Efficacy and tolerability of a combined lipid-lowering nutraceutical on cholesterolemia, hs-CRP level and endothelial function in moderately hypercholesterolemic subjects.

Our aim was to test, by a double-blind, placebo-controlled randomized clinical trial, whether a short-term treatment with a combined lipid-lowering nutraceutical could improve endothelial function in a cohort of moderately hypercholesterolemic subjects. Thus, 80 healthy, moderately hypercholesterolemic subjects were consecutively enrolled and, after 4 weeks of stabilization diet, they were randomized to either the tested lipid-lowering nutraceutical or placebo for 8 weeks. At the beginning and end of treatment a complete lipid pattern, safety parameters, hs-CRP and endothelial function were measured. When compared to placebo, during nutraceutical treatment patients experienced a more favorable percentage change in total cholesterol (TC vs baseline: -17.9%; TC vs placebo: -5.6%), LDL-cholesterol (LDL-C vs baseline: -23.3%; LDL-C vs placebo: -2.8%), hs-CRP (hs-CRP vs baseline: -2.4%; hs-CRP vs placebo: -1.5%), and endothelial function (pulse volume displacement vs baseline: +17%; pulse volume displacement vs placebo treatment: -3.3%). No significant difference was observed in respect to effects on triglycerides, HDL-cholesterol and safety parameters. On the basis of our data, the tested lipid-lowering nutraceutical seems to significantly improve endothelial function in moderately hypercholesterolemic subjects. These results have to be confirmed on larger patient samples and over longer periods.

A novel computational model of mouse myocyte electrophysiology to assess the synergy between Na+ loading and CaMKII.

Ca(2+)-calmodulin-dependent protein kinase II (CaMKII) hyperactivity in heart failure causes intracellular Na(+) ([Na(+)]i) loading (at least in part by enhancing the late Na(+) current). This [Na(+)]i gain promotes intracellular Ca(2+) ([Ca(2+)]i) overload by altering the equilibrium of the Na(+)-Ca(2+) exchanger to impair forward-mode (Ca(2+) extrusion), and favour reverse-mode (Ca(2+) influx) exchange. In turn, this Ca(2+) overload would be expected to further activate CaMKII and thereby form a pathological positive feedback loop of ever-increasing CaMKII activity, [Na(+)]i, and [Ca(2+)]i. We developed an ionic model of the mouse ventricular myocyte to interrogate this potentially arrhythmogenic positive feedback in both control conditions and when CaMKIIδC is overexpressed as in genetically engineered mice. In control conditions, simulation of increased [Na(+)]i causes the expected increases in [Ca(2+)]i, CaMKII activity, and target phosphorylation, which degenerate into unstable Ca(2+) handling and electrophysiology at high [Na(+)]i gain. Notably, clamping CaMKII activity to basal levels ameliorates but does not completely offset this outcome, suggesting that the increase in [Ca(2+)]i per se plays an important role. The effect of this CaMKII-Na(+)-Ca(2+)-CaMKII feedback is more striking in CaMKIIδC overexpression, where high [Na(+)]i causes delayed afterdepolarizations, which can be prevented by imposing low [Na(+)]i, or clamping CaMKII phosphorylation of L-type Ca(2+) channels, ryanodine receptors and phospholamban to basal levels. In this setting, Na(+) loading fuels a vicious loop whereby increased CaMKII activation perturbs Ca(2+) and membrane potential homeostasis. High [Na(+)]i is also required to produce instability when CaMKII is further activated by increased Ca(2+) loading due to ß-adrenergic activation. Our results support recent experimental findings of a synergistic interaction between perturbed Na(+) fluxes and CaMKII, and suggest that pharmacological inhibition of intracellular Na(+) loading can contribute to normalizing Ca(2+) and membrane potential dynamics in heart failure.

Quadriplegia due to pachymeningitis, vasculitis and sepsis in a patient with rheumatoid arthritis: a case report.

We report the case of a 84-year-old man, with history of rheumatoid arthritis, admitted the Hospital for a fall and complaining of dysaesthesia and pain located to the cervical spine and arms. Within a few hours after admission, fever and acute, progressive, ascendant quadriplegia became evident. Magnetic resonance imaging (MRI) of cervical spine showed spinal canal stenosis between C4-C6 with spinal cord compression. Hemocultures resulted positive for Staphylococcus aureus. The clinical picture rapidly evolved to sepsis with a fatal multi-organ failure. An autopsy found a osteosclerosis narrowing the neurocanal at the level of C3-C6, and recent cervical medulla infarction. A histological exam revealed the presence of a suppurative pachymeningitis with local phenomenas of periradiculitis, vasculitis and thrombosis of the anterior medullar artery, associated with coagulative necrosis of the neural tissue.

High frequency of p53 gene alterations associated with protein overexpression in human squamous cell carcinoma of the larynx.

A series of 58 primary human squamous cell carcinomas of the larynx (LSCCs) was examined for the expression of the p53 tumor-suppressor gene by a combined immunohistochemical and molecular approach. About 60% of the cases displayed nuclear p53 overexpression as revealed by immunostaining with PAb1801, PAb122 and PAb240 monoclonal antibodies. This phenomenon was associated with the presence of structural and/or transcriptional alterations of the p53 gene. Our results provide evidence that p53 abnormalities constitute the most frequent genetic alteration identified so far in LSCC and indicate that the abnormal accumulation of the protein correlates with the presence of p53-mutated versions. These findings, taken together with the peculiar biochemical properties of p53, support the hypothesis of a possible pathogenetic relationship between smoke carcinogen exposure and p53 inactivation in the development of this tumor type.

Out-of-hospital sudden death referring to an emergency department.

Over an 11-year period, autopsies were performed on 957 of 1038 nontraumatic deaths in the Emergency Department of the Central Hospital in Ferrara, Italy. Of these 957 cases, 732 (76.5%) met criteria for sudden death. In 100 (14%) of these cases, the death could be attributed to pulmonary embolism (55 cases), stroke (17), or rupture of aortic aneurysm (28). Acute myocardial infarction accounted for 403 (55%) of all sudden deaths. Severe coronary artery disease was found in 340 (84%) of these 403 deaths, with plaque fissuring or thrombi in 189 or 151 cases, respectively. Among the 229 sudden deaths for whom no immediate cause could be determined (31% of the total population), all had evidence of heart disease: 147 individuals had severe coronary artery disease, with plaque fissuring or thrombi found in 72 or 43, respectively. The remaining cases with no immediate cause of death had evidence of a cardiomyopathy (61) or valvular disease (21). We conclude that acute myocardial infarction accounts for the majority of cases of nontraumatic sudden death in our Emergency Department. Altogether, 84% of these patients had severe coronary artery disease. In approximately one-third of cases for whom no immediate cause of sudden death could be determined, all had evidence of heart disease, and about two-thirds had severe coronary artery disease.

Structural changes of duodenum brush border in lung cancer patients treated with cisplatin plus etoposide.

The effects of cisplatin plus etoposide chemotherapy (PE) on the structure of proximal intestine villi and brush border were investigated in 10 patients with lung cancer. The day before starting chemotherapy (time 1); 8 days after its initiation (time 2), and one month after the 3rd course of PE (time 3) they underwent esophagogastroduodenoscopy and three biopsies were taken from the descending duodenum. Intestinal villi were examined by light microscopy; brush border by transmission electron microscopy. No significant histological changes of villous pattern were observed at times 2 and 3. The height of microvilli was reduced in seven patients at time 2 (P < 0.05). Microvilli abnormalities (i.e. rarefaction and/or heterogeneity in their height) were present in nine patients at time 2 (P < 0.05). Brush border appearance at time 3 did not differ from that at time 1. PE chemotherapy seems to have short-term toxic effects on small intestine brush border, but does not cause chronic enteropathy.

Lymphoepithelial cyst of the pancreas.

A rare case of lymphoepithelial cyst of the pancreas is reported. Microscopically the cyst content consisted of keratinous material and the walls were lined by mature squamous epithelium surrounded by dense lymphoid tissue. Immunohistochemistry showed diffuse reactivity for CD20 and CD3 in the lymphoid tissue and uniform positivity for cytokeratins in the squamous epithelium. Although the histogenesis of lymphoepithelial cysts of the pancreas is not understood, awareness of this lesion is helpful in differentiating it from other pancreatic cystic lesions.

Sudden death in diabetic subjects: evidence for a peculiar circadian variation in occurrence.

Anatomo-physiopathological and chronobiological features of 59 diabetic subjects out of 610 non hospitalized individuals observed for sudden death (SD) in an Emergency Room, over an 8-year period, were studied. Mean age and anatomopathological causes of SD were not different between diabetic (DMs) and non-diabetic subjects (NDs). However the frequency of DMs was higher among subjects who died from circulatory failure death (CFD), rather than from arrhythmic death (AD). Diabetics presented a prevalent peak incidence of SD in the afternoon-late evening; whereas in NDs two peaks were present, respectively in the morning and in the afternoon. According to anatomo-physiopathological causes, DMs presented a higher incidence of acute myocardial infarction (AMI) and CFD between 21:01 and 24:00, whereas in NDs the prevalent peak of AMI was observed in the early afternoon (13:01 to 16:00). Moreover, in DMs SD from acute myocardial failure prevalently occurred in the early afternoon (13:01 to 16:00), whereas in NDs it was uniformly distributed throughout the day. The present study seems to indicate that different anatomo-physiopathological causes of SD may present specific temporal patterns in diabetics.

Eccrine spiradenoma of the ear: case report.

A case of eccrine spiradenoma of the left pinna is described. To the best of our knowledge, this is the first report regarding this site. The treatment was a surgical excision in safe margins. This rare benign tumour should be considered for the differential diagnosis of solitary or multiple soft tissue lesions of the head and neck.

Risk factors in vulvar carcinoma recurrences.

18 patients with invasive vulvar carcinoma treated by radical vulvectomy and bilateral groin lymphadenectomy have been evaluated. An 18% of local and 22% of pelvic or distant recurrences occurred. The local recurrences had favorable prognosis, whereas the pelvic or distant recurrences a worse prognosis. The staging, the tumour size, the nodes involvement, the stromal infiltration and the lymphoplasmacytic infiltration, as prognostic factors, have been evaluated. All these factors, except the tumour size, influenced the pelvic or distant recurrences. The pelvic or distant recurrences were contemporaneously associated with mild phlogistic infiltration and depth of invasion > 5 mm.

Surgical treatment of invasive carcinoma of the vulva. A reappraisal.

The Authors studied three groups of patients affected by invasive vulvar carcinoma. The first group (19 cases), treated by radical vulvectomy and bilateral inguinal lymphadenectomy, had a survival rate at 5 years of 89% in Stage I and 56% in Stage II. The second group (9 cases) which presented poor general health conditions, had a survival rate at 4 years of 33% and 14% in Stage I and in Stage II, respectively. The third group of patients (7 cases), who refused any type of treatment, died within 12 months. Nodal involvement influenced survival rate. In fact, regardless of the stage, a survival rate at 5 years of 92% and 26% was seen in patients with negative nodes and positive nodes, respectively. In conclusion, the study confirms that radical surgery is the therapy of choice in advanced carcinoma of the vulva. However, early diagnosis remains the most important agent in reducing the extension of the surgical treatment.

[Clinical and instrumental study program of nodular diseases of the thyroid]. / Programma di studio clinico-strumentale delle affezioni nodulari della tiroide.

Authors have passed from a combined clinical and radioisotopic analysis to an integrated polyinstrumental approach by adding thermography and above all echography. In order to achieve the purpose Authors have confronted in retrospective a "clinico-radioisotopic group" of 103 cases, from 1965 to 1975, and an "integrated polyinstrumental group" of 53 cases, since 1976. Comparing the "clinico-radioisotopic method" with "polyinstrumental approach" the main results could be summarized as follows: the diagnostic specificity improved in benign lesions from 77% to 96%, however in malignant lesions it remained about the same (63%). Considering these results the Authors have subdivided thyroid nodules, mainly based on echography, in two distinct categories with the following orientation: I. Solitary Thyroid Nodule: a) definitely cystic -- demonstrated by echography; b) "cold" -- by conventional scintygraphy; c) "negative" -- by thermography; d) non uptake of tumor seeking radiopharmaceutical. The control, therapy and surveilance of these cases should be limited to needle aspiration of the cystic cavity followed, of course, by citologic examination. This aspirations is both diagnostic and possibly therapeutic. II. Solitary Thyroid Nodule: a) definite solid -- echography; b) "cold" -- convential scintygraphy; c) "positive" --thermography (possibly "negative"); d) non uptake of tumor seeking radiopharmaceutical. Here the therapeutic orientation is clearly surgical.

[Analysis of membrane proteins in pernicious anemia and various primary and secondary erythropathies]. / Analisi delle proteine di membrana nell'anemia perniciosa ed in alcune eritropatie primitive e secondarie

A study of membrane proteins in pernicious anaemia and other haemolitic and anhaemolytic erythropathies is reported. Cellulose acetate and acrylamide gel electrophoresis was carried out and acid, neutral and basic amino acid contents were determined. Relatively specific alterations were noted. Chromatographic analysis of the amino acids suggested that in pernicious anaemia, as in other conditions, structural changes take place in the red cell membrane, though these may be confined to certain sectors. A constant alteration related to the concomitance or otherwise of erythrocyte hyperhaemolysis, however, could not be discerned.

[Dermoid cyst associated with planocellular carcinoma]. / Cisti dermoide con associato carcinoma a cellule piatte.

The case of an ovarian mature cystic teratoma with an associated squamous cell carcinoma is described. The patient, in advanced stage, died a few months after surgery, during the treatment by chemo and radiotherapy.

Anatomoclinical and chronobiological aspects of sudden death in elderly subjects.

Anatomoclinical and chronobiological aspects of sudden death (SD) of 671 subjects observed at the Emergency Room of Ferrara Hospital from January 1983 to December 1991 were prospectively investigated. 3 groups stratified by age were considered: group A with age < 65 years (no. = 251, 37.4%), group B with age between 65 and 74 years (no. = 210, 31.3%), and group C with age > or = 75 years (no. = 210, 31.3%). SD was classified on the basis of either anatomopathological (i.e.: acute myocardial infarction, acute myocardial failure, intracerebral hemorrhage, rupture of aortic aneurysm, pulmonary embolism), and clinical findings (i.e.: arrhythmic death and circulatory failure death). Patients were grouped into six 4-hour periods according to the time of onset of symptoms, and circadian distribution was tested for uniformity by a chi 2 test for goodness of fit. The analysis found in group C an increased frequency of SD due to pulmonary embolism and rupture of aortic aneurysm, and an increment of males/females ratio in deaths from cardiac causes. In group C the mean age of SD, in particular from acute myocardial infarction, pulmonary embolism or arrhythmic death proved higher in females compared to males. Only for group B was a significant circadian periodicity found for SD from acute myocardial infarction and arrhythmic death, with a peak in the morning.

Pulmonary blastoma: case report in an adult.

We present a case of biphasic pulmonary blastoma, a rare primary malignant lung neoplasm, in a 48 year old man. Despite its resection followed by postoperative chemotherapy, the neoplasm recurred and the patient survived only 41 months after the diagnosis.

Prenatal diagnosis of cystic adenomatoid malformation of the lung.

Two cases of congenital cystic adenomatoid malformation of the lung (CCAML) are described. In the light of recent literature the prenatal diagnosis and management are discussed.

[Fatal pulmonary embolism. Risk factors and anatomo-pathological findings related to gender and age]. / Embolies pulmonaires fatales. Facteurs de risque et constatations anatomo-pathologiques liés au sexe et á l'âge.

OBJECTIVES: The aim of this study was to evaluate possible variations in clinical risk factors and anatomopathological findings in fatal pulmonary embolism in relation to sex and age. METHODS: The total sample consisted of 230 subjects (mean age 72 +/- 11 years), 103 males and 127 females, of which 74 died out-of-hospital and 156 in the course of hospitalization. 124 cases were then considered also separately as "sudden death group". The sample was stratified by sex and into 4 groups by age: subjects aged less than 60 years, between 60 and 69, between 70 and 79, and more than 80 years. RESULTS: Age at occurrence of pulmonary embolism was significantly higher in females, compared with males (75 +/- 11 vs 69 +/- 11 years, p < 0.001), and the men/women ratio was higher in younger age groups, tending to inversion with aging. An increased frequency of males was found between subgroups of subjects affected by valvular heart disease (10.6% vs 2.3%, p = 0.019), and chronic pulmonary disease (7.7% vs 1.8%, p = 0.049), whereas an increased frequency of women was found in a group of subjects suffering from trauma or fracture (12.6% vs 2.9%, p = 0.016). As concerns age subgroups, a significant increased frequency of subjects aged < 60 years was found in risk groups "surgery" (36%, p < 0.001) and "malignancy" (40%, p = 0.002). Moreover, in subjects aged less than 80 years, main predisposing factors were recent trauma and/or a fracture (16.2%, p = 0.013). CONCLUSION: The difference in frequency of risk factors between sexes could depend on the higher life expectancy in women, with consequent increase in likelihood of risk factors specifically related to the elderly.

[Clinical and biological considerations on adenocystic carcinoma of the head]. / Considerazioni cliniche e biologiche sul carcinoma adenoidocistico dell'estremità cefalica.

The purpose of the present work was to define some aspects (i.e. the influence of histological grading on prognosis and the possibility of an eventual hormone dependency) of adenoidocystic carcinoma, a highly controversial form of carcinoma still open to debate. A study is thus reported of 33 cases of adenoidocystic carcinoma of the head and neck seen from 1965-1985 at the E.N.T. Clinic of Ferrara. The individual histological samples were seen over a period of time by a single histopathologist who was not informed as to the patients' clinical progression. In this manner the diagnostic criteria was kept constant. Tumoral grading was then performed on the basis of the Marsh and Allen classification. The overall actuarial survival curves are presented according to site and grading. Besides confirming the already known data regarding the decrease in survival rate well beyond the fifth year, local recurrences and the frequency of lymph node and secondary metastases, the results indicate a direct relationship between grading and prognosis. In fact, overall survival decreases for the less differentiated forms while the frequency of local recurrences increases as does that of lymph node and systemic metastases. Furthermore, in 63.3% of the female patients a genital hormone dependent pathology was noted prior to the appearance of a salivary gland tumor. These observations would suggest that hormones may play a role in the genesis of adenoidocystic carcinoma.

[Malignant fibrous histiocytoma of the larynx. Presentation of a clinical case and review of the literature]. / L'istiocitoma fibroso maligno della laringe. Presentazione di un caso clinico e revisione della Letteratura.

Malignant Fibrous Histiocytoma (MFH) is a tumor of mesenchymal origin which rarely occurs in head and neck. At the laryngeal level this neoplasm manifests itself as a sessile or peduncolate mass with ulcerations. Histological diagnosis of small biopsy samples is difficult and is, therefore, performed on the full surgical piece. The treatment of choice is complete exeresis of the mass within a safety margins. The Authors present a case report, the 37th laryngeal MFH reported in the literature and, in particular, the 5th case presented in a supraglottic site. Surgical treatment performed in this patient was exeresis of the neoplasm through pharyngothyrotomy conduced with safety margins and reconstruction by thyrohyoidpexy.