Validation of the SAA-102 home blood pressure monitor according to the protocols of the European Society of Hypertension, the Association for the Advancement of Medical Instrumentation and the British Society of Hypertension

OBJECTIVE: To determine the accuracy of a new oscillometric home blood pressure (BP) monitor for arm BP measurement, the SAA-102, developed by the Sensacare Company. DESIGN: Evaluation of the SAA-102 was performed using validation protocols of the European Society of Hypertension (ESH), the Association for the Advancement of Medical Instrumentation (AAMI), and the British Hypertension Society (BHS). METHODS: The SAA-102 monitor was assessed on 33 participants according to ESH requirements, which are based on four zones of accuracy differing from the mercury standard by 5, 10, 15 mmHg or more. Then the oscillometric monitor was tested on 85 participants according to AAMI criteria which require a mean device-observers discrepancy within 5+/-8 mmHg. Finally, the electronic device was evaluated on 93 participants according to BHS requirements, which are based on five phases: before-use calibration, in-use assessment, after-use calibration, static device validation and report of the results. RESULTS: The SAA-102 passed all phases of the ESH international protocol for both systolic and diastolic blood pressure (SBP and DBP). The SAA-102 passed also AAMI criteria for SBP and DBP. The mean discrepancy between the SAA-102 and observers was 0.1+/-4.6 and -2.7+/-5.2 mmHg, for SBP and DBP, respectively. According to BHS protocol, the oscillometric monitor achieved final grading of A/A for SBP and DBP, respectively. CONCLUSION: These data show that the SAA-102 device satisfies ESH, AAMI, and BHS protocols for both SBP and DBP and may be recommended for everyday use for BP monitoring at home and in clinical practice.     

Neridronate inhibits angiogenesis in vitro and in vivo

The effects of the amino-bisphosphonate neridronate on endothelial cell functions involved in angiogenesis, namely, proliferation and morphogenesis on Matrigel were tested in vitro, whereas its effects on angiogenesis were studied in vivo, by using the chick embryo chorioallantoic membrane (CAM) assay. In vitro, neridronate inhibited endothelial cell proliferation in a dose-dependent fashion, peaking at 30 μM. At the same concentration, neridronate inhibited fibroblast growth factor-2 (FGF-2)-induced capillary-like tube formation in the morphogenesis assay on Matrigel. In vivo, when tested in the CAM assay, neridronate again displayed the capability to inhibit FGF-2-induced angiogenesis. Overall, these results suggest that anti-angiogenesis by neridronate could be used to treat a wide spectrum of angiogenesis-dependent diseases, including certain chronic inflammatory diseases and cancer.     

Impact of hepatitis C virus infection on lifestyle

AIM: To evaluate the impact of the diagnosis of hepatitis C infection on lifestyle habits such as smoking, drinking, sports activity and diet.METHODS: A self-administered, anonymous question-naire was offered to out-patients with HCV infection consecutively attending three clinical centres in Italy.RESULTS: Of the 275 respondents, 62.2% (171) were male. Mean age was 51 (range 20-80) years. Overall, after the diagnosis of hepatitis C, 74.5% of drinkers had modified (giving up or reducing) alcohol consumption, 21.3% of smokers had modifi ed their habits and 32.3% of subjects who reported sports activity had either stopped or reduced frequency of activity or chose a less fatiguing sport. Sixty-four percent of the respondents reported having modified their diet, most of them on physician's advice. CONCLUSION: After the diagnosis of hepatitis C many patients correctly modif ied their alcohol consumption and a minority their smoking habits. The reason for reported changes in diet and physical activity needs further investigations.     

Enhanced sensitivity to IGF-II signaling links loss of imprinting of IGF2 to increased cell proliferation and tumor risk

Loss of imprinting (LOI) of the insulin-like growth factor-II gene (IGF2), leading to abnormal activation of the normally silent maternal allele, is a common human epigenetic population variant associated with a 5-fold increased frequency of colorectal neoplasia. Here, we show first that LOI leads specifically to increased expression of proliferation-related genes in mouse intestinal crypts. Surprisingly, LOI(+) mice also have enhanced sensitivity to IGF-II signaling, not simply increased IGF-II levels, because in vivo blockade with NVP-AEW541, a specific inhibitor of the IGF-II signaling receptor, showed reduction of proliferation-related gene expression to levels half that seen in LOI(−) mice. Signal transduction assays in microfluidic chips confirmed this enhanced sensitivity with marked augmentation of Akt/PKB signaling in LOI(+) cells at low doses of IGF-II, which was reduced in the presence of the inhibitor to levels below those found in LOI(−) cells, and was associated with increased expression of the IGF1 and insulin receptor genes. We exploited this increased IGF-II sensitivity to develop an in vivo chemopreventive strategy using the azoxymethane (AOM) mutagenesis model. LOI(+) mice treated with AOM showed a 60% increase in premalignant aberrant crypt foci (ACF) formation over LOI(−) mice. In vivo IGF-II blockade with NVP-AEW541 abrogated this effect, reducing ACF to a level 30% lower even than found in exposed LOI(−) mice. Thus, LOI increases cancer risk in a counterintuitive way, by increasing the sensitivity of the IGF-II signaling pathway itself, providing a previously undescribed epigenetic chemoprevention strategy in which cells with LOI are “IGF-II addicted” and undergo reduced tumorigenesis in the colon upon IGF-II pathway blockade.     

A 5-drug regimen maximizing the dose of cyclophosphamide is effective therapy for adult Burkitt or Burkitt-like lymphomas

Burkitt lymphoma (BL) and Burkitt-like lymphomas (BLL) are clinically and biologically aggressive B-cell malignancies. Brief-duration, high intensity multidrug regimens with central nervous system (CNS) prophylaxis have proven to be effective, with published series of adult patients documenting complete response (CR) rates of 80 to 100 percent and 2-year event-free survival (EFS) rates ranging from 60 to 90 percent. Based upon the known sensitivity of BL to cyclophosphamide and favorable results reported from the Dana Farber Cancer Center using high-dose CHOP in diffuse aggressive lymphomas, we tested a regimen designed to maximize the administered dose of cyclophosphamide while eliminating other agents commonly used in BL protocols. Eleven patients with Burkitt or Burkitt-like lymphoma were treated with 4 cycles of a 5-drug regimen, called high-dose CHOP, which contains a cyclophosphamide dose of 4 gm/m2 with each cycle. Intrathecal methotrexate and midcycle high-dose methotrexate were added as CNS prophylaxis. Ten patients achieved a complete response (91 percent) and with a median follow up of 38 months, the 3-year EFS is 64 percent and the 3-year overall survival (OS) is 72 percent. Three patients recurred after the achievement of a CR. Treatment-related toxicities included myelosuppression, neutropenic fevers/infections, and tumor lysis syndrome requiring hemodialysis in 2 patients. There were no treatment-related deaths and none of the patients had to discontinue therapy secondary to toxicity. In conclusion, the high-dose CHOP with midcycle methotrexate regimen produces response rates and EFS rates comparable to other regimens, with an acceptable toxicity profile. Utilization of high dose cyclophosphamide may eliminate the need for several other agents in Burkitt lymphoma regimens.     

Diagnosis of Cushing's syndrome: A retrospective evaluation of clinical practice

BACKGROUND: The aim of this study was to evaluate the efficiency of the clinical diagnosis of Cushing's syndrome (CS). METHODS: A retrospective study was conducted of 72 consecutive patients with CS who, from 1995 to 2002, had been referred to the endocrinology department of a University Hospital by either endocrinologists or non-endocrinologists. Symptoms, signs, and biochemical screening tests used for confirmation of the diagnosis were recorded. Symptoms that led patients to a consultation were defined as reasons for consultation and were distinguished from other symptoms identified only by the referring physician. RESULTS: Fifty-one patients requested a consultation for reasons related to CS, predominantly weight gain (44%) and muscle weakness (21%). In contrast, 21 patients did not request a consultation for symptoms related to CS. Assessment of physical signs demonstrated that the clinical presentation of patients was similar in both groups. However, endocrinologists referred significantly more patients who had not expressed symptoms related to CS than non-endocrinologists (38% vs. 17%, p<0.05). Appropriate screening tests (overnight 1-mg dexamethasone suppression test and/or urinary free cortisol) were used in all patients referred by endocrinologists and in 45% of patients referred by non-endocrinologists. CONCLUSION: Our data show that many patients with CS do not spontaneously request a consultation for symptoms related to their condition. These patients are mostly identified by endocrinologists, who seem to have a better knowledge of physical signs and screening tests. Because endocrinologists are highly dependent upon non-endocrinologists for the recruitment of their patients, an improvement in the educational program is needed at the non-endocrinologist level. Our results may be of help in drafting the lines of this improvement by stressing the importance of the most specific physical signs and the most relevant screening tests for CS.     

Erythropoietin is involved in angiogenesis in human primary melanoma

In this study, the extent of angiogenesis, evaluated as microvascular volume density, immunoreactivity of tumour cells to erythropoietin (Epo) and of endothelial cells to Epo receptor (EpoR) have been correlated in human primary melanoma specimens. Results showed that Epo/EpoR expression correlate with angiogenesis and tumour thickness. These findings suggest that Epo is secreted by tumour cells and it affects vascular endothelial cells via its receptor and promotes angiogenesis in a paracrine manner, playing an important role in melanoma angiogenesis.     

Sclerosing polycystic adenosis of the parotid gland: Report of one case diagnosed by fine‐needle cytology with in situ malignant transformation

Sclerosing polycystic adenosis (SPA) is a rare pathological condition affecting the salivary glands, first described by Smith etal. in 1996. Even though this lesion is being increasingly diagnosed, less than 50 cases have been published in the world literature to date. In line with numerous other pathological analogies between breast and salivary gland lesions, SPA shares with fibrocystic disease of the breast many histopathological features, i.e., fibrosis, oncocytic (apocrine) changes, hyperplasia of ductal and acinar epithelium, cystic dilation of ducts, and, often, atypical epithelial changes. Most of the described cases have followed a benign clinical course, despite the frequent possibility of atypical hyperplasia in more than 50% of the cases and of the more than occasional in situ malignant transformation. In this article, we introduce a new case occurring in the parotid gland of a 57‐year‐old male showing atypical epithelial hyperplasia and low‐grade in situ mucoepidermoid carcinoma. Fine‐needle cytology (FNC) was performed on the lesion and, when a diagnosis of SPA was prospected, the variegated cytological features of the obtained sample posed several differential diagnostic problems. The spectrum of pathological lesions entering differential diagnosis comprised sebaceous adenoma, Warthin's tumors with presence of sebaceous remnants, and low‐grade mucoepidermoid carcinoma. Histopathological examination disclosed SCA with intraductal neoplastic transformation resembling noninvasive low‐grade mucoepidermoid carcinoma. The cytological diagnosis of SPA should be entertained whenever a polymorphous picture is found on FNC samples comprising oncocytic/apocrine changes, sebaceous cells, cystic background, and epithelial hyperplasia with low‐grade cytological atypias. Diagn. Cytopathol. 2010. © 2009 Wiley‐Liss, Inc.