The karyotype of a child with severe mental retardation, microcephaly, minor facial anomalies, and urinary tract outflow obstruction was found to be 46,XY,13q+mat. Trypsin-Giemsa banding studies showed an inherited translocation, t(4q−;13q+), in several asymptomatic members of the family including the propositus9 mother. This indicates that the propositus had partial trisomy for the distal one-third of the long arm of chromosome 4. Review of the literature suggests that urinary tract and genital anomalies may be a consistent feature of this partial trisomy.
Clinical trials demonstrate significant benefit from cholesterol management for patients with cardiovascular disease (CVD). National guidelines recommending goals for screening and treatment were published in 1993 and widely disseminated. This study examines cholesterol screening and management by primary care physicians after the guidelines were released.
Methods
Medical records and patient surveys provided data for 603 patients with CVD, aged 27 to 70 years, from 45 practices in 4 states during 1993 to 1995. Physician surveys measured estimated performance and other variables. Physician and patient factors associated with adherence, or lack of adherence, to national guidelines were examined using univariate and multivariate analyses.
Results
A total of 199 patients (33%) with CVD were not screened with lipid panels, 271 patients (45%) were not receiving dietary counseling, and 404 (67%) were not receiving cholesterol medication. Only 84 patients (14%) with CVD had achieved the recommended low-density lipoprotein level of less than 2.58 mmol/L (100 mg/dL) and 302 (50%) had triglyceride levels lower than 2.26 mmol/L (200 mg/dL). Patients with a revascularization history and higher low-density lipoprotein and/or triglyceride levels were more likely to receive treatment, but other patient factors, including CVD risk factors, did not predict treatment. Physician specialty was not associated with differences in treatment, but physicians in practice for fewer years ordered more lipid panels.
Conclusions
Most patients with CVD in primary care were not receiving cholesterol screening and management as recommended by the National Cholesterol Education Program guidelines in the 2 years after their release. Increasing cholesterol screening and treatment should be a priority for practice quality improvement and could result in significant reductions in CVD events for high-risk patients.
Combination therapy to improve the total lipid profile may achieve greater coronary risk reductions than lowering low-density lipoprotein cholesterol (LDL-C) alone. A new extended-release niacin (niacin ER)/lovastatin tablet substantially lowers LDL-C, triglyceride, and lipoprotein(a) levels and raises high-density lipoprotein cholesterol (HDL-C) level. We evaluated these serum lipid responses to niacin ER/lovastatin at all clinically reasonable doses.
Methods
Men (n = 85) and women (n = 79) with type IIa or IIb primary hyperlipidemia after diet were randomized among 5 parallel treatment arms. Each arm had 5 sequential 4-week treatment periods: niacin ER (starting at 500 mg/d, increasing in 500-mg increments to 2500 mg/d); lovastatin (starting at 10 mg, increasing to 20 mg, then 40 mg/d); and 3 combinations arms, each with a constant lovastatin dose and escalating niacin ER doses.
Results
For primary comparisons, mean LDL-C level reductions from baseline were greater with niacin ER/lovastatin (1500/20 mg) than with lovastatin (20 mg) (35% vs 22%,P<.001) and with niacin ER/lovastatin (2000/40 mg) than with lovastatin (40 mg) (46% vs 24%,P<.001). Each 500-mg increase in niacin ER, on average, decreased LDL-C levels an additional 4% and increased HDL-C levels 8%. The maximum recommended dose (2000/40 mg/d) increased HDL-C levels 29% and decreased LDL-C levels 46%, triglyceride levels 38%, and lipoprotein(a) levels 14%. All lipid responses were dose dependent and generally additive. Graphs of the dose-response relationships as 3-dimensional surfaces documented the strength and consistency of these responses.
Conclusions
Niacin ER/lovastatin combination therapy substantially improves 4 major lipoprotein levels associated with atherosclerotic disease. Dose-response surfaces provide a practical guide for dose selection.
Remarkable progress in adapting specific chromosomal and biochemical tests to amniotic fluid samples has allowed intrauterine diagnosis for an increasing number of inherited conditions. However, the lack of any specific tests for autosomal dominant diseases, especially those affecting the nervous system and muscle, has precluded such prenatal evaluation in genetic counseling. Genetic linkage offers a potentially useful alternative approach to such diseases. The gene for a particular disorder must be closely linked to a genetic marker which can be analyzed in amniotic fluid or cells obtained in the second trimester of pregnancy. We have recently applied linkage studies to the prediction of myotonic dystrophy (Dm) during pregnancy. Dm is known to be closely linked to the secretor locus (Se) , which determines the secretion of ABH blood-group substances into saliva and other body fluids, including the amniotic fluid of the fetus. Only certain families will be suitable for this analysis: the affected parent must have thesecretor-positive phenotype and be heterozygous (Se/se) at the secretor locus; the coupling of the Dm allele to the Se or se allele must be determined; and the spouse must be either secretor-negative or heterozygous secretor-positive. Secretor genotypes can be inferred from secretor phenotypes of close relatives, including the fetus at risk. Unfortunately, these criteria will be satisfied in only 5-10 percent of couples at risk to transmit myotonic dystrophy. In suitable couples, however, linkage analysis can be quite helpful.
In 875 predominantly white (89%), postmenopausal women, aged 45–-65 years, enrolled in the Postmenopausal Estrogen/Progestin Interventions Trial, univariate analysis showed that mean total cholesterol, low-density lipoprotein cholesterol (LDL-C), apolipoprotein B, and triglyceride (TG) levels were positively associated with age (p < 0.01) across 5-year age groups, whereas high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I did not vary by age. HDL-C levels were positively associated with leisure time exercise level (p < 0.01), income (p < 0.01), alcohol intake (p < 0.01), and education level (p < 0.05). Current smokers have lower HDL-C levels than former smokers and those who never smoked (p < 0.01). TG levels were negatively associated with leisure time exercise (p < 0.01) and education (p < 0.01), and higher TG levels occurred in current smokers compared with former smokers and those who never smoked (p < 0.05). LDL-C showed no significant associations with these lifestyle variables. Increased adiposity, as determined by body mass index (BMI) or in body fat distribution as defined by waist/hip ratio (WHR), was significantly negatively associated with HDL-C levels and positively associated with total cholesterol, LDL-C, and TG. Multivariate models showed that 27% of the variance of log triglyceride was explained by WHR, BMI, and smoking, and 31% of the variance of HDL-C was explained by these factors plus alcohol and leisure time exercise.
From 2,874 school children participating in the 1971 and 1973 Muscatine Coronary Risk Factor Survey, we selected three groups of index cases for detailed family study: the HIGH group (n = 56), with cholesterol levels greater than the 95th percentile twice; the MIDDLE group (n = 46), cholesterol levels between the 5th and 95th percentile; and the LOW group (n = 46), cholesterol levels less than the 5th percentile twice. Coronary mortality determined from death certificates was increased in the young relatives (ages 30-59) of the HIGH group index cases, as follows: twofold excess in HIGH male relatives compared with the MIDDLE or LOW group (p less than 0.05); tenfold excess in the HIGH female relatives compared with the MIDDLE and LOW group combined (p less than 0.01). After correction for years at risk, there was an approximately twofold significantly-increased coronary mortality. Stroke mortality was higher, although not significantly, in the older relatives (ages greater than or equal to 60) of the HIGH index cases. Cancer mortality was not significantly different among the relatives of the three groups of index cases. This study indicates that school children's cholesterol levels cluster with those of their family members and that persistent hypercholesterolemia in children identifies families at risk for coronary artery disease.
Prenatal prediction of the inheritance of myotonic dystrophy in a family with affected individuals feasible in special cases when analysis of linkage to the secretor gene (determing ABH substances) can be carried out. We report a large kindred having multiple members affected with variable degrees of severity of myotonic dystrophy and having several matings for which linkage analysis is feasible. Even though this approach is not applicable for most families and although the process of genetic recombination complicates the analysis, in individual cases the use of linkage in prenatal or postnatal prediction of myotonic dystrophy may be very helpful for early diagnosis, more precise genetic counseling, and family planning.
