Changing indications and surgical techniques for corneal transplantation between 2004 and 2009 at a tertiary referral center.

PURPOSE: The aim of this study is to report the indications, techniques, and clinical outcomes of corneal transplantation and investigate any changing trends in surgical techniques over a 6 year period. MATERIALS AND METHODS: Records of patients who had undergone any kind of corneal transplantation at Labbafinejad Medical Center, Tehran, Iran, from January 2004 to December 2009 were reviewed to determine the indications and types of corneal transplantation. Postoperative best-corrected visual acuity, refractive error, graft clarity, and complications were reported. RESULTS: During this period, 1859 eyes of 1624 patients with a mean age of 41.3 ± 21.3 years underwent corneal transplantation. The most common indication was keratoconus (38.4%) followed by aphakic/pseudophakic bullous keratopathy (11.7%), previous failed grafts (10.6%), infectious corneal ulcers (10.1%), non-herpetic corneal scars (7.6%), trachoma keratopathy (4.7%), stromal corneal dystrophies (4.6%), post-herpetic corneal scar (3.7%), Fuchs' endothelial dystrophy (0.8%), and congenital hereditary endothelial dystrophy (0.4%). Techniques of corneal transplantation included penetrating keratoplasty (PKP; 70.9%), deep anterior lamellar keratoplasty (DALK; 20.1%), conventional lamellar keratoplasty (LKP; 4.4%), and Descemet's stripping automated endothelial keratoplasty (DSAEK; 2.3%). Over the study period, there was a significant increase in the relative frequency of infectious corneal ulcers, failed grafts, and trachoma keratopathy. Additionally, a significant reduction was observed in PKP and LKP procedures, and volume of DALK and DSAEK increased significantly. At final follow-up, 69.0% of grafts were clear in the PKP group. This figure was 82.6%, 82.7%, and 97.6% in the DALK, LKP, and DSAEK groups, respectively. CONCLUSION: Keratoconus was the most common indication and PKP was the most prevalent technique used for corneal transplantation. However, significant changes in the indications and surgical techniques were observed from 2004 to 2009.

Tinnitus as an unusual presentation of Schneiderian papillomatosis.

INTRODUCTION: Primary Schneiderian papillomatosis of the middle ear and mastoid cavity is extremely rare. It is frequently associated with intermittent unilateral otorrhoea and mass in the middle ear and mastoid cavity. METHODS: Case presentation, symptoms, diagnostic criteria, management and literature review are discussed. CONCLUSION: Schneiderian papillomatosis is an important differential diagnosis of mass in the middle ear and mastoid cavity, and tinnitus as a presenting symptom has not been reported before. Primary radical treatment is essential in preventing tumour recurrence.

Post-tonsillectomy bleeding: a regional hospital experience.

INTRODUCTION: Post-tonsillectomy bleeding (PTB) is still one of the most common complications of tonsillectomy. The rate of PTB varies with different methods. METHODS: We retrospectively reviewed all charts of patients who underwent tonsillectomy in a regional hospital. RESULTS: Post-tonsillectomy bleeding occurred in 33 patients (6.68%); 3 experienced primary haemorrhage and 30 had secondary haemorrhage. The rate of PTB was higher in males and in the over 15-year group (9.41%). The commonest surgical techniques used were cold steel dissection with bipolar diathermy for haemostasis (55.87%). The lowest PTB was observed with 'cold steel and ties technique' (3.14%). Operations which used bipolar diathermy throughout had the highest level of haemorrhage (8.47%). CONCLUSION: In conclusion, the overall risk of bleeding is related to surgical technique. A 'hot' technique had a higher risk of bleeding than 'cold' technique.

Weight gain after laparoscopic cholecystectomy.

INTRODUCTION: Laparoscopic cholecystectomy (LC) relieves symptomatic cholelithiasis (SC) but may facilitate postoperative gluttony. AIM: To examine changes in body mass index (BMI) and general health of a cohort of patients three years after uncomplicated LC for SC. METHODS: Patients were studied three years after uncomplicated LC and compared to age- and gender-matched controls who had undergone non-biliary surgery. RESULTS: Forty-two patients and 42 controls were studied. The mean age of the patients was 55 years (range 29-82) versus 54 years (25-82) for controls. Patients undergoing LC increased their mean BMI by 1.8 kg/m2. Females were particularly likely to gain weight (mean change in BMI=+2.1), with no significant difference being found between premenopausal and postmenopausal women. Of the 24 LC patients who claimed to continue their low fat diet, the mean BMI changed from 27.6 to 29.6 kg/m2. The mean BMI of the 17 people who claimed regular exercise changed less markedly (+1.4) than those who admitted infrequent exercise (+2.1). CONCLUSION: Selection for LC may identify patients at risk of continuing or resumed aetiological contributors to obesity. Follow-up long after the surgery may therefore be necessary to facilitate additional healthcare interventions.

The modified human DNA repair enzyme O(6)-methylguanine-DNA methyltransferase is a negative regulator of estrogen receptor-mediated transcription upon alkylation DNA damage.

Cell proliferation requires precise control to prevent mutations from replication of (unrepaired) damaged DNA in cells exposed spontaneously to mutagens. Here we show that the modified human DNA repair enzyme O(6)-methylguanine-DNA methyltransferase (R-MGMT), formed from the suicidal repair of the mutagenic O(6)-alkylguanine (6RG) lesions by MGMT in the cells exposed to alkylating carcinogens, functions in such control by preventing the estrogen receptor (ER) from transcription activation that mediates cell proliferation. This function is in contrast to the phosphotriester repair domain of bacterial ADA protein, which acts merely as a transcription activator for its own synthesis upon repair of phosphotriester lesions. First, MGMT, which is constitutively present at active transcription sites, coprecipitates with the transcription integrator CREB-binding protein CBP/p300 but not R-MGMT. Second, R-MGMT, which adopts an altered conformation, utilizes its exposed VLWKLLKVV peptide domain (codons 98 to 106) to bind ER. This binding blocks ER from association with the LXXLL motif of its coactivator, steroid receptor coactivator-1, and thus represses ER effectively from carrying out transcription that regulates cell growth. Thus, through a change in conformation upon repair of the 6RG lesion, MGMT switches from a DNA repair factor to a transcription regulator (R-MGMT), enabling the cell to sense as well as respond to mutagens. These results have implications in chemotherapy and provide insights into the mechanisms for linking transcription suppression with transcription-coupled DNA repair.

Implication of localization of human DNA repair enzyme O6-methylguanine-DNA methyltransferase at active transcription sites in transcription-repair coupling of the mutagenic O6-methylguanine lesion.

DNA lesions that halt RNA polymerase during transcription are preferentially repaired by the nucleotide excision repair pathway. This transcription-coupled repair is initiated by the arrested RNA polymerase at the DNA lesion. However, the mutagenic O6-methylguanine (6MG) lesion which is bypassed by RNA polymerase is also preferentially repaired at the transcriptionally active DNA. We report here a plausible explanation for this observation: the human 6MG repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) is present as speckles concentrated at active transcription sites (as revealed by polyclonal antibodies specific for its N and C termini). Upon treatment of cells with low dosages of N-methylnitrosourea, which produces 6MG lesions in the DNA, these speckles rapidly disappear, accompanied by the formation of active-site methylated MGMT (the repair product of 6MG by MGMT). The ability of MGMT to target itself to active transcription sites, thus providing an effective means of repairing 6MG lesions, possibly at transcriptionally active DNA, indicates its crucial role in human cancer and chemotherapy by alkylating agents.

Effect of nicotine on arachidonic acid metabolites and epithelial parameters in rat oral mucosa.

This study examined the effects of nicotine on oral mucosal levels of eicosanoids and on histologic parameters, including keratinocyte proliferation. Surgically-created canals in the mandibular lips of 20 male Sprague Dawley rats received either nicotine or saline in a cotton pellet twice daily for six weeks. Thromboxane B2 (TxB2) levels were depressed (P < 0.05) in nicotine treated tissues compared to saline treatment (5.8 +/- 1.0 vs 13.4 +/- 2.1 pg/mg). Within the nicotine group, TxB2 concentrations were lower (P < 0.05) at the nicotine site compared to the posterior site (18.3 +/- 5.4 pg/mg). There was also a trend towards reduced 6-keto-PGF1 alpha in the nicotine-treated tissues compared to saline-exposed sites. These alterations in cyclooxygenase metabolites were not accompanied by changes in epithelial proliferation or histologic parameters. 12(S)-hydroxyeicosatetranoic acid (12-HETE) and leukotriene B4 (LTB4) were not affected by nicotine. Therefore, nicotine may not be directly responsible for the hyperplasia at habitual tobacco placement sites, but may contribute to alterations in cyclooxygenase products of arachidonic acid metabolism.

Conformational change in human DNA repair enzyme O6-methylguanine-DNA methyltransferase upon alkylation of its active site by SN1 (indirect-acting) and SN2 (direct-acting) alkylating agents: breaking a "salt-link".

Human O6-methylguanine-DNA methyltransferase (MGMT) repairs DNA by transferring alkyl (R-) adducts from O6-alkylguanine (6RG) in DNA to its own cysteine residue at codon 145 (formation of R-MGMT). We show here that R-MGMT in cell extracts, which is sensitive to protease V8 cleavage at the glutamic acid residues at codons 30 (E30) and 172 (E172), can be specifically immunoprecipitated with an MGMT monoclonal antibody, Mab.3C7. This Mab recognizes an epitope of human MGMT including the lysine 107 (K107) which is within the most basic region that is highly conserved among mammalian MGMTs. Surprisingly, the K107L mutant protein is repair-deficient and readily cleaved by protease V8 similar to R-MGMT. We propose that R-MGMT adopted an altered conformation which exposed the Mab.3C7 epitope and rendered that protein sensitive to protease V8 attack. This proposal could be explained by the disruption of a structural "salt-link" within the molecule based on the available structural and biochemical data. The specific binding of Mab.3C7 to R-MGMT has been compared with the protease V8 method in the detection of R-MGMT in extracts of cells treated with low dosages of methyliodide (SN2) and O6-benzylguanine. Their identical behaviors in producing protease V8 sensitive R-MGMT and Mab.3C7 immunoprecipitates suggest that probably methyl iodide (an ineffective agent in producing 6RG in DNA) can directly alkylate the active site of cellular MGMT similar to O6-benzylguanine. The effectiveness of MeI in producing R-MGMT, i.e., inactivation of cellular MGMT, indicates that this agent can increase the effectiveness of environmental and endogenously produced alkylating carcinogens in producing the mutagenic O6-alkylguanine residues in DNA in vivo.

Intracellular localization of human DNA repair enzyme methylguanine-DNA methyltransferase by antibodies and its importance.

The human DNA repair enzyme, methylguanine-DNA methyltransferase (MGMT, M(r) 21,000), which protects cells against the mutagenic effect of alkylating carcinogens, was found to be localized in the cell nucleus (except the nucleolus) by immunofluorescence staining using polyclonal and monoclonal antibodies. The supporting experiments came from differential staining of the MGMT-deficient (mer-) and -proficient (mer+) cells, Western blotting analysis, and specific antibody depletion studies with the immobilized fusion protein, GSTMGMT-glutathione-Sepharose. Its localization in the nucleus agrees with its biological function and possibly explains the ineffective protection of mammalian cells (mer-) transfected with the Escherichia coli MGMT genes from bifunctional alkylating agents.