Citations

Background and purpose The clinical characteristics of colony stimulating factor 1 receptor ( CSF 1R) related adult‐onset leukoencephalopathy with axonal spheroids and pigmented glia ( ALSP ) have been only partially elucidated. Methods Clinical data from CSF 1R mutation carriers who had been seen at our institutions or reported elsewhere were collected and analysed using a specific investigation sheet to standardize the data. Results In all, 122 cases from 90 families with CSF 1R mutations were identified. The mean age of onset was 43 years (range 18–78 years), the mean age at death was 53 years (range 23–84 years) and the mean disease duration was 6.8 years (range 1–29 years). Women had a significantly younger age of onset than men (40 vs. 47 years, P = 0.0006, 95% confidence interval 3.158–11.177). There was an age‐dependent penetrance that was significantly different between the sexes ( P = 0.0013). Motor dysfunctions were the most frequent initial symptom in women whose diseases began in their 20s. Thinning of the corpus callosum, abnormal signalling in pyramidal tracts, diffusion‐restricted lesions and calcifications in the white matter were characteristic imaging findings of ALSP . The calcifications were more frequently reported in our case series than in the literature (54% vs. 3%). Seventy‐nine per cent of the mutations were located in the distal part of the tyrosine kinase domain of CSF 1R (102 cases). There were no apparent phenotype−genotype correlations. Conclusions The characteristics of ALSP were clarified. The phenotype of ALSP caused by CSF 1R mutations is affected by sex.

Microspheres of different sizes, 125 I-labeled antipyrine (I-Ap), and 42 KCl or 86 RbCl were injected into the aortic inflow of isolated, Langendorff, perfused, nonworking dogs hearts at blood flows of 1.3-4.8 ml/min g -1 . After 15 seconds to 5 minutes, the left ventricle was sectioned into about 300 ordered pieces, and the amount of each tracer was determined. For all tracers, the relative density of deposition was generally higher in the endocardial region, except in one heart in which the aortic pressure and the total coronary flow were low. The deposition of 42 K and that of I-Ap were essentially similar in three hearts over a large range of regional variation. This finding suggests either that both tracers were distributed in proportion to flow or that a small diminution in relative density of deposition of 42 K in high-flow regions due to lower transcapillary extraction was quantitatively similar to a decrease in the residual fraction of I-Ap in these same regions due to faster washout in the first 15-30 seconds after injection. Large microspheres were deposited preferentially in regions of high flow, exaggerating the apparent heterogeneity of regional flows. The distribution of the smaller microspheres was closer to that for I-Ap or 42 K.

The exchanges of 125 I-labeled 4-iodoantipyrine (I-Ap), 14 C-labeled antipyrine ( 14 C-Ap), and tritiated water (THO) were studied in isolated blood-perfused, beating, nonworking dog hearts. From a first set of experiments, analysis of externally monitored myocardial clearance curves of I-Ap after its injection into coronary artery blood showed its washout to be flow limited at flows ranging from 0.8 to 3.8 ml. g -1 . min -1 . Therefore, these curves can be used for estimating coronary blood flow. In a second set of experiments, coronary sinus dilution curves of simultaneously injected I-Ap and THO were found to be indistinguishable in shape at high coronary flows. At low flows (<1.8 ml. g -1 . min -1 ), THO curves showed an earlier upslope and higher peak than antipyrine, indicating either a diffusional shunt for water or a larger volume of distribution for antipyrine. 14 C-Ap had a slightly faster washout than I-Ap. The differences are partially attributable either to differences in solubility of I-Ap, 14 C-Ap, and THO in erythrocytes or to differences in their volumes of distribution, and partially to diffusional shunting of water.

Left ventricular (LV) performance was studied during mild exercise (100 kg-m/min for 3 minutes) in 19 cases of coronary artery disease (CAD). Each patient suffered from a severe anginal syndrome. None had ventricular aneurysm, cardiomegaly, or clinical heart failure. Mean resting values follow: LV end-diastolic pressure (LVEDP), 19 ± 7 mm Hg; LV systolic pressure (LVSP), 150 ± 16 mm Hg; stroke volume index (SVI), 48 ± 10 ml/beat/m 2 ; and LV stroke work index (LVSWI), 81 ± 19 g-m/m 2 . During exercise LVEDP rose to 30 ± 8 mm Hg ( P ≤0.001) and LVS to 160 ± 20 (not significant [NS]); SVI diminished to 46 ± 11 (NS) and LVSWI, to 76 ± 24 (NS). Patients with decreased or asynchronous areas of LV myocardium identified on cine left ventriculograms had higher mean LVEDPs during exercise than did those with normal ventriculograms (34 ± 10 versus 26 ± 4 mm Hg; P ≤0.05). The difference between responses to exercise of patients who experienced angina during the study and of those who did not was NS. Administration of nitroglycerin reduced the increase in LVEDP during exercise. An abnormality in LV performance-a significant rise in LVEDP without a significant increase in SVI or LVSWI-was observed in 13 of 19 cases of CAD.