A case of infectious esophagitis caused by human papilloma virus.

Esophageal infections may be caused by diverse pathogens that alter the mucosal lining and produce mild symptoms or sometimes critical clinical diseases with a high risk of mortality, particularly among the immunocompromised. The most common causes of infectious esophagitis are: herpes virus, candida, cytomegalovirus (CMV), and human immunodeficiency virus (HIV); human papilloma virus (HPV) infections are rare in Western countries. Endoscopic features of infectious esophagitis are specific for different agents; nonetheless, differential diagnosis is difficult and requires biopsy, cultures and brushing. We present the clinical case of a young woman admitted to the Department of General Surgery of A.O.U. Federico II, Naples, for a large, deep ulcerative lesion of the esophagus caused by HPV infection.

Tissue ghrelin level and gastric emptying rate in adult patients with celiac disease.

Celiac disease (CD) patients show a number of gastrointestinal motor abnormalities. Ghrelin, a gastric peptide implicated in short-term feeding control and long-term body weight regulation, has been recently considered a key regulator of gastric motility. The aim of this study was to evaluate the gastric emptying rate of solids and the density of ghrelin-immunopositive cells in adult CD patients before and at least 1 year after starting a gluten-free diet. Twenty CD patients (M 8/F 12; mean age 36 years) and 10 controls underwent endoscopy with gastric and duodenal biopsies and 13C-octanoic acid breath test to measure gastric emptying of solids. Celiac disease patients repeated the protocol at least 1 year after starting gluten-free diet. Ghrelin tissue levels were evaluated by immunohistochemistry on gastric mucosa specimens. Gastric emptying time was normal in all control subjects (t(1/2) = 89 +/- 16 min) while it was delayed in CD patients prior to gluten-free diet (t(1/2) = 252 +/- 101 min; P < 0.005). The mean number of ghrelin-positive cells/field (x 400) was 14.4 +/- 2.7 in controls and 25.3 +/- 5.7 in CD patients respectively (P < 0.0001). Gluten withdrawal was effective in normalizing gastric emptying time in all CD patients (97 +/- 14 min; P < 0.0001) and resulted in a significant reduction of the density of ghrelin-immunopositive cells (19.8 +/- 5.4; P < 0.0001). The density of ghrelin-positive cells correlated directly with the degree of duodenal damage (P < 0.001) and inversely with the body mass index of CD patients (P < 0.0001). However, in neither CD patients nor controls, a correlation between tissue ghrelin levels and gastric emptying rate was detected. In conclusion, tissue ghrelin level does not correlate with gastric emptying rate in adult CD patients and in controls.

A case of chronic actinic dermatitis treated with topical tacrolimus.

INTRODUCTION: The treatment of chronic actinic dermatitis (CAD), a sun-induced disorder characterized by a persistent eczematous eruption, involves photoprotective measures, topical corticosteroid therapy and, in more severe cases, systemic immunosuppression. The potential side effects of systemic immunosuppressant drugs prompted us to evaluate the efficacy of topical tacrolimus for treatment of CAD. PATIENT AND TREATMENT: A 58-year-old man with CAD, resistant to previous treatment with topical and systemic corticosteroids, oral cyclosporine and PUVA-photochemotherapy, was treated with tacrolimus ointment 0.1% once a day. RESULTS: Tacrolimus ointment led to significant improvement of pruritus and severe eczematous skin lesions after 20 days of treatment. CONCLUSIONS: Tacrolimus shows a beneficial effect on CAD; this could be attributed to the fact that CAD is characterized by a lymphohistiocytic infiltrate producing a chronic eczema and that tacrolimus blocks the activation of lymphocytes and other immune system cells, also inhibiting the release of mediators from cutaneous mast cells and basophils.

Squamous cell carcinoma of the lower lip: FAS/FASL expression, lymphocyte subtypes and outcome.

Squamous cell carcinoma (SCC) of the lip is a relatively common malignancy of the head and neck region. Tumour thickness, grading and perineural invasion are significant prognostic indicators. However, there is still the need of new reliable biological markers able to predict the prognosis of the single cases with an unfavourable biological behaviour unpredictable by the classic clinical-pathological parameters. 32 cases of (SCC) of the lower lip were analysed for their clincopathologic features, and immunohistochemical expression of Fas/FasL in neoplastic cells and in inflammatory infiltrate. Moreover the density and phenotype of tumour-infiltrating lymphocytes (TIL) were analysed. The results were related with the follow-up of the patients ranging from 2 to 6 years. The cases with over-expression of Fas/FasL in neoplastic cells and Fas+ in T cells preferentially showed a more aggressive clinical behaviour (P<0.01). Moreover we found an alteration of the normal expression of CD4 and CD8 lymphocyte types in ten cases. This data suggest that the Fas/FasL pathway is involved in the close relation between neoplastic cells and T cells and so in the biological behaviour of these tumours.

Cigarette smoking and appendectomy are risk factors for extraintestinal manifestations in ulcerative colitis.

OBJECTIVE: Two common factors, cigarette smoking and appendectomy, have been found to play a role in ulcerative colitis (UC). Data on their role in the development of extraintestinal manifestations (EIM) are scarce. METHODS: The relationship between cigarette smoking, appendectomy, and EIM was examined in a prospective study involving 535 (M/F = 319/216) consecutive UC patients followed up for 18 yr. We considered the major EIM: seronegative spondyloarthropathy, pyoderma gangrenosum/erythema nodosum, acute anterior uveitis, and primary sclerosing cholangitis. We excluded patients with a history of EIM or those colectomized before study entry, ex-smokers, and those who started to smoke during the course of UC. RESULTS: In UC patients, seronegative spondyloarthropathy and dermatologic complications were found increased in smokers (p < 0.0001; p = 0.001) or in subjects with appendectomy (p = 0.0003; p = 0.02), while acute anterior uveitis and primary sclerosing cholangitis did not differ. The Kaplan-Meier analysis showed 18-yr rates for EIM of 71% in smokers and 45% in nonsmokers (log-rank test, p = 0.0001), and of 85% in patients with appendectomy and 48% in those without (p = 0.0001). Cox proportional-hazard model showed that cigarette smoking and appendectomy are independent factors promoting EIM. In smokers with appendectomy the adjusted hazard ratio (3.197, 95% CI 1.529-6.684) was higher than in patients with appendectomy alone (2.617, 95% CI 1.542-4.442) or smoking alone (1.947, 95% CI 1.317-2.879). CONCLUSIONS: In UC patients, appendectomy and cigarette smoking are prognostic factors for the development of EIM. The unfavorable effect of cigarette smoking on EIM is additive to that of appendectomy.

Loss of oestrogen receptor beta, high PCNA and p53 expression and aneuploidy as markers of worse prognosis in ovarian granulosa cell tumours.

AIMS: Ovarian granulosa cell tumour (OGCT) is a sex-cord stromal tumour with a general trend toward late relapse and/or metastasis. However, mortality rate corrected for long-term follow-up shows that about 50% of patients die within 20 years of diagnosis. Classical clinicopathological parameters are unable to predict the biological behaviour of OGCT. The involvement of a recently characterized subtype of oestrogen receptor, ERbeta, in ovarian carcinogenesis has been hypothesized. METHODS AND RESULTS: We examined by immunohistochemistry the expression of ERbeta, proliferating cell nuclear antigen (PCNA) and p53 in a selected series of 30 OGCT, to evaluate their role in the prognostic evaluation of this tumour. Immunohistochemistry was performed on formalin-fixed paraffin-embedded sections. Results were compared with the DNA-ploidy of the tumours (evaluated by image analysis) and with the follow-up data of the patients. CONCLUSIONS: Loss of ERbeta expression, high PCNA expression and aneuploidy, characterized a subgroup of OGCT with a worse outcome. The identification of a high-risk subclass of OGCT may be of primary importance in addressing appropriate therapeutic strategies, offering the chance to prevent relapses and metastases by using adjunctive, specifically targetted, more aggressive therapies.

Is there a link between environmental factors and a genetic predisposition to cancer? A lesson from a familial cluster of gastric cancers.

To determine the prevalence of gastric precancerous lesions and mucosal genetic alterations in relatives of a cluster of familial gastric cancer (FGC), we studied a kindred spanning two generations. The founder, daughter and niece underwent surgery for gastric cancer (GC); a son and other two daughters of the founder, presented with chronic dyspepsia. In all subjects, gastric mucosa samples were analysed for pathological features, Helicobacter pylori infection, microsatellite (MIN) and chromosomal (CIN) instability. The overexpression of mp53 and c-myc, and cytoplasmic beta-catenin delocalisation were found in the 2 younger cancer patients. All GC and gastritis patients had normal E-cadherin expression and were MIN-negative. Aneuploidy characterised all GC cases, and mixed euploid and aneuploid cell populations were present in the gastric biopsies from two of three 'at-risk' relatives. These two subjects, one of whom had severe active gastritis, and gastric mp53 and c-myc expression, were CagA-positive H. pylori-infected. DNA aneuploidy, p53 and c-myc expression disappeared after H. pylori eradication. In this FGC cluster, genetic abnormalities were found in first-degree relatives (3 patients) only in presence of H. pylori infection (2 cases H. pylori-positive versus 1 case H. pylori-negative) supporting the hypothesis that, besides the influence of a genetic profile, FGC may be, at least partly, mediated by intrafamilial clustering of H. pylori infection.

Biochemical markers of bone turnover, serum levels of interleukin-6/interleukin-6 soluble receptor and bisphosphonate treatment in Erdheim-Chester disease.

Erdheim-Chester disease (ECD) is a rare non-Langherans form of histiocytosis characterized radiologically by symmetrical sclerosis of the metaphysis and the diaphysis of long tubular bones. Macrophages are potent interleukin-6 (IL-6) producers and elevated IL-6 serum levels have been described in pathological conditions characterized by increased bone resorption. In a patient with ECD, during the acute phase of the disease we found high serum levels of IL-6 and IL-6 soluble receptor (sIL-6R) and high levels of bone turnover markers. After 5 years of combination therapy with oral prednisone and intravenous clodronate a significant reduction in the above mentioned biological parameters was seen. We suggest that the systemic disorders present in ECD could be related to the high serum levels of IL-6 and sIL-6R. We also propose the use of bisphosphonates in the clinical management of ECD.

Chronic treatment with sulfhydryl angiotensin-converting enzyme inhibitors reduce susceptibility of plasma LDL to in vitro oxidation, formation of oxidation-specific epitopes in the arterial wall, and atherogenesis in apolipoprotein E knockout mice.

The effects of chronic treatment with the new sulfhydryl angiotensin-converting enzyme (ACE)-inhibitor, zofenopril, in comparison with the classical sulfhydryl ACE-inhibitor captopril or enalapril or placebo on the development of atherosclerosis were determined in apolipoprotein-E knockout (apoE(-/-)) mice. Groups of 2-month-old male mice received either placebo (N=10), 0.05 mg/kg/day of zofenopril (N=10), 1 mg/kg/day of zofenopril (N=10), 5 mg/kg/day of captopril (N=10) or 0.5 mg/kg/day of enalapril (N=8). After 29 weeks of treatment, computer-assisted imaging analysis revealed that zofenopril reduced the aortic cumulative lesion area by 78% at 0.05 mg/kg/day and by 89% at 1 mg/ml/day of zofenopril compared to that of the placebo (P<0.0001). Captopril reduced by 52% aortic lesions compared to placebo (P<0.01 vs. placebo; P<0.05 vs. zofenopril at both doses). Enalapril did not reduce aortic lesions. Furthermore, 0.05 mg/kg/day of zofenopril reduced susceptibility of plasma LDL to in vitro oxidation compared to captopril, enalapril or placebo, as shown by significant reduction of malondialdehyde content (P<0.001 vs. placebo or enalapril; P<0.05 vs. captopril), as well as by the prolongation of lag-time (P<0.01 vs. placebo or enalapril P<0.05 vs. captopril). More importantly, mice treated with 1 mg/ml/day of zofenopril had a significant decrease in the intimal immunohistochemical presence of oxidation-specific epitopes on oxLDL (NA59 monoclonal antibody, P<0.01), macrophages derived foam cells (F4/80 monoclonal antibody, P<0.05) and native LDL (NP monoclonal antibody, P<0.01) compared to placebo, captopril or enalapril. Thus, chronic treatment with the new sulfhydryl ACE-inhibitor zofenopril has antiatherosclerotic and antioxidant effects in the arterial wall of hypercholesterolemic apoE(-/-) mice. This protection was significantly higher than that reached with captopril and at lower doses of the drug. Treatment with 0.5 mg/kg/day of enalapril did not provide any protective effect.

Colonoscopic removal of a polypoid arteriovenous malformation.

A 53-year-old male presenting with a 3-month history of intermittent mild rectal bleeding was found, on double contrast barium enema, to have a large polyp on a long stalk in the sigmoid colon. Large bowel endoscopy confirmed the presence of a 2 cm pedunculated polyp which was removed using a diathermic snare, with slight bleeding following the procedure that did not require endoscopic haemostasis. Only after histologic examination was the polyp shown to be a colonic arteriovenous malformation. Endoscopically, arteriovenous malformations generally appear as flat or elevated bright red lesions. A pedunculated polypoid appearance is extremely uncommon. In this case, no gastrointestinal bleeding or polypoid recurrence was observed during the 12 months of clinical and endoscopic follow-up.

P53 and hMSH2 expression in basal cell carcinomas and malignant melanomas from photoexposed areas of head and neck region.

Ultraviolet (UV) radiation plays a pivotal role in skin damage and photocarcinogenesis. The basic mechanism of phototoxicity lies in DNA damage, and involves mutation of tumor suppressor genes, oncogenes and genes directly involved in the control of the stability of genome, such as the mismatch repair (MR) genes. The goal of this study was to evaluate the role of p53 and hMSH2 in the UV-related carcinogenetic process. An immunohistochemical study for p53 and hMSH2 was performed in a series of 43 basal cell carcinomas (BCC) and 60 melanomas (MM) from photoexposed areas of head and neck region, comparing the findings with follow-up. A deregulated p53 expression characterized less differentiated, more aggressive BCC (BCC2) but not the well-differentiated ones (BCC1). The hMSH2 protein was present, though expressed at varying levels, in 18 out of 21 BCC1 cases and in 4 out of 22 BCC2. In the remaining 3 cases of BCC1 and 18 cases of BCC2, a complete absence of hMSH2 expression was found, correlating directly with the presence of recurrence and/or death of the disease in case of melanoma (p<0.05). Overall, the expression of hMSH2 correlated inversely with the p53 overexpression (p<0.01). In MM, p53 was found overexpressed in 81.6% of the cases, and this correlated positively with the level of infiltration and with the presence of relapses (p<0.01) or metastasis (p<0.01) and inversely with the disease-free interval (p<0.05). These results are in agreement with the reported association between p53 deregulation and a more aggressive cancer phenotype. The evaluation of the expression of p53 and hMSH2 could improve the management of patients with BCC and MM, and could have a role also in the evaluation of the early cutaneous photo-inducted damage, contributing to the identification of presymptomatic patients predisposed to the development of UV-related new skin tumors, who could become candidates for chemoprevention trials.

[Echographic study with high-frequency and high-spatial resolution transducer in the evaluation of renal transplant in pediatric age]. / Studio ecografico con sonda con alta frequenza ed elevata risoluzione spaziale nella valutazione del rene trapiantato nell'età pediatrica.

PURPOSE: We investigated the role of power Doppler US with a high-frequency and high-resolution transducer (13 MHz) in the visualization of interlobular arterioles in patients with normally functioning renal transplants or with chronic rejection. MATERIAL AND METHODS: We examined 15 patients (mean age 15 years; range 10-18 years) with a General Electric 500 MD unit using 7.5 and 13 MHz linear transducers. In all the patients serum creatinine and diuresis were evaluated; 4 patients underwent US-guided biopsy that resulted in the diagnosis of chronic rejection. RESULTS: Normally functioning renal transplants were found in 11 patients and chronic rejection was seen in 4. In normally functioning renal transplants, interlobular vessels could be depicted as "cortical blush" with the 7.5 MHz transducer; in the same patients power Doppler US with the 13 MHz transducer permitted a correct evaluation of interlobular vessels that were arranged in series like a palisade. In chronic rejection power Doppler US with the 13 MHz transducer better depicted cortical vascularity and showed irregular, narrow arteries. CONCLUSION: Power Doppler US with a 13 MHz transducer is particularly useful in children after renal transplants due to their reduced tissutal thickness. The lateral resolution of 13 MHz transducers (< 0.3 mm) allows to separate interlobular vessels from each other and the high frequency of the probe can depict interlobular vessels in the peripheral cortex. The optimal visualization of cortical vascularity with a 13 MHz transducer allows early detection of chronic rejection.

[Mesothelial cyst of the diaphragm. Presentation of an unusual case]. / Cisti mesoteliale del diaframma. Presentazione di un inusuale caso.

The authors report a case of mesothelial cyst of the diaphragm in a boy 11 years old who was examined for pain in the right hypochondrium with exacerbation during respiratory movements. Ultrasonography and CT suggested the diagnosis. However the final diagnosis of mesothelial cyst of the diaphragm was possible only after laparotomy and histological examination. The topographical, clinical, radiological, therapeutic and histological aspects of primary cysts of the diaphragm are presented and a survey of the literature is made.

Beneficial effects of ACE-inhibition with zofenopril on plaque formation and low-density lipoprotein oxidation in watanabe heritable hyperlipidemic rabbits.

The effects of angiotensin-converting enzyme (ACE)-inhibition with zofenopril on the development of atherosclerosis and low-density lipoprotein (LDL) oxidation were determined in Watanabe Heritable Hyperlipidemic (WHHL) rabbits. Rabbits received either placebo (n = 6) or 0.5 mg/kg/day of zofenopril (n = 6). After 6 weeks of treatment, the computer-assisted analysis revealed that zofenopril reduced the aortic and common carotid corrected cumulative lesion area by 34% and 39%, respectively (p < 0.05 vs placebo-treated group). The intimal/medial ratio of the largest fatty streaks was 0.426+/-0.158 in the zofenopril-treated group and 0.875+/-0.238 in the placebo-treated group (p < 0.05). Furthermore, we found in the zofenopril-treated group smaller lesions with an intimal/medial ratio of zofenopril also reduced plasmatic LDL oxidation, as shown by significant reduction of malondialdehyde content (p < 0.01) and relative agarose gel mobility (p < 0.05), as well as by the prolongation of the lag-time (p < 0.05). Compared to zofenopril-treated rabbits, arterial sections of the placebo-group had significant increase in the intimal presence of macrophages-derived foam cells (p < 0.05), ox-LDL (p < 0.01), and native LDL (p < 0.01) detected by immunocytochemistry with RAM-11, MDA2 and NP1533975 monoclonal antibodies, respectively. To investigate the amount of platelet accumulation in the atherosclerotic plaque we also measured platelet-associated radioactivity. Autologous platelets were labeled with 111Indiumoxine and injected intravenously. After 2 hours, WHHL were sacrificed and arterial sections were counted for platelet-associated radioactivity. In the placebo-treated group, platelet radioactivity was 0.52+/-0.12 equivalent of radioactivity per mg of tissue in the common carotid and 0.25+/-0.18 in the abdominal aorta; in contrast, rabbits treated by zofenopril had 0.20+/-0.12 in the common carotid and 0.06+/-0.01 in the abdominal aorta. These data indicate that ACE-inhibition with zofenopril has antiatherosclerotic and antioxidant effects in WHHL-rabbits. Our results also shows that these effects could be linked to a reduced wall-associated platelet deposition at the site of atherosclerotic lesions.

Infection with Mycobacterium tuberculosis complicating a pulmonary sequestration.

Pulmonary sequestration is a relatively rare malformation. Infection with common pyogenes is a frequent feature in the evolution of this disease. We report a case of intralobar sequestration infected with Mycobacterium tuberculosis in the absence of any other site of tuberculous infection. The patient underwent surgical removal of the affected lobe and subsequent antituberculous chemotherapy. At 1-year follow-up his clinical status is excellent.

Effects of vitamin E and HMG-CoA reductase inhibition on cholesteryl ester transfer protein and lecithin-cholesterol acyltransferase in hypercholesterolemia.

BACKGROUND: The enzyme lecithin-cholesterol acyl transferase (LCAT) esterifies free cholesterol on high-density lipoprotein (HDL) and the cholesteryl ester transfer protein (CETP) transfers cholesteryl ester to very-low-density lipoprotein (VLDL) and low-density lipoproteins (LDL). Using statins, contradictory findings have been made regarding CETP activity in normolipidemic individuals and in those with familial dysbetalipoproteinemia. In contrast, LCAT activity appears to be unaffected by simvastatin. Antioxidants have also been proposed for the use of anti-atherosclerotic treatment, because the oxidation of LDL may have a key role in the pathophysiology of atherogenesis. OBJECTIVE: To investigate, in hypercholesterolemic patients, whether a combination of pravastatin with the antioxidant, vitamin E, has greater effects on the activity of CETP and of LCAT than does pravastatin alone. METHODS: This placebo-diet-controlled multicenter trial included 220 hypercholesterolemic patients who were assigned randomly to groups to receive: diet and 20-40 mg pravastatin (n = 52), diet and alpha-tocopherol (n = 60), or diet associated with placebo (n = 52). Plasma LCAT activity was determined using excess exogenous substrate, containing [3H]cholesterol. Plasma CETP activity was measured in the supernatant fraction after precipitation of endogenous apo B-containing lipoproteins with phosphotungstate-Mg2+. The exchange of cholesteryl esters between [14C]cholesteryl ester-labeled LDL and unlabeled HDL was measured during a 16-h incubation, while LCAT was inhibited. RESULTS: The addition of pravastatin to the diet induced a significant decrease in plasma CETP activity (P < 0.05); this effect was less evident in the group cotreated with vitamin E. For the first time, it was shown that CETP concentrations increased significantly after vitamin E alone (P < 0.05). No significant differences in the plasma activity of LCAT were observed among the groups. CONCLUSIONS: Pravastatin reduced CETP activity, but not that of LCAT. Addition of vitamin E prevented the decrease in CETP activity and had no effect on LCAT activity. The mechanism responsible for these effects is unknown, but could involve the prevention of radical-induced damage to CETP by vitamin E.

Occurrence of the same peroxidative compounds in low density lipoprotein and in atherosclerotic lesions from a homozygous familial hypercholesterolemic patient: a case report.

Oxidative modification of low density lipoprotein (LDL) and its byproducts may play a fundamental role in atherosclerosis. We report an in vitro analysis of LDL peroxidative compounds in an homozygous familial hypercholesterolemic (HFH) patient who subsequently died. During the autopsy, we analyzed lipids extracted directly from different atherosclerotic plaques, and we also provided an immunocytochemical analysis using the specific monoclonal antibody MDA2 (directed against malondialdeyde-lysine epitopes of oxidized LDL). The results showed that the same species of peroxidative compounds were present both in LDL in vitro and in lipids extracted directly from atherosclerotic lesions. Moreover, the immunocytochemistry analysis revealed a positive staining of atherosclerotic plaques, confirming the presence of LDL oxidation-specific epitopes. Although observation of a single case is necessarily limited, our findings are consistent with the hypothesis that oxidative modification of LDL is involved in human atherogenesis.