Celiac sprue: another autoimmune syndrome associated with hepatitis C?
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Biomedical subjects
Publications and source records attributed to E Colombo.
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BACKGROUND: Cutaneous metastasis from neuroendocrine carcinomas of visceral origin is rarely described in indexed literature. The primary sites of origin include: lung (Wick et al., J Am Acad Dermatol 1985; 13: 134), larynx (Zambruno et al., Ann Dermatol Venereol 1989; 116: 855; Schmidt et al., J Laryngol Otol 1994; 108: 272; Guerzider et al., Ann Pathol 1991; 11 (4): 253), mediastinum (Yoshimasu et al., J Dermatol 2001; 28 (3): 168), uterus (Fogaca et al., J Cutan Pathol 1993; 20: 455), and thymus (Wick et al., J Am Acad Dermatol 1985; 13: 134). METHODS: In this report, the authors present the clinical, histological, immunohistochemical, and ultrastructural characteristics of secondary skin localizations of a neuroendocrine laryngeal tumor that occurred in a 61-year-old man. The complete follow up of the case is described and a brief revision of the terminology and classification of neuroendocrine neoplasms of the larynx is discussed, since a significant relationship exists between the degree of differentiation and biological behavior. RESULTS: On histological examination, the secondary cutaneous localization appeared to be more dedifferentiated compared to the primary tumor. The immunohistochemical patterns of reactivity were similar in both neoplasms, showing expression of neuroendocrine and epithelial markers. CONCLUSIONS: An important issue of prognostic significance is to differentiate a cutaneous metastasis of a neuroendocrine carcinoma from the primary small cell-undifferentiated carcinoma of the skin (Merkel cell carcinoma).
We evaluated the toxicity and activity of bleomycin, methotrexate and vinorelbine (BMV) combination chemotherapy in cisplatin-pretreated patients with squamous cell carcinoma of the head, neck and esophagus (SCC-HN&E) with the aim of identifying a second-line therapy combination and schedule that might offer an improved therapeutic index. BMV (bleomycin 15 I.U., total dose, methotrexate 30 mg/m2, and vinorelbine 30 mg/m2) was administered intravenously every 2 weeks until disease progression, to 26 consecutive patients. Clinical and CT-scan evaluations revealed 7 partial responses (PR) 127%, 95% confidence interval: 9.6%-44.4%], and 13 patients with stable disease (SD) [50%]. The mean progression-free survival for patients who achieved a PR or SD was 6.47 months (range 4-13 months), with 75% of these patients experiencing partial relief of symptoms, mainly pain and dysphagia. BMV, administered second-line in an outpatient setting, has activity similar to that of the taxanes, but with a more acceptable toxicity profile including an absence of alopecia.
Benign juvenile melanoma was originally described and differentiated from malignant melanoma by Sophie Spitz in 1948. The solitary form is the most frequent and usually appears on the face and extremities of young children and adolescents as a solitary, hairless, dome-shaped papule or nodule, varying in size from 3 to 15 mm. It can be of a wide spectrum of colors including pink, yellow, red, brown, purple and black, representing 1% to 8% of melanocytic tumors in children. Histologically, Spitz nevus has been subdivided into junctional, compound and intradermal type according to the location of neoplastic melanocytes in the skin. Rarely multiple benign juvenile melanoma arranged in clusters (agminated) or widespread (disseminated) are described. Less than 50 cases have been reported in the world literature. The grouped form usually occurs on the face of children on normal, but also hyperpigmented or hypopigmented skin, while the disseminated one in adults. A case of multiple agminated Spitz nevus arised on the face of a 2 years old girl is reported. The clinical presentations with a 3 years follow-up and the histologic features of this nevus are described as well as the therapeutic approach.
Homeobox genes encode a particular class of transcription factors that are involved in several different developmental processes such as specification of regional identity, cell determination and proliferation. In particular, during early brain morphogenesis, they provide a genetic code, which generates single rhombomere identity in the hindbrain (Science 284 (1999) 2168) and interneurons specification in the ventral neural tube (Nat. Rev. Genet. 1 (2000) 20). We have isolated a paired homeobox containing gene, which has been recently named Dmbx1 (Mech. Dev. 110 (2002) 241). Dmbx1 protein can be listed into the paired-like class, due to the highest homology in its homeodomain, with several other members of this family. With the exception of olfactory neurons, Dmbx1 is expressed only in the developing central nervous system and in particular during early determination and successive differentiation of the midbrain and caudal diencephalon. Interestingly, Dmbx1 expression labels cerebellar granule progenitors at the onset of differentiation and spinal cord V0 interneurons.
BACKGROUND: Efficacy of infliximab in treatment of patients with moderate-to-severe refractory and fistulizing Crohn's disease has been shown in controlled clinical trials. Moreover, audit data from North America and North Europe have confirmed efficacy in clinical practice comparable to that in clinical trials. AIM: To report clinical experience using infliximab in treatment of Crohn's disease in Italy, comparing efficacy and safety with those reported in clinical trials and other published series. PATIENTS AND METHODS: The study population comprised 63 patients (31 males and 32 females, median age 33 years) treated with infliximab for refractory/inflammatory (31 patients) and/or fistulizing Crohn's disease (32 patients). All patients received an infusion of infliximab at a dose of 5 mg/kg at weeks 0, 2 and 6. After the first infusion, clinical and laboratory assessments were repeated at weeks 2, 6 and 10. For refractory inflammatory Crohn's disease, clinical remission was defined as a Crohn's Disease Activity Index of < or = 150 at each scheduled visit, clinical response as a reduction in the Crohn's Disease Activity Index score of > or = 70 points in comparison to baseline. For fistulizing Crohn's disease, a complete response was defined as closure of any draining fistulae at week 10. A fistula was defined as closed when it no longer drained despite gentle finger pressure. A partial response was defined as reduction in number, size or drainage of fistulae, at the same visit. RESULTS: According to an intention-to-treat evaluation on the 31 patients with refractory/inflammatory Crohn's disease, at week 2, 42.5% (14 patients) had a clinical response and 31.3% of patients (10 patients) were in clinical remission. At week 10 (4 weeks after the end of third infusion), 80.6% (25 patients) had a clinical response and 71% (22 patients) were in clinical remission and 14/19 (74%) had discontinued steroid treatment. Of the 32 patients with fistulizing Crohn's Disease, 15 (46.9%) had a complete response, 8 (25%) a partial response, and 9 (28.1%) no response at week 10 check-up. The incidence of side-effects was low (16%) and not influenced by concurrent immunomodulatory therapy. CONCLUSION: The present experience with infliximab in clinical practice confirms its efficacy, in particular in inflammatory/refractory Crohn's disease and its safety, at least, in short-term follow-up.
BACKGROUND AND AIM: It has been reported that atorvastatin increases high-density lipoprotein cholesterol (HDL-C) more in patients with low than in those with high baseline HDL-C levels. This may have a biological explanation, but also suggests a statistical artifact known as the regression to the mean. METHODS AND RESULTS: Atorvastatin 10 mg/day led to a 4% increase in HDL-C after two months in 67/121 patients with hypercholesterolemia (55%), who had lower baseline HDL-C levels than the patients in whom HDL-C did not increase. In the patients with baseline HDL-C below the median, HDL-C significantly increased whereas no change was observed in patients with baseline HDL-C above the median. The correlation coefficient between pre- and post-treatment HDL-C was 0.84, thus suggesting a regression to the mean. However, the regression artifact did not entirely explain the increase in HDL-C in patients with low baseline HDL-C or the lack of an increase in those with high baseline HDL-C. The adjusted mean increase was 5.4% in patients with low pretreatment HDL-C, and 2.4% in the patients with high pretreatment HDL-C. Multiple regression analysis with the changes in HDL-C as the dependent variable showed that baseline HDL-C and the changes in serum triglycerides independently contributed to the change in HDL-C levels. CONCLUSIONS: Atorvastatin 10 mg/day increases HDL-C more in patients with low pretreatment HDL-C levels, an effect that seems to be related to the hypotriglyceridemic activity of the drug.
OBJECTIVE: A closed suction system (CS) maintains connection with the mechanical ventilator during tracheal suctioning and is claimed to limit loss in lung volume and oxygenation. We compared changes in lung volume, oxygenation, airway pressure and hemodynamics during endotracheal suctioning performed with CS and with an open suction system (OS). DESIGN: Prospective, randomized study. SETTING: Intensive care unit in a university hospital. PATIENTS: We enrolled ten patients, volume-controlled (VC) ventilated with a Siemens Servo 900 ventilator (PaO2/FIO2 192 +/- 70, PEEP 10.7 +/- 3.9 cmH2O). INTERVENTIONS: We performed four consecutive tracheal suction maneuvers, two with CS and two with OS, at 20-min intervals. During the suction maneuvers continuous suction was applied for 20 s. MEASUREMENTS AND MAIN RESULTS: We measured end-expiratory lung volume changes (delta VL), tidal volume (VTrt), respiratory rate (RR) and minute volume (VErt) by respiratory inductive plethysmography; arterial oxygen saturation (SpO2), airway pressure and arterial pressure (PA). Loss in lung volume during OS (delta VL 1.2 +/- 0.7 l) was significantly higher than during CS (delta VL 0.14 +/- 0.1 l). During OS we observed a marked drop in SpO2, while during CS the change was only minor. During CS ventilation was not interrupted and we observed an immediate increase in RR (due to the activation of the ventilator's trigger), while VTrt decreased, VErt was maintained. CONCLUSIONS: Avoiding suction-related lung volume loss can be helpful in patients with an increased tendency to alveolar collapse; CS allows suctioning while avoiding dramatic drops in lung volumes and seems to be safe during the VC ventilation setting that we used.
BACKGROUND: Simvastatin 40 to 80 mg/d has been found to increase high-density lipoprotein cholesterol (HDL-C) levels significantly more than atorvastatin at equipotent doses (ie, 20-80 mg/d). Data on the effects of lower doses of the 2 drugs on HDL-C levels are conflicting. OBJECTIVE: The purpose of this study was to investigate the effects of simvastatin 20 mg/d and atorvastatin 10 mg/d on HDL-C levels in patients with hypercholesterolemia. METHODS: Patients with primary hypercholesterolemia (total cholesterol [TC] >250 mg/dL) who were not taking any lipid-lowering agents and who were following a low-fat diet were randomized to receive 1 of 2 treatments: simvastatin 20 mg/d or atorvastatin 10 mg/d. Serum TC, triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and HDL-C levels were measured using standard methods after 2 months of therapy. In a secondary analysis, lipids and lipoprotein cholesterol were measured after 1 year in patients who continued treatment. RESULTS: Of the 240 patients enrolled (108 men and 132 women; age range, 23-77 years, mean [SEM] 56.7 [0.69]), 235 completed the study. After 2 months of therapy, TC, LDL-C, and serum TG levels decreased significantly versus baseline in both groups (P < 0.001), with no significant differences between treatment groups. HDL-C levels increased by 9.0% (P < 0.001 vs baseline) in the simvastatin group and by 4.3% (P < 0.02) in the atorvastatin group. The difference between the 2 groups in the percentage increase in HDL-C was statistically significant (P < 0.05). In 113 patients who continued treatment, HDL-C levels at 1 year were still significantly higher than baseline levels in the simvastatin group (6.3%, P = 0.034), but not in the atorvastatin group (2.8%, P = 0.587). CONCLUSIONS: The findings from this study suggest that the HDL-C-increasing effect of simvastatin 20 mg is significantly greater than that of atorvastatin 10 mg. Since increasing HDL-C levels is thought to lower the risk for atherosclerosis and coronary heart disease, these results warrant further investigation.
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OBJECTIVES: High hepatocyte proliferation has been recently proposed as a risk factor for the development of hepatocellular carcinoma (HCC). The aim of this study was to assess whether hepatocyte proliferation is an independent risk factor for HCC when considered together with clinical and demographic characteristics. METHODS: We retrospectively evaluated 97 consecutive patients with a histological diagnosis of cirrhosis and preserved liver function, enrolled in a surveillance program for early diagnosis of HCC. Hepatocyte proliferation was evaluated by flow-cytometric analysis in liver samples collected at the time of histological diagnosis of cirrhosis. All patients were followed with abdominal US and serum alpha-fetoprotein (AFP) assays every 6 months. RESULTS: During a mean follow-up of 53 months (range, 12-120 months), 12 patients developed HCC, giving an annual incidence of 2.8%. The mean S-phase fraction was 2.5%+/-1.6 in patients who developed HCC and 0.9%+/-0.6 in those who did not (p < 0.0001). By univariate analysis, S-phase fraction 1.8% or higher and AFP higher than 20 ng/ml were the only two variables significantly correlated with the development of HCC (p < 0.0001, p < 0.0001). Multivariate analysis found that both variables were independently associated with HCC development (p < 0.003 and p < 0.005, respectively), with hazard ratios of 8.0 and 7.3 (confidence intervals, 2.1-31.2 and 1.8-29.2). Among patients with high AFP and/or high S-phase fraction, 11 (39%) developed HCC, compared with only one (1%) with a low S-phase fraction and normal AFP, corresponding to HCC yearly incidences of 9.5% and 0.3% (p < 0.00009). CONCLUSIONS: Patients with high S-phase fraction and/or above-normal serum AFP are at higher risk of developing HCC and should be offered a close surveillance program.
A 35-year-old male patient with long lasting HIV infection presented with confusion, haemolytic anaemia and thrombocytopenia. After a stable course over 7 days he suddenly developed coma and cardiogenic shock and died. Autopsy revealed thrombotic thrombocytopenic purpura with fibrin-rich deposits in the microvasculature of the brain, heart and pancreas. The pathogenesis and differential diagnosis of this fulminant disease are discussed.
Repetitive elements flanked by exons 2 and 3 of the human transaldolase gene, thus termed transaldolase-associated repetitive elements, TARE, were identified in human DNA. Nonpolyadenylated TARE transcripts were detected by Northern blot analysis and cloned by reverse transcriptase-mediated polymerase chain reaction from human T lymphocytes. A dominant 1085-nucleotide long transcript, TARE-6, contained two adjacent Alu elements, a right monomer and a complete dimer, oriented opposite to the direction of transcription of the transaldolase gene. Reverse transcriptase-polymerase chain reaction and in vitro transcription analyses showed that transcription of TARE-6 proceeded in the orientation of the RNA pol III promoter of the Alu dimer and opposite to the orientation of the TAL-H gene. TAREs lacking RNA polymerase III promoter showed no transcriptional activity. In vitro transcription of TARE-6 was resistant to 1 microg/ml alpha-amanitin but sensitive to 100 microg/ml alpha-amanitin and tagetitoxin, suggesting involvement of RNA polymerase III. TAREs in both the transaldolase and HSAG-1 genomic loci were surrounded by TA target site duplications. Homologies between transaldolase and HSAG-1 break off internally at splice donor and acceptor sites. The results suggest RNA polymerase III-mediated transcription of TARE may be a source of repetitive elements, contributing to distinct genes and thus shaping the human genome.
RAR and AML1 transcription factors are found in leukemias as fusion proteins with PML and ETO, respectively. Association of PML-RAR and AML1-ETO with the nuclear corepressor (N-CoR)/histone deacetylase (HDAC) complex is required to block hematopoietic differentiation. We show that PML-RAR and AML1-ETO exist in vivo within high molecular weight (HMW) nuclear complexes, reflecting their oligomeric state. Oligomerization requires PML or ETO coiled-coil regions and is responsible for abnormal recruitment of N-CoR, transcriptional repression, and impaired differentiation of primary hematopoietic precursors. Fusion of RAR to a heterologous oligomerization domain recapitulated the properties of PML-RAR, indicating that oligomerization per se is sufficient to achieve transforming potential. These results show that oligomerization of a transcription factor, imposing an altered interaction with transcriptional coregulators, represents a novel mechanism of oncogenic activation.
AIM: To investigate the efficacy of a 1-week triple therapy with amoxycillin, clarithromycin, and omeprazole or ranitidine bismuth citrate (RBC) in curing Helicobacter pylori infection and healing duodenal ulcers. METHODS: One hundred and ninety-two consecutive out-patients with duodenal ulcer, in whom H. pylori infection was confirmed by histology and a urease biopsy test, were randomly assigned to a 1-week treatment with either 400 mg b.d. ranitidine bismuth citrate (RAC group) or 20 mg omeprazole b.d. (OAC group) in combination with 1 g amoxycillin b.d. and 500 mg clarithromycin b.d. RESULTS: Eradication of H. pylori was successful in 77% (per protocol) and 61% (intention-to-treat) of the patients in the RAC group and in 79% (per protocol) and 70% (intention-to-treat) of those in the OAC group. The difference was not significant. Per protocol analysis showed ulcers were healed in 97% of patients in the RAC group and 96% in the OAC group. Adverse effects were seen in four patients in each group: they caused discontinuation of the therapy in one patient of the OAC group. CONCLUSIONS: Eradication rates obtained in this study were lower than those expected on the basis of previously reported studies. The two 1-week treatment regimens were equally effective in healing H. pylori associated duodenal ulcer disease.
Visual disorders secondary to TBI are common, often multiple, associated with complex clinical pictures; in developmental age they may particularly interfere with the development process, and compromise the rehabilitation and outcome processes. The aim of this study is to identify visual disorders in 56 post-traumatic children admitted to the Traumatic Brain Injury Unit. All patients underwent a complete clinical, neurological and neuroophthalmological assessment. Correlations were studied between visual disorders and clinical parameters of acute phase, age at trauma, neuroimaging data and outcome, in order to identify possible risk factors for their occurrence. A high incidence was found of complex visual disorders following head trauma: decreased visual acuity, together with a convergence oculo-motor deficit, is the most frequently detected deficit. Trauma severity, indicated by duration of coma, is associated with most of the visual disorders and appears to be the main risk factor conducive to their appearance.
Peptic ulcer disease (PUD) has been described in the absence of Helicobacter pylori (Hp) infection, suggesting that different factors are involved in its etiopathogenesis. We investigated prevalence and characteristics of Hp-negative (Hp-) PUD in an area of Northern Italy and calculated the rate of Hp-positive (Hp+) patients with PUD in whom Hp might be coincidental and not causal. Four hundred nine consecutive patients with endoscopically diagnosed PUD were enrolled in seven hospitals. Hp infection was assessed by rapid urease test and histologic examination. The attributable risk percentages in different age groups were calculated by appropriate formulas. Of 409 patients, 31 (7.6%) were Hp- (gastric, 8.3%; duodenal, 7.6%). Age, nonsteroidal antiinflammatory drug (NSAID) consumption, and complication rates were significantly higher in Hp-than Hp+ patients with duodenal ulcers (DUs). Of the Hp-patients with DU, 58% did not use NSAIDs. In patients with Hp+ DU, the attributable risk percentage for Hp infection in patients aged <40 years, 40-60 years, or >60 years was 98%, 88%, and 66%, respectively. The prevalence of Hp- PUD was about 8%, mainly unrelated to any known etiologic factor. In about one-third of Hp+ patients with PUD aged over 60 years, Hp infection might be coincidental and not causal.
Aim of the paper is to describe the variability of clinical symptoms in hand, foot and mouth disease, especially among patients belonging to the same family. In spring 1999, during an epidemic of hand, foot and mouth disease, nineteen cases were observed by the authors. In eight cases also some members of the family were affected. A great variability in the clinical expression of the disease, above all among the members of the same family were observed. No cases in children below twelve months or in elderly members of the family were found. Children below three years had more stressed general symptoms, but in no case hospitalization was necessary. Hand, foot and mouth disease does not always show vesicles and aphthae in the affected areas. Clinical expression can also be lacking, but in this case diagnosis can be made easy by the presence of an epidemic or of other cases in the same family.