Risk factors for sudden unexpected cardiac death in young women in Rochester, Minnesota, 1960 through 1974

A case-control study of sudden unexpected death (SUD) as the initial manifestation of coronary heart disease in women younger than 60 years of age was conducted in Rochester, Minnesota. Risk factors among the 15 SUD cases identified during the years 1960 through 1974 were compared with those in two control groups--a population group of 60 (4 age-matched controls per case) and the 59 cases of myocardial infarction diagnosed in women younger than 60 years of age in Rochester during the same period. By using Miettinen's matched analysis for comparison of SUD cases and matched controls, the relative risks for the accepted coronary heart disease risk factors of ever smoking and hypertension were 8.6 (95% confidence interval [CI], 1.3 to 57.3) and 5.7 (95% CI, 1.2 to 26.9), respectively. In a comparison of SUD cases and myocardial infarction cases by using the Mantel-Haenszel procedure and stratifying by five age groups, the odds ratios were 1.2 for ever smoking and 0.8 for hypertension. Six of the 15 SUD cases had a diagnosis of alcoholism compared with 2 of the 60 controls and 4 of the 59 myocardial infarction cases; thus, the relative risks were 12.0 (95% CI, 3.4 to 41.9) and 4.8 (95% CI, 1.3 to 18.2), respectively. Ever married SUD cases were nulliparous or had fewer children more often than the controls or the myocardial infarction cases. The combination of major psychiatric diagnosis and major tranquilizer use occurred with greater frequency among SUD cases than among controls (relative risk, 2.9; 95% CI, 0.6 to 14.1), whereas comparison of SUD cases and myocardial infarction cases for this variable resulted in a relative risk of 0.7 (95% CI, 0.3 to 1.9).     

海马区星形胶质细胞培养上清液体外诱导人脂肪基质细胞向神经元样细胞的分化

目的:观察海马区星形胶质细胞培养上清液能否在体外诱导人脂肪基质细胞向神经元样细胞分化。方法:实验于2004-10/2005-06在华北煤炭医学院中心实验室完成。在无菌条件下从Wistar乳鼠分离出海马组织,从分离的海马组织中获得星形胶质细胞,并收集其培养上清液。取外科手术获得的人腹部皮下脂肪组织进行人脂肪基质细胞的原代培养。30例患者均知情同意。取第3代人脂肪基质细胞接种到培养孔中,预先放置无菌盖玻片的24孔培养板,制备细胞爬片或者接种到培养瓶中,细胞生长达50%～60%融合时,去除培养液,换为海马区星形胶质细胞培养上清诱导液进行诱导,对照组培养液为无血清培养基。倒置相差显微镜下连续观察细胞生长情况和形态变化,应用免疫细胞化学、鉴定神经前体细胞的特异性标志神经巢蛋白、神经细胞的特异性标志神经元特异性烯醇化酶、微管联合蛋白2和神经胶质细胞的特异性标志胶质纤维酸性蛋白的表达。结果:①诱导培养第3天,部分人脂肪基质细胞开始变形,从原先的细长梭状细胞变成神经元样细胞,可见细胞伸出突起,多为双极或多极细胞。②刚分离接种的人脂肪基质细胞镜下呈圆形,悬浮状态,接种后24h内贴壁,并开始伸展,多呈梭形。1周后细胞融合成单层,排列出现方向性,但有少量圆形及卵圆形细胞混杂生长。③第4,5代人脂肪基质细胞在诱导48h后形态即开始发生变化,扁平的胞体较预诱导后逐渐回缩,向外伸出突起,72h后扁平的胞浆向胞核收缩,突起继续延长,以后随时间进展,具有典型神经细胞形态特点的细胞数量逐渐增多,形成双极或多极细胞。④免疫细胞化学检测人脂肪基质细胞诱导5d后发现有(10.5±3.7)%神经巢蛋白、(38.4±5.2)%胶质纤维酸性蛋白、(15.7±2.3)%神经元特异性烯醇化酶表达,未见微管联合蛋白2的表达。结论:海马区星形胶质细胞培养上清液可以在体外诱导人脂肪基质细胞向神经元样细胞方向分化。     

Epinephrine is a Hypophosphatemic Hormone in Man. PHYSIOLOGICAL EFFECTS OF CIRCULATING EPINEPHRINE ON PLASMA CALCIUM, MAGNESIUM, PHOSPHORUS, PARATHYROID HORMONE, AND CALCITONIN

The physiologic effects of epinephrine on mineral metabolism are not known. In six healthy men, insulin-induced hypoglycemia, a potent stimulus to endogenous epinephrine secretion, resulted in a decrement of 0.9+/-0.1 mg/dl (mean+/-SE, P < 0.001) in serum inorganic phosphorus and smaller increments in magnesium and total and ionized calcium. Plasma immunoreactive parathyroid hormone (iPTH) decreased and plasma immunoreactive calcitonin (iCT) increased appropriately with the increments in calcium and magnesium. We wished to determine to what extent these changes in mineral metabolism might be attributable to epinephrine. Therefore, in the same protocol, we infused the hormone over 60 min in these six men, in doses that resulted in steady-state plasma epinephrine concentrations ranging from 52 to 945 pg/ml (levels that span the physiologic range), for a total of 25 studies. Serum ionized calcium, iPTH, and iCT concentrations were unaltered by these physiologic elevations of plasma epinephrine. However, epinephrine resulted in dose-dependent decrements in serum inorganic phosphorus of 0.6+/-0.1 mg/dl (P < 0.005) for the highest epinephrine infusion rate. The plasma epinephrine concentration threshold for this hypophosphatemic effect was approximately 50-100 pg/ml. Thus, the sensitivity of the hypophosphatemic response to epinephrine is comparable to that of the cardiac chronotropic, systolic pressor, and lipolytic responses to epinephrine, and considerably greater than that of the diastolic depressor, glycogenolytic, glycolytic, and ketogenic responses to the hormone in human beings. In view of its rapidity, the hypophosphatemic effect of epinephrine is probably the result of a net shift of phosphate from the extracellular compartment to intracellular compartments. We suggest that it is a direct effect of epinephrine, in that it is not mediated by changes in availability of the primary regulatory hormones PTH and CT, although indirect effects mediated by changes in other hormones, such as insulin, cannot be excluded. The hypophosphatemic response is also not attributable to increments in plasma calcium. These data indicate that epinephrine in physiologic concentrations is a hypophosphatemic hormone in man.     

Physiologic and plasma hormone correlates of survival in endotoxic dogs: effects of opiate antagonists

Two groups of awake dogs were given an iv bolus of endotoxin (3.0 mg/kg from Salmonella typhimurium); one group (n = 9) was pretreated with either naloxone (2.0 mg/kg iv bolus with 1.7 mg/kg.h; n = 6) or naltrexone (2.0 mg/kg iv bolus with repeat bolus of 1.0 mg/kg at 1, 3 and 5 h; n = 3) and the second group (n = 10) received no opiate antagonist. All of nine dogs that were pretreated with an antagonist survived for 24 h, compared to only five of ten dogs that were not pretreated. Survival correlated with improved BP (mean of 91 vs. 61 mm Hg) and cardiac output (3.9 vs. 2.45 L/min) measured during the first 3 h after the infliction of shock. However, both antagonist-treated and nonantagonist-treated survivors had BP and cardiac output which were statistically lower than their baseline values or saline-treated controls at comparable times. Nonsurvivors had significantly higher levels of norepinephrine (peak level: 1149 ng/ml) and epinephrine (peak level: 31.29 ng/ml) than survivors. Opiate antagonists thus appeared to increase survival in a subgroup of dogs that might not otherwise have survived if they had not been so treated; this survival was associated with improved hemodynamics, but not with increased adrenergic activity.     

Benign positional vertigo: incidence and prognosis in a population-based study in Olmsted County, Minnesota

A retrospective review of our population-based medical records linkage system for residents of Olmsted County, Minnesota, revealed 53 patients (34 women and 19 men; mean age, 51 years) with newly diagnosed benign positional vertigo in 1984. The age- and sex-adjusted incidence was 64 per 100,000 population per year (95% confidence interval, 46 to 81 per 100,000). The incidence of benign positional vertigo increased by 38% with each decade of life (95% confidence interval, 23 to 54%). One patient had an initial stroke during follow-up; thus, the relative risk for new stroke associated with benign positional vertigo was 1.62 (95% confidence interval, 0.04 to 8.98) in comparison with the expected occurrence based on incidence rates for an age- and sex-adjusted control population. The observed survival among the 53 Olmsted County residents with benign positional vertigo diagnosed in 1984 was not significantly different from that of an age- and sex-matched general population. Patients with benign positional vertigo seem to have a good prognosis.     

Optimism-pessimism assessed in the 1960s and self-reported health status 30 years later

OBJECTIVE: To study the association between explanatory style, using scores from the Optimism-Pessimism (PSM) scale of the Minnesota Multiphasic Personality Inventory (MMPI), and self-reported health status, using scores from the 36-Item Short-Form Health Survey (SF-36). PATIENTS AND METHODS: A total of 447 patients who completed the MMPI between 1962 and 1965 as self-referred general medical outpatients and also completed the SF-36 thirty years later compose the current study sample. The associations between the scores on the SF-36 and the MMPI PSM scale were evaluated by analysis of variance and linear regression analysis. RESULTS: Of 447 patients, 101 were classified as optimistic, 272 as mixed, and 74 as pessimistic. Scores on all 8 health concept domains from the SF-36 were significantly poorer in the pessimistic group than in both the optimistic and the mixed group. CONCLUSION: A pessimistic explanatory style, reflected by higher PSM scale scores, was significantly associated with a self-report of poorer physical and mental functioning on the SF-36 30 years later.     

Quality-of-care assessment. II. Outpatient medical care following hospital dismissal after myocardial infarction.

This study was undertaken to compare process and outcome methods of quality assessment of medical care in outpatient office practice. Follow-up care after hospitalization for first acute myocardial infarction was used as the model. One hundred fifty-two patients followed up for a minimum of 2 years comprised the study group. An expert committee of cardiologists and internists in community practice established the process criteria for satisfactory care and predicted outcomes of continuing disability and mortality. Using weighted process criteria and a weighted performance index permitted demonstration of a significant association between process items performed at the first posthospitalization visit and 2-year mortality. A significant association could not be demonstrated between later process of care and outcome at 2 years. The outcome assessment study disclosed that predicted disability and mortality rates compared closely with observed outcomes. However, this method for evaluating the quality of outpatient medical care is weakened because little information is available to provide the basis of prediction of satisfactory outcome rates in complicated cases. Although both the process and outcome methods of quality assessment have short comings, the latter method is recommended because satisfactory outcomes is the essential criterion of quality medical care. Moreover, when process items are not specified outcome assessment maintains the flexibility of individual physician practice. Refinement of satisfactory outcome prediction for common illnesses managed in office practice should be the goal for future studies.     

Nicotine-replacement therapy with use of a transdermal nicotine patch--a randomized double-blind placebo-controlled trial

The rate of smoking was significantly reduced in volunteer subjects by providing effective nicotine replacement, self-help material, and weekly visits with a nurse for 6 weeks. Nicotine-replacement therapy with a transdermal nicotine patch (Nicolan) almost doubled the 6-week smoking-cessation rate in comparison with that in a placebo group (77% versus 39%; P = 0.002) among subjects who were smoking at least 20 cigarettes per day at baseline. Although most subjects who used the active nicotine patches had skin reactions, the reactions were primarily mild. For use of both active and placebo patches, the level of patient compliance was high. Among subjects who continued to smoke, the use of cigarettes was decreased to less than 50% of the baseline smoking level in 7 of 7 with active nicotine patches and in 15 of 19 with placebo patches. Outcomes beyond 6 weeks showed a substantial relapse rate in both groups. Thus, when nicotine-replacement therapy is provided, a need exists for concurrent behavioral intervention and training for prevention of a relapse, neither of which was part of this protocol.     

Child well-being in single-mother families.

OBJECTIVES: Children from single-mother families are at increased risk of psychosocial morbidity. This article examines the strength of association between single-mother family status and child outcome, both alone and controlling for other sociodemographic and personal (maternal/family) variables. METHOD: Data from the Canadian National Longitudinal Survey of Children and Youth Cycle 1 (1994-1995) were used. Children aged 6 to 11 years in single-mother and two-parent families were included (n = 9,398). Child functioning measures included social impairment, psychiatric problems, and math score. RESULTS: Single-mother family status on its own is a significant predictor of all child difficulties, but the explained variance is limited and the effect size decreases when other variables known to influence child functioning are included. Household income, a sociodemographic variable, is inversely associated with social impairment and positively associated with math score. Hostile parenting and maternal depression are the personal variables most strongly associated with social impairment and psychiatric problems. Children in single-mother families where there is hostile parenting are at significantly increased risk of psychiatric problems. CONCLUSIONS: The results suggest that children from single-mother families develop difficulties for the same reasons as children from two-parent families. Specific interventions for single-mother families may be warranted in the areas of parenting and other areas of concentrated risk.     

Use of a water-soluble busulfan formulation--pharmacokinetic studies in a canine model

In a canine model we investigated the toxicity and pharmacokinetics of a water soluble busulfan preparation. Busulfan was dissolved in dimethylsulfoxide (DMSO) and administered either orally or intravenously in a single dose of 1 mg/kg. The application in either preparation was well tolerated. In seven dogs, peak levels in the range of 730 ng/mL to 1,000 ng/mL were measured after intravenous injection with an area under curve (AUC) of 75 ng.h/kg.mL to 146 ng.h/kg.mL. It was of note that even the oral administration of the same busulfan preparation resulted in AUC values in the same range as observed after parenteral application. The absorption rate of busulfan tablets in our model was as unpredictable as documented in clinical trials. On the basis of the present study, clinical trials using busulfan dissolved in DMSO given either intravenously or orally appear warranted. This approach should lead to predictable blood levels, reduced toxicity, and increased efficacy of busulfan-containing regimens.