Left ventricular mass, carotid wall thickness, and angiotensinogen gene polymorphism in patients with hypertension.

A missense gene mutation with methione-to-threonine amino acid substitution at codon 235 (M235T) of angiotensinogen (AGT) has been associated with higher plasma AGT levels and may influence the pathogenesis of cardiac hypertrophy and atherosclerosis. This study was undertaken to investigate the relationship of the M235T polymorphism of the AGT gene with left ventricular mass (LVM) and carotid intima-media thickness (IMT) in 175 Chinese patients with hypertension. The M235T mutation was detected by a mispairing primer method to create a BstUI restriction site in the polymerase chain reaction. The LVM was calculated with M-mode echocardiographic measures of the left ventricle. The IMT was measured in the common carotid and carotid bifurcation by B-mode ultrasound. Patients with the TT genotype (n = 106) were found to have significantly greater LVM index than those with the MM (n = 32) and MT (n = 37) genotypes (129.2 +/- 34.3 v 112.5 +/- 38.3 and 107.4 +/- 30.0 g/m2, P = .002), but the carotid IMT showed insignificant differences among three genotypic groups (1.320 +/- 0.703, 1.349 +/- 0.777, and 1.309 +/- 0.797 mm, P = .97). The M235T polymorphism (P = .004) was a significant predictor for LVM on multiple regression analysis, controlling all the potential confounding factors including age (P = .04), gender (P = .000), body mass index (P = .000), and so on, but the carotid IMT correlated only with age (P = .000), smoking (P = .02), and tissue plasminogen activator antigen (P = .02). These results indicated that the TT genotype of the AGT gene could be considered a risk factor for the development of cardiac hypertrophy, but not for carotid atherosclerosis in the hypertensive population.     

Phenytoin-Induced Pseudolymphoma: Reevaluation Using Modern Molecular Biology Techniques

Summary: Patients receiving phenytoin (PHT) may develop pseudolymphoma or, rarely, malignant lymphoma. Previously, distinguishing the two diseases based solely on histopathology has been difficult. The recent introduction of molecular biological techniques has provided a powerful tool to reassess this problem. A 17-year-old girl developed systemic lymphadenopathy after receiving PHT for 1 year for generalized tonic-clonic seizures (GTCS). Biopsy of a cervical lymph node showed diffuse proliferation of large lymphoid cells mimicking a large cell lymphoma. Immunophenotypic, immunoglobulin gene rearrangement, and cytogenetic studies, however, showed polyclonal B-cell proliferation, consistent with PHT-induced pseudolymphoma. After PHT discontinuation, lymphadenopathy resolved in 1 month and no recurrence developed in the subsequent 10 months. Obtaining a history of drug use is crucial to recognizing this group of patients. Molecular biology and chromosome studies have become the definitive basis differentiating pseudolymphoma from malignant lymphoma in patients receiving chronic PHT therapy.     

Quantitative trait locus mapping of human blood pressure to a genetic region at or near the lipoprotein lipase gene locus on chromosome 8p22.

Resistance to insulin-mediated glucose disposal is a common finding in patients with non-insulin-dependent diabetes mellitus (NIDDM), as well as in nondiabetic individuals with hypertension. In an effort to identify the generic loci responsible for variations in blood pressure in individuals at increased risk of insulin resistance, we studied the distribution of blood pressure in 48 Taiwanese families with NIDDM and conducted quantitative sib-pair linkage analysis with candidate loci for insulin resistance, lipid metabolism, and blood pressure control. We found no evidence for linkage of the angiotensin converting enzyme locus on chromosome 17, nor the angiotensinogen and renin loci on chromosome 1, with either systolic or diastolic blood pressures. In contrast, we obtained significant evidence for linkage or systolic blood pressure, but not diastolic blood pressure, to a genetic region at or near the lipoprotein lipase (LPL) locus on the short arm of chromosome 8 (P = 0.002, n = 125 sib-pairs, for the haplotype generated from two simple sequence repeat markers within the LPL gene). Further strengthening this linkage observation, two flanking marker loci for LPL locus, D8S261 (9 cM telomeric to LPL locus) and D8S282 (3 cM centromeric to LPL locus), also showed evidence for linkage with systolic blood pressure (P = 0.02 and 0.0002 for D8S261 and D8S282, respectively). Two additional centromeric markers (D8S133, 5 cM from LPL locus, and NEFL, 11 cM from LPL locus) yielded significant P values of 0.01 and 0.001, respectively. Allelic variation around the LPL gene locus accounted for as much as 52-73% of the total interindividual variation in systolic blood pressure levels in this data set. Thus, we have identified a genetic locus at or near the LPL gene locus which contributes to the variation of systolic blood pressure levels in nondiabetic family members at high risk for insulin resistance and NIDDM.     

Lysosomal enzyme activity in human aqueous humor.

Activity of the lysosomal enzymes N-acetyl-beta-D-hexosaminidase, alpha-D-mannosidase, beta-D-glucuronidase, and beta-D-galactosidase was detected in aqueous humor from eyes undergoing intraocular surgery. There was no correlation between lysosomal enzyme activity and age. Lysosomal enzyme activity in human released by ocular tissues surrounding the anterior chamber including the cornea, trabecular meshwork, ciliary body, iris, and lens. Their release into aqueous humor may have a role in regulating aqueous outflow in normal and glaucomatous eyes.     

NIDDM病人胰岛素进入单核细胞能力的改变

本研究测定了NIDDM病人(n=6)和正常人(n=7)循环血中单核细胞(Mo)结合~(125)I-胰岛素总能力、胰岛素-受体复合物进入能力、胰岛素降解能力和趋溶酶体制剂氯喹对受体后过程的影响。结果显示NIDDM时Mo对胰岛素的结合能力、进入能力和降解能力均明显低于正常人。这些改变可能与NIDDM胰岛素抵抗性有关。     

Clinical observations and virological study of aseptic meningitis in the Kaohsiung area

During 1988, an endemic outbreak of aseptic meningitis was noted in the Kaohsiung area. Throughout the year, a total of 89 cases were identified by cerebrospinal fluid (CSF) examination at the Pediatric Department of Kaohsiung Medical College. The peak incidence was from June to October. Scattered cases still occurred during November and December. The male to female ratio was 1.7:1 and the age distribution ranged from 1 month to 15 years old. Two peaks of age distribution were observed; one in infancy and the other in the 4-7 year old age group. Most of them exhibited fever (94.4%), headache (68.9%), and vomiting (68.5%). Other associated symptoms and signs included neck stiffness, sore throat, cough, Brudzinski's sign, abdominal pain, seizure, dizziness, rhinorrhea, diarrhea, Kernig's sign, skin rash, hyperemic conjunctiva, apnea, and oral ulcers. Most of them had CSF white blood cell (WBC) counts less than 1000/mm3, normal or mild elevated protein, and normal CSF/plasma sugar ratio. Three patients were found to have a virus in their CSF without pleocytosis. Virus isolations from CSF throat swabs and/or rectal swabs were performed in 65 patients, half of them (35/65, 53.8%) had positive results including echovirus type 9 (sixteen), echovirus type 30 (eighteen), and adenovirus type 3 (one). Echovirus type 9 was predominant during July and August whereas echovirus type 30 became predominant after September. All patients recovered spontaneously without any sequelae.     

The evaluation of percutaneous central venous catheters —a convenient technique in pediatric patients

Objective To evaluate the feasibility and effectiveness of 3 different types of silastic catheters that were used for percutaneous central venous catheterization (PCVC) through peripheral veins.Design and setting The study was prospective and consecutive for 6 years at a pediatric/neonatal intensive care unit and pediatric ward in Veterans General Hospital-Taipei, a university-affiliated medical center, in Taiwan, ROC.Participants and interventions The patients who had PCVC were consecutively enrolled from January 1988 to December 1993. Three types of silastic catheters were used. The classification was according to the caliber as small catheter (SC, 0.30 mm ID), mid-size catheter (MC, 0.51 mm ID) and large catheter (LC, 0.64 mm ID). The same insertion technique, catheter-through-needle, was used for all PCVC placements through the peripheral vein. After insertion, each catheter was connected to a conventional short cannula (24-, 22-, or 20-gauge) of compatible caliber, and then linked to the infusion system.Results 1318 PCVCs were used in 1126 consecutive patients, that included 754 SCs in 649 infants (among them 60.9% were less than 1500 g), 383 MCs in 319 toddlers, and 181 LCs in 158 children. Mean (SD) body weight at the time of catheter insertion was SC 1.7(0.9) kg, MC 12.1(6.5) kg and LC 19.3(7.6) kg. Overall, mean (SD) duration of these PCVC was 16.4(8.4) days. A significantly longer duration was noted in: (a) SC group with 19.7(10.4) days than the other two groups [MC 12.4(6.5) days, LC 11.2(5.0) days]; (b) patients with body weight equal to or less than 3.0 kg [18.7(8.6) versus 14.1(6.1)]; and (c) insertion sites other than external jugular vein (EJV) [18.8(9.7) versus 11.7(6.0)]. These PCVCs provided reliable venous access for multiple purposes such as hyperalimentation, venous access or sampling of blood, antibiotic therapy and chemotherapy. MC and LC were also used for monitoring the central venous pressure. Most of the time, SC and MC were inserted through the superficial peripheral vein of the scalp, neck and extremities, while LC was almost approached via the EJV. The overall success rate of insertion was 92.4% (1318/1427). No significant difference was observed among the different catheter groups [93.4% (754/807) in SC, 90.5% (383/423) in MC and 91.9% (181/197) in LC] and the different insertion sites. Within each group of PCVC, more than eighty percent of catheters were removed electively: 83.3% in SC, 89.6% in MC and 84.5% in LC. Probable catheter-related sepsis accounted for 2.7% (36/1, 318) of all PCVCs. With this study, the cost of each PCVC set is 3.0 US dollars.Conclusion This study indicates that the use of three different calibers of silastic catheter is feasible and effective for PCVC in pediatric practice.     

Mechanism of action of the phorbol ester tumor promoters: Specific receptors for lipophilic ligands

Cells and tissue preparations specifically bind the phorbol ester tumor promoters. The agreement in structure-activity relationships between binding and biological response strongly argues that these binding sites function as phorbol ester receptors. Upon subcellular fractionation, the phorbol ester binding activity is particulate. In addition, a phorbol ester apo-receptor can be detected in cytosol which requires phospholipids for reconstitution. This apo-receptor appears to correspond to protein kinase C. Diacylglycerols, the probable natural activators of protein kinase C, competitively inhibit phorbol ester binding, consistent with their being the postulated endogenous phorbol ester analogs. In certain systems, heterogeneity of phorbol ester binding is found. An outstanding issue therefore is whether protein kinase C is the phorbol ester receptor or whether it is only the most abundant class of receptor. Although this question remains unresolved, we can demonstrate heterogeneity of phorbol ester binding by reconstitution of apo-receptor into a heterogeneous lipid environment.