[Neurological evolution in traumatic spinal cord injury according to the size of the intraparenchymal hemorrhage]. / Evolución neurológica en la lesión medular traumática en función del tamaño de la hemorragia intraparenquimatosa.

INTRODUCTION AND OBJECTIVES: The presence of spinal cord hemorrhage is considered as a poor prognostic factor in traumatic spinal cord injury (SCI). However, it has been suggested in published works that the prognosis of small hemorrhages is not so negative. The aim of this paper is to assess the neurological evolution in individuals with intraparenchymal hemorrhage according to its size. MATERIAL AND METHODS: Retrospective observational study. Selected all the patients admitted for acute traumatic SCI between 2010 and 2018 with early magnetic resonance study and spinal cord hemorrhage. Two groups were established depending on the size of the bleeding: microhemorrhages (less than 4mm) and macrohemorrhages (greater than 4mm). The neurological examination at admission and discharge was compared according to the AIS grade and the motor score (MS). RESULTS: Forty-six cases collected, 17 microhemorrhages and 29 macrohemorrhages. 70.6% of the microhemorrhages were AIS A while among macrohemorrhages the percentage was 89.6%. At the time of discharge, an improvement in the AIS grade was observed in 40.0% of the microhemorrhages compared to 4.0% of the macrohemorrhages (P=.008). Initial MS was similar, 45.2±22.2 in the microhemorrhages and 40.9±20.4 in the macrohemorrhages (P=.459), but at discharge it was higher in the first group: 60.4±20.5 for 42.7±22.8 (P=.033). Eight patients (17.4%) died during admission. CONCLUSIONS: There is a relationship between the size of the intraparenchymal hemorrhage and the neurological prognosis of SCI, with hemorrhages smaller than 4mm presenting a better evolution.

Th22 response induced by Mycobacterium tuberculosis strains is closely related to severity of pulmonary lesions and bacillary load in patients with multi-drug-resistant tuberculosis.

The role of interleukin-22 (IL-22) in the pathogenesis or tissue repair in human tuberculosis (TB) remains to be established. Here, we aimed to explore the ex-vivo and in-vitro T helper 22 (Th22) response in TB patients and healthy donors (HD) induced by different local multi-drug-resistant (MDR) Mvcobacterium tuberculosis (Mtb) strains. For this purpose, peripheral blood mononuclear cells from drug-susceptible (S-TB) MDR-TB patients and HD were stimulated with local MDR strains and the laboratory strain H37Rv. IL-22 and IL-17 expression and senescent status were assessed in CD4+ and CD8+ cells by flow cytometry, while IL-22 amount was measured in plasma and culture supernatants by enzyme-linked immunosorbent assay (ELISA). We found lower IL-22 amounts in plasma from TB patients than HD, together with a decrease in the number of circulating T cells expressing IL-22. In a similar manner, all Mtb strains enhanced IL-22 secretion and expanded IL-22+ cells within CD4+ and CD8+ subsets, being the highest levels detected in S-TB patients. In MDR-TB, low systemic and Mtb-induced Th22 responses associated with high sputum bacillary load and bilateralism of lung lesions, suggesting that Th22 response could be influencing the ability of MDR-TB patients to control bacillary growth and tissue damage. In addition, in MDR-TB patients we observed that the higher the percentage of IL-22+ cells, the lower the proportion of programmed cell death 1 (PD-1)+ or CD57+ T cells. Furthermore, the highest proportion of senescent T cells was associated with severe lung lesions and bacillary load. Thus, T cell senescence would markedly influence Th22 response mounted by MDR-TB patients.

Epidemiology of traumatic spinal cord injury in childhood and adolescence in Galicia, Spain: report of the last 26-years.

OBJECTIVE: To analyze the characteristics of traumatic spinal cord injury in children of Galicia (Spain). DESIGN: Descriptive and retrospective study. METHODS: Data extracted from the internal registry of the Spinal Cord Injury Unit and the patient's medical records, between March 1988 and December 2014. Inclusion criteria: patients aged ≤ 17 years with a traumatic spinal cord injury.Outcome measures: Total patients, percentages, incidence, ASIA scale results and improvement. RESULTS: A total of 68 patients were included. The incidence was 5.6 cases/1,000,000 inhabitants/year. The mean age was 14.4 years (median: 16). Only 25% were younger than 15. Male patients accounted for 73.5% of the total. The main cause were traffic accidents (60.3%; n = 41), being higher (77.8%) in children ≤ 10 years. Other etiologies included falls (19.1%), diving accidents (16.2%) and other causes (4.4%). Eleven patients (16.2%) had injuries classified as SCIWORA, 8 (72.7%) of them aged ≤ 10 years. The mean age of the SCIWORA group was 7.5 years versus 15.7 years in the non-SCIWORA group (P < 0.001). Half (50%) of these patients had a complete spinal cord injury and, of these, 64.6% were paraplegic. CONCLUSIONS: Traumatic spinal cord injuries are rare in children, and most cases occur between 15 and 17 years. Unlike in adults, SCIs in children mostly involve the thoracic spine. Most patients aged ≤ 10 years have SCIWORA. The most common etiology continues to be traffic accidents, although sports accidents prevail among adolescent patients.

Epidemiology of traumatic spinal cord injury in Galicia, Spain: trends over a 20-year period.

STUDY DESIGN: Observational study with prospective and retrospective monitoring. OBJECTIVE: To describe the epidemiological and demographic characteristics of traumatic spinal cord injury (TSCI), and to analyze its epidemiological changes. SETTING: Unidad de Lesionados Medulares, Complejo Hospitalario Universitario A Coruña, in Galicia (Spain). METHODS: The study included patients with TSCI who had been hospitalized between January 1995 and December 2014. Relevant data were extracted from the admissions registry and electronic health record. RESULTS: A total of 1195 patients with TSCI were admitted over the specified period of time; 76.4% male and 23.6% female. Mean patient age at injury was 50.20 years. Causes of injury were falls (54.2%), traffic accidents (37%), sports/leisure-related accidents (3.5%) and other traumatic causes (5.3%). Mean patient age increased significantly over time (from 46.40 to 56.54 years), and the number of cases of TSCI related to traffic accidents decreased (from 44.5% to 23.7%), whereas those linked to falls increased (from 46.9% to 65.6%). The most commonly affected neurological level was the cervical level (54.9%), increasing in the case of levels C1-C4 over time, and the most frequent ASIA (American Spinal Injury Association) grade was A (44.3%). The crude annual incidence rate was 2.17/100 000 inhabitants, decreasing significantly over time at an annual percentage rate change of -1.4%. CONCLUSIONS: The incidence rate of TSCI tends to decline progressively. Mean patient age has increased over time and cervical levels C1-C4 are currently the most commonly affected ones. These epidemiological changes will eventually result in adjustments in the standard model of care for TSCI.

Update on traumatic acute spinal cord injury. Part 1. / Actualización en lesión medular aguda postraumática. Parte 1.

Traumatic spinal cord injury requires a multidisciplinary approach both for specialized treatment of the acute phase and for dealing with the secondary complications. A suspicion or diagnosis of spinal cord injury is the first step for a correct management. A review is made of the prehospital management and characteristics of the acute phase of spinal cord injury. Respiratory monitoring for early selective intubation, proper identification and treatment of neurogenic shock are essential for the prevention of secondary spinal cord injury. The use of corticosteroids is currently not a standard practice in neuroprotective treatment, and hemodynamic monitoring and early surgical decompression constitute the cornerstones of adequate management. Traumatic spinal cord injury usually occurs as part of multiple trauma, and this can make diagnosis difficult. Neurological examination and correct selection of radiological exams prevent delayed diagnosis of spinal cord injuries, and help to establish the prognosis.

Update on traumatic acute spinal cord injury. Part 2. / Actualización en lesión medular aguda postraumática. Parte 2.

The aim of treatment in acute traumatic spinal cord injury is to preserve residual neurologic function, avoid secondary injury, and restore spinal alignment and stability. In this second part of the review, we describe the management of spinal cord injury focusing on issues related to short-term respiratory management, where the preservation of diaphragmatic function is a priority, with prediction of the duration of mechanical ventilation and the need for tracheostomy. Surgical assessment of spinal injuries based on updated criteria is discussed, taking into account that although the type of intervention depends on the surgical team, nowadays treatment should afford early spinal decompression and stabilization. Within a comprehensive strategy in spinal cord injury, it is essential to identify and properly treat patient anxiety and pain associated to spinal cord injury, as well as to prevent and ensure the early diagnosis of complications secondary to spinal cord injury (thromboembolic disease, gastrointestinal and urinary disorders, pressure ulcers).

The IL-17A rs2275913 single nucleotide polymorphism is associated with protection to tuberculosis but related to higher disease severity in Argentina.

Mycobacterium tuberculosis (Mtb) causes nearly 10 millions of new tuberculosis disease cases annually. However, most individuals exposed to Mtb do not develop tuberculosis, suggesting the influence of a human genetic component. Here, we investigated the association of the rs2275913 SNP (G → A) from IL-17A and tuberculosis in Argentina by a case-control study. Furthermore, we evaluated in vitro the functional relevance of this SNP during the immune response of the host against Mtb and analyzed its impact on clinical parameters of the disease. We found an association between the AA genotype and tuberculosis resistance. Additionally, within the healthy donors population, AA cells stimulated with a Mtb lysate (Mtb-Ag) produced the highest amounts of IL-17A and IFN-γ, which further support the genetic evidence found. In contrast, within the tuberculosis patients population, AA Mtb-Ag stimulated cells showed the lowest immunological parameters and we evidenced an association between the AA genotype and clinical parameters of disease severity, such as severe radiological lesions and higher bacilli burden in sputum. Overall, our findings demonstrated that the AA genotype from the IL-17A rs2275913 SNP is positively associated with protection to active tuberculosis but related to higher disease severity in the Argentinean population.

Mycobacterium tuberculosis multi-drug-resistant strain M induces IL-17+ IFNγ- CD4+ T cell expansion through an IL-23 and TGF-ß-dependent mechanism in patients with MDR-TB tuberculosis.

We have reported previously that T cells from patients with multi-drug-resistant tuberculosis (MDR-TB) express high levels of interleukin (IL)-17 in response to the MDR strain M (Haarlem family) of Mycobacterium tuberculosis (M. tuberculosis). Herein, we explore the pathways involved in the induction of Th17 cells in MDR-TB patients and healthy tuberculin reactors [purified protein derivative healthy donors (PPD+ HD)] by the M strain and the laboratory strain H37Rv. Our results show that IL-1ß and IL-6 are crucial for the H37Rv and M-induced expansion of IL-17+ interferon (IFN)-γ- and IL-17+ IFN-γ+ in CD4+ T cells from MDR-TB and PPD+ HD. IL-23 plays an ambiguous role in T helper type 1 (Th1) and Th17 profiles: alone, IL-23 is responsible for M. tuberculosis-induced IL-17 and IFN-γ expression in CD4+ T cells from PPD+ HD whereas, together with transforming growth factor (TGF-ß), it promotes IL-17+ IFN-γ- expansion in MDR-TB. In fact, spontaneous and M. tuberculosis-induced TGF-ß secretion is increased in cells from MDR-TB, the M strain being the highest inducer. Interestingly, Toll-like receptor (TLR)-2 signalling mediates the expansion of IL-17+ IFN-γ- cells and the enhancement of latency-associated protein (LAP) expression in CD14+ and CD4+ T cells from MDR-TB, which suggests that the M strain promotes IL-17+ IFN-γ- T cells through a strong TLR-2-dependent TGF-ß production by antigen-presenting cells and CD4+ T cells. Finally, CD4+ T cells from MDR-TB patients infected with MDR Haarlem strains show higher IL-17+ IFN-γ- and lower IL-17+ IFN-γ+ levels than LAM-infected patients. The present findings deepen our understanding of the role of IL-17 in MDR-TB and highlight the influence of the genetic background of the infecting M. tuberculosis strain on the ex-vivo Th17 response.

Sexual satisfaction in women with spinal cord injuries.

STUDY DESIGN: Structured interview based on a predesigned survey. OBJECTIVE: To examine the factors that affect the degree of sexual satisfaction in a sample of women with spinal cord injury (SCI). SETTING: The study participants were women with SCIs, from the area of the SCI Unit of A Coruña, a reference unit for the Community of Galicia in the northwest of Spain. All study participants were selected consecutively in the outpatient clinic in 2013. METHODS: The study included women with the American Spinal Injury Association (ASIA) A-D spinal injuries, between the ages of 18 and 65 years, who completed rehabilitation therapy and live in the community. A total of 32 women formed the final study group. RESULTS: When comparing the group of women who were sexually active with those who were not, variables such as age, neurological level, time since the SCI, ASIA or Spinal Cord Independence Measure score, urinary incontinence, chronic pain and spasticity were not related to sexual activity. The only factors that we found to be related to sexual activity were not having a stable partner (P=0.017) and a lack of sensation in the genital area (P=0.039). CONCLUSION: The only variables related to sexual activity were not having a partner and a lack of sensation in the genital area. Improving sexual satisfaction, information and specific programs during rehabilitation can help women with SCI explore and investigate new erotic possibilities, thereby improving their self-esteem and social relationships.

CD4(+) CD25(high) forkhead box protein 3(+) regulatory T lymphocytes suppress interferon-γ and CD107 expression in CD4(+) and CD8(+) T cells from tuberculous pleural effusions.

Tuberculous pleural effusion is characterized by a T helper type 1 (Th1) profile, but an excessive Th1 response may also cause tissue damage that might be controlled by regulatory mechanisms. In the current study we investigated the role of regulatory T cells (Treg ) in the modulation of Th1 responses in patients with tuberculous (TB) pleurisy. Using flow cytometry we evaluated the proportion of Treg (CD4(+) CD25(high) forkhead box protein 3(+) ), interferon (IFN)-γ and interleukin (IL)-10 expression and CD107 degranulation in peripheral blood (PB) and pleural fluid (PF) from patients with TB pleurisy. We demonstrated that the proportion of CD4(+) CD25(+) , CD4(+) CD25(high) FoxP3(+) and CD8(+) CD25(+) cells were increased in PF compared to PB samples. Mycobacterium tuberculosis stimulation increased the proportion of CD4(+) CD25(low/neg) IL-10(+) in PB and CD4(+) CD25(low/neg) IFN-γ(+) in PF; meanwhile, CD25(high) mainly expressed IL-10 in both compartments. A high proportion of CD4(+) CD107(+) and CD8(+) CD107(+) cells was observed in PF. Treg depletion enhanced the in-vitro M. tuberculosis-induced IFN-γ and CD4(+) and CD8(+) degranulation responses and decreased CD4(+) IL-10(+) cells in PF. Our results demonstrated that in TB pleurisy Treg cells effectively inhibit not only IFN-γ expression but also the ability of CD4(+) and CD8(+) cells to degranulate in response to M. tuberculosis.

CD3 expression distinguishes two gammadeltaT cell receptor subsets with different phenotype and effector function in tuberculous pleurisy.

Tuberculous pleurisy is a naturally occurring site of Mycobacterium tuberculosis (Mtb) infection. Herein, we describe the expression of activation, natural killer (NK) and cell migration markers, as well as effector functions from gammadeltaT cells in peripheral blood (PB) and pleural effusion (PE) from tuberculosis patients (TB). We observed a decreased percentage of circulating gammadeltaT from TB patients and differential expression of NK as well as of chemokine receptors on PB and PE. Two subsets of gammadeltaT cells were differentiated by the CD3/gammadeltaT cell receptor (gammadeltaTCR) complex. The gammadeltaTCR(low) subset had a higher CD3 to TCR ratio and was enriched in Vdelta2(+) cells, whereas most Vdelta1(+) cells belonged to the gammadeltaTCR(high) subset. In PB from TB, most gammadeltaTCR(high) were CD45RA(+)CCR7(-) and gammadeltaTCR(low) were CD45RA(+/-)CCR7(+)CXCR3(+). In the pleural space the proportion of CD45RA(-)CCR7(+)CXCR3(+) cells was higher. Neither spontaneous nor Mtb-induced interferon (IFN)-gamma production was observed in PB-gammadeltaT cells from TB; however, PE-gammadeltaT cells showed a strong response. Both PB- and PE-gammadelta T cells expressed surface CD107a upon stimulation with Mtb. Notably, PE-gammadeltaTCR(low) cells were the most potent effector cells. Thus, gammadeltaT cells from PB would acquire a further activated phenotype within the site of Mtb infection and exert full effector functions. As gammadeltaT cells produce IFN-gamma within the pleural space, they would be expected to play a beneficial role in tuberculous pleurisy by helping to maintain a T helper type 1 profile.

Long-term follow-up study of intraurethral stents in spinal cord injured patients with detrusor-sphincter dyssynergia.

STUDY DESIGN: Retrospective study. OBJECTIVES: To assess in the long-term clinical and urodynamic results of intraurethral stents in a group of patients with spinal cord injury. SETTING: Spinal Cord Injury Unit, Juan Canalejo Hospital, A Coruña, Spain. METHODS: Forty-seven consecutive male patients were studied from 1993 to 2002. All of them suffered from hyperreflexia with detrusor-sphincter dyssynergia (DSD) owing to spinal cord injury, and were treated by means of the placement of an intraurethral stent at the external sphincter. RESULTS: After surgery, significant decreases in all the parameters studied were observed. The number of patients with symptoms of urinary tract infection decreased by 25% (P<0.031). Post-void residual urine volume experienced an average decrease of 224.3 cm(3) (P=0.001). Episodes of dysreflexia decreased from 35.1 to 16.2% (P=0.039). The urodynamic study showed an average reduction of 44.36 cm H(2)O in the maximum detrusor pressure (P<0.0001). Complications in the upper urinary tract descended from 46.8 to 23.4% after placing the stent (P=0.013). The most frequent stent complication was displacement, followed by stenosis, lithiasis and intraprosthetic calcification. In all, 8.5% required the stent removal. CONCLUSIONS: Intraurethral stent is a good choice for the long-term management of DSD in spinal cord-injured patients, even in those who had been previously submitted to prior sphincterotomy. It has the advantage of being a potentially reversible procedure, so patients prefer it to more invasive therapies such as sphincterotomy.

IL-9 promotes anti-Mycobacterium leprae cytotoxicity: involvement of IFNgamma.

Interleukin 9 (IL-9) is a T-cell derived factor preferentially expressed by CD4+ Th2 cells and it has been characterized both in human and murine systems. It is a pleiotropic cytokine with multiple functions on cells of the lymphoid, myeloid and mast cell lineages, as well as on lung epithelial cells. Other activities described for IL-9 support its contribution to asthma and its important role in helminthic infections, where a Th2 response can be protective and IL-9 enhances resistance or is responsible for elimination of the nematode. Nevertheless, until recently there were no studies on its role in bacterial infections in man. We have demonstrated that cytokines can modulate the specific cytotoxicity generation in peripheral blood mononuclear cells from leprosy patients and normal controls. In the present report we studied the effect of IL-9 in this experimental model. Our results indicate that IL-9 can counteract the negative effect mediated by IL-4 on the generation of M. leprae-induced cytotoxic T lymphocytes. Moreover, it can increase this lytic activity in controls and enhance the stimulatory effect of IL-2 or IL-6 in cells from leprosy patients and controls. IL-9 is also able to revert the inhibitory effect of IL-10 and IL-13 on the M. leprae-induced cytotoxic activity. Although the exact mechanism of action of IL-9 remains to be determined, interferon gamma seems to be required for the effect of IL-9 in this experimental model. These data suggest that IL-9 may have an atypical Th2 behaviour and play a role in the modulation of the immune response to mycobacterial infections.

Toll-like receptors in human infectious diseases.

Toll-like receptors (TLRs) have emerged as critical players in immunity. They are capable of sensing organisms ranging from protozoa to bacteria, fungi or viruses upon detection of the pathogen as well as recognizing endogenous ligands, and triggering transduction pathways. Following activation of the innate immune system, strong inflammatory signals are generated inducing inflammation and activation of the adaptive immune response. However, the deregulation of TLRs signaling pathways may be conducive to the pathogenesis of many infectious diseases. Therefore, innate and adaptive immunity are not simply sequential and complementary mechanisms of resistance to pathogen, they regulate each other through cellular contacts and the secretion of soluble mediators. Herein, we summarize recent findings on TLRs signaling in infectious diseases and how pathogens have developed strategies to evade these pathways. In this context, a potential modulation of the innate immune response could have therapeutic benefit through the development of new drugs as well as vaccination strategies to be employed in infectious diseases.

Sexual issues in a sample of women with spinal cord injury.

STUDY DESIGN: Semistructured interview. OBJECTIVES: To assess the degree of participation in sexual intercourse of a sample of women with spinal cord injury (SCI) in our community, to establish to what extent their sexual lives have been affected in comparison to before the injury, and to search for those factors that may have a major influence on both aspects. SETTING: Spinal Cord Injuries Unit, A Coruna, Spain. PARTICIPANTS: A total of 37 women, average age 40 years, time since onset average 10 years. RESULTS: In all, 62% claimed regular sexual activity after the injury. The women who suffered the injury before reaching the age of 18 years run a higher risk of not having physical relationships than those who were above that age when they incurred the SCI (P=0.04, OR 4.75). We discovered a significant drop in the frequency of intercourse (P=0.003) and the ability to reach an orgasm (P=0.008), after the injury. Of these women, 69% were satisfied with their current sexual activity and 77.4% considered the information they received from their doctors on the changes the SCI would cause in their sexuality to be either insufficient or nonexistent. CONCLUSIONS: There is a noticeable decrease in the frequency of intercourse as well as a significant reduction in the capability of reaching orgasm. Despite these changes and problems that ensue during intercourse as a result, most show satisfaction with their current sexual lives. On the other hand, the occurrence of the injury before the age of 18 years may imply a greater risk of not having an active sex life in adult years. We consider it is essential to provide the appropriate sexual information during the process of rehabilitation, aimed at helping women with SCI to adapt to their new situation.

IL-10 down-regulates costimulatory molecules on Mycobacterium tuberculosis-pulsed macrophages and impairs the lytic activity of CD4 and CD8 CTL in tuberculosis patients.

Activation of T cells requires both TCR-specific ligation and costimulation through accessory molecules during T cell priming. IFNgamma is a key cytokine responsible for macrophage activation during Mycobacterium tuberculosis (Mtb) infection while IL-10 is associated with suppression of cell mediated immunity in intracellular infection. In this paper we evaluated the role of IFNgamma and IL-10 on the function of cytotoxic T cells (CTL) and on the modulation of costimulatory molecules in healthy controls and patients with active tuberculosis (TB). gamma-irradiated-Mtb (i-Mtb) induced IL-10 production from CD14(+) cells from TB patients. Moreover, CD3(+) T cells of patients with advanced disease also produced IL-10 after i-Mtb stimulation. In healthy donors, IL-10 decreased the lytic activity of CD4(+) and CD8(+) T cells whereas it increased gammadelta-mediated cytotoxicity. Furthermore, we found that the presence of IL-10 induced a loss of the alternative processing pathways of antigen presentation along with a down-regulation of the expression of costimulatory molecule expression on monocytes and macrophages from healthy individuals. Conversely, neutralization of endogenous IL-10 or addition of IFNgamma to either effector or target cells from TB patients induced a strong lytic activity mediated by CD8(+) CTL together with an up-regulation of CD54 and CD86 expression on target cells. Moreover, we observed that macrophages from TB patients could use alternative pathways for i-Mtb presentation. Taken together, our results demonstrate that the presence of IL-10 during Mtb infection might contribute to mycobacteria persistence inside host macrophages through a mechanism that involved inhibition of MHC-restricted cytotoxicity against infected macrophages.

NK cells modulate the cytotoxic activity generated by Mycobacterium leprae-hsp65 in leprosy patients: role of IL-18 and IL-13.

Protection against intracellular pathogens such as Mycobacterium leprae is critically dependent on the function of NK cells at early stages of the immune response and on Th1 cells at later stages. In the present report we evaluated the role of IL-18 and IL-13, two cytokines that can influence NK cell activity, in the generation of M. leprae-derived hsp65-cytotoxic T lymphocytes (CTL) from peripheral blood mononuclear cells (PBMC) of leprosy patients. We demonstrated that IL-18 modulates hsp65-induced CTL generation and collaborates with IL-12 for this effect. In paucibacillary (PB) patients and normal controls (N) depletion of NK cells reduces the cytolytic activity. Under these conditions, IL-12 cannot up-regulate this CTL generation, while, in contrast, IL-18 increases the cytotoxic activity both in the presence or absence of NK cells. IL-13 down-regulates the hsp65-induced CTL generation and counteracts the positive effect of IL-18. The negative effect of IL-13 is observed in the early stages of the response, suggesting that this cytokine affects IFNgamma production by NK cells. mRNA coding for IFNgamma is induced by IL-18 and reduced in the presence of IL-13, when PBMC from N or PB patients are stimulated with hsp65. Neutralization of IL-13 in PBMC from multibacillary (MB) leprosy patients induces the production of IFNgamma protein by lymphocytes. A modulatory role on the generation of hsp65 induced CTL is demonstrated for IL-18 and IL-13 and this effect takes place through the production of IFNgamma.

Specific lytic activity against mycobacterial antigens is inversely correlated with the severity of tuberculosis.

The ability of peripheral blood mononuclear cells (PBMC) from patients with active tuberculosis to display cytotoxic responses against autologous Mycobacterium tuberculosis (Mtb)-pulsed macrophages was evaluated. Non-MHC restricted cell-dependent lytic activity was observed in ex vivo effector cells from tuberculosis patients and was mediated mainly by CD3(+)gammadelta TCR(+) T (gammadelta T) cells bearing CD56 and/or CD16 molecules. MHC-restricted and non-MHC restricted cytotoxic T cells (CTL) were differentially expanded upon stimulation with Mtb in tuberculosis patients and normal controls (N). Class-I restricted CD8(+) CTL and class-II restricted CD4(+) CTL were generated in PPD(+)N and to a lesser extent in PPD(-)N. Mtb-stimulated effector cells from tuberculosis patients became progressively non-MHC restricted CD4(-)CD8(-)gammadelta T cells, while lytic activity of CD4(+) and CD8(+)CTL decreased gradually as the disease became more severe. On the other hand, target cells were lysed by ex vivo cells from tuberculosis patients through the Fas-FasL and perforin pathways. Mtb-induced CD4(+) CTL from tuberculosis patients and N controls preferentially employed the Fas-FasL mechanism. Mtb-induced CD8(+) CTL effector cells from patients used the perforin-based mechanism while cells from N controls also used the Fas-FasL pathway. While Mtb-induced gammadelta CTL from patients and PPD(-)N employed the latter mechanism cells from PPD(+)N individuals also used the perforin pathway. It can be concluded that shifts in the CTL response and the cytolytic mechanisms take place as the pulmonary involvement becomes more severe.

Spinal cord infarction: prognosis and recovery in a series of 36 patients.

OBJECTIVE: To study the clinical evolution and the functional outcome of patients suffering from spinal cord infarction who were treated at the Spinal Cord Injuries Unit. To try to determine the factors that could have influence in their functional outcome. SETTING: In a Spinal Cord Injuries Unit, regionally-based, and which forms part of a general hospital with a high level of specialization. METHOD: Retrospective study of the medical records of patients suffering from vascular spinal cord ischemia, as acute anterior spinal artery syndrome or associated with aortic surgery or rupture. Cases that were due to compressive, tumoral or inflammatory pathologies were excluded. Assessment of the neurological syndrome followed the ASIA/IMSOP criteria. Age, sex, history and magnetic resonance imaging (MRI) findings were analyzed. Assessment of functional outcome was made regarding ambulatory ability or wheelchair use, and bladder/sphincter control. RESULTS: Thirty-six cases were selected, the commonest group being spinal cord ischemia due to idiopathic causes (36.1%). Following these, there were cases associated with aortic surgery (25%), systemic arteriosclerosis (19.4%) and acute deficit of perfusion (11.1%). The average age of the patients was 59.3 years, with a mortality of 22.2% during the hospital stay. Regarding the functional outcomes at the moment of discharge, it must be pointed out that 57.1% of the patients were wheelchair users, 25% were ambulatory, using technical aids, and 17.9% were fully ambulatory. The group who could perform some kind of walking was significantly younger than the group of wheelchair users (48.17 vs 61.38 years). Additionally, it became evident that those patients who did not show voluntary muscle contraction at the time of admission (ASIA groups A and B) presented a higher risk of being wheelchair users. CONCLUSION: Acute spinal cord ischemia syndrome has a severe prognosis with permanent and disabling sequelae. Initial neurological assessment following ASIA/IMSOP classification proves to be the best predictor of prognosis, and the patient's advanced age constitutes a negative factor for functional recovery.

Immune complexes (IC) down-regulate the basal and interferon-gamma-induced expression of MHC class II on human monocytes.

The interaction of Fc receptors for IgG (FcgammaRs) on monocytes/macrophages with immune complexes (IC) triggers regulatory and effector functions. Previous studies have shown that FcgammaR-IC interactions inhibit the IFN-gamma-induced expression of MHC class II in murine macrophages. However, the mechanism(s) responsible for these effects have not been elucidated. In addition, whether this IC-dependent effect also occurs in human cells is not known. Taking into account the fact that IC and IFN-gamma are frequently found in infections and autoimmune disorders, together with the crucial role MHC class II molecules play in the regulation of immune response, we explored the effect and mechanism of IC-induced MHC class II down-regulation in human peripheral blood mononuclear cells (PBMC). This effect was studied either in the presence or absence of IFN-gamma. We demonstrate that IC exert a drastic inhibition of basal and IFN-gamma-induced expression of MHC class II on human monocytes. This effect was mediated through the interaction of IC with both FcgammaRI and FcgammaRII. Moreover, similar results were obtained using supernatants from IC-treated PBMC. The IC-induced down-regulation of MHC class II is abrogated by pepstatin and phosphoramidon, supporting the role of aspartic protease(s) and metalloprotease(s) in this process. In parallel with MHC class II expression, antigen presentation was markedly inhibited in the presence of IC.