Vincristine efficacy and safety in treating immune thrombocytopenia: a retrospective study of 35 patients

Although vincristine (VCR) is sometimes prescribed for newly diagnosed immune thrombocytopenia (ITP), its efficacy in refractory ITP and sustained efficacy has yet to be demonstrated. We describe our clinical experience and recommend vincristine's correct place in ITP management. This retrospective study analysed data from 35 patients with newly diagnosed (ND), persistent (P) or chronic (C) ITP treated with VCR. The initial response rate, defined as >30 × 10⁹ platelets/L, reached 86% after a median of 7 [interquartile range (IQR) 6–13] days. In ND and P ITP, even when previous therapies were inefficient, initial response was 87.5%, suggesting that this treatment could be used particularly in rescue. Median survival time, without failure or relapse, was 15 months (Kaplan–Meier curve). Predictive factors (univariate analysis) of an initial and long‐term response were a small number of prior treatments received. However, at 2 yr, only seven patients had sustained response. Eight (23%) patients experienced adverse events: neuropathy for seven and bowel obstruction for one. Vincristine efficacy in ITP was confirmed, and it could be a good strategy for treating resistant ITP, especially in emergencies. In this era of new therapeutics, VCR deserves to remain on the list of ITP treatments because of its initial efficacy, safety and low cost.     

Topical methyl nicotinate-induced skin vasodilation in diabetic neuropathy

OBJECTIVE: To evaluate the vasodilation induced by topical application of methyl nicotinate (MN) and to compare it with the vasodilatory response to acetylcholine (ACh) and sodium nitroprusside (SNP) in healthy subjects and diabetic neuropathic patients. RESEARCH DESIGN AND METHODS: Ten diabetic patients with peripheral neuropathy (DN) and 10 age- and sex-matched healthy control subjects (C) were enrolled. The vasodilatory response to topical application of 1% MN and a placebo emulsion at the forearm and dorsum of the foot skin at 5, 15, 30, 60 and 120 min was measured using Laser Doppler Perfusion Imaging. The vasodilatory response to iontophoresis of 1% ACh and 1% SNP solutions was also evaluated. RESULTS: The maximal vasodilatory response to ACh, SNP and MN was similar at the forearm and foot level in the diabetic patients. In the control group, the responses to MN, ACh and SNP were similar on the forearm but in the foot, the MN vasodilatory response was higher when compared to the ACh and SNP responses. MN-related vasodilation was present 5 min after the application, reached its peak at 15-30 min and declined to pre-application levels 120 min afterward. CONCLUSIONS: Topical application of MN at the forearm and foot levels of diabetic neuropathic patients results in skin vasodilation that is comparable to the maximal vasodilation that can be induced by iontophoresis of ACh or SNP and lasts for less than 2 h. Further studies will be required to explore the potential of MN to increase blood flow and to prevent diabetic foot problems in clinical practice.     

Cheesy material on macroscopic on-site evaluation after endoscopic ultrasound-guided fine-needle biopsy: Don't miss the tuberculosis

Endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) is an excellent investigation to diagnose pancreatic lesions and has shown high accuracy for its use in pathologic diagnosis. Recently, macroscopic on-site evaluation (MOSE) performed by an endoscopist was introduced as an alternative to rapid on-site cytologic evaluation to increase the diagnostic yield of EUS-FNB. The MOSE of the biopsy can estimate the adequacy of the sample directly by the macroscopic evaluation of the core tissue obtained from EUS-FNB. Isolated pancreatic tuberculosis is extremely rare and difficult to diagnose because of its non-specific signs and symptoms. Therefore, this challenging diagnosis is based on endoscopy, imaging, and the bacteriological and histological examination of tissue biopsies. This uncommon presentation of tuberculosis can be revealed as pancreatic mass mimicking cancer. EUS-FNB can be very useful in providing a valuable histopathological diagnosis. A calcified lesion with a cheesy core in MOSE must be suggestive of tuberculosis, leading to the request of the GeneXpert, which can detect Mycobacterium tuberculosis deoxyribonucleic acid and resistance to rifampicin. A decent diagnostic strategy is crucial to prevent unnecessary surgical resection and to supply conservative management with antitubercular therapy.     

In-vitro effect of Peganum harmala total alkaloids on spermatozoa quality and oxidative stress of epididymal ram semen

Objective: To determine the in-vitro effect of the total alkaloid extract of Peganum (P.) harmala seeds on ram epididymal sperm. Methods: Semen was divided into...     

Identification of citrullinated vimentin peptides as T cell epitopes in HLA–DR4–positive patients with rheumatoid arthritis

Objective

Antibodies directed against citrullinated proteins (ACPAs) are highly specific for rheumatoid arthritis (RA). The production of ACPAs is most likely dependent on the presence of T cells, since ACPAs undergo isotype switching and are associated with the shared epitope (SE)–containing HLA–DRB1 alleles. Vimentin is a likely candidate protein for T cell recognition, since >90% of patients positive for ACPAs that are reactive with (peptides derived from) citrullinated vimentin carry SE‐containing HLA–DRB1 alleles. The aim of this study was to identify citrullinated vimentin peptides that are presented to HLA–DRB1*0401–restricted T cells.

Methods

HLA–DR4–transgenic mice were immunized with all possible citrulline‐containing peptides derived from vimentin, and T cell reactivity was analyzed. Peptides recognized in a citrulline‐specific manner by T cells were selected and analyzed for their ability to be processed from the entire vimentin protein. A first inventory of the selected epitopes recognized by T cells was performed using peripheral blood mononuclear cells (PBMCs) from ACPA+, HLA–DR4+ patients with RA.

Results

A citrulline‐specific response was observed for 2 of the peptides analyzed in DR4‐transgenic mice. These peptides were found to be naturally processed from the vimentin protein, since citrullinated vimentin was recognized by peptide‐specific T cells. T cell reactivity against these peptides was also observed in cultures of PBMCs from RA patients.

Conclusion

This study identifies, for the first time, 2 naturally processed peptides from vimentin that are recognized by HLA–DRB1*0401–restricted T cells in a citrulline‐specific manner. These peptides can be recognized by T cells in ACPA+, HLA–DR4+ patients with RA, as shown in a first inventory.

     

Glycan profiling of anti–citrullinated protein antibodies isolated from human serum and synovial fluid

Objective

Anti–citrullinated protein antibodies (ACPA) exhibit unique specificity for rheumatoid arthritis. However, it is incompletely understood whether and how ACPA contribute to disease pathogenesis. The Fc part of human IgG carries 2 N‐linked glycan moieties that are crucial for the structural stability of the antibody and that modulate both its binding affinity to Fcγ receptors and its ability to activate complement. We undertook this study to analyze Fc glycosylation of IgG1 ACPA in serum and synovial fluid (SF) in order to further characterize the immune response to citrullinated antigens.

Methods

ACPA were isolated by affinity purification using cyclic citrullinated peptides as antigen. IgG1 Fc glycosylation was analyzed by mass spectrometry. ACPA IgG1 glycan profiles were compared with glycan profiles of total serum IgG1 obtained from 85 well‐characterized patients. Glycan profiles of paired SF and serum samples were available from 11 additional patients.

Results

Compared with the pool of serum IgG1, ACPA IgG1 lacked terminal sialic acid residues. In SF, ACPA were highly agalactosylated and lacked sialic acid residues, a feature that was not detected for total SF IgG1. Moreover, differential ACPA glycan profiles were detected in rheumatoid factor (RF)–positive and RF‐negative patients.

Conclusion

ACPA IgG1 exhibit a specific Fc‐linked glycan profile that is distinct from that of total serum IgG1. Moreover, Fc glycosylation of ACPA differs markedly between SF and serum. Since Fc glycosylation directly affects the recruitment of Fc‐mediated effector mechanisms, these data could further our understanding of the contribution of ACPA to disease pathogenesis.

     

Posterior cerebral fossa medulloepithelioma: report of a case

Background

Medulloepithelioma is a rare primitive neuroectodermal tumor of the central nervous system, usually developing in childhood. Due to its rarity, the optimal management is still unknown. The prognosis is poor, especially when resection is incomplete. Adjuvant radiochemotherapy is often indicated.

Case presentation

We report a rare case of infratentorial medulloepithelioma in a 3 year old girl. She presented symptoms of increased intracranial pressure. On examination, she had coordination problems, ptosis and exotropia of the right eye. Magnetic resonance imaging demonstrated a large cerebellar vermix tumor. Immuno-histochemistry revealed a diffuse positivity for Vimentin and focal positivity for the epithelial membrane antigen, but Glial Fibrillary Acidic Protein and Synaptophysin were negative, the MIB-1 antibody was very high. She received postoperative craniospinal irradiation and died 7 months later.

Conclusion

We describe the features (epidemiological, clinical, histological, immunohistochemical and therapeutic outcomes) of our case and confront it to literature data.