Leptomeningeal carcinomatosis from squamous cell carcinoma of the supraglottic larynx

Leptomeningeal carcinomatosis is an uncommon but devastating form of metastatic spread. To our knowledge, only 16 cases originating from a head and neck cancer have been reported. We describe the first case of a patient with leptomeningeal carcinomatosis arising from a laryngeal squamous cell carcinoma. Shortly after completing treatment for an advanced supraglottic laryngeal cancer, this 63‐year‐old man presented with lower limb neurological symptoms and signs. Radiological and cytological evidence of leptomeningeal carcinomatosis of the distal spinal canal was identified. He was treated with intrathecal methotrexate and palliative radiotherapy. Although his pain improved, his lower limb weakness worsened. He died 3 weeks after completing radiotherapy. Presumed mode of spread was via the haematogenous route. The natural history and management of leptomeningeal carcinomatosis are discussed. Clinicians should be aware of the uncommon possibility of leptomeningeal carcinomatosis in a patient presenting with an appropriate constellation of symptoms and signs, and a past history of cancer.     

Mayan alleles of the HLA-DRB1 major histocompatibility complex might contribute to the genetic susceptibility to systemic lupus erythematosus in Mexican patients from Tapachula,Chiapas

Clinical Rheumatology - Systemic lupus erythematosus (SLE) is the prototypic autoimmune disease that disrupts numerous immunity mechanisms with the potential to exert damage to any organ or tissue....     

Nutritional status and wound severity of overweight and obese patients with venous leg ulcers: A pilot study

Obesity is a chronic disease that is linked to the presence of numerous chronic illnesses, including venous disease. Venous disease can lead to chronic wounds, which may be exacerbated by vitamin, mineral, and macro-nutritional deficiencies. A cross-sectional observational design was used to examine the nutritional status of patients with chronic venous leg ulcers (VLUs) who are overweight or obese and to explore the relationship between nutritional status and severity of venous ulceration. Nutritional status was evaluated using anthropometric measurements, nutrient analysis from a 3-day dietary intake log, serum albumin, vitamins A and C, and zinc levels. Wound severity was assessed using the Leg Ulcer Measurement Tool (LUMT). Eight patients participated; six patients were men, and all eight patients were more than 50 years of age. Patients had an average daily caloric intake below their estimated caloric need. When compared with recommended daily intake levels, dietary nutrient intake was suboptimal for protein, vitamin C, and zinc. Serum levels were below normal for at least one of these nutrients in six patients. A positive correlation was found only between serum albumin, average daily intake, and percent recommended daily intake of protein (r(s) = 0.93, P = .003). An inverse relationship was found between LUMT score and serum vitamin A levels (r(s) = -0.83, P = .01), and a positive correlation was observed between LUMT score and serum vitamin C (r(s) = 0.74, P = .04). No clear relationships were shown among serum zinc, albumin, and LUMT scores. Overweight and obese patients with VLU show nutritional deficits that are similar to those of the broader population of patients with leg ulcers. The relationships found between vitamins A and C and leg ulcer severity warrant further exploration. The nutritional differences in the study need to be examined in a larger sample of overweight and normal-weight patients to determine whether overweight patients are at greater risk for prolonged VLU because of poor nutrition than non-overweight patients.     

Role of functional MR in determining language dominance in epilepsy and nonepilepsy populations: a Bayesian analysis

PURPOSE: To determine the role of functional magnetic resonance (MR) imaging in assessing hemispheric language dominance in epilepsy and nonepilepsy populations. MATERIALS AND METHODS: A Bayesian analysis study was performed. The study was based on data from the published literature; thus, institutional review board approval was not required. The literature was reviewed to obtain pretest probabilities and likelihood ratios, which were analyzed to determine the posttest probability of language dominance by using functional MR imaging. Pretest probabilities of different hand dominances in epilepsy and nonepilepsy populations were obtained from the largest studies available in the literature. Likelihood ratios were derived from the sensitivity and specificity of functional MR imaging by using electrocortical stimulation (ECS) and the Wada test as reference standards. RESULTS: Likelihood ratios for functional MR in determining language dominance were 9.3 and 12.3 with ECS and the Wada test as reference standards, respectively. Use of functional MR increased the final posttest probabilities of hemispheric language dominance in epilepsy and nonepilepsy populations. In the nonepilepsy population, regardless of hand dominance, there was very high posttest probability (>or=96%) of a correlation between functional MR hemisphere activation and definite left-hemisphere language dominance. In the epilepsy population with right-hand dominance or ambidexterity, there was very high posttest probability (>or=95%) of a correlation between functional MR hemisphere activation and definite left-hemisphere language dominance. In the left-handed nonepileptic subjects, there was high posttest probability (81%-83%) of a correlation between functional MR hemisphere activation and definite right-hemisphere language dominance. In the left-handed epilepsy population, there was high posttest probability (80%-97%) of a correlation between functional MR hemisphere activation and definite left-hemisphere language dominance. In the epilepsy population with ambidexterity, there was high posttest probability (80%-87%) of correlations between functional MR hemisphere activation and both definite right-hemisphere and bilateral language dominance. CONCLUSION: Use of functional MR increases importantly the posttest probabilities of hemispheric language dominance in multiple subgroups of individuals with and without epilepsy.     

Proapoptotic activity of cell-permeable anti-Akt single-chain antibodies

We developed anti-Akt1 single-chain antibodies (scFv) by panning a mouse phage-displayed scFv recombinant antibody library. Recombinant scFv that bound glutathione S-transferase (GST)-Akt1 were screened for their ability to inhibit Akt activity in vitro in a kinase reaction containing human recombinant Akt1 and an Akt/serum glucocorticoid-inducible kinase (SGK) substrate. Michaelis-Menten analysis of kinase inhibition by a selected scFv was consistent with scFv-mediated competition with enzyme's substrate for the catalytic site of Akt. To generate a membrane-permeable version of the anti-Akt1 scFv, the scFv gene was subcloned into a GST expression vector carrying a membrane-translocating sequence (MTS) from Kaposi fibroblast growth factor. A purified GST-anti-Akt1-MTS fusion protein accumulated intracellularly in 293T, BT-474, and PyVmT cells in a dose- and time-dependent fashion. Intracellular accumulation correlated temporally with inhibition of p-Ser(473) Akt and GSK-3alpha/beta phosphorylation, suggesting that Ser(473) is an Akt autophosphorylation site. Phosphorylated (activated) phosphoinositide-dependent kinase 1, mitogen-activated protein kinase, p38, and HER2 (erbB2) were not affected, supporting Akt kinase specificity for the inhibitory scFv. Exogenously expressed constitutively active Akt2 and Akt3 were also inhibited in vitro by the anti-Akt1 fusion protein. Furthermore, GST-anti-Akt1-MTS induced apoptosis in three cancer cell lines that express constitutively active Akt. Finally, systemic treatment with the anti-Akt scFv reduced tumor volume and neovascularization and increased apoptosis in PyVmT-expressing transgenic tumors implanted in mouse dorsal window chambers. Thus, GST-anti-Akt1-MTS is a novel cell-permeable inhibitor of Akt, which selectively inhibits Akt-mediated survival in intact cells both in vitro and in vivo.     

Prospective clinical trial comparing outcome measures between Furlow and von Langenbeck Palatoplasties for UCLP

The goal of this prospective randomized clinical trial was to compare 2 cohorts of standardized cleft patients with regard to functional speech outcome and the presence or absence of palatal fistulae. The 2 cohorts are randomized to undergo either a conventional von Langenbeck repair with intravelar velarplasty or the double-opposing Z-plasty Furlow procedure. A prospective 2 × 2 × 2 factorial clinical trial was used in which each subject was randomly assigned to 1 of 8 different groups: 1 of 2 different lip repairs (Spina vs. Millard), 1 of 2 different palatal repair (von Langenbeck vs. Furlow), and 1 of 2 different ages at time of palatal surgery (9-12 months vs. 15-18 months). All surgeries were performed by the same 4 surgeons. A cul-de-sac test of hypernasality and a mirror test of nasal air emission were selected as primary outcome measures for velopharyngeal function. Both a surgeon and speech pathologist examined patients for the presence of palatal fistulae. In this study, the Furlow double-opposing Z-palatoplasty resulted in significantly better velopharyngeal function for speech than the von Langenbeck procedure as determined by the perceptual cul-de-sac test of hypernasality. Fistula occurrence was significantly higher for the Furlow procedure than for the von Langenbeck. Fistulas were more likely to occur in patients with wider clefts and when relaxing incisions were not used.     

Skin-derived micro-organs induce angiogenesis in rabbits

We have recently reported an alternative cell therapy approach to induce angiogenesis. The approach is based on small organ fragments--micro-organs (MOs)--whose geometry allows preservation of the natural epithelial/mesenchymal interactions and ensures appropriate diffusion of nutrients and gases to all cells. We have shown that lung-derived MOs, when implanted into hosts, transcribe a wide spectrum array of angiogenic factors and can induce an angiogenic response that can rescue experimentally induced ischemic regions in mice. From a clinical perspective, skin-derived MOs are particularly appealing as they could readily be obtained from a skin biopsy taken from the same target patient. In the present work we have investigated the angiogenesis-inducing capacity of rabbit and human skin-derived micro-organs in vitro and in vivo. Rabbit skin MOs were implanted into homologous adult rabbits and human skin MOs were encapsulated and implanted into xenogenic mice. Skin-derived MOs, as lung-derived MOs, were found to secrete a whole array of angiogenic factors and to induce a powerful angiogenic response when implanted back into animals. We believe the approach presented suggests a novel, efficacious and simple approach for therapeutic angiogenesis.     

Nasalance and nasality at experimental velopharyngeal openings in palatal prosthesis: a case study

The use of prosthetic devices for correction of velopharyngeal insufficiency (VPI) is an alternative treatment for patients with conditions that preclude surgery and for those individuals with a hypofunctional velopharynx (HV) with a poor prognosis for the surgical repair of VPI. Understanding the role and measuring the outcome of prosthetic treatment of velopharyngeal dysfunction requires the use of tools that allow for documenting pre- and post-treatment outcomes. Experimental openings in speech bulbs have been used for simulating VPI in studies documenting changes in aerodynamic, acoustic and kinematics aspects of speech associated with the use of palatal prosthetic devices. The use of nasometry to document changes in speech associated with experimental openings in speech bulbs, however, has not been described in the literature. Objective: This single-subject study investigated nasalance and nasality at the presence of experimental openings drilled through the speech bulb of a patient with HV. Material and Methods: Nasometric recordings of the word "pato" were obtained under 4 velopharyngeal conditions: no-opening (control condition), no speech bulb, speech bulb with a 20 mm2 opening, and speech bulb with 30 mm2 opening. Five speech-language pathologists performed auditory-perceptual ratings while the subject read an oral passage under all conditions. Results: Kruskal-Wallis test showed significant difference among conditions (p=0.0002), with Scheffé post hoc test indicating difference from the no-opening condition. Conclusion: The changes in nasalance observed after drilling holes of known sizes in a speech bulb suggest that nasometry reflect changes in transfer of sound energy related to different sizes of velopharyngeal opening.