Safety of long-term interruption of successful antiretroviral therapy: the ATHENA cohort study

We studied the dynamics of CD4 cell counts after the interruption of virologically successful highly active antiretroviral therapy (HAART) in 139 patients. Changes in CD4 cell counts during HAART interruption followed a biphasic pattern: an initial rapid decline during the first month followed by a slow decrease. During 48 weeks of follow-up mean CD4 cell counts remained just above the mean pre-HAART level. This limits the feasibility of structured treatment interruptions for patients with low nadir CD4 cell counts.     

Permanent intra-hisian atrioventricular block induced during right intraventricular exploration]

A 47 year old patient underwent endocavitary electrophysiological investigation for recurrent syncopal episodes occuring three years after an inaugural enterior myocardial infarction. Syncopal ventricular tachycardia was induced during the investigation when the bipolar catheter was in contact with the Bundle of His and several external electric shocks were required for its reduction. During cardioversion a complete intra-hisian atrio venticular block was observed and remained permanently although the values of the conduction intervals had previously been normal. This complication of defibrillation is thought to be the result of an induction phenomenon.     

The QT interval in clinical hypercalcemia

Corrected QT intervals were determined in 13 patients with severe, chronic hypercalcemia. The Q_OT_C interval was short in only 2 of 14 instances; Q_AT_C in 5 of 15 instances, and Q_ET_C in 5 of 16 instances. The correlations between serum calcium and the QT_C measurement were not significant when evaluating either linear or curvilinear (quadratic) relationships. Small and inconsistent changes were found when comparing the QT intervals before the development of the hypercalcemic episode, during hypercalcemia, or after successful treatment. We conclude that shortening of the QT interval is an unreliable index of clinical (chronic) hypercalcemia.     

European study of ambulatory management of heart failure by cardiologists

INTRODUCTION AND OBJECTIVES: This cross-sectional study examined the overall clinical characteristics and management of 1252 outpatients with heart failure in 3 countries (Spain, France and Germany). MATERIAL AND METHOD: A standardized questionnaire was used to record demographic, diagnostic, clinical and treatment data for all patients seen on one day (26 April 2001) by 465 outpatient cardiologists. RESULTS: Men accounted for 62.1% of the patients in the population, and mean age of the patients was 68.3 years. In the twelve months prior to the study 78% of the patients consulted their physician at least once because of heart failure, and 36.2% had hospital admissions. Differences between the three countries were observed in reported causes of heart failure (alone or in combination) such as ischemic heart disease (France 40.7%, Germany 41.3%, Spain 26%, P<.0001) and hypertension (France 10.7%, Germany 16.7%, Spain 43.6%, P<.0001). How-ever the proportion of patients with prior myocardial infarction was very similar (France 63.7%, Germany 69.5%, Spain 65%, P=NS). Diuretics were not prescribed in 19.7% of the patients, ACE inhibitors were not prescribed in 27.9%, and beta blockers were not prescribed in 52.3%. CONCLUSIONS: The study provides further information on the consumption of large amounts of medical resources because of heart failure. The reported etiologies differed between countries. However, the proportion of patients with prior myocardial infarction was very similar. Treatment with ACE inhibitors and beta blockers was slightly more common than previously reported, although beta blockers continue to be underused.     

Pituitary ACTH dependency of nodular adrenal hyperplasia in Cushing's syndrome: Report of two cases and review of the literature

Cushing's syndrome due to nodular adrenal hyperplasia comprises a clinically and biochemically heterogeneous group of disorders whose pathogenesis is unclear. We describe two patients with atypical steroid dynamics and large unilateral adrenal nodules who had pituitary ACTH-dependent disease. In the differential diagnosis of Cushing's syndrome, we recommend repeated ACTH measurement and selective venous sampling—particularly in those patients with impaired dexamethasone suppressibility and abnormal findings on computerized tomography.     

The effects of proinsulin pretreatment on the combined actions of insulin and proinsulin in normal man

With the recent availability of biosynthetic human proinsulin there has been a renewed interest in evaluating its metabolic effects, either alone or in combination with insulin. It has been suggested that pretreatment with proinsulin enhances the hypoglycemic response to subsequently administered insulin. On the other hand, the simultaneous administration of proinsulin and insulin has additive, not synergistic, effects. To clarify this question we used the euglycemic glucose clamp technique in 10 normal subjects to compare the steady state effects on glucose disposal of combined infusions of insulin (0.54 microgram/M2 . min, equivalent to 15 mU/M2 . min) and proinsulin (2.75 micrograms/M2 . min) given both simultaneously and sequentially. The mean +/- SEM steady state glucose disposal rates were similar whether the two hormones were given simultaneously (7.2 +/- 0.7 mg/min . kg), after proinsulin pretreatment (7.7 +/- 0.7 mg/min . kg), or after insulin pretreatment (7.1 +/- 0.7 mg/min . kg). The serum proinsulin concentration of 5.39 +/- 0.3 pmol/ml during the infusion of proinsulin alone was unchanged by the simultaneous infusion of insulin, suggesting that in the doses used, insulin did not affect proinsulin clearance. We conclude that in normal subjects there is no enhancement of the combined action of insulin and proinsulin to stimulate glucose disposal by pretreatment with proinsulin or insulin.     

Non-compliance in surveillance for patients with previous resection of large (≥1 cm) colorectal adenomas

AIM: To assess the extent and reasons of noncompliance in surveillance for patients undergoing polypectomy of large (≥ 1 cm) colorectal adenomas.METHODS: Between 1995 and 2002, colorectal adenomas ≥ 1 cm were diagnosed in 210 patients and subsequently documented at the Erlangen Registry of Colorectal Polyps. One hundred and fifty-eight patients (75.2%) could be contacted by telephone and agreed to be interviewed. Additionally, records were obtained from the treating physicians.RESULTS: Fifty-four out of 158 patients (34.2%)neglected any surveillance. Reasons for non-compliance included lack of knowledge concerning surveillance intervals (45.8%), no symptoms (29.2%), fear of examination (18.8%) or old age/severe illness (6.3%).In a multivariate analysis, the factors including female gender (P = 0.036) and age ≥ 62 years (P = 0.016)proved to be significantly associated with non-compliance in surveillance.CONCLUSION: Efforts to increase compliance in surveillance are of utmost importance, This applies particularly to women's compliance. Effective strategies for avoiding metachronous colorectal adenoma and cancer should focus on both the improvement in awareness and knowledge of patients and information about physicians for surveillance.     

Comparison of biplane and single plane left ventricular volumes in atrial septal defect

The close agreement between biplane (BP) and single-plane (SP) angiographic estimates of left ventricular (LV) volumes results from the similarity of the minor axes measured in the right anterior oblique (RAO) and left anterior oblique (LAO) views. Disease states that alter LV geometry may change the length of one minor axis more than the other, producing a discrepancy between BP and SP volumes. To examine this hyposthesis, angiographically derived volumes in 21 patients with atrial septal defects (ASD) in which the LV appears to be compressed and flattened by an enlarged right ventricle, were compared to 100 normal control patients. In the control patients, the median SP estimate of end-diastolic volume (EDV) was 7.6% larger than the BP determination, whereas in patients with ASD, the median SP EDV estimate was 16.7% larger than the BP EDV (P<0.0001). The SP end-systolic volume (ESV) underestimated the BP value by 3.4% in controls but overestimated the BP ESV in patients with ASD by 4.3% (P<0.02). The overestimate of the SP EDV and SP ESV when compared to the BP volumes may be due to changes in either the minor axes or the appearance of the longest major axis in the LAO view. The longest major axis was found in the RAO view in 99% (99/100) of normals and 95% (20/21) of ASD patients (P?NS). The median ratio of RAO to LAO end-diastolic minor axes, however, was 1.07 in the normals and 1.17 for ASD patients. The median ratio of end-systolic minor axes was 0.97 for controls and 1.04 for ASD patients. Compression of the LV in patients with ASD shortens the LAO minor axis, resulting in a significantly greater SP overestimation of LV volume than occurs in normals. The degree of SP volume overestimate was not predicted by the magnitude of the left-to-right shunt or pulmonary pressure. This source of error affects all SP methods for determining left ventricular volume, including radionuclide techniques using static images.     

Adenoviral low density lipoprotein receptor attenuates progression of atherosclerosis and decreases tissue cholesterol levels in a murine model of familial hypercholesterolemia

Familial hypercholesterolemia is an autosomal codominant disease characterized by high concentrations of pro-atherogenic lipoproteins and premature atherosclerosis secondary to low density lipoprotein receptor (LDLr) deficiency. In the current study, the effects of gene transfer with 5 x 10(10) particles of E1E3E4-deleted adenoviral vectors expressing the LDLr (AdLDLr) or VLDLr (AdVLDLr) under control of the hepatocyte-specific human alpha(1)-antitrypsin promoter and 4 copies of the human apo E enhancer in C57BL/6 LDLr(-/-) mice were investigated. Evaluation was performed in both sexes and in mice fed either standard chow or an atherogenic diet containing 0.2% cholesterol and 10% coconut oil. Compared to control mice, AdLDLr and AdVLDLr persistently decreased plasma non-HDL cholesterol in both sexes and on both diets. Six months after LDLr gene transfer in mice fed the atherogenic diet, average intimal area was 2.5-fold (p<0.01) and 3.2-fold (p<0.001) lower in male and female mice, respectively, compared to controls. In mice fed standard chow, intimal area was reduced 22-fold (p<0.001) and 21-fold (p<0.001) after LDLr gene transfer in male and female mice, respectively. We show that non-HDL lipoproteins are more atherogenic in female mice, independent of sex differences of plasma HDL cholesterol levels, and that saturated fat does not have an effect on atherosclerosis independent of plasma cholesterol levels. Finally, quantification of tissue cholesterol levels indicates that AdLDLr does not induce cholesterol accumulation in the liver and reduces cholesterol content in the myocardium, quadriceps muscle and kidney. In conclusion, hepatocyte-specific LDLr gene transfer significantly improves cholesterol homeostasis in LDLr(-/-) mice.