A retrospective review of pharyngeal pouch surgery in 56 patients

We retrospectively reviewed 56 consecutive patients treated surgically for a pharyngeal pouch at our institution between 1989-1999 (10 years). Various surgical procedures were performed including endoscopic stapling (20), external excision (23), Dohlman's procedure (9), pouch inversion (3), cricopharyngeal myotomy only (3), and pouch suspension (1). There were 12 patients (18%) with complications and one mortality (2%). Four patients (7%) had a recurrence with 2 requiring further surgery. Over the latter 3 years, endoscopic stapling has emerged as the primary procedure for pharyngeal pouch surgery in our unit; with the advantages of an earlier commencement of diet and earlier hospital discharge. However, results were not as good as for external excisions. Furthermore, there were difficulties with 3 cases that commenced as endoscopic stapling procedures but had to he converted to external excisions due to inaccessibility in one case and iatrogenic perforations in two cases. As with any new technique, problems may occur and a learning curve has been appreciated in our unit. Surgeons must he prepared, with informed consent, to convert to an external approach should difficulties arise during endoscopic stapling. Elderly and frail patients who are at risk from a general anaesthetic may benefit from endoscopic stapling. External excision of pharyngeal pouches may be more appropriate in the young, the medically fit, and when malignancy is a concern.     

Association of LAR-like receptor protein tyrosine phosphatases with an enabled homolog in Hirudo medicinalis

Receptor protein tyrosine phosphatases (RPTPs) are thought to play important functions in pathfinding and target recognition by growing neuronal processes. The leech RPTPs HmLAR1 and HmLAR2 are expressed selectively by central neurons, Comb cells, and peripheral muscle tissues in the Hirudo medicinalis embryo. To explore the functions of HmLARs, we have sought to determine their physiological substrates. We report here the cloning and embryonic expression of Lena, the leech homolog of Enabled, a cytosolic protein implicated in actin-based cell motility. Lena is expressed in embryonic central neurons and in the Comb cell. We present experimental evidences indicating that Lena associates selectively with the intracellular domain of HmLAR1 and HmLAR2. Additionally, RNA interference (RNAi) of HmLAR1 in intact leech embryos leads to the hyperphosphorylation of Lena. We propose, therefore, that Lena is an in vivo substrate of HmLAR1 in neurons and perhaps of HmLAR2 in the Comb cells.     

Proteasomal degradation of human peptidyl prolyl isomerase pin1-pointing phospho Bcl2 toward dephosphorylation

Microtubule inhibitor-induced Bcl2 phosphorylation is detrimental to its antiapoptotic function. Phosphorylation of Bcl2 predominantly occurs on two serine residues (70 and 87) in cells arrested at G2-M phase by microtubule disarraying agents. Phospho Bcl2 can associate with a cis-trans peptidyl prolyl isomerase, Pin1. Pin1 and its homologues are known to target the proline residue carboxyl terminal to the phosphorylated threonine or serine residue of mitotic phosphoproteins, such as Bcl2. However, it was not clear how an extranuclear protein could associate with nuclear Pin1. The confocal images of the immunofluorescence studies employing phospho Bcl2-specific antibody developed in the laboratory demonstrated the translocation of phospho Bcl2 inside the nucleus. Interestingly, proteasomal degradation of Pin1 facilitates dephosphorylation of phospho Bcl2 due to longer exposure of Taxol. Here we show for the first time that proteasomal degradation of Pin1 is the key factor to determine the fate of phosphoforms of Bcl2. When Pin1 is degraded by proteasomes, phospho Bcl2 is converted to its native form. Thus, transient conformational change of Bcl2 due to association with peptidyl prolyl isomerase can contribute to irreversible apoptotic signaling.     

Growth hormone secretion in growth retarded asthmatic children

Summary Fifteen asthmatic children were studied for serum growth hormone response to Bovril, who were growth retarded with severe asthma, and the growth hormone was found to be normal. Ten subjects, who were receiving corticosteroids, have been small for their age before starting corticosteroid therapy. It is concluded that there is no case for treating growth retarted asthmatic children with growth hormone. From the Departments of Medicine, Paediatrics, Tuberculosis and Chest Diseases, and Physiology, M.L.B. Medical College, Jhansi-284001, U.P. Paper read in the Interasma Congress VIII, Vlissingen, The Netherlands, October 6–10, 1975.     

An intra-individual comparison of the previous conventional hearing aid with the bone-anchored hearing aid: The Nijmegen group questionnaire

By spring 2000, a total of 351 patients were implanted in the Birmingham bone-anchored hearing aid (BAHA) programme. This group consisted of 242 adults and 109 children. The aim of this retrospective questionnaire study was to directly assess patient satisfaction with their current bone-anchored hearing aid in comparison with their previous conventional air and/or bone-conduction hearing aids. The Nijmegen group questionnaire was sent by post to 312 patients who used their BAHA for six months or longer. The questionnaire used was first described by Mylanus et al. (Nijmegen group) in 1998. The total response rate was 72 per cent (227 of 312 patients). The bone-anchored hearing aid was found to be significantly superior to prior conventional hearing aids in all respects.     

Leptin levels are appropriate for body mass index in older men who experience involuntary weight loss

OBJECTIVES: To determine the relationship between leptin and unintentional weight loss in older adults. DESIGN: Prospective cohort study over 2 years. SETTING: University-affiliated Veterans Affairs Medical Center. PARTICIPANTS: The subjects were 105 community-dwelling male veterans aged 65 and older who had participated in a prospective cohort study on nutrition and health conducted at the Veterans Affairs Puget Sound Health Care System from 1986 to 1989. MEASUREMENTS: Anthropometric data and fasting blood specimens were collected at baseline and annually for the subsequent 2 years. Stored blood specimens were analyzed for leptin, insulin, glucose, C-reactive protein, sex hormone binding globulin, and testosterone levels. RESULTS: Over 2 years, 75 men were weight stable (weight loss <4% of baseline) and 30 men had unintentional weight loss (weight loss>4% of baseline). The baseline body mass index (BMI) and leptin levels for the two groups were not statistically different. Positive correlations existed between leptin level and BMI at each time point for weight-stable and weight-loss subjects. Furthermore, a significant relationship existed between changes in leptin and changes in BMI over 1 year in multiple regression analysis (r =.436, P <.001 after the first year; and r =.630, P =.027 after the second year). CONCLUSIONS: Like in younger adults, plasma leptin levels remained proportional to BMI, and changes in BMI were accurately reflected by changes in leptin levels in older individuals. Fasting leptin levels did not predict involuntary weight loss over 2 years of follow-up.     

Increased incidence of mitochondrial cytochrome c-oxidase gene mutations in patients with myelodysplastic syndromes

Mitochondria (mt) play an important role in both apoptosis and haem synthesis. The present study was conducted to determine DNA mutations in mitochondrial encoded cytochrome c-oxidase I and II genes. Bone marrow (BM) biopsy and aspirate, peripheral blood (PB) and buccal smear samples were collected from 20 myelodysplastic syndrome (MDS) patients and 10 age-matched controls. Cytochrome c-oxidase I (CO I) and II (CO II) genes were amplified using polymerase chain reaction and sequenced. CO I mutations were found in 13/20 MDS patients and the CO II gene in 2/10 normal and 12/20 MDS samples, irrespective of MDS subtype. Mutations were substitutional, deletional and insertional. CO I mutations were most common at nucleotide positions 7264 (25%) and 7289 (15%), and CO II mutations were most common at nucleotide positions 7595 (40%) and 7594 (30%), suggesting the presence of potential 'hot-spots'. Mutations were not found in buccal smears of MDS patients and were significantly higher in MDS samples compared with age-matched controls in all cell fractions (P < 0.05), with bone marrow high-density fraction (BMHDF) showing a higher mutation rate than other fractions (P < 0.05). MDS marrows showed higher levels of apoptosis than normal controls (P < 0.05), and apoptosis in BMHDF was directly related to cytochrome c-oxidase I gene mutations (P < 0.05). Electron microscopy revealed apoptosis affecting all haematopoietic lineages with highly abnormal, iron-laden mitochondria. These results suggest a role for mt-DNA mutations in the excessive apoptosis and resulting cytopenias of MDS patients.