Robotic endoscopic transforaminal lumbar interbody fusion: A single institution case series.

Background: Robotic-assisted, endoscopic transforaminal lumbar interbody fusion (RE-TLIF) is a promising, minimally invasive surgical option for degenerative lumbar spondylosis/spondylolisthesis; however, outcomes data and efficacy are limited, especially in multilevel disease. Here, we present the first reported series of patients that underwent either single or multilevel RE-TLIF. Methods: A retrospective review was performed on 23 consecutive patients who underwent a single level or multilevel RE-TLIF by a single surgeon. Variables included demographics, perioperative results, pain scores, and functional outcome scores. Results: Eighteen patients (78.3 %) underwent single level RE-TLIF and 5 patients (21.7 %) underwent multilevel RE-TLIF. The median reduction of visual analog scale (VAS) for low back pain (LBP) of all subjects was 6 (IQR = 4.5, 6.5) with no significant difference between single level and multilevel RE-TLIF (p = 0.565). The median reduction of VAS for leg pain of all subjects 7 (IQR = 6, 8) with no significant difference between single level and multilevel RE-TLIF (p = 0.702). Median blood loss was 25 cc (IQR = 25, 25) and 50 cc (IQR = 25, 100) for single and multilevel RE-TLIF, respectively (p = 0.025), whereas median length of stay was 1 (IQR = 1, 1; mean = 1.0 ± 00.18) days and 1 (IQR = 1, 2; mean = 1.4 ± 00.54) days, respectively (p = 0.042). One major complication was observed requiring reoperation for demineralized bone matrix migration resulting in an L5 radiculopathy. Conclusions: Single and multi-level RE-TLIF appears to be a safe and efficacious approach with comparable outcomes to open and other minimally invasive approaches. Additionally, we observed favorable accuracy in robot-assisted pedicle screw, endoscope, and interbody device placement.

Combining jobs and motherhood: is it worse when raising children alone?

BACKGROUND: Paid employment has been shown to benefit childless women's health, while employed mothers experience poorer health, and more pronounced fatigue. This study measures the association between job characteristics and the health and well-being of employed mothers and the differential susceptibility to job characteristics between coupled and single-parent mothers. METHODS: We used data from the 5th Portuguese National Health Survey from 1649 employed women (aged 25-54) living with a child under 16. We modelled depression (assessed by the Personal Health Questionnaire-8) and self-reported health as a function of job characteristics, adding interaction terms to compare coupled and single-parent mothers, using logistic regressions. RESULTS: Working part-time was associated with depression (odds ratio (OR) = 3.39, 95% confidence interval (CI) = 3.31-3.48) and less-than-good health (OR = 1.28, 95%CI = 1.26-1.31), compared to working full time. Compared to high-skill jobs, the likelihood for depression among low-skill occupations was lower among coupled mothers (OR = 0.25, 95%CI = 0.24-0.26), and higher among single-parent mothers (OR = 1.75, 95%CI = 1.54-1.99). Unstable jobs were associated with depression among coupled mothers. CONCLUSIONS: Part-time jobs are detrimental for mothers' mental health, but high-skilled jobs are protective for single-parent mothers. Part-time and unstable jobs are linked to poorer self-reported health among coupled mothers. Results question the gendered arrangements that may face employed coupled mothers.

MGMT-inhibitor in combination with TGF-BRI inhibitor or CDK 4/6 inhibitor increases temozolomide sensitivity in temozolomide-resistant glioblastoma cells

Background Glioblastoma (GB) remains an incurable and deadly brain malignancy that often proves resistant to upfront treatment with temozolomide. Nevertheless, temozolomide remains the most commonly prescribed FDA-approved chemotherapy for GB. The DNA repair protein methylguanine-DNA methyl transferase (MGMT) confers resistance to temozolomide. Unsurprisingly temozolomide-resistant tumors tend to possess elevated MGMT protein levels or lack inhibitory MGMT promotor methylation. In this study, cultured human temozolomide resistance GB (43RG) cells were introduced to the MGMT inhibitor O6-benzylguanine combined with temozolomide and either LY2835219 (CDK 4/6 inhibitor) or LY2157299 (TGF-βRI inhibitor) seeking to overcome GB treatment resistance. Methods Treatment effects were assessed using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, western blot, cell viability, and cell cycle progression. Results Our in vitro study demonstrated that sequential treatment of O6-Benzylguanine with either LY2385219 or LY2157299-enhanced temozolomide enhanced sensitivity in MGMT+ 43RG cells. Importantly, normal human neurons and astrocytes remained impervious to the drug therapies under these conditions. Furthermore, LY2835219 has additional anti-proliferative effects on cell cycling, including induction of an RB-associated G (1) arrest via suppression of cyclin D-CDK4/6-Rb pathway. LY2157299 enhances anti-tumor effect by disrupting TGF-β–dependent HIF-1α signaling and by activating both Smad and PI3K-AKT pathways towards transcription of S/G2 checkpoints. Conclusion This study establishes the groundwork for the development of a combinatorial pharmacologic approach by using either LY2385219 or LY2157299 inhibitor plus O6-Benzylguanine to augment temozolomide response in temozolomide-resistant GB cells (AU)

Iron triggers the early stages of cartilage degeneration in vitro: The role of articular chondrocytes.

Objective: Arthropathy is a major clinical problem in patients with hemochromatosis, the most common genetic disorder of iron overload. The pathological features of hemochromatosis arthropathy (HA) are heterogeneous and its specific nature remains unknown. One important drawback is the lack of proper in vitro models. The aim of the present study was to set up a model to investigate the biological response of cartilage to iron exposure. Design: Bovine articular cartilage explants were incubated with ferric citrate for up to 9 days. We evaluated chondrocyte viability, iron deposition, and biomarkers of cartilage degradation in the conditioned medium. Results: Iron accumulated within chondrocytes, which was associated with programmed cell death through chondroptosis. Iron treatment increased the release of sulfated glycosaminoglycans (sGAG), a component of the extracellular matrix, into the medium (p=0.0189). This was dependent on the presence of viable chondrocytes and was associated with increased activity of matrix-degrading metalloproteinases (MMP) (pro/active MMP-9, p=0.0317; pro MMP-2, p=0.0092; active MMP-2, p=0.0288). Co-treatment with the broad MMP/aggrecanase inhibitor prinomastat reduced iron-mediated sGAG release (0.02 â€‹µM, p=0.0425; 2 â€‹µM, p=0.0014), confirming that iron induces sGAG release via the activation of catabolic enzymes. Notably, iron-treated cartilage continued to release an increased amount of sGAG into the medium for 6 days after termination of the ferric citrate treatment (p=0.0259). Conclusions: Iron triggers the early stages of cartilage degeneration. Removal of iron exposure does not prevent further damage to the cartilage, thus providing a possible explanation why HA is not prevented after iron depletion by phlebotomy treatment.

MGMT-inhibitor in combination with TGF-ßRI inhibitor or CDK 4/6 inhibitor increases temozolomide sensitivity in temozolomide-resistant glioblastoma cells.

BACKGROUND: Glioblastoma (GB) remains an incurable and deadly brain malignancy that often proves resistant to upfront treatment with temozolomide. Nevertheless, temozolomide remains the most commonly prescribed FDA-approved chemotherapy for GB. The DNA repair protein methylguanine-DNA methyl transferase (MGMT) confers resistance to temozolomide. Unsurprisingly temozolomide-resistant tumors tend to possess elevated MGMT protein levels or lack inhibitory MGMT promotor methylation. In this study, cultured human temozolomide resistance GB (43RG) cells were introduced to the MGMT inhibitor O6-benzylguanine combined with temozolomide and either LY2835219 (CDK 4/6 inhibitor) or LY2157299 (TGF-ßRI inhibitor) seeking to overcome GB treatment resistance. METHODS: Treatment effects were assessed using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, western blot, cell viability, and cell cycle progression. RESULTS: Our in vitro study demonstrated that sequential treatment of O6-Benzylguanine with either LY2385219 or LY2157299-enhanced temozolomide enhanced sensitivity in MGMT+ 43RG cells. Importantly, normal human neurons and astrocytes remained impervious to the drug therapies under these conditions. Furthermore, LY2835219 has additional anti-proliferative effects on cell cycling, including induction of an RB-associated G (1) arrest via suppression of cyclin D-CDK4/6-Rb pathway. LY2157299 enhances anti-tumor effect by disrupting TGF-ß-dependent HIF-1α signaling and by activating both Smad and PI3K-AKT pathways towards transcription of S/G2 checkpoints. CONCLUSION: This study establishes the groundwork for the development of a combinatorial pharmacologic approach by using either LY2385219 or LY2157299 inhibitor plus O6-Benzylguanine to augment temozolomide response in temozolomide-resistant GB cells.

Evaluating anti-tumor activity of palbociclib plus radiation in anaplastic and radiation-induced meningiomas: pre-clinical investigations.

PURPOSE: Meningiomas are common brain tumors, the majority of which are considered benign. Despite surgery and/or radiation therapy, recurrence rates are approximately 8-10%. One likely cause is the dysregulation of cyclin D-cyclin-dependent kinases 4 and 6 (CDK4/6)-retinoblastoma (Rb) pathway, which controls the cell cycle restriction point. This pathway is commonly dysregulated in anaplastic meningioma cell lines (AM) and radiation-induced meningioma cells (RIM), making it a rational target for anti-meningioma therapy. In this study, we investigate the effect of a CDK4/6 inhibitor, palbociclib, with radiation in relevant pre-clinical models. METHODS: In vitro cell culture, ex vivo slice culture and in vivo cell line-derived orthotopic xenograft animal models of AM/RIM were utilized to assess treatment efficacy with palbociclib plus radiation. Treatment effects were examined by immunoblot, cell viability, apoptosis, and cell cycle progression. RESULTS: The in vitro and ex vivo studies demonstrate that palbociclib plus radiation treatment reduced proliferation and has additional effects on cell cycling, including induction of an RB-associated G (1) arrest in Rb+ AM and RIM cells, but not in Rb- cells. Our results also demonstrated reduced CDK4 and CDK6 expression as well as reduced E2F target gene expression (CCNA2 and CCNE2) with the combination therapy. MRI results in vivo demonstrated reduced tumor size at 5 weeks when treated with 14 days palbociclib (10 mg/kg) plus 6 Gy radiation compared to saline-treated tumors. Finally, no hepatic toxicity was found after treatments. CONCLUSION: A pre-clinical murine model provides preclinical evidence for use of palbociclib plus radiation as a therapeutic agent for Rb+ meningiomas.

Tissue iron quantification in chronic liver diseases using MRI shows a relationship between iron accumulation in liver, spleen, and bone marrow.

AIM: To investigate iron loading within the liver, pancreas, spleen, and bone marrow using magnetic resonance imaging (MRI) transverse relaxation rate (R2*), in patients with diffuse liver diseases; to evaluate the relationships between iron accumulation in these tissue compartments; and to assess the association between tissue iron overload and the pattern of hepatic cellular iron distribution (hepatocytes versus Kupffer cells). MATERIAL AND METHODS: Fifty-six patients with diffuse liver diseases had MRI-derived R2* values, using a multi-echo chemical-shift encoded MRI sequence, of the liver, pancreas, spleen, and vertebral bone marrow. All patients had liver biopsy samples scored for hepatic iron grading (0-4) and iron cellular distribution (within hepatocytes only or within both hepatocytes and Kupffer cells). RESULTS: Liver R2* increased with histological iron grade (RS=0.58, p<0.001) and correlated with spleen (RS=0.71, p<0.001) and bone marrow R2* (RS=0.66, p<0.001), but not with pancreatic R2* (RS=0.22, p=0.096). Splenic and bone marrow R2* values were also correlated (RS=0.72, p<0.001). Patients with iron inside Kupffer cells had the highest R2* in liver, spleen and bone marrow. CONCLUSIONS: Patients with chronic diffuse liver diseases have concomitant hepatic, splenic, and bone marrow iron loading. The highest hepatic iron scores and iron inside Kupffer cells were associated with the highest splenic and bone marrow deposits, suggesting systemic iron accumulation in the mononuclear phagocytic system.

Expression of iron-related proteins in feline and canine mammary gland reveals unexpected accumulation of iron.

Dysregulation of cellular iron homeostasis in human breast cancer is reflected by the altered expression of regulatory proteins. The expressions of iron-related proteins in the mammary glands of cats and dogs have not been assessed. We evaluated the expressions of ferritin, ferroportin, hepcidin and transferrin receptor 1 in benign and malignant mammary gland lesions in cats and dogs. Iron deposition was detected using Perls' Prussian blue staining. We found no major differences in the expression of iron-related proteins between benign and malignant mammary gland lesions in either cats or dogs; however, these species exhibited accumulation of iron in benign lesions. Our findings provide an explanation for the absence of higher iron requirements by tumor cells in these animals. Further investigation of local iron homeostasis in cats and dogs and differences in their physiology compared to human breast cancer is required.

Infecciones bacterianas en pacientes con Pie Diabético. Hospital Regional de Ciudad del Este, Paraguay. Año 2015 / Bacterial infections in patients with Diabetic Foot. Regional Hospital of Ciudad del Este, Paraguay. Year 2015

Infecciones bacterianas en pacientes con Pie Diabético. Hospital Regional de Ciudad del Este, Paraguay. Año 2015 RESUMEN La Organización Mundial de la Salud define el pié diabético como una "situación de infección, ulceración o también destrucción de los tejidos profundos de los pies, asociada a anormalidades neurológicas y varios grados de enfermedad vascular periférica en los miembros inferiores de pacientes con Diabetes Mellitus. El objetivo del trabajo fue identificar la prevalencia de microorganismos que causaron infecciones en pacientes diagnosticados con pie diabético atendidos en el Hospital Regional de Ciudad del Este, Paraguay, durante el año 2015. Estudio descriptivo, transversal y retrospectivo. El muestreo fue no probabilístico, por conveniencia, y se incluyeron 115 muestras correspondientes a 94 pacientes. Fue utilizada la base de datos del Laboratorio de Bacteriología del Hospital Regional de Ciudad del Este. De los 94 pacientes con pie diabético, 52% fueron hombres. El 25% de las infecciones se produjeron en pacientes con edades comprendidas entre 51 a 60 años. Fueron aislados 21 microorganismos diferentes en las 115 muestras. El 80% (75) fueron monomicrobianos, y 20% (40) polimicrobianos. Entre los Gram positivos, el microorganismo más frecuentemente aislado fue el Staphylococcus aureus 19% (22) y el Enterococcus spp. 6% (6) y entre los Gram negativos fueron la Klebsiella pneumoniae13% (16) y Acinetobacter spp. 12% (14). Los resultados de las pruebas de sensibilidad antimicrobiana demostraron que el 100% de las cepas de S. aureus fueron resistentes a la Oxacilina y alta resistencia de las cepas de K. pneumoniae a las Cefalosporinas. Las cepas de Acinetobacter spp. fueron 100% resistentes a las cefalosporinas y Piperacilina. Los microorganismos aislados y el perfil de resistencia antimicrobiana que los mismos presentan, coinciden con la bibliografía, y es muy importante implementar programas de prevención a esta patología a fin de evitar amputaciones en este tipo de pacientes. Palabras claves: bacterias; pie; diabético; hospital; Paraguay.

The World Health Organization defines the diabetic foot as a "situation of infection, ulceration or destruction of the deep tissues of the feet. It is associated with neurological abnormalities and various degrees of peripheral vascular disease in the lower limbs of patients with Diabetes Mellitus". The objective of the research was to identify the prevalence of microorganisms which caused infections in patients diagnosed with diabetic foot treated at the Regional Hospital of Ciudad del Este, Paraguay, during the year 2015. It is a descriptive, crosssectional and retrospective study. The sampling was nonprobabilistic, for convenience, and 115 samples were included corresponding to 94 patients. The database of the Department of Bacteriology of the Regional Hospital of Ciudad del Este was used. Of the 94 patients with diagnosed diabetic foot, 52% were men. 25% of the infections occurred in patients with ages ranging from 51 to 60 years. 21 microorganisms were isolated in the 115 different samples. 80% (75) were monomicrobial, and 20% (40) polymicrobial. The most isolated bacterium in this group of bacteria was the Staphylococcus aureus (19%). Among the Gram positive bacilli, the most frequently isolated microorganism was Staphylococcus aureus, 19% (22) and Enterococcus spp. 6% (6) and among Gram negatives: Klebsiella pneumoniae 13% (16) and Acinetobacter spp. 12% (14). The results of the sensitivity tests demonstrated that 100% of the strains of S. aureus were resistant to Oxacillin and 100% of the strains of K. pneumoniae showed resistance to cefhems. 100% of the strains of Acinetobacter spp were resistant to Cefotaxime and Piperacillin. The isolated microorganisms and the antimicrobial resistance profile they present coincide with the literature, and it is of most importance to implement prevention programs regarding this pathology in order to avoid amputations in this type of patients. Key words: bacteria; foot; diabetic; h Palabras claves: bacterias; pie; diabético; hospital; Paraguay.

Validation of a reaction volume reduction protocol for analysis of Y chromosome haplotypes targeting DNA databases.

The use of Y chromosome haplotypes, important for the detection of sexual crimes in forensics, has gained prominence with the use of databases that incorporate these genetic profiles in their system. Here, we optimized and validated an amplification protocol for Y chromosome profile retrieval in reference samples using lesser materials than those in commercial kits. FTA® cards (Flinders Technology Associates) were used to support the oral cells of male individuals, which were amplified directly using the SwabSolution reagent (Promega). First, we optimized and validated the process to define the volume and cycling conditions. Three reference samples and nineteen 1.2 mm-diameter perforated discs were used per sample. Amplification of one or two discs (samples) with the PowerPlex® Y23 kit (Promega) was performed using 25, 26, and 27 thermal cycles. Twenty percent, 32%, and 100% reagent volumes, one disc, and 26 cycles were used for the control per sample. Thereafter, all samples (N = 270) were amplified using 27 cycles, one disc, and 32% reagents (optimized conditions). Data was analyzed using a study of equilibrium values between fluorophore colors. In the samples analyzed with 20% volume, an imbalance was observed in peak heights, both inside and in-between each dye. In samples amplified with 32% reagents, the values obtained for the intra-color and inter-color standard balance calculations for verification of the quality of the analyzed peaks were similar to those of samples amplified with 100% of the recommended volume. The quality of the profiles obtained with 32% reagents was suitable for insertion into databases.

Alcohol abusive use increases facial trauma?

BACKGROUND: Trauma is among the main death causes and morbidity in the world and is often related to the use of alcohol and its abuse has reached massive proportions, no matter if the country is developed or not, being considered as public health problem. Since there are very few randomized and prospective studies in literature about the association of facial trauma and the use of alcohol, this study aims to investigate the impact of alcohol use in facial trauma. MATERIAL AND METHODS: This was a prospective and cross sectional study, involving facial trauma patients attended at Oral Maxillofacial Surgery Division of a State Hospital. Variables included patient's profile, trauma etiology, facial region involved, type of injury and treatment and days of hospitalization. AUDIT test was applied to identify risks and damages of alcohol use and chemical dependence. Absolute distribution, uni and mutilvaried percentages were made for data evaluation. Pearson's qui-squared and Fisher's Exact tests were also used. RESULTS: One hundred patients were evaluated. The patient's mean age was 33.50 years-old, 48% had between 17 and 29 years old, 28% had 30 to 39, and 24% 40 or more. Most of them were male (86%). The most frequent etiology was traffic accident (57%), the extraoral area was most committed (62%), the most frequent type of injury was fractures (78%) and the most affected bone was the mandible (36%). More than half of the patients (53%) had surgical treatment. 38% had their discharge from hospital right after the first attendance. The AUDIT most frequent answer was "moderate use" (46%) and use at risk (39%). There was significant difference between the use of alcohol (AUDIT) and hematoma (0.003) and number of days of hospitalization (p=0.005). CONCLUSIONS: In this study it was not observed association between alcohol consumption using the AUDIT and trauma etiology, but patient victims of traffic accidents were classified as with risk in the scale. Most of the trauma were caused by traffic accidents using motorcycles and occurred in young aged men.

Invariant Natural Killer T Cells are Reduced in Hereditary Hemochromatosis Patients.

PURPOSE: Invariant natural killer T (iNKT) cells are CD1d restricted-T cells that react to lipid antigens. iNKT cells were shown to be important in infection, autoimmunity and tumor surveillance. Alterations in the number and function of these cells were described in several pathological conditions including autoimmune and/or liver diseases. CD1d is critical for antigen presentation to iNKT cells, and its expression is increased in liver diseases. The liver is the major organ affected in Hereditary Hemochromatosis (HH), an autosomal recessive disorder caused by excessive iron absorption. Herein, we describe the study of iNKT cells of HH patients. METHODS: Twenty-eight HH patients and 24 control subjects from Santo António Hospital, Porto, were included in this study. Patient's iron biochemical parameters (serum transferrin saturation and ferritin levels) and the liver function marker alanine transaminase (ALT) were determined at the time of study. Peripheral blood iNKT cells were analyzed by flow cytometry using an anti-CD3 antibody and the CD1d tetramer loaded with PBS57. RESULTS: We found a decrease in the percentage and number of circulating iNKT cells from HH patients when compared with control population independently of age. iNKT cell defects were more pronounced in untreated patients, relating with serum ferritin and transferrin saturation levels. No correlation was found with ALT, a marker of active liver dysfunction. CONCLUSIONS: Altogether, our results demonstrate that HH patients have reduced numbers of iNKT cells and that these are influenced by iron overload.

Burnout syndrome in oral and maxillofacial surgeons: a critical analysis.

The aim of this study was to determine the prevalence of burnout syndrome among Brazilian oral and maxillofacial surgeons and its relationship with socio-demographic, clinical, and habit variables. The sample of this study comprised 116 surgeons. The syndrome was quantified using the Maslach Burnout Inventory (General Survey), which defines burnout as the triad of high emotional exhaustion, high depersonalization, and low personal accomplishment. The criteria of Grunfeld et al. were used to evaluate the presence of the syndrome (17.2%). No significant differences between the surgeons diagnosed with and without the syndrome were observed according to age (P=0.804), sex (P=0.197), marital status (P=0.238), number of children (P=0.336), years of professional experience (P=0.102), patients attended per day (P=0.735), hours worked per week (P=0.350), use of alcohol (P=0.148), sports practice (P=0.243), hobbies (P=0.161), or vacation period per year (P=0.215). Significant differences occurred in the variables sex in the emotional exhaustion subscale (P=0.002) and use or not of alcohol in the personal accomplishment subscale (P=0.035). Burnout syndrome among Brazilian surgeons is average, showing a low personal accomplishment.

Development of temporomandibular joint ankylosis in rats using stem cells and bone graft.

64 male Wistar rats were used: 24 for the removal of stem cells, 4 as a control group, and 36 for the experiment, in which either stem cells or bone graft was used. The rats were divided into groups according to the type of procedure and time span (15, 30 or 60 days). The joints were submitted to histological study in order to score the ankylosis. The mean differences between initial and final maximal mouth opening (MMO) were gradually increased from 15 to 60 days, for all times of evaluation for both groups, being statistically significant at 15 days (p=0.045) in the bone-graft group. When both groups were compared, the mean differences between initial and final MMO were statistically significant at 15 days (p=0.018) and 30 days (p=0.029). In relation to the histological scores, in the bone-graft group almost all animals had intra-articular fibrosis at all times of evaluation (n=17). In the stem-cell group, there was new bone at 15 days (n=4), 30 days (n=3) and 60 days (n=4). The study model permitted the development of fibrous ankylosis in the majority of animals for both groups and no bony bridge was observed.

Treatment of chronic mandibular dislocations using a new miniplate.

Temporomandibular joint (TMJ) dislocation is defined as an excessive forward movement of the condyle beyond the articular eminence with complete separation of the articular surfaces and fixation in that position. The aim of this study was to describe a modified miniplate designed for treating chronic mandibular dislocations and evaluate the results of its placement in one patient, who was followed for 18 months. The treatment of chronic mandibular dislocation using this modified miniplate was shown to be efficient in relation to the postoperative maximal mouth opening, recurrence and articular function.

Erythropoietin production by distal nephron in normal and familial amyloidotic adult human kidneys.

BACKGROUND/AIM: the kidney is the major site of erythropoietin production. Many efforts have been made to identify renal erythropoietin-producing cells. Previous studies showed conflicting results, but the predominant localization reported was the peritubular interstitial and tubular epithelial cells. This study was conducted to identify the erythropoietin-producing cells in renal biopsies from 10 cadaveric donors and 45 patients with familial amyloidosis ATTR V30M, thirteen of them with anemia. Familial amyloidosis Type I (FAP-I) is a genetic disorder caused by a transthyretin (TTR) protein variant presenting a single amino acid substitution of methionine for valine at position 30 of the polypeptide chain (TTR V30M). Anemia in FAP-I is associated with inappropriately low serum erythropoietin levels. METHODS: erythropoietin expression was detected by in situ hybridization (ISH) and confirmed by laser capture microdissection followed by PCR. Renal segments were identified by immunohistochemistry. RESULTS: erythropoietin was mainly expressed by epithelial distal tubular cells and collecting tubules and additionally, in a few biopsies, by glomerular cells. A similar expression pattern was observed in donors and FAP-I patients. No increased mRNA erythropoietin expression was found in anemic patients, all of them presenting only a slight expression in medulla and cortex. CONCLUSIONS: these results suggest the distal nephron as the major site of erythropoietin production, and support the notion that an inappropriate erythropoietin production is the cause of anemia in familial amyloidosis ATTR V30M.

Low numbers of CD8+ T lymphocytes in hereditary haemochromatosis are explained by a decrease of the most mature CD8+ effector memory T cells.

Low CD8(+) T lymphocyte numbers have long been described in hereditary haemochromatosis (HH). Recently, two conserved haplotypes localized near the microsatellite D6S105 at the major histocompatibility complex (MHC) class I region were described predicting the clinical expression of HH and the CD8(+) T lymphocyte numbers. The A-A-T haplotype was associated with a severe clinical expression of HH and low CD8(+) T lymphocyte numbers, while the G-G-G haplotype was associated with a milder clinical expression of HH and high CD8(+) T lymphocyte numbers. As CD8(+) T lymphocytes are a very heterogeneous population, in this study we analysed the CD8(+) subpopulations of naive, central memory (T(CM)) and effector memory (T(EM)), and further subsets of CD8(+) T(EM) cells in 47 HH patients and 68 controls. In addition, association studies were conducted between the conserved haplotypes and the CD8(+) T cell subpopulations in HH. Variations of the numbers of naive and central memory cells with age were similar between HH patients and controls. For T(EM) cells and the T(EM) CD27(-)CD28(-) subset no effect of age was observed in HH [R(2) = 0.001, not significant (n.s.) and R(2) = 0.01, n.s., respectively] contrasting with the increasing of these subpopulations with age in controls (R(2) = 0.09, P = 0.017 and R(2) = 0.22, P = 0.0005, respectively). Interestingly, patients homozygous for the A-A-T haplotype have lower numbers of CD8(+) T(EM) cells due especially to lower numbers of T(EM) CD27(-)CD28(-) (0.206 +/- 0.119 and 0.066 +/- 0.067 x 10(6) cells/ml, respectively) than patients carrying the G-G-G haplotype (0.358 +/- 0.195 and 0.246 +/- 0.202 x 10(6) cells/ml, respectively). This may suggest an inability of HH patients to differentiate the CD8(+) T cells into the most mature phenotype.

Treatment of chronic mandibular dislocations using miniplates: follow-up of 8 cases and literature review.

Temporomandibular joint (TMJ) dislocation is an excessive forward movement of the condyle beyond the articular eminence with complete separation of the articular surfaces and fixation in that position. This study reports 8 cases using miniplates for chronic mandibular dislocations, evaluates the results and critically reviews the literature. The sample was obtained from the records of the Oswaldo Cruz University Hospital and comprises patients undergoing chronic mandibular dislocation treatment using 2.0mm titanium miniplates between August 2002 and March 2004. Pre- and postoperative assessment included a thorough history and physical examination to determine the maximal mouth opening, presence of pain and sounds, frequency of luxations, recurrence rate and presence of facial nerve paralysis. The mean maximal mouth opening preoperatively was 42.75+/-11.53 mm and was 45.62+/-8.52 mm postoperatively. There was no facial nerve paralysis. Miniplate fracture was observed in 2 cases and there was one recurrence. Treating chronic mandibular dislocation using miniplates was shown to be efficient in relation to postoperative maximal mouth opening, recurrence and articular function, however, the possibility of the miniplate fracturing must be considered.

Development of temporomandibular joint ankylosis in rats: a preliminary experimental study.

The objective of this study was to evaluate a model for the development of temporomandibular joint ankylosis in rats using disc removal and articular damage. In 30 adult male Wistar rats, articular damage was induced and disc removal performed in the right joint to induce ankylosis. The rats were divided into groups according to the time of killing (7, 15, 30, 60 and 90 days). Maximal mouth opening, mandibular deviation, initial and final weights, and duration of surgery were recorded and evaluated. After death, the joints were submitted to histological study in order to score the ankylosis. The mean duration of surgery was 14.23 min. Mean difference between initial and final maximal mouth opening was 3.38 mm, being greatest at the 15-day evaluation and lowest at 90 days, and was statistically significant at 15 days (p=0.043), 30 days (p=0.027) and 60 days (p=0.027). No mandibular deviation was observed at any of the evaluation times. Histological scores increased with time of evaluation from 7 to 30 days, when they started to fall. This study model permitted the development of fibrous ankylosis in the majority of the animals, and no bony bridge was observed between the mandibular condyle and the temporal bone.