Prevalence and correlates of advanced retinopathy in a large selected hypertensive population. The Evaluation of Target Organ Damage in Hypertension (ETODH) study

OBJECTIVE: To describe the prevalence of advanced retinal microvascular lesions and their associations with cardiac and extracardiac signs of target organ damage (TOD) in a large selected hypertensive population. METHODS: A total of 2172 non-diabetic untreated and treated uncomplicated essential hypertensives consecutively attending for the first time our hospital outpatient hypertension clinic and included in the Evaluation of Target Organ Damage in Hypertension (ETODH), an observational ongoing registry of hypertension-related TOD, were considered for this analysis. Advanced hypertensive retinopathy was defined by the presence of any of the following lesions: flame-shaped haemorrhages, soft exudates or cotton wool spots and papilloedema. Left ventricular hypertrophy (LVH), carotid structural abnormalities, such as plaques and intima media (IM) thickening, and microalbuminuria were diagnosed according to the 2003 ESH/ESC guidelines criteria. RESULTS: Among the whole study population, 33 patients (1.5%) were found to have advanced hypertensive retinopathy. Patients with these retinal lesions were similar to those without for age, body mas index, known duration of hypertension, smoking habit, total serum cholesterol, fasting blood pressure and prevalence of antihypertensive treatment; whereas mean systolic and diastolic blood pressures were higher in the former group. The prevalence rates of LVH, carotid plaques, carotid IM thickening and microalbuminuria in patients with and without retinopathy were 57%, 67%, 69%, 19% and 25%, 47%, 44%, 12%, respectively. In a multivariate logistic regression analysis, advanced retinopathy was significantly associated with LVH (OR = 4.0), carotid IM thickening (OR = 2.9), carotid plaques (OR = 2.8), but not with microalbuminuria. CONCLUSIONS: Our study indicated that: (i) advanced retinopathy is a rare finding in non-diabetic hypertensive patients seen in a specialist setting; (ii) a strong relation exists between retinal microvascular lesions and cardiac and macrovascular markers of TOD.     

Acquisition of i(8q) as an early event in malignant triton tumors

Malignant triton tumors (MTT) are rare soft-tissue tumors characterized by a mixture of cells with nerve sheath and skeletal muscle differentiation. MTT is a histological variant of malignant peripheral nerve sheath tumors (MPNST). No characteristic cytogenetic anomaly has been detected in MPNST or MTT. In this paper, we report on the cytogenetic findings of an MTT from a 20-year old male with neurofibromatosis (NF1). The tumoral karyotype showed the modal number to be near-diploid and an abnormal karyotype with a Robertsonian translocation and 4 markers: 49,XY,der(14;15)(q10;q10),+4mar. Spectral karyotyping revealed the karyotype: 49,XY, der(14;15)(q10;q10),+i(8)(q10)x4. Fluorescence in situ hybridization analysis of the tissue confirmed the presence of the additional i(8)(q10) in all tumoral cells. The sequence analysis of p53 revealed a polymorphism in exon 9, codon 329. The two alleles, TTC and TCC, codify for phenylalanine and serine, respectively. Our results indicate that all neoplastic cells have the same cytogenetic pattern, suggesting that both cell lines, which show nerve sheath and skeletal muscle differentiation, are derived from a unique stem cell. The acquired Robertsonian chromosomal recombinants might represent an event in the tumorigenesis of MTT, and the present data suggest that genes located on 8q can be involved in the development of MTT.     

Libman-Sacks endocarditis associated with antiphospholipid syndrome and infection

INTRODUCTION: Antiphospholipid syndrome (APS) is a systemic autoimmune disease, associated not only with a hypercoagulable state and recurrent fetal loss but with many diverse clinical manifestations including heart involvement, neurological manifestations, as well as skin, kidney and hematologic abnormalities. Cardiac manifestations include coronary by-pass graft and angioplasty occlusions, cardiomyopathy, cyanotic congenital heart disease, intracardiac thrombus and complications of cardiovascular surgery. The valvular heart disease was defined as Libman-Sacks nonbacterial endocarditis. Previously, we have shown a linear subendothelial deposition of anti-cardiolipin/beta2 glycoprotein I (beta2GPI) antibodies in the valve specimens derived from APS patients. The involvement of complement C3c in the pathogenesis was documented. We assessed the beta2GPI-related target epitope recognized by the anti-beta2GPI Abs on the valves. MATERIALS AND METHODS: In order to find the beta2GPI-related target epitopes recognized by the anti-beta2GPI antibodies on the valves, we used beta2GPI-related synthetic peptides. The presence of anti-beta2GPI Abs on the studied valves was detected by anti-idiotypic antibody, followed by immunoperoxidase analysis. Biotin attached to the N-terminal of beta2GPI-related synthetic peptides and control peptide were used to identify the epitope addressed by the anti-beta2GPI Abs deposited on the patient's valve. The binding was probed by streptavidin-peroxidase and appropriate substrate. The specificity was confirmed by competition assays with control peptide and anti-idiotypic antibody. RESULTS: Among the beta2GPI-related synthetic peptides, two peptides were found in previous studies to mimic common pathogens either bacteriae or viruses, which raised a possible infectious origin for APS. One of these peptides, TLRVYK, is a specific target for anti-beta2GPI Abs deposited on the APS valves. This synthetic peptide was able to displace the anti-anti-beta2GPI anti-idiotypic Abs for binding the anti-beta2GPI Abs on the valve by a competition assay. CONCLUSION: We point to the possibility that Libman-Sacks nonbacterial endocarditis may have an infectious origin.     

Intravascular Doppler technique for monitoring renal venous blood flow in man

BACKGROUND: To measure renal blood flow (RBF) from the renal veins in men using the intravascular Doppler technique (IVD). METHODS: In nine hypertensive male patients (age 46-64 years) undergoing diagnostic renal artery angiography and renal vein catheterization to determine plasma renin activity (PRA), a 3F Doppler catheter was positioned in the renal veins using a 7F guide catheter with a "basket" shaped tip. The radiopaque sectors of the catheter, leaning against the vessel wall, serve to measure the internal diameter of renal veins, and therefore to calculate RBF, by multiplying renal vein cross-sectional area by mean blood flow velocity. The resulting RBF from the left and right renal veins were compared with those obtained by the local thermodilution method (TD). RESULTS: We found good agreement (Bland and Altman's method) between the RBF measurements made with IVD (ranging from 46 mL/min to 1,220 mL/min) and with the TD technique (45-1,030 mL/min) (mean bias, 13+/-20 mL/min, 95% CI -54.77 to 28.77 mL/min). In stenotic kidneys a significant correlation was found between the renal vein PRA and RBF calculated with both methods (IVD: r = 0.96, p = 0.002; TD: r = 0.90, p = 0.01). CONCLUSIONS: The IVD technique applied to the venous side of the renal circulation provides a simple and reliable method for separate measurement of RBF in kidneys with and without renal artery stenosis.     

Comparison of the conventional 'box technique' with two different 'conformal' beam arrangements for prostate cancer treatment.

PURPOSE: To quantify the possible advantages arising from the use of 'conformal' radiotherapy of localized prostate cancer, and to compare the dose distributions obtained with two different 'conformal' techniques. PATIENTS AND METHODS: Twelve patients with localized prostate cancer were enrolled in the study. For each patient, three techniques were planned: the standard 'box technique' (A), a four-fields 'conformal' technique (B), and a 6-fields conformal technique (C). For each of the 36 3D plans, dose-volume histograms (DVH) were obtained, along with the mean, maximum and minimum doses for the clinical and planning target volumes (CTV, PTV) for the rectum, the bladder, and the femoral heads. The resulting data were compared. RESULTS: On average, the standard technique resulted in the exposure of a significantly larger bladder volume to the higher doses; a similar, but less remarkable difference has been observed for the rectal volume. The coverage of the PTV appears to be significantly more homogeneous with the two conformal techniques. CONCLUSIONS: The results presented here add to the evidence available in the literature and suggest a possible advantage of both the conformal techniques over the standard 'box technique' for the treatment of localized prostate cancer. The 6-field conformal technique does not seem superior to the four field one.     

Association between hepatitis B or hepatitis C virus infection and risk of pancreatic adenocarcinoma development: A systematic review and meta-analysis

BackgroundPancreatic adenocarcinoma (PAC) is an aggressive cancer with a poor prognosis. To date, PAC causes are still largely unknown. Antigens and replicative sequences of oncogenic hepatitis B (HBV) and hepatitis C (HCV) virus were detected in different extra-hepatic tissues, including pancreas.Objectivea systematic review and meta-analysis of epidemiological studies assessing PAC risk in patients with HBV/HCV chronic infections.MethodsIn September 2012, we extracted the articles published in Medline, Embase and the Cochrane Library, using the following search terms: “chronic HBV” and “HCV”, “hepatitis”, “PAC”, “risk factors”, “epidemiology”. Only case/control (C/C), prospective/retrospective cohort studies (PCS/RCS) written in English were collected.Resultsfour hospital-based C/C studies and one PCS, in HBV-infected patients and two hospital-based C/C studies and one RCS in HCV-infected subjects met inclusion criteria. In these studies HBsAg positivity enhanced significantly PAC risk (RR = 1.18, 95% CI:1.04–1.33), whereas HBeAg positivity (RR = 1.31, 95% CI:0.85–2.02) as well as HBsAg negative/HBcAb positive/HBsAb positive pattern (RR = 1.12, 95% CI:0.78–1.59) and HBsAg negative/HBcAb positive/HBsAb negative pattern (RR = 1.30, 95% CI:0.93–1.84) did not. Relationship between PAC risk and anti-HCV positivity was not significant, although it reached a borderline value (RR = 1.160, 95% CI:0.99–1.3).ConclusionsHBV/HCV infection may represent a risk factor for PAC, but the small number of available researches, involving mainly populations of Asian ethnicity and the substantial variation between different geographical areas in seroprevalence of HBV/HCV-antigens/antibodies and genotypes are limiting factors to present meta-analysis.     

Ketoconazole therapy for women with acne and/or hirsutism

The effects of ketoconazole, a synthetic imidazole derivate, were evaluated in 42 women affected by acne (17 cases) and/or hirsutism (36 cases) treated with 400 mg/day for 3-6 months. Androstenedione, total and free testosterone, 5 alpha dihydrotestosterone and dehydroepiandrosterone levels progressively dropped during treatment while 17 alpha hydroxyprogesterone, estradiol, ACTH, cortisol, LH and FSH levels increased. Dehydroepiandrosterone sulfate decreased only towards the end of treatment, while estrone, sex hormone binding globulin, and PRL remained unchanged. Daily mean +/- SD rate of hair growth, measured by a special image analysis processor, decreased within 3 months of therapy from 0.258 +/- 0.058 to 0.184 +/- 0.039 mm/day (P less than 0.02) and mean +/- SD hair diameter from 0.123 +/- 0.015 to 0.110 +/- 0.013 mm (P less than 0.05) together with decreasing hormone levels. The therapeutic effects of ketoconazole on hirsutism was evident at 6 months in only 14 subjects, while no significant change in hirsutism score was recorded in 22 women who failed to complete the therapy. Acne improved in all cases. Several side effects and complications arose during treatment, such as headache, nausea, loss of scalp hair, hepatitis, and biochemical changes. Even though ketoconazole improves hyperandrogenism, only selected patients are eligible for treatment as scrupulous monitoring is required.