Clinical and molecular aspects of juvenile hemochromatosis in Saguenay-Lac-Saint-Jean (Quebec, canada)

We report the clinical, biochemical, and genetic characteristics of 13 hemochromatosis patients from Saguenay-Lac-Saint-Jean in whom the first symptoms appeared before age 30. Although the mean age at onset of the first symptoms was 21. 5 years, their mean age at diagnosis was 23.8 years; the diagnosis was particularly delayed among women. Seventy-seven percent of the patients had hypogonadotrophic hypogonadism and 69% heart failure and/or cardiac arrhythmias. Genetic analysis of the HFE gene revealed heterozygosity for the C282Y mutation in 2 patients and for the S65C mutation in 2 others and homozygosity for the H63D mutation in 1 patient. The remaining 8 patients had no identified mutation in the HFE gene, although sequencing of all seven codons and intron-exon junctions was performed (5 patients). All 13 patients fulfill the clinical criteria of juvenile hemochromatosis and represent the largest cluster thus far reported.     

碘杂环化合物IHC-72、利多卡因及维拉帕米抗心律失常作用的比较

在大鼠和豚鼠整体模型上,比较观察了等毒剂量(1/ LD₅₀)的IHC-72、利多卡因和维拉帕米对乌头碱、哇巴因致心脏毒性的保护作用,以及对急性缺血再灌注心律失常和缺血心肌室颤阈的影响。IHC-72抗乌头碱致大鼠心脏毒性作用,与利多卡因相当,而比维拉帕米强;IHC-72抗哇巴因致豚鼠心脏毒性作用,与利多卡因相当而比维拉帕米弱;对提高大鼠缺血电室颤阈值的作用,IHC-72比利多卡因及维拉帕米弱;对预防大鼠急性缺血再灌注的心律失常作用,三者作用近似。     

赛庚啶对离体大鼠心脏缺钙/复钙损伤(钙反常)的保护作用

离体大鼠心脏经无钙灌流(灌流液为不含Ca²⁺的K-H液,通以95%O₂和5%CO₂的混合气体)5min后,用正常K-H液进行复钙灌流20min,可导致心肌细胞内酶(CPK,LDH)及蛋白的大量漏出,心脏变苍白,甚至出现心脏挛缩,心肌组织抗氧自由基酶(SOD,GSH-Px)活性明显降低,但MDA含量无明显改变。赛庚啶(2.5～5μmol/L)能明显减少心脏Ca²⁺反常时心肌组织内酶及蛋白的漏出,显著保护心肌组织抗氧自由基酶的活性。     

Nucleic acid composition of bone marrow mononuclear cells in cobalamin deficiency

Recent studies using anion exclusion chromatography have suggested that uracil is misincorporated into the DNA of patients with megaloblastic anemia to levels detectable by nonradioactive methods. We have investigated the nucleotide composition of DNA from the bone marrow mononuclear cells of eight patients with cobalamin deficiency and compared this with that found in normal subjects. The median level of uracil in the megaloblastic group was 0.082 mol% of cytosine (approx. 0.02 mol% of all bases in DNA), which was similar to that found in the control group (median 0.085 mol% of cytosine) and may be attributable, at least in part, to artefactual deamination of deoxycytidine monophosphate during the DNA hydrolysis. Our findings give no support for the view that, by overwhelming the uracil N-glycosidase mechanism, the degree of uracil misincorporation in megaloblastic anemia is sufficient to increase the steady state level of uracil in the DNA by amounts detectable by nonradioactive methods. Using high performance liquid chromatography, we have also demonstrated normal levels of methylcytosine in the DNA of megaloblastic subjects.     

Effect of axial loading on neural foramina and nerve roots in the lumbar spine

The hypothesis that the neural foramina in some patients are critically narrowed by axial compression of the spine has not been studied with direct imaging techniques. Frozen cadaveric motion segments of the lumbar spine (intervertebral disk and contiguous vertebrae) were imaged with computed tomography (CT). The segments were thawed and compressed in a hydrostatic press to simulate axial loading, and then the segments were frozen and imaged again. The motion segments were subsequently sectioned with a cryomicrotome, and the chronic degenerative changes present in the disks were classified. Pre- and post-compression CT images were compared, and anatomic relationships were studied. In 41 randomly selected segments (some with preexisting radial, transverse, and concentric annular tears), compression diminished the diameters and cross-sectional areas of the spinal canal and neural foramina. In no cases were nerve roots displaced, distorted, or compressed by axial loading. This study suggests that axial loading, such as that produced by ordinary weight bearing, does not critically compromise the neural foramina even in the presence of chronic degenerative disk changes.