Smoking, Alzheimer's disease, and confounding with genes.
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Alleles↗
Biomedical subjects
M J Helms
Publications and source records attributed to M J Helms.
Alzheimer's disease in the National Academy of Sciences-National Research Council Registry of Aging Twin Veterans. III. Detection of cases, longitudinal results, and observations on twin concordance.
OBJECTIVES: To detect cases of Alzheimer's disease (AD) in a large population of twins living throughout the United States and to examine concordance for AD in twins as a function of age and genotype for apolipoprotein E (APOE). SETTING: Nationwide survey. DESIGN: Multistage screening and field evaluation beginning with two telephone interviews and culminating with laboratory tests, longitudinal neuropsychological measures, physician examination, and diagnostic consensus among experts. PARTICIPANTS: Membership in 1990-1991 of intact pairs in the National Academy of Sciences--National Research Council Registry of veteran twins, then aged 62 to 73 years. MAIN OUTCOME MEASURES: Completeness of case detection was examined in collateral studies. Zygosity and APOE genotypes were determined by restriction mapping. Concordance was calculated by the proband method. RESULTS: Ninety subjects who screened positively for AD were studied in person, and 60 whose differential diagnoses included AD were followed up, as were their co-twins. Sensitivity of screening was estimated at greater than 99%, but 24% of subjects refused participation after initial screening. Seven of 38 diagnoses of AD have been confirmed at autopsy, and 31 other subjects eventually met criteria for probable or possible AD (prevalence estimate, 0.42%, 95% confidence interval, 0.29% to 0.56%), with good interrater reliability (intraclass r = .86). Excluding one discordant pair with unknown zygosity, concordance rates were 21.1% (4/19) for monozygotic and 11.1% (2/18) for dizygotic probands. Concordance was 50% for twins sharing the epsilon 4/epsilon 4 genotype at APOE, but there were no affected co-twins of 15 probands with onset before age 70 years, no epsilon 4 allele, and no family history of AD. The mean (SD) period of discordance in the latter pairs was 11.3 (3.3) years. CONCLUSIONS: The multistage case-detection approach achieved reliable and valid diagnoses of AD with high apparent sensitivity but substantial attrition after initial screening. Genetic influences in AD at this age are limited, except among homozygotes for allele epsilon 4 at APOE. Subjects with early-onset AD who lack the epsilon 4 allele are not rare, and their condition appears to have little genetic influence. They should be ideal for studies on environmental cause of AD.
Aged↗
Are vaginal and rectal pressures equivalent approximations of one another for the purpose of performing subtracted cystometry?
OBJECTIVE: To determine if rectal and vaginal pressures are clinically equivalent to one another for the purpose of calculating subtracted detrusor pressure during routine filling cystometry and pressure-flow voiding studies. METHODS: A total of 140 consecutive filling and voiding cystometrograms were performed at separate sessions on 127 female patients undergoing routine clinical cystometry for a variety of clinical indications, usually urinary incontinence. In all cases, intravaginal as well as intrarectal pressures were measured simultaneously using microtip transducer pressure catheters, and two subtracted detrusor pressures were calculated throughout each study. Rectal and vaginal pressure measurements from the same patient were compared with the patient in the supine position with an empty bladder, in the erect position with a full bladder, and in the sitting position during voiding at the point of maximum urinary flow. RESULTS: The mean pressures were similar in all cases. Although there was no statistical difference in the mean differences between the rectal and vaginal pressures in the supine-empty position (P = .5528), significant differences were noted between them in the erect-full and sitting-voiding positions (P = .0016 and P = .0033, respectively). Linear regression analysis of the data obtained in each position was carried out, plotting vaginal pressure on the x axis and rectal pressure on the y axis. The corresponding r values for each position were 0.431 for the supine-empty position, 0.547 for the erect-full position, and 0.478 for the sitting-voiding position, indicating poor correlation between pressures in individual patients. In nine patients (6.5%) with significant vaginal relaxation and large cystoceles, a steady rise in vaginal pressure was noted during bladder filling. In six patients (4.4%), one or more spontaneous vaginal contractions were noted during the course of the study, whereas in 68 (48.9%), spontaneous rectal contractions were present. Of the 68 cases where spontaneous rectal contractions were noted, these contractions faded away in 53 cases (77.9%) as the study progressed. CONCLUSIONS: Rectal pressure and vaginal pressure are not the same during filling and voiding cystometry. Although they are reasonable approximations of each other for most qualitative clinical diagnostic purposes, potentially significant differences in subtracted detrusor pressure may occur, depending on which pressure is used as the approximation of intra-abdominal pressure. This may affect clinical management decisions in individual patients. The technique used for approximating abdominal pressure must be stated clearly in any report or publication dealing with subtracted cystometry.
Adult↗
Inverse association of anti-inflammatory treatments and Alzheimer's disease: initial results of a co-twin control study.
We conducted a co-twin control study among 50 elderly twin pairs with onsets of Alzheimer's disease (AD) separated by 3 or more years. Twenty-three male pairs (46%) were screened from the (U.S.) National Academy of Sciences-National Research Council Registry (NAS-NRC Registry) of World War II veteran twins; others (mostly women) had responded to advertisements or were referred from AD clinics. Twenty-six pairs (52%) were monozygous. The onset of AD was inversely associated with prior use of corticosteroids or ACTH (odds ratio [OR], 0.25; 95% confidence interval [CI], 0.06 to 0.95; p = 0.04). Similar but weaker trends were present among pairs discordant for history of arthritis or for prior daily use of nonsteroidal anti-inflammatory drugs (NSAIDs) or aspirin. The association was strongest when we combined use of steroids/ACTH or NSAIDs post hoc into a single variable of anti-inflammatory drugs (AIs) (OR, 0.24; CI, 0.07 to 0.74; p = 0.01). The inverse relation was strong in female (volunteer) twin pairs but was not present in the younger men from the NAS-NRC Registry. AIs had typically been taken for arthritis or related conditions, but a similar result was apparent after controlling statistically for the arthritis variable (OR, 0.08; CI, 0.01 to 0.69; p = 0.02). AIs have been proposed as a means of retarding the progression of AD symptoms, and these data suggest that AIs may also prevent or delay the initial onset of AD symptoms. Because of limitations in the case-control method, our results require corroboration with hypothesis-driven research designed to control bias and confounding.
Age Factors↗
Normal values for single exhalation diffusing capacity and pulmonary capillary blood flow in sitting, supine positions, and during mild exercise.
Previous approaches to the measurements of pulmonary diffusing capacity (DL) and pulmonary capillary blood flow (QC) utilized either the rebreathing or the single inhalation technique in conjunction with radioisotope gas and mass spectrometry. In the present study, we utilized a newly developed rapid infrared analyzer in conjunction with the slow single exhalation technique on 100 healthy volunteers to establish normal values for DL and QC under sitting, supine, and exercise conditions. The exercise level was determined by a target heart rate: HRex = ([HRmax - HRrest]/3) + HRrest. Prediction equations based on regressions on age, sex, height, or weight were then computed for sitting, supine, and exercise values. We found that mean DL and QC increased by approximately 12 percent and 8 percent, respectively, from sitting to supine posture, and by approximately 30 percent and 100 percent, respectively, from sitting (rest) to mild exercise. These results provided a database for further studies in the single exhalation method in various clinical settings.
Acetylene↗
Dose response relationship between plasma ACTH and cortisol after the infusion of ACTH1-24.
The authors examined the dose response relationship between plasma ACTH and cortisol concentrations after the administration of various doses of ACTH1-24 (0.025 micrograms, 0.125 micrograms, 0.25 micrograms, 1 microgram, 250 micrograms) in dexamethasone-suppressed normal volunteers. A logarithmic dose-response relationship between the dose of ACTH administered and plasma cortisol concentration was found. Although there was considerable variability in plasma ACTH concentrations, there was, however, a definite correlation between area under the curve for ACTH and area under the curve for cortisol after the various doses of ACTH.
Adrenocorticotropic Hormone↗
Acute childbirth morbidity: its measurement using hospital charges.
OBJECTIVES: An analytic descriptive analysis of acute childbirth morbidity was carried out at Duke University Medical Center, comparing patients delivered by primary cesarean section with those delivered vaginally. STUDY DESIGN: All primary cesarean deliveries and vaginal deliveries from July 1, 1981, through June 30, 1986, were combined with maternal and infant charge data. A total of 7256 patients were analyzed. A description of the charges for the associated diagnoses was carried out. A morbidity index was used to identify differences in predicted median hospital charges with 95% confidence intervals. RESULTS: The ratio of mean primary cesarean delivery to mean vaginal delivery total charges was 2.5:1. The magnitude of the mean hospital charges was inversely related to the frequency of the indication with the lowest charges associated with dystocia and the highest with multiple pregnancy. Antepartum risk factors (increased maternal age, patient referral) were associated with increases in maternal and infant morbidity as measured by the morbidity index. Chronic maternal hypertension resulted in decreased maternal morbidity but increased infant morbidity when primary cesarean delivery was used. Although preterm delivery was associated with large increases in charges, it was not significantly altered by using primary cesarean delivery. Risk factors associated with the management of abnormalities of labor were associated with decreases in maternal and infant morbidity when primary cesarean delivery was used. CONCLUSION: Analysis of acute childbirth morbidity, as measured by hospital charges, showed marked variation of diagnosis and risk-specific charges for patients delivered by primary cesarean section.
Adult↗
Dysphagia following brain-stem stroke. Clinical correlates and outcome.
We studied 23 individuals (16 men, seven women; mean age 57 years) who had brainstem strokes confirmed by computed tomography of the head or magnetic resonance imaging. Videofluoroscopic modified barium-swallowing examination showed aspiration in 15 of 23 patients. Of the 15 aspirating patients, the majority had bilateral strokes with multiple lesion loci, most often in association with large-vessel disease. All 15 patients had involvement of the pons or medulla. Statistical analyses revealed a significant association between aspiration and pharyngeal residue observed under videofluoroscopy, cranial nerve IX abnormality, vocal fold weakness, and severe dysarthria. Despite initial severity, recovery was good. Following an aggressive program of aspiration prevention, over 80% of patients resumed full oral nutrition at the last follow-up.
Adult↗
Predictors of response to monoamine oxidase inhibitors: do they exist?
Multiple regression analysis was conducted on potential response predictors in a double-blind study of monoamine oxidase inhibitors (MAOI) and placebo treatment in 130 depressed outpatients. Positive main effects were found for sex (female), lack of prior hospitalization, presence of precipitating events. A negative main effect was found for concurrent physical illness. Treatment x predictor effects were found for distinct quality and non-reactivity. Non-reactivity was associated with positive outcome in the active drug group, but with negative outcome in the placebo group [corrected]. Distinct quality demonstrated a more complex effect, its presence being associated with decreased improvement in the treatment group and greater improvement in the control group. No atypical depressive symptoms predicted MAOI response, and we were unable to characterize a specifically responsive MAOI syndrome.
Adult↗
Performance of new criteria for right ventricular hypertrophy and myocardial infarction in patients with pulmonary hypertension due to cor pulmonale and mitral stenosis.
Historically, electrocardiographic criteria for right ventricular (RV) hypertrophy has achieved high specificity but low sensitivity. Recently, however, Butler-Leggett et al. have introduced three criteria that attained a 66% sensitivity in a population with RV hypertrophy due to mitral stenosis while maintaining a 95% specificity in an extensive normal control group. Electrocardiographic diagnosis of RV hypertrophy is principally dependent on changes in the QRS complex that may be masked or mimicked by myocardial infarction (MI). This dilemma has been confirmed by documentation of the low specificity of both the Selvester QRS scoring system for MI size estimation (greater than 3 points) and its screening subset (greater than 0 points) in a pure mitral stenosis population. This study introduces the population characterized by RV hypertrophy due to cor pulmonale, which has a mean pulmonary arterial systolic pressure that is higher than the mean for the mitral stenosis population and consequently suggests more severe RV hypertrophy. When compared, the Butler-Leggett criteria for RV hypertrophy are more sensitive in the new population than in the mitral stenosis population (89% versus 60%) and the Selvester QRS scoring system is less specific (12% versus 60%). Three sequential steps are suggested for electrocardiographic analysis: (1) diagnosis of RV hypertrophy using the Butler-Leggett criteria, (2) diagnosis of MI using the Selvester screening criteria in those patients with step 1 negative, and (3) estimation of MI size using the complete Selvester scoring system in patients with step 1 negative and step 2 positive.
Cardiomegaly↗
Extravascular extravasation of radiographic contrast media. Effects of conventional and low-osmolar agents in the rat thigh.
We compared the damage resulting from intradermal injection of four commonly used radiographic contrast media in laboratory rats. Sixty percent meglumine diatrizoate (Reno M 60) and ioxaglate (Hexabrix) produced significantly more ulceration and crusting on gross inspection and more necrosis, edema, and hemorrhage on histologic evaluation than iopamidol 300 (Isovue) or 0.9% (normal) saline. Thirty percent meglumine diatrizoate (Reno M Dip) had an intermediate toxicity, resulting in significantly more visible swelling and more microscopically detected hemorrhage than iopamidol or saline, but less ulceration/crusting and necrosis than Reno M 60 and ioxaglate. Since the three contrast agents of similar osmolality produced different degrees of tissue damage, our results suggest that factors other than high osmolality are partially responsible for determining the severity of injuries from extravasated contrast media.
Animals↗
Clinical characteristics useful in screening for renovascular disease.
In an effort to detect renovascular hypertension, clinical characteristics are used to select patients likely to have renal artery stenosis. We prospectively evaluated the ability of commonly used clinical features to predict the presence of renal artery stenosis in 100 hypertensive adults. All subjects had conventional renal arteriography. Renal artery stenosis was diagnosed if there was 50% or more stenosis of a main renal artery. Eighteen of the 100 had renal artery stenosis. The presence of a bruit was strongly associated with renal artery stenosis (P less than .0005). In patients without a bruit, only refractory hypertension was associated with the presence of renal artery stenosis (P = .051). These data suggest that a bruit and refractory hypertension are associated with renal artery stenosis, but that other clinical features investigated may not be and that other means of screening for renovascular disease are needed.
Adult↗
The effect of a telephone family assessment intervention on the functional health of patients with elevated family stress.
A randomized trial of a telephone family assessment intervention was conducted during a 2.5 month period on 224 ambulatory primary care patients, aged 18-49 years, who were selected according to self-report of elevated family stress levels. Family physicians conducted telephone interviews to collect information from patients on their supportive and stressful family members. The working hypothesis was that this process would lead to reduction in the patient's family stress and to improvement in family support and personal health status. Patients reported that the intervention caused them to think about their family support and helped them to feel better. Comparison of family factor and functional health scores before and after intervention also indicated a limited beneficial effect, but only for a small subset of black patients. These results suggest that the telephone family assessment alone is inadequate as an intervention and should be strengthened to include professional assistance to patients for the family problems that are identified by the assessment.
Adult↗
A health promotion program for medical students.
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Adult↗
Changing rates of cesarean delivery: the Duke experience, 1978-1986.
There was a steady increase in the yearly cesarean delivery rate, from 14.0 to 24.8%, between July 1, 1978 and June 30, 1986 at Duke University Medical Center; this was associated predominantly with an increase in the rate of primary cesarean deliveries. The three most frequent major diagnoses associated with primary cesarean delivery changed significantly over the study period. Fetal compromise became the most commonly associated diagnosis (from third), dystocia second (from first), and maternal disease third (from second). The categories of fetal positional abnormalities (fourth), abnormalities of placentation (fifth), and multiple pregnancy (sixth) did not change in rank. Primary cesarean delivery patients were compared with patients who delivered vaginally using odds ratios, prevalence, and population-attributable fractions. The risk factors of nulliparity, gestational age less than 37 weeks, late decelerations, and referral had the largest impact on the primary cesarean rate. Decreases in rates related to an increased tolerance of abnormalities of labor were overshadowed by the effects of increased concerns related to fetal health.
Academic Medical Centers↗
Early-onset Alzheimer's disease: clinical predictors of institutionalization and death.
Follow-up observations were made of 92 white patients with early-onset Alzheimer's disease to determine the demographic, clinical, and neuropsychological factors predictive of institutionalization or death. The cumulative mortality rate 5 years after entry into the study was 23.9%, compared with an expected rate of 9.5%. The 5-year cumulative rate of admission to nursing homes was 62.8%. The language ability of the patients on entry to the study, their scores on a brief screening test of cognitive function, and their overall ratings of clinical dementia were found to be predictors of subsequent institutional care and death. The age of the patients had a significant modifying effect on these predictive factors, resulting in a greater risk of institutionalization and death in younger patients with severe cognitive impairment as compared with older individuals with the same degree of dysfunction.
Aged↗
Alzheimer's disease: a study of epidemiological aspects.
A case-control study was performed to determine the possible roles of various environmental factors, prior illnesses, drug use, and personal habits in the development of Alzheimer's disease. Such information was collected from 40 patients with onset of dementia prior to age 70 and from 80 community control subjects matched for age, sex, and race. No significant differences were found between patients and control subjects in toxic environmental exposures, animal contacts, smoking, drinking, or unusual dietary habits. A significantly higher frequency of prior thyroid disease was found in women patients than in women control subjects (25.0% and 7.1%, respectively). A history of severe head injury was also obtained significantly more often among the patients than among the controls (15.0% and 3.8%, respectively). Aside from these differences, which may prove to be important associative factors in this illness, there appeared to be no major premorbid demographic or clinical factors associated with this form of dementia. There was evidence, however, of a genetic factor that was manifested in an excess of dementia and mental retardation (including Down's syndrome) in families of patients with Alzheimer's disease.
Alzheimer Disease↗
Normal sister chromatid exchange levels in hospital sterilization employees exposed to ethylene oxide.
This study was undertaken to determine whether a specific group of hospital workers exposed to ethylene oxide (ETO) in sterilizing areas showed evidence of increased levels of sister chromatid exchange (SCE) formation. SCE frequencies were determined for 14 sterilizer workers and 14 matched controls. Time-weighted average (TWA) and peak ambient levels of ETO were measured in the sterilizing areas. Results indicated that all sterilizer workers were exposed to less than 5 parts per million TWA of ETO and that there were no statistically significant differences in SCE levels between sterilizer workers and controls. Smoking habits did appear to be associated with increased SCE levels. In this particular hospital setting no evidence of genetic effects stemming from employees' exposure to low levels of ETO was found.
Adult↗