Characterization of the thymus in Lrp4 myasthenia gravis: Four cases

Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction. Most patients have pathogenic autoantibodies against the acetylcholine receptor (AChR). In the last years a novel subpopulation of MG patients has been described that harbors antibodies against low-density lipoprotein receptor-related protein 4 (Lrp4), another postsynaptic neuromuscular antigen. In early-onset AChR MG (EOMG), the thymus plays an important role in immunopathogenesis, and early thymectomy is beneficial. It is still unknown if the thymus plays any role in Lrp4-MG. In this pilot study, we compared thymus samples from four patients with Lrp4-MG (one pre-treated with immunosuppressive drugs), four non-MG controls and five EOMG patients (not pretreated with immunosuppressive drugs). Immunohistochemistry of the Lrp4-MG thymi revealed normal architecture, with normal numbers and distribution of B-cells, lymphoid follicles and Hassall's corpuscles. Primary CD23⁺ lymphoid follicles were similarly infrequent in Lrp4-MG and control thymic sections. In none of the control or Lrp4-MG thymi did we find secondary follicles with CD10⁺ germinal centers. These were evident in 2 of the 5 EOMG thymi, where primary lymphoid follicles were also more frequent on average, thus showing considerable heterogeneity between patients. Even if characteristic pathological thymic changes were not observed in the Lrp4 subgroup, we cannot exclude a role for the thymus in Lrp4-MG pathogenesis, since one Lrp4-MG patient went into clinical remission after thymectomy alone (at one year follow-up) and one more improved after thymectomy in combination with immunosuppressive therapy.     

Bronchiolitis needs a revisit: Distinguishing between virus entities and their treatments

Current data indicate that the “bronchiolitis” diagnosis comprises more than one condition. Clinically, pathophysiologically, and even genetically three main clusters of patients can be identified among children suffering from severe bronchiolitis (or first wheezing episode): (a) respiratory syncytial virus (RSV)‐induced bronchiolitis, characterized by young age of the patient, mechanical obstruction of the airways due to mucus and cell debris, and increased risk of recurrent wheezing. For this illness, an effective prophylactic RSV‐specific monoclonal antibody is available; (b) rhinovirus‐induced wheezing, associated with atopic predisposition of the patient and high risk of subsequent asthma development, which may, however, be reversed with systemic corticosteroids in those with severe illness; and (c) wheeze due to other viruses, characteristically likely to be less frequent and severe. Clinically, it is important to distinguish between these partially overlapping patient groups as they are likely to respond to different treatments. It appears that the first episode of severe bronchiolitis in under 2‐year‐old children is a critical event and an important opportunity for designing secondary prevention strategies for asthma. As data have shown bronchiolitis cannot simply be diagnosed using a certain cutoff age, but instead, as we suggest, using the viral etiology as the differentiating factor.     

Sclerostin and Dickkopf-1 in Post-menopausal Renal Allograft Recipients

Background

Age, pre-existing renal osteodistrophy, impaired renal function, and chronic use of immunosuppressive drugs are the main factors involved in the onset and development of bone metabolism disturbances and skeletal alterations occurring after renal transplantation. However, at the state of the art, no reports have analyzed the additional post-menopausal physiological mechanisms associated with the onset and development of bone complications in renal transplant recipients.

Methods

We measured by means of molecular strategies (enzyme-linked immunoassay, chemiluminescence) the serum levels of Sclerostin and Dickkopf-1 (DKK1), two major antagonists of the Wnt/β-catenin pathway, and several bone resorption/formation biomarkers (N-terminal procollagen type 1, bone-specific alkaline phosphatase, and serum C-terminal telopeptides of type I collagen) in 19 post-menopausal kidney transplant patients and 12 post-menopausal chronic kidney disease patients (CKD group) matched for age and renal function.

Results

Our results showed that the levels of both Wnt antagonists were similar in the two study groups (P = .15 and .96, respectively). Additionally, no correlation was found between Sclerostin and DKK1 serum levels in all patients included in the study (R² = 0.03, P = .2). After statistical analysis, we found no differences in the bone resorption/formation biomarkers between renal transplant and CKD patients. Multivariate analysis showed that Sclerostin levels were significantly positively correlated with serum phosphorus levels (P = .008) and inversely correlated with renal function (P = .026). Surprisingly, no significant correlation was found between all the analyzed demographic and clinical parameters and DKK1.

Conclusions

Our study demonstrated for the first time that renal transplantation per se and immunosuppressive treatments do not represent additional factors contributing to bone metabolic/biochemical alterations in post-menopausal women. However, our results emphasized that a better preservation of the graft function could significantly slow down the progression of bone metabolic deregulations and prevent clinical bone complications.     

Renal Mechanisms of Association between Fibroblast Growth Factor 1 and Blood Pressure

The fibroblast growth factor 1 (FGF1) gene is expressed primarily in the kidney and may contribute to hypertension. However, the biologic mechanisms underlying the association between FGF1 and BP regulation remain unknown. We report that the major allele of FGF1 single nucleotide polymorphism rs152524 was associated in a dose-dependent manner with systolic BP (P=9.65×10⁻⁵) and diastolic BP (P=7.61×10⁻³) in a meta-analysis of 14,364 individuals and with renal expression of FGF1 mRNA in 126 human kidneys (P=9.0×10⁻³). Next-generation RNA sequencing revealed that upregulated renal expression of FGF1 or of each of the three FGF1 mRNA isoforms individually was associated with higher BP. FGF1-stratified coexpression analysis in two separate collections of human kidneys identified 126 FGF1 partner mRNAs, of which 71 and 63 showed at least nominal association with systolic and diastolic BP, respectively. Of those mRNAs, seven mRNAs in five genes (MME, PTPRO, REN, SLC12A3, and WNK1) had strong prior annotation to BP or hypertension. MME, which encodes an enzyme that degrades circulating natriuretic peptides, showed the strongest differential coexpression with FGF1 between hypertensive and normotensive kidneys. Furthermore, higher level of renal FGF1 expression was associated with lower circulating levels of atrial and brain natriuretic peptides. These findings indicate that FGF1 expression in the kidney is at least under partial genetic control and that renal expression of several FGF1 partner genes involved in the natriuretic peptide catabolism pathway, renin-angiotensin cascade, and sodium handling network may explain the association between FGF1 and BP.     

Transient Effects of Anesthesia on Leukocyte Apoptosis and Monocyte Cytokine Stimulation: A Clinical Study

The effects of anesthetics on immune cell apoptosis and cytokine stimulation were studied in a prospective study. American Society of Anesthesiologists I/II patients underwent elective inguinal hernia repair or varicose veins stripping surgery and were randomized to either epidural anesthesia (n = 14) or general anesthesia with sevoflurane (n = 19) or propofol (n = 15). Blood was sampled before anesthesia induction (T0), at the end of surgery (T1), and 6 h later (T2). Apoptosis was determined by ANNEXIN-V staining of white blood cells; monocytes were isolated and stimulated for cytokine production. Results were compared with 10 healthy volunteers well-matched for age and gender. Apoptosis of lymphocytes and monocytes was increased in the epidural and sevoflurane groups at T2. Propofol group had increased production of interleukin-6 at T1 and sevoflurane and epidural groups had decreased production of tumor necrosis factor-alpha at T2. Results emphasize the modulation of immune function by epidural and sevoflurane but not propofol anesthesia in a clinical setting.     

Management of Appendiceal Mass and Abscess. An 11-Year Experience

The aim of our study is to compare the results of emergency surgery versus conservative treatment with interval surgery in patients diagnosed with appendiceal mass and abscess. A retrospective review of 48 patients with appendiceal mass and abscess treated from January 2002 to January 2013 at General Surgery Department of Kipshidze Central University Hospital was performed. Patients with emergency surgery were compared to patients treated by nonoperative management with interval surgery. Demographics, clinical profile, and operative outcomes were studied. The emergency surgery group included 25 patients, and the interval surgery group included 23 patients. The clinical characteristics of the emergency surgery and interval surgery groups were not statistically different. In the emergency surgery group, an open appendectomy was performed on 17 patients, and colonic resections (ileocecectomy or right hemicolectomy) were performed on 8 patients. In the interval surgery group, an open appendectomy was performed on 21 patients, and colonic resections were performed on 2 patients. There were no statistical differences in types of surgery, postoperative complications, operation time without colonic resections, and postoperative hospitalization period among these 2 groups. Operation time with colonic resections was of greater duration in the emergency surgery group than in the interval surgery group (P = 0.04). Both treatment methods for appendiceal mass and abscess have the same results. The surgeon must consider clinical symptoms and results of investigations in each particular case when choosing an appropriate treatment method. Prospective randomized controlled trials are required for comparing the results of all 3 treatment methods of appendiceal mass.Key words: Appendicitis, Mass, Abscess, Appendectomy, Ileocecectomy, Right hemicolectomyAcute appendicitis is one of the most frequent acute surgical pathologies. The inflammation in acute appendicitis may sometimes be fixed by the patient''s own defense mechanisms, by the formation of an inflammatory mass (an appendiceal phlegmon) or a circumscribed abscess (an appendiceal abscess), often presenting as a palpable mass days following the onset of symptoms. This complication occurs in 2 to 7% of all cases of appendicitis.^1,2Management of appendiceal mass and abscess is either operative or conservative. More evidence is needed to identify which method is superior.¹ Immediate appendectomy may be technically demanding because of the distorted anatomy and difficulties in closing the appendiceal stump due to the inflamed tissues. According to the aforementioned, the operation could be finished with colonic resections (ileocecectomy or right hemicolectomy).^2–4Conservative management with interval appendectomy has traditionally remained the gold standard management. The need for interval appendectomy after a successful nonsurgical treatment has recently been questioned as the risk of recurrence is relatively small.^5–7 After successful nonsurgical treatment of an appendiceal mass, the true diagnosis is uncertain in some cases and underlying diagnosis of cancer or Crohn''s disease (CD) may be delayed.^1,8,9The aim of our study is to compare the results of emergency surgery versus conservative treatment followed by elective surgery in patients diagnosed with appendiceal mass and abscess.     

T1R3 and gustducin in gut sense sugars to regulate expression of Na+-glucose cotransporter 1

Dietary sugars are transported from the intestinal lumen into absorptive enterocytes by the sodium-dependent glucose transporter isoform 1 (SGLT1). Regulation of this protein is important for the provision of glucose to the body and avoidance of intestinal malabsorption. Although expression of SGLT1 is regulated by luminal monosaccharides, the luminal glucose sensor mediating this process was unknown. Here, we show that the sweet taste receptor subunit T1R3 and the taste G protein gustducin, expressed in enteroendocrine cells, underlie intestinal sugar sensing and regulation of SGLT1 mRNA and protein. Dietary sugar and artificial sweeteners increased SGLT1 mRNA and protein expression, and glucose absorptive capacity in wild-type mice, but not in knockout mice lacking T1R3 or alpha-gustducin. Artificial sweeteners, acting on sweet taste receptors expressed on enteroendocrine GLUTag cells, stimulated secretion of gut hormones implicated in SGLT1 up-regulation. Gut-expressed taste signaling elements involved in regulating SGLT1 expression could provide novel therapeutic targets for modulating the gut's capacity to absorb sugars, with implications for the prevention and/or treatment of malabsorption syndromes and diet-related disorders including diabetes and obesity.     

Contribution of computed tomography guided percutaneous drainage of tuberculous cold abscesses adjunctive to pharmaceutical anti-tubercular treatment

Purpose

To determine the efficiency and safety of the percutaneous aspiration and drainage of rare touberculous cold abscesses under CT guidance.

Materials and methods

We retrospectively studied 63 cases of 44 patients, treated in our hospital during the last two years. They suffered from tuberculous infection complicated with tuberculous cold abscesses variously located. All these patients underwent percutaneous aspiration and drainage under CT imaging, following the trocar puncture technique. The catheter remained in place for about a week. A follow up CT scan was performed in all cases before the catheter removal. Some of the patients were under anti tuberculosis medication.

Results

All the patients had a successful recovery from the abscesses. There were no major or minor complications observed. No recurrence occurred until today.

Conclusion

CT guided percutaneous aspiration and drainage of tuberculous cold abscesses is a safe, minimal invasive and effective method of treatment. Drainage and specific antituberculosis therapy leads to a satisfactory conclusion.