Distinct muscle imaging patterns in myofibrillar myopathies.

OBJECTIVE: To compare muscle imaging findings in different subtypes of myofibrillar myopathies (MFM) in order to identify characteristic patterns of muscle alterations that may be helpful to separate these genetic heterogeneous muscular disorders. METHODS: Muscle imaging and clinical findings of 46 patients with MFM were evaluated (19 desminopathy, 12 myotilinopathy, 11 filaminopathy, 1 alphaB-crystallinopathy, and 3 ZASPopathy). The data were collected retrospectively in 43 patients and prospectively in 3 patients. RESULTS: In patients with desminopathy, the semitendinosus was at least equally affected as the biceps femoris, and the peroneal muscles were never less involved than the tibialis anterior (sensitivity of these imaging criteria to detect desminopathy in our cohort 100%, specificity 95%). In most of the patients with myotilinopathy, the adductor magnus showed more alterations than the gracilis muscle, and the sartorius was at least equally affected as the semitendinosus (sensitivity 90%, specificity 93%). In filaminopathy, the biceps femoris and semitendinosus were at least equally affected as the sartorius muscle, and the medial gastrocnemius was more affected than the lateral gastrocnemius. The semimembranosus mostly showed more alterations than the adductor magnus (sensitivity 88%, specificity 96%). Early adult onset and cardiac involvement was most often associated with desminopathy. In patients with filaminopathy, muscle weakness typically beginning in the 5th decade of life was mostly pronounced proximally, while late adult onset (>50 years) with distal weakness was more often present in myotilinopathy. CONCLUSIONS: Muscle imaging in combination with clinical data may be helpful for separation of distinct myofibrillar myopathy subtypes and in scheduling of genetic analysis.

Dysferlin expression in monocytes: a source of mRNA for mutation analysis.

Dysferlin protein is expressed in peripheral blood monocytes. The genomic analysis of the DYSF gene has proved to be time consuming because it has 55 exons. We designed a mutational screening strategy based on cDNA from monocytes to find out whether the mutational analysis could be performed in mRNA from a source less invasive than the muscle biopsy. We studied 34 patients from 23 families diagnosed with dysferlinopathy. The diagnosis was based on clinical findings and on the absence of protein expression using either immunohistochemistry or Western blot of skeletal muscle and/or monocytes. We identified 28 different mutations, 13 of which were novel. The DYSF mutations in both alleles were found in 30 patients and only in one allele in four. The results were confirmed using genomic DNA in 26/34 patients. This is the first report to furnish evidence of reliable mutational analysis using monocytes cDNA and constitutes a good alternative to genomic DNA analysis.

SMN2 copy number predicts acute or chronic spinal muscular atrophy but does not account for intrafamilial variability in siblings.

Spinal muscular atrophy (SMA) is an autosomal recessive disorder that affects motor neurons. It is caused by mutations in the survival motor neuron gene 1 (SMN1). The SMN2 gene, which is the highly homologous SMN1 copy that is present in all the patients, is unable to prevent the disease. An SMN2 dosage method was applied to 45 patients with the three SMA types (I-III) and to four pairs of siblings with chronic SMA (II-III) and different phenotypes. Our results confirm that the SMN2 copy number plays a key role in predicting acute or chronic SMA. However, siblings with different SMA phenotypes show an identical SMN2 copy number and identical markers, indicating that the genetic background around the SMA locus is insufficient to account for the intrafamilial variability. In our results, age of onset appears to be the most important predictor of disease severity in affected members of the same family. Given that SMN2 is regarded as a target for potential pharmacological therapies in SMA, the identification of genetic factors other than the SMN genes is necessary to better understand the pathogenesis of the disease in order to implement additional therapeutic approaches.

Timing of chemoradiotherapy and patient selection for locally advanced nasopharyngeal carcinoma.

AIMS: Predictors of outcome after radiotherapy alone for nasopharyngeal carcinoma (NPC) are now available from several retrospective studies. On the basis of these, it is theoretically possible to separate patients at risk of local failure from patients at risk of distant metastases (DM). According to classical principles of chemoradiotherapy timing, patients at risk of local failure would benefit mostly from concomitant chemoradiotherapy, whereas patients at risk distantly would benefit from sequential combinations. MATERIALS AND METHODS: We reviewed the literature on combined chemoradiotherapy treatment for nasopharyngeal carcinoma to assess whether timing of combined treatment matches pattern of failure. RESULTS: Available data show a significant overlap of activity, sequential treatments reducing local failure and concomitant treatments reducing DM. Therefore, in the individual patient, the strict adoption of traditional risk profiles in therapeutic decision-making may not fully exploit all the potential therapeutic effects derived from the maximal association of both sequential and concomitant therapies. CONCLUSION: Whether such combination is clinically worthwhile in every patient with locoregionally advanced nasopharyngeal carcinoma needs prospective validation, because of the high toxicity of this modality.

[Angioplasty and stenting in severe stenosis of basilar artery refractory to pharmacotherapy]. / Angioplastia y stent en la estenosis severa de arteria basilar refractaria al tratamiento farmacológico.

Stenoses in the posterior cerebral circulation often have a bad prognosis. There may be a high rate of morbi-mortality and recurrences of ischemic events in this territory. Currently we have no evidence or consensus about what the best pharmacological option is for these patients. We report a case of a 75 year old woman with sever stenosis of the proximal part of the basilar artery with recurrent transient ischemic events unresponsive to different combinations of antiagregant and anticoagulant treatments. A percutaneous transluminal angioplasty with the addition of a stent in the basilar artery was performed successfully. At present, there are few studies and a low number of patients treated by this technique. The results obtained are promising, with a low rate of morbi-mortality, the most frequent complications being embolization of the atherosclerotic lesion, dissection, rupture or restenosis.

Angioplastia y stent en la estenosis severa de arteria basilar refractaria al tratamiento farmacológico / Angioplasty and stenting in severe stenosis of basilar artery refractary to pharmacotherapy

Las estenosis en el territorio vascular posterior implican un mal pronóstico, tanto por la elevada morbimortalidad como por el alto índice de recurrencia de eventos isquémicos en este territorio. En el momento actual no existe una clara evidencia ni un consenso sobre qué tratamiento se debe administrar a estos pacientes. Presentamos el caso de una paciente de 75 años con una estenosis severa de la arteria basilar sintomática, en forma de accidente isquémico transitorio de repetición a pesar de las diversas combinaciones farmacológicas aplicadas. Dicha paciente se sometió con éxito a una angioplastia transluminal percutánea con la colocación de un stent en la arteria basilar. Actualmente existen pocos estudios y un bajo número de pacientes tratados mediante esta técnica. Los resultados obtenidos son prometedores habiendo un escaso índice de morbimortalidad, siendo las complicaciones más frecuentes la embolización de material de la placa, disecciones, ruptura y reestenosis (AU)

Inflammation in dysferlin myopathy: immunohistochemical characterization of 13 patients.

Inflammation was detected in 9 of 13 patients with different phenotypes of dysferlin myopathy. Endomysial or perivascular infiltrates consisted of 11.1% +/- 6.6% CD8(+) cells, 40.6% +/- 22.8% CD4(+) cells, 36.7% +/- 23.7% macrophages, and no B cells. Major histocompatibility complex class I was not upregulated in normal muscle fibers. In young patients with sporadic proximal weakness, very high creatine kinase levels, necrotic fibers and inflammation in the muscle biopsy, a diagnosis of dysferlin myopathy should be considered.

Homeostasis of naive and memory T cell subpopulations in peripheral blood and lymphoid tissues in the context of human immunodeficiency virus infection.

To understand the nature of naive and memory T cell depletion in human immunodeficiency virus (HIV) immunopathogenesis, their homeostasis in peripheral blood (PB) and lymph node (LN) compartments of HIV-infected patients was examined. Although the percentage of naive CD4+ cells was higher in LN than in PB mononuclear cells (LNMC and PBMC, respectively), the memory cells were higher in PBMC than in LNMC. The ratio of naive:memory CD4+ cells from PB positively correlated with that in LNs and with the absolute CD4+ cell counts and recall antigen responses, and the ratio inversely correlated with the cellular virus load from the corresponding compartment. These findings indicate that although the pattern of naive and memory cells in the LN and PB compartments appear divergent, their relationship is nonrandom and is significant. The naive&rcolon;memory ratio in PB appears to reflect the lymphoid microenvironment and may potentially be useful as a surrogate marker for treatment efficacy and immune reconstitution.

The role of topical antibiotic prophylaxis in patients undergoing contaminated head and neck surgery with flap reconstruction.

OBJECTIVES/HYPOTHESIS: Patients undergoing contaminated head and neck surgery with flap reconstruction have wound infection rates of 20% to 25% with parenteral antibiotic prophylaxis. Studies suggest that perioperative antimicrobial mouthwash reduces oropharyngeal flora and may prevent wound infections. We hypothesized that the addition of topical antibiotics to a parenteral prophylactic regimen would reduce the incidence of wound infection in these high-risk patients. STUDY DESIGN: We performed a randomized, prospective clinical trial. METHODS: Patients received either 1) parenteral piperacillin/tazobactam (3.375 g every 6 hours for 48 h) or 2) parenteral piperacillin/tazobactam plus topical piperacillin/tazobactam administered as a mouthwash immediately before surgery and once a day for 2 days postoperatively, with piperacillin/tazobactam added to the intraoperative irrigation solution. The wounds of all patients were evaluated daily using predefined objective criteria. RESULTS: Sixty-two patients met inclusion criteria and were enrolled in the study. The overall wound infection rate was 8.1% (95% confidence interval [CI], 2.7%-17.8%). Two of 31 patients (6.4%) who received parenteral antibiotics alone developed a wound infection compared with 3 of 31 patients (9.7%) randomly assigned to receive topical plus parenteral antibiotics. This difference was not statistically significant (P = >.05). Infection rate was not associated with flap type (rotational vs. free tissue transfer), mandibular reconstruction, age, gender, tumor site, stage, surgical duration, or blood loss. CONCLUSIONS: These results suggest that piperacillin/tazobactam is a highly effective antibiotic for prevention of wound infection in patients undergoing flap reconstruction following contaminated head and neck surgery. However, the addition of topical piperacillin/tazobactam does not appear to enhance the prophylactic benefit of parenteral antibiotics alone.

Chemokine/CD4 receptor density ratios correlate with HIV replication in lymph node and peripheral blood of HIV-infected individuals.

OBJECTIVES: Lymphoid tissue is a major reservoir for virus replication in HIV-infected subjects. The relationship of CCR5 and CXCR4 coreceptor density and HIV replication in peripheral blood mononuclear cells (PBMC) and lymph node (LN) mononuclear cells (LNMC) of HIV-infected subjects was examined. METHODS: PBMC and cervical LNMC from 12 HIV-infected patients were examined for virological and immunological parameters including chemokine receptor density, HIV plasma and cellular viral load, coreceptor usage and CD38/HLA-DR expression. RESULTS: The number of CCR5 and CXCR4 molecules on CD4 lymphocytes in the LN were significantly higher than in PBMC. In contrast the number of CD4 molecules/CD4 T cell was higher in PBMC than in LNMC. The CXCR4/CD4 and CCR5/CD4 ratios in the LN were significantly higher than in the PBMC. This was associated with a cellular viral load in the LN that was approximately 110-fold higher than in PBMC. The absolute number of coreceptor molecules per cell did not correlate with the viral load. However, the CCR5/CD4 and CXCR4/CD4 ratios in the LN positively correlated with HIV cellular and plasma RNA. Characterization of the viral isolates suggested an association between clinical isolates using a distinct coreceptor and the upregulation of the corresponding chemokine receptor. CONCLUSIONS: The ratios of chemokine receptors to CD4 molecules in CD4 T cells from LN is higher than in PBMC and may account for the relative difference in cellular viral load in these compartments. Additionally, the coreceptor/CD4 ratios, particularly in the lymphoid tissue, were highly related to HIV replication.

[Crossed aphasia: description of a case]. / Afasia cruzada: descripción de un caso.

We describe a new case of crossed aphasia in a right-handed patient with a right hemispheric lesion. A right-handed man, 76 year-old, developed a sudden left hemiparesis with sensitive impairment and mutism. He has neither family history of left handeness or ambidexterity or vascular risk factors. CT cerebral scan showed a large infarct of the middle cerebral artery on the right side, with haemorrhagic suffusion. Cerebral MRI and EEG-cartography confirmed the indemnity of the left hemisphere. Aphasia studies confirmed a mutism with spared verbal comprehension, but alexia was present. A year later, left hemiparesis was recovered but aphasia remained. Crossed aphasia is rarely seen. It is caused by a right hemispheric lesion in right-handed subjects. Fluency is most commonly impaired. At onset, mutism is the common symptom, which evolves to expressive aphasia. Several hypothesis have been raised about the possible mechanisms involved. The few number of PET or SPECT studies performed in these patients have disclosed extensive areas of hypometabolism in the right hemisphere, that exceed the size of the image observed with CT scan or MRI.

Afasia cruzada: descripción de un caso / Crossed aphasia: description of one case

El objetivo del trabajo es la descripción de un nuevo caso de afasia cruzada en un paciente diestro con lesiones en el hemisferio derecho. Se trata de un varón de 76 años, diestro, sin antecedentes familiares de zurdera y sin factores de riesgo vascular, que presentó de forma brusca hemiparesia izquierda con compromiso sensitivo y cuadro de mutismo. La TC craneal confirmó la existencia de un extenso infarto isquémico con componente hemorrágico en el territorio córtico-subcortical de la arteria cerebral media derecha. El estudio mediante RM y la cartografía-EEG confirmaron la indemnidad del hemisferio izquierdo. Los tests de afasia pusieron de manifiesto un cuadro de mutismo con comprensión preservada para el lenguaje oral, pero alterada para el escrito. El paciente recuperó progresivamente el déficit motor, persistiendo una grave afasia de expresión. La afasia cruzada es una alteración del habla poco frecuente. Se produce por una lesión hemisférica derecha en personas diestras y suele manifestarse por trastornos de la fluencia, con mutismo inicial que evoluciona hacia una afasia motora. Se han planteado diversas hipótesis referentes a los mecanismos responsables. Los estudios con PET o SPECT han demostrado zonas de hipometabolismo en el hemisferio derecho, que sobrepasan la lesión demostrada por TC o RNM (AU)

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Prevalence of herpes simplex virus in malignant laryngeal lesions.

OBJECTIVE: To determine the prevalence of herpes simplex virus (HSV) in malignant laryngeal lesions. STUDY DESIGN: Retrospective review. MATERIALS AND METHODS: Paraffin-embedded, histologically confirmed specimens containing benign laryngeal lesions, squamous cell carcinoma of the larynx, and squamous cell carcinoma of the oral cavity were identified from archived surgical specimens. Biopsies of normal-appearing oral cavity tissue were also obtained from fresh-frozen cadavers. These tissues were analyzed for the presence of HSV DNA using polymerase chain reaction techniques. Patient charts were reviewed for patient demographics, risk factors, stage, clinical course, treatment, and outcome. RESULTS: HSV was detected in nine laryngeal squamous cell carcinomas (75%) and in none of the benign laryngeal lesions (P = .0001). HSV was also found in three oral cavity squamous cell carcinomas (25%) and in none of the controls (P = .049). CONCLUSION: HSV is more prevalent in squamous cell carcinoma of the larynx and oral cavity than in their respective control groups, suggesting a role for carcinogenesis. HSV is more prevalent in squamous cell carcinoma of the larynx than of the oral cavity. Further studies to determine the role of HSV as a cocarcinogen and its interrelationship with other environmental factors in laryngeal cancer are warranted.

FNAC in the diagnosis of recurrent dermatofibrosarcoma protuberans of the forehead. A case report.

BACKGROUND: Dermatofibrosarcoma protuberans is a rare cutaneous soft tissue tumor of intermediate malignant potential with a characteristic tendency for recurrence. Metastases are unusual. This tumor usually occurs in the trunk and extremities and, infrequently, on the face and scalp. Its cytologic appearance on fine needle aspiration has only been rarely reported. It is characterized by numerous fibroblastlike cells that arrange as single cells or in clusters of spindle cells arrayed in a storiform pattern. CASE: A 42-year-old male presented with a one-year history of an enlarging left forehead mass (lateral brow) that was adjacent to an old surgical scar. Fine needle aspiration revealed a low grade spindle cell neoplasm morphologically identical to a dermatofibrosarcoma protuberans excised 15 years earlier, indicating tumor recurrence. CONCLUSION: Distinguishing dermatofibrosarcoma protuberans from other spindle cell tumors and fibrohistiocytic lesions may pose significant challenges to the pathologist. However, in the appropriate clinical setting and applying strict diagnostic criteria, fine needle aspiration cytology is a reliable tool in establishing the diagnosis of this neoplasm.

Laryngeal framework surgery for the management of aspiration.

BACKGROUND: During the past decade, laryngeal framework surgery has become the treatment of choice for the management of adductor paralysis of the vocal fold. The primary impetus for the use of this technique has been on the rehabilitation of voice. The purpose of this study was to ascertain the effectiveness of laryngeal framework surgery, including medialization laryngoplasty with silicone (MLS), with or without arytenoid adduction (AA), on eliminating aspiration, improving diet, and aiding in the subsequent decannulation of individuals with glottic insufficiency secondary to vocal fold palsy. METHODS: A retrospective chart review was performed on all patients initially seen with vocal cord paralysis who were treated with laryngeal framework surgery from June 1992 to April 1996. The study comprised 70 patients, including 31 women and 39 men, with a median age of 57 years. Clinical information was obtained regarding the etiology of the lesion, characteristics of the vocal cord deficit, history of aspiration, the presence of other neurologic deficits or concurrent pulmonary disease, treatment, and outcome. To determine the effectiveness of MLS, with or without AA, we assessed the final outcome regarding the presence and degree of aspiration, diet, history of aspiration pneumonia, and decannulation. RESULTS: Seventy patients underwent 77 MLS (three bilateral, four revisions), and 21 AA. Decreased aspiration was obtained in 96% of our patients. Seventy-five percent of those patients who had required a tracheotomy were decannulated. CONCLUSIONS: These results support the use of laryngeal framework surgery for the effective treatment of aspiration in selected patients initially seen with deficits of the glottic closure secondary to vocal fold paralysis or paresis.

[Oral anticoagulation in the secondary prevention of cerebrovascular disease. Long-term follow-up of 169 patients]. / Anticoagulación oral en la prevención secundaria de la enfermedad vascular cerebral. Seguimiento a largo plazo de 169 pacientes.

INTRODUCTION: Although the indications for oral anticoagulation (AO) in the treatment of cerebral vascular disease (CVD) are well established, their potential side effects continue to give cause for worry. OBJECTIVES: To describe the complications and ischemic relapses in patients treated with AO for secondary prevention of CVD of cardiac embolic origin. PATIENTS AND METHODS: We included 169 patients with embologenic cardiopathy who, following an CVD, were treated with AO and followed-up at our medical centre for at least three months. We recorded their past clinical history and risk factors, occurrence of vascular relapses (VR), complications involving hemorrhage (CH), and data regarding course and follow-up. RESULTS: During an average follow-up of 50.3 months of a total of 707.9 patient/years, 20 VR (2.8% per year) were recorded; 15 of these were cerebro-vascular and mainly mild. We recorded 59 CH in 41 patients (8.3% per year) of which 6 were considered to be major. There was a 30% drop-out rate from follow-up at our centre, mainly due to death from other causes or to change of referral centre. CONCLUSIONS: There is a low incidence of relapse and of complications (usually mild) following AO for the secondary prevention of CVD of cardio-embolic origin. Efficacy and security are maintained in the long term.

Repair of laryngeal fractures using adaptation plates.

BACKGROUND: There is a need to evaluate the effectiveness of laryngeal fracture repair using rigid adaptation plates. METHODS: A retrospective chart review of patients undergoing open repair of laryngeal fractures using metal alloy plates, from 1987 to 1995, was performed. Postoperative airway, deglutition, and voice were assessed. Postoperative follow-up ranged from 1 to 58 months (median, 27 months). All 10 patients sustained blunt or penetrating laryngeal trauma. After patients were resuscitated according to the ABC principles recommended by the American College of Surgeons, each underwent open repair of laryngeal fractures using rigid adaptation plates. RESULTS: Outcome was measured by perceptual analysis of the postoperative airway, swallowing, and voice, as well as biocompatibility. Ten patients underwent repair and stabilization of the larynx using adaptation plates. Nine patients sustained blunt trauma, and one patient sustained penetrating trauma. Voice was subjectively graded as good if it resembled the preinjury status, fair if it differed, and poor if it represented aphonia, whisper, or unintelligible speech. Airway was graded as good if it resembled preinjury status, fair if mild exercise intolerance or aspiration existed, and poor if the patient could not be decannulated. Nine patients had a good airway following repair, and six of seven patients requiring tracheotomy were decannulated. All patients tolerated the plates well and suffered no surgical complications. CONCLUSION: Repair of the laryngeal framework using adaptation plates provides adequate, immediate stabilization with restoration of function and is an alternative to traditional methods of repair.

Multiple endocrine involvement in two pediatric patients with Kearns-Sayre syndrome.

We present 2 cases of progressively severe Kearns-Sayre syndrome (KSS) with multisystemic affectation and atypical endocrine and cutaneous features, a 16-year-old patient (case 1) and a 5-year-old patient (case 2). Endocrine studies showed high glucose and glycohemoglobin concentrations with normal pancreatic reserve and low values of ACTH, cortisol, LH and FSH in case 1. Normal ACTH values with low concentrations of cortisol and PTH were observed in case 2. Southern blot analysis and PCR amplification revealed the presence of a deletion of approximately 6.7 kb in the mitochondrial DNA of both patients. Endocrinological studies suggest that adrenal insufficiency may be an additional feature of KSS that worsens the clinical evolution of the patients. In spite of a normal pancreatic reserve, insulin therapy should be considered in patients with diabetes mellitus of mitochondrial origin.