Kenneth P. Offord

Differential changes in bone mineral density of the appendicular and axial skeleton with aging: relationship to spinal osteoporosis.

Patterns of bone loss in the axial and the appendicular skeleton were studied in 185 normal volunteers (105 women and 82 men; age range, 20--89 yr) and in 76 women and 9 men with vertebral fractures due to osteoporosis. Bone mineral density was measured in vivo at the lumbar spine (predominantly trabecular bone) by dual photon absorptiometry and at the midradius (greater than 95% cortical bone) and distal radius (75% cortical and 25% trabecular bone) by single photon absorptiometry. In normal women, bone diminution from the vertebrae began in young adulthood and was linear. In the appendicular skeleton, bone diminution did not occur until age 50 yr, was accelerated from aged 51 to 65 yr, and then decelerated somewhat after age 65 yr. Overall bone diminution throughout life was 47% for the vertebrae, 30% for the midradius, and 39% for the distal radius. In normal men, vertebral and appendicular bone diminution with aging was minimal or insignificant. Mean bone mineral density was lower in patients with osteoporosis than in age- and sex-matched normal subjects at all three scanning sites, although spinal measurements discriminated best; however, there was considerable overlap. By age 65 yr, half of the normal women (and by age 85 yr, virtually all of them) had vertebral bone mineral density values below the 90th percentile of women with vertebral fractures and, thus, might be considered to have asymptomatic osteoporosis. For men, the degree of overlap was less. The data suggest that disproportionate loss of trabecular bone from the axial skeleton is a distinguishing characteristic of spinal osteoporosis.

Exposure to an Aeroallergen as a Possible Precipitating Factor in Respiratory Arrest in Young Patients with Asthma

BACKGROUND Exposure to airborne spores of the common mold Alternaria alternata has been implicated in asthma attacks. Such exposure is particularly frequent in the Midwest during the summer and fall months. To determine the role of A. alternata in triggering severe asthma attacks, we investigated the cases of 11 patients with asthma who had sudden respiratory arrest and determined the frequency of sensitivity to this allergen in these patients. METHODS The 11 patients (age range, 11 to 25 years) with initial episodes of respiratory arrest, which was fatal in 2 patients, were identified in the course of their care in our pediatric and adult clinical allergy practice and by a retrospective review of all Mayo Clinic records of patients with severe asthma cared for between 1980 and 1989. Skin-test reactivity to A. alternata and levels of IgE antibody against this mold in the 11 patients were compared with those in 99 matched controls with asthma who had no history of respiratory arrest. RESULTS All the patients came from the upper Midwest, and the episodes of respiratory arrest occurred in the summer or early fall. Ten of the 11 patients with asthma who had respiratory arrest (91 percent) had positive skin-puncture tests for sensitivity to alternaria, as compared with 31 percent of the controls (P less than 0.001), and the serum levels of IgE antibodies to alternaria were elevated in all 9 patients tested. Among the covariates we examined (age, sex, and distance from the Mayo Clinic), only age was a significant confounder. After adjustment for age, alternaria skin-test reactivity was found to be associated with an increase of approximately 200-fold in the risk of respiratory arrest (adjusted odds ratio, 189.5; 95 percent confidence interval, 6.5 to 5535.8). CONCLUSIONS Exposure to the aeroallergen A. alternata is a risk factor for respiratory arrest in children and young adults with asthma.

Mortality Following Inpatient Addictions Treatment: Role of Tobacco Use in a Community-Based Cohort

OBJECTIVE To determine the impact of tobacco- and alcohol-related deaths on overall mortality following inpatient treatment for alcoholism and other nonnicotine drugs of dependence. DESIGN Population-based retrospective cohort study. SETTING Olmsted County, Minnesota (the Rochester Epidemiology Project), and the Inpatient Addiction Program (IAP) at Mayo Clinic, Rochester. PATIENTS All 845 Olmsted County residents admitted to an inpatient addiction program for treatment of alcoholism and other nonnicotine drugs of dependence during the period 1972 through 1983. METHODS Patients were followed up through the medical record linkage system of the Rochester Epidemiology Project through December 1994 to obtain vital status, and death certificates were obtained for those who died. The underlying cause of death was classified as alcohol related, tobacco related, both, or neither based on the classification from the Centers for Disease Control and Prevention. The observed number of deaths by underlying cause were compared with the expected number using cause-specific 1987 death rates for the white population of the United States. All-cause mortality was also compared with that expected for persons in the West North Central Region of the United States of like age, sex, and year of birth. Univariate and multivariate assessments were made to identify predictors of all-cause mortality from baseline demographic information. RESULTS At admission, the mean (SD) age of the 845 patients was 41.4 (14.5) years, and 35% were women. Altogether, 78% had alcohol as their only nonnicotine drug of dependence and 18% had alcohol and other nonnicotine drugs of dependence, while 4% were classified as having a nonalcohol, nonnicotine drug dependence alone. At admission, 75% were current and 8% former cigarette smokers, 3% were current cigar or pipe smokers, and 2% were current users of smokeless tobacco. Follow-up after the index IAP admission totaled 8913 person-years (mean [SD] of 10.5 [5.6] years per patient). Death certificates were obtained for 96% (214) of the 222 patients who died. Of these 214 deaths, 50.9% (109) had a tobacco-related and 34.1% (73) had an alcohol-related underlying cause (P<.001). The cumulative mortality significantly exceeded that expected (P<.001); at 20 years, the observed mortality was 48.1% vs an expected 18.5%. Multivariate predictors of mortality, even after adjusting for expected mortality, were older age at admission (P<.001) and male sex (P<.001). CONCLUSIONS Patients previously treated for alcoholism and/or other nonnicotine drug dependence had an increased cumulative mortality that was due more to tobacco-related than to alcohol-related causes. Nicotine dependence treatment is imperative in such high-risk patients.

Five- to fifteen-year follow-up after Fontan operation.

BackgroundThe purpose of this study was to estimate survival and quality of outcome and assess factors associated with outcome for patients out 5 to 15 years from their Fontan operation. Methods and ResultsWe studied 352 patients who had the Fontan operation prior to 1985. The overall 1-, 5-, and 10-year survival was 77%, 70%, and 60%, respectively. The following factors were significantly associated with lower survival: univentricular heart or complex congenital anomalies other than tricuspid atresia, early calendar year of operation, heterotaxia syndromes, early age at operation, increased pulmonary artery pressure, atrioventricular valve dysfunction, and higher (worse) New York Heart Association class. Reoperations were necessary for 103 of the 352 patients. At least 20%, of the survivors have or have had cardiac arrhythmias requiring antiarrhythmic medication or mechanical pacemaker insertion. Between 7% and 10% of the patients have had or had protein-losing enteropathy/hypoproteinemia. At 5 years postoperatively, 122 patients (34.7%) were alive with a better New York Heart Association functional classification than preoperatively. Fifty-eight patients (16.5%) were alive and in the same functional classification, but 126 (35.8%) died within the first 5 years or were in a worse functional classification. Thirty-nine patients were doing excellently and 29 patients poorly 5 years after the operation. Of the surviving patients, 43% can do as much exercise as their peers, whereas 3% are incapable of exercise. ConclusionsTo assure good functional long-term outcome in addition to survival, clinicians must exclude from selection for Fontan operation patients known to be at high risk for death or poor outcome.

A Controlled Trial of Fish Oil in IgA Nephropathy

BACKGROUND The n-3 fatty acids in fish oil affect eicosanoid and cytokine production and therefore have the potential to alter renal hemodynamics and inflammation. The effects of fish oil could prevent immunologic renal injury in patients with IgA nephropathy. METHODS In a multicenter, placebo-controlled, randomized trial we tested the efficacy of fish oil in patients with IgA nephropathy who had persistent proteinuria. The daily dose of fish oil was 12 g; the placebo was a similar dose of olive oil. Serum creatinine concentrations, elevated in 68 percent of the patients at base line, and creatinine clearance were measured for two years. The primary end point was an increase of 50 percent or more in the serum creatinine concentration at the end of the study. RESULTS Fifty-five patients were assigned to receive fish oil, and 51 to receive placebo. According to Kaplan-Meier estimation, 3 patients (6 percent) in the fish-oil group and 14 (33 percent) in the placebo group had increases of 50 percent or more in their serum creatinine concentrations during treatment (P = 0.002). The annual median changes in the serum creatinine concentrations were 0.03 mg per deciliter (2.7 mumol per liter) in the fish-oil group and 0.14 mg per deciliter (12.4 mumol per liter) in the placebo group. Proteinuria was slightly reduced and hypertension was controlled to a comparable degree in both groups. The cumulative percentage of patients who died or had end-stage renal disease was 40 percent in the placebo group after four years and 10 percent in the fish-oil group (P = 0.006). No patient discontinued fish-oil treatment because of adverse effects. CONCLUSIONS In patients with IgA nephropathy, treatment with fish oil for two years retards the rate at which renal function is lost.

Morbidity and mortality in cirrhotic patients undergoing anesthesia and surgery.

Several studies have demonstrated increased morbidity and mortality in patients with cirrhosis undergoing anesthesia and surgery. Cirrhosis is a chronic liver disease, which may affect all body systems. The severity of the disease, assessed by the Child-Pugh classification, has a substantial effect on patient outcome. The extent of surgery and co-morbid conditions also have a major impact. In the past few years, changes have been made in the diagnosis, preoperative preparation, surgical and anesthetic management and perioperative care of patients with liver disease. The aim of this review is to examine whether these changes have resulted in improved perioperative outcomes.

Epidemiology of adult polycystic kidney disease, Olmsted county, Minnesota: 1935-1980

Between January 1, 1935 and December 31, 1980, adult polycystic kidney disease (APKD) was diagnosed in 40 residents of Olmsted County, Minnesota, resulting in an age- and sex-adjusted annual incidence rate of 1.38/100,000 person-years. In addition, 16 cases were detected at autopsy, increasing the rate to 2.06. It is estimated that 16 additional cases would have been discovered had all deaths come to autopsy, resulting in a rate of 2.75, or approximately twice the incidence rate of cases diagnosed during life. Because of improvements in medical care and diagnostic techniques, APKD has been diagnosed earlier and more frequently in the recent decades. This, along with therapeutic advances, explains the improvement in kidney and patient survival for the patients diagnosed during 1956-1980, as compared to those diagnosed during 1935-1955. Normotension at diagnosis tended to be associated with better kidney and/or patient survival. Cardiovascular disease was the leading cause of death.

Protein-losing enteropathy after the Fontan operation

Patients were observed after the Fontan operation to determine the frequency and severity of protein-losing enteropathy. A total of 427 patients who survived for 30 days after the Fontan operation, performed between 1973 and January 1987, were analyzed and, thus far, protein-losing enteropathy has developed in 47 of 427. The cumulative risk for the development of protein-losing enteropathy by 10 years was 13.4% among 30-day survivors, and 5-year survival after the diagnosis was 46%. Hemodynamic studies done coincident with the diagnosis of protein-losing enteropathy have shown increased systemic venous pressure, decreased cardiac index, increased pulmonary vascular resistance, and increased ventricular end-diastolic pressure. Medical management of protein-losing enteropathy was only partially successful. Statistical analysis has shown that factors related to protein-losing enteropathy were ventricular anatomy, increased preoperative ventricular end-diastolic pressure, longer operative bypass time, increased length of hospital stay, and postoperative renal failure. This study suggests that scrupulous selection of cases for the Fontan operation is mandatory and that certain perioperative factors may predispose to this serious complication of the Fontan procedure.

A Short Test of Mental Status: Description and Preliminary Results

A short test of mental status (encompassing about 5 minutes) was administered to 93 consecutive neurologic outpatients without dementia, 67 outpatients with Alzheimer-type dementia, and 20 outpatients with dementia of miscellaneous causes. The mean scores for patients with Alzheimer-type dementia were lower than those for the nondemented patients in the total scoring and on all subtests (P less than 0.001). When a total score of 29 or less (maximal attainable score, 38) was used as a screen for dementia, a sensitivity of 92% and a specificity of 91% were reached. For patients older than 60 years of age, a score of 29 or less resulted in a sensitivity of 95% and a specificity of 88%. Thus, in general, this easily administered test distinguishes demented from nondemented patients, but it should not be used as the sole means of diagnosing dementia.

Regional anesthesia and local anesthetic-induced systemic toxicity: seizure frequency and accompanying cardiovascular changes.

We sought to determine the contemporary frequency of seizures, and the associated cardiovascular changes, resulting from local anesthetic-induced seizures in all patients undergoing brachial plexus, epidural, and caudal regional anesthetics. We investigated the following variables: development and treatment of seizure or cardiac arrest during the regional anesthetic, type of anesthetic (including local anesthetic used), gender, age, ASA physical status class and type of operation (elective or emergent). In addition, each patient who experienced a seizure underwent retrospective review of the acute event to determine the arterial blood pressure and heart rate changes accompanying the seizure, as well as details of the regional block technique. There was a significant difference between the rate of seizure development between epidural, brachia, and caudal anesthetics, with caudal > brachial > epidural. A significant difference was also noted in the rate of seizure development within types of brachial block, with supraclavicular and interscalene > axillary. No adverse cardiovascular, pulmonary or nervous system events were associated with any of the seizures, including the 16 patients who received bupivacaine blocks. The frequency of local anesthetic-induced seizures stratified by block type has a wide range, and cardiovascular collapse after bupivacaine-associated seizure has a low incidence. (Anesth Analg 1995;81:321-8)