Intercepting Parkinson disease non-motor subtypes: A proof-of-principle study in a clinical setting.

The construct of non-motor symptoms (NMS) subtyping in Parkinson Disease (PD) is emerging as a line of research in the light of its potential role in etiopathological interpretation of PD heterogeneity. Different approaches of NMS subtyping have been proposed: an anatomical model suggests that NMS aggregate according to the underpinning pathology; other researchers find aggregation of NMS according to the motor phenotype; the contribution of genetic background to NMS has also been assessed, primarily focusing on cognitive impairment. We have analyzed NMS burden assessed through an extensive clinical and neuropsychological battery in 137 consecutive non-demented PD patients genotyped for MAPT haplotypes (H1/H1 vs H2 carriers) in order to explore the applicability of the "anatomo-clinical", "motor" or "genetic" models for subtyping PD in a clinical setting; a subsequent independent analysis was conducted to verify a possible cluster distribution of NMS. No clear-cut NMS profiles according to the previously described models emerged: in our population, the autonomic dysfunctions and depressive symptoms represent the leading determinant of NMS clusters, which seems to better fit with the hypothesis of a "neurotransmitter-based" model. Selective preferential neurotransmitter network dysfunctions may account for heterogeneity of PD and could address translational research.

Adaptation and psychometric properties of the Italian version of the Non-Motor Symptoms Questionnaire for Parkinson's disease.

Although non-motor symptoms (NMS) of Parkinson's disease (PD) are very common also in early stages of the disease, they are still under-recognized. Screening tools for non-motor symptoms, such as non-motor symptoms questionnaire (NMSQuest), help clinicians to recognize NMS and to evaluate if patients could require further assessment or specific treatments. To validate an adapted Italian version of NMSQuest and study its psychometric properties, Italian PD patients self-completed Italian NMSQuest, and then underwent a standard clinical evaluation including motor assessment (by Hoehn and Yahr staging, unified Parkinson's disease rating scale part III) and non-motor assessment (by Montreal cognitive assessment, Beck depression inventory, neuropsychiatric inventory, Epworth sleepiness scale, scale for outcomes in Parkinson's disease-Autonomic and movement disorder society-sponsored revision of the unified Parkinson's disease rating scale part I). Somatic comorbidities were quantified using the modified cumulative illness rating scale (CIRS). Seventy-one subjects were assessed (mean age years 69.8 ± 9.6 SD; 31% women; mean duration of disease 6.3 ± 4.6 years; H&Y median 2). Italian NMSQuest showed adequate satisfactory clinimetrics in terms of data quality, precision, acceptability, internal consistency and reliability. A significant correlation was found between NMSQuest and most of non-motor assessment scales, while no significant correlation appeared with motor severity as well as with age of patients, disease duration, levodopa equivalent daily dose, L-DOPA/dopamine agonists assumption and CIRS total score. The Italian version of the NMSQuest resulted as a reliable instrument for screening NMS in Italian PD patients.

Validation of the Italian version of the Non Motor Symptoms Scale for Parkinson's disease.

OBJECTIVE: To validate the adapted Italian version of the Non-Motor Symptoms Scale (NMSS), a tool to assess non-motor symptoms (NMS) in Parkinson's disease (PD). METHODS: A cross cultural adaptation of the NMSS into Italian and a psychometric analysis of the translated version of the NMSS was carried out in patients with PD from two university centres-affiliated hospitals. The quality of data and the acceptability, reliability and construct validity of NMSS were analyzed. The following standard scales were also applied: Hoehn and Yahr staging, Unified Parkinson's Disease Rating Scale (UPDRS) part III, Montreal Cognitive Assessment, Beck Depression Inventory, Neuropsychiatric Inventory, Epworth Sleepiness Scale, Autonomic Scale for Outcomes in Parkinson's disease-Motor, Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale part I and Modified Cumulative Illness Rating Scale (CIRS). Levodopa equivalent daily dose (LEDD) was calculated. RESULTS: Seventy-one patients with PD were assessed (mean age years 69.8 ± 9.6 SD; 31% women; mean length of disease 6.3 ± 4.6 years; H&Y median: 2). Mean NMSS was 39.76 (SD 31.9; skewness 0.95). The total score of NMSS was free of floor or ceiling effects and showed a satisfactory reliability (Cronbach's alpha coefficient on total score was 0.72 [range for domains: 0.64-0.73], SEM value was 3.88 [½ SD = 31.90]). Significant positive correlations were found among total NMSS and other NMS standard tests, but no significant correlation appeared with UPDRS part III, CIRS and LEDD. CONCLUSIONS: The Italian NMSS is a comprehensive and helpful measure for NMS in native Italian patients with PD.

Low-dose lansoprazole and clarithromycin plus metronidazole vs. full-dose lansoprazole and clarithromycin plus amoxicillin for eradication of Helicobacter pylori infection.

AIM: To compare, in a randomized controlled trial, the efficacy and tolerability of two 1-week triple therapies for Helicobacter pylori eradication. METHODS: One hundred and thirty-four consecutive patients with non-ulcer dyspepsia and H. pylori infection were randomized to receive lansoprazole 30 mg once daily, clarithromycin 250 mg twice daily, and metronidazole 500 mg twice daily (LCM group), or lansoprazole 30 mg twice daily, clarithromycin 500 mg twice daily, and amoxicillin 1000 mg twice daily (LCA group). H. pylori status was assessed by rapid urease test, histology and 13C-urea breath test before and after therapy. RESULTS: At 3 months, H. pylori eradication (intention- to-treat/per protocol analysis) was 92.4%/93.8% in the LCM group and 83.1%/85.7% in the LCA group (P=N.S.). Side-effects were more frequently reported in the LCA group (37.9%) than in the LCM group (19.7%) (P < 0.05). CONCLUSIONS: In this open, randomized controlled trial, eradication of H. pylori by low-dose lansoprazole and clarithromycin plus metronidazole was higher with significantly less side-effects than by full-dose lansoprazole and clarithromycin plus amoxicillin. This finding may be related to the stronger synergism of clarithromycin plus metronidazole, even at lower doses, than of clarithromycin plus amoxicillin. Considering the lower cost as well, LCM should be preferred to LCA in the eradication of H. pylori.

Silent oophoritis due to cytomegalovirus in a patient with advanced HIV disease.

A case of isolated necrotizing cytomegalovirus (CMV) oophoritis disclosed only by necropsy studies in a patient with AIDS, is described. This unusual case report is discussed with a review of the literature dealing with CMV involvement of genital organs in the immunocompromised host, and in patients with HIV infection and AIDS.

Evaluation of short-term low-dose triple therapy for the eradication of Helicobacter pylori by factorial design in a randomized, double-blind, controlled study.

BACKGROUND: Studies demonstrating the efficacy of short-term low-dose triple therapies including omeprazole (O), clarithromycin (C) and a nitroimidazole (tinidazole, T) for Helicobacter pylori eradication have largely been open and uncontrolled, and have not assessed antibiotic sensitivity. Simpler regimens using the component drugs have not been evaluated. AIM: To evaluate the OCT regimen in a randomized, controlled trial, testing for pre- and post-treatment antibiotic resistance and comparing, in a factorial design, the OCT regimen with simpler combinations of its components. METHODS: One hundred and twenty-eight patients (68 males, 60 females, age 22-80 years, mean 53 years) with H. pylori gastritis were randomly assigned to one of the following four treatment groups: (C) clarithromycin 250 mg b.d.; (OC) omeprazole 20 mg o.d. + clarithromycin 250 mg b.d.; (CT) clarithromycin 250 mg b.d. + tinidazole 500 mg b.d.; (OCT) omeprazole 20 mg q.d.s. + clarithromycin 250 mg b.d. + tinidazole 500 mg b.d. The drugs were administered for 1 week. Medical interview, upper gastrointestinal endoscopy (with four antral and four corpus biopsies) and the 13C-urea breath test were carried out for all patients prior to and 4 weeks after treatment. Biopsy specimens were used for the urease test, histology, and culture and sensitivities. RESULTS: All but one patient completed treatment. Side-effects were rare and mild in all groups. The eradication rate was 93.8% in group OCT, 59.4% in group CT, 31.3% in group OC and 6.3% in group C. Pre-treatment metronidazole resistance was 12.8%, clarithromycin 1.1% and, to both antibiotics, 2.1%. In patients with pre-treatment metronidazole resistance, the eradication rate was 75% in group OCT and 33% in group CT. Post-treatment resistance to clarithromycin was induced in 28.5% of the failures in group C, but in none of group OC. Resistance to both antibiotics occurred in 22.2% of the failures in group CT and in none of group OCT. CONCLUSIONS: (i) The high efficacy of the OCT regimen is proved and each of the individual components of the regimen is essential to the result, possibly via a synergistic effect. (ii) Pre-treatment metronidazole resistance is scarcely relevant to the outcome. (iii) Acquired resistance is essentially nil if omeprazole is part of the regimen.

AIDS-related visceral aspergillosis: an underdiagnosed disease during life?

Five out of nine consecutive patients with HIV-related visceral aspergillosis observed by us since 1984 were diagnosed only at necropsy examination. The histopathological features of these five patients [two with isolated pneumonia, one with central nervous system (CNS) involvement, one with brain abscess and respiratory disease and one with pulmonary, pleural and kidney infection] have been evaluated according to epidemiological, clinical and radiological features. On the basis of our experience, life-threatening aspergillosis, which is often misdiagnosed or missed in the setting of HIV infection and AIDS, should be suspected in patients with far-advanced underlying disease and unexplained signs and symptoms, even in the absence of some presumed risk factors (i.e. neutropenia and prior steroid treatment). Plain chest radiography and bronchoscopy with broncholaveolar lavage may fail to reveal respiratory disease, CNS aspergillosis is not necessarily associated with suggestive neuroradiological features and disseminated disease may present with multiorgan failure. The unfavorable outcome of this emerging AIDS complication can be improved only by earlier diagnosis based on invasive techniques and appropriate and timely treatment.

Colitis associated to chemotherapy with 5-fluorouracil.

Antitumoral agents, especially when administered in combination, can induce pseudomembranous colitis, due to their antimitotic and antibacterial properties. Although patients given 5-fluorouracil frequently show nonspecific colitis or diarrhea without colitis, very few cases of proven pseudomembranous colitis have been described during 5-fluorouracil monotherapy. We describe the second case reported in the English literature of a typical pseudomembranous colitis occurring in a patient given 5-fluorouracil as a single antimitotic agent for colonic cancer. Intestinal injury was not preceded by antibiotic therapy. Although both stool and pseudomembrane culture did not yield C. difficile, oral vancomycin was started. This treatment led to a prompt improvement of intestinal symptoms and colitis was resolved in one week.

[The surgical treatment of a rare primary cardiac tumor: hemangioma. A report of 2 cases]. / Trattamento chirurgico di un raro tumore primitivo cardiaco: l'emangioma. Osservazione di due casi.

Primary benign tumors of the heart are particularly rare; cardiac hemangioma is one of the most rare primary benign cardiac tumors. Natural history, symptoms and prognosis of the disease depend on the potential complications due to the location and diffusion of the mass. We report on 2 cases of cardiac hemangioma, diagnosed occasionally in the first patient or due to gastroenteric symptoms in the second patient. The diagnosis was obtained by 2-D-echo and magnetic resonance imaging. In both cases the hemangioma was located on the right ventricle. Both patients underwent tumor resection in hypothermic cardiopulmonary bypass. In one case, a graft to the right coronary artery was associated; in the other case, the right ventricular outflow tract was reconstructed with an infundibular patch. Histology showed mixed hemangioma in one case and cavernous hemangioma in the other. The postoperative course was uneventful. At a follow-up of 8 years and 1 year, respectively, both patients are classified as NYHA 1 and both 2-D-echo and magnetic resonance imaging did not show any residual tumoral mass. This experience demonstrates that, depending on their location, benign neoplastic masses may be radically resected with acceptable operatory risks and excellent long-term results.

Cancer of the appendix in long-standing ulcerative colitis: a case report.

Cancer of the appendix was found in a 69-year-old female patient affected by long-standing ulcerative colitis (UC). On histological examination the cancer was a typical cystadenocarcinoma of the appendix. The appendiceal mucosa not invaded by the neoplastic process was normal. Histological examination of the colorectal mucosa did not show dysplasia or cancer. These findings suggest that appendiceal cancer and UC may be unrelated diseases. A surveillance program for early detection of cancer of the appendix in patients with long-standing UC does not seem mandatory.

[Quality control at the Istituto di Anatomia e Istologia patologica at the Università di Bologna]. / Controllo di qualità dell'Istituto di Anatomia e Istologia patologica dell'Università di Bologna.

The growing importance in medical practice of a standardized diagnosis in cyto- and histopathology and the recent recommendations for the adoption of standardized schemes for quality control in anatomic pathology by International Committees stimulated the medical staff of the Institute of Anatomic Pathology of the University of Bologna to adopt a pertinent method. The method used by the Department of Pathology of the Yale University (New Haven, Connecticut, USA) was chosen. A Committee for the quality control was appointed and two kinds of controls were set up: an External Quality Assessment (review of the difficult cases by external experts, slide seminars) and an Internal Quality Assessment performed by the members of the Committee on the diagnostic and laboratory routine of the Institute. Such a survey is periodically monitored during the monthly meetings of the Committee and described in the monthly reports. The present paper illustrates the method adopted and the preliminary results obtained in order to stimulate the discussion of such a critical theme in contemporary Anatomic Pathology at a national level.

Right ventricular cardiomyopathy in identical and nonidentical young twins.

We describe the first sets of identical and nonidentical twins with right ventricular cardiomyopathy (RVC). Pair A: A 12-year-old boy was referred because of palpitation and syncope. Clinical and instrument examinations revealed an enlarged and depressed right ventricle (end-diastolic volume = 110 ml/m2; ejection fraction = 44%), spontaneous ventricular tachycardia, and fatty-fibrous infiltrates in the biopsy specimens. His asymptomatic, monozygotic twin showed localized involvement of the right ventricle with isolated, ventricular extrasystoles. Pair B: These 18-year-old nonidentical twin boys showed diffuse right ventricular involvement (end-diastolic volume = 110 ml/m2 and 114 ml/m2; ejection fraction = 30% and 24%, respectively), induction of sustained and nonsustained ventricular tachycardia, respectively, and fibrosis on endomyocardial biopsy. One of the boys died suddenly at rest after documented ventricular fibrillation. These cases support the hypothesis of a genetic etiology with a minor role for genotype and point to the important influence of environmental factors in determining the clinical features of the disease.

Malignant sarcomatoid mesothelioma of the pleura: a histological and immunohistological study of a case.

The authors describe the case of a 70 year-old asymptomatic female, who showed nodular pleural growths at an occasional chest roentgenogram. Histological examinations and laboratory findings excluded the possibility of an inflammatory granulomatous process, but they did not allow differentiation between malignant sarcomatoid pleural mesothelioma and malignant fibrous histiocytoma. Only at immunohistochemistry was the differential diagnosis made. In fact, the co-expression of vimentin and cytokeratins by neoplastic cells, along with their negativity for macrophage markers strongly supported the hypothesis that the neoplastic growth originated from subpleural mesenchymal stem cells.

Acute idiopathic interstitial giant cell myocarditis. A histological and immunohistological study of a case.

The Authors report on a case of acute idiopathic giant cell myocarditis, which occurred in a young man without previous history of immunodeficiency or tumours, and displayed a rapidly fatal clinical course. Autoptic examination showed diffuse damage to the myocardium, with myocytolysis, granuloma formation and abundant giant cell reaction. No significant changes were observed in the other organs and systems . Immunohistochemistry revealed that the giant cells strongly reacted with the antibody KP1--raised to the macrophage-associated antigen CD68--whereas they did not stain with the monoclonal against the muscle-specific marker desmin. In the light of their findings and previous reports in the literature, the Authors discuss the possible origin of giant cells, along with the pathogenesis of the condition.

Human immunodeficiency virus type 1 antigen detection in endomyocardial biopsy: an immunomorphological study.

A virological and immunomorphological study has been performed on endomyocardial biopsy from an AIDS patient. Some data suggest the possible involvement of HIV in the pathogenesis of the cardiomyopathy.

Brain stem encephalitis in a patient with gastroduodenal and cardiovascular dysfunction: a case report.

The authors describe a case of a 38-year-old woman suffering from long-standing epigastric pain, abdominal fullness and vomiting due to functional alteration of gastroduodenal motility. Following a surgical procedure, a supraventricular tachyarrhythmia and hemodynamic disturbances suddenly appeared and led to death in a few hours. A histopathological study carried out on the brain stem revealed inflammatory lesions suggestive of a viral infection, whereas the study of the conduction system of the heart did not show any alterations. A clinicopathological correlation is suggested between the clinical picture and anatomical lesions of the tegmental region.

[Idiopathic restrictive cardiomyopathy: clinical, hemodynamic, histologic and prognostic profile]. / Cardiomiopatia restrittiva idiopatica: profilo clinico, emodinamico, istologico e prognostico.

Idiopathic restrictive cardiomyopathy is a rare myocardial disease characterized by restrictive physiology without a specific histologic basis. To assess its clinical, hemodynamic, morphologic and prognostic details we retrospectively evaluated all the patients hospitalized in our Institute from 1974 to 1988. Nine patients, aged 42 +/- 16 years, M/F ratio = 0.29, who represent 64% of all the restrictive myocardial diseases biopsied were identified. Severe cardiac heart failure (3-4 NYHA) and arrhythmias (ventricular and supraventricular) were extremely common. The electrocardiogram showed several non specific signs: low voltage of QRS in peripheral leads (4/7), pseudo-infarctional aspects (3/7), mono or biventricular hypertrophy (3/7) disturbance of ventricular conduction (3/7), aspecific abnormalities of ventricular repolarization (3/7). All patients showed a prolonged QTc. M-mode and 2-dimensional echocardiography demonstrated in 6 cases biatrial enlargement, normal or slightly enlarged ventricles, normal or moderately depressed fractional shortening; biventricular concentric hypertrophy was detected in 3 cases, asymmetrical septal hypertrophy in 1. Five patients showed pericardial effusion. Cardiac catheterization disclosed an increase of left and right ventricular end-diastolic pressures (8/8) with a dip-plateau pattern and/or characteristic W waveform in the atrial pressure tracing (9/9). Passive pulmonary hypertension was detected in 6/9 cases. The cardiac index was decreased in 4/8 cases. Left ventricular angiography showed mitral regurgitation in 5/8 patients, tricuspidal in 5/8. Ejection fraction was decreased in 3/8 cases. Endomyocardial biopsy showed interstitial fibrosis (8/9), cellular hypertrophy and/or nuclear alterations (7/9), slight endocardial thickening (2/9). At a mean follow-up of 22 +/- 15 months 3 patients died and 2 underwent heart transplantation. In conclusion idiopathic restrictive cardiomyopathy is one of the most frequent forms of restrictive myocardial diseases in our geographic area. Severe congestive heart failure and arrhythmias are extremely common. The disease can be suspected by clinical, electrocardiographic and echocardiographic features, but the final diagnosis requires cardiac catheterization and endomyocardial biopsy. Prognosis is severe and heart transplantation must be considered in the cases with severe heart failure.

Distribution of basement membrane antigens in bladder carcinomas: an additional prognostic parameter. Immunohistochemical study.

A retrospective study of basement membrane (BM) components (laminin and type IV collagen) in urothelial tissues was performed by applying an immunoperoxidase method to 64 formalin-fixed specimens. The distribution of laminin and type IV collagen was investigated in normal and non-cancerous epithelium (11 cases), where the staining of the basement membrane was continuous. In the invasive bladder carcinomas (53 cases), two distinct staining patterns were observed both with type IV collagen and with laminin: preserved or thin and discontinuous (pattern I) and fragmented or absent (pattern II). These patterns were largely related to the type of growth of the bladder neoplasias ("pushing margin" or "finger-like") and to the cellular arrangement. Furthermore, five-year survival exceeded 70% in patients with pattern I, whereas only three of the 18 patients with pattern II survived for five years or more.

Ultrastructural and immunohistochemical contribution to the histogenesis of human cardiac myxoma.

The ultrastructural features of 8 human cardiac myxomas were analyzed and correlated with immunohistochemical data, with the aim to clarify the characteristics of the cell lines involved in the tumor genesis. Immunohistochemical studies were performed to detect the presence and the distribution of intracytoplasmic filaments (vimentin, desmin, actin, myosin) as well as myoglobin and factor VIII-related antigen, albumin, and lysozyme. Eighty percent of myxoma cells were simultaneously positive for vimentin, desmin, and actin, whereas 30% of them stained with antifactor VIII and antivimentin antibodies. The submicroscopic analysis revealed two main cell populations: (1) one composed of stellate-shaped cells with scanty organelles and sparse hyaloplasmic filaments scattered throughout the myxoid stroma and forming a loose network with their projections; (2) another one included cells with more cytoplasmic organelles, intermediate filaments, and myofilaments arranged either singly or in both solid and hollow cord-like structures. Our results support the hypothesis that cardiac myxoma may originate from a reserve multipotent mesenchymal cell able to differentiate more or less completely along two major evolutional lines: myoid and endothelial. The tumor tissue thus seems to be involved in vessel formation, suggesting a growth pattern akin to that manifested in other forms of endocardial pathological reactivity in which reserve mesenchymal cells are engaged.

A rare case of mucous-secreting villous adenoma of the bladder.

A case of mucous-secreting villous adenoma of the urinary bladder associated with cystitis glandularis is reported which led to radical cystectomy because of the extensive bladder involvement. An immunohistochemical study was performed in order to detect ABH tissue antigens. The histogenesis and the possible malignant potential of this neoplasm are discussed.