Severe and refractory myositis in mixed connective tissue disease: a description of a rare case

Mixed connective tissue disease (MCTD) is a rare disease that includes clinical and laboratorial manifestations of systemic lupus erythematosus, scleroderma and polymyositis that is associated with high titers of anti-U1RNP antibodies. In general, muscle involvement is subclinical, usually appearing as an increase in muscle enzyme levels that tends to be a characteristic of the initial phases of the disease. Severe clinical muscle weakness is not observed in this disease. The objective of this study is to report a rare case of a patient who presented a severe onset of myositis characterized by dysphagia, an increase in myopathy and a weakening of the cervical musculature. While there was no response to the administration of an initial dose of corticosteroids, improvement was observed after increasing the dose of corticosteroids, in addition to the initiation of pulse therapy with methylprednisolone accompanied by methotrexate treatment. The authors emphasize that there is only one previously reported case regarding a child with MCTD and severe clinical myopathy on electromyography and muscle biopsy, and they report in this article one adult female patient who presented severe myositis and was refractive to corticotherapy. Lupus (2010) 19, 1659-1661.

Skeletal Microstructural Abnormalities in Postmenopausal Women With Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is associated with osteoporosis and fragility fractures. The objectives of this study were to assess static and dynamic indices of cancellous and cortical bone structure in postmenopausal women with COPD. Twenty women with COPD who had not received chronic oral glucocorticoids underwent bone biopsies after double tetracycline labeling. Biopsies were analyzed by histomorphometry and mu CT and compared with age-matched controls. Distribution of the patients according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) was: Type I (15%), Type II (40%), Type III (30%), and Type IV (15%). Mean (+/-SD) cancellous bone volume (15.20 +/- 5.91 versus 21.34 +/- 5.53%, p = .01), trabecular number (1.31 +/- 0.26 versus 1.77 +/- 0.51/mm, p = .003), and trabecular thickness (141 +/- 23 versus 174 +/- 36 mu m, p = .006) were lower in patients than in controls. Connectivity density was lower in COPD (5.56 +/- 2.78 versus 7.94 +/- 3.08 mu m, p = .04), and correlated negatively with smoking (r = -0.67; p = .0005). Trabecular separation (785 +/- 183 versus 614 +/- 136 mu m, p = .01) and cortical porosity (4.11 +/- 1.02 versus 2.32 +/- 0.94 voids/mm(2); p < .0001) were higher in COPD while cortical width (458 +/- 214 versus 762 +/- 240 mu m; p < .0001) was lower. Dynamic parameters showed significantly lower mineral apposition rate in COPD (0.56 +/- 0.16 versus 0.66 +/- 0.12 mu m/day; p = .01). Patients with more severe disease, GOLD III and IV, presented lower bone formation rate than GOLDI and II (0.028 +/- 0.009 versus 0.016 +/- 0.011 mu m(3)/mu m(2)/day;p = 04). This is the first evaluation of bone microstructure and remodeling in COPD. The skeletal abnormalities seen in cancellous and cortical bone provide an explanation for the high prevalence of vertebral fractures in this disease. (C) 2010 American Society for Bone and Mineral Research.

Dipyridamole Stress and Rest Myocardial Perfusion by 64-Detector Row Computed Tomography in Patients With Suspected Coronary Artery Disease

Recently, stress myocardial computed tomographic perfusion (CTP) was shown to detect myocardial ischemia. Our main objective was to evaluate the feasibility of dipyridamole stress CTP and compare it to single-photon emission computed tomography (SPECT) to detect significant coronary stenosis using invasive conventional coronary angiography (CCA; stenosis >70%) as the reference method. Thirty-six patients (62 +/- 8 years old, 20 men) with previous positive results with SPECT (<2 months) as the primary inclusion criterion and suspected coronary artery disease underwent a customized multidetector-row CT protocol with myocardial perfusion evaluation at rest and during stress and coronary CT angiography (CTA). Multidetector-row computed tomography was performed in a 64-slice scanner with dipyridamole stress perfusion acquisition before a second perfusion/CT angiographic acquisition at rest. Independent blinded observers performed analysis of images from CTP, CTA, and CCA. All 36 patients completed the CT protocol with no adverse events (mean radiation dose 14.7 +/- 3.0 mSv) and with interpretable scans. CTP results were positive in 27 of 36 patients (75%). From the 9 (25%) disagreements, 6 patients had normal coronary arteries and 2 had no significant stenosis (8 false-positive results with SPECT, 22%). The remaining patient had an occluded artery with collateral flow confirmed by conventional coronary angiogram. Good agreement was demonstrated between CTP and SPECT on a per-patient analysis (kappa 0.53). In 26 patients using CCA as reference, sensitivity, specificity, and positive and negative predictive values were 88.0%, 79.3%, 66.7%, and 93.3% for CTP and 68.8, 76.1%, 66.7%, and 77.8%, for SPECT, respectively (p = NS). In conclusion, dipyridamole CT myocardial perfusion at rest and during stress is feasible and results are similar to single-photon emission CT scintigraphy. The anatomical-perfusion information provided by this combined CT protocol may allow identification of false-positive results by SPECT. (C) 2010 Elsevier Inc. All rights reserved. (Am J Cardiol 2010;106:310-315)

A transgenic mouse model that recapitulates the clinical features of both neonatal and adult forms of the skin disease epidermolytic hyperkeratosis

Keratins are the major structural proteins of keratinocytes, which are the most abundant cell type in the mammalian epidermis. Mutations in epidermal keratin genes have been shown to cause severe blistering skin abnormalities. One such disease, epidermolytic hyperkeratosis (EHK), also known as bullous congenital ichthyosiform erythroderma, occurs as a result of mutations in highly conserved regions of keratins K1 and K10. Patients with EHK first exhibit erythroderma with severe blistering, which later is replaced by thick patches of scaly skin. To assess the effect of a mutated K1 gene on skin biology and to produce an animal model for EHK, we removed 60 residues from the 2B segment of HK1 and observed the effects of its expression in the epidermis of transgenic mice. Phenotypes of the resultant mice closely resembled those observed in the human disease, first with epidermal blisters, then later with hyperkeratotic lesions. In neonatal mice homozygous for the transgene, the skin was thicker, with an increased labeling index, and the spinous cells showed a collapse of the keratin filament network around the nuclei, suggesting that a critical concentration of the mutant HK1, over the endogenous MK1, was required to disrupt the structural integrity of the spinous cells. Additionally, footpad epithelium, which is devoid of hair follicles, showed blistering in the spinous layer, suggesting that hair follicles can stabilize or protect the epidermis from trauma. Blisters were not evident in adult mice, but instead they showed a thick, scaly hyperkeratotic skin with increased mitosis, resulting in an increased number of corneocytes and granular cells. Irregularly shaped keratohyalin granules were also observed. To date, this is the only transgenic model to show the typical morphology found in the adult form of EHK.

Liver transplantation and quality of life: relevance of a specific liver disease questionnaire

Aim: A positive effect of liver transplantation on health-related quality of life (HRQOL) has been well documented in previous studies using generic instruments. Our aim was to re-evaluate different aspects of HRQOL before and after liver transplantation with a relatively new questionnaire the `liver disease quality of life` (LDQOL). Methods: The LDQOL and the Short Form 36 (SF-36) questionnaires were applied to ambulatory patients, either in the transplant list (n=65) or after 6 months to 5 years of liver transplant (n=61). The aetiology of cirrhosis, comorbidities, model for end-stage liver disease (MELD) Child-Pugh scores and recurrence of liver disease after liver transplantation were analysed using the Mann-Whitney and Kruskall-Wallis tests. Results: In patients awaiting liver transplantation, MELD scores >= 15 and Child-Pugh class C showed statistically significant worse HRQOL, using both the SF-36 and the LDQOL questionnaires. HRQOL in pretransplant patients was found to be significantly worse in those with cirrhosis owing to hepatitis C (n=30) when compared with other aetiologies (n=35) in 2/7 domains of the SF-36 and in 7/12 domains of the LDQOL. Significant deterioration of HRQOL after recurrence of hepatitis C post-transplant was detected with the LDQOL questionnaire although not demonstrated with the SF-36. The statistically significant differences were in the LDQOL domains: symptoms of liver disease, concentration, memory and health distress. Conclusions: The LDQOL, a specific instrument for measuring HRQOL, has shown a greater accuracy in relation to liver symptoms and could demonstrate, with better reliability, impairments before and after liver transplantation.

Identification of intracellular and extracellular domains mediating signal transduction in the inhibitory glycine receptor chloride channel

Fast synaptic neurotransmission is mediated by transmitter-activated conformational changes in ligand-gated ion channel receptors, culminating in opening of the integral ion channel pore. Human hereditary hyperekplexia, or startle disease, is caused by mutations in both the intracellular or extracellular loops flanking the pore-lining M2 domain of the glycine receptor alpha 1 subunit. These flanking domains are designated the M1-M2 loop and the M2-M3 loop respectively. We show that four startle disease mutations and six additional alanine substitution mutations distributed throughout both loops result in uncoupling of the ligand binding sites from the channel activation gate. We therefore conclude that the M1-M2 and M2-M3 loops act in parallel to activate the channel. Their locations strongly suggest that they act as hinges governing allosteric control of the M2 domain. As the members of the ligand-gated ion channel superfamily share a common structure, this signal transduction model may apply to all members of this superfamily.

Negative Pressure Therapy for Complex Wounds in Patients with Sickle-Cell Disease: A Case Study

Sickle-cell disease is the most prevalent genetic disease in the Brazilian population. Lower limb ulcers are the most frequent cutaneous complications, affecting 8% to 10% of the patients. These ulcers are usually deep and may take many years to heal. Evidence about the effectiveness of systemic or topical treatment of these wounds is limited, apart from stabilization of the anemia. A 28-year old woman with sickle-cell disease was admitted for treatment of three deep chronic lower leg ulcers. All wounds had tendon exposure and contained firmly adherent fibrin slough. Following surgical debridement and before grafting, the wounds were managed with three different dressings: a rayon and normal saline solution dressing, a calcium alginate dressing covered with gauze, and negative pressure therapy. All three wounds healed successfully and their grafts showed complete integration; only the rayon-dressed wound required a second debridement. The alginate and rayon-dressed wounds recurred after 9 months and required additional skin grafts. Helpful research on managing ulcers in patients with sickle-cell disease is minimal, but the results of this case study suggest that topical treatment modalities may affect outcomes. Research to explore the safety and effectiveness of NPT in patients with sickle-cell wounds is warranted.

Transanal endorectal pull-through in children with Hirschsprung`s disease-technical refinements and comparison of results with the Duhamel procedure

Purpose: Transanal endorectal pull-through (TEPT) has drastically changed the treatment of Hirschsprung`s disease (HD). A short follow-up of children Submitted to TEPT reveals results that are similar to the classic transabdominal pull-through procedures. However, few reports compare the late results of TEPT with transabdominal pull-through procedures with respect to complication rates and the fecal continence. The aims of the present work are to describe some technical refinements that we introduced in the procedure and to compare the short and long-term outcome of TEPT with the outcomes of a group of patients with HD who previously underwent the Duhamel procedure. Methods: Thirty-five patients who underwent TEPT were prospectively studied and compared to a group of 29 patients who were treated with colostomy followed by a classical Duhamel pull-through. The main modifications introduced in the TEPT group were no preoperative colon preparation, operation conducted under general anesthesia in addition to regional sacral anesthesia, use of only one purse-string Suture in the rectal mucosa before transanal submucosal dissection, and no use of retractors and electrocautery during file submucosal dissection. Results: The most frequent early complications of TEPT group were perineal dermatitis (22.8%) and anastomotic strictures (8.6%). The comparison with patients who underwent Duhamel procedure revealed no difference in the incidence of preoperative enterocolitis, the patients of the TEPT group were younger at the time of diagnosis and of surgery, they had shorter operating times, and they began oral feeding more quickly after the operation. The incidence of wound infection was lower in the TEPT group. Moreover, the TEPT and Duhamel groups showed no difference in the incidences of mortality, postoperative partial continence, and total incontinence. Although the incidences of complete continence and postoperative enterocolitis were not different, a tendency to the increased incidence in the TEPT group was observed. Conclusions: This study further supports the technical advantages, the simplicity, and the decreased incidence of complications of a primary TEPT procedure when compared to a classical form of pull-through. Sonic technical refinements are described, and no preoperative colon preparation was necessary for the patients studied here. The results show that the long-term outcomes of the modified TEPT procedure are generally better than those obtained with classical approaches. Published by Elsevier Inc.

Voiding Dysfunction in Patients With Parkinson`s Disease: Impact of Neurological Impairment and Clinical Parameters

Aims: We assessed the lower urinary tract symptoms (LUTS) of patients with Parkinson`s disease (PD) and their association with different clinical parameters. Methods: We prospectively evaluated 110 patients (84 men), with a mean age of 61.8 +/- 9.6 years. Mean duration of the disease was 12.3 +/- 7.2 years. Neurological impairment was assessed by the Hoehn-Yahr and the Unified Parkinson Disease Rating scales. LUTS were assessed by the International Continence Society questionnaire. We evaluated the impact of age, PD duration, neurological impairment, gender, and use of anti-Parkinsonian drugs on the voiding function. Results: On multivariate analysis, voiding dysfunction increased with the neurological impairment, but not with patient`s age or disease duration. Quality of life (QOL) was affected by the severity of LUTS, and the symptoms with the worst impact were frequency and nocturia. Sixty-three (57.2%) patients were symptomatic. They did not differ with the asymptomatic as to age and disease duration, but had more severe neurological impairment. No impact on LUTS was associated with the use of levodopa, anticholinergics, and dopamine receptor agonists. Men and women were similarly affected by urinary symptoms. Conclusions: The severity of the neurological disease is the only predictive factor for the occurrence of voiding dysfunction, which affects men and women alike. Neztrourol. Urodynam. 28.510-515, 2009. (C) 2009 Wiley-Liss, Inc.

Falling incidence of amputations for peripheral occlusive arterial disease in western Australia between 1980 and 1992

Objectives: To assess temporal trends in the incidence of surgical procedures for peripheral occlusive arterial disease (POAD) and associated changes in outcome as measured by the rate of major lower limb amputations for POAD. Design: a retrospective descriptive population-based study was conducted of the geographically isolated population of Western Austrialia between 1980 and 1992. Methods: Vascular procedures with an accompanying diagnosis of POAD were identified in a computerised system of name-identified records of all discharges from hospital for the population. These procedures were detected using relevant codes from the International Classification of Disease and Procedures. Records of angioplasty and thrombolysis procedures were augmented by searches of hospital-based registers of invasive radiological procedures. The data for the remaining procedures were validated by a review of a random sample of medical records. Results: over the 13 years of the study, rates of major amputations fell significantly for in non-amputation vascular surgery for individuals under the age of 60. In addition, rather than an overall rise in surgery there was shift away from sympathectomy and thromboendarterectomy to angioplasty and bypass surgery. Furthermore, an increasing proportion of all major amputations had a prior attempt at arterial reconstruction. Conclusion: These observations suggest the decrease in major amputations for POAD may reflect a fall in the incidence of POAD, possibly aided by move effective surgery, rather than increased rates of vascular surgery.

Adult-onset Still`s Disease with Pulmonary and Cardiac Involvement and Response to Intravenous Immunoglobulin

Cardiopulmonary manifestations of adult-onset Still`s disease (AOSD) include pericarditis, pleural effusion, transient pulmonary infiltrates, pulmonary interstitial disease and myocarditis. Serositis are common but pneumonitis and myocarditis are not and bring elevated risk of mortality. They may manifest on disease onset or flares. Previously reported cases were treated with high-dose glucocorticoids and immunosupressants and, when refractory, intravenous immunoglobulin (IVIG). We report an AOSD patient whose flare presented with severe pleupneumonitis and myopericarditis and, following nonresponse to a methylprednisolone pulse, high dose of prednisone and cyclosporine A, recovered after a 2-day 1g/kg/day IVIG infusion.

Digital vasculitis in systemic lupus erythematosus: a minor manifestation of disease activity?

The objective of this study is to determine if digital vasculitis (DV), a clinical manifestation with a high systemic lupus erythematosus disease activity index (SLEDAI) score, is associated with lupus severity. DV and other clinical manifestations defined according to the SLEDAI were evaluated in 168 consecutive patients with systemic lupus erythematosus (SLE). Two groups were defined according to presence (DV+, n = 27) or absence of DV (DV-, n = 141) at the time of evaluation. The exclusion criterion was the presence of antiphospholipid syndrome (Sapporo`s criteria). The two groups were comparable with regard to age (P = 0.09), gender (P = 1.00), white race (P = 0.81), and disease duration (P = 0.78). Compared to the DV-group, the DV+ group had a significantly higher frequency of mucocutaneous manifestations (66.7 vs. 39.0%, P = 0.01), haematological abnormalities (22.2 vs. 6.4%, P = 0.02) and constitutional symptoms (11.1 vs. 0.7%, P = 0.01). Renal and neurological involvements were similar in both groups ( P = 0.57 and P = 1.00, respectively). The evaluation of each SLEDAI parameter confirmed that the DV+ group had higher frequencies of mild manifestations, such as new rash (P = 0.02), alopecia (P = 0.02), oral ulcers (P = 0.045), fever (P = 0.01) and leucopenia (P = 0.005). In contrast, both groups had similarly increased anti-dsDNA (P = 0.78) and decreased complement levels (P = 0.29). In conclusion, DV in patients with SLE identifies a subgroup of a mild disease. The high `weighted` index attributed to this alteration in the SLEDAI score should therefore be revised. Lupus (2009) 18, 990-993.

Juvenile onset systemic lupus erythematosus thyroid dysfunction: A subgroup with mild disease?

The aim of this study was to evaluate the frequency of thyroid dysfunction and thyroid antibodies in patients with juvenile onset Systemic Lupus Erythematosus (JOSLE) and its association with clinical and immunological features. Seventy-seven patients with JOSLE, 64 females, median age 19 years, were consecutively enrolled from March to December 2007. Clinical data related to thyroid dysfunction and lupus were obtained by chart review and patient interview. Serum levels of TSH, free T4, anti-thyroglobulin (TgAb), anti-thyroperoxidase (TPOAb), TRAb and lupus related autoantibodies were analyzed by standard techniques. Nine patients were diagnosed as hypothyroidism and 4 hyperthyroidism. 28% JOSLE patients had moderate/high titer of thyroid antibodies: 23% TgAb, 2.6% TPOAb and 3.9% TRAb. JOSLE patients with positive thyroid autoantibodies had higher frequency of anti-U1RNP antibodies than patients without these antibodies (40.9 vs. 14.5%, OR:0.25, CI:0.08-0.76, p = 0.017). Furthermore, renal/neurological/hematological involvement was less frequently observed in patients with hypothyroidism (55.6 vs. 87.5%, OR:0.18, CI:0.04-0.81, p = 0.035) and with thyroid antibodies (68.4 vs. 90.9%, OR:0.22, CI:0.06-0.82. p = 0.027) than in patients without these alterations. No association with PTPN22 polymorphism was found. In conclusion, JOSLE patients have high prevalence of subclinical hypothyroidism. The novel association of anti-thyroid antibodies with anti-U1RNP antibodies in JOSLE seems to identify a subgroup of patients with less life-threatening organ involvement. (C) 2009 Elsevier Ltd. All rights reserved.

Mesenchymal Stem Cells Delivered at the Subcapsule of the Kidney Ameliorate Renal Disease in the Rat Remnant Kidney Model

Stem cells (SC) are potential therapeutic tools in the treatment of chronic renal diseases. Number and engraftment of SC in the injured sites are important for possible differentiation into renal cells and paracrine effect. The aim of this study was to analyze the effect of subcapsular injection of mesenchymal stem cells (MSC) in the 5/6 nephrectomy model (5/6 Nx). MSC obtained from Wistar rats were isolated by their capacity to adhere to plastic surfaces, characterized by flow cytometry, and analyzed by their differentiation potential into osteoblasts. MSC (2 X 105) were injected into the subcapsule of the remnant kidney of male Wistar rats, and were followed for 15 or 30 days. 5/6 Nx rats showed significant hypertension at 15 and 30 days, which was reduced by MSC at 30 days. Increased albuminuria and serum creatinine at 15 and 30 days in 5/6 Nx rats were also reduced by subcapsular injection of MSC. We also observed a significant reduction of glomerulosclerosis index 30 days after injection of MSC. 4-6 diamidino-2-phenylindole dihydrochloride (DAPI)-stained MSC showed a migration of these cells into renal parenchyma 5, 15, and 30 days after subcapsular injection. In conclusion, our data demonstrated that subcapsular injection of MSC in 5/6 Nx rats is associated with renoprotective effects. These results suggest that locally implanted MSC in the kidney allow a large number of cells to migrate into the injured sites and demonstrate that subcapsular injection represent an effective route for MSC delivery.