Uncommon tumors in multiple endocrine neoplasia (MEN) type 1: Do they have a relationship with the prognosis of these patients?

INTRODUCTION: The prognosis of MEN 1 patients is not only determined by pancreatic disease; it is also related to other uncommon tumors. The objective of this study is to analyze the tumors associated with MEN 1 outside the classic triad and to investigate their relationship with mortality. MATERIALS AND METHODS: One hundred and five MEN 1 patients were studied in a tertiary referral hospital (1980-2019). RESULTS: With a follow-up of 11 ± 4 years, seven patients died (8%), four as a consequence MEN syndrome. Thirty-three percent had adrenal gland tumors. One patient died of adrenal cancer. Eight percent presented with a neuroendocrine thoracic neoplasm, and one patient died. Another patient died due to cutaneous T-cell lymphoma. A further patient died because of a gastrinoma with liver metastasis. CONCLUSIONS: To conclude, 75% of MEN-related deaths were the result of an uncommon pathology, and we, therefore, recommend that these tumors should be taken into account in the screening and follow-up of these patients.

Effectiveness of ustekinumab in patients with psoriatic arthritis in a real-world, multicenter study.

OBJECTIVE: To assess the effectiveness and survival of ustekinumab (UST) among patients with psoriatic arthritis (PsA) treated under routine clinical care. METHODS: Multicenter study. Epidemiological and clinical data was collected through electronic medical records of all patients with PsA who started UST in 15 hospitals of Spain. RESULTS: Two hundred and one patients were included, 130 (64.7%) with 45 mg and 71 (35.3%) with 90 mg. One hundred and thirty one patients (65.2%) had previously received another biological therapy. The median baseline DAS 28 ESR was 3.99, and Psoriasis Area and Severity Index (PASI) was 3. Overall, there was a significant decrease in DAS66/68 CRP, swollen joint count (SJC), tender joint count (TJC), and PASI in the first month of treatment, with earlier improvement in skin (PASI) than joints outcomes. Survival was numerically lower in patients with UST 45 mg (58.1%) than 90 mg (76.1%), although significant differences were not found (p = 0.147). When comparing naïve and < 1 TNF blocker versus > 2 TNF blocker-experienced patients, a significantly earlier response was seen in the former group regarding SJC (p = 0.029) at 1 month. Fifty-one patients (25.3%) stopped UST due to joint inefficacy and 4 patients due to adverse events (1.9%). Drug survival was significantly better in patients with fewer lines of previous biological agents (p = 0.003 for < 1 TNF blocker versus > 2 TNF blocker users). CONCLUSIONS: UST was effective in PsA patients in a routine clinical care setting. Patients with UST 90 mg and fewer lines of previous biologics achieved better and faster responses. Key Points • Largest cohort of patients with PsA in treatment with UST with specific rheumatological indication. • First cohort of patients with PsA comparing effectiveness of UST according to 45/90 mg dose.

Knowledge of the Brain Death Concept Among Older People.

BACKGROUND: The concept of brain death (BD) is not well understood in the general population; this lack of knowledge is one of the main factors that generates an attitude against organ donation. Older people are a population group that has rarely been studied in relation to organ donation and transplantation (ODT), and it is important to investigate the most important aspects of ODT, such as people's concept of BD. OBJECTIVES: To analyze the level of understanding of the concept of BD in people > 65 years of age and the factors that influence their mode of thinking. METHODS: A multicenter study was carried out with a representative sample of people > 65 years of age, stratified by sex and geographic location in the southeast of Spain (n = 420). Knowledge of BD as well as the influence of other variables were analyzed through a validated questionnaire about ODT. SPSS version 21.0 (IBM Corp, Armonk, NY, United States) software was used for statistical analysis. Descriptive analysis included Student t test and the χ2 test. RESULTS: The questionnaire had a completion rate of 84% (n = 351). In 36% (n = 127) of cases, people ˃ 65 years of age understood the concept of BD. In general, knowledge of this concept has not been associated with other variables including social-family interaction about ODT (P > .05). CONCLUSIONS: Older people do not understand the concept of BD. It is, therefore, necessary to carry out informative campaigns on ODT explaining this concept. This would improve organ donation awareness in this particular group of people.

The Influence of Mass Media on Organ Donation and Transplantation in Older People.

BACKGROUND: Worldwide population aging has resulted in changes in the approach to the organ donation and transplantation (ODT) process, forcing us to include older people on transplant waiting lists and to assess older patients as potential donors. However, this is a sector of the population that has not been studied in great detail in terms of the information they receive about ODT. OBJECTIVES: To analyze what kinds of media provide people > 65 years of age with information about ODT and which sources of information affect their attitude about this subject. METHODS: A multicentric study was undertaken using a sample of people > 65 years of age stratified by sex and geographic location in southeastern Spain (n = 420). Questions about ODT and methods of receiving information were analyzed using a questionnaire. Statistical analysis was performed using SPSS version 21.0 (IBM Corp, Armonk, NY, United States). Descriptive analyses were performed with a Student t test and χ2 test. RESULTS: The questionnaire completion rate was 84% (n = 351). People aged > 65 years received information about ODT, mainly positive, from the television (82%), followed by films (35%), the radio (30%), the press (26%), family (26%), and friends (17%). Receiving information through one of the following sources was associated with a more favorable attitude toward organ donation: the family (76% vs 45%; P < .001), friends (77% vs 48%; P = .01), and the press (62% vs 49%; P = .034). CONCLUSIONS: Older people mainly receive information about ODT from the mass media. However, social and family circles have the greatest influence on their attitudes toward organ donation.

Attitude of Older People Toward Living Donation.

BACKGROUND: Living donation is a potential source of organs that could help to reduce the organ transplant deficit. Given that we have a worldwide aging population, it is important to assess the opinion of older people toward this type of donation. OBJECTIVES: To analyze the attitude of people aged > 65 years toward living kidney donation (LKD) and living liver donation (LLD) and to investigate the variables affecting their attitudes. METHODS: A multicentric study was carried out using a representative sample of people > 65 years stratified by sex and geographic location in southeastern Spain (n = 420). The measurement instrument was a validated questionnaire about LKD and LLD. Statistics were analyzed using SPSS version 21.0 (IBM Corp, Armonk, NY, United States) software. Descriptive analysis was carried out using Student t test, χ2 test, and a multivariate analysis. RESULTS: The questionnaire completion rate was 84% (n = 351) with 88% (n = 310) in favor of LKD, and 89% (n = 311) in favor of LLD. Favorable attitude decreased to 3% when the donation under consideration was unrelated. Attitudes toward LKD and LLD were associated with having received information from the television (P = .016 and P = .045) and from friends (P = .017 and P = .03); accepting an autopsy after death (P = .001 and P = .002); and not being worried about scars (P = .015 and P = .044). In the multivariate analysis, the following variables continued to be significant: having received information from the television (odds ratio [OR], 2) and from friends (OR, 10.3); and the acceptance of an autopsy (OR, 2). CONCLUSIONS: Older people are in favor of both LKD and LLD, assuming it is a related donation. In addition, the information the elderly population receives regarding organ donation and transplantation affects their attitudes.

Teenagers in Rural Areas Faced With Organ Donation and Transplantation.

INTRODUCTION: In rural areas it is common to find unfavorable attitudes toward organ donation, and therefore it is important to find out the attitude and profile of new generations for improving predisposition to organ donation in these areas. Our objective was to analyze the attitude toward organ donation and the related variables of teenagers in a rural area. MATERIALS AND METHODS: Students in the final year of compulsory education (mostly 15-16 years of age) were selected from secondary schools in a rural area in southeastern Spain (n = 319; population density <300 inhabitants/km2). The instrument of measurement used was a validated psychosocial questionnaire. Completion was anonymous and self-administered. Descriptive statistical analysis, Student t test, χ2 test, and multivariate analysis were employed. RESULTS: There was a completion rate of 96% (n = 306). Overall, 65% (n = 200) were in favor of donating their organs, 30% (n = 90) were undecided, and 5% (n = 16) were against. Attitude toward the donation of one's own organs was related with sex (P = .015), previous experience of organ donation or transplantation (P = .046), comment on the topic of organ donation within the family (P = .003; odds ratio 2.155), knowing one's mother's opinion about the matter (P = .021), knowing the correct concept of brain death (P = .012; odds ratio 2.076), and religion (P = .014). CONCLUSIONS: A favorable attitude of teenagers in rural areas toward organ donation is slightly higher than in the adult population and is determined by many psychosocial variables, above all family discussion about organ donation and transplantation and correct knowledge of the brain death concept.

Importance for the Elderly of Discussion in the Family and Society About Attitude Toward Organ Donation.

BACKGROUND: The aging of the population has changed some of the approaches to the organ donation and transplant (ODT) process, such as considering elderly people as potential donors. We aimed to assess social and family discussions among the elderly about ODT and its effect on their attitude toward organ donation. METHODS: A study was carried out at 2 publicly-funded social centers for the elderly. Contact was made with individuals >65 years of age (n = 120) to seek their participation in the study. A questionnaire was distributed to them with questions about ODT. A descriptive assessment was performed with the Student t test and χ2 test used for statistical analysis. RESULTS: The completion rate was 87% (n = 104). Of the respondents with a partner and children, 48% had discussed the topic of ODT. It was found that talking about the subject with one's partner, children, or friends had a favorable influence on attitude compared with when this was not done (93%, 86%, and 83% vs 19%, 30%, and 31%, respectively; P < .001). In addition, the opinion of one's partner and children toward ODT also had an influence; if favorable, the respondent's attitude was more favorable, compared with when they did not know their opinion (92% to 88% vs 58% to 37%, respectively; P < .001). Other ODT-related variables did not affect their attitude (P > .05). CONCLUSIONS: Almost half of the elderly people had discussed ODT socially or with their family. This discourse has a favorable influence on their attitude toward organ donation and, therefore, it is important to encourage social and family dialog among this group.

Aetiology and clinical characteristics of male osteoporosis. Have they changed in the last few years?

OBJECTIVE: The aim of this study was to analyse the clinical characteristics and etiological factors related to male osteoporosis in patients attending an out-patient rheumatology department during an 11-year period (1995-2006), as well as to compare them with the observed characteristics in a previous study performed 12 years ago. METHODS: 232 males aged 21-88 (mean 56.1+/-14) with osteoporosis were included in the study. Previous skeletal fractures and family history of osteoporosis were recorded. Bone mass assessment, automated biochemical profile and hormonal measurements (including PTH, 25-OH vitamin D, cortisol, thyroid and sexual hormones) were performed on most patients as well as 24 h urinary calcium, and bone markers. In patients with idiopathic osteoporosis 1-25-OH2 vitamin D was also determined. In addition, x-rays of the spine were obtained for all patients. RESULTS: 67% of the patients had previous skeletal fractures and 51% had vertebral fractures. 57% of the patients had idiopathic and 43% had secondary osteoporosis whereas in the previous series only 22% of the patients had idiopathic disease. The most frequent causes of secondary osteoporosis were corticosteroid therapy, hypogonodism and alcoholism. 38% of the patients with idiopathic osteoporosis had associated hypercalciuria. Patients with secondary osteoporosis were older, shorter, had lower femoral neck T-score and lower serum values of 25-OH vitamin D and testosterone, as well as higher gonadotrophin and PTH values than the patients with idiopathic osteoporosis, whereas patients with idiopathic osteoporosis had higher urinary calcium and more frequent family history of osteoporosis. Hypercalciuric patients were younger, had lower lumbar BMD, higher urinary calcium and greater incidence of lithiasis than normocalciuric patients with idiopathic osteoporosis. Back pain, frequently associated with vertebral fractures, was the most common cause of referral in all groups of patients. CONCLUSION: Idiopathic osteoporosis is the most frequent cause of male osteoporosis in this study. In these patients, family history of osteoporosis and associated hypercalciuria are frequent. The most frequent causes of secondary osteoporosis in males include corticosteroid therapy, hypogonadism and alcoholism. Although clinical characteristics of male osteoporosis are similar to that previously reported, in this study the percentage of patients with idiopathic osteoporosis was higher than previously observed.

[Video-polysomnography in preterm infants with birth weight under 1,800 g]. / Estudio vídeo-polisomnográfico en prematuros menores de 1.800g.

INTRODUCTION: Neonatal video-polysomnography (VPSG) in preterm infants is indicated to rule out sleep-related respiratory disturbances before discharge from neonatal units and to study neonatal sleep patterns and associated pathologic conditions. OBJECTIVE: To study the presence of apnea, hypopnea, and periodic breathing in preterm infants with low birth weight (< 1,800 g) and to describe their cardio-respiratory variability, electroencephalogram (EEG) abnormalities, and brain maturity in connection with sleep stages. METHOD: We performed a cross-sectional, descriptive study through review of the clinical histories of preterm infants with a birth weight < 1,800 g who had undergone VPSG (2001-2003). The most common indication for VPSG was the presence of sleep apneas and oxygen desaturation. The data obtained were used for descriptive statistical analysis. RESULTS: Thirty-one infants were studied, with a mean gestational age of 27.8 weeks and a mean birth weight of 1,158 g. The most frequently associated condition was hyalin membrane disease (68 %). Cardiorespiratory impairment was detected in 65 %, altered sleep pattern in 6 %, immature EEG recording in 32 %, abnormal pattern in 13 %, and immature plus abnormal pattern in 3 %. Sixty-nine percent of the infants required home monitoring and 23 % needed oxygen at home. Four infants were readmitted on several occasions due to apnea. CONCLUSION: We wish to stress the importance of carrying out VPSG with suitable methodology in preterm infants with cardiorespiratory or neurological impairment in order to detect abnormalities on EEG and to assess brain maturity and sleep-related abnormal respiratory events.

Serum osteoprotegerin and its ligand in Paget's disease of bone: relationship to disease activity and effect of treatment with bisphosphonates.

OBJECTIVE: To test the following hypotheses: 1) osteoprotegerin (OPG) and receptor activator of nuclear factor kappa B ligand (RANKL) serum levels in patients with Paget's disease are related to disease activity and are different from those in healthy individuals; 2) interleukin-6 (IL-6), a cytokine that has been shown to have higher levels in Paget's disease, modulates these factors; and 3) the antiresorptive effect of bisphosphonates in Paget's disease of bone may be mediated through these local factors. METHODS: The study group comprised 31 patients with Paget's disease who received 400 mg/day of oral tiludronate for 3 months. Serum levels of OPG, RANKL, IL-6, bone alkaline phosphatase (AP), N-terminal type I procollagen propeptide, urinary N-terminal crosslinking telopeptide of type I collagen, and urinary alpha-C-terminal crosslinking telopeptide of type I collagen were measured at baseline and 1 month after the end of therapy. In addition, the RANKL:OPG ratio was calculated, and disease activity was evaluated at baseline by quantitative bone scintigraphy. RESULTS: Mean baseline OPG values were higher in patients with Paget's disease than in healthy control subjects (P < 0.005), but RANKL and IL-6 values and RANKL:OPG ratios in the 2 groups were similar. OPG concentrations decreased significantly after treatment with tiludronate (P < 0.005), whereas no significant changes were observed in serum RANKL values. No correlation was found between either bone markers or quantitative scintigraphic indices and serum levels of OPG, RANKL, IL-6, and RANKL:OPG ratios. Serum OPG decreased significantly only in those patients with baseline OPG values >4.1 pM/liter. CONCLUSION: Serum OPG increases in Paget's disease and decreases after treatment with tiludronate, especially in patients with the highest OPG values. In contrast, RANKL serum levels and RANKL:OPG ratios are unmodified in patients with Paget's disease. Although serum OPG, RANKL, and IL-6 values were unrelated to disease activity, the increase in OPG may reflect a protective mechanism of the skeleton to compensate for increased bone resorption.

Pregnancy associated osteoporosis: the familial effect.

OBJECTIVE: The etiology and pathogenesis of pregnancy associated osteoporosis is unclear. Whether pregnancy has simply been an aggravating factor or is a direct etiologic cause responsible for severe bone loss needs to be elucidated. METHODS: In order to evaluate the contribution of familial factors to pregnancy osteoporosis, we analyzed the bone mass of 15 relatives of 5 women with pregnancy osteoporosis. Most of the patients suffered from severe back pain associated with vertebral fractures in their first pregnancy. Extensive clinical, laboratory and radiological investigations were performed to exclude secondary causes of osteoporosis. Bone mineral density measurements were performed on 15 first order family members and the results were compared with those of a control group of 20 healthy members of 5 families. RESULTS: Osteoporosis was present in 53% of the relatives of patients with pregnancy osteoporosis and in 15% of the controls (P < 0.05). CONCLUSION: These results highly suggest that some patients with pregnancy associated osteoporosis have a genetic determination of low peak bone mass, and gestation, due to its association with physiological metabolic disturbances, constitutes a risk factor for the development of skeletal fractures in these patients.

Usefulness of biochemical markers of bone turnover in assessing response to the treatment of Paget's disease.

The aim of this study was to investigate the usefulness of biochemical markers of bone turnover for monitoring treatment efficacy of Paget's disease of bone, and also to evaluate the utility of biological variation data in choosing the best markers for assessment of biochemical response to therapy. Thirty-eight patients with Paget's disease were included in a prospective study. All received 400 mg/day of oral tiludronate for 3 months. In 31 patients that completed treatment, biochemical markers were measured at baseline and at 1 and 6 months after treatment ended. In serum we determined the levels of total alkaline phosphatase (tAP), bone alkaline phosphatase (bAP), procollagen type I N-terminal propeptide (PINP), and C-terminal telopeptide of type I collagen (sCTx). Urine samples were analyzed for hydroxyproline (Hyp) and for C- and N-terminal telopeptides of type I collagen (CTx and NTx, respectively). Quantitative bone scintigraphy was performed at baseline and at 6 months after discontinuation of therapy. A ratio for monitoring response to treatment was obtained for each marker. This ratio reflected the size of treatment response of the marker in relation to the value of its critical difference. Thus, ratio values of >1 indicated a significant decrease of the marker after therapy. In addition, response to therapy was evaluated according to disease activity. Mean values of all markers of bone turnover decreased significantly after therapy. Serum bAP and PINP and urinary NTx showed the highest percentage reduction (between 58% and 68%). Furthermore, serum bAP and PINP showed the highest ratios for monitoring changes induced by treatment, followed by serum tAP and urinary NTx. sCTx and urinary CTx as well as Hyp showed mean ratios for monitoring changes of <1, indicating a low sensitivity for monitoring treatment. Patients with polyostotic disease showed a continuous decrease in mean values for all markers at 6 months from the end of therapy, whereas, in monostotic patients, there was a trend toward increased levels at this timepoint. In conclusion, serum bAP and PINP were the most sensitive markers for monitoring treatment efficacy in Paget's disease, although serum tAP and urinary NTx were also sensitive markers for monitoring changes. Data on biological variation are useful for assessing actual changes induced by treatment.

Kin protein expression: laminar specificity during rat cerebral cortex development.

Kin is a mammalian nuclear protein involved in DNA recombination-repair and the regulation of gene expression. The present study explored the expression of the Kin nuclear protein during postnatal development of the rat cerebral cortex, using immunocytochemistry with anti-RecA antibodies. The immunostaining of the Kin protein preferentially occurs within layers IV-V and VIb of the cortex in early postnatal developing brain, whereas in the adult rat this expression is observed unequivocally in all cortical layers. 35S-isotopic in situ hybridization for Kin-17 mRNA confirmed this Kin protein expression pattern and demonstrated its transcription in cortical neurons. This gradual age-related expression during development may have functional implications in the maturation processes of the cortex.

Idiopathic hypoparathyroidism associated with adult rheumatoid arthritis.

A 48-year-old female patient with adult onset idiopathic hypoparathyroidism diagnosed at the age of 28 years developed a typical seropositive rheumatoid arthritis (RA) at 46 years of age after several years of evolution of a palindromic rheumatism. Only one case of an association between idiopathic hypoparathyroidism and RA has been described in the medical literature. Autoimmunity seems to play a pivotal role in the aetiopathogenesis of both diseases, and could explain the nature of this association; nevertheless, a chance association could not be excluded.

Clinical features of the 1992 outbreak of equine viral arteritis in Spain.

During 1992, a widespread outbreak of Equine viral arteritis (EVA) occurred at a riding establishment near Barcelona, Spain. A total of 31 out of 186 horses on the premises displayed clinical signs, most frequently, fever, depression, mild ventral and limb oedema and a vesicular-erosive stomatitis, with hypersalivation, petechiations and small ulcerations. Affected horses developed illness of varying severity with only a few exhibiting a severe form of the disease and no mortality was recorded. Haematological and blood biochemical examination the most severely affected horses revealed a thrombocytopenia, slight leucocytosis with neutrophilia, lymphopenia and eosinopenia, an increase in plasma fibrinogen and a small rise in serum proteins and indirect bilirubin values. Diagnosis was confirmed by demonstration of seroconversion to equine arteritis virus in acute and convalescent phase sera. Attempted isolation of the virus from citrated blood samples proved unsuccessful.

Early steps in fusion between Epstein-Barr virus and a human hepatoma cell line (Li7A).

Epstein-Barr virus, the causative agent of mononucleosis and several human cancers, infects cells via complement receptor type 2 (CR2). Expression of this receptor is restricted to B lymphocytes, some epithelial cells and immature thymocytes; expression of CR2-like proteins has been also found on T cells. In the present report, we identified the presence, on the membrane of Li7A cells, of a novel EBV receptor distinct from CR2 capable of triggering fusion with EBV virions with more rapid kinetics than that found with lymphoblastoid cells (Raji).

[Bronchiolitis obliterans with organizing pneumonia]. / Bronquiolitis obliterante con neumonía organizada.

Obliterant Bronchiolitis is an anatomo-clinical entity known years ago. It is recognized as a evolutive form of different processes, including Extrinsic Allergic Alveolitis, Pneumonitis due to gas inhalation, viral processes and Rheumatoid Lung. It has been recently identified as a disease with specific characteristics in the context of interstitial idiopathic pneumonia with bronchiolar involvement and a distinctive anatomo-pathological character. From the clinical and radiological point of view it requires a broad differential diagnosis, which is confirmed definitively in the anatomopathological exam obtained through minithoracotomy. Therapeutic response to corticosteroids is good even thought it shows a trend to relapse when they are decreased or stopped. We discuss the cases of three patients who were studied recently, showing their clinical, radiological and anatomopathological features together with the therapeutic response, which is positive, in different periods of the evolution course.

Use of octadecylrhodamine fluorescence dequenching to study vesicular stomatitis virus fusion with human aged red blood cells.

Human erythrocytes were separated into five fractions representing different age groups. In each group phospholipid inside-outside translocation was determined by quantitation of the amino phospholipids phosphatidylserine and phosphatidylethanolamine and their lyso-derivatives by thin layer chromatography. To assess the role of transbilayer phospholipid distribution in the recognition and fusion of vesicular stomatitis virus (VSV) and human aged erythrocytes, we monitored the fusion kinetics using the octadecylrhodamine dequenching assay. Fusion of VSV with each single group of red blood cells (RBC) was not detectable with the youngest cells (F1 group) but increased with RBC aging (F2-F5 groups). The same increase in fusion was observed with microvesicles generated from RBC in which aging was mimicked by incubating the cells with Ca2+ in the presence of the Ca2+ ionophore A23187. Conversion of the aminophospholipids to the trinitrophenyl derivative by reaction with trinitrobenzensulfonate completely inhibits fusion on ghosts in which aging was artificially induced by translocation of aminophospholipids in the outer leaflet (symmetric ghosts). These results indicate that RBC become susceptible to VSV fusion during aging and in all pathology related to the aging process.