Biochemical markers of bone turnover and clinical outcome in patients with renal cell and bladder carcinoma with bone metastases following treatment with zoledronic acid: The TUGAMO study.

BACKGROUND: Levels of bone turnover markers (BTM) might be correlated with outcome in terms of skeletal-related events (SRE), disease progression, and death in patients with bladder cancer (BC) and renal cell carcinoma (RCC) with bone metastases (BM). We try to evaluate this possible correlation in patients who receive treatment with zoledronic acid (ZOL). METHODS: This observational, prospective, and multicenter study analysed BTM and clinical outcome in these patients. Serum levels of bone alkaline phosphatase (BALP), procollagen type I amino-terminal propeptide (PINP), and beta-isomer of carboxy-terminal telopeptide of type I collagen (ß-CTX) were analysed. RESULTS: Patients with RCC who died or progressed had higher baseline ß-CTX levels and those who experienced SRE during follow-up showed high baseline BALP levels. In BC, a poor rate of survival was related with high baseline ß-CTX and BALP levels, and new SRE with increased PINP levels. Cox univariate analysis showed that ß-CTX levels were associated with higher mortality and disease progression in RCC and higher mortality in BC. Bone alkaline phosphatase was associated with increased risk of premature SRE appearance in RCC and death in BC. CONCLUSION: Beta-isomer of carboxy-terminal telopeptide of type I collagen and BALP can be considered a complementary tool for prediction of clinical outcomes in patients with BC and RCC with BM treated with ZOL.

Usefulness of bone turnover markers as predictors of mortality risk, disease progression and skeletal-related events appearance in patients with prostate cancer with bone metastases following treatment with zoledronic acid: TUGAMO study.

BACKGROUND: Owing to the limited validity of clinical data on the treatment of prostate cancer (PCa) and bone metastases, biochemical markers are a promising tool for predicting survival, disease progression and skeletal-related events (SREs) in these patients. The aim of this study was to evaluate the predictive capacity of biochemical markers of bone turnover for mortality risk, disease progression and SREs in patients with PCa and bone metastases undergoing treatment with zoledronic acid (ZA). METHODS: This was an observational, prospective and multicenter study in which ninety-eight patients were included. Patients were treated with ZA (4 mg every 4 weeks for 18 months). Data were collected at baseline and 3, 6, 9, 12, 15 and 18 months after the beginning of treatment. Serum levels of bone alkaline phosphtase (BALP), aminoterminal propeptide of procollagen type I (P1NP) and beta-isomer of carboxiterminal telopeptide of collagen I (ß-CTX) were analysed at all points in the study. Data on disease progression, SREs development and survival were recorded. RESULTS: Cox regression models with clinical data and bone markers showed that the levels of the three markers studied were predictive of survival time, with ß-CTX being especially powerful, in which a lack of normalisation in visit 1 (3 months after the beginning of treatment) showed a 6.3-times more risk for death than in normalised patients. Levels of these markers were also predictive for SREs, although in this case BALP and P1NP proved to be better predictors. We did not find any relationship between bone markers and disease progression. CONCLUSION: In patients with PCa and bone metastases treated with ZA, ß-CTX and P1NP can be considered suitable predictors for mortality risk, while BALP and P1NP are appropriate for SREs. The levels of these biomarkers 3 months after the beginning of treatment are especially important.

Mobility and postural limitations perceived by transtibial amputees undertaking agricultural activities: a qualitative study.

PURPOSE: In Colombia, 98% of landmines occur in rural areas, where the main victims of amputation are farmers. The challenges these amputees face in their agricultural work remain unknown. The aim of this study is to determine the mobility and postural limitations these farmers face in carrying out their daily activities. METHOD: Forty-nine participants meeting the following criteria were interviewed: transtibial amputee, 18 years and over, performs agricultural labour and wears the prosthesis daily. Subsequently, the interview transcripts were subjected to a content conventional analysis and responses were organized according to the abstraction process to identify categories and subcategories of the problems. RESULTS: Main problems reported were walking on sloping, uneven and wet terrain, problems associated with the stump skin, squatting, kneeling, using vehicles or animals for transportation and carrying objects over 30 kg. Postures such as sitting, running, jumping, and standing on tiptoes were mentioned less frequently. CONCLUSIONS: In conclusion, the prostheses worn by transtibial amputee farmers are not suitable for working on sloping and uneven terrain, nor for performing postures such as kneeling or squatting. These postures are very common in agricultural and livestock tasks in countries with mountainous areas such as Latin American countries. The recognition of problems reported by farmers transtibial amputees, may help to improve the design of prostheses so that they meet the needs of this population and decrease secondary injuries associated with prosthetic use. This information is useful to identify compensatory postures that facilitate prosthetic adaptation and rehabilitation for amputees.

Magnetic Resonance Image-Guided Radiotherapy (MRIgRT): A 4.5-Year Clinical Experience.

AIMS: Magnetic resonance image-guided radiotherapy (MRIgRT) has been clinically implemented since 2014. This technology offers improved soft-tissue visualisation, daily imaging, and intra-fraction real-time imaging without added radiation exposure, and the opportunity for adaptive radiotherapy (ART) to adjust for anatomical changes. Here we share the longest single-institution experience with MRIgRT, focusing on trends and changes in use over the past 4.5 years. MATERIALS AND METHODS: We analysed clinical information, including patient demographics, treatment dates, disease sites, dose/fractionation, and clinical trial enrolment for all patients treated at our institution using MRIgRT on a commercially available, integrated 0.35 T MRI, tri-cobalt-60 device from 2014 to 2018. For each patient, factors including disease site, clinical rationale for MRIgRT use, use of ART, and proportion of fractions adapted were summated and compared between individual years of use (2014-2018) to identify shifts in institutional practice patterns. RESULTS: Six hundred and forty-two patients were treated with 666 unique treatment courses using MRIgRT at our institution between 2014 and 2018. Breast cancer was the most common disease, with use of cine MRI gating being a particularly important indication, followed by abdominal sites, where the need for cine gating and use of ART drove MRIgRT use. One hundred and ninety patients were treated using ART in 1550 fractions, 67.6% (1050) of which were adapted. ART was primarily used in cancers of the abdomen. Over time, breast and gastrointestinal cancers became increasingly dominant for MRIgRT use, hypofractionated treatment courses became more popular, and gastrointestinal cancers became the principal focus of ART. DISCUSSION: MRIgRT is widely applicable within the field of radiation oncology and new clinical uses continue to emerge. At our institution to date, applications such as ART for gastrointestinal cancers and accelerated partial breast irradiation (APBI) for breast cancer have become dominant indications, although this is likely to continue to evolve.

Expression analysis and chromosomal mapping of a novel human gene, APRIL, encoding an acidic protein rich in leucines.

Clone 120041 was selected from the EST database for sequence similarity to DEK and SET proteins rearranged in leukemias. The ends of the cDNA were isolated by RACE technique. The assembled cDNA encodes an LRR-containing protein of 251 amino acids designated APRIL (acidic protein rich in leucines). APRIL has high similarity to human pp32, also named PHAPI (bovine I[PP2A]1), and to rat LANP, respectively. APRIL shows tissue-specific expression as shown by Northern blot analysis. It was localized to 15q25 by FISH.

Identification of essential aspartic acid and histidine residues of hormone-sensitive lipase: apparent residues of the catalytic triad.

It is expected that hormone-sensitive lipase (HSL), like most other lipases and esterases, adopts an alpha/beta-hydrolase fold and has a catalytic triad of serine, aspartic or glutamic acid, and histidine. Recently, we have published a three-dimensional model for the C-terminal catalytic domain of HSL, having an alpha/beta-hydrolase fold and with Ser-423(1), Asp-703 and His-733 in the catalytic triad (Contreras et al. (1996) J. Biol. Chem. 271, 31426-31430). It has been shown that Ser-423, situated in the motif GXSXG, is essential for catalysis (Holm et al. (1994) FEBS Lett. 344, 234-238). The suggested aspartic acid and histidine were here probed by site-directed mutagenesis. Mutants of residues Asp-703 and His-733 are devoid of both lipase and esterase activity, which is not the case for mutants of other tested aspartic acid and histidine residues. Thus, the presented data support the three-dimensional model structure with Asp-703 and His-733 as part of the traid.

Cholesteryl ester transfer activity in lipoprotein lipase deficiency and other primary hypertriglyceridemias.

Cholesteryl ester transfer protein (CETP) activity was measured in d > 1.21 g/ml plasma from hypertriglyceridemic patients and compared with normolipidemic subjects. The assay consisted in measuring the specific transfer of [3H]cholesteryl oleate from a prelabelled, apo E-poor HDL fraction to VLDL after incubation at 37 degrees C in the presence of the d > 1.21 g/ml plasma sample: the lipoproteins were then separated by precipitation with dextran sulfate/Mg2+ solution. Increasing the volume of d > 1.21 g/ml plasma or purified human CETP in the assay produced linear responses in measured activity, whereas, either during incubation at 4 degrees C or in the presence of rat plasma instead of human plasma, the transfer of [3H]cholesteryl oleate to VLDL was not stimulated. Thus, the assay reflects changes in CETP in the sample and appears to be suitable for measuring CETP activity in d > 1.21 g/ml plasma. CETP activity was very similar in the two groups of normolipidemic subjects considered: adolescents (203 +/- 11 nmol esterified cholesterol transferred per 8 h/ml plasma) and adults (215 +/- 5). Patients were grouped into lipoprotein-lipase (LPL)-deficient and non-LPL-deficient according to their enzyme activity in postheparin plasma. CETP activity was highly increased in LPL-deficient, severe hyperchylomicronemic patients (430 +/- 42) and was directly correlated with VLDL levels in the non-LPL-deficient individuals. Marked differences were observed in the lipid composition of HDL and apolipoprotein A-I levels among patients and controls. In the control group, CETP activity was correlated only with HDL-triglyceride and HDL-triglyceride/apo A-I mass ratio, which is compatible with the physiological role of CETP in transferring triglyceride to HDL from other lipoprotein particles. When all hypertriglyceridemic patients were considered together, CETP activity was inversely correlated with apo A-I and HDL-cholesterol, whereas it was directly correlated with HDL-triglyceride/HDL-cholesterol and HDL-triglyceride/apo A-I mass ratios. The results indicate that the enhanced CETP activity associated with hypertriglyceridemia contributes to the compositional change of HDL, which in turn may be responsible for the reduction of HDL levels in this condition.

The quantitative anatomy of the normal human heart in fetal and perinatal life.

A total of 367 human fetuses and newborn subjects weighing from 60 to 5000 g provided the material for a morphometric study of the heart. A total of 17 interventricular parameters were measured in each specimen, one of the parameters representing an innovation with regard to the classically used set of measurements. A new anatomo-geometric configuration is described for each ventricle along with a new component for the left ventricular outflow tract, designated as the aortic outflow tract. The appropriate stereometric formulas were used to calculate real ventricular volumes rather than the previously studied volumetric indices. Additionally, correlation indices were calculated for ventricular wall thickness as well as the circumferences and diameters of the atrioventricular and arterial valves. The results show that, in fetuses of up to 2700 g in body weight, ventricular wall thickness is greater in the right than in the left ventricle, although the opposite is true in fetuses weighing above 2700 g. Throughout the range of weights studied, ventricular volume was greater in the left than in the right chamber. Tricuspid and pulmonary valve circumference and diameter were consistently greater than in the mitral and aortic valves, respectively. We believe the new morphometric data and their innovative interpretation to have immediate applications in both the morphological and functional areas of cardiology.

Morphometric data concerning the great arterial trunks and their branches.

In a total of 496 fetuses and newborns ranging in body weight from 60 to 5000 g, we performed a morphometric study of the vascular complex, that is the orifices of the great arterial trunks, ascending aorta, aortic arch, vessels branching from the aortic arch, the aortic isthmus, descending aorta, pulmonary trunk, orifices of the pulmonary arteries and arterial duct. In all, 17 different parameters were measured in each specimen, using several new parameters in addition to the measurements classically used in the aortic isthmus, arterial duct and pulmonary trunk. Anatomo-geometric models of these structures were developed, and stereometric formulas used to calculate the real volumes of the aortic isthmus, arterial duct and pulmonary trunk. The variations in the correlations between two measurable characteristics, that is, body weight and each of the morphometric parameters were analyzed, and the minimum, normal and maximum patterns of normality for each parameter were obtained with regression equations. The results show that the volume of the aortic isthmus increases by 0.03 ml for each millilitre increase in left ventricular volume. The isthmic volume increases by 0.32 ml for each millilitre increase in volume of the arterial duct and the volume of the pulmonary trunk increases by 6.4 ml for each increase of 1 millilitre in the volume of the aortic isthmus. The inner circumference of the aortic isthmus is greater than that of the arterial duct, whereas the former vessel is always shorter than the latter. We believe that these morphological data, when appropriately interpreted, have immediate clinical and surgical applications in the treatment of fetal and perinatal cardiovascular disorders.

Clinical and microbiologic findings in lambs inoculated with Pasteurella haemolytica after infection with ovine adenovirus type 6.

Colostrum-deprived lambs (10 to 20 days old) were inoculated with either ovine adenovirus type 6 (OAV-6; n = 6), Pasteurella haemolytica type A1 (n = 6), or OAV-6 followed by P haemolytica 5 days later (n = 10). Another group (n = 3) served as sham-inoculated controls. Lambs inoculated with OAV-6 or P haemolytica developed mild and moderate respiratory tract disease of 6 and 3 days' duration, respectively. Lambs inoculated with virus and bacteria developed clinical signs of respiratory tract disease of greater intensity and duration (9 days) than with either agent alone. Within 3 hours of bacterial inoculation, all lambs that received P haemolytica were anorectic, listless, and febrile, and had hyperpnea and dyspnea. Ovine adenovirus type 6 was isolated from all virus-inoculated lambs. Although P haemolytica was not recovered from all bacteria-inoculated lambs, it was recovered for a longer period in the group that received both agents. Antibody to OAV-6 was detected in virus-inoculated lambs as early as day 6 after inoculation. The control lambs remained clinically normal and neither virus nor bacteria were recovered at necropsy.

[Risk factors for bronchial asthma in patients with rhinitis]. / Factores de riesgo asociados con asma bronquial en pacientes con rinitis.

OBJECTIVES: To identify risk factors for bronchial asthma in a large sample of patients with rhinitis. PATIENTS AND METHODS: One thousand seven hundred sixty patients with rhinitis treated at the respiratory medicine out-patient service of Hospital Universitario Virgen de Rocío in Seville (Spain) in 1997 and 1998 were studied. Six hundred forty-one (36.4%) had isolated rhinitis and 1,119 (63.6%) had rhinitis and bronchial asthma. The following variables were analyzed for both groups: 1) age, 2) sex, 3) clinical diagnosis, 4) age of onset of symptoms, 5) a family history of asthma and/or atopy, 6) housing conditions, 7) smoking, 8) a history of skin allergy, 9) recurrent episodes of respiratory infection with wheezing during early childhood, 10) a diagnosis of nasosinus polyposis, 11) atopy and sensitivity (pollens and/or household allergens), 12) peripheral blood eosinophil count. RESULTS: The variables that best differentiated the group with rhinitis from the group with both rhinitis and asthma were age, family history of asthma and/or atopy, exposure to household humidity or damp, a history of skin allergy, recurrent episodes of respiratory infection with wheezing in early childhood, atopy, sensitivity to household allergens and peripheral blood eosinophil count. The probability of correctly classifying patients in the appropriate group using this model was 69.7%. Among atopic patients, the best predictive variables were the same, with the exception of household humidity/damp. The probability of correct classification using this model was 69.7%. CONCLUSIONS: Patients with rhinitis have risk factors for bronchial asthma. As many such patients as possible should be identified so that long-term follow-up can take place and strategies to prevent bronchial asthma can be implemented.

[Cerebral hydatidosis. Analysis of a series of 23 cases]. / Hidatidosis cerebral. Análisis de una serie de 23 casos.

BACKGROUND: The aim of the present study was to contribute to the knowledge of cerebral hydatidosis so as to improve the prognosis of a benign condition with a malignant behavior, as it has a high relapse rate with a high morbidity. METHODS: A retrospective study of cerebral hydatidosis has been carried out in 23 patients, seen at the University Hospital Virgen del Rocío during the last 20 years. The following variables were recorded: 1) Sex and age at presentation; 2) epidemiological data; 3) number, size, localization and rate of growth of cysts; 4) latency period; 5) clinical features; 6) yield of imaging procedures; 7) surgical approaches and medical therapy; and 8) relapses and sequelae. A comparative study was made of patients aged 14 years or less and those above this age. RESULTS: The mean age of the patients was 15.1 +/- 10.3 years (65% were younger than 14 years). 24% were males. 65% came from Extremadura and 74% had a rural background. The latency period was 7.9 +/- 9.2 months (range 15 days-36 months), and it was shorter in children (4.2 +/- 3.8 vs 12.6 +/- 12.7 months) (p less than 0.05). 74% had a single cyst. The cyst size was greater in children (91 +/- 46 vs 67 +/- 35 mm), as it was the rate of growth, particularly in patients younger than 10 years (13.5 +/- 7 vs 9.2 +/- 2 mm/year) (p less than 0.001). 48% had intraparenchymal localization and 70% were in the right hemisphere. In two cases the localization was intraventricular and it was cerebellar in one. Cranial computed tomography was the imaging procedure with the highest yield. The diagnosis was confirmed with pathological examination. In 6 patients (26%) the Dowling and Orlando technique (hydatid delivery) was carried out without subsequent relapses. In 7 cases (30%), and owing to surgical technique difficulties or accidents, puncture and aspiration were carried out, with 4 relapses (57%). In 10 cases cyst rupture occurred, with 6 relapses (60%). The growth rate of the relapses was 9.4 +/- 6.5 mm/month. 87% had severe sequelae, associated with relapses and multiplicity, two patients died (9%). CONCLUSIONS: 1) Cerebral hydatidosis predominates in children and young adult males of a rural background; 2) usually there is a long latency period, which is shorter in children; 3) the size and the growth rate of the cysts is greater in children; 4) computed tomography is the imaging technique with the highest yield; 5) Dowling and Orlando technique is the most effective surgical procedure; 6) the incidence of relapses is high, depending on the type of surgical approach.

Behavioral and stimulant treatment of hyperactive children: a therapy study with methylphenidate probes in a within-subject design.

Eight hyperactive children were treated with a behavioral intervention focusing on teacher and parent training over a period of 5 months. Three times, before therapy and after 3 weeks and 13 weeks of intervention, children received methylphenidate during 3-week probe periods. Each week in a probe they received either a placebo, .25 mg/kg, or .75 mg/kg methylphenidate. Classroom observation of on-task behavior suggested that effectiveness of the behavioral intervention was between that of the two dosages of medication before therapy. Both dosages resulted in higher levels of on-task behavior when administered after 13 weeks of behavioral intervention than when administered before therapy. Teacher rating data showed equivalent effects of therapy and the low dosage of methylphenidate alone but a stronger effect of the high dose alone; only the high dose resulted in improved behavior after 13 weeks of behavioral intervention. As a group, only when they received the high dose of methylphenidate after 13 weeks of behavioral intervention did children reach the level of appropriate behavior shown by nonhyperactive controls. However, this level was also reached by two children with the low dose and by one child without medication, and it was not reached by one child. The results suggest that the combination of psychostimulant medication and behavior therapy may be more effective in the short-term than either treatment alone for hyperactive children in school settings. In addition, parent ratings and clinic observation of parent-child interactions suggested that children had improved in the home setting, high-lighting the importance of behavioral parent training in the treatment of hyperactivity.

[Hydatidosis of the posterior fossa]. / Hidatidosis de fosa posterior.

The hydatid cyst is an endemic zoonosis in Spain. The central nervous system is seldom affected, the hydatid cyst in cerebellum being very rare. A patient with hydatid cyst affecting the vermis and right cerebellar hemisphere is presented. The case is described and discussed. The use of CT scan is encouraged as the most worthwhile election of diagnosis techniques. We highlight the need for very careful surgical treatment, preserving the hydatid cyst complete, to avoid relapses and to prevent the change of a benign disease to a chronic one with very high mortality.

Stomatopods (Crustacea: Hoplocarida) from the Gulf of Tehuantepec, Mexico.

A total of 1,173 specimens of Stomatopoda were captured in 27 localities at different depths (20 to 73 m) during three oceanographic cruises in the Mexican Pacific along the continental shelf of the states of Oaxaca and Chiapas. Seven species were identified of the families Eurysquillidae, Lysiosquillidae and Squillidae. Squilla hancocki and Squilla parva were the most abundant species and the most frequently found together. The relationships between total length and carapace length were obtained for these species, which show that males of S. hancocki have a longer carapace length than females having the same total length, whereas for S. parva the opposite occurs. Larger sizes than previously reported were obtained for Lysiosquilla panamica and Squilla mantoidea. Squilla bigelowi was recorded for the first time in the Gulf of Tehuantepec. All the species were found in the intermediate platform (25-60 m); E. veleronis, S. hancocki and S. parva extended their distributions to the external platform (60-120 m), and S. hancocki and S. parva reached the circalittoral zone (10-25 m).

[Evaluation of the satisfaction with a care coordination program between Primary Care and general internists]. / Evaluación de la satisfacción de un programa de colaboración entre Atención Primaria y Medicina Interna.

OBJECTIVES: To evaluate the level of knowledge, participation and satisfaction with a continuity of care program between Primary Care and a group of general internists, and to analyse the most frequent reasons for consulting. MATERIAL AND METHODS: Cross-sectional study including all primary care physicians from 10 Family Practice Care Centres using a questionnaire containing these objectives. RESULTS: Eighty-three family physicians (92.2%) answered the survey. All physicians knew of the collaboration program and had also participated. The most common clinical problems seen were: patients with multiple health problems(26.5%), cardiovascular risk factors (16.8%) and diagnosis of the asthenia syndrome (141%), with these three problems obtaining the best evaluation in the satisfaction survey. Almost all (98.8%) of the family physicians were satisfied with the program. CONCLUSIONS: Our continuity care program was very well evaluated in the satisfaction survey by family physicians. The participation index was very high and the clinical problems most frequently consulted and best evaluated were those that traditionally have been seen by the internists.

[Prognostic value of the sTREM-1 plasma values in patients with sepsis: a cohort study]. / Valor pronóstico de los niveles plasmáticos de sTREM-1 en pacientes con sepsis: un estudio de cohortes.

OBJECTIVE: To evaluate the association between plasma levels of soluble Triggering Receptor Expressed on Myeloid Cells-1 (sTREM-1) and mortality of patients with sepsis. DESIGN: Prospective cohort study. SETTING: Two general Intensive Care Units. PATIENTS: Patients with sepsis in whom sTREM-1 plasma levels were determined daily in the first 3 days of their presentation. VARIABLES OF INTEREST: Mortality at 28 days. RESULTS: We analyzed 121 patients (23% severe sepsis, 44% septic shock, 33% non-severe sepsis). Mortality at 28 days was 24.8%. The initial sTREM-1 levels were slightly higher in nonsurvivors than in survivors (median 366.9 versus 266.5 pg/ml, p=0.2668). An increase in sTREM-1 levels higher than 90 pg/ml within the first 3 days (delta-TREM) was associated with an excess of mortality (hazard ratio [HR] 2.68, p=0.0047), with a sensitivity of 47% and a specificity of 78%. This excess of mortality disappeared after adjusting for severity by Cox analysis (adjusted HR 1.07, p=0.8665). CONCLUSIONS: The increase in the levels of sTREM-1 during the first 3 days of evolution is associated with an excess of mortality in critically ill patients with sepsis. This is explained by the greater initial severity of these patients. The discriminative capacity of this finding is insufficient to be clinically useful.