[Morphological study of the palatine tonsils: clinical and histopathological considerations]. / Considerazioni cliniche ed istopatologiche in uno studio morfologico della tonsilla palatina.

This study examined 71 pediatric tonsillectomy patients through accurate case history and clinical examination, placing particular emphasis on pathologies concomitant to tonsillopathy. In an attempt to find anatomo-clinical correlations, these data were processed together with the results of a histomorphological study of thetonsil epithelium, performed on all tonsillectomy samples. The majority of these patients were females and none more than 13 years of age. Numerous pathologies were found associated with the tonsillopathy and in varying combinations, first and foremost of which was adenoid hypertrophy. Only approximately one fifth of the patients did not show any concomitant pathology of note. All patients presented a history of recurrent pharyngotonsillitis (at least 4 episodes a year) with symptoms arising from 1 to 10 years prior to surgery. The concomitant pathologies included: respiratory, cutaneous and food allergies, asthma, obstructive sleep apnea, rheumatic diseases, etc. From the histomorphological point of view, particular modifications were found in the follicle epithelium and interstitial cells of the palatine tonsil. An exasperated fibrotic interstitial reaction and chronic duration of the disease appeared to prevent tonsil filter function, facilitating chronicization of the tonsillopathy or onset of recurrent infections and concomitant allergies. In the allergic patients the tonsil epithelium was thickened and compact and showed various degrees of chorion edema, in agreement with what is found in the literature. On the contrary, few morphostructural palatine tonsil mutations were found in those subjects which did not present any concomitant pathology or were affected by tonsillopathy of brief duration. All the histomorphological modifications encountered appear related to the individual patient history, confirming the hypothesis that tonsil epithelium can not only condition the evolution of tonsillopathy--reflecting the effect of various factors--but, above all, it directs the immune response, thus playing a role in the development of various concomitant pathologies.

[Description of a particular case of the so-called Schmincke lymphoepithelioma and study of the correlation with Epstein-Barr virus]. / Descrizione di un caso particolare del cosiddetto linfoepitelioma di schmincke e studio delle correlazioni con il virus di Epstein-Barr.

For poorly differentiated rhinopharyngeal carcinomas, the clinical presentation (association with the Epstein-Barr virus, paraneoplastic syndromes, onset of lymphoma) and the histopathological features can be polymorphous and they can confound or delay diagnosis and preparation of an adequate treatment plan (radio-chemotherapy). Often these neoplasms arise as clinically primitive laterocervical metastases, masked by clinical findings and a history that can lead to the mistaken diagnosis of systemic lymphoproliferative processes such as Hodgkin's disease. Here an observation of this type is presented in a young patient (19 years old) who came under observation for a laterocervical tumefaction recurrent from a previous exeresis performed at another hospital and symptoms of serotine febricula, dysphagia and serology positive for the Epstein-Barr virus (EBV). The patient underwent surgery and then radiotherapy and has been under close post-operative follow-up for two years. To date the patient's condition--both local and general--is good. The particular histology of the neoformation lies in the abundant infiltration of plasma cell and lymphocyte eosinophils, at times in blastic form. Moreover, elements with a large clear nucleus and evident nucleolus (Hodgkin-like) and scattered multinucleate Langhans-type giant cells can be seen. Immunohistologically the tumor cells markedly express for cytokeratin and the latent membrane protein (LMP1) of the Epstein-Barr virus (EBV) and show a high growth fraction. Under the electron microscope, the plurinucleate giant cells present large nuclei with morphology similar to that of tumor cells. The clear cytokeratin-positivity of the tumor elements and the histological and ultrastructural features mentioned led to the diagnosis of a massive metastasis from lymphoepithelial carcinoma, the Schmincke variant, plus EBV infection of the neoplastic cells. The authors conclude assuming that the particular granulomatous reaction is due to the host's reaction to the tumor cells, but also to the reaction to the viral antigens. In the former case we find an attempt to limit the carcinomatous process; in the latter it is a response caused by the EBV and is not, apparently, aimed at protecting against the neoplasm rather it facilitates the neoplastic process.

[Upper maxillary cysts: embryogenic and surgical considerations in our cases]. / Cisti del mascellare superiore: considerazioni embriogenetiche e chirurgiche su una nostra casistica.

Upper maxillary cysts are a chapter in otorhinolaryngological pathology which have been relatively neglected by the Literature. The reason for this most likely lies in the difficulty in producing a nosographic picture of these pathologies which border on other surgical fields (dentistry, maxillofacial surgery), and because they show significant clinical and etiopathogenic polymorphism. The elements that characterize upper maxillary cysts as a separate clinical entity are basically their cystic nature and origin within the upper maxillary bone, although they can expand widely within the medio-facial region (nasal vestibule, oral vestibule, nasolabial region, palate, maxillary sinus). After having reviewed the various classification schemes proposed over the years, and briefly examining the main clinical and etiopathogenic characteristics and principles for surgical treatment, the present work offers a surgical case study, together with the related iconography. Moreover this work does not neglect embryogenic considerations which are indispensable for the study of some of these pathologies. In this manner the results for 35 surgical procedures on upper maxillary cysts performed from 1989 to 1996 are presented and classified following the Cudennec classification module (1991). This study shows the variety of possible clinical manifestations for these pathologies. Such a variety makes correct diagnosis imperative--today facilitated by modern imaging techniques--and requires diversifying the surgical approach, conditioned not only by the site, extension and nature of the specific lesion, but also by the related symptoms. The significant progress in surgical techniques has made increasingly functional surgery possible and led to the abandonment of such conventional radical techniques as the Caldwell-Luc procedure. Moreover, CT and NMR have provided good image definition, specifying precisely the limits and extensions and, in most cases, facilitating diagnosis of the nature of the disorder with direct and indirect signs of the cystic nature of the lesions whenever the clinical data proves inadequate.

[Benign extracranial cervical-facial schwannomas: anatomo-clinical and diagnostic considerations on our case reports and review of literature]. / Schwannomi benigni extracranici del distretto cervico-facciale: considerazioni anatomo-cliniche e diagnostiche su una nostra casistica e revisione letteraria.

Schwannoma is a rare neoplasm in the E.N.T. areas although it is characteristic of this discipline. Indeed, examination of the most recent data in the literature shows that approximately 45% of all neoplasms of the peripheral nerve linings occur in the head and neck district, the most common neurogenic tumors are schwannomas and these constitute 35% of all head and neck tumors. In reviewing the literature attention was focused on schwannomas originating in unusual sites, neglecting the most common sites originating in the eighth and seventh pair of cranial nerves. It was seen that the site of origin and clinical manifestation of these lesions varies widely and the four cases presented here are no exception. These are four schwannomas which came under observation between 1994 and 1997. The sites of origin were, respectively: the floor of the mouth, the submandibular region (corresponding to the Warthon duct), the anterior wall of the external auditory canal and the hypopharynx (corresponding to the pyriform sinus). All of these cases proved quite rare in the literature. All the cases underwent accurate anatomopathological examination and the paper discusses the particular histological and immunohistochemical features encountered. Reference is also made to the problems of differential diagnosis vs. other types of soft tissue tumors. Emphasis is placed on the demonstrated difficulty in recognizing schwannomas from the macroscopic and surgical points of view. The absence of mitoses, necroses, invasiveness and specific features--i.e. hyperchromia and pleomorphism of the nuclei or the presence of large atypical cells--are all parameters confirming that the lesions observed in the present study were benign. No anatompathological features were observed that could justify any particular expression of the schwannoma in the specific sites involved. Nevertheless, the authors present these case because a review of the literature indicated that they are extremely rare and because differential diagnosis of these unusual manifestations is so complex.

Liver steatosis and chronic hepatitis C: a spurious association?

OBJECTIVE: Based on the observation of steatosis in the majority of liver biopsy specimens from hepatitis C virus (HCV) infected patients, it has been suggested that HCV may be pathogenetically implicated. We aimed to determine the influence of possible underlying metabolic disorders on this association. DESIGN: In a series of 148 consecutive patients with chronic hepatitis, with and without HCV infection, we evaluated by logistic regression analysis the association between steatosis and HCV, controlling for diabetes, obesity, hyperlipidaemia and alcohol. These are all known to be factors associated with a fatty liver, and also with the histological degree of liver disease. RESULTS: Antibodies to HCV were detected in 121 of 148 (81.8%) patients. Steatosis, distributed in different histological patterns, was found in 73 of 121 (60%) HCV-positive and in 14 of 27 (52%) HCV-negative patients (P = NS). Using simple logistic regression, the association Of HCV to steatosis was weak and not statistically significant (OR, 1.14; 95% CI, 0.61-3.27). The same was true for hyperlipidaemia (OR, 4.45; 95% CI, 0.52-37.9). A strong and statistically significant association was found, however, between obesity and steatosis (OR, 4.18) and between steatosis and the highest degree of histological severity (Liver cirrhosis vs chronic persistent hepatitis: OR, 12.8). Using multivariate analysis, the association between steatosis and HCV was shown to be not significant. Hyperlipidaemia, among all the independent variables tested, was shown to be co-linear with obesity. CONCLUSION: Our findings seem to suggest that HCV is irrelevant as a risk factor for a fatty liver. The results indicated that there is a 'confounding' role of obesity and hyperlipidaemia, and that the severity of liver disease is associated with steatosis and HCV.

Biological and clinical significance of neutralizing and binding antibodies to interferon-alpha (IFN-alpha) during therapy for chronic hepatitis C.

It is known that IFN therapy can induce the development of anti-IFN antibodies. In order to evaluate the biological and clinical significance of both neutralizing (NA) and non-neutralizing (binding) antibodies, 123 patients with chronic hepatitis C treated with recombinant IFN-alpha were examined. Among them, 15 were positive for NA and 24 for binding antibodies. The kinetics of NA appearance show that, in general, they develop early during the first 3 months of treatment. Moreover, NA seem to be clinically relevant, since they may be responsible for non-responsiveness to treatment in 53% of patients who develop them. The evaluation of the clinical significance of binding antibodies is more difficult. They appear significantly earlier in non-responders than in responders, but no differences were observed in the overall percentage of seroconversion between responders and non-responders. Thus, it is not possible at the moment to establish their possible role in inducing non-responsiveness.

Prevalence of antibodies to hepatitis C virus among family members of patients with chronic hepatitis C.

In this study, 108 family members of 40 chronically HCV-infected patients (19 post-transfusion and 21 sporadic), and 45 families of 16 anti-HCV-negative index cases (control group) were tested for anti-HCV antibodies. Anti-HCV antibodies were found in 16 (14.8%) families of anti-HCV-positive index cases (15% males and 14.6% females; p = NS), with no difference between families of index cases with post-transfusion and those with sporadic HCV infection. Out of the 16 anti-HCV positive family members, 12 (75%) had clinical and/or serological evidence of chronic liver damage. None of the control group subjects were anti-HCV-positive (p < 0.01). The rate of anti-HCV positivity was 34.4% among spouses, 14.3% among siblings, 16.7% among cohabitants and 2.3% among children; anti-HCV antibodies were not detected among parents. We found a positive correlation between the prevalence of anti-HCV antibodies among families and the severity of the HCV-related chronic liver damage of the index cases (p < 0.00005). In addition, to confirm that HCV infection and HCV-related chronic hepatitis may be transmitted intrafamiliarly, our findings also indicate that horizontal, especially sexual contact, is a more important route of HCV infection than vertical/perinatal transmission. Finally, the risk of acquiring HCV infection among families appears to be the highest when index cases are suffering from severe HCV-related chronic hepatitis.

Disseminated intravascular coagulation associated with disseminated cryptococcosis in a patient with acquired immunodeficiency syndrome.

Disseminated intravascular coagulation (DIC) is uncommon in acquired immunodeficiency syndrome (AIDS), despite the high incidence of infectious diseases. We describe an HIV-infected patient presenting with disseminated cryptococcosis, who had clear-cut laboratory evidence of progressively worsening DIC (thrombocytopenia, prolonged prothrombin time and partial thromboplastin time, hypofibrinogenemia, increased fibrin(ogen) degradation products and D-Dimer, reduced antithrombin III), although the clinical signs of the disease were rather scarce. The patient died despite intense treatment, which included heparin and fresh frozen plasma, and DIC was confirmed histologically. It is suggested that, in a patient with AIDS presenting with an opportunistic infection, laboratory signs of DIC should be carefully checked to early recognize this complication and promptly initiate the required therapy.

2',5'-Oligoadenylate synthetase activity as a responsive marker during interferon therapy for chronic hepatitis C.

The 2',5'-oligoadenylate (2-5A) synthetase is an intracellular enzyme induced by interferon (IFN). We evaluated the serum level of this enzyme in 25 patients affected by chronic hepatitis C and treated with recombinant IFN-alpha 2b. At the end of treatment, 14 patients were classified as responders and 11 as nonresponders. Before therapy initiation no significant differences in 2-5A synthetase levels among the patients were detected, while during therapy responders showed higher mean levels of 2-5A synthetase than nonresponders. An increase in the enzyme activity was observed after 1 month of therapy, and this trend was maintained in the following 2 months. The peak of 2-5A synthetase activity was found at the end of therapy. 2-5A synthetase levels were negatively correlated with serum alanine aminotransferase (ALT). This study suggests that 2-5A synthetase may be a useful marker to monitor IFN efficacy during treatment and to predict the clinical response.

Occurrence of hepatitis delta virus infection in hepatitis B virus-infected patients with different serum patterns of preS gene-encoded proteins.

The occurrence of delta superinfection among viremic and nonviremic HbsAg-positive carriers with different serum patterns and levels of preS1 and preS2 antigens was investigated. PreS1 and preS2 antigens in serum, as well as their levels, were found to be independent of hepatitis B virus (HBV) replicative activity. Serological evidence of hepatitis delta virus (HDV) superinfection was found in 34 out of 233 (14.6%) HBsAg-positive carriers; all these 34 patients resulted positive for antibody to hepatitis B 'e' antigen, and 33 of them were negative for circulating HBV-DNA. Delta superinfection occurred only among HBsAg-positive carriers whose sera were reactive for both preS1 and preS2 antigens (30 out of 142; 21.1%) or at least for preS1 alone (4 out of 63; 6.3%), but not among the patients with undetectable levels of both these antigens. Serum levels of both preS1 (p < 0.005) and preS2 (p < 0.001) antigens were found to be significantly higher in delta-positive HBsAg-positive carriers than in patients with HBV infection uncomplicated by HDV. In addition to confirm previous observations that the detection of both preS antigens in HBsAg-positive sera is independent of HBV replication, these findings clearly show that HDV infection requires not only the presence of HBsAg, but also the presence of preS peptides, and seem to suggest a low susceptibility of HBsAg-positive carriers with low or undetectable synthesis and secretion of HBV surface proteins to delta superinfection.

Prolonged viral hepatitis type A with cholestasis: case report.

We describe a clinical case of an eleven year old boy with a protracted cholestatic form of viral hepatitis type A. The role of a macrolide antibiotic in the determinism of this form of hepatitis is discussed.

Hepatitis C virus infection in anti-HBe-positive HBsAg carriers with chronic liver disease.

In the present study, sera from chronic hepatitis B surface antigen (HBsAg) carriers positive for antibody to hepatitis B 'e' antigen (anti-HBe) with evolutive liver disease as correlated with anti-HBe-positive healthy carriers, were examined for antibodies to hepatitis C virus (HCV). Anti-HCV antibodies were detected in 32/124 (25.8%) anti-HBe-positive carriers with chronic liver disease and in none of the 46 healthy carriers. When anti-HCV positivity was evaluated in relationship to the degree of severity of liver disease and possible confounding factors such as hepatitis B virus replication or other potential hepatolesive factors were eliminated by using logistic regression, the odds ratio of liver cirrhosis versus chronic persistent hepatitis was 18 (95%, CI 3.5-92.5). Therefore, our results indicate that HCV may be implicated in the determinism and severity of liver damage in a significant proportion of anti-HBe-positive chronic HBsAg carriers.

[Munchausen syndrome. Apropos of a case]. / Sindrome di Munchausen. Considerazioni a proposito di un caso.

The study of a case of Munchausen's syndrome allows for considerations of problems involved in factitious illness, both in terms of clinical methods and evaluation of psychosocial conditions. The case described is interesting not only because of the diagnostic commitment involved but also for the role which environmental situations may have in aiding or conditioning such a form of factitious illness.

Overnight comparable anacidity by standard large and half-single bedtime doses of H2 antagonists in duodenal ulcer patients: a clinical pharmacological study.

We continuously monitored 24-h intragastric pH in eight ulcer patients--who received orally at 10 PM in double-blind, randomized fashion either placebo, ranitidine 150 mg and 300 mg, or famotidine 20 mg and 40 mg, on five separate occasions--in order to determine whether half the commonly used bedtime doses of the H2 antagonists would suppress overnight acidity to the same extent as the large doses. Our results show that, during the nocturnal period (from 11 PM to 8 AM), significantly higher pH values were obtained with the large doses than with the half doses of both ranitidine (p = 0.00005) and famotidine (p = 0.00004). However, hydrogen ion activity was virtually nil with each H2 blocker dose regimen, and the percent inhibition of acidity over placebo was 100% for all of them (p = approximately equal to 0). Further more, with regard to the nocturnal period elapsed in min above 5.0 pH units, there was no significant difference between the two ranitidine doses (p = 0.39) and the two famotidine doses (p = 0.81). Therefore, the two dosing schedules of each H2 antagonist increased intragastric pH differently, but both the half and the standard large regimens produced similar overnight virtual anacidity. It is suggested that ranitidine and famotidine should be evaluated in the acute treatment of duodenal ulcer, using single bedtime doses half those commonly employed.

24-hour study of intragastric acidity in duodenal ulcer patients and normal subjects using continuous intraluminal pH-metry.

The circadian pattern of intragastric acidity was assessed in 19 healthy subjects and 37 patients with active, endoscopically proven duodenal ulcer using 24-hr continuous intraluminal pH-metry. The median pH 24-hr profiles showed that ulcer patients had lower postprandial pH elevations and a smaller decline in acidity during the early morning hours when compared with controls. The after-lunch and -dinner area under the curve and maximum pH values were significantly higher in controls compared to ulcer patients. In the nighttime, the median pH values in controls were significantly higher during 9 PM to 12 PM (P = 0.02), 12 PM to 4 AM (P = 0.01), and 4 AM to 8 AM (P = 0.0008) compared to the ulcer patients. We conclude that the 24-hr acidity is higher in ulcer patients compared to healthy subjects and that the differences are particularly evident in the postprandial and nocturnal periods.

Once and twice daily doses of H2 antagonists revisited, using continuous intragastric pH monitoring.

Eight patients with previous duodenal ulcer in symptomatic remission underwent continuous intraluminal pH monitoring on five separate occasions to compare the effects on 24-h intragastric acidity of placebo, 300 mg ranitidine at night, 150 mg ranitidine twice daily, 40 mg famotidine at night, and 20 mg famotidine twice daily. All H2 blocker treatments were superior to placebo (p congruent to 0), whereas the twice daily doses of both ranitidine and famotidine were significantly better (p congruent to 0 and p = 0.00006, respectively) than the single ones in reducing 24-h intragastric acidity. The higher acid inhibitory effect of the twice daily dose regimens than of the single ones was evident during the daytime, whereas no difference between them was found during the nighttime (from 2200 to 0800 h). These data are at variance with those previously published, and the slight effect of the single nightly doses of H2 blockers on daytime acidity seems to confirm further that the suppression of nocturnal acidity may really be the decisive factor in the success of this dosing schedule in treating duodenal ulcer.

A comparison of the effects on intragastric acidity of bedtime or dinnertime administration of a once daily dose of famotidine.

In order to assess whether dinnertime administration of a once daily dose of famotidine is more advantageous than a bedtime dose in suppressing evening and nocturnal gastric acidity, we gave nine patients with a past history of duodenal ulcer in double-blind, randomized fashion either (1) placebo at 6 p.m. and 10 p.m., (2) famotidine 40 mg at 6 p.m. (Fam 6) + placebo at 10 p.m. or (3) placebo at 6 p.m. + famotidine at 10 p.m. (Fam 10) on three separate occasions. Comparison of the 24-h median pH values showed that the two administrations of famotidine were superior to placebo, while Fam 6 was significantly more effective than Fam 10. The gain in acid suppression of Fam 6 with respect to Fam 10 was particularly evident from 6 p.m. to midnight. Although the antisecretory effectiveness of Fam 6 was lower than that of Fam 10 from 4 a.m. to 8 a.m., it remained clearly higher than that of placebo and ensured virtual anacidity (median pH = 6.7) even in this time segment. We conclude that a once daily dose of famotidine at 6 p.m. is better than bedtime administration at covering the long period of continuous unbuffered intragastric acidity which extends from after the evening meal to breakfast.

[Changes in laboratory and clinical parameters in subjects with chronic brucellosis treated with an immunomodulator: methisoprinol]. / Modificazioni di alcuni parametri di laboratorio e clinici in soggetti con brucellosi cronica trattati con un immunomodulante: il metisoprinolo.

In order to evaluate the immunomodulating activity of isoprinosine in chronic infections, 7 patients with chronic brucellosis unresponsive to antibiotic and corticosteroid therapy were treated with 4 g/die of isoprinosine in association with antibiotic therapy from 3 to 6 months. Immunoserologic and clinical evaluation were obtained at regular intervals from each patient. The treatment induced a significant increase of E rosette formation, reduction of erythrocyte sedimentation rate, associated with improvement or disappearance of clinical symptoms. These data suggest that isoprinosine may favourably influence the clinical course of chronic brucellosis, probably modifying host cell-mediated immune response.