Proximal sacral deformity: a common element in lytic isthmic spondylolisthesis at L5 and in degenerative spondylolisthesis at L4-L5 segment. Two apparently very different etiopathogenic entities. / Deformidad sacra proximal: elemento común a la espondilolistesis ístmica lítica de L5 y a la degenerativa del segmento L4-L5, 2 entidades de etiopatogenia muy diferente, aparentemente.

A radiographic study was carried out to investigate the relationship between proximal sacral sagittal anatomy (either kyphosis or lordosis) and either isthmic or degenerative spondylolisthesis. In addition, we studied whether there is a relationship between proximal sacral kyphosis and the degree of such listhesis in the case of L5 isthmic spondylolisthesis. Lateral standing x-rays were used from 173 patients, ninety of whom had degenerative spondylolisthesis L4-L5, and eighty-three an isthmic spondylolisthesis of L5 (67 low-grade and 16 high-grade) and compared with a control group of 100 patients adjusted by age and gender, without any type of spondylolisthesis. Listhesis was graded using Meyerding's classification and the proximal sacral kyphosis angle (CSP) was measured between S1 and S2 posterior walls, according to Harrison's method. In our series, there was a proximal sacral kyphosis in both types of spondylolisthesis, greater in the lytic type. By contrast, the control group had a proximal sacral lordosis. The differences were statistically significant. Therefore, we concluded that there was a proximal sacral kyphosis in patients with both degenerative and isthmic lytic spondylolisthesis, but with our results, we were not able to ascertain whether it is a cause or a consequence of this listhesis.

3D printed tablets loaded with polymeric nanocapsules: An innovative approach to produce customized drug delivery systems.

The generation of multi-functional drug delivery systems, namely solid dosage forms loaded with nano-sized carriers, remains little explored and is still a challenge for formulators. For the first time, the coupling of two important technologies, 3D printing and nanotechnology, to produce innovative solid dosage forms containing drug-loaded nanocapsules was evaluated here. Drug delivery devices were prepared by fused deposition modelling (FDM) from poly(ε-caprolactone) (PCL) and Eudragit® RL100 (ERL) filaments with or without a channelling agent (mannitol). They were soaked in deflazacort-loaded nanocapsules (particle size: 138nm) to produce 3D printed tablets (printlets) loaded with them, as observed by SEM. Drug loading was improved by the presence of the channelling agent and a linear correlation was obtained between the soaking time and the drug loading (r2=0.9739). Moreover, drug release profiles were dependent on the polymeric material of tablets and the presence of the channelling agent. In particular, tablets prepared with a partially hollow core (50% infill) had a higher drug loading (0.27% w/w) and faster drug release rate. This study represents an original approach to convert nanocapsules suspensions into solid dosage forms as well as an efficient 3D printing method to produce novel drug delivery systems, as personalised nanomedicines.

Posthemipelvectomy hernia.

We report the case of a white male who underwent a classic hemipelvectomy due to a femur fibrosarcoma with inguinal metastases, which 33 years later, developed into a posthemipelvectomy hernia in the amputation stump that impaired the use of his Canadian prosthesis. The hernia was repaired with a polypropylene mesh in a subaponeurotic position. A seroma was drained in the postoperative and it was only 2 months after the operation that he could use his prosthesis with any difficulty. A year after the operation, the hernia had not recurred. Only seven similar cases have been published, and there are only four cases with details of their correction, two with a mesh as was our case, and the rest with a primary suture of the aponeurotic borders. A brief review of the bibliography is given on this subject.

Prognostic value of an immediate lateral standing X-ray with a TLSO in patients with a thoracolumbar burst fracture.

UNLABELLED: The final collapse of a "stable" thoracolumbar burst fracture is difficult to predict. This collapse was prospectively studied radiologically in patients with T12 or L1 burst fractures who, after evaluating the admission x-rays and the CT scan with the patients themselves, opted for a rigid thoracolumbar brace with support in the sternal manubrium (TLSO). On the other hand, patients with rigid braces sometimes have low back pain on follow-up (due to overload of the L5-S1 joints). HYPOTHESIS: the standing lateral x-ray with only a TLSO for support (intrinsic mechanical stability) provides information on the final collapse and could also provide information on the low back pain. The study included 50 patients (20 males and 30 females, age: 63+14 years) admitted during 2011 and 2012, with 2 losses to follow-up. VARIABLES: Farcy index and local kyphosis (Cobb at 3 vertebrae). X-Rays: admission, with TLSO (immediate: Rx0), and at 3 and 6 months. They were compared with the final clinical and radiological results. It was decided to surgically intervene in 4 patients after Rx0. There were no painful sequelae at the fracture level, and 16/44 (31%) had low back pain. Using linear regression mathematical models, the increase in the Farcy index (Rx0-Rx admission) was associated with the appearance of low back pain and with local kyphosis (Rx0-Rx admission), and with the final kyphosis. It is advisable to perform a lateral standing X-ray after TLSO for information on the final collapse of the fracture and the appearance of accompanying low back pain.

[Inveterate subaxial cervical dislocations: a discussion on the best therapeutic strategy]. / Luxación subaxial cervical inveterada. Discusión de cuál es la mejor estrategia terapéutica.

It is difficult to decide the appropriate treatment for inveterate cervical dislocations because of the difficulty of their reduction, as well as due to the risk of inducing iatrogenic injuries during this reduction. The literature on the most appropriate surgical strategy for their management is also limited as well as controversial. We report one clinical case treated in the Spine Unit of the Orthopedic Surgery and Trauma Service of the University Hospital of Santiago de Compostela, discussing the currently most used treatment options, the anterior-posterior-anterior and the posterior-anterior-posterior approach. After analyzing the results, it could be concluded that the surgical approach to these lesions is generally difficult, with any of two techniques described above being suitable, but always with the precaution to remove the entire affected intervertebral disc before axial correction maneuvers, thus avoiding the risk of extrusion into the medullary canal. After the surgical procedure, a proper release and reduction of the joint facets should be performed, sometimes with the need to add osteotomies in them.

C4d DNA sequence of complement C4B93 and recombination mechanisms for its generation.

The present work reports the DNA sequence of the polymorphic region from the uncommon complement allele C4B93. It shows a new combination of Chido and Rodgers antigenicities and expresses reverse antigenicity because it carries Rodgers 1, 2, and 3. C4B93 could have arisen from an ancient, non-homologous recombination between C4A3 (or C4A6) and C4B1a or from a homologous recombination between C4B1a and C4B5. These events would be enhanced by the presence of recombination promoting Escherichia colichi-like signals in the fragment between positions 1157 and 1186. The generation of the C4 polymorphism by recombination would explain the concerted evolution of C4 genes in primates.

Retinol (vitamin A) is a cofactor in CD3-induced human T-lymphocyte activation.

Immunomodulatory effects of different retinoids have been demonstrated, both in vivo and in vitro, in different cellular lineages including human and murine thymocytes, human lung fibroblasts, Langerhans' cells, tumoral cells and natural killer (NK) cells; however, any attempt to demonstrate the effect of retinoids on human peripheral blood mononuclear cells (PBMC) resulted in negative results. In the present work, it is shown that retinol and retinoic acid induce a marked increase of proliferation on human PBMC from 32 unrelated healthy individuals, which had previously been stimulated with anti-CD3 antibodies 48 hr before. Serum-free medium, specific retinoid concentration (10(-7) M) and a particular timing of retinol addition to the cultures (48 hr after CD3 stimulation) was necessary clearly to detect this retinol-enhancing effect. The increased proliferative response is specifically mediated via the clonotipic T-cell receptor-CD3 complex and correlates with the up-regulation of certain adhesion/activation markers on the T-lymphocyte surface: CD18, CD45RO and CD25; also Th1-type of cytokines (interleukin-2 and interferon-gamma) are found concordantly increased after retinoid costimulation, both measured by a direct protein measurement and by a specific mRNA increase. In addition, it is shown that the in vitro retinol costimulation is only present in immunodeficient patients who have no defect on CD3 molecules and activation pathway. The fact that retinol costimulate lymphocytes only via CD3 (and not via CD2 or CD28) and the lack of response enhancement in immunodeficients with impaired CD3 activation pathway indicates that retinoids may be used as therapeutic agents in immune system deficiencies that do not affect the clonotypic T-cell receptor.

Immunodeficiency associated with anorexia nervosa is secondary and improves after refeeding.

Several studies have addressed the question of starvation effects on immune function by means of changes in lymphocyte subsets, cytokine induction or lymphocyte activation. Anorexia nervosa (AN) patients are severely malnourished and contradictory results have been obtained regarding the accompanying immunodeficiency, including its assignation as a part of the primary nervous disorder. In the present work, an extensive immunological function examination was carried out on 40 AN patients who were compared with a control group of 14 healthy girls. The AN patients were also classified according to their nutritional status (by the Body Mass Index: BMI), this being critical for a better understanding of these secondary immunodeficiency bases. Moreover, another immune system study was performed on five patients after refeeding. Lymphocyte subsets and function, cytokine induction and peripheral blood concentrations, and innate as well as humoral immunity were evaluated. Deregulation in the cytokine network, owing to the interaction of the central nervous (CNS) and immune systems, seems to be the initial immune alteration in AN immunodeficiency but it has not been disproved that the immunodeficiency is a direct consequence of the original psychiatric perturbation. Spontaneous high levels of circulating interleukin-1beta (IL-1beta) and tumour necrosis factor-alpha (TNF-alpha) have been observed; this is probably one of the causes of the anomalies found in the T-cell subpopulations (mainly the naive CD4+CD45RA+ reduction and the cytotoxic CD8+ increase) and T-cell activation status (mainly the down-regulation of the CD2 and CD69 activation pathways). This finally leads to an impairment, not only in T-cell function but also in T-cell to B-cell co-operation. The AN specificity of these results is confirmed by the fact that these immune alterations improve after refeeding and when nutritional status becomes less critical, which also suggests that AN immunodeficiency is indeed secondary to malnutrition.

A point mutation in a domain of gamma interferon receptor 1 provokes severe immunodeficiency.

Gamma interferon (IFN-gamma) and the cellular responses induced by it are essential for controlling mycobacterial infections. Most patients bearing an IFN-gamma receptor ligand-binding chain (IFN-gammaR1) deficiency present gross mutations that truncate the protein and prevent its expression, giving rise to severe mycobacterial infections and, frequently, a fatal outcome. In this report a new mutation that affects the IFN-gammaR1 ligand-binding domain in a Spanish patient with mycobacterial disseminated infection and multifocal osteomyelitis is characterized. The mutation generates an amino acid change that does not abrogate protein expression on the cellular surface but that severely impairs responses after the binding of IFN-gamma (CD64 and HLA class II induction and tumor necrosis factor alpha and interleukin-12 production). A patient's younger brother, who was also probably homozygous for the mutation, died from meningitis due to Mycobacterium bovis. These findings suggest that a point mutation may be fatal when it affects functionally important domains of the receptor and that the severity is not directly related to a lack of IFN-gamma receptor expression. Future research on these nontruncating mutations will make it possible to develop new therapeutical alternatives in this group of patients.

Role of Nijmegen breakage syndrome protein in specific T-lymphocyte activation pathways.

Nijmegen breakage syndrome (NBS) is a genetic disorder characterized by immunodeficiency, microcephaly, and "bird-like" facies. NBS shares some clinical features with ataxia telangiectasia (AT), including increased sensitivity to ionizing radiation, increased spontaneous and induced chromosome fragility, and strong predisposition to lymphoid cancers. The mutated gene that results in NBS codes for a novel double-stranded DNA break repair protein, named nibrin. In the present work, a Spanish NBS patient was extensively characterized at the immunological and the molecular DNA levels. He showed low CD3(+)-cell numbers and an abnormal low CD4(+) naive cell/CD4(+) memory cell ratio, previously described in AT patients and also described in the present report in the NBS patient. The proliferative response of peripheral blood lymphocytes in vitro to mitogens is deficient in NBS patients, but the possible link among NBS mutations and the abnormal immune response is still unknown.