Prenatal diagnosis and postnatal follow-up of a child with two de novo unrelated balanced reciprocal translocations

Two unrelated, apparently balanced, reciprocal translocations involving chromosomes 3 and 17, and 10 and 15 were found in cultured amniotic fluid cells from a 41-year-old 10-gravida. Chromosome analysis of peripheral blood lymphocytes of both parents revealed normal karyotypes. Post-partum examination of lymphocyte cultures from the proband confirmed the chromosome rearrangements. The child showed normal development during follow-up examinations up to the age of 4 years.     

BOLD background gradient contributions in diffusion‐weighted fMRI—comparison of spin‐echo and twice‐refocused spin‐echo sequences

The interaction (‘cross terms’) between diffusion‐weighting gradients and susceptibility‐induced background gradient fields around vessels has an impact on apparent diffusion coefficient (ADC) measurements and diffusion‐weighted functional magnetic resonance imaging (DFMRI) experiments. Monte‐Carlo (MC) simulations numerically integrating the Bloch equations for a large number of random walks in a vascular model were used to investigate to what extent such interactions would influence the extravascular signal change as well as the ADC change observed in DFMRI experiments. The vascular model consists of a set of independent, randomly oriented, infinite cylinders whose internal magnetic susceptibility varies as the state changes between rest and activation. In such a network, the cross terms result in the observation of a functional increase in ADC accompanied by a descending percent signal change with increasing diffusion weighting. It is shown that the twice‐refocused spin‐echo sequence permits sufficient yet not total suppression of such effects compared to the standard Stejskal‐Tanner spin‐echo diffusion weighting under experimentally relevant conditions. Copyright © 2010 John Wiley & Sons, Ltd.     

Mechanism of protection from alloxan diabetes provided by n-butanol.

Pretreatment with n-butanol (10 mmol/kg i.p.) 30 minutes before alloxan (100 mg/kg) protects mice from the permanent hyperglycemic effects (measured at 72 hours) of the diabetogenic agent. This dose of n-butanol caused an elevation of serum glucose at 30 minutes, the time of alloxan administration. Since glucose administration can protect animals from alloxan, the possibility that alcohol-induced hyperglycemia protected mice from alloxan was investigated. Mannoheptulose, an antagonist of glucose action at the pancreatic beta-cell, when given 24 minutes after n-butanol and 6 minutes before alloxan, eliminated the alcohol-induced protection. Fasted mice did not exhibit n-butanol-induced hyperglycemia at 30 minutes and alloxan given at that time produced diabetes. No protection was observed in fed animals when n-butanol was given 5 minutes before alloxan. The high serum levels of butanol and normal serum glucose which were observed at 5 minutes after alcohol administration indicated that the lack of protection was not due to a lack of circulating alcohol but resulted from an absence of hyperglycemia. The results indicate that pretreatment with n-butanol protects mice from alloxan-induced diabetes by the indirect mechanism of producing hyperglycemia at the time of alloxan administration.     

Changes in fatty acid metabolism in dilated cardiomyopathy and hypertrophic cardiomyopathy in childhood

The aetiology and the pathomechanisms in both types of cardiomyopathy (CM) are still unknown. In vivo measurements of myocardial metabolism in CM may be useful, but there is hardly any information on this subject. Free fatty acids (FFA) are the main source of energy for the normal myocardium. A method for external measurement of the FFA extraction rate (FFA-ER) in different myocardial regions by the simultaneous use of two isotopes has been developed. 201 TI indicates the myocardial perfusion and 15-(p-123 I-phenyl)-pentadecanoid acid (IPPA) represents the FFA uptake. The relation of IPPA/TI reflects the FFA-ER. 8 patients with hypertrophic CM (HCM), age 0.2-20 years, and 8 patients with dilated CM (DCM), age 0.2-18 years were investigated. 12 healthy adults and 4 infants after an arterial switch operation were used as a control group. All patients with HCM showed normal myocardial perfusion but the FFA uptake was strongly diminished, resulting in a reduction in FFA-ER to 42 +/- 12% of the normal value. The maximal influx rate (IR) of FFA was diminished too. In patients with DCM both the myocardial perfusion and the FFA uptake were globally reduced, resulting in a virtually normal FFA-ER. The IR was slightly increased. In HCM and DCM FFA utilisation was disturbed. The alterations were significantly different in both types of CM and different pathomechanisms can be assumed.     

Dilatation of the pulmonary veins in atrial fibrillation: a transesophageal echocardiographic evaluation

Ectopic beats originating from sleeves of atrial tissue within the pulmonary veins (PVs) can induce and sustain paroxysmal atrial fibrillation (AF). Left atrial stretch and dilatation favors the development of atrial ectopy and AF. Similarly, PV dilatation, if present, might trigger PV ectopy in patients with AF. This study was designed to evaluate whether PV dilatation is present in patients with nonfocal AF and whether the PV diameter correlates to the left atrial diameter (LAD). The diameters of the right superior (RSPV) and left superior PV (LSPV) were measured at the ostium and at a depth of 1 cm in 170 patients (AF, n = 75; sinus rhythm [SR], n = 95) using transesophageal echocardiography. The LAD was determined by transthoracic echocardiography. The diameters of the PVs were significantly larger in patients with AF than in patients with SR (LSPV(ostium): AF 13.6 +/- 3.5 mm vs SR 10.6 +/- 2.7 mm, P < 0.001; LSVP(1cm): AF 12.5 +/- 2.9 mm vs SR 10.2 +/- 2.5 mm, P < 0.001; RSPV(ostium): AF 13.9 +/- 3.5 mm vs SR 11.7 +/- 2.9 mm, P < 0.001; RSVP(1cm): AF 12.8 +/- 2.8 mm vs SR 10.6 +/- 2.6 mm, P < 0.05). Similarly, LAD was larger in patients with AF (44.7 +/- 7.7 mm) as compared to patients with SR (38.8 +/- 6.8 mm, P < 0.001). Neither for the SR nor the AF group did the PV size correlate to the LAD. AF is associated with a significant enlargement of the RSPV, LSPV, and LAD. There is no correlation between LAD and PV diameters. This raises the question whether PV dilatation in patients with AF is a cause or a consequence of AF and whether it may contribute to the development and perpetuation of AF.     

Influence of age and dietary fish oil on plasma soluble adhesion molecule concentrations

Soluble forms of intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and E-selectin (termed sICAM-1, sVCAM-1 and sE-selectin respectively) are found in the plasma, and are elevated during inflammatory conditions in which there is increased expression of the cellular forms of the molecules on endothelial and other cells. sICAM-1, sVCAM-1 and sE-selectin concentrations were measured in the plasma of 140 healthy Caucasian subjects aged between 18 and 75 years (100 males/40 females). sICAM-1 concentrations varied between 59.9 and 299.7 ng/ml (median 150 ng/ml), sVCAM-1 concentrations varied between 222.8 and 1672.9 ng/ml (median 662 ng/ml) and sE-selectin concentrations varied between 12.4 and 90.3 ng/ml (median 45.5 ng/ml). There were significant positive linear correlations between age and the plasma concentrations of sICAM-1 (r=0.580; P<0.001) and sVCAM-1 (r=0.392; P<0.001), which were retained when the effects of gender, body mass index and fasting plasma triacylglycerol and total cholesterol concentrations were controlled for. The significant positive linear correlation between age and the plasma concentration of sE-selectin (r=0.234; P=0.027) was lost when other variables were controlled for. Male subjects <40 years of age had significantly lower plasma concentrations of both sICAM-1 and sVCAM-1 than males >55 years of age (both P<0.001), but the difference in plasma sE-selectin concentrations between the age groups did not reach significance (P=0.073). Subgroups of 16 males aged <40 years and 12 elderly subjects (>55 years of age) participated in a doubled-blind, placebo-controlled study of fish oil supplementation over 12 weeks. The level of eicosapentaenoic acid in plasma phospholipids did not change with placebo supplementation, but was significantly increased with fish oil supplementation in both young male and elderly subjects (median increase 200%). sICAM-1, sVCAM-1 and sE-selectin concentrations were unaffected by supplementation with placebo in either young male or elderly subjects. sICAM-1 concentrations were unaffected by fish oil supplementation. sE-selectin concentrations were significantly increased by fish oil supplementation in young males (P=0.043; median increase 38%), but fish oil tended to decrease plasma sE-selectin concentrations in the elderly subjects (P=0.075), with a median decrease of 11%. sVCAM-1 concentrations were unaffected by fish oil supplementation in young males. Fish oil supplementation significantly decreased plasma sVCAM-1 concentrations in the elderly subjects (P=0.043), with a median decrease of 20% (range 16-60%). These observations suggest that fish oil decreases endothelial activation in elderly subjects.     

Physical characteristics and lipoprotein distribution of liposomal nystatin in human plasma.

The physical characteristics and lipoprotein distribution of free nystatin (NYS) and liposomal NYS (L-NYS) in human plasma were investigated. To determine the percentage of NYS that was lipid associated following incubation in human plasma, C18 reverse-phase extraction columns were used. To assess plasma drug distribution, NYS and L-NYS (20 microg/ml) were incubated in human plasma for 5, 60, and 120 min at 37 degrees C. After each interval, plasma was removed and separated into its lipoprotein and lipoprotein-deficient plasma (LPDP) fractions by ultracentrifugation and assayed for NYS by high-pressure liquid chromatography. Further studies evaluated the liposome structure of L-NYS by filtering through a 0.14-microm-pore-size microfilter before and after the addition of human plasma. When reconstituted L-NYS (mean particle diameter +/- standard deviation, 321 +/- 192 nm) was applied to a C18 column, 67% +/- 4% of the initial NYS concentration was associated with the lipid. When plasma samples containing L-NYS that had been incubated for 5 to 120 min at 37 degrees C were applied to C18 columns, 66 to 76% of the NYS was lipid associated. Incubation of NYS in human plasma for 5 min at 37 degrees C resulted in 3% +/- 1% of the initial NYS concentration incubated in the low-density lipoprotein (LDL) fraction, 23% +/- 4% of that in the high-density lipoprotein (HDL) fraction, and 66% +/- 10% of that in the LPDP fraction. In contrast, the distribution of NYS following incubation of L-NYS in human plasma for 5 min was 13% +/- 2% in the LDL fraction, 44% +/- 5% in the HDL fraction, and 42% +/- 5% in the LPDP fraction. Similar results were observed following 60 and 120 min of incubation. In addition, the liposome structure of L-NYS was quickly lost when mixed with plasma. These findings suggest that rapid disruption of the L-NYS structure upon incubation in human plasma is consistent with its rapid distribution in plasma. The preferential distribution of NYS into the HDL fraction upon incubation of L-NYS may be a function of its phospholipid composition.