQ and COM are similar, those from the latter one are worse and its use may lead to patients' evolution seeming more positive than it actually is. NDI seems to be the best instrument for measuring NP-related disability, since its results are the most consistent with patient's assessment of their own clinical status and evolution. It takes two more minutes to answer the NDI than to answer the COM, but it can be reliably filled out by the patient without assistance. TRIAL REGISTRATION Clinical Trials Register NCT00349544.

Late pulmonary metastases of renal cell carcinoma immediatelyafter post-transplantation immunosuppressive treatment: a case report

INTRODUCTION We report a case of pulmonary metastatic recurrence of renal adenocarcinoma soon after radical nephrectomy that was followed by renal transplant and immunosuppressive medication. Increased risk of metastatic recurrence of renal cell carcinoma should be considered in the immediate post-transplant period when immunosuppressive medication is administered, even if nephrectomy had been performed many years earlier. CASE PRESENTATION In 1986 the patient demonstrated renal insufficiency secondary to mesangial glomerulonephritis. In 1992 he underwent left side radical nephrectomy with histopathological diagnosis of clear cell adenocarcinoma. Mesangial glomerulonephritis in the remaining right kidney progressed to end-stage renal failure. In October 2000 he received a kidney transplant from a cadaver and commenced immunosuppressive medication. Two months later, several nodules were found in his lungs, which were identified as metastases from the primary renal tumor that had been removed with the diseased kidney 8 years earlier. CONCLUSION Recurrence of renal cell carcinoma metastases points to tumor dormancy and reflects a misbalance between effective tumor immune surveillance and immune escape. This case demonstrates that a state of tumor dormancy can be interrupted soon after administration of immunosuppressant medication.