Clinical and Genetic Advances in Paget's Disease of Bone: a Review.

Paget's disease of bone (PDB) is the second most common metabolic bone disorder, after osteoporosis. It is characterised by focal areas of increased and disorganised bone turnover, coupled with increased bone formation. This disease usually appears in the late stages of life, being slightly more frequent in men than in women. It has been reported worldwide, but primarily affects individuals of British descent. Majority of PDB patients are asymptomatic, but clinical manifestations include pain, bone deformity and complications, like pathological fractures and deafness. The causes of the disease are poorly understood and it is considered as a complex trait, combining genetic predisposition with environmental factors. Linkage analysis identified SQSTM1, at chromosome 5q35, as directly related to the disease. A number of mutations in this gene have been reported, pP392L being the most common variant among different populations. Most of these variants affect the ubiquitin-associated (UBA) domain of the protein, which is involved in autophagy processes. Genome-wide association studies enlarged the number of loci associated with PDB, and further fine-mapping studies, combined with functional analysis, identified OPTN and RIN3 as causal genes for Paget's disease. A combination of risk alleles identified by genome-wide association studies led to the development of a score to predict disease severity, which could improve the management of the disease. Further studies need to be conducted to elucidate other important aspects of the trait, such as its focal nature and the epidemiological changes found in some populations. In this review, we summarize the clinical characteristics of the disease and the latest genetic advances to identify susceptibility genes. We also list current available treatments and prospective options.

Association of IL1Β (-511 A/C) and IL6 (-174 G > C) polymorphisms with higher disease activity and clinical pattern of psoriatic arthritis.

The objective of this study is to analyze whether IL1ß (-511G > A) and IL6 (-174 G > C) polymorphisms are associated with inflammatory activity, radiographic damage or clinical pattern of psoriatic arthritis (PsA). One hundred twenty-five patients classified as PsA according to the Classification of Psoriatic Arthritis (CASPAR) criteria were included. Patients were stratified according to their clinical pattern at inclusion as peripheral, axial, or mixed involvement. Disease activity in peripheral or mixed forms was measured using the number of swollen and tender joints, pain analog visual scale, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and disease activity score 28 (DAS28). Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was used for axial and mixed forms, as were pain visual analog scale, ESR and CRP. Radiographic damage was evaluated using a modified Sharp score and modified stoke ankylosing spondylitis spinal score (SASSSm). The polymorphisms for the promoter region of IL1ß (-511 G/A) and IL-6 (-174 G/C) were analyzed. The G allele of IL1B (-511G/A) polymorphism was associated with higher peripheral joint disease activity (OR 3.13; p < 0.0004; CI 95 % 1.43-6.82, p (corrected) <0.008), while the G allele of the IL6 (174G > C) polymorphism presented a strong trend to be associated with peripheral forms (70.86 %) (OR 1.89; p < 0.03; CI 95 % 1.06-3.39, p-corrected 0.05). In addition, this allele showed a lower association with HLA-B27 (15.78 %) compared with C allele (28.57 %) (OR 0.469; p = 0.02; CI 95 % 0.238-0.923, p-corrected 0.03). This study suggests that the G allele polymorphism of IL1B (-511 A/C) is associated with higher peripheral joint disease activity. On the other hand, the IL6 (-174 G/C) polymorphism showed a strong trend to be associated with the peripheral pattern of PsA.

Clinical practice guidelines for posmenopausal, glucocorticoid-induced and male osteoporosis. Spanish Society for Research on Bone and Mineral Metabolism (3rd updated version 2014).

These guidelines update issues covered in previous versions and introduce new ones that have arisen in recent years. The former refer mainly to the therapeutic developments that have been made during this time (zoledronate, denosumab, bazedoxifene), which have led to a change in the drug selection algorithm. The latter deal with therapeutic management, the description of new adverse effects (which have led to changes in therapeutic behaviour patterns, as is the case with atypical fracture of the femur), treatment duration (with consideration for the so-called "therapeutic holidays"), the so-called sequential treatment and changes in treatment imposed by certain circumstances. A new algorithm has been introduced for sequential treatment. Attention has also been paid to vertebroplasty and kyphoplasty.

Consensus statement: recommendations for the management of metabolic bone disease in human immunodeficiency virus patients / Documento de consenso: Recomendaciones para el manejo de la enfermedad ósea metabólica en pacientes con virus de la inmunodeficiencia humana

"OBJECTIVE: To provide practical recommendations for the evaluation and treatment of metabolic bone disease in human immunodeficiency virus (HIV) patients. PARTICIPANTS: Members of scientific societies related to bone metabolism and HIV: Grupo de Estudio de Sida (GeSIDA), Sociedad Española de Endocrinología y Nutrición (SEEN), Sociedad Española de Investigación Ósea y del Metabolismo Mineral (SEIOMM), and Sociedad Española de Fractura Osteoporótica (SEFRAOS). METHODS: A systematic search was carried out in PubMed, and papers in English and Spanish with a publication date before 28 May 2013 were included. Recommendations were formulated according to GRADE system (Grading of Recommendations, Assessment, Development, and Evaluation) setting both their strength and the quality of supporting evidence. Working groups were established for each major part, and the final resulting document was later discussed in a face-to-face meeting. All the authors reviewed the final written document and agreed with its content. CONCLUSIONS: The document provides evidence-based practical recommendations on the detection and treatment of bone disease in HIV-infected patients"

"Objetivo Proporcionar unas recomendaciones prácticas para el manejo de la enfermedad metabólica ósea en pacientes con virus de la inmunodeficiencia humana (VIH). Participantes Miembros de diferentes sociedades científicas relacionadas con el metabolismo óseo y con la enfermedad VIH: Grupo de Estudio de Sida (GeSIDA), Sociedad Española de Endocrinología y Nutrición (SEEN), Sociedad Española de Investigación Ósea y del Metabolismo Mineral (SEIOMM) y Sociedad Española de Fractura Osteoporótica (SEFRAOS). Métodos Se realizó una búsqueda sistemática en PubMed de la evidencia disponible para cada aspecto, y se revisaron artículos escritos en inglés y en castellano con fecha de inclusión hasta 28 de mayo de 2013. Las recomendaciones se formularon según el sistema GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) para establecer tanto la fuerza de las recomendaciones como el grado de evidencia. Los autores trabajaron por grupos en la formulación de cada apartado de las recomendaciones y posteriormente el documento global se discutió en una reunión conjunta. Todos los autores revisaron el documento escrito final y lo consensuaron. Conclusiones El documento establece unas recomendaciones prácticas basadas en la evidencia acerca de la evaluación y el tratamiento de la enfermedad metabólica ósea en pacientes con VIH"

Hearing and vestibular disorders in patients with systemic lupus erythematosus.

OBJECTIVES: Systemic lupus erythematosus (SLE) is associated with several comorbidities, including hearing and vestibular disorders. We recently described an increase of SLE prevalence in patients with Menierés disease (MD). The aim of this study is to explore if a subset of SLE patients may have a common inner ear disorder and determine the potential relationship with migraine. METHODS; Eighty-nine patients with SLE (according to the American College of Rheumatology criteria for the diagnosis of SLE) were evaluated for audiovestibular symptoms by a telephone interview carried out by two experienced otoneurologists. Twenty-one patients with SLE were referred to the otoneurology clinic for a detailed clinical history for criteria assessment for MD and a complete audiovestibular examination (audiogram, oculomotor, and caloric testing with video-oculography). RESULTS: Recurrent headache was found in 50/89 patients, and 26 of them had diagnostic criteria for migraine. Twenty-four percent of patients reported sensorineural hearing loss (SNHL) or episodic vertigo. Among the eight patients (9%) with episodic vertigo, one had criteria for definite MD and another two patients had criteria for possible MD. SNHL was found to be associated with a history of episodic vertigo (Fisher's test, p=0.02), but not with headache or migraine. SLE and episodic vertigo were not associated with tinnitus, migraine, lupus nephritis, antinuclear antibodies or antiphospholipid syndrome. CONCLUSIONS: Migraine, SNHL and episodic vertigo are comorbid conditions in patients with SLE, but migraine is not associated with SNHL or vertigo in these patients. However, SNHL and vertigo are associated conditions in SLE, suggesting a common audiovestibular dysfunction.

Secular changes in Paget's disease: contrasting changes in the number of new referrals and in disease severity in two neighboring regions of Spain.

SUMMARY: We studied the changes in the number of new referrals with Paget's disease of bone (PDB) and severity of PDB in a high prevalence focus and its neighboring region. Referral of patients changed only in the high prevalence focus. The severity of PDB decreased in both regions. These results could suggest the effects of an environmental influence on disease activity. INTRODUCTION: The prevalence and severity of PDB have decreased in several countries over recent years. We previously reported a high radiological prevalence of PDB in Vitigudino. Here we sought to determine if secular changes in the number of new referrals and severity of PDB had occurred over recent years. METHODS: We studied 280 patients with clinically diagnosed PDB who were evaluated at a regional referral center for metabolic bone disease between 1986 and 2009. Changes in the number of new referrals were calculated by relating these data to the number of subjects at risk as determined by population registers. Trends in disease severity were analyzed with alkaline phosphatase (ALP) activity and disease extent on scan. RESULTS: Referrals from the Vitigudino region increased substantially between 1986 and 2003 but fell markedly between 2004 and 2009, although by this time there had been depopulation of the region due to emigration. No significant changes in the rates of referral occurred in the remainder of Salamanca. ALP activity and disease extent decreased in Salamanca, but only ALP activity decreased in Vitigudino. Referrals rate and severity of PDB in Vitigudino were greater than in the remainder of Salamanca. CONCLUSIONS: Referral of patients with clinically diagnosed PDB has remained stable for most of Salamanca during the past 24 years, but substantial changes have been observed in Vitigudino. In agreement with other reports, the severity of PDB has decreased in both regions consistent with the effects of an environmental influence on disease activity.

Association of aromatase and estrogen receptor gene polymorphisms with hip fractures.

UNLABELLED: Two polymorphisms of the aromatase and estrogen receptor genes appeared to interact to influence the risk of hip fractures in women. INTRODUCTION: Allelic variants of the aromatase gene have been associated with bone mineral density and vertebral fractures. Our objective was to analyze the relationship between two polymorphisms of the aromatase and estrogen receptor genes and hip fractures. METHODS: We studied 498 women with hip fractures and 356 controls. A C/G polymorphism of the aromatase gene and a T/C polymorphism of the estrogen receptor alpha gene were analyzed using Taqman assays. Aromatase gene expression was determined in 43 femoral neck samples by real-time RT-PCR. RESULTS: There were no significant differences in the overall distribution of genotypes between the fracture and control groups. However, among women with a TT genotype of the estrogen receptor, the CC aromatase genotype was more frequent in women with fractures than in controls (39 vs. 23%, p = 0.009). Thus, women homozygous for T alleles of estrogen receptor and C alleles of aromatase were at increased risk of fracture (odds ratio 2.0; 95% confidence interval 1.2-3.4). The aromatase polymorphism was associated with RNA levels in bone tissue, which were three times lower in samples with a CC genotype (p = 0.009). CONCLUSIONS: These common polymorphisms of the aromatase and estrogen receptor genes appear to interact, influencing the risk of hip fractures in women.

Inhaled steroids do not decrease bone mineral density but increase risk of fractures: data from the GIUMO Study Group.

Although the negative effect of systemic steroids on bone is well documented, there is not clear evidence about possible adverse effects of inhaled steroids on bone metabolism and fractures. A cross-sectional study was performed on 105 women suffering from bronchial asthma treated with inhaled steroids and 133 controls. Bone mineral density (BMD) was measured by quantitative ultrasonography (QUS) at the calcaneus and by dual X-ray absorptiometry (DXA), at both the lumbar spine and proximal femur. Patients suffering from bronchial asthma showed no statistically significant changes in BMD as measured by DXA or QUS, compared with controls. A higher prevalence of fractures was found in the group of women with bronchial asthma, with an age-adjusted odds ratio of 2.79 (95% CI: 1.19-6.54). Inhaled steroids do not appear to decrease BMD, but are associated with an increased risk of fracture in women.

[Health-related quality of life in Spanish women with osteoporosis]. / Qualidade de vida relacionada à saúde em espanholas com osteoporose.

OBJECTIVE: To analyze the health-related quality of life in patients with osteoporosis and to compare it with the overall population. METHODS: A cross-sectional descriptive study was carried out with 60 female patients of the rheumatology service at a university hospital, in Spain, from April to October 2003. The Short Form-36 (SF-36) questionnaire was applied in order to obtain demographic data, clinical characteristics and data about lifestyles related to health. Patients were classified in age groups. The statistics tests performed were Chi-square, general linear model, Student's t-test. RESULTS: The interviewees' average age was 65.57 years old (SD: +/- 9.7 years), and average time interval for diagnosis was 3.4 +/- 2.84 years. The best scores were in social functioning (89), emotional aspects (72.2), mental health (63), and vitality (53.7). The lowest scores were in general health (45.1), physical capacity (47.7), pain (52.3) and physical aspects (59.9). The patients' average scores were lower than the general Spanish population's scores in the following dimensions: functional capacity, physical aspects, pain and overall health status. The greatest differences between the average SF-36 scores for patients and for the overall Spanish population were in the age group ranging from 55 to 64 years old. Scores were lower or similar to the general Spanish population in all other dimensions of the questionnaire. No significant associations were found between the dimensions of the SF-36 contemplated in this study and the clinical, demographic and lifestyle data. CONCLUSIONS: The patients presented bad quality of life, particularly with respect to those dimensions that are most relevant with respect to osteoporosis, when compared with the overall Spanish population. The physical dimensions were the ones most affected.

Qualidade de vida relacionada à saúde em espanholas com osteoporose / Health-related quality of life in Spanish women with osteoporosis

OBJETIVO: Analisar a qualidade de vida relacionada à saúde de pacientes com osteoporose e compará-la com a população geral. MÉTODOS: Foi realizado um estudo descritivo transversal com 60 pacientes do sexo feminino no serviço de reumatologia de um hospital universitário na Espanha, de abril a outubro de 2003. Foi aplicado o questionário Short Form-36, abordando dados demográficos, características clínicas e dados sobre estilos de vida relacionados à saúde. As pacientes foram classificadas em grupos etários. Foram utilizados os seguintes testes estatísticos: qui-quadrado, modelo linear geral, t de Student. RESULTADOS: As entrevistadas tinham idade média de 65,57 (DP: ±9,7 anos), e tempo de diagnóstico médio de 3,4±2,84 anos. As melhores pontuações foram obtidas nas dimensões aspectos sociais (89), aspectos emocionais (72,2) e saúde mental (63). As mais baixas foram em estado geral de saúde (45,1), capacidade funcional (47,7), dor (52,3) e aspectos físicos (59,9). As pontuações médias dos pacientes resultaram inferiores às pontuações conhecidas da população geral espanhola nas dimensões capacidade funcional, aspectos físicos, dor e estado geral de saúde. As máximas diferenças entre as pontuações médias do SF-36 dos pacientes e os valores populacionais espanhóis correspondem ao grupo de idade de 55 a 64 anos. Nas demais dimensões do SF-36, as pontuações foram inferiores ou similares aos valores populacionais espanhóis. Não se encontraram associações significativas entre as dimensões do SF-36 estudadas e os dados clínicos, demográficos e de estilos de vida analisados. CONCLUSÕES: Os pacientes apresentaram baixa qualidade de vida, sobretudo nas dimensões mais relevantes da enfermidade, quando comparada com valores da população espanhola em geral. As áreas físicas foram as mais afetadas.

Postmenopausal women with colles' fracture have lower values of bone mineral density than controls as measured by quantitative ultrasound and densitometry.

Measurement of ultrasonographic parameters provides information concerning not only bone density but also bone architecture. We investigated the usefulness of ultrasonographic parameters and bone mineral density (BMD) to evaluate the probability of Colles' fracture. Two-hundred eighty-nine postmenopausal women (62.3 +/- 8.7 yr) with (n = 76) and without (n = 213) Colles' fracture were studied. BMD of lumbar spine and proximal femur was evaluated in all women by dual-energy X-ray absorptiometry (DXA) and speed of sound (SOS), broadband ultrasound attenuation (BUA), and stiffness in the calcaneus were measured by a Sahara ultrasonometer (Hologic). Patients suffering from Colles' fracture had lower values of BMD adjusted by height at the lumbar spine, L2-L4 (0.797 g/cm2 vs 0.860 g/cm2), femoral neck (0.685 g/cm2 vs 0.712 g/cm2 ), SOS (1518 m/sg vs 1525 m/sg), and stiffness (74.6 vs 77.7) (p < 0.05). Nevertheless, BUA values were similar in both groups. After stepwise logistic regression analysis, the area found under receiver operating characteristic (ROC) curves was 0.60 for L2L4 and 0.63 for a formula combining L2L4 and height. Our data suggest that patients suffering from Colles' fracture have lower values of BMD by DXA, SOS, and stiffness. However, the ability of these techniques to discriminate is low because the values for the area under ROC curve are 0.60 for L2-L4 and 0.63 for a formula derived of the combination of L2-L4 and height.

Calcitriol improves streptozotocin-induced diabetes and recovers bone mineral density in diabetic rats.

Vitamin D analogs exert a preventative effect on experimental diabetes, but whether or not they are able to halt progress of established diabetes is not yet known. Moreover, it is widely accepted that diabetes may induce osteoporosis, but the efficacy of vitamin D on diabetic osteoporosis is not clear. In order to help clarify these issues, we have tested the efficacy of calcitriol streptozotocin-induced diabetes. Streptozotocin (60 mg/Kg body weight) was injected in 3-month-old Wistar rats, randomly distributed into two groups: vehicle (olive oil) treated diabetic rats (D) and diabetic rats treated with 1.25-(OH)2D3 250 mg, three times a week (DT). Control animals (C) were treated with vehicle alone. The experiment lasted 8 weeks. The histology of the pancreata was evaluated. Blood glucose and calcium and phosphate in serum and urine were measured. Finally, bone mineral density (BMD) of tibia and lumbar vertebrae were evaluated. After 8 weeks, diabetes persisted in 85% of the diabetic rats (D group), but in only 45% of vitamin D-treated group (DT). At the end of the experiment, DT animals were separated into two groups, those still remaining diabetic (DT-NR) and reversed animals (DT-R). Moreover, bone loss was observed in diabetic animals (D), whereas BMD of DT-R rats showed similar values to those of controls (C). Our results suggest that 1.25(OH)2D3 improves diabetes and, as such, may recover BMD in streptozotocin-induced diabetic rats.

Low bone density with normal bone turnover in ovariectomized and streptozotocin-induced diabetic rats.

Diabetes and estrogen deficit are known causes of osteopenia, diabetes being associated with a low bone turnover and estrogen deficit with a high bone turnover. In the present work, we studied the effect of combined ovariectomy and diabetes on bone mineral content (BMC) and bone mineral density (BMD) and several bone markers in the rat. Four groups of rats were studied: control (C), ovariectomized (O), diabetic (D), and ovariectomized and diabetic (DO). Twelve weeks after starting the experiments, BMC and BMD of the first six lumbar vertebrae were measured; a bone formation marker (BGP) and a bone resorption marker (free collagen cross-links, PYD) were also analyzed. Diabetic rats showed diminished gain in bone mass, BMC (D: 0.417 +/- 0.028 g, DO: 0.422 +/- 0.020 g) and BMDs (D: 0.171 +/- 0.006 g/cm2, DO: 0.174 +/- 0.006 g/cm2) both being significantly (P < 0.001) lower than those of control (C: BMC 0.727 +/- 0.024 g and BMD 0.258 +/- 0.004 g/cm2) and ovariectomized (O: BMC 0.640 +/- 0.044 g and BMD 0.240 +/- 0.009 g/cm2) groups. Moreover, the BMC and BMD of the C group were significantly (P < 0.05) higher than that of the O group. BGP and PYD levels were significantly (P < 0.01) higher in the O group (BGP: 138.2 +/- 16.8 ng/ml, PYD: 270.2 +/- 17.8 nM/mM) than those found in the control rats (BGP: 44.7 +/- 4.8 ng/ml, PYD: 165.6 +/- 12.5 nM/mM); the D group showed significantly (P < 0.01) lower values (BGP: 27.4 +/- 14.6 ng/ml, PYD: 55.0 +/- 7.4 nM/mM) than those of the control group. The DO group showed similar levels (BGP: 43.4 +/- 5.1 ng/ml, PYD: 146.7 +/- 14.6 nM/mM) to those found in the C group. Although bone marker levels in the O and D groups were in accordance with those expected in these situations, in the DO group the corresponding levels are apparently "normal." Also, the decrease of gain in bone mass observed after combining estrogen deficit and diabetes (DO group) did not seem to be more marked than that caused by diabetes alone.

Natural anticoagulant proteins and antiphospholipid antibodies in systemic lupus erythematosus.

OBJECTIVE: Thrombosis is a relatively common complication in patients with systemic lupus erythematosus (SLE) and is strongly associated with the presence of antiphospholipid antibodies (aPL). The mechanism involved in the pathogenesis of this prothrombotic state remains obscure. We studied 4 natural anticoagulant proteins: protein C, protein S, antithrombin III, and plasminogen in 50 patients diagnosed with SLE. METHODS: Protein C, antithrombin III, and plasminogen were measured by chromogenic substrates and total and free protein S by electrophoresis. We also determined the prevalence of different aPL (lupus anticoagulant and antibodies against cardiolipin, phosphatidylserine, and phosphatidylinositol). RESULTS: Ten patients (20%) had a history of thrombosis. Some type of aPL was present in 26 patients (52%). Nine of the 10 patients with history of thrombosis had aPL (p = 0.007). Functional assays for protein C, antithrombin III, and plasminogen were in the normal range in all patients. Low free protein S levels were documented in 19 patients and were associated with the presence of aPL (13/19 were aPL positive) (p < 0.05). Only 4 patients with acquired free protein S deficiency had a history of thrombosis. CONCLUSION: This study shows an association between aPL and reduced free protein S levels in patients with SLE. Further studies are needed to determine the mechanism and role of this acquired deficiency in the pathogenesis of thrombotic episodes in patients with SLE.

Epidemiological study of Paget's disease of bone in a zone of the Province of Salamanca (Spain). The Paget's disease of the bone study group of Salamanca.

Bone Paget's disease is heterogeneously distributed and several foci of high prevalence have been reported in Spain. The aim of the present work was to determine the prevalence of the disease in a zone situated in the northwestern sector of the Province of Salamanca (Spain) using a cross sectional epi-demiological study. Sample choice was based on a stratified sampling according to the residence, age and sex of the inhabitants of the zone. A sampling error of 5% and a confidence level of 95% were considered; these afforded a sample of 378 units. Final choice of the subjects was based on a random pathway method. Data collection was accomplished with a personal interview using a 31-item questionnaire and analytical screening (AP and GGT). The field work was carried out over a one-year period. The data were input onto a calculation sheet for analysis and epidemiological interpretation. Finally, clinico-radiological confirmation of the cases deemed positive in the screening was accomplished. The prevalence of PBD in the zone studied is 5.7% (95% CI: 4.5-6.9). The highest percentage of patients lies within the age group between 70-79 years; most of these patients were women. The mean residence time in the zone was 66 years. According to the findings, this geographic zone has a high prevalence of PBD.

[The identification of plasma calcitonin in liver cirrhosis]. / Identificacón de la calcitonina plasmática en la cirrosis hepática.

Increased levels of plasmatic calcitonin (PC) have been found in patients afflicted with liver cirrhosis (LC). Different circulating polypeptides of calcitonin with contrasting molecular weight (MW) have been observed by way of several methods of identification. The aim of our study is identify these types of PC in patients afflicted with LC, using a gel chromatography technique, comparing them with those obtained from patients with thyroid medullar carcinoma (TMC). A first PC peak with MW of 30,000 daltons (D) corresponding to macromolecular types of PC of LC was observed. Furthermore, a second peak of PC, corresponding to a synthetic human calcitonin and to monomers of PC in patients with TMC was noted. This indicates is a slight increase of monomeric PC in patients with LC, although its biological function is unknown.

[Heterogeneity of calcitonin in liver cirrhosis]. / Heterogeneidad de la calcitonina en la cirrosis hepática.

Elevated serum calcitonin (SC) levels have been observed in cirrhotic patients although the biological activity of this hormone in such patients is not known. Twenty one patients diagnosed histologically of alcoholic hepatic cirrhosis (AC) and 12 healthy controls were studied evaluating the degree of hepatocellular failure by means of clinical and biological criteria. Serum calcitonin was determined by means of a radioimmuno assay (RIA) and a radioimmunometric assay (IRMA) in which by combining two monoclonal antibodies, mature calcitonin is determined. These levels almost correspond to levels of biologically active calcitonin. The results obtained show a significant increase in SC in patients with AC when compared to controls, both by RIA (280 +/- 197 pg/ml, p less than 0.001) and IRMA (18 +/- 6 pg/ml, p less than 0.01). Control values were 57 +/- 23 pg/ml and 12 +/- 7 pg/ml respectively. Mean SC values in cirrhotic patients obtained by RIA were 4.9 times greater than their controls while the increase in SC in cirrhotics determined by IRMA was 1.5 times the control, thus obtaining a significant direct correlation between SC and severity of hepatic failure. According to our results, the elevated SC found in cirrhotics is mainly due to immature or non active forms directly related with the degree of severity of the hepatic failure and probably to high Molecular Weight molecules. The slight increase in mature SC in this type of patients is probably due to hormonal mechanism of bone regulation, defendants of hepatic osteodystrophy.

[Sepsis: clinical course study of 126 patients in an internal medicine department]. / Sepsis: estudio clínico-evolutivo de 126 pacientes en un Servicio de Medicina Interna.

126 cases of sepsis were retrospectively studied in an Internal Medicine Department, giving special attention to the clinical evolution. 67 males and 59 females with a median age of 65 years old were discovered. 92% had one or more diseases, mainly COLD (30%) and diabetes mellitus (28%). The septic sources were urinary (37%) and respiratory (31%). 84% of the germs were gram (-), mainly E. Coli and Proteus sp. A mortality rate of 36% was found, the primary rates being: eighth decade (52%), patients with neoplastic disease (46%), biliary tract diseases (64%), endocarditis (66%), infection by Serratia (60%), Pseudomonas (50%), shock (55%) and DIC (50%). These last two complications were analysed and found to be the more frequent (35% and 6.3% respectively), also being those with higher mortality rate. Finally, the prognostic factors are established based on the results obtained.