Low density lipoprotein receptors and polyamine levels in human colorectal adenocarcinoma

The low density lipoprotein receptor (LDLR) is a cell surface protein that binds with LDL, providing the cell with cholesterol for new membrane synthesis. Rapidly growing cells have high numbers of LDLRs, and these proteins have also been detected in neoplastic samples of human colorectal mucosa. Polyamines, putrescine, spermidine, and spermine, play an important role in cellular growth, and studies on colorectal cancers have demonstrated higher polyamine levels in neoplastic mucosa samples than in surrounding mucosa. The aim of this study was to investigate LDLR and polyamine levels in the neoplastic tissue of 43 patients (28 males and 15 females) with colorectal adenocarcinoma, using enzymatic immunoassay and high performance liquid chromatography, respectively. Specimens of neoplastic mucosa were considered LDLR-positive or LDLR-negative when the amount of bound anti-LDLR Ab/mg protein), respectively. Twenty-one subjects were LDLR-positive and 22 LDLR-negative. Polyamine levels (nmol/g tissue) were higher in LDLR-positive specimens; this increase was significant for total polyamines (P<0.05). These findings, reporting the presence of increased polyamine content in LDLR-positive colorectal neoplastic specimens, suggest an association between LDLR levels and gastrointestinal neoplastic proliferative activity.     

Improvement of growth hormone deficiency in patients with primary hyperparathyroidism after parathyroidectomy: results of a prospective study

GH secretion is impaired in most patients with primary hyperparathyroidism (PHP), although the secretion of the other anterior pituitary hormones is unaffected. However, whether restoration of euparathyroidism is associated with reversal of GH deficiency in PHP patients is not known. To address this issue, we studied 30 consecutive patients with PHP due to a single parathyroid adenoma before and after parathyroidectomy. GH secretion was evaluated by peak serum GH after the maximal GHRH + arginine (Arg) stimulation test. A group of 35 age- and sex-matched normal subjects served as controls. Serum IGF-I concentration was below the normal age- corrected values in six of 30 patients before surgery and in four of 30 patients after parathyroidectomy (P = not significant). Mean serum peak GH values after the GHRH + Arg test were 17.5 +/- 2.8 micro g/liter before surgery and 23.8 +/- 2.5 micro g /liter after surgery (P = 0.0008). The GH response to the GHRH + Arg test was reduced in 20 (67%) and normal in 10 (33%) of 30 PHP patients at baseline; after surgery, 22 of 30 (73%) PHP patients had a normal GH response to the GHRH + Arg test, and only eight (27%) had an impaired GH secretion (P < 0.02). In conclusion, this study confirms that GH secretion is impaired in PHP patients and indicates that it is reversed in many patients after parathyroidectomy. Accordingly, GH deficiency in PHP patients must be considered a functional phenomenon for which GH therapy is not recommended.     

Usefulness of right ventricular fractional area change to predict death, heart failure, and stroke following myocardial infarction (from the VALIANT ECHO Study)

Severe right ventricular dysfunction independent of left ventricular ejection fraction increased the risk of heart failure (HF) and death after myocardial infarction (MI). The association between right ventricular function and other clinical outcomes after MI was less clear. Two-dimensional echocardiograms were obtained in 605 patients with left ventricular dysfunction and/or clinical/radiologic evidence of HF from the VALIANT echocardiographic substudy (mean 5.0 +/- 2.5 days after MI). Clinical outcomes included all-cause mortality, cardiovascular (CV) death, sudden death, HF, and stroke. Baseline right ventricular function was measured in 522 patients using right ventricular fractional area change (RVFAC) and was related to clinical outcomes. Mean RVFAC was 41.9 +/- 4.3% (range 19.2% to 53.1%). The incidence of clinical events increased with decreasing RVFAC. After adjusting for 11 covariates, including age, ejection fraction, and Killip's classification, decreased RVFAC was independently associated with increased risk of all-cause mortality (hazard ratio [HR] 1.61, 95% confidence interval [CI] 1.31 to 1.98), CV death (HR 1.62, 95% CI 1.30 to 2.01), sudden death (HR 1.79, 95% CI 1.26 to 2.54), HF (HR 1.48, 95% CI 1.17 to 1.86), and stroke (HR 2.95, 95% CI 1.76 to 4.95), but not recurrent MI. Each 5% decrease in baseline RVFAC was associated with a 1.53 (95% CI 1.24 to 1.88) increased risk of fatal and nonfatal CV outcomes. In conclusion, decreased right ventricular systolic function is a major risk factor for death, sudden death, HF, and stroke after MI.     

Effect of valsartan added to background ACE inhibitor therapy in patients with heart failure: results from Val-HeFT

AIMS: To investigate the effect of valsartan in the Valsartan-Heart Failure Trial (Val-HeFT) when added to angiotensin-converting enzyme inhibitor (ACEi) alone in patients with heart failure (HF). METHODS: Subjects in Val-HeFT receiving ACEi but not beta-blocker at baseline were analysed; 1532 were assigned to valsartan and 1502 assigned to placebo. Primary outcome events (all-cause mortality, hospitalisation for adjudicated heart failure, sudden death with resuscitation and need for >4 h of parenteral therapy for worsening heart failure) were monitored. RESULTS: Mortality was not affected by valsartan but morbidity endpoints were significantly reduced (36.3% in placebo, 31.0% in valsartan, p=0.002) in patients receiving an ACEi but no beta-blocker. Quality of life (QOL) was significantly improved, ejection fraction (EF) significantly increased, left ventricular (LV) diameter significantly reduced and plasma B-type natriuretic peptide, norepinephrine and aldosterone levels significantly reduced with valsartan compared to placebo. The morbidity benefit was significant in patients on ACEi doses below the median (22% reduction, p=0.003) and not statistically significant in those receiving ACEi doses above the median (14% reduction, p=0.143). CONCLUSION: Valsartan reduces heart failure hospitalisations and slows LV remodelling in patients treated with an ACEi in the absence of beta-blockade, particularly in those on lower doses of ACEi.     

Predictive factors for hepatocellular carcinoma in type 1 autoimmune hepatitis

OBJECTIVE:  Hepatocellular carcinoma (HCC) is an uncommon but serious occurrence in autoimmune hepatitis. Our objective was to determine predictors for this neoplasm to improve screening strategies.
METHODS:  Two hundred twenty-seven patients underwent hepatic ultrasonography and serum alpha fetoprotein determinations at 6–12-month intervals.
RESULTS:  Nine patients developed HCC (4%), and each had cirrhosis ≥73 months prior to the malignancy (mean, 110 ± 7 months). By univariate Cox analysis, features at accession associated with a higher risk of HCC were: male gender (Hazard Ratio [HR] 7.0, 95% Confidence Interval [CI] 1.87–26.1, P = 0.004), history of blood transfusion (HR 5.6, 95% CI 1.51–21.1, P = 0.01), thrombocytopenia (HR 7.3, 95% CI 1.89–28.3, P = 0.004), ascites (HR 23.8, 95% CI 4.65–121.8, P = 0.0001), esophageal varices (HR 7.9, 95% CI 1.96–31.8, P = 0.004), and any sign of portal hypertension (HR 19.1, 95% CI 3.91–93.3, P = 0.0003). Features after accession associated with a higher risk of malignancy were: treatment for ≥3 yr (HR 7.6, 95% CI 1.25–18.2, P = 0.02), worsening laboratory tests during corticosteroid therapy (HR 7.6, 95% CI 1.81–32.1, P = 0.006), and cirrhosis for ≥10 yr (HR 8.4, 95% CI 1.69–41.9, P = 0.009).
CONCLUSIONS:  Male gender, features of portal hypertension, history of blood transfusions, immunosuppressive treatment for ≥3 yr, treatment failure, and cirrhosis of ≥10 yr duration identify patients at risk for HCC. These risk factors should focus screening in autoimmune hepatitis.     

Cardiovascular secondary prevention: patients' knowledge of cardiovascular risk factors and their attitude to reduce the risk burden, and the practice of family doctors. The "Help Your Heart Stay Young" study.

BACKGROUND: Whether the practice of family doctors of assessing the global cardiovascular risk profile improves the knowledge of cardiovascular risk factors and the attitude to lifestyle change in patients' secondary cardiovascular prevention is unknown. METHODS: We evaluated subjects who visited their family doctors and those with self-reported cardiovascular disease in the urban area of Naples, Italy. Patients self-administered a simple standard questionnaire to evaluate their knowledge of cardiovascular risk factors and of simple lifestyle modifications to reduce the cardiovascular risk burden. For each participant, family doctors, blinded to the information provided by patients, had to provide a global coronary risk based on the risk factors recorded in their electronic database, or report the missing information. RESULTS: The study sample comprised 560 subjects, 61% male, with mean age 60 +/- 9 years. Angina pectoris (49%) and myocardial infarction (40.9%) were the most frequently self-reported cardiovascular diseases in the study sample. The self-reported data revealed that 46% of the sample was overweight and an additional 20% overtly obese. Among those who self-reported arterial hypertension, approximately 11% admitted that they were unaware of their blood pressure, and 26% believed that they were normotensive but reported a recently detected blood pressure > 140/90 mmHg. Approximately 8% were not aware of whether they had high cholesterol levels, and among those who declared having normal cholesterol levels, 9% referred levels > 200 mg/dl. Of the sample, 22% self-reported diabetes, but 7% did not know whether they were diabetic or not. Thirty percent of the sample were smokers and among these, 40% smoked > 20 cigarettes/day. A low level of education was reported in 66% of the study sample. Women were more frequently obese, more often reported high cholesterol levels, had a low level of education and achieved a lower score from the questionnaire on knowledge of cardiovascular risk factors than men. Patients > 55 years more often reported an elevated blood pressure among those who defined themselves as normotensive, and achieved a lower score from the questionnaire on knowledge of cardiovascular risk factors than younger patients. CONCLUSIONS: With regard to secondary cardiovascular prevention, the study population was found to have insufficient knowledge of cardiovascular risk factors and of the correct approach to reduce their global risk despite the fact that the attitude of their family doctors in detecting and recording risk factors was above average.     

Hip-Op: an innovative software to plan total hip replacement surgery

This paper describes an innovative surgical simulation software environment for the pre-operative planning of total hip replacement surgery. The software is a CT-based three-dimensional planning environment, with a user-friendly graphic user interface based on the multimodal display visualization paradigm. Although it relies on a fully three dimensional internal representation, this approach represents the relevant anatomical objects by means of multiple views, each simulating a different medical imaging modality familiar to the medical professional. In the Hip-Op program the multimodal display interface integrates four different display modalities: orthogonal radiographs, Blended slices, CT slices, and arbitrary slices. A conventional surface rendering view is also available. The user 'navigates' the prosthetic components, which are dynamically selected from a library of available parts, within the CT volume while the implant and the patient anatomy are simultaneously rendered in each specialized view. Beside a consideration of anatomical compatibility, the surgeon may evaluate the planned implant type, size and position, also on the basis of two analysis modules that compute the achieved level of implant fitting and filling. After being evaluated in an internal clinical trial, the software is currently made available as freeware at http:// www.ior.it/hipop/.