The hemochromatosis gene affects the age of onset of sporadic Alzheimer's disease.

In the present study we analysed the genotype of HFE, the gene involved in hemochromatosis, in 107 patients with sporadic late-onset AD and in 99 age-matched non-demented controls. We observed that patients carrying the mutant HFE-H63D allele had a mean age at onset of 71.7 +/- 6.0 years versus 76.6 +/- 5.8 years of those who were homozygous for the wild-type allele (p = 0.001). The frequency of the HFE-H63D mutation was highest (0.22) in the patients aged <70 years at the time of disease onset, whereas it was 0.12 in those with disease onset at an age of 70-80 years, and 0.04 in those aged more than 80 years. The APOE genotype did not significantly modify the effect of HFE on age at onset. We conclude that mild disturbances of iron homeostasis associated with a common genetic determinant may interact with other pathogenic mechanisms involved in AD. HFE mutations may anticipate AD clinical presentation in susceptible individuals.

Alpha-1-antichymotrypsin and oxidative stress in the peripheral blood from patients with probable Alzheimer disease: a short-term longitudinal study.

To evaluate the stability and reproducibility of selected peripheral oxidative stress markers and their possible relation to cognitive performance, three different blood samples were taken at 7- to 10-day intervals from 11 patients with probable Alzheimer disease (AD) and 11 nondemented controls. Blood samples were also collected once from 6 patients with vascular dementia (VD). Alpha-1-antichymotrypsin (ACT), C-reactive protein (CRP), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), lactoferrin (LTF), and total lipid peroxidation (LPO) were then measured. Blood levels of ACT and GSH-Px were increased in AD patients but not in patients with VD. Levels of LTF, CRP, and LPO were comparable between AD patients and controls. Erythrocyte SOD activity was increased in AD patients. Blood levels of ACT negatively correlated with LPO levels and positively correlated with scores of the Global Deterioration Scale of AD patients. ACT might be implicated in controlling oxidative damage of blood lipids and their turnover during the progression of AD.

Aloe-Emodin quinone pretreatment reduces acute liver injury induced by carbon tetrachloride.

Aloe contains several active compounds including aloin, a C-glycoside that can be hydrolyzed in the gut to form aloe-emodin anthrone which, in turn, is auto-oxidized to the quinone aloe-emodin. On the basis of the claimed hepatoprotective activity of some antraquinones, we studied aloe-emodin in a rat model of carbon tetrachloride (CCl4) intoxication, since this xenobiotic induces acute liver damage by lipid peroxidation subsequent to free radical production. Twelve rats were treated with CCl4 (3 mg/kg) intraperitoneally and six were protected with two intraperitoneally injections of aloe-emodin (50 mg/kg; CCl4+aloe-emodin); six other rats were only aloe-emodin injected (aloe-emodin) and six were untreated (control). Histological examination of the livers showed less marked lesions in the CCl4+aloe-emodin rats than in those treated with CCl4 alone, and this was confirmed by the serum levels of L-aspartate-2-oxoglutate-aminotransferase (394+/-38.6 UI/l in CCl4, 280+/-24.47 UI/l in CCl4+aloe-emodin rats; P<0.05). We also quantified changes in hepatic albumin and tumour necrosis factor-alpha mRNAs. Albumin mRNA expression was significantly lower only in the liver of CCl4 rats (P<0.05 versus control) and was only slightly reduced in the CCl4+aloe-emodin rats. In contrast tumour necrosis factor-alpha mRNA was significantly higher (P<0.05) in the CCl4 than the control rats and almost equal in the CCl4+aloe-emodin, aloe-emodin and control groups. In conclusion, aloe-emodin appears to have some protective effect not only against hepatocyte death but also on the inflammatory response subsequent to lipid peroxidation.

Age-dependent expression of fibrosis-related genes and collagen deposition in rat kidney cortex.

Because progressive fibrosis is a histological hallmark of the aging kidney, we sought to characterize the course of some fibrosis-related genes [pro-alpha2(I)collagen (COL-I), pro-alpha1(III)collagen (COL-III), and transforming growth factors beta1 and beta3 (TGF-beta1 and TGF-beta3)] of interstitial collagen accumulation [COL-I and COL-III proteins, hydroxyproline (PRO-OH), histology] and its degradation (matrix metalloproteinase MMP-1 and -2) during maturation and early aging in rats. During the lifespan considered we observed no changes in the mRNA, except that COL-I mRNA tended to be up-regulated from 2 to 19 months of age. However, progressive fibrosis was histologically detectable, with COL-I accumulation (p < .05 and p < .01 in 12-month- and 19-month-old rats vs the youngest), and confirmed by the PRO-OH tissue levels (p = .0001); COL-III seemed to be less involved. The MMP-1 protein level decreased significantly in the cortex of 12-month- and 19-month-old rats (p < .05), whereas MMP-2 protein level and activity remained essentially unchanged. These results show that, during aging of the kidney, (i) renal cortex fibrosis is explained by COL-I accumulation as a consequence of an altered balance between its synthesis and degradation, and (ii) the expression of the pleiotropic factor TGF-beta in the renal cortex is not modified.

BsmI polymorphism of the vitamin D receptor gene in hyperparathyroid or hypoparathyroid dialysis patients.

Since bone mineral density may be influenced by the polymorphisms of the vitamin D receptor (VDR) gene, we studied whether VDR genotypes might drive the progression toward hyperparathyroidism or hypoparathyroidism in patients with end-stage renal disease. On the basis of their parathyroid hormone (PTH) levels, we divided 99 patients undergoing dialysis into 2 groups: 56 patients with hypoparathyroidism (PTH < 104 pg/mL [< 11 pmol/L]) and 43 with hyperparathyroidism (PTH > 261 pg/mL [> 27.5 pmol/L]). The BB polymorphism was more frequent in patients with hypoparathyroidism (34%) than in patients with hyperparathyroidism (16%), but the difference did not reach statistical significance. Patients with the B allele and BB genotype had a significantly lower dialytic age and serum PTH and alkaline phosphatase levels than patients with the b allele and bb genotype. These results suggest that in end-stage renal disease, the BB genotype may mark a higher risk of developing hypoparathyroidism and diminished bone turnover.

Comparison of iohexol-240 versus iohexol-300 in abdominal CT.

Forty patients without evidence of liver, kidney, or significant cardiac disease were prospectively divided into two groups of 20, receiving either iohexol-240 or iohexol-300. A contrast load of 150 ml was administered in conjunction with a rapid scanning technique at a preselected, fixed level to include liver, renal cortex, and aorta. Peak enhancement was calculated as change in Hounsfield units (HU) over baseline for each area of interest. Mean peak enhancement and standard deviation were calculated for each organ, and the difference between the means for the two contrast agents was compared using the Student's t test. Differences were not statistically significant with all p values greater than 0.05. Our results suggest iohexol-240 is preferred to iohexol-300 for body computed tomography (CT) due to its lower cost and iodine load without statistically significant change in diagnostic quality of the examination.

CT evaluation of wall thickening in the alimentary tract.

Computed tomography (CT) of the alimentary tract, when performed with adequate distention of the organ being examined and in the true axial plane, provides valuable information about the intramural or extramural extent of pathologic conditions. Neoplastic, vascular, and inflammatory diseases can all result in wall thickening of the alimentary tract. Wall thicknesses greater than 5 mm in the esophagus, stomach, and colon and 4 mm or greater in the small bowel are considered abnormal. If the thickened wall has a target or double-ringed appearance, it is most likely caused by benign disease. In general, the CT findings of asymmetric or focal wall thickening, nodularity, and thickening greater than 1.5 cm suggest a malignant process. Although it is commonly associated with benign disease, diffuse thickening can also result from some infiltrating malignant diseases. Careful review of CT scans for evidence of metastatic disease and adenopathy and correlation with clinical information aid in the differential diagnosis.

Abdominal desmoids: CT findings in 25 patients.

Desmoids are histologically benign but locally aggressive fibrous tumors. Although overall they are rare lesions, they are a common manifestation of Gardner syndrome. We retrospectively reviewed clinical records and CT scans of 25 patients with abdominal desmoids. The number, location, and CT characteristics of the lesions were recorded for each patient. Tumors were solitary in 72% of patients and multiple in 28%. Fifty percent were located in the abdominal wall, 41% in the mesentery, and 9% in the retroperitoneum. More than two thirds of the lesions had well-defined borders, with the remainder displaying an infiltrative outer margin. The majority of tumors had attenuation values equal to (47%) or greater than (41%) the attenuation of muscle on contrast-enhanced CT scans. Complications attributable to the desmoid were commonly detectable on CT (hydronephrosis occurred in 36% and small-bowel obstruction in 20%). Our results detail the spectrum of CT findings and complications caused by abdominal desmoids.

Case report 610: Amyloid arthropathy of the left ankle.

In summary, a case of amyloid arthropathy of the left ankle in a 64-year-old patient with multiple myeloma is presented. The asymmetric presentation and site of deposition in the ankle were taken to be unusual. Involvement of both hips and the right shoulder was also suspected on subsequent evaluation. The patient's history and MR studies were essential in establishing the preoperative diagnosis. The extent of involvement, destruction of underlying cartilage, associated effusion and tenosynovitis were optimally defined by the MR images. The MR images also provided preoperative guidance in determining the approach and optimum site of biopsy.