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SummaryIntravenous heparin followed by oral anticoagulant therapy (e. g. with coumarin) is still the most widely used treatment for deep venous thromboembolism. Self-administered subcutaneous injections of heparin have been thought of as a promising alternative to coumarin, but the high doses required for ongoing prophylaxis have raised concerns about the possible development of bone disease. Certainly, long-term heparin therapy has been reported to cause osteoporosis in both laboratory animals and humans.This study aimed to compare the efficacy and safety of unfractionated (UF) heparin with that of a low molecular weight heparin (Fragmin®, Kabi Pharmacia) in the prevention of recurrent deep venous thrombosis (DVT) and pulmonary embolism (PE) in a consecutive series of patients with contraindications to coumarin therapy. The patients comprised 40 men and 40 women, aged between 19 and 92 years (mean age, 68 years). They had all previously been diagnosed as having acute DVT and had been treated with conventional doses of heparin while in hospital. All patients had at least one of the following conditions: recent blood loss (either spontaneous or during admission while receiving heparin therapy); active gastroduodenal ulcer disease; psychological or physical inability or unwillingness to understand and accept the need for regular laboratory monitoring during coumarin treatment; chronic alcoholism; dementia; pregnancy; recent neurosurgery, and pericardial effusion; or were over 80 years of age. They were randomly allocated to receive either UF heparin, 10,000 IU s.c. b.d., or Fragmin®, 5000 IU anti-Factor Xa s. c. b. d., for a period of 3-6 months.Two patients taking UF heparin were readmitted to hospital 2 and 3 months after discharge, owing to symptomatic, scintigraphically proven recurrent PE. No patients receiving Fragmin® had recurrent PE. There were 10 reports of minor bleeding: six in patients receiving UF heparin and four in patients on Fragmin®. Furthermore, there were seven cases of spinal fracture: six in patients on UF heparin, and one in a patient taking Fragmin®.We conclude that fixed doses of both UFH and Fragmin® appear to be quite effective and safe for use in patients with a high risk of bleeding. In our experience, however, UF heparin is associated with an unacceptably high incidence of spinal fracture.

Bone mineral density (BMD) as assessed by dual energy X-ray absorptiometry (DXA) constitutes the gold standard for osteoporosis diagnosis. However, DXA does not take into account bone microarchitecture alterations. The aim of our study was to evaluate the ability of trabecular bone score (TBS) at lumbar spine to discriminate subjects with hip fracture. We presented a case–control study of 191 Spanish women aged 50 years and older. Women presented transcervical fractures only. BMD was measured at lumbar spine (LS-BMD) using a Prodigy densitometer. TBS was calculated directly on the same spine image. Descriptive statistics, tests of difference and univariate and multivariate backward regressions were used. Odds ratio (OR) and the ROC curve area of discriminating parameters were calculated. The study population consisted of 83 subjects with a fracture and 108 control subjects. Significant lower spine and hip BMD and TBS values were found for subjects with fractures (p

The publication of the new Technical Report IEC/TR 62271-208 allow transformer substation (TS) manufacturers and users to assess the generated magnetic fields (MF) since it describes standard methods for its evaluation and opens the possibility of employing simulation tools for this purpose.

This paper presents a 64-bits chaotic block cryptosystem, which uses as noise generator one-dimensional chaotic maps with 8 bits sub-blocks data. These chaotic maps use a control parameter that allows them to operate in the chaotic region, which guarantees that each sub-block of data is mixed with unpredictable random noise. Statistical mechanic tools such as: bifurcation diagram, Lyapunov exponent, and invariant distribution have been used to analyze and evaluate the behavior of the noise generator. The cryptosystem has been evaluated using concepts of information theory, such as: entropy, as a diffusion measure in the encryption process, and mutual information as a measure of relationship between plaintext and its respective cryptogram. The noise generator has been used on the non-balanced and dynamic network proposed by L. Kocarev. The randomness of the cryptograms has been evaluated using the NIST random tests. The proposed cryptosystem can be a component in software applications that provides security to stored or communicated information. The proposed cryptosystem has a similar behavior to the one of currently used cryptosystems and it has been designed with chaotic sequence generators, which are aperiodic by definition.

A surgical procedure in which a tendon graft is used to reconstruct the hood of the proximal interphalangeal joint for the correction of the postburn boutonnière deformity is described. The intent is to use the potential of the lateral bands for simultaneous extension of the interphalangeal joints, avoiding their excessive palmar displacement. The technique has been employed in 22 fingers with satisfactory results, except in the small finger.

A model adequately describing the lipase production by Candida rugosa has been developed, calibrated and validated using new experimental data. Process modelling has been done using CAMBIO software (Computer Aided Modelling of BIOprocesses), allowing to easy and interactively test various hypothesis and reaction schemes.

In this paper, the Birkhoff's Ergodic Theorem, mixing property of the one-dimensional maps, strong convergence criterion and Kullbak-Leibler divergence are applied in order to design chaotic analogical noise generators using MOS QT Circuits, which are governed by one-dimensional chaotic maps. In this work an analogical circuit is used, which have a structure of transistors MOS that operates in current-mode and that uses the transconductance linear principle.

BACKGROUND: Reduced bone mass predisposes patients to the development of vertebral fractures. Measurement of bone mass by non-invasive methods is used to detect patients with involutional osteoporosis at risk from fractures. These methods have not been assessed in patients with steroid dependent osteoporosis. The objective of this study was to assess the value of a predictive fracture threshold value of bone density in patients with steroid dependent asthma. METHODS: Three groups of patients were studied. Group 1 (67 patients) had steroid dependent asthma (mean daily dose of prednisone 11.7 mg) and no vertebral fractures, group 2 (32 patients) had steroid dependent asthma (mean daily dose of prednisone 12 mg) and vertebral fractures, and group 3 (55 patients) were not taking steroids but had involutional osteoporosis and a recent non-traumatic vertebral fracture. Bone mineral density was measured by dual photon absorptiometry and vertebral fractures by radiography of the lumbar spine. A fracture threshold was determined in the two groups with fractures as the 90th percentile of the mean bone mineral density measured in the lumbar spine. RESULTS: Bone mineral density was significantly higher in the steroid dependent group with fractures (group 2) than in group 3 patients, who had involutional osteoporosis and fractures (0.946 (0.18) g/cm2 v 0.830 (0.16) g/cm2). The fracture threshold value was therefore higher for patients with steroid related vertebral fractures (group 2, 1.173 g/cm2) than for those with involutional osteoporosis (group 3, 0.979 g/cm2). Vertebral fractures were more likely to occur in steroid dependent asthmatic patients with bone density above the fracture threshold value (obtained from subjects with involutional osteoporosis) than in subjects in group 3 (34% v 9%). CONCLUSION: Vertebral fractures occur in patients treated with steroids in the presence of higher bone mineral density than is the case with patients with involutional osteoporosis. The findings suggests that the assessment of the efficacy of preventive treatment requires measurement of bone mineral density and radiology.

To evaluate the applicability of the WHO densitometric criteria for the diagnosis of spinal osteoporosis in men and to compare it with women with vertebral fractures, as well as to analyze the role of vertebral dimensions in the development of spinal fractures.For these purposes we analyzed, using DXA, vertebral projected area and lumbar bone mineral density (BMD), as well as T and Z-scores in lumbar spine in a cohort of 66946 individuals; 2556 of these subjects had one or more atraumatic vertebral fracture (396 men and 2160 postmenopausal women).Men and women with fractures showed significantly lower mean BMD, T-score and Z-score values than individuals without fractures while vertebral dimensions were similar in both groups of patients. When comparing men and women with vertebral fractures, the former showed a significantly greater projected area (46.89+/-5.5 vs. 39.13+/-4.6 cm(2) p0.001) and lumbar BMD (0.991+/- 0.21 vs. 0.938+/- t0.19 g/cm(2) p0.001). However, the median lumbar T-score values were similar for both sexes (-2.3 in women vs. -2.2 in men; p: NS). In addition, a similar percentage of men and women with vertebral fractures showed T-score values-2.5 in the lumbar spine (44% vs. 46%, p=NS).We conclude that although men with vertebral fractures have greater vertebral dimensions and BMD than women, the lumbar T-scores are similar. Therefore, it seems reasonable to adopt the same T-score values for the diagnosis of osteoporosis in men and women.

Parasympathetic activity during acute coronary artery occlusion (CAO) can protect against ischaemia-induced malignant arrhythmias; nonetheless, the mechanism mediating this protection remains unclear. During CAO, myocardial electrotonic uncoupling is associated with autonomically mediated immediate (i.e. type 1A) arrhythmias and can modulate pro-arrhythmic dispersion of repolarization. Therefore, the effects of acutely enhanced or decreased cardiac parasympathetic activity on early electrotonic coupling during CAO, as measured by myocardial electrical impedance (MEI), were investigated. Anaesthetized dogs were instrumented for MEI measurements, and left circumflex coronary arterial occlusions were performed in intact (CTRL) and vagotomized (VAG) animals. The CAO was followed by either vagotomy (CTRL) or vagal nerve stimulation (VNS, 10 Hz, 10 V) in the VAG dogs. Vagal nerve stimulation was studied in two additional sets of animals. In one set heart rate (HR) was maintained by pacing (220 beats min(-1)), while in the other set bilateral stellectomy preceded CAO. The MEI increased after CAO in all animals. A larger MEI increase was observed in vagotomized animals (+85 +/- 9 Omega, from 611 +/- 24 Omega, n = 16) when compared with intact control dogs (+43 +/- 5 Omega, from 620 +/- 20 Omega, n = 7). Acute vagotomy during ischaemia abruptly increased HR (from 155 +/- 11 to 193 +/- 15 beats min(-1)) and MEI (+12 +/- 1.1 Omega, from 663 +/- 18 Omega). In contrast, VNS during ischaemia (n = 11) abruptly reduced HR (from 206 +/- 6 to 73 +/- 9 beats min(-1)) and MEI (-16 +/- 2 Omega, from 700 +/- 44 Omega). These effects of VNS were eliminated by pacing but not by bilateral stellectomy. Vagal nerve stimulation during CAO also attenuated ECG-derived indices of ischaemia (e.g. ST segment, 0.22 +/- 0.03 versus 0.15 +/- 0.03 mV) and of rate-corrected repolarization dispersion [terminal portion of T wave (TPEc), 84.5 +/- 4.2 versus 65.8 +/- 5.9 ms; QTc, 340 +/- 8 versus 254 +/- 16 ms]. Vagal nerve stimulation during myocardial ischaemia exerts negative chronotropic effects, limiting early ischaemic electrotonic uncoupling and dispersion of repolarization, possibly via a decreased myocardial metabolic demand.

We experimentally demonstrate the possibility of retrieving the spatial coherence of an infrared source by using an up-conversion interferometer. Sum-frequency generation in Ti-diffused periodically poled lithium-niobate waveguides in both arms of the interferometer is used to convert the infrared into the visible domain. The fringe contrast of the interference pattern in the visible domain permits us to resolve the spatial separation of two uncorrelated pointlike infrared sources, which simulate a binary star. The validity of these measurements is confirmed through a simultaneous comparison with a reference interferometer working in the infrared domain.

In a study of lipase production byCandida rugosa growing on olive oil, the relationship between the consumption of substrate and lipase production is presented. Two stages could be observed in the consumption of the olive oil: a first one, related with the glycerol depletion without lipase production, and a second one, associated with the fatty acids consumption when the enzyme appears in the medium.

The impact that project complexity, student prior academic achievement, and quality of instructional materials might have on student academic achievement was studied during a required device physics course, in which technology computer-aided design (TCAD) tools were introduced to first-year graduate students. Preliminary analysis of student performance and project complexity showed that students who attempted the most complex projects had the lowest student academic achievement, despite there being no significant differences in prior academic achievement as measured by grades in the first exam in the course. Further analysis of student achievement data from other electrical engineering courses taught in a similar open laboratory format, for which enhanced instructional materials were developed, suggest that when well-developed learning resources are easily accessible to students, project complexity has no negative impact on student academic achievement and can sometimes enhance student academic performance. Cognitive load theory was used to explain why well-developed instructional tools, such as enhanced tutorials, can help students better learn or work with complex material.

Introduction Several methods are used to measure infliximab (IFX), adalimumab (ADL), antibodies to IFX (ATI) and antibodies to ADL (ATA). These agents elicit an unwanted immune response leading to loss of response. Measurement of drug levels (DL) and anti-drug antibodies (ADA) are often required for routine patient monitoring. The aim of this study was to compare different commercially available ELISA tests for the measurement of DL and ADA for IFX and ADL. Method A total of 109 samples (69 IFX and 40 ADL) from 71 patients with IBD were included in the study. DL and ADA trough levels were measured with Promonitor kits (Progenika, Spain) and LISA-TRACKER (LT) Duo IFX and ADL kits (Theradiag, France). In addition, drug-spiked samples were analysed to ascertain trueness. Pearson and Bland-Altman analysis was used to study the association and agreement between DL methods. Cohen´s kappa was used to study agreement of ADA assays. Results Correlation coefficients between each Promonitor test and the corresponding LT assay were 0.99 and 0.83 (p Conclusion Performances of both assays were comparable for all measurements. However, the systematic differences in the magnitude of DL and limited measurement ranges observed for LT tests should be taken with caution since this could impact patient management. Disclosure of interest D. Nagore Employee of: Progenika, A. Ruiz del Agua Employee of: Progenika, J. Pascual Employee of: Progenika, F. Llinares-Tello: None Declared, B. Herreros: None Declared, A. Martinez Employee of: Progenika, S. Martin Grant/ Research Support from: Progenika, R. Navarro: None Declared, L. del Rio Employee of: Progenika.

Objectives Assess TBS to categorize skeletal status in adult subject which history of Poliomyelitis sequels in limbs. Methods We scan total body, lumbar spine (L1-L4) and both hips (Total femur and Femoral Neck ROI9s) in 58 patients with history of poliomyelitis infection and limb paralysis (men: 14 -57.5 years; women: 48 -57±8.5 years). A DXA device GE-iDXA model was used. The difference between affected extremity and the opposite in BMD T-score and trabecular microarchitecture assessed by TBS (TBS® Insight; Medimaps) were used. The results were stratified as normal, low bone density or osteoporosis taking the lower T-score of the scanned regions of interest. TBS results were categorized as normal (TBS N) ≥1.350; partially deteriorated-(TBS-PD) between: 1.250 -1.349, and significantly deteriorated (TBS-SD): Results Three patients had hip fracture history. The left limb was the extremity most affected in this group (32 vs 20). Five patients had both extremities affected, with more severe affectation on the right side (4/5). Only 7 patients had normal BMD of the hip, which contrasts with the 43.1% of patients with normal lumbar BMD. The TBS was normal in 16 patients (27.6%). Stratification was more similar in patients who had a low bone density (48.3% in the hip and 50% in lumbar spine) and TBS-PD (50%). In patients categorized as osteoporotic the lowest T-score of BMD was found in proximal femur (39.7%) of the most affected limb, the T-score BMD of the lumbar spine in 6.9% of the patients, while the TBS-SD was found at 22.4%. The DXA spine images showed a spondyloarthritis and scoliosis signs in 25 patients. 16.7% of patients had a osteoporotic T-score in affected femur and had normal BMD at the lumbar spine and opposite femur, but interestingly had a deteriorated TBS (TBS-PPD and TB SSD). Conclusions A degradation TBS allow identify a greater number of patients who had polio with low bone status than assess BMD of lumbar spine and femur. Postural instability could increase irregular mechanical charges to lumbar spine and femur unaffected that may decrease the sensitivity of DXA when only the BMD is used to classify patients. Disclosure of Interest None declared

Traumatic rupture of the thoracic aorta has a high mortality. The endovascular alternative has been considered for aortic repair in high-risk patients with multiple trauma. We report a case of a 20 year-old man who suffered a multiple trauma secondary to motor vehicle accident. Arteriography revealed the existence of a pseudoaneurysm at the origin of left common carotid artery. A short and immediate control of the thoracic aorta is needed in cases with active bleeding of the aorta when the patient is unstable. Endovascular treatment as a definitive repair or first control before performing surgical repair seems a good choice. Our experience in this patient suggests that the combined endovascular and surgical treatment can be a valuable therapeutic alternative when treating a blunt aortic lesion. It is less invasive surgery and avoids aortic cross-clamping, circulatory assistance and high dose heparinization. Further studies are required to determine the relevance of the endovascular treatment in the management of traumatic rupture of the aorta in young patients.

The aim of this study was to describe findings of bone scintiscans and their clinical significance for patients infected with human immunodeficiency virus type 1 (HIV-1); 33 HIV-1-infected patients (22 men and 11 women) free of osteoarticular symptoms were included in the study. Plain bone roentgenograms, bone mineral contents (measured by dual-photon absorptiometry), and scintiscans (determined with 99mTc diphosphonate) were obtained for all subjects. Plain bone roentgenograms showed no abnormalities, and bone mineral contents were within the normal range for all patients. Radionuclide bone scans were unremarkable for eight patients (24%) and showed symmetrical abnormally increased uptake in the epiphyseal region of the appendicular skeleton in 25 (76%). Follow-up of the patients for > or = 1 year ruled out subsequent development of osteoarticular disorders. Generalized, symmetrical increased radionuclide uptake on bone scans is a common finding for HIV-1 infected patients free of osteoarticular symptoms. This finding is probably related to bone marrow hypercellularity and is of no clinical significance; therefore, other diagnostic procedures are not required in the workup of these patients.

Chlamydophila abortus, the aetiological agent of ovine enzootic abortion, induces a strong inflammatory reaction that leads to the T helper cell (Th1) specific immune response necessary for the clearance of infection. Because the role of natural killer (NK) cells during the first stages of this response has received little attention, this study focused on determining the function of these cells in a mouse model of infection. The location of NK cells in the liver and spleen of infected mice was examined immunohistochemically with an anti-Ly49G monoclonal antibody. The number of NK cells increased during the infection both in spleen and liver. In subsequent experiments, an anti-asialo GM1 polyclonal antibody was injected to deplete the NK cells. NK-depleted mice showed a substantial increase in their susceptibility to C. abortus infection, with high mortality rates and an increased burden of bacteria in the liver. Histopathological studies showed that inflammatory foci, composed mainly of neutrophils, were greater in size and number in depleted mice, while numerous chlamydial inclusions were associated with the foci. Serum concentrations of IFN-gamma, a key cytokine in the control of C. abortus infection, were substantially reduced in the NK-depleted mice. To establish the relationship between NK cells and other components of the innate immune response, neutrophils were depleted with the RB6-8C5 antibody. These cells were shown to be crucial in the recruitment of NK cells to the inflammatory foci.

The objectives of the study were (1) to determine the time interval for repeat dual-energy X-ray absorptiometry (DXA) to detect significant bone loss, i.e., greater than the coefficient of variation (CV) of the center (2.8 × CV%) and (2) to assess how long hormone replacement therapy can be maintained to avoid undetected development of low bone mass and to not unduly delay appropriate treatment. A total of 3,826 healthy women, aged 40–65 years, participated in a prospective cohort study, 807 of whom were treated with transdermal estrogen replacement therapy and 626 with transdermal estrogen/progesterone regimens. The untreated group included the remaining 2,393 women. Between 1996 and 2002 they underwent a baseline DXA scan, and DXA scans were then repeated annually. There were no differences among the study groups at entry into the study. Treatment with estrogen was a protective factor for loss of bone mass at the lumbar spine (odds ratio [OR] =0.431, 95% confidence interval [CI] 0.344 to 0.522) and at the femoral neck (OR =0.433, 95% CI 0.352 to 0.521). Treatment with estrogen/progesterone also showed a protective effect against significant changes in follow-up BMD (>2.8 × 1.05% CV of densitometry at L1–L4, >2.8 × 2.3% CV at the femoral neck). In the treated group, significant differences in BMD at the lumbar spine (OR =1.593, 95% CI 1.423 to 2.355) did not appear within the first 3 years, and differences in BMD at the femoral neck (OR =3.555, 95% CI 2.782 to 4.905) did not appear within the first 4 years. It is concluded that in women aged 45–65 years, receiving transdermal hormone replacement therapy without risk factor for loss of bone mass, such as age < 55 years and body mass index

Colles’ fracture (CF) in postmenopausal women has been linked to low bone mass at the lumbar spine and hip. However, the diverse methodological approaches of previous studies make the results difficult to compare and thus the implications of CF in osteoporosis daily clinical practice are not clear. We explored the association between CF and low bone mineral density (BMD) in an incident case-control study in 58 postmenopausal Spanish women aged 45–80 years with recent CF and in 83 population-based controls of the same age range. The BMD of ultradistal distal forearm, lumbar spine and hip was measured by dual-energy X-ray absorptiometry (DXA) and WHO criteria were used to define osteoporosis and osteopenia. BMD was significantly lower in cases for all three areas (p

Although the cell-mediated immune response is known to be a critical factor in host defence against intracellular mycobacterial infection, the different components of the T-cell response are unclear, particularly in caprine infection. In this study we examine the differences in the lymphocyte population of peripheral blood, spleen and mediastinal and superficial lymph nodes in 11 naturally infected goats showing positive reactions in the comparative tuberculine intradermal test. According to the different types of lesion showing, the goats were classified into proliferative or exudative tuberculosis. The results obtained by fflow cytometry analysis indicated that the main differences in peripheral blood were in the CD4 T-cell population, which decreased markedly in goats with exudative tuberculosis, while the CD8 and B cells increased in number. The gamma/delta T cells did not show significant differences in either type of tuberculosis, while interleukin-2 receptor cells decreased slightly in the exudative tuberculosis. The CD4:CD8 ratio was higher than 1 in goats with proliferative tuberculosis and lower than 1 in goats with exudative tuberculosis. In general, the lymphoid organs of the goats with exudative tuberculosis showed a significant increase in the number of CD8 T cells (CD4:CD8 ratio of less than 1) whereas no significant differences were observed in the CD4 T population between either type of tuberculosis.

The immune mechanisms in response to Chlamydophila abortus (Chlamydia psittaci serotype 1) infection were studied in C57BL/6 and CBA mice. The infection was monitored and the following aspects of the immune response were evaluated: the nature of the leucocyte infiltrate in the liver, the percentages of polymorphonuclear neutrophils (PMNs), macrophages and lymphocytes in the spleen, and the concentrations of cytokines in serum. In addition, the serum concentrations of IgG1 and IgG2a were determined. Both mouse strains showed a Th1-like immune response, with high concentrations of IFN-γ and minimal levels of IL-4; however, C57 mice differed from CBA mice in showing milder clinical signs and earlier resolution of infection. The greater ability of C57 mice than CBA mice to eliminate chlamydophilae was related to the establishment of an earlier innate immunity, based on a more pronounced PMN response, and on a greater presence of CD8+T cells.

CBA/J mice were used in the present study to establish differences between the immune response to three chlamydial strains: AB7 (Chlamydia psittaci wild-type strain), 1B (C. psittaci vaccinal strain) and iB1 (C. pecorum). The evolution of chlamydial infection was evaluated in each strain by studying the clinical signs, the number of bacteria isolated from the spleen and the pathology of the liver. Three aspects of the immune response were then studied: the characterization of the infiltrate of leukocytes in the liver, the percentages of T- and B-cells, macrophages and neutrophils in the spleen, and the presence of cytokines in the serum. Infection followed a different course in the C. psittaci-infected mice; 1B-infected mice showed milder levels in all the parameters analysed than their AB7-infected counterparts. The resolution of infection was earlier in 1B-infected mice and, although the immune response to both strains was Th1-like, a more intense CD8+ T-cell response and an earlier presence of TNF-alpha in serum were observed in this group. C. pecorum infection was controlled mainly by a non-specific immune response, since these mice showed no signs of a systemic specific immune response. Neutrophil depletion experiments showed that these cells play a very limited role in the non-specific response against C. pecorum.

To assess whether vertebral fractures are associated with osteopenia in chronic alcoholic patients, a transversal study was carried out in 76 chronic alcoholic males and 62 age-matched healthy males. Lumbar bone mineral density (BMD) by dual photon absorptiometry and spinal chest X-ray films were done in all patients. Twenty-seven patients (36%) had vertebral fractures, but only 5 of them had a BMD below the fracture threshold. Twenty-two patients (29%) had osteoporosis by densitometric criteria. There were no significant differences in lumbar BMD between alcoholic patients with and without vertebral fractures (1.11 +/- 0.2 versus 1.13 +/- 0.2, P = ns). Previous trauma was recorded in 24 of the 27 patients with vertebral fractures and in 28 of the 49 patients without vertebral fractures (P < 0.001). Moreover, patients with vertebral fractures had more peripheral fractures than patients without vertebral fractures (81% versus 49%, P = 0.01). Only one patient was aware of a previous episode of traumatic vertebral fracture. In conclusion, chronic alcoholics frequently have traumas and vertebral fractures, the latter despite having a lumbar BMD above the fracture threshold, suggesting a frequent but unrecognized association between both processes. These results suggest that both spine films and BMD measurements should be obtained for diagnosis of osteoporosis in alcoholic patients.

Bone mineral content was measured by dual-energy x-ray absorptiometry in the lumbar spine at the L2-L4 level with a Lunar DPX densitometer model in 471 healthy white Mediterranean Spanish children and adolescents (256 boys and 215 girls) randomly selected from the urban area of Barcelona. Ages ranged from 3 mo to 21 y. Weight, height, and pubertal development were in the normal age distribution. Bone mineral content values were corrected by the vertebral surface area scanned and expressed as bone mineral density (BMD) values. BMD increased progressively from infancy to adulthood, and values were similar in both sexes, with the only differences related to the earlier onset of puberty in girls. A statistically significant correlation (p < 0.001) was found between BMD values and age, height, and weight. BMD values increased annually, but the periods of higher increase were observed during the first 3 y of life and late puberty. A significant (p < 0.001) increase in BMD was observed between Tanner pubertal stages III and IV and between Tanner stage IV and adult values. Lumbar BMD values peaked in a similar way to growth height velocity during pubertal development. However, the BMD peak seemed to occur somewhat later than height velocity peak, particularly in girls. In conclusion, we report normative data for BMD values at the lumbar level in our normally growing pediatric population and show that the first 3 y of life and adolescence are critical periods for bone mineralization. These data provide a tool for the investigation and follow-up of pediatric populations at risk for low bone mineralization.

Intravenous heparin followed by oral anticoagulant therapy (e. g. with coumarin) is still the most widely used treatment for deep venous thromboembolism. Self-administered subcutaneous injections of heparin have been thought of as a promising alternative to coumarin, but the high doses required for ongoing prophylaxis have raised concerns about the possible development of bone disease. Certainly, long-term heparin therapy has been reported to cause osteoporosis in both laboratory animals and humans. This study aimed to compare the efficacy and safety of unfractionated (UF) heparin with that of a low molecular weight heparin (Fragmin, Kabi Pharmacia) in the prevention of recurrent deep venous thrombosis (DVT) and pulmonary embolism (PE) in a consecutive series of patients with contraindications to coumarin therapy. The patients comprised 40 men and 40 women, aged between 19 and 92 years (mean age, 68 years). They had all previously been diagnosed as having acute DVT and had been treated with conventional doses of heparin while in hospital. All patients had at least one of the following conditions: recent blood loss (either spontaneous or during admission while receiving heparin therapy); active gastroduodenal ulcer disease; psychological or physical inability or unwillingness to understand and accept the need for regular laboratory monitoring during coumarin treatment; chronic alcoholism; dementia; pregnancy; recent neurosurgery, and pericardial effusion; or were over 80 years of age. They were randomly allocated to receive either UF heparin, 10,000 IU s.c. b.d., or Fragmin, 5000 IU anti-Factor Xa s.c. b.d., for a period of 3-6 months.(ABSTRACT TRUNCATED AT 250 WORDS)

e18144 Background: Patients (Pts) with SCLC progressing after first-line chemotherapy (FL) have a poor prognosis and evidence of a benefit of SL is still limited. This retrospective analysis evalua...

Low-bone-turnover osteoporosis is a common complication of primary biliary cirrhosis (PBC). Since sodium fluoride stimulates bone formation we assessed the effect of this drug on bone mass in a 2-year, prospective, double-blind trial including 22 women with PBC who were randomly assigned to receive sodium fluoride (50 mg/day) or placebo. All received calcium supplements and low doses of vitamin D. Bone mineral density of the lumbar spine was measured by dual-photon absorptiometry initially and every 6 months. Vertebral fractures were evaluated in thoracic and lumbar spine initially, and after 1 and 2 years. Seven patients in the fluoride group and eight in the placebo group completed the trial. In the fluoride group, bone mineral density did not change after 2 years (initial 1.05 +/- 0.07, final 1.07 +/- 0.06 g/cm2; p = n.s.). In the placebo group, however, bone mineral density decreased significantly (initial 1.00 +/- 0.07, final 0.93 +/- 0.06 g/cm2; p = 0.03). Moreover, in the fluoride group bone mineral density increased by 2.9 +/- 3.6%, and in the placebo group decreased by 6.6 +/- 2.6% (p = 0.04). None of the patients developed new vertebral or non-vertebral fractures. Treatment with sodium fluoride did not impair liver function or cholestasis in PBC. These results indicate that sodium fluoride prevents bone loss in PBC and therefore might be considered as a possible therapeutic agent for osteoporosis associated with this liver disease. Since a small number of patients completed the trial, further studies are required.

6068 Background: Standard treatment for advanced HNSCC is concurrent chemoradiation. Erlotinib (e) is an oral tyrosine-kinase inhibitor of EGFR, which has activity in HNSCC. The Spanish Group of Cl...

16544 Background: Concurrent chemoradiation is considered the optimal treatment for advanced HNSCC, including post-resected status. Erlotinib is an oral EGFR TKI, with activity in recurrent and metastatic HNSCC.The Spanish Group of Clinical Research in Radiation Oncology (GICOR) leads a phase I/II study to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of adding erlotinib (e) to chemoradiation to patients (p) with surgically resected locally advanced HNSCC Methods: p had surgically resected advanced HNSCC, with a least one of the following criteria: T3 or T4 primary lesion (except T3N0 with negative resection margins), pathologic N2-N3 disease, and poor prognostic findings (i.e. extranodal spread, positive resection margins, perineural or perivascular involvement). Additional eligibility criteria included: age 18–70 y; life expectancy = 12 w; PS 0–1; no evidence of metastasis; adequate organic function; and written informed consent. Dose-escalating phase I study consisted on 3 cohorts of 3–6 p each, with increasing doses of erlotinib (100–150 mg po qd) and cisplatin (30–40 mg/m2, iv, d 1) for 7 w. Radiotherapy was delivered as a fixed standard regimen of daily 1.8 Gy (5 fractions/w) to a total dose of 63 Gy in high risk areas along 7 w. Results: By the time of this analysis, 7 p have entered the phase I component of the study. Median age: 52 y; male 100%. Complete data for 4 pats included in cohort 1 (e 100 mg/d, c 30 mg/m2) are available. One p withdrew prematurely the study due to a grade 2 toxicity (not considered DLT) and was considered unevaluable by the Scientific Committee. Among evaluable p, 2 developed mucositis (1g.3), vomiting (g.1) and nausea (g.1). All p developed skin rash (mild in all the cases). Haematological toxicities were single cases of anaemia, leukopenia and thrombocytopenia (g.1). All 3 p completed 7 weeks of treatment and no dose reduction was required. No DLT as per protocol has been described and study went subsequently further to cohort 2. Conclusions: This study demonstrates the safe addition of erlotinib to chemoradiotherapy in the treatment of this p population. Full data from the phase I study will be presented. No significant financial relationships to disclose.

7334 Purpose: To evaluate the efficacy and safety of biweekly docetaxel and vinorelbine in previously treated patients with advanced NSCLC. Patients and Methods: Patients with stage IIIB and IV NSC...