Modified Campbell diagram to assess respiratory muscle action in speech

Ten normal and four moderate to severe stutterers participated in the study. Pleural (Ppl) and abdominal (Pab) pressure was studied using oesophageal and gastric balloon catheter systems and VL (VL) was studied using magnetometry. The classical Campbell diagram was modified by plotting Pab versus VL. In a preliminary study we determined whether a surrogate curve could be substituted for the true curve in the Campbell diagram. We obtained true relaxation curves in six subjects. We obtained surrogate chest wall relaxation curves by joining the Pab value at functional residual capacity (FRC) to a point on the dynamic expiratory Pab, VL curve where Pab had decreased to half its maximum inspiratory excursion. In order to obtain the mirror image of the elastic recoil curve of the lung subjects breathed slowly from FRC to total lung capacity. Dynamic Pab, VL and Ppl, VL measurements during quiet breathing and speech were superimposed on static lung and chest wall curves. The simultaneous plot of Ppl and Pab provided a continuous measure of transdiaphragmatic pressure as a function of VL. We inferred non-diaphragmatic muscle recruitment vis-à-vis the diaphragm by the relationship of Pab to Ppl and Pab to the relaxation curve. We compared dynamic Ppl during phonation with that during breath-holding with the glottis open at the same VL, as an estimate of subglottic pressure (Psg). Analysis of variance testing showed that the true, surrogate and predicted relaxation slopes were not significantly different. The strategies that stutterers used to speak were either higher or lower VL than normal subjects and they had a different pattern of respiratory muscle recruitment. Stutterers were unable to achieve the appropriate degree of recruitment to develop and maintain a normal Psg for conversational speech and this contributed to dysfluency. We conclude that the quiet breathing loops can provide a reasonable approximation to the relaxation curve in normal healthy subjects and that modifications to the Campbell diagram provide useful means of measuring Psg and assessing respiratory muscle recruitment patterns.     

How do neurons degenerate in transmissible spongiform encephalopathies?

Neuroaxonal dystrophy is a feature of neuronal degeneration encountered in all subacute spongiform virus encephalopathies including scrapie and Creutzfeldt-Jakob disease (CJD). By immunohistochemical techniques, the accumulation of 200 kDa neurofilament protein was demonstrated in affected neurites in human CJD. These neurites exhibited the ultrastructural features of dystrophic neurites encountered in other neurodegenerative disorders, particularly Alzheimer's disease. These findings support the hypothesis that impairment of slow axoplasmic transport is a common pathogenetic mechanism for CJD and many other neurodegenerative conditions.     

Microsurgical anatomy of the foramen of Luschka in the cerebellopontine angle,and its vascular supply

Cerebellopontine angle and vascular supply of adjacent brainstem and cerebellum are susceptible to compression and eventual damage by tumors. Delicate and complicated neurosurgical operations in the cerebellopontine angles of the brainstem, where lateral recesses of fourth ventricle empty, are abundant especially operations in which foramina of Luschka are used as possible access to the floor of the fourth ventricle. So awareness and knowledge of the normal anatomical features of the region is valuable for neurosurgeons. Arteries of 40 human cerebella were injected with colored gelatin to investigate the microsurgical anatomy around the foramen of Luschka in the cerebellopontine angle. Two compartments of the foramen of Luschka were distinguished, choroidal part and the patent part. Seventy-four (92.5%) of foramina were open and only 6 (7.5%) foramina were closed. The mean distance between the foramen of Luschka and the anterior inferior cerebellar artery was 3.90 mm on the left side and 3.89 on the right side. The distance from the posterior inferior cerebellar artery was 7.08 and 5.81 mm to the left and right foramina of Luschka, respectively. In ten cases, tortuous vertebral artery was occupying the left cerebellopontine angle space and the foramen of Luschka.     

Potential breakthroughs with investigational drugs for hairy cell leukemia

Introduction: Hairy cell leukemia (HCL) is a rare subtype of B-cell chronic lymphoid leukemia. It is characterized by progressive pancytopenia, splenomegaly and infiltrations of the bone marrow, liver and spleen. Over the last few years, several new immunological drugs, particularly immunotoxins, BRAF inhibitors and B-cell receptor (BCR) pathway inhibitors have been developed and investigated as potential treatment options.

Areas covered: This article summarizes recent investigational therapies of HCL, looking at their: mechanism of action, pharmacological properties, clinical activity and toxicity, as well as their emerging role in its treatment. The authors conducted a literature review of the MEDLINE database for articles in English concerning immunotoxins, BRAF inhibitors and BCR pathway inhibitors via PubMed. Publications from 2000 through to June 2015 were scrutinized. The search terms used were: BRAF, vemurafenib, dabrafenib, ibrutinib, monoclonal antibodies, immunotoxins, moxetumomab pasudotox, and rituximab in conjunction with HCL. The authors also searched manually the conference proceedings from the previous 5 years of the American Society of Hematology, European Hematology Association, American Society of Clinical Oncology, and ACR/ARHP Annual Scientific Meetings were searched manually. Additional relevant publications were obtained by reviewing the references from the chosen articles.

Expert opinion: The use of vemurafenib and moxetumomab pasudotox is a promising new strategy for the treatment of HCL. Data from ongoing and future clinical trials will aid in better defining the status of new drugs in the treatment of HCL.     

Local production of the chemokines CCL5 and CXCL10 attracts CD8+ T lymphocytes into esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma (ESCC) is a very common malignant tumor with poor prognosis in China. Chemokines secreted by tumors are pivotal for the accumulation of CD8⁺ T lymphocytes within malignant lesions in several types of cancers, but the exact mechanism underlying CD8⁺ T lymphocyte homing is still unknown in ESCC. In this study, we revealed that, compared with marginal tissues, the expression of both chemokine (C-C motif) ligand 5 (CCL5) and (C-X-C motif) ligand 10 (CXCL10) was upregulated in ESCC tissues. CCL5 expression was positively associated with the overall survival of patients. Meanwhile, RT-PCR data showed that the expression of CCL5 and CXCL10 was positively correlated with the local expressions of the CD8⁺ T lymphocyte markers (CD8 and Granzyme B) in tumor tissues. Correspondingly, CD8⁺ T lymphocytes were more frequently CCR5- and CXCR3-positive in tumor than in peripheral blood. Transwell analysis showed both CCL5 and CXCL10 were important for the chemotactic movement of CD8⁺ T lymphocytes. Our data indicate that CCL5 and CXCL10 serve as the key chemokines to recruit CD8⁺ T lymphocytes into ESCC tissue and may play a role in patient survival.     

Hepatocyte steatosis in HCV patients promotes fibrosis by enhancing TGF-β liver expression

Aim:  The objective of this study was to examine the relationship between TGF-β expression in steatotic liver and the stage and yearly progression rate of fibrosis in chronic hepatitis C (CHC) patients.
Methods:  We examined 44 CHC fatty liver patients, using 76 non-steatotic CHC patients as controls. The stage of hepatic fibrosis was assessed on a score scale. TGF-β expression was determined with the use of monoclonal serum and the ABC three-step method.
Results:  We demonstrated a positive correlation of steatosis with the stage of fibrosis ( P  < 0.05). No relationship of thiskind was found with the yearly progression rate of fibrosis ( P  > 0.09). In steatotic biopsies, TGF-β expression index in portal spaces and lobules was found to be higher as compared to TGF-β expression in biopsies without steatosis ( P  < 0.05).
Conclusion:  In CHC patients steatosis induces the development of fibrosis by elevating the hepatic expression of TGF-β.