Can intravascular lymphomatosis mimic sinus thrombosis? A case report with 8 months' follow-up and fatal outcome.

We report a case of intravascular lymphomatosis of the brain with 8 months' follow-up and fatal outcome. Several MRI investigations revealed variegated, rapidly changing infarct-like lesions and invasion of the walls of the superior sagittal sinus and deep veins. When disturbances of the venous outflow are detected with multifocal infarct-like lesions, intravascular lymphomatosis should be considered in the differential diagnosis. Brain biopsy may ensure the proper diagnosis ante mortem, but failure of biopsy is frequent, as in our case.

Baseline and stimulated ANF plasma levels: is an impaired stimulus-response coupling diagnostically meaningful?

Plasma levels of ANF were determined and chromatographically analysed in normotensive controls, cirrhotic patients with and without ascites, hypertensive patients, patients with congestive heart failure and heart transplant recipients. A comparison of baseline plasma levels allowed for the conclusion that cirrhotic patients do not differ in this regard from control subjects (9.0 +/- 1.3, n = 41 vs. 9.6 +/- 1,0 fmol/ml, n = 51). Cirrhotic patients with ascites do not have lower plasma levels than cirrhotic patients without ascites (8.8 +/- 1.4, n = 8 vs 8.6 +/- 1.5 fmol/ml, n = 10). Stimulation of the ANF-system by head-out water immersion, however, revealed an impaired increase in ANF release in cirrhotic patients with ascites (146 +/- 18% vs 204 +/- 16%). Patients with cardiovascular disease display tonically-elevated ANF plasma levels. Heart failure patients displayed the highest plasma concentration (81.5 +/- 32.7 fmol/ml, n = 17), whereas plasma levels in hypertensive patients ranged from normal to greatly elevated (61.7 +/- 13.2 fmol/ml, n = 36). Heart transplant recipients also had significantly elevated plasma levels as compared to control subjects (31.2 +/- 7.9 fmol/ml, n = 14) but levels were lower than in hypertensive patients in spite of a comparable arterial pressure. Short term ventricular pacing (f = 150/min for 5 min) revealed an impaired phasic activity of the ANF system in heart failure patients and heart transplant recipients.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial natriuretic factor in plasma of patients with arterial hypertension, heart failure or cirrhosis of the liver.

Since the discovery of the atrial natriuretic factor (ANF) an endocrine function has been attributed to the mammalian heart. This function may include definition of optimal conditions for efficient performance of the heart, e.g. by reduction of afterload in hypertension or of preload and afterload in heart failure. Plasma ANF levels were measured in various cardiovascular disease states and compared with those of controls and of patients with liver cirrhosis. Plasma ANF levels in hypertensive patients were sevenfold higher than in controls, and in patients with heart failure 40-fold higher than normal values. Small differences were detected between controls and patients with cirrhosis of the liver, in spite of the impaired renal sodium handling seen in cirrhotics. Plasma ANF levels were significantly correlated with haemodynamic parameters and were inversely related to the cardiac index. Treatment with an angiotensin converting enzyme inhibitor led to a significant decrease in plasma ANF levels in parallel with the haemodynamic improvement. Preliminary chromatographic analysis suggested differences in the structure of plasma ANF between normotensive and hypertensive subjects.

Molecular weight heterogeneity of plasma-ANF in cardiovascular disease.

Structural differences of circulating ANF may partly explain why the physiological response of the heart in controlling volume/pressure loading in cardiovascular disease states remains insufficient in spite of elevated ANF plasma levels. Structural analysis of plasma ANF immunoreactivity was performed by means of gel permeation of plasma extracts subsequent to radioimmunoassay. ANF plasma levels in hypertensive patients or patients with congestive heart failure (CHF) were significantly elevated as compared to normotensive controls or cirrhotics. (61.7 +/- 13.2 or 81.5 +/- 32.7 versus 9.6 +/- 1.0 or 10.3 +/- 1.3 fmol/ml, p less than 0.01). In CHF patients, ANF plasma concentrations were significantly correlated to right atrial and pulmonary capillary wedge pressures. ANF release was stimulated by head-out water immersion both in normotensive controls and cirrhotic patients. No higher molecular weight forms were detected in plasma of control subjects. 15,000-dalton ANF, in addition to 3080-dalton ANF, was present in plasma of hypertensive patients and, in trace amounts, of cirrhotic patients. In some CHF patients, elevated ANF plasma levels predominantly comprised higher molecular weight forms of approx. 15,000 daltons MW, in addition to considerable amounts of ANF immunoreactivity presumably bound to larger proteins that eluted in the void volume. The data suggest that a dysregulation of post-translational processing of ANF may contribute to the pathophysiology of cardiovascular disease.

Regression of heart muscle hypertrophy after nifedipine therapy: changes in cardiac gene expression.

Changes in cardiac gene expression were studied during development and regression of cardiac hypertrophy in spontaneously hypertensive rats (SHR) in an attempt to determine some of the biochemical factors responsible for alterations in cardiac mass. Chronic nifedipine treatment of SHR (30 mg/kg per day for 20 weeks) led to a marked reduction in arterial blood pressure and to a subsequent regression of cardiac hypertrophy. Cardiac mRNA concentration decreased, whereas cardiac protein concentration remained unchanged. Changes in cardiac gene expression, as reflected by the decrease in cardiac mRNA concentration, were thus identified as a major factor responsible for the regression of cardiac hypertrophy after nifedipine therapy of SHR.

Demonstration and characterization of alpha-human atrial natriuretic factor in human plasma.

This paper describes a highly specific and sensitive radioimmunoassay for alpha-human atrial natriuretic factor (alpha-hANF), the C-terminal 28-amino-acid residue portion of human prepro-ANF in human plasma. A novel extraction and prepurification procedure allowed for detection of levels of immunoreactive-alpha-hANF as low as 0.5 fmol/ml. In normotensive subjects, levels in the range 1-23 fmol/ml (mean = 8.9 fmol/ml) were found. Combined gel permeation and HPLC analysis demonstrated that this ir-alpha-hANF was comprised virtually exclusively of authentic 28-residue alpha-hANF. No evidence for occurrence of larger precursor forms in human plasma was acquired. A heterogenous group of hypertensive patients displayed considerably higher levels (mean = 62.2 fmol/ml), of interest in view of the hypotensive properties of ANF.

Virus myocarditis: molecular hybridization allows the detection of virus-RNA in heart muscle after virus infection.

In most patients with virus myocarditis, the diagnosis is still based on clinical data alone. Endomyocardial biopsies subjected to electron microscopy, immunofluorescence techniques and virus isolation procedures provide additional, but only occasionally conclusive information. In this communication we describe a new method which could possibly be used to improve the diagnostic possibilities in patients with suspected virus myocarditis. The method is based on the hybridization of radioactive complementary nucleotide sequences to virus-RNA. It is shown that in an experimental model (reovirus infected baby mice) this method can be used to demonstrate the virus infection of cardiac muscle. It is suggested that the method could be adapted to other viruses (e.g. coxsackie virus) and to endomyocardial biopsies derived from patients with suspected virus myocarditis.

Gene expression in cardiac hypertrophy in rat and human heart muscle.

Changes in the cardiac contents of microsomal RNA and poly(A)-containing mRNA have been examined during induction and regression of heart muscle hypertrophy in rat hearts, as well as possible changes in the subcellular distribution and protein-synthetic activity of cardiac mRNA. In addition, cardiac biopsies from patients with mitral valve diseases were evaluated for their mRNA contents. Induction of heart muscle hypertrophy was accompanied by substantial increases in cardiac microsomal RNA (30-60%) and cardiac mRNA (20-80%). During regression of hypertrophy increased levels of cardiac microsomal RNA and mRNA returned to normal values within 10-16 days. In general, cardiac mRNA levels were lower in human heart muscle than in rat heart muscle. Since the subcellular distribution of the microsomal RNA and of the mRNA as well as the protein-synthetic activity of the mRNA were not changed in the hypertrophied animals as compared with normal animals, and since the cardiac contents of most specific cardiac mRNA species (mRNAs for MHC, MLC1 and MLC2, actin, tropomyosin, troponin-T, myoglobin) increased proportionately, it is concluded that during induction of hypertrophy activation of gene expression occurs and affects the genes coding for the major cardiac proteins to a similar extent. This does, however, not exclude the possibility of more specific shifts in isoprotein patterns and in the levels of their corresponding mRNAs. It is proposed that changes in cardiac mRNA levels are the major regulatory factor in causing changes in cardiac protein synthesis rates leading to the induction and regression of cardiac hypertrophy.