Association of antibodies to ganglioside complexes and conduction blocks in axonal Guillain‐Barré syndrome presenting as acute motor conduction block neuropathy

A close relationship between acute motor conduction block neuropathy and antibodies against the complex of GM1 and GalNAc‐GD1a has been reported. This study investigates the hypothesis that conduction block at the early phase of axonal Guillain‐Barré syndrome (GBS) is also associated with such ganglioside complexes. Sera were obtained from seven French patients with initial evidence of isolated conduction blocks that resolved or progressed to acute motor axonal neuropathy. Serum IgG to asialo‐GM1 and gangliosides of LM1, GM1, GM1b, GD1a, GalNAc‐GD1a, GD1b, GT1a, GT1b, and GQ1b as well as their complexes were measured. Five of seven patients progressed within the first month of disease to AMAN. One patient had IgG antibodies against the complex of asialo‐GM1 and each of the other ganglioside antigens. Another patient carried IgG antibodies against GM1 complex with GM1b, GD1a, and GT1a as well as asialo‐GM1 complex with GD1a and GT1a. None had IgG antibodies against GM1/GalNAc‐GD1a complex. Six patients had IgG against single antigens GM1, GD1a, GalNAc‐GD1a, GD1b, and asialo‐GM1. In three patients, a reduced reaction against GM1/GalNAc‐GD1a complex was observed. The presence of conduction block in axonal GBS is not always associated with anti‐GM1/GalNAc‐GD1a complex antibodies.     

Bullous pemphigoid in children. Report of three cases

Bullous pemphigo?d (BP) is an acquired immunobullous disease that usually affects adults and rarely children. About 60 cases of infant PB have been reported. Diagnosis is based on immunofluorescence investigations. Clinical, histological and immunopathological findings in childhood PB appear to be not different from the adult. Nevertheless, oral mucosal and palm and sole lesions seem to occur more frequently. We report 3 cases of children BP in one girl and 2 boys, aged respectively of 7.2 and 3 years. Palm and sole were affected in 1 case, and no oral mucosal lesion was noted. Recovery was reached in all cases under dapsone. Characteristics of BP in children are discussed with comparison to literature data.     

Aberrant stabilization of c-Myc protein in some lymphoblastic leukemias.

Overexpression of the c-Myc oncoprotein is observed in a large number of hematopoietic malignancies, and transgenic animal models have revealed a potent role for c-Myc in the generation of leukemias and lymphomas. However, the reason for high c-Myc protein levels in most cases is unknown. We examined whether aberrant protein stabilization could be a mechanism of c-Myc overexpression in leukemia cell lines and in primary bone marrow samples from pediatric acute lymphoblastic leukemia (ALL) patients. We found that c-Myc protein half-life was prolonged in the majority of leukemia cell lines and bone marrow samples tested. There were no mutations in the c-myc gene in any of the leukemia cell lines that could account for increased c-Myc stability. However, abnormal phosphorylation at two conserved sites, Threonine 58 and Serine 62, was observed in leukemia cell lines with stabilized c-Myc. Moreover, stabilized c-Myc from the ALL cell lines showed decreased affinity for glycogen synthase kinase3beta, the kinase that phosphorylates c-Myc at Threonine 58 and facilitates its degradation. These findings reveal that deregulation of the c-Myc degradation pathway controlled by Serine 62 and Threonine 58 phosphorylation is a novel mechanism for increased expression of a potent oncoprotein known to be involved in hematopoietic malignancies.     

Variation of biochemical parameters of the first morning urine during month of Ramadan

The purpose of this study is to evaluate the effect of fluid and diet restriction in fasting on biochemical factors of stone formation. Our study concernes 90 patients divided in three groups: healthy fasting patient (GI), healthy non fasting patient (G2) and non fasting patient with calcium lithiasis (G3). The promotors (oxalate, calcium, uric acid, phosphates) and inhibitors (citrate, magnesium) are statistically significant between G1, G2 and G3, G2. Supersaturation of urine with oxalate, uric acid and brushite are the same for (G1) and (G3) and higher than (G2). Crystalluria is more important in lithiasis subjects compared with healthy non fasting patients (58% vs 11,4%). Oxalate monohydrate (Whewellite) and uric crystal don't exist in the healthy non fasting people but reached 4% and 12% respectively in the lithiasis patient. The crystalluria profil is the same in the heathy fasting patients and calcium lithiasis patients. However healthy patients have equilibria between promotors and inhibitors of crystal formation which minimize the risk of crystalluria and subsequent stone formation.     

Highly Discriminatory Variable-Number Tandem-Repeat Markers for Genotyping of Trichophyton interdigitale Strains

Trichophyton interdigitale is the second most frequent cause of superficial fungal infections of various parts of the human body. Studying the population structure and genotype differentiation of T. interdigitale strains may lead to significant improvements in clinical practice. The present study aimed to develop and select suitable variable-number tandem-repeat (VNTR) markers for 92 clinical strains of T. interdigitale. On the basis of an analysis of four VNTR markers, four to eight distinct alleles were detected for each marker. The marker with the highest discriminatory power had eight alleles and a D value of 0.802. The combination of all four markers yielded a D value of 0.969 with 29 distinct multilocus genotypes. VNTR typing revealed the genetic diversity of the strains, identifying three populations according to their colonization sites. A correlation between phenotypic characteristics and multilocus genotypes was observed. Seven patients harbored T. interdigitale strains with different genotypes. Typing of clinical T. interdigitale samples by VNTR markers displayed excellent discriminatory power and 100% reproducibility.     

Distinct functions of macrophage-derived and cancer cell-derived cathepsin Z combine to promote tumor malignancy via interactions with the extracellular matrix

During the process of tumor progression, cancer cells can produce the requisite growth- and invasion-promoting factors and can also rely on noncancerous cells in the tumor microenvironment as an alternative, cell-extrinsic source. However, whether the cellular source influences the function of such tumor-promoting factors remains an open question. Here, we examined the roles of the cathepsin Z (CtsZ) protease, which is provided by both cancer cells and macrophages in pancreatic neuroendocrine tumors in humans and mice. We found that tumor proliferation was exclusively regulated by cancer cell-intrinsic functions of CtsZ, whereas tumor invasion required contributions from both macrophages and cancer cells. Interestingly, several of the tumor-promoting functions of CtsZ were not dependent on its described catalytic activity but instead were mediated via the Arg–Gly–Asp (RGD) motif in the enzyme prodomain, which regulated interactions with integrins and the extracellular matrix. Together, these results underscore the complexity of interactions within the tumor microenvironment and indicate that cellular source can indeed impact molecular function.     

Optimal Duration of MRI Follow-up to Safely Identify Middle Ear Residual Cholesteatoma

BACKGROUND AND PURPOSE:Previous studies have demonstrated the usefulness of non-EPI DWI for detection of residual cholesteatoma. However, limited data are available to determine the suitable duration of imaging follow-up after a first MR imaging with normal findings has been obtained. The present study aimed to determine the optimal duration of non-EPI DWI follow-up for residual cholesteatoma.MATERIALS AND METHODS:A retrospective, monocentric study was performed between 2013 and 2019 and included all participants followed up after canal wall up tympanoplasty with at least 2 non-EPI DWI examinations performed on the same 1.5T MR imaging scanner. MR images were reviewed independently by 2 radiologists. Sensitivity and specificity values were calculated as a function of time after the operation. Receiver operating characteristic curves were analyzed to determine the optimal follow-up duration.RESULTS:We analyzed 47 MRIs from 17 participants. At the end of the individual follow-up period, a residual cholesteatoma had been found in 41.1% of cases. The follow-up duration ranged from 20 to 198 months (mean, 65.9 [SD, 43.9] months). Participants underwent between 2 and 5 non-EPI DWI examinations. Analyses of the receiver operating characteristic curves revealed that the optimal diagnostic value of non-EPI DWI occurred 56 months after the operation when the first MR imaging performed a mean of 17.3 (SD, 6.8) months after the operation had normal findings (sensitivity = 0.71; specificity = 0.7, Youden index = 0.43).CONCLUSIONS:Repeat non-EPI DWI is required to detect slow-growing middle ear residual cholesteatomas. We, therefore, recommend performing non-EPI DWI for at least the first 5 years after the initial operation.

The development of DWI has profoundly changed the management of middle ear cholesteatomas. An increasing number of surgeons no longer systematically perform second-look surgery, and MR imaging follow-up is performed if revision surgery is not needed to treat conductive hearing loss. Numerous studies have evaluated the sensitivity and specificity of EPI DWI and non-EPI DWI sequences for the detection of residual cholesteatoma. Non-EPI DWI sequences offer the best sensitivity and specificity and are suitable for the detection of residual cholesteatomas as small as 2 mm.¹ A recent meta-analysis of 26 studies concerning non-EPI DWI showed a pooled sensitivity and specificity of 0.91 (95% CI, 0.87–0.95) and 0.92 (95% CI, 0.86–0.96), respectively.¹ Another meta-analysis reported a similar pooled sensitivity and specificity of 0.89 (95% CI, 0.52–0.99) and 0.93 (95% CI, 0.81–0.98), respectively.²However, data on the diagnostic value of non-EPI DWI sequences regarding the optimal timing after the initial operation remain limited. Lingam et al³ reported a sensitivity of 0.91 (95% CI, 0.79–0.97) and a specificity of 0.88 (95% CI, 0.69–0.97) with a median time to MR imaging of 5.4 months after the operation. Khemani et al⁴ found a sensitivity of 0.82 (95% CI, 0.63–0.94) and a specificity of 0.90 (95% CI, 0.55–1.00) when MR imaging was performed 10–24 months after the operation.Most authors agree that imaging follow-up should not start <12 months postsurgery,^5-8 to reduce the number of false-negatives due to residual cholesteatomas measuring <2 mm.⁹ Nevertheless, the optimal duration of follow-up necessary to exclude the existence of a residual cholesteatoma if the findings of the first MR imaging are considered normal is unclear. In a recent retrospective series, follow-up non-EPI DWI detected residual cholesteatoma in 12 of 88 patients only after a mean interval of 3.8 years after the initial cholesteatoma surgery (median, 3.7 years; range, 1.6–7.9 years).¹⁰ Pai et al¹⁰ suggested that imaging follow-up should be performed for a minimum of 5 years postoperatively, without defining how this was calculated.To provide more information on the optimal imaging follow-up duration, we describe the long-term follow-up imaging of participants with ≥2 non-EPI DWI examinations for residual middle ear cholesteatoma. The sensitivity and specificity values were calculated as a function of the duration of the follow-up, and the receiver operating characteristic curves were analyzed to determine the optimal follow-up time.