Biomedical subjects
Publications and source records attributed to C Sepe.
Cholesteatoma is a disease that involves almost exclusively the middle ear structures and the mastoid bone. In rare cases it involves the external auditory canal. The author would like to present case report of a patient affected by external ear canal cholesteatoma associated to fibrous dysplasia of the temporal bone. The problems related to the pathogenesis and the diagnosis of the disease are presented and discussed.
To investigate possible biochemical mechanisms underlying the "toxic gain of function" associated with polyglutamine expansions, the ability of guinea pig liver tissue transglutaminase to catalyze covalent attachments of various polyamines to polyglutamine peptides was examined. Of the polyamines tested, spermine is the most active substrate, followed by spermidine and putrescine. Formation of covalent cross links between polyglutamine peptides and polyamines yields high-M(r) aggregates--a process that is favored with longer polyglutamines. In the presence of tissue transglutaminase, purified glyceraldehyde-3-phosphate dehydrogenase (a key glycolytic enzyme that binds tightly to the polyglutamine domains of both huntingtin and dentatorubral-pallidoluysian atrophy proteins) is covalently attached to polyglutamine peptides in vitro, resulting in the formation of high-M(r) aggregates. In addition, endogenous glyceraldehyde-3-phosphate dehydrogenase of a Balb-c 3T3 fibroblast cell line overexpressing human tissue transglutaminase forms cross-links with a Q60 polypeptide added to the cell homogenate. Possibly, expansion of polyglutamine domains (thus far known to occur in the gene products associated with at least seven neurodegenerative diseases) leads to increased/aberrant tissue transglutaminase-catalyzed cross-linking reactions with both polyamines and susceptible proteins, such as glyceraldehyde-3-phosphate dehydrogenase. Formation of cross-linked heteropolymers may lead to deposition of high-M(r) protein aggregates, thereby contributing to cell death.
Delayed onset of facial palsy is possibly an underestimated but distressing complication of acoustic neuroma surgery. The incidence of this complication reported in the literature has varied from 11.7 to 41%. This study reviewed retrospectively 60 primary acoustic neuroma surgeries performed by a single neurotologist. The delayed onset of facial dysfunction was defined according to the guidelines described by of Lalwani Butt, Jackler, Pitts and Jingling in 1995. They considered either a deterioration of facial function from normal to abnormal or an increased severity of the degree of facial paralysis, which was grouped using the House-Brackmann scale system. Fifteen of the 60 patients (25%) were found to have a deterioration of facial function. The incidence of delayed facial palsy was not influenced by age, sex or tumor size. The majority of the patients had a favorable prognosis. Only three patients had a grade III-IV facial function at 1 year. It is possible that these latter cases might have benefited from intraoperative meatal facial nerve decompression, as advocated by Sargent, Kartush and Graham.
We have developed a computer program for the rapid assessment of the primary structure differences between a protein of unknown sequence and a homologous known protein. Both proteins are reduced, alkylated, and digested with the same hydrolytic agent. The unfractionated peptide mixtures are submitted to automatic sequence analysis. Based on the knowledge of the reference sequence, the program utilizes the analysis data to identify all the potential peptides present in the two mixtures, determining their primary structure, homology degree, and molecular weight calculated both as integer MH+ and average mass variables. These fingerprints allow the user to easily identify the structural differences between the two proteins and clarify possible doubts by a mass spectrometric analysis of the two mixtures. In order to verify the utility of the program, we provide an application example using the already reported data of two homologous proteins.
This paper describes a series of patients with a petrous temporal bone cholesteatoma paying particular attention to the complications and their management. Sixteen patients who underwent surgery in our department were reviewed. Topographically, the petrous bone cholesteatomas were grouped into five categories according to the classification proposed by Sanna et al. There were five massive labyrinthine; five infralabyrinthine; one apical; four supralabyrinthine; and one infralabyrinthine-apical. Clinically, the presenting symptom of these lesions were facial nerve paralysis (10 patients) and unilateral deafness (13 patients). Total removal of the cholesteatomas was achieved in all patients using different surgical approaches according to their site and extent. Recurrences were observed in two patients after 8 months and 24 months, respectively. The facial nerve was infiltrated and compressed by the cholesteatoma in eight patients. Seven were managed with cable grafts using sural nerve. One of these patients was treated using a facial-hypoglossal anastomosis because of the failure of the graft. In the remaining patient, a baby-sitter procedure was employed. In the other two patients, the preoperative facial paralysis was due to compression by the cholesteatoma, and its removal allowed partial recovery of facial function. The rationale of the surgical management of petrous bone cholesteatoma is its radical and total removal. Our present policy is to prefer approaches which result in a closed cavity obliterating the eustachian tube and closing the auditory canal as a blind sac. Facial nerve function is the main complication of these lesions, Facial nerve involvement requires rapid management because the duration of the paralysis is directly related to poor recovery of facial function.
AIM OF THE STUDY: Postoperative sensory component of the facial nerve after acoustic tumor surgery has received little attention in the literature. The object of the present investigation was to review this specific topic analyzing the postoperative frequency of taste and lacrimation (crocodile tears or dry eye) abnormalities. MATERIAL AND METHODS: 54 patients who underwent acoustic tumor removal were selected for this study. Each of these patients was recalled and pre and postoperative evolution of the sensory dysfunction were assessed. The latters were correlated with the facial function evaluated according to the House-Brackmann classification. RESULTS: Postoperative taste dysfunction (reduced or changed sensation) was complained by 38.5% of the patients. After surgery, 42.3% of the cases had crocodile tears, while in 59.6% altered tearing occurred. DISCUSSION: The present study, according to the Irving et al's experience confirmed a significant incidence of postoperative abnormal function of the sensory facial nerve. The influence of the motor component on these outcomes was variable. Lacrimation worsened when facial function was poor. On the other hand, grades V or VI did rarely manifest crocodile tears. Clinically, these findings implies the importance of a preoperative counseling of such particular aspect in the candidates to surgery of acoustic neuroma in order to adequately motivate them and, at the same time, to reduce their psychological discomfort.
OBJECTIVE: Postoperative cerebrospinal fluid leak (CSF) is a serious complication of the cerebellopontine angle surgery. In the current literature, CSF leak rates vary from 8.1 to 20%. The various options in managing this troublesome complication include conservative treatment or invasive surgical repair. The focus of this report is to retrospectively analyze our experience on this specific topic reviewing the incidence of CSF leak and the outcomes of its treatment in a group of patients who underwent surgery for different pathology of the cerebellopontine angle. METHOD: Eighty-five patients who underwent primary surgical procedures performed by a single neurologist were selected for this study. There were 70 surgical removals of acoustic neuromas, and 15 other cerebellopontine lesions. RESULTS: The overall incidence of CSF leak in the total group analyzed was 17.6%. There were five CSF rhinorrheas and 10 wound CSF leaks. Ten acoustic neuromas and five other cerebellopontine angle lesions exhibited this complication. The leak was cured in 53.3% of the cases using a continuous lumbar cerebrospinal fluid drainage (CLCFD). In two patients, the leak was treated with an extradural repair. CONCLUSIONS: Although CLCFD is not routinely used in the treatment of the CSF leak, it proved to be an efficacious and safe option, confirmed by no meningitis observed in our patients treated with this method.
HYPOTHESIS: The objective of this study was to present the authors' experience in the management of labyrinthine fistula caused by cholesteatoma. METHODS: The clinical charts of 92 patients who underwent surgical procedures for cholesteatoma complicated by labyrinthine fistula between 1979 and 1975 were reviewed retrospectively. In this period, 1,205 patients were operated on for cholesteatoma. In each patient, the site and size of the fistula were evaluated during surgery and the hearing thresholds were compared before and after surgery. RESULTS: The fistula involved the lateral semicircular canal in 71 patients. Multiple fistulas were observed in nine patients. Postoperative hearing levels were unchanged or improved in 83.7% of patients. Comparison between hearing outcomes and size of the fistula showed better findings when smaller size fistulas were found. No significant differences between open and closed techniques were detected. Favorable outcomes were obtained in patients treated with surgical obliteration of the interrupted labyrinth. CONCLUSIONS: The current study confirmed that careful manipulation of the labyrinthine fistula is mandatory to preserve hearing functions for these patients. According to the authors' experience, the future trend for fistula treatment could be directed toward less conservative techniques compared with the previous indications favoring methods of interruption and subsequent obliteration of the semicircular canals.
We designed a computer program for the assignment of protein disulphides using mass spectrometric data. All the theoretical linear peptides containing from one to three cysteines are generated on the basis of the protein sequence. Their combination ways are determined in order to create all the possible disulphide-bridged fragments containing from two to six cysteines and to calculate their molecular weight. One, two and three S-S bridges per linked fragment were considered, taking into account the possibility that the fragments contain unabridged residues. The mass data obtained from the spectral analysis of peptide mixtures of the digested protein are then associated to the fitting structures of disulphide-bridged peptides, giving rise to the primary output. This output can then be screened by using information on the specificity of the proteolytic agent(s) used and/or any further mass data provided by Edman degradation and/or carboxypeptidase treatment of the peptide mixtures. The need for such a computer aid is discussed and examples of application are given.
We have designed and implemented on a personal computer a program for identifying and quantifying the fragments present in a peptide mixture obtained by hydrolysing a polypeptide of known sequence using digesting agents. The qualitative data utilized by the main algorithm consist of the target sequence of the intact molecule and the amino acid residues identified at each step of the automatic sequence analysis of the unfractionated digestion mixture. In this way, the sequence of each fragment present in the mixture is quickly reconstructed. Furthermore, if the quantitative data of the amino acid residues identified at each step of the sequence analysis are utilized, the program will correlate the sequence of each fragment to its amount. We furnish an example of the application intended for the rapid identification and characterization of the extracellular proteinases produced by a basidiomycete fungus, utilizing the bovine insulin beta-chain as target substrate. A variety of uses for the method are discussed.
With the aim of limiting peptide purification steps and unambiguously ascertaining protein sequences, we have designed and implemented on a personal computer an algorithm to determine sequence alignment by utilizing data obtained from automatic Edman degradation performed on a single peptide mixture and individual peptides. The protein under study is digested by two different hydrolysis methods and fragments are just isolated from one mixture and sequenced, while the second mixture is submitted unfractionated to sequence analysis. The algorithm provides for the exact alignment of the individual peptides using the mixture data for the overlapping. We report an example of application of this approach by utilizing experimental data obtained from a protein of known sequence.
The aim of the present study was to explore the association between memory impairment and primary headache. 100 headache patients (71 females, 29 males, mean age 35.6 +/- 13.8) and 20 healthy subjects (14 females, 6 males, mean age 37.3 +/- 12.1) as control group, were examined: a significant difference between the two groups was found (p < 0.001). The patients were divided into different groups according to the kind of headache, the use of analgesics, the pain side and the illness length: significant differences were found between patients who made a low use of analgesics and the others (p < 0.001); the illness duration also seems to be relevant in the progressive memory impairment, because it strengthens some immunologic and biochemical mechanisms able to favour a progressive mnemonic damage.
The fast atom bombardment (FAB) mass spectrometric analysis of proteolytic digests of proteins is currently used in protein structural characterization. The major current limitation of this procedure is that not all the peptides generated by enzyme digestion can be observed in the spectra. Previous studies showed that in a mixture the more hydrophilic peptides are suppressed. Several enzymatic digests of 18 different proteins ranging from 10 kDa to 67 kDa in molecular weight were examined using FAB mass spectrometry. It was observed that, even though the hydrophobicity of peptides is a factor in determining their presence or absence in the spectra, the predictions of whether or not a peptide would be detected based on this criterion varies in a wide range of values. Moreover, present results seem to indicate that the presence of particular amino acid side chains within a peptide sequence capable of forming hydrogen bonds with the matrix heavily affects the behaviour of that peptide in the mixture, despite the overall hydrophobicity of the peptide itself.
A computer program allowing the correct alignment of peptides generated by a first cleaving agent during protein sequence determination studies has been developed. The program elaborates data obtained from fast atom bombardment mass spectrometric analysis of different digests of the protein. The recorded mass values are used to identify peptides in these digests that overlap peptides from the first cleavage, thus making it possible to establish unambiguously the correct order of these peptides in the protein chain. This procedure has been tested on a model protein by reconstructing the complete sequence of human beta-globin chain, determining the correct alignment of 14 tryptic peptides.
PROLANG is an improved version of the PROSOFT program. Improvements to the old commands were made and new ones were added, PROLANG is an open software that users with BASIC programming experience can easily expand.
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