Blood leucocyte telomere DNA content predicts vascular telomere DNA content in humans with and without vascular disease.

AIMS: Previous studies have suggested that reduced telomere length in circulating leucocytes in humans is associated with premature vascular disease and by implication, accelerated vascular ageing. Importantly, a link between telomere length in circulating leucocytes and the blood vessel wall has never been established. We, thus, investigated the relationship between vascular wall and circulating leucocyte telomere length in humans with and without overt vascular disease. METHODS AND RESULTS: Aortic biopsies and paired blood leucocytes were obtained from 20 patients with asymptomatic abdominal aortic aneurysms (AAAs), undergoing elective open repair, and 12 morphologically normal aortas from a group of cadaveric organ donors of similar mean age. Telomere content was compared by quantitative PCR and expressed as telomere:genomic DNA ratio. The telomere:genomic DNA content was significantly reduced in wall biopsies of AAA vs. normal aorta, and this difference remained after adjusting for age and gender. There were strong correlations between leucocyte and vascular telomere content when the AAA and control groups were analysed either separately or grouped irrespective of the presence of vascular disease (r = 0.62, P < 0.001). CONCLUSION: The findings demonstrate that leucocyte DNA content is predictive of vascular telomere content and is an accurate surrogate for human vascular age.

Hereditary hemochromatosis.

BACKGROUND: The understanding of hereditary hemochromatosis, along with the availability of genetic testing, is changing the approach to diagnosis of the disease. METHODS: A MEDLINE search was performed using multiple key words related to hemochromatosis and iron metabolism. RESULTS: Most cases of hereditary hemochromatosis are caused by a single mutation to the HFE gene, resulting in unregulated dietary iron uptake. The signs and symptoms of hereditary hemochromatosis are nonspecific and common in family practice settings. Measuring the transferrin saturation level is a cost-effective way to screen for suspected disease. Subsequent workup includes serum ferritin levels, hepatic enzyme levels, and HFE gene testing, or liver biopsy. HFE gene testing can provide a definitive diagnosis in many patients. Liver biopsy is useful and indicated when liver disease is clinically evident. CONCLUSION: For many patients, hereditary hemochromatosis can be diagnosed and treated in the physician's office. After iron mobilization with therapeutic phlebotomy, most patients will require phlebotomy 2 to 4 times each year throughout their lifetime. Treatment before organ toxicity occurs leads to a normal life span. Treatment after symptoms appear is less effective but can improve some signs and symptoms of iron toxicity.

Apolipoprotein B, ratio of total cholesterol to HDL-C, and blood pressure in abdominally obese white and black American women.

OBJECTIVE: To compare the association of apolipoprotein B (ApoB) and total cholesterol to high-density lipoprotein cholesterol (TC/HDL) with blood pressure in abdominally obese white and black American women. We also sought to determine if there are ethnic differences in blood pressure values that could be explained by differences in mean values of ApoB and TC/HDL. METHODS: Data (n = 1844) from the Third US National Health and Nutrition Examination Survey were used in this study. Abdominal obesity was defined as waist circumference (WC) of > or =88cm or having WC greater than what was expected as predicted from residuals obtained from linear regression of WC on BMI. Bi-variate Pearson's correlation analysis was used to quantify the degree of association of ApoB and TC/HDL with blood pressure and other lipids. Multiple linear regression analysis was used to assess the independent contribution of ApoB and TC/HDL to blood pressure, adjusting for age, total cholesterol, alcohol intake, and smoking. To determine ethnic differences in blood pressure values associated with ApoB or TC/HDL, dummy variables were used to compare blacks with whites fitted in multiple regression models, while adjusting for age, total cholesterol, alcohol intake and smoking. RESULTS: Elevated ApoB was positively associated with diastolic and systolic blood pressure (DBP/SBP) in blacks and whites, independent of age, total cholesterol, alcohol intake and smoking (P < 0.01). Elevated TC/HDL was also positively associated with increased DBP and SBP in whites (P < 0.05). For the same value of ApoB and TC/HDL whites had higher values of DBP and SBP than blacks, adjusting for confounding variables. CONCLUSIONS: Compared with TC/HDL, ApoB was more strongly associated with DBP and SBP in both abdominally obese white and black women. Since ApoB is associated with hypertension, the combination of elevated ApoB and hypertension may identify a group of patients with more marked risk of vascular disease, thus, warranting further investigation.

The relationship between volume status, hydration, and radiographic findings in the diagnosis of community-acquired pneumonia.

BACKGROUND: Many clinicians believe the radiographic expression of community-acquired pneumonia (CAP) is affected by the fluid volume status of the patient. However, there are very few data to support or refute this concept. With this study we began to examine the relationship between admission fluid volume status and the radiographic expression of CAP. METHODS: Using a retrospective chart review, we examined 376 consecutive inpatient encounters with the diagnosis of pneumonia at discharge from a community teaching hospital. Patients were evaluated by age, sex, admission serum sodium, blood urea nitrogen (BUN) level, creatinine, and fluid administered in the first 48 hours of treatment. We classified these patients as either showing radiographic progression (P) or no radiographic progression (NP) by comparison of admission and follow-up radiographs. RESULTS: A total of 125 patient encounters satisfied inclusion criteria for the study. Using the Student t test we noted a statistically significant difference between the P and NP groups for BUN level (P=.02), volume of fluid administered during the first 48 hours (P=.04), and marginally for age (P=.05). The P group had higher BUN levels (mean=34 vs 24), more 48-hour fluid intake (mean=5824 mL vs 4764 mL), and younger age (mean=59 years vs 66 years) than the NP group. Logistic regression poorly predicted which patients would have worsening infiltrate on the second radiograph. CONCLUSIONS: Elevated admission BUN level and higher fluid volume administered in the first 48 hours of admission were associated with worsening radiographic findings of pneumonia after hydration. Prospective studies are needed for confirmation of our results.

Cushing's disease: clinical manifestations and diagnostic evaluation.

The most common endogenous cause of Cushing's syndrome is Cushing's disease. Frequent clinical findings include weight gain, truncal obesity, striae, hypertension, glucose intolerance and infections. Cranial nerve II may be affected by enlarging pituitary adenomas in Cushing's disease; cranial nerves III, IV and VI may also be affected. The evaluation of patients with suspected Cushing's disease and syndrome requires an understanding of the proper use and limitations of the tests commonly included in the diagnostic work-up. The best screening test for Cushing's syndrome is a 24-hour urine collection with analysis for urinary free cortisol excretion. Low-dose and high-dose dexamethasone suppression tests, corticotropin assays, a corticotropin-releasing hormone stimulation test and inferior petrosal sinus catheterization may be required for a definitive diagnosis. Magnetic resonance imaging is useful in localizing the lesion. Surgical removal of the lesion by a transphenoidal approach is usually successful, but long-term follow-up is required. Some patients require lifetime glucocorticoid replacement therapy.

Intravascular radiographic contrast media: issues for family physicians.

BACKGROUND: Family physicians frequently order and in some instances supervise diagnostic tests using intravascular radiographic contrast media. METHODS: MEDLINE database was searched from 1966 to the present using the key terms "contrast media," "adverse reaction," "anaphylaxis," "anaphylactoid," "nephropathy," "renal failure," "kidney failure," and "MRI" in combinations. Other sources were found by back referencing these articles and in recent texts. RESULTS AND CONCLUSIONS: The adverse reactions likely to be encountered in most patients are acute anaphylactoid and cardiovascular reactions, delayed reactions, and renal effects. Mild acute reactions usually require no treatment, but if more severe reaction symptoms occur, emergency treatment is indicated. Acute reactions can be prevented or reduced by close attention to risk factors and pretreatment. Delayed reactions seldom require specific treatment. The type of contrast agent used might lessen the risk of immediate reactions. Contrast-associated nephropathy is most likely to occur in patients who have preexisting renal disease, heart failure, and volume depletion. Optimization of precontrast hydration can lessen the renal effects of contrast material. Magnetic resonance imaging contrast agents might be safer, because of smaller volumes administered, but adverse reactions have occurred.

Anemia secondary to combined deficiencies of iron and cobalamin.

The focus of attention on combined-deficiency anemia is often on concurrent deficiencies of cobalamin (vitamin B12) and folate, emphasizing the correction of megaloblastic changes with folate alone and risking neurologic sequelae of uncorrected simultaneous cobalamin deficiency. Simultaneous deficiencies of cobalamin and iron, however, may be a more common cause of combined-deficiency anemia. Variability in red blood cell morphologic characteristics in this setting reflects the relative degree of deficiency of each of these substrates. A patient with combined cobalamin and iron deficiency anemia with microcytic, hypochromic indices and the absence of hypersegmented neutrophils was treated. This case and the literature reviewed emphasize the need to consider combined-deficiency states in all cases of anemia.