Clinical practice guidelines for the diagnosis and management of Charcot-Marie-Tooth disease.

INTRODUCTION: Charcot-Marie-Tooth disease (CMT) is classified according to neurophysiological and histological findings, the inheritance pattern, and the underlying genetic defect. The objective of these guidelines is to offer recommendations for the diagnosis, prognosis, follow-up, and treatment of this disease in Spain. MATERIAL AND METHODS: These consensus guidelines were developed through collaboration by a multidisciplinary panel encompassing a broad group of experts on the subject, including neurologists, paediatric neurologists, geneticists, physiatrists, and orthopaedic surgeons. RECOMMENDATIONS: The diagnosis of CMT is clinical, with patients usually presenting a common or classical phenotype. Clinical assessment should be followed by an appropriate neurophysiological study; specific recommendations are established for the parameters that should be included. Genetic diagnosis should be approached sequentially; once PMP22 duplication has been ruled out, if appropriate, a next-generation sequencing study should be considered, taking into account the limitations of the available techniques. To date, no pharmacological disease-modifying treatment is available, but symptomatic management, guided by a multidiciplinary team, is important, as is proper rehabilitation and orthopaedic management. The latter should be initiated early to identify and improve the patient's functional deficits, and should include individualised exercise guidelines, orthotic adaptation, and assessment of conservative surgeries such as tendon transfer. The follow-up of patients with CMT is exclusively clinical, and ancillary testing is not necessary in routine clinical practice.

A new approach to laparoscopic implantation of the artificial urinary sphincter: Vesicovaginal approach to the bladder neck. / Nueva aproximación al implante laparoscópico del esfínter urinario artificial: abordaje vesicovaginal al cuello vesical.

INTRODUCTION: The artificial urinary sphincter (AUS) is not used extensively in the treatment of female urinary stress incontinence (USI) due to the poor reproducibility of the techniques used. We describe a new approach to laparascopic implantation, of which dissection of the vesicovaginal space is an essential step. This enables an approach under direct vision to the posterior surface of the bladder neck. MATERIAL AND METHODS: We present two cases where this approach was used. A transperitoneal approach was made in the Trendelenburg position. The main steps were: creating the vesicovaginal space until identifying the bladder neck, creating two laterovesical spaces, communicating these with the vesicovaginal space, and dissecting the anterior surface of the bladder neck, attempting to preserve the pubovesical ligament. The cuff and reservoir were inserted through the 12mm infraumbilical trocar. The connections were externalised through a left suprapubic incision and a subcutaneous tunnel created up to the labia majora where the activation pump was placed. The procedure was completed with closure of the peritoneum. It is essential to use a vaginal valve to facilitate dissection. RESULTS: Surgery time: 140 and 135minutes, with no intraoperative complications. After removing the urinary catheter, one patient had elevated postvoid residual urine volume, which was managed conservatively. Hospital stay: 72h. At 3 and 9 months the patients were fully continent. CONCLUSIONS: We present the preliminary results of laparoscopic implantation of an AUS through a vesicovaginal approach to the posterior surface of the bladder neck, which might reduce potential complications that have been observed after the routine techniques.

Cryotherapy versus high-intensity focused ultrasound for treating prostate cancer: Oncological and functional results. / Crioterapia frente a high intensity focused ultrasound en el tratamiento del cáncer de próstata: resultados oncológicos y funcionales.

CONTEXT AND OBJECTIVE: The increasingly early diagnosis of prostate cancer requires a search for therapeutic alternatives with good oncological results that in turn facilitate a good long-term quality of life. This review analyses 2 minimally invasive therapies for treating localised prostate cancer in terms of oncological and functional results, as well as the complications resulting from the therapies. ACQUISITION OF EVIDENCE: A systematic literature review was conducted of the treatment of localised prostate cancer with 2 ablative techniques as the primary therapy: cryosurgery or cryotherapy and high intensity focused ultrasound (HIFU). We included patients who underwent procedures that included the entire gland, with hemiablation or focal therapy, which were indicated for low to intermediate-risk prostate cancer according to the D'Amico criteria. We excluded patients with high-risk prostate cancer and those who underwent any prior treatment for prostate cancer. SYNTHESIS OF THE EVIDENCE: After conducting the literature search and excluding the studies that did not meet the protocol criteria, we reviewed a total of 14 studies, with a total of 350 patients treated using cryotherapy and 1107 treated with HIFU. All studies were either prospective or retrospective and were not randomised. The patients' mean age was younger than 75 years. Overall, the rate of disease recurrence in the patients treated with cryotherapy varied between 13.2% and 26%, while the rate for those treated with HIFU varied between 7.3% and 67.9%. The overall demonstrated continence at 12 months was 97.6-100% for cryotherapy and 96-100% for HIFU. In terms of sexual potency rates, cryotherapy showed complete potency at 12 months for 86-100% of the patients treated with focal cryotherapy and slightly lower rates for hemiablation (76.9-100%) and total therapy (39%). HIFU showed potency rates of 89%, 52-80% and 33-78% for focal therapy, hemiablation and total therapy, respectively. CONCLUSIONS: Both techniques have comparable functional results, although the somewhat poorer oncological results for HIFU reflect a steeper learning curve, which could lead to its use in centres with high volumes of patients.

[Atrioventricular block in unstable angina. Results of the ARIAM registry]. / Bloqueo auriculoventricular en la angina inestable. Resultados del registro ARIAM.

OBJECTIVE: Describe the frequency of high degree atrioventricular block (HDAVB) in patients with unstable angina (UA), analyze the variables associated with their appearance and evaluate whether HDAVB is independently associated with increased mortality or increased length of ICU stay. DESIGN: Retrospective descriptive study of patients with UA included in the ARIAM registry. SETTING: ICUs from 129 hospitals in Spain. PATIENTS: From June 1996 to December 2003 a total of 14,096 patients were included in the ARIAM registry with a diagnosis of UA. MAIN VARIABLES OF INTEREST: Variables associated with the development of HDAVB, variables associated with the mortality of patients with UA, variables associated with the length of ICU stay of patients with UA. RESULTS: HDAVB frequency was 1%. Development of HDAVB was independently associated with the Killip classification and the presence of sustained ventricular tachycardia or ventricular fibrillation. Crude mortality of patients was significantly increased when HDAVB was present (9% versus 1%, p < 0,001). When adjusted for other variables, HDAVB was not associated with increased mortality. Development of HDAVB in patients with UA was independently associated with an increase in the length of ICU stay (adjusted odds ratio 1.89: 95% confidence interval: 1.33-5.69). CONCLUSIONS: Patients with UA complicated with HDAVB represent a high-risk population with an increased ICU stay.

Mustard allergy confirmed by double-blind placebo-controlled food challenges: clinical features and cross-reactivity with mugwort pollen and plant-derived foods.

BACKGROUND: Mustard IgE-mediated allergy is supposed to be a rare cause of food allergy, and its clinical features and cross-reactivities have not been fully elucidated. METHODS: A prospective study was carried out, recruiting mustard allergic patients, and paired control subjects. A clinical questionnaire was administered, and skin-prick tests (SPT) with panels of aeroallergens and foods, serum extraction for in vitro tests and double-blind placebo-controlled food challenges (DBPCFC) were performed. RESULTS: Thirty-eight mainly adult patients, with 10.5% reporting systemic anaphylaxis, were included in the study [age (mean +/- SD): 21.9 +/- 8.6 years]. DBPCFC were performed in 24 patients, being positive in 14 cases (58.3%). Patients with positive outcome showed significantly greater mustard SPT than those with negative outcome (8.2 +/- 3.7 vs 5.3 +/- 2.4 mm, P <0.05), and the receiver-operating characteristic (ROC) curve analysis yielded a cut-off value for mustard commercial SPT of 8 mm, with a specificity of 90% (95% CI, 55.5-98.3), and a sensitivity of 50% (95% CI, 23.1-76.9). A significant association between mustard hypersensitivity and mugwort pollen sensitization was found (97.4% of patients), with partial cross-reactivity demonstrated by UniCAP System inhibition assays. All patients showed sensitization to other members of Brassicaceae family, and cross-reactivity among them was also confirmed. Moreover, significant associations with nut (97.4%), leguminous (94.7%), corn (78.9%), and Rosaceae fruit (89.5%) sensitizations were also shown. Around 40% of these food sensitizations were symptomatic, including food-dependent exercise-induced anaphylaxis in six patients. CONCLUSIONS: Mustard allergy is a not-uncommon disorder that can induce severe reactions. Significant associations with mugwort pollinosis and several plant-derived food allergies are demonstrated, suggesting a new mustard-mugwort allergy syndrome. A relationship between this syndrome and food-dependent exercise-induced anaphylaxis is also reported.

Altered expression of CD43-hexasaccharide isoform on peripheral T lymphocytes from HIV-infected individuals.

OBJECTIVE: To examine if peripheral T lymphocytes from HIV-infected individuals show abnormalities in the surface expression of CD43, the major sialoglycoprotein of leukocytes. DESIGN: A series of 86 HIV-positive individuals was studied. The subjects, grouped by their peripheral CD4 cell count, were in different stages of the disease as defined by the Centers for Disease Control and Prevention (CDC). METHODS: Peripheral leukocytes and isolated lymphocytes were examined by double and triple immunofluorescence flow cytometric and Western blot analyses with monoclonal antibodies, which discriminate between CD43 isoforms. RESULTS: We found elevated percentages of the surface expression of CD43-hexasaccharide isoform on T lymphocytes from 82 out of 86 individuals tested. Increasing percentages are progressively found in CDC groups 1, 2 and 3 patients. The expression of the molecule is remarkably biased towards the CD8 cell subpopulation. The percentage of cells bearing human leukocyte antigen-DR locus molecules (HLA-DR) is also augmented. Two subsets expressing T305 have been identified: a minor subset that co-expresses HLA-DR and T305; and a second population formed by the majority of T305-positive cells, which lack surface HLA-DR. Finally, we found CD43 bands with altered electrophoretic mobility in lysates from peripheral lymphocytes from all HIV-positive individuals tested. CONCLUSION: The augmented expression of CD43-hexasaccharides and the observed cellular distribution suggest an important regulatory role for this molecule in HIV-specific responses.

Functional expression of CD43 on human natural killer cells.

CD43 is the major leukocyte sialoglyco-protein that plays important functional roles in neutrophils and lymphocytes. However, the expression of CD43 on human natural killer (NK) cells and its participation in the regulation of NK activity has not been studied. We have therefore investigated the expression of CD43 isoforms on human NK cell subpopulations as well as the role of this molecule in NK cell activation and cytotoxicity. We found that CD56bright and CD56dim NK cells express different sialylated forms of CD43, observing that activation of the CD56bright NK cells induces the change of tetrasaccharide O-glycans to hexasaccharide O-glycans on CD43. Cross-linking of the molecule with mAbs results in a metalloprotease-dependent loss of CD43 from the NK cell surface, whereas soluble anti-CD43 mAbs induce a vigorous NK cell proliferation. This property is distinct from T cells, which proliferate after CD43 cross-linking only in the presence of monocytes. Occupancy of the CD43 receptor on NK cells transduces specific signals, leading to enhanced killing activity and tyrosine phosphorylation and de-phosphorylation of several substrates. We therefore propose that CD43 significantly contributes to the regulation of the NK cell function by participating in the control of effector/target interactions and, if pertinent, by transducing activation signals.

Defective actin reorganization and polymerization of Wiskott-Aldrich T cells in response to CD3-mediated stimulation.

The Wiskott-Aldrich syndrome (WAS) is a severe immunodeficiency and platelet deficiency disease arising from mutation(s) in the WASP gene, which in normal cells encodes an intracellular protein able to interact with other proteins relevant to the control of cytoskeleton organization. Immunodeficiency is mainly due to T-cell progressive malfunction. Salient defects of WAS T cells are a CD3-restricted impairment in proliferative responses and cytoskeletal abnormalities, including the frequent appearance of T cells with atypical morphology. We have investigated the possibility that the CD3-restricted defect and some of the cytoskeletal defects of WAS T cells are linked. For this purpose, we immortalized by means of infection with Herpesvirus Saimiri a number of previously described allospecific WAS T-cell lines. The resulting cells preserve the surface, molecular, and functional phenotypes of their parental lines, including a negligible WASP mRNA expression as well as the CD3-restricted defect and cytoskeleton abnormalities. Results show that, in CD3-stimulated WAS T cells, the pattern of temporal changes in cell shape and F-actin distribution is substantially different from that of control cells. Furthermore, polymerization of actin, a critical step in the CD3-mediated cytoskeleton reorganization, does not occur in WAS T-cell lines in response to OKT3 stimulation. In conclusion, our data link both CD3 and cytoskeletal defects in WAS T cells, strongly suggesting that cytoskeleton abnormalities are an underlying cause for WAS immunodeficiency.