Rui Celso Martins Mamede

Systemic and Local Characterization of Regulatory T Cells in a Chronic Fungal Infection in Humans

The long-term persistence of pathogens in a host is a hallmark of certain infectious diseases, including schistosomiasis, leishmaniasis, and paracoccidioidomycosis (PCM). Natural regulatory T (Treg) cells are involved in control of the immune responses, including response to pathogens. Because CTLA-4 is constitutively expressed in Treg cells and it acts as a negative regulator of T cell activation in patients with PCM, here we investigated the involvement of Treg cells in the control of systemic and local immune response in patients with PCM. We found that the leukocyte subsets were similar in patients and controls, except for CD11c+CD1a+ cells. However, a higher frequency of CD4+CD25+ T cells expressing CTLA-4, glucorticoid-inducible TNFR, membrane-bound TGF-β, and forkhead-box 3 were observed in PBMC of patients. In accordance, these cells exhibited stronger suppressive activity when compared with those from controls (94.0 vs 67.5% of inhibition of allogeneic T cell proliferation). In addition, the data showed that CD4+CD25+ T cells expressing CTLA-4+, glucocorticoid-inducible TNFR positive, CD103+, CD45RO+, membrane-bound TGF-β, forkhead-box 3 positive, and the chemokines receptors CCR4 and CCR5 accumulate in the Paracoccidioides brasiliensis-induced lesions. Indeed, the secreted CCL17 and CCL22, both associated with the migration of Treg cells to peripheral tissues, were also detected in the biopsies. Moreover, the CD4+CD25+ T cell derived from lesions, most of them TGF-β+, also exhibited functional activity in vitro. Altogether, these data provide the first evidence that Treg cells play a role in controlling local and systemic immune response in patients with a fungal-induced granulomatous disease advancing our understanding about the immune regulation in human chronic diseases.

Prognostic factors in squamous cell carcinoma of the oral cavity

UNLABELLED Researchers have been looking for factors that can influence the prognosis of oral cancer, because its outcome is highly uncertain. AIM To evaluate variables that can impact the survival rate of patients with squamous-cell carcinoma of the oral cavity. MATERIAL AND METHODS Data analysis of 45 patients from January, 2001 to January, 2006. Survival rate curves have been estimated using the Kaplan-Meier method and they have been compared through the log-rank test and the Cox regression standard. STUDY DESIGN Retrospective analysis. RESULTS Total five-year survival rate was of 39% fpr these patients. Only the neck metastases (p=0.017), postoperative radiotherapy (p=0.056) and diseased margin(p=0.004) variables had statistic relevance. Survival rate was lower in patients with neck metastases, margins involved and those who underwent postoperative radiotherapy, in other words, those with the most aggressive tumors. After adjustment, radiotherapy did not prove to be statistically relevant. It is likely that the survival rate of 39% was due to the high number of patients with metastasis (52%) and because the samples were mostly of tongue and mouth floor diseases (82%), which are the hardest to control. CONCLUSION Neck metastases and diseased margins of oral cavity carcinomas are the prognostic factors that can most impact the survival rate.

Expression of cancer testis antigens in head and neck squamous cell carcinomas

There is considerable interest in the expression of cancer testis (CT) antigens in human cancers, because they may serve as the basis for diagnostic tests or an immunologic approach to therapy, or as prognostic markers.

Effect of gastroesophageal reflux on hypertrophy of the base of the tongue

The objective of this study was to determine a possible association between pharyngolaryngeal signs of gastroesophageal reflux (GER) and hypertrophy of the lymphoid follicles at the base of the tongue (HBT). For this purpose, 306 patients submitted to videolaryngoscopy were studied retrospectively and classified according to the presence and size of follicles on the base of the tongue. HBT was considered to be present when the follicles prevented the view of the vallecula. The patients were grouped according to the presence of videolaryngoscopic signs of GER and further subdivided according to the presence of esophageal, pharyngolaryngeal, and esophagopharyngolaryngeal symptoms, with an attempt made to relate these symptoms to the presence of HBT. HBT was detected in 62.4% (63/101) of the patients with signs of GER and in 29.3% (60/205) of patients with no signs of GER. When HBT incidence was studied according to the symptoms reported by the patient, the condition was found to be present in 57.2% (8/14) of patients with exclusively esophageal symptoms, in 63.6% (21/33) with esophagopharyngolaryngeal symptoms, and in 75% (15/20) with exclusively pharyngolaryngeal symptoms. We conclude therefore that HBT is associated with GER.

High expression of cancer testis antigens MAGE-A, MAGE-C1/CT7, MAGE-C2/CT10, NY-ESO-1, and gage in advanced squamous cell carcinoma of the larynx

Despite diagnostic and therapeutic advances in head and neck cancer, the 5‐year survival of patients with laryngeal cancer has not improved in the last 30 years. Several recent studies indicate that specific targets for immunotherapeutic approaches can be useful in the control of cancer. There is considerable interest in the expression of cancer testis antigens in human cancers since they may serve as the basis for an immunologic approach to therapy.

Fatores prognósticos no carcinoma espinocelular de cavidade oral

Devido a incerteza da evolucao do câncer oral e que os pesquisadores procuram fatores que possam influenciar no prognostico. OBJETIVO: Avaliar em pacientes com carcinoma espinocelular de cavidade oral variaveis que possam influenciar no tempo de sobrevida. MATERIAIS E METODOS: Analisados dados de 45 pacientes no periodo de Janeiro de 2001 a Janeiro de 2006. As curvas de sobrevida foram estimadas pelo metodo de Kaplan-Meier e para compara-las os testes de log-rank e o modelo de regressao de Cox. Desenho do Estudo: Analise retrospectiva. RESULTADOS: A sobrevida global foi de 39% em 5 anos. Apenas as variaveis, metastase cervical (p=0,017), radioterapia pos-operatoria (p=0,056) e margens comprometidas (p=0,004) tiveram significância estatistica. A sobrevida foi menor em pacientes: com metastase cervical; com margens comprometidas e os submetidos a radioterapia pos-operatoria, ou seja, nos tumores mais agressivos. Apos ajustamento, a radioterapia nao mostrou significância estatistica. Provavelmente a sobrevida de 39% seja pelo elevado numero de pacientes com metastase (52,2%) e pelo fato da amostra ser basicamente de cânceres de lingua e assoalho (82%), os de controle mais dificil. CONCLUSAO: A metastase cervical e o comprometimento das margens cirurgicas sao os fatores prognosticos no carcinoma de cavidade oral que influenciaram na sobrevida.

Severe hypertrophy of the base of the tongue in adults.

The lymphoid follicles at the base of the tongue can be detected when examining the pharynx of adults, but the presence of large follicles, denoted “severe” hypertrophy of the base of the tongue (HBT) is rare. The objective of the present study was to identify severe HBT cases and their symptoms and to correlate them with the presence of pharyngolaryngeal signs and esophageal symptoms of gastroesophageal reflux (GER) in patients seen at a laryngology clinic. Severe HBT was considered to be present when the follicles prevented the view of the epiglottis or were massively distributed through the pharynx and larynx. Five cases of severe HBT were detected among 306 patients submitted to videolaryngoscopy over a period of 2 years, corresponding to 1.6% (5/306) of the total sample studied. However, this index markedly increases to 4% (4/101) among patients with pharyngolaryngeal signs of GER and reached 7.5% (4/53) among patients presenting GER symptoms such as heartburn, regurgitation, retrosternal burning feeling, and dysphagia. The complaints due to severe HBT were noisy respiration, hoarseness, throat clearing, dry cough, globus pharyngeus, and nasal voice. We conclude that the frequency of hypertrophied follicles is increased in the presence of signs and symptoms of GER and those HBT symptoms are confused with those of GER, except for nasal voice and noisy respiration.

Central mucoepidermoid carcinoma : Report of 2 cases

Central mucoepidermoid carcinoma is a rare mandibular neoplasm. The objective of this paper was to report two cases.

Influence of esophageal motility on esophageal speech of laryngectomized patients.

After laryngectomy for treatment of cancer of the larynx, the patient may have vocal rehabilitation by esophageal speech. Some patients fail to achieve the esophageal speech due to reasons involving surgery, radiotherapy, and psychological alterations. Our hypothesis is that the esophageal motility alterations consequent to laryngectomy may be involved in the failure to achieve esophageal speech. Using manometry with continuous perfusion, we studied the esophageal motility of 25 laryngectomized patients, 10 of them able to produce esophageal speech and 15 unable to produce esophageal speech, and 40 asymptomatic normal volunteers. The lower esophageal sphincter (LES) pressure was measured by the rapid pull-through method and the upper esophageal sphincter (UES) pressure by the station pull-through method. The contractions were measured at 5, 10, and 15 cm above the LES after the subjects performed 10 swallows with a 5-mL bolus of water. By comparing volunteers and laryngectomized patients, we found a lower UES pressure, lower amplitude of contractions, and increased percentage of simultaneous contractions in laryngectomized patients (p <0.05). There was no difference between patients able and unable to produce esophageal speech in LES and UES pressure, esophageal contraction duration and velocity, or in the percentage of failed and simultaneous contractions. The esophageal contraction amplitude was lower in patients who acquired esophageal speech than in patients who did not (p <0.05 at 10 cm from LES). We conclude that there are esophageal motility alterations in laryngectomized patients but only the decrease of esophageal contraction amplitude seems to be associated with the acquisition of esophageal speech.

Motility of the transverse colon used for esophageal replacement.

The authors studied the motility of transverse colon used for reconstruction of the pharyngogastric transit after esophagectomy. The study included 10 patients who underwent esophagectomy 15 to 201 months (median, 48.5 months) before motility evaluation. Nine patients underwent operation because of caustic injury and one, because of esophageal cancer. The age of the patients ranged from 19 to 54 years (median, 36 years). A manometric esophageal catheter with five side holes spaced 5 cm apart (using the continuous perfusion method) was used to record motility. In three patients, it was not possible to introduce the manometric catheter inside the colon interposition. In the other seven, most of the time there was no contraction when motility was recorded. In four, there was contraction only in the segment 2 to 5 cm below the upper esophageal sphincter. In three, there were peristaltic or simultaneous contractions of long duration, sometimes associated with dry or wet swallows. The motility of colon interposition used to restore transit after esophagectomy is similar to that described for the colon. The contractions may be the consequence of graft distention after successive swallows.