Transoral radiofrequency of the terminal branches of the recurrent nerve in the treatment of adductor spasmodic dysphonia: our experience over 11 patients.

PURPOSE: Spasmodic dysphonia (SD) or laryngeal dystonia is as a rare vocal disorder characterized by involuntary action-induced endolaryngeal contraction. In the last decade, botulin toxin injection has become the standard treatment in adductor spasmodic dysphonia necessitating repetitive injections. The purpose of this study is to analyze retrospectively data from patients treated with the minimal-invasive transoral radiofrequency-induced thermotherapy (RFITT) of the terminal branches of the recurrent nerve. METHODS: Between 2009 and 2015, 11 patients (six females and five males aged from 32 to 91 years) with adductor SD were treated with RFITT. Pre-operative and post-operative vocal assessments (VHI-30, GRBASI, and acoustic-aerodynamics measurements), number of surgical revisions, delay between procedures, and post-operative complications were recorded. Statistical analyses were carried out on the first vocal assessment performed 2-8 weeks after the first procedure. RESULTS: Based on available data from ten patients, voice handicap index (VHI) showed improvement with a mean value of -17.7 points (p-value (pval) = 0.014, adjusted p-value (adj pval) = 0.21); instability has also revealed improvement in six patients (pval = 0.05, adj pval = 0.31). Four patients underwent only one procedure including one patient showing still long-term beneficial results after 5 years of follow-up. Other patients required one to three new procedures with an average time between procedures of 15.3 months. Over 24 surgeries performed on a total of 11 patients, one definitive treatment-related severe adverse event was reported. CONCLUSION: Thanks to long-lasting effect, repetitive treatments are less frequent compared to botulin toxin therapy. In our opinion, RFITT is a promising alternative to botulin toxin as a second-step procedure in case of toxin resistance or patient's lack of compliance.

Gene transfer in inner ear cells: a challenging race.

Recent advances in human genomics led to the identification of numerous defective genes causing deafness, which represent novel putative therapeutic targets. Future gene-based treatment of deafness resulting from genetic or acquired sensorineural hearing loss may include strategies ranging from gene therapy to antisense delivery. For successful development of gene therapies, a minimal requirement involves the engineering of appropriate gene carrier systems. Transfer of exogenous genetic material into the mammalian inner ear using viral or non-viral vectors has been characterized over the last decade. The nature of inner ear cells targeted, as well as the transgene expression level and duration, are highly dependent on the vector type, the route of administration and the strength of the promoter driving expression. This review summarizes and discusses recent advances in inner ear gene-transfer technologies aimed at examining gene function or identifying new treatment for inner ear disorders.

Evaluation of a urology specialist therapeutic radiographer implemented radiotherapy pathway for prostate cancer patients.

INTRODUCTION: The role of the Urology Specialist Therapeutic Radiographer (USTR) was introduced to support a busy NHS uro-oncology practice. Key objectives were to improve patient preparedness for and experience of radiotherapy, focussed on prostate cancer. Pre-radiotherapy information seminars were developed, and on-treatment patient review managed by the USTRs. To evaluate the revamped patient pathway and direct further improvements, a patient experience survey was designed. METHODS: An 18-point patient questionnaire was produced. The questionnaire captured patient experience and preparedness; pre, during and at completion of treatment. The patient population comprised men receiving radiotherapy for primary prostate cancer within one UK Trust. RESULTS: Two-hundred and fifty-one responses were received. Seventy-three percent of patients felt completely prepared for radiotherapy, higher in those who attended a seminar (77%) compared to those who did not (61%). Eighty-nine and eighty-six percent of respondents were completely satisfied with verbal and written information received prior to commencing radiotherapy respectively. Seventy-three percent of responders would have found additional resources helpful. With respect to on-treatment clinics; eighty-five percent were seen on time or within 20 minutes, eighty-three percent felt fully involved in decisions regarding their care and ninety-one percent reported complete satisfaction with the knowledge of the health care professional reviewing them. The follow-up process was completely understood by eighty-eight percent and overall patient experience rated excellent by eighty-five percent of responders. CONCLUSION: The revamped pathway implemented by USTRs has achieved high levels of satisfaction at all stages of the prostate patient's radiotherapy. By diversifying the format of information giving, the USTRs hope to further meet the information needs of patients. IMPLICATIONS FOR PRACTICE: Validation of a prostate cancer radiotherapy pathway which employs USTRs and utilises a patient preparation seminar. This model could support the introduction of Specialist Therapeutic Radiographers in other Trusts and treatment sites.

Retinoic acid induces TGFbeta-dependent autocrine fibroblast growth.

To evaluate the role of murine TFIID subunit TAF4 in activation of cellular genes by all-trans retinoic acid (T-RA), we have characterized the T-RA response of taf4(lox/-) and taf4(-/-) embryonic fibroblasts. T-RA regulates almost 1000 genes in taf4(lox/-) cells, but less than 300 in taf4(-/-) cells showing that TAF4 is required for T-RA regulation of most, but not all cellular genes. We further show that T-RA-treated taf4(lox/-) cells exhibit transforming growth factor (TGF)beta-dependent autocrine growth and identify a set of genes regulated by loss of TAF4 and by T-RA corresponding to key mediators of the TGFbeta signalling pathway. T-RA rapidly and potently induces expression of connective tissue growth factor (CTGF) via a conserved DR2 type response element in its proximal promoter leading to serum-free autocrine growth. These results highlight the role of TAF4 as a cofactor in the cellular response to T-RA and identify the genetic programme of a novel cross talk between the T-RA and TGFbeta pathways that leads to deregulated cell growth.

IGF-II in primary human colorectal tumors: peptide level, activated promoters, parental imprinting and gene rearrangement.

IGF-II is a polypeptide growth factor with growth and differentiation promoting activities, involved in human development. We have reported previously IGF-II mRNA and peptide overexpression in primary human colon cancers. Here we show that the IGF-II peptide content is increased in six primary colon cancers compared to the corresponding healthy tissues. The IGF-II transcripts in healthy and cancerous colon tissues were identified by Northern blotting and RT-PCR. Promoters P3 and P4 were active in most tissues. Relaxation of parental imprinting was observed in two tumors and one healthy tissue, without any correlation with the IGF-II transcript levels. Rearrangements of the IGF-II gene in two tumors containing very high amounts of IGF-II mRNA are described. Fragments containing the breakpoints were cloned by the vectorette-PCR strategy. In both tumors, the breakpoints occurred in repetitive sequences. In one tumor (T11), the breakpoint was localized 2 kb downstream the end of exon 9. The second tumor (T18) contains two modified alleles. In one rearranged allele the breakpoint is located in exon 9. The exact position of the breakpoint in the second rearranged allele has not been identified. In future experiments, the correlation between the gene rearrangements and IGF-II mRNA overexpression will be studied.

Characterization of the IGF system and analysis of the possible molecular mechanisms leading to IGF-II overexpression in a mesothelioma.

The expression of members of the IGF system in a mesothelioma from a patient suffering from hypoglycemia, in term placenta and HT29 colon adenocarcinoma cells were compared. Very high levels of IGF-II mRNA and protein were detected in the mesothelioma. Moreover, half of the IGF-II protein took the high-molecular-weight form. We also analyzed the parental imprinting status and the promoter usage of the IGF-II gene. Our results showed loss of imprinting (LOI) in the mesothelioma while the imprinting was maintained in HT29 cells, expressing moderate levels of the transcript. Promoter P4 was active in the three tissues we analyzed, whereas IGF-II mRNA transcription from promoter P3 was only detected in the mesothelioma and the placenta, expressing comparably high levels of the transcript. IGF-II gene structure was identical in the analyzed tissues and cells. The type-I receptor mRNA expression was very low in the tumor. IGFBP-2, -4 and -5 mRNAs were detected in the mesothelioma, while IGFBP-2, -3 and -5 transcripts were detected in the placenta. IGFBP-1 and -6 transcripts were not detected.