Apolipoprotein E genotype is not associated with cardiovascular disease in heterozygous subjects with familial hypercholesterolemia

Background

Familial hypercholesterolemia (FH) is a genetic disorder characterized by high low-density lipoprotein cholesterol levels and premature cardiovascular disease (CVD). There are important differences in the presence of CVD among heterozygous subjects with FH. Some of this variability can be explained by genetic factors, and the apolipoprotein (apo) E genotype has been proposed as a useful marker.

Methods

We analyzed the apo E genotype in 706 non-related subjects who were heterozygous for FH from Spain. CVD was present in 198 subjects (28%), 132 men (41%) and 66 women (17%).

Results

Apo E allele frequencies for the ε3, ε4, and ε2 alleles were 0.89, 0.09, and 0.02 respectively. Age, body mass index, smoking status, high blood pressure, diabetes mellitus, presence of tendon xanthomas, total cholesterol level, triglyceride levels, high-density lipoprotein cholesterol level, low-density lipoprotein cholesterol level, and Lp(a) did not differ among genotypes. The incidence of CVD and the age of onset of CVD did not differ among genotypes either. In the multivariant analysis, apo E genotype did not contribute significantly to CVD.

Conclusions

Heterozygous men with FH have a very high risk of coronary disease in a Mediterranean country, and the apo E genotype in this large group of adults with FH is not associated either with CVD or lipid values, in contrast with the established effect in the general population.     

Neu／c─erbB─2癌基因在颊粘膜上皮良性及恶性病变中的表达及其定量研究

目的：观察Ｎｅｕ／ｃ－ｅｒｂＢ－２癌基因在颊粘膜上皮良性、癌前以及癌变状态下的表达，并确立图像分析系统定量的方法．方法：用三种抗Ｎｅｕ抗体，通过微波暴露抗原，进行标准化的ＥｌｉｔｅＡＢＣ染色，并通过半定量及图像分析系统确立Ｎｅｕ基因在不同标本病变中的表达．结果：Ｎｅｕ基因在恶变组有高表达（６３．５％），以转移和复发的病变反应强度最高．此外，在癌前病变中也有较高的表达（５６．３％）．结论：本研究建立的免疫组化定量方法检测Ｎｅｕ基因表达的系统精确、可靠、重复性好，选取的指标可充分反映Ｎｅｕ基因表达的量以及细胞的阳性表达率．结果证实了Ｎｅｕ基因与口腔鳞癌的癌变关系密切，在癌变的早期以及转移和复发的病变中有较高的表达．     

Early sequelae of gunshot wounds to the spine: radiologic diagnosis

During a 6-month period, 11 consecutive patients who had delayed neurologic deterioration after sustaining a gunshot wound to the spine were prospectively evaluated clinically, radiologically, and surgically. The patients had dysesthetic burning pain in an anesthetic area, hyperhidrosis, flexor spasm, and additional motor deficit above the level of cord injury 2-22 weeks after injury. Radiologic evaluation consisted of plain radiography of the spine and metrizamide myelography followed by computed tomography. A syringomyelic cavity was found in seven patients, an arachnoid cyst in three, and osteomyelitis in one. Seven of these patients also had cord atrophy. Postoperatively, dysesthetic pain was relieved in all the patients. There was no recurrence during a 2-year follow-up. These results emphasize the need for immediate radiologic investigation in patients with gunshot wounds of the spine who have further deterioration superimposed on their initial deficit.     

Principles for use of intraoperative enteroscopy for hemorrhage from the small bowel

Most patients with bleeding from the small bowel are frequently difficult to diagnose and treat because the rate of bleeding is slow and because this is the "blind area" of gastrointestinal endoscopy. We used a colonoscope passed by mouth intraoperatively in order to determine the site of bleeding in four patients. All patients required resection with one requiring laser therapy as well. We found that the following principles were important in maximizing the value of this technique: (1) Good communication between the endoscopist and operating surgeon during the procedure, (2) clamping the distal small bowel to prevent air accumulation in the colon (3) examining the bowel on the way in and avoiding the use of suction to minimize scope trauma artifact, (4) turning off the room lights in order to examine the transilluminated bowel externally, (5) examining the entire small bowel if possible, and (6) marking each site externally with a suture as it is identified.     

Extrarenal abnormalities in Tc-99m-DTPA renal blood flow studies

We observed extrarenal abnormalities during renal flow scintigraphy and retrospectively reviewed 90 patient studies to determine the types and frequencies of such abnormal findings. For each routine Tc-99m-DTPA renal flow study, we obtained nine 2-second sequential images, which included the heart, abdominal aorta, spleen and kidneys. Eighty abnormalities, observed in 62 patients, were divided into three categories: aortic, 37 cases (aneurysms, ectasia, thrombosis, tortuosity, and abruptly decreased flow); splenic, 40 cases (enlarged, small, or absent spleen); and miscellaneous, 3 cases (hepatic arterialization and very slow circulation). Other correlative studies including Tc-99m sulfur colloid-spleen scintigraphy, ultrasonography (US), CT, aortography, and surgical and/or autopsy findings were available for corroboration in 56 of 80 lesions.     

Seminal plasma alpha-glucosidase activity and male infertility

Measurement of alpha-glucosidase (alpha-GLUC) activity by means of a simple colorimetric test using a commercial kit (EpiScreen; FertiPro, Lotenhulle, Belgium) yielded results that were strongly correlated with the values obtained for the neutral iso-enzyme measured by a fluorimetric reference method (r=0.85, P=0.003, n=13). The former method was characterized by a low intra- and inter-coefficient of variation (6.6 and 4.3% respectively). Vasectomized men with azoospermia (n=27) had a significantly lower alpha-GLUC activity in semen than vasectomized men with residual spermatozoa present (n=11, P < 0.01) and men with azoospermia of primary testicular origin (n=33, P < 0.01). Receiver operating curve (ROC) analysis showed alpha-GLUC measurement to be reasonably accurate in differentiation between cases with obstructive versus testicular azoospermia at criterion value 13.5 U/l (sensitivity=82%, specificity= 70%). In cases with spermatozoa present, alpha-GLUC activity and output per ejaculate were positively correlated with sperm concentration (r=0.53 and 0.38, n=472), linear velocity (r=0.35 and 0.30, n=224), curvilinear velocity (r=0.32 and r=0.29, n=224), semen adenosine triphosphate (r=0.35 and 0.26, n=64), the concentration of 5alpha-dihydrotestosterone (r=0.31 and 0.29, n=74), and gamma-glutamyltransferase activity (r=0.62 and 0.32, n=275) in seminal plasma. The activity of alpha-GLUC was inversely correlated with ROS generation after 12-myristate, 13-acetate phorbol ester stimulation (r=-0.27, n=104), and both alpha-GLUC activity and total output were inversely correlated with the concentration of peroxidase- positive white blood cells among samples with > or =1x10(6)/ml of these cells (r=-0.30 and -0.19, n=165). It is concluded that simple photometric measurement of alpha-GLUC activity in seminal plasma reflects the functional state of the epididymis and may be helpful for the differential diagnosis of certain cases with azoospermia.