CORRELATION BETWEEN THE NUMBER OF MITOTIC FIGURES AND THE PERCENTAGE OF Ki67-POSITIVE CELLS IN NON-HODGKIN’S LYMPHOMAS

ＣＯＲＲＥＬＡＴＩＯＮＢＥＴＷＥＥＮＴＨＥＮＵＭＢＥＲＯＦＭＩＴＯＴＩＣＦＩＧＵＲＥＳＡＮＤＴＨＥＰＥＲＣＥＮＴＡＧＥＯＦＫｉ６７－ＰＯＳＩＴＩＶＥＣＥＬＬＳ　ＩＮＮＯＮ－ＨＯＤＧＫＩＮ’ＳＬＹＭＰＨＯＭＡＳＨｕａｎｇＧａｏｓｈｅｎｇ；（黄高升）Ｆｅ...     

Abnormalities of iron metabolism and erythropoiesis in vitamin E- deficient rabbits

Rabbits fed a vitamin E-deficient diet developed severe muscular dystrophy in 3-4 wk, but they did not become anemic. Nevertheless, reticulocyte counts increased in deficient rabbits (3.2%) compared to control rabbits (0.9%), and erythroid hyperplasia was evident in the bone marrow. Comparing deficient rabbits to controls, the plasma iron concentration was lower (134.4 versus 206.6 microgram/dl); the TIBC was higher (335.9 versus 228.3 microgram/dl); the whole blood protoporphyrin concentration was higher (131.6 versus 81.7 microgram/dl); and the total iron content was lower in spleen (71 versus 153 microgram), higher in skeletal muscle (4956 versus 3054 microgram), and unchanged in bone marrow, liver, and heart. Studies of iron absorption and excretion using 59Fe showed no abnormalities in deficient rabbits. There were abnormalities of ferrokinetics, however. The half-time of disappearance of 59Fe was shorter (100.6 versus 169.4 min), the plasma iron turnover was greater (1.25 versus 0.95 mg/dl blood/day), and the reappearance of 59Fe in circulating erythrocytes at day 9 was greater (77.2% versus 57.2%) in deficient rabbits. Anemia induced by phlebotomy accentuated the abnormal iron metabolism of deficient rabbits, and the animals were unable to correct the anemia. These findings show that vitamin E deficiency in rabbits causes abnormal erythropoiesis associated with abnormal iron metabolism and sequestration of iron in skeletal muscle.     

Effects of cholinergic modulation on responses of neocortical neurons to fluctuating input

Neocortical neurons in vivo are spontaneously active and intracellular recordings have revealed strongly fluctuating membrane potentials arising from the irregular arrival of excitatory and inhibitory synaptic potentials. In addition to these rapid fluctuations, more slowly varying influences from diffuse activation of neuromodulatory systems alter the excitability of cortical neurons by modulating a variety of potassium conductances. In particular, acetylcholine, which effects learning and memory, reduces the slow alterhyperpolarization, which contributes to spike frequency adaptation. We used whole-cell patch-clamp recordings of pyramidal neurons in neocortical slices and computational simulations to show, first, that when fluctuating inputs were added to a constant current pulse, spike frequency adaptation was reduced as the amplitude of the fluctuations was increased. High- frequency, high-amplitude fluctuating inputs that resembled in vivo conditions exhibited only weak spike frequency adaptation. Second, bath application of carbachol, a cholinergic agonist, significantly increased the firing rate in response to a fluctuating input but minimally displaced the spike times by < 3 ms, comparable to the spike jitter observed when a visual stimulus is repeated under in vivo conditions. These results suggest that cholinergic modulation may preserve information encoded in precise spike timing, but not in interspike intervals, and that cholinergic mechanisms other than those involving adaptation may contribute significantly to cholinergic modulation of learning and memory.      

Parental mosaicism and autosomal dominant mutations causing structural abnormalities of collagen I are frequent in families with osteogenesis imperfecta type III/IV

Abstract Protein-chemical and molecular studies were conducted on all osteogenesis imperfecta (OI) type III/IV patients referred to our hospital during the last 15 y. Of a total of 16 OI type III/IV patients studied, 15 patients were heterozygous for a mutation in one of the two genes coding for collagen I, COL1A1 or COL1A2. Cultured fibroblasts from these 15 patients produced both normal and abnormal collagen I molecules, pointing to a dominant-negative effect of the mutation. Nine mutations had not been described previously. Parental mosaicism was demonstrated in three families. In the 16th child the causative mutation was not found. In conclusion, OI type III/IV in most patients of Western European ancestry is caused by dominant mutations in the genes for collagen I, and recurrence of OI is caused in most cases by parental gonadal mosaicism.     

Obesity: Risk Factor for Increased Resource Utilization at Bidirectional Glenn

Background

Underweight infants with single‐ventricle cardiac physiology have been shown to have increased morbidity, mortality, and resource utilization. The purpose of this study was to determine whether patients who were overweight, as defined by weight‐for‐length z score >90th percentile, were similarly at risk for increased resource utilization, as defined by mechanical ventilation hours (VHs) and intensive care unit length of stay (ICU LOS).

Methods

We evaluated resource utilization for 109 patients from our institution who underwent bidirectional Glenn surgery from January 2010 to June 2015 and met prespecified inclusion criteria. Patients were divided into 3 groups: underweight (z score, <5th percentile), normal weight (z score, 5th–90th percentile), and overweight (z score, >90th percentile).

Results

ICU LOS was longer in the overweight group (median, 18.5 days) when compared with the under‐ and normal‐weight groups (median LOS, 11 and 9 days, respectively) but did not reach statistical significance. VHs were also increased in the overweight group (median, 72 hours) when compared with the underweight (median, 27 hours) and normal weight (median, 25 hours) groups. This increase in VHs was statistically significant (P = .03).

Conclusions

This study suggests that patients with single‐ventricle physiology who are overweight at the time of their bidirectional Glenn surgery may be at risk for increased resource utilization as compared with those who meet or fail to meet their caloric recommendations. These findings represent an underappreciated risk factor in this already‐vulnerable patient population, providing potential opportunity for intervention and improved outcomes.     

Combination therapy in rheumatoid arthritis: updated systematic review

In a second update of a systematic review, many new developments in the combined drug treatment of rheumatoid arthritis (RA) are highlighted. In early RA patients, step-down bridge therapy that includes corticosteroids leads to much enhanced efficacy at acceptable or low toxicity. The effects on joint damage may be persistent, but the symptomatic effects are probably dependent on continued corticosteroid dosing. In late patients, cyclosporin improves a suboptimal clinical response to methotrexate, and the triple combination of methotrexate, sulphasalazine and hydroxychloroquine appears to be clinically better than the components. Other combinations are either untested, tested at low sample size, or show negative interaction. In view of the low volume of evidence, most studies need confirmation by replication.