Oropharyngoesophageal scintigraphy in the evaluation of swallowing disorders after surgery for oral cancer.
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Biomedical subjects
Publications and source records attributed to J Galli.
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The major diabetes quantitative trait locus (Niddm1), which segregates in crosses between GK rats affected with spontaneous type 2-like diabetes and normoglycemic F344 rats, encodes at least two different diabetes susceptibility genes. Congenic strains for the two subloci (Niddm1f and Niddm1i) have been generated by transfer of GK alleles onto the genome of F344 rats. Whereas the Niddm1f phenotype implicated insulin resistance, the Niddm1i phenotype displayed diabetes related to insulin deficiency. Individual islets from 16-week-old congenic rats were characterized for insulin release and oxygen tension (pO(2)). In the presence of 3 mmol/l glucose, insulin release from Niddm1f and Niddm1i islets was approximately 5 pmol. g(-1). s(-1) and pO(2) was 120 mmHg. Similar recordings were obtained from GK and F344 islets. When glucose was raised to 11 mmol/l, insulin release increased significantly in Niddm1f and F344 islets but was essentially unchanged in islets from GK and Niddm1i. The high glucose concentration lowered pO(2) to the same extent in islets from all strains. Addition of 1 mmol/l tolbutamide to the perifusion medium further increased pulsatile insulin release threefold in all islets. The pulse frequency was approximately 0.4 min(-1). alpha-Ketoisocaproate (11 mmol/l) alone increased pulsatile insulin release eightfold in islets from Niddm1f, Niddm1i, and control F344 rats but had no effect on insulin release from GK islets. These secretory patterns in response to alpha-ketoisocaproate were paralleled by reduction of pO(2) in Niddm1f, Niddm1i, and control F344 islets and no change of pO(2) in GK islets. The results demonstrate that Niddm1i carries alleles of gene(s) that reduce glucose-induced insulin release and that are amenable to molecular identification by genetic fine mapping.
Wegener's granulomatosis is characterized by necrotizing granulomas with vasculitis in the upper and lower respiratory tracts, systemic vasculitis and focal necrotizing glomerulonephritis. Along with this so-called classic form, a new clinical entity has been added in recent years: granulomatosis located in a single site without any form of systemic manifestation. In otorhinolaryngology the disease is manifest at the outset in 72% of the cases while it appears later in an extremely high percentage of the cases (92-100%). The nasal sinus site is the region most often affected while the areas least affected are the larynx (16% with only 2% at onset) and oropharynx (10% with only 2.5% at onset). The authors present a clinical case of pharyngeal-laryngeal localization and list the most important otorhinolaryngological sites for onset of this disorder. They discuss the diagnostic aspects of this pathology: clinical history, histopathological findings, serological results and, in particular, the positive testing of anticytoplasmatic antibodies vs. neutrophil polymorphonucleate granules (c-ANCA). In this regard, emphasis is placed on the fact that c-ANCA are highly specific being positive in 97% of the cases. Sensitivity appears to depend on activity and extension of the disease with values fluctuating from 60% for locoregional forms to 93% for generalized forms. The authors indicate that the location found in the present case--at the laryngeal-pharyngeal region boundary--is important for the clinical history, histopathological data and response to specific therapy (cyclophosphamide and desamethasone) for a diagnosis of localized Wegener granulomatosis, even when c-ANCA do not test positive.
PURPOSE: This study was designed to add new data about laryngeal carcinogenesis, a multistep process in which chemical and/or viral agents induce and promote successive alterations in growth factor-linked signal transmission pathways, genetic instability, and mutations in key genes involved in cell growth control. Epidemiological evidence suggests that human papillomavirus (HPV) infection may be associated with the development of laryngeal cancer. EXPERIMENTAL DESIGN: In this report, we have analyzed the prevalence of HPV infection and epidermal growth factor receptor (EGFR) expression in a series of 42 laryngeal squamous cell carcinomas by PCR with HPV consensus primers and by a radioligand receptor assay, respectively. RESULTS: HPV DNA was detected in 15 of 42 (35.7%) tumors, and it belonged almost exclusively to the highly oncogenic HPV-16, HPV-18, and HPV-33 genotypes. At analysis by Mann-Whitney nonparametric statistical test, EGFR level was found to be significantly higher in HPV-infected than in HPV-negative cases (T = 440; P = 0.002). EGFR overexpression (EGFR-positive status >6 fmol/mg protein, the arbitrary cutoff value chosen) was found in 20 of 42 (47.6%) tumors, and it was associated with HPV infection in a statistically significant extent (chi(2) = 4.686; P = 0.03). CONCLUSIONS: Viral oncoproteins have been shown to induce a perturbation of the cell response to signals for growth and differentiation; these findings confirm that enhanced EGFR expression and activation in laryngeal squamous cell carcinoma may occur also as a consequence of HPV infection and support the hypothesis of an involvement of HPV infection in laryngeal carcinogenesis.
Gastro-esophageal reflux (GER) is a complex pathology characterized by many clinical symptoms: gastroenterological (typical symptoms) and odontostomatological, pneumological and, more frequently, otorhinolaryngological (atypical symptoms). For this last manifestations no cause-effect relationship has yet been proven. Using a validated questionnaire about the typical reflux symptoms and the use of substances of abuse (tobacco and alcohol) and with the application of instrumental means such as electronic videolaryngoscopy and multi-electrode 24 hours esophageal pH monitoring, the Authors have studied 34 selected patients (16 female, 18 male) suffering from chronic clinical laryngeal symptoms and presenting a peculiar pharyngeal-laryngeal objectivity. Both these manifestations could be ascribed to atypical GER symptoms. Analysis of the data showed that 67.6% of the subjects presented pathological reflux, with a significant prevalence of inflammatory lesions in the posterior portion of the larynx (in 47.8% laryngitis and retrocricoid edema). The validated questionnaire on typical reflux symptoms showed that 69.5% did not complain of the typical gastro-esophageal symptoms thus indicating that pharyngeal-esophageal reflux can be totally asymptomatic. While confirming the strong association between inflammatory pathologies and GER, not enough cases have been studied to identify a direct cause-effect relationship and this is complicated by the presence of other concomitant risk factors such as cigarette smoking or alcohol consumption. Therefore the Authors underline the importance of an in-depth, multi-discipline approach in the evaluation of pharyngeal-laryngeal phlogoses. This approach must make use of all available modern diagnostic techniques (Electronic videolaryngoscopy, multi-electrode pH monitoring) in order to obtain as much information as possible to throw light on the pathogenic mechanism responsible for the damage and find more effective forms of anti-reflux therapy.
The major risk factors for the onset of precancerous lesions and squamous cell carcinoma of the larynx are, above all, tobacco smoke, alcohol abuse and exposure to viral and toxic agents. In recent years, however, gastro-esophageal reflux (GER) has also aroused significant interest not only as carcinogen but also as co-carcinogen in association with smoking and alcohol consumption. The purpose of the present work is to provide an objective evaluation of the presence of distal and proximal esophageal reflux using multi-electrode pH monitoring in patients with precancerous lesions of the larynx and laryngeal and pharyngolaryngeal neoplasms. A total of 24 patients consecutively hospitalized during 2000 were evaluated: 20 with squamous cell carcinoma of the larynx and/or pharynx-larynx and 4 with precancerous vocal cord lesions. All the patients provided a case history using a validated questionnaire and underwent electronic videolaryngoscopy and 24-hour pH monitoring. Data analysis showed that in 83.3% of the cases (20/24) pH monitoring was indicative of pathological GER and 63.7% of these patients had no complaints related to reflux. Moreover, 7/24 patients have had a previous gastrectomy (Billroth II) strictly related to the presence of bile reflux. The Authors conclude that, according with recent literature, pH monitoring data further indicate that patients with precancerous or neoplastic pharyngeal-laryngeal lesions present often a positive history of GER, even though no direct cause-effect relationship can yet be established because of the co-existence of other important risk factors such as smoking and alcohol consumption. Additionally, the achlorhydria found in 7/24 patients with an history of gastrectomy could suggest a possible, as yet unproven, role of other reflux components--in particular, of bile (alkaline) and chlorhydro-peptic (acid) components--as a risk factor or co-factor for tonset of precancerous and/or neoplastic lesions of the larynx.
Genetic analysis of the diabetic GK rat has revealed several diabetes susceptibility loci. Congenic strains have been established for the major diabetes locus, Niddm1, by transfer of GK alleles onto the genome of the normoglycemic F344 rat. Niddm1 was dissected into two subloci, physically separated in the congenic strains Niddm1b and Niddm1i, each with at least one disease susceptibility gene. Here we have mapped Niddm1b to 1 cM by genetic and pathophysiological characterization of new congenic substrains for the locus. The gene encoding insulin-degrading enzyme (IDE:) was located to this 1 cM region, and the two amino acid substitutions (H18R and A890V) identified in the GK allele reduced insulin-degrading activity by 31% in transfected cells. However, when the H18R and A890V variants were studied separately, no effects were observed, demonstrating a synergistic effect of the two variants on insulin degradation. No effect on insulin degradation was observed in cell lysates, indicating that the effect is coupled to receptor-mediated internalization of insulin. Congenic rats with the IDE: GK allele displayed post-prandial hyperglycemia, reduced lipogenesis in fat cells, blunted insulin-stimulated glucose transmembrane uptake and reduced insulin degradation in isolated muscle. Analysis of additional rat strains demonstrated that the dysfunctional IDE: allele was unique to GK. These data point to an important role for IDE: in the diabetic phenotype in GK.
We investigated by immunocytochemistry the expression of the Ca(2+) binding protein S100A2 in 62 cases of laryngeal squamous-cell carcinoma (SCC). S100A2 was detected in 18/19 (95%) low-grade tumors and in 22/43 (51%) high-grade tumors, which were partially keratinizing. The remaining 21/43 (49%) high-grade tumors were non-keratinizing, anaplastic tumors and clearly S100A2-negative. In normal laryngeal squamous epithelium and in laryngeal SCC, S100A2 expression was strictly associated with that of cytokeratins 14 (P = 0.0002) and 17 (P = 0.0021), suggesting an association of S100A2 expression and cell commitment to squamous differentiation. A correlation was found between S100A2 tumor positivity and longer relapse-free (P = 0.0005) and overall (P = 0.0095) survival.
Nine patients with laryngeal polyps, four with Reinke's edema, three with leukoplakia, one with papilloma and one with malignant tumor were studied by means of laryngeal contact endoscopy during microlaryngoscopy. This technique allowed in vivo and in situ visualization of the superficial layer of the laryngeal epithelium after staining with methylene blue. Cell structures evaluated were the size and color of the nuclei, the nucleus/cytoplasm ratio, nuclear and cytoplasmic contours, the presence of nucleoli, mitoses and keratoses, as well as the microvascular network of the mucosa and superficial cellular changes from normal to pathological. The normal squamous epithelium of the vocal cord showed a homogeneous cellular population with regular nuclear and cytoplasmic morphological characteristics and a uniform nucleus-to-cytoplasm ratio. Specific cellular epithelial patterns and several alterations of the vascular distribution were found in different pathological conditions. Cytological pictures obtained at contact endoscopy were consistent with histological findings in all the patients studied.
The aim of this study was to evaluate the efficacy of percutaneous treatment of pulmonary lesions from invasive aspergillosis in immunocompromised patients. From 1992 to 1998, ten patients (seven men and three women; mean age 56 years) affected by hematological neoplasms (8 acute myeloid leukemias, 2 non-Hodgkin's lymphomas) and post-chemotherapy prolonged neutropenia developed pulmonary lesions from invasive aspergillosis. A total of 13 lesions (diameter 2-7 cm, median 5 cm) were treated percutaneously due to insufficiency of the high-dose i.v. therapy; under CT guidance, a median of 10 cm3 per session of a 1 mg/cm3 diluted solution of amphotericin B was injected through a fine needle (21-22 G); 45 sessions overall were performed (one to five per lesion, median four), according to the volume of the nodules, tolerance, and complications. The results were retrospectively evaluated either radiologically or clinically. Complications were cough, mild hemoptysis, and small pneumothorax and/or pleural effusion. No major complications occurred. One month after the beginning of treatment, 8 lesions completely resolved, 4 greatly improved, and 1 was not significantly reduced. In all ten patients symptoms improved (eight of ten could restart chemotherapy as scheduled). After antiblastic retreatment, 1 patient had mycotic recurrence. In our experience transthoracic topical treatment with amphotericin B of single or few lung lesions from invasive aspergillosis was effective, affording a rapid improvement of the lesions and symptoms, and allowing continuation of chemotherapy as scheduled, thereby reducing the risk of recurrences.
PURPOSE: This was a radioisotope study of nasal mucociliary clearance of total and subtotal nasal obstruction. METHODS: Rhinoscintigraphy was performed by insufflating 1.85 MBq (69 mCi) Tc-99m MAA in 20 patients. Six cases were regarded as the control group, because the presence of small spurs does not affect nasal patency. The remaining 14 patients had various rhinopathic conditions. Two regions of interest were selected, one in the nasal cavity and one in the pharynx. Mucociliary transport speed was calculated. RESULTS: This parameter appeared to be a sensitive index for the assessment of the degree of mucociliary alteration. It showed that polyposis impairs mucociliary transport most severely, thus confirming the results of other published studies. CONCLUSIONS: Rhinoscintigraphy proved to be a reliable, easily reproducible, and harmless method, so it may be used for follow-up examinations in patients who have had surgery of the nose and paranasal sinuses, and for drug therapy of rhinopathic conditions.
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Previous studies have suggested that reactive oxygen species (ROS) are mediators in the teratogenic process of diabetic pregnancy. In an animal model for diabetic pregnancy, offspring of the H rat strain show minor dysmorphogenesis when the mother is diabetic, whereas the offspring of diabetic rats of a sister strain, U, display major morphologic malformations. Earlier studies have shown that embryonic catalase activity is higher in the H than in the U strain, and maternal diabetes increases this difference in activity. The aim of this study was to characterize the influence of genetic predisposition on diabetic embryopathy by comparing the mRNA levels of ROS-metabolizing enzymes in the two strains. We determined the mRNA levels of catalase, glutathione peroxidase, gamma-glutamylcystein-synthetase, glutathione reductase, and superoxide dismutase (CuZn-SOD and Mn-SOD) in day 11 embryos of normal and diabetic H and U rats using semiquantitative reverse transcription-polymerase chain reaction. The mRNA levels of catalase and Mn-SOD were increased in H embryos as a response to maternal diabetes, and no differences were found for the other genes. Sequence analysis of the catalase promoter indicated that the difference in mRNA levels may result from different regulation of transcription. Sequence analysis of the catalase cDNA revealed no differences between the two strains in the translated region, suggesting that the previously observed difference in the electrophoretic mobility in zymograms is due to posttranslational modifications. An impaired expression of scavenging enzymes in response to ROS excess can thus be an integral part of a genetic predisposition to embryonic dysmorphogenesis.
In recent years there has been a marked increase in mycosis infections of the paranasal sinuses, attributed both to an increase in the survival of subjects at risk and improved diagnostic techniques (endoscopy, CT, MR) able to identify cases which had previously gone unrecognized and treated as aspecific chronic sinusitis. The present study involves 45 cases (4.3%) out of a total of 1050 patients who had undergone endoscopic surgery for sinusopathy between April 1994 and December 1998. Following the Katzenstein classification, the cases were broken down into non-invasive chronic mycoses or fungus ball (34 cases), allergic mycoses (7), chronic indolent invasive mycoses (3) and fulminating invasive mycosis (1 case). The mycetes most often involved was Aspergillus Fumigatus (76.9%). The recurrent symptom was facial algia, followed by nasal obstruction. Paranasal sinuses endoscopy did not modify the specific picture. CT presented such indicative signs as focal areas with non-homogeneous intensity, images of metal-like foreign bodies and endosinus calcifications in 84.4% of the cases. MR--performed in only 6 cases--always presented T2 images showing the typical signal void area corresponding to pathological lesions. All patients underwent endoscopic surgery of the paranasal sinus. The effectiveness of this treatment differed according to the clinical form. In the fungus balls surgery always resolved the pathology without requiring subsequent pharmacological treatment. In allergic mycosis, surgery improved the symptom of nasal respiratory obstruction but local drug treatment was required. With the aid of drug treatment, surgery resolved chronic indolent invasive mycoses and prevented the endocranial progression of complications. In the cases of fulminating invasive mycosis, timely surgery prevented the onset of endocranial complications and made it possible to perform antimycotic polychemotherapy to control the disease. This experience shows how important a protocol involving several different tests is in diagnosing the many clinical forms of paranasal sinus mycoses and distinguishing them from sinusopathies. Endoscopic surgery is indicated for all forms of paranasal sinus mycoses although the realistic objectives differ according to type.
The aggressiveness of hypopharyngeal cancer makes broad resectioning of the circular pharyngolaryngoesophageal segments necessary, followed by reconstruction to restore the anatomical gap created as fully as possibly creating a neoesophagus with thin walls that can easily be released. Over the years several procedures have been fine tuned for reconstruction of the upper digestive tract employing transposed viscera, miocutaneous pedunculated flaps, revascularized fascio-cutaneous or visceral free flaps. Currently the revascularized jejunum loop is one of the most commonly used methods in the reconstruction of the hypopharynx. Its popularity is due to some anatomical and physiological advantages: it requires transposition of a brief intestinal tract anatomically well adapted to the reconstruction site, ensuring rapid functional recovery. The authors report the oncological and functional results obtained in 25 patients who underwent circular pharyngolaryngectomy followed by reconstruction with a revascularized jejunum loop. The percentage of transplant survival was 90% and local and general complications were reduced to a minimum. The functional results--both in terms of deglutition and phonation--were satisfactory while patient survival (6-37 months follow-up) was in line with that reported by other authors for the same tumor (47%). Although prognosis for hypopharyngeal-esophageal neoplasms is still quite poor, this experience shows that circular pharyngolaryngectomy followed by reconstruction with autotransplant of the jejunum is an excellent choice since it offers the patient a prompt, acceptable functional recovery and a fair quality for his remaining life.
The initial diagnosis and subsequent treatment of rhino-orbital mucormycoses is quite difficult, particularly because the patient may find it difficult to accept aggressive therapeutic protocols, even when free of any endocranial involvement. The authors draw inspiration from a clinical case of rhino-orbital mucormycosis in a patient suffering from decompensated type I diabetes mellitus to discuss the main clinical-diagnostic and therapeutic aspects of this disorder. Timely medical-surgical treatment proves extremely important for prognosis, preventing the intracranial extension of the lesion which is the cause of death in 80% of such cases. As regards the diagnostic protocol, careful clinical, radiological monitoring with CT and NMR--in strict interdisciplinary cooperation between otorhinolaryngologist, radiologist, ophthalmologist, microbiologist and histopathologist--is especially important. Radical surgery, at times demolition, associated with correction of the metabolic decompensation, systemic therapy with Amphotericin B and localbi-weekly medication for three months constitutes the best therapeutic protocol for treatment of this disorder.
We report the case of a patient with a laryngeal carcinoma in whom asymptomatic hyperparathyroidism was also detected during the preoperative work-up. A planar (201)Thallium/(99m)Tc-pertecnetate subtraction scintigraphy was performed in order to locate the suspected parathyroid adenoma. The study showed a single area of increased (201)Thallium uptake just above the thyroid isthmus, likely due to the laryngeal tumor. The scintigraphic study was repeated using (99m)Tc-Sestamibi and (99m)Tc-pertechnetate and employing the SPECT technique. Both SPECT studies made it possible to identify correctly the parathyroid adenoma, located inferiorly and in a posterior position to the lower third of the right thyroid lobe. The laryngeal tumor and parathyroid adenoma could be excised in a single surgery session. This case is of interest due to the rarity of the coexistence of two neck tumors and the clear advantage shown by the SPECT technique with (99m)Tc-Sestamibi over the planar technique with 201Thallium.