Comparative study of laser versus radiofrequency myringotomy in rabbits: The effectiveness of mitomycin C application.

OBJECTIVE: To compare laser-assisted tympanostomy (LAT) with radiofrequency myringotomy (RFM), as well as the effectiveness of mitomycin C (MC) on the above techniques, in rabbits. STUDY DESIGN: Experimental animal research protocol. SETTING: University of Crete, School of Medicine, Medical Experimental Education and Research Center. METHODS: Bilateral myringotomies were performed under general anesthesia on 40 rabbits. LAT was performed on 20 animals (40 ears) and RFM on the remaining 20 animals (40 ears). MC (0.3 mg/mL) pledgets were applied to the right ears and saline pledgets to the left ears. Animals were monitored weekly using otomicroscopy until myringotomy closure. Kaplan-Meier survival techniques were used to compare myringotomy patency times. INTERVENTIONS: Under general anesthesia, bilateral LAT was performed on 20 rabbits and bilateral RFM on 20 rabbits. MAIN OUTCOME MEASURES: Myringotomy patency time. RESULTS: The mean patency times of the saline-treated ears were: 1.85 weeks (95% confidence interval [CI], 1.556-2.144 wk) for the LAT group and 1.70 weeks (95% CI, 1.494-1.906 wk) for the RFM group. This difference was not significant (p > 0.5). MC application significantly prolonged mean patency time (p < 0.0001) in both LAT and RFM groups. The mean patency times in the MC-treated ears were 5.45 weeks (95% CI, 5.226-5.674 wk) for the LAT group and 5.55 weeks (95% CI, 5.285-5.815 wk) for the RFM group. This difference was not significant (p > 0.5). CONCLUSION: There is no significant difference in myringotomy patency times between LAT and RFM techniques in rabbits, whereas MC significantly prolongs the patency rate of either technique.     

Prolonged exposure of intraocular lens implant with preservation of globe integrity and visual function.

A 70-year-old woman had corneal ulcer and melting after complicated cataract surgery with polymethylmethacrylate lens implant insertion. A conjunctival flap was initially used to cover the defect with a plan to perform keratoplasty later. Fifteen months postoperatively, she presented with total absence of central corneal tissue and iris and exposure of the implant. The eye was not inflamed, painful, or hard on palpation and visual acuity was counting fingers at 3 m. The preservation of globe integrity despite exposure of the polymethylmethacrylate implant implies a stable adhesion between polymethylmethacrylate and residual corneal tissue and may prove useful in keratoprosthesis design.     

The Hemodynamic Mechanisms of Lung Injury and Systemic Inflammatory Response Following Brain Death in the Transplant Donor

Brain-dead donors are the major source of lungs for transplantation. Brain death is characterized by two hemodynamic phases. Initially, massive sympathetic discharge results in a hypertensive crisis. This is followed by neurogenic hypotension. Up-regulation of pro-inflammatory mediators occurs in all organs and lung injury develops; this can adversely affect graft function post-transplantation. The mechanisms of the systemic and lung inflammation are unknown. We hypothesized that the hemodynamic changes are responsible for these inflammatory phenomena. Brain death was induced by intra-cranial balloon inflation in rats. This resulted in hypertensive crisis, followed by hypotension. There was a significant increase in blood neutrophil CD11b/CD18 expression and pro-inflammatory cytokine levels in serum and bronchoalveolar lavage, compared with control animals. Rupture of the capillary-alveolar membrane was demonstrated by electron microscopy. Elimination of the hypertensive response by α-adrenergic antagonist pre-treatment prevented inflammatory lung injury, reduced the systemic inflammatory markers and preserved capillary-alveolar membrane integrity. Correction of the neurogenic hypotension with noradrenaline ameliorated the systemic inflammatory response and improved oxygenation. We conclude that the sympathetic discharge triggers systemic and lung inflammation, which can be further enhanced by neurogenic hypotension. Management of the brain-dead donor with early anti-inflammatory treatment and vasoconstrictors is warranted.     

Monitoring motor function during resection of tumours in the lower brain stem and fourth ventricle

Objectives Even in the days of modern microsurgery, the removal of a brain stem lesion remains a surgical challenge. Especially when operating on children, the prognosis is directly related to the radicality of the resection; however, a radical resection is often associated with surgical morbidity. Intraoperative neuromonitoring could help to minimise the surgical morbidity, but few studies have been performed to clarify the value of this monitoring. We investigated a prospective series of 21 patients with lesions involving the brain stem for the prognostic value and benefits of neuromonitoring.Methods We performed intraoperative neuromonitoring of cranial nerve function by electromyography (EMG) and motor evoked potential (MEP). The results were correlated with postoperative neurological deficits.Conclusions There is a good correlation between intraoperative neurophysiological events and postoperative neurological deficits in patients with lesions of the brain stem. In general, transient, prolonged, spontaneous activity in EMG is associated with a transient paresis of the respective muscle, whereas a permanent spontaneous activity is associated with a permanent deficit. Intraoperative neuromonitoring reliably predicts postoperative neurological function in patients with tumours of the lower brain stem and fourth ventricle. This neuromonitoring guides the neurosurgeon in the operation and may decrease surgical morbidity. We recommend using monitoring of MEP and EMG of the lower cranial nerves in surgery on all patients with lesions involving the lower brain stem and fourth ventricle.     

Carboplatin as opposed to cisplatin does not stimulate the expression of the human immunodeficiency virus long terminal repeat sequences.

The recombinant plasmid pBHIV1 carrying the long terminal repeat (LTR) of the human immunodeficiency virus 1 (HIV-1), linked to the chloramphenicol acetyl transferase (CAT) gene, was introduced into human and rat fibroblasts. Stable transfectants resistant to geneticin expressed CAT activity from the HIV-1 LTR. It was found that the cytotoxic drug cis-diammine(1,1-cyclobutanedicarboxylato)platinum(II) (carboplatin) at concentrations from 1 x 10(-6) to 1 x 10(-4) M does not stimulate the expression of CAT from the HIV-1 LTR. These results differ from previous studies with the related drug cis-diamminedichloroplatinum(II) which showed stimulation of gene expression from the HIV-1 LTR and suggest that carboplatin could be used in the treatment of cancer patients with Acquired Immune Deficiency Syndrome.     

Increased incidence of papillary thyroid cancer among total thyroidectomies in Crete.

OBJECTIVE: To investigate the increased incidence of papillary thyroid cancer as found in specimens of total thyroidectomies and potential correlation with etiological factors. STUDY DESIGN AND SETTING: A retrospective study on patients who underwent total thyroidectomy, from 1990 to 2004, in an academic tertiary referral medical center. Patients' records were placed in a database, which included medical condition, history, and demographics. Histopathological slides were reviewed with special focus on papillary cancer. RESULTS: Our series consisted of 2379 patients. Thyroid cancer was confirmed in 354 patients (14.88%). Papillary carcinoma represented the most frequent type (316 patients, 89.26%). Increased incidence of papillary carcinomas was noticed after 1995, reaching the maximum value in the year 2000. After 2000, there was a descending trend and then a plateau. CONCLUSION: The increased incidence of papillary thyroid cannot be attributed to dietary patterns or increased diagnostic and therapeutic activity. It is likely to be associated with increased radiation and may be associated with the Chernobyl fallout.     

Cellular metabolism of 1-β-d-arabinofuranosyl-5-azacytosine and incorporation into DNA and RNA of human lymphoid CEM/0 and CEM/dCk(−) cells

Summary 1--d-arabinosyl-5-azacytosine (ara-AC) is a relatively new antitumor agent under clinical investigation, which has the 2- arabinosyl configuration found in the tumoricidal drug ara-C and the nitrogen substitution in the 5-position of the pyrimidine ring found in 5-azacytidine (5-aza-C). The present study examined the cellular metabolism and the effect on DNA methylation of ara-AC in human CCRF/CEM cells sensitive and resistant to ara-C. The triphosphate anabolite of the drug, ara-ACTP, was the major anabolite in the CEM cellular extracts, peaking at 50.6±23 M 4 h after incubation with IC₅₀ concentrations (0.25 M) of [³H]ara-AC. The mono- and diphosphate anabolites accumulated 10-fold lower cellular concentrations than ara-ACTP. The nucleoside triphosphate (NTP) pools and, especially, cellular ATP declined significantly by 9 h after the initiation of drug treatment and remained depleted for the 24-h treatment. The drug anabolite was gradually incorporated into both RNA and DNA, peaking in CEM/0 at 3.44 and 0.14 nmol/10⁷ cells, respectively. The DNA methylation levels in these cells declined rapidly after treatment with ara-AC, attaining a nadir plateau at 29% of control methylation value. The deoxycytidine kinase (dCk) mutant CEM cell line [CEM/dCk(–)] neither activated ara-AC at appreciable levels nor induced DNA hypomethylation at low concentrations (0.25–1 M). However, the drug was activated at 0.2–1 M extracellular concentrations of ara-AC, probably by an as yet unknown nucleoside kinase at approximately 10% of the amount in CEM/0 cells. Ara-AC appears to mediate its cytotoxic action through the accumulation of its triphosphate anabolite, ara-ACTP, and the subsequent incorporation into nucleic acids. DNA methylation may also contribute to its cytotoxicity.Abbreviations 5-aza-C 5-azacytidine - ara-AC 1--d-arabinofuranosyl-5-azacytosine - ara-ACTP 1--d-arabinofuranosyl-5-azacytosine 5-triphosphate - dCk deoxycytidine kinase - PCA perchloric acid - SAX strong anion exchange - PBS phosphate-buffered saline Supported by research grant CA 38905 from the National Institute of Health, NCI, and the T. J. Martell Foundation for Leukemia and Cancer Research, The Neil Bogart Memorial Laboratories     

Peripheral-type benzodiazepine receptor (PBR) gene amplification in MDA-MB-231 aggressive breast cancer cells

Recent studies using human breast cancer cell lines, animal models, and human tissue biopsies have suggested a close correlation between the expression of the peripheral-type benzodiazepine receptor (PBR) and the progression of breast cancer. This study investigates the genetic status of the PBR gene in two human breast cancer cell lines: MDA-MB-231 cells, which are an aggressive breast cancer cell line that contains high levels of PBR, and MCF-7 cells, which are a nonaggressive cell line that contains low levels of PBR. Both DNA (Southern) blot and fluorescence in situ hybridization analyses indicate that the PBR gene is amplified in MDA-MB-231 relative to MCF-7 cells. These data suggest that PBR gene amplification may be an important indicator of breast cancer progression.     

Hyper immunoglobulin M syndrome due to CD40 deficiency: clinical, molecular, and immunological features

Summary: CD40 is a member of the tumor necrosis factor receptor family, which is expressed by a variety of cells including B cells, macrophages, dendritic cells, and other nonimmune cell types. CD40 activation is critical for B‐cell proliferation, immunoglobulin (Ig)‐isotype switching, and germinal center formation. In physiological conditions, the activation of CD40 occurs by binding to its natural ligand, CD154, which is expressed on activated T cells. The in vivo critical role of CD40–CD154 interaction on B‐cell differentiation and isotype switching is provided by the discovery that mutations in either CD40 or CD154 gene cause the hyper IgM syndrome, termed HIGM3 or HIGM1, respectively, characterized by very low levels of serum IgG, IgA, and IgE, with normal or elevated IgM, associated with a defective germinal center formation. Originally considered humoral primary immunodeficiencies, the clinical features and the defect of T‐cell priming, resulting from a defective T–B cell or dendritic cell interaction, is now considered as combined immunodeficiencies. In this article, we present a comprehensive overview of the clinical, genetic, and immunological features of patients with hyper IgM syndrome due to CD40 mutations.