Different mechanisms account for extracellular-signal regulated kinase activation in distinct brain regions following global ischemia and reperfusion.

Oxidative stress after cerebral ischemia and reperfusion activates extracellular signal-regulated kinases (ERK) in brain. However, the mechanism of this activation has not been elucidated. We have previously reported that in an in vitro model of oxidative stress in immature cortical neuronal cultures, the inhibition of ERK phosphatase activity contributes to ERK1/2 activation and subsequent neuronal toxicity. This study examined whether ERK activation was associated with altered activity of ERK phosphatases in a rat cardiac arrest model. Rats in experimental groups were subjected to asphyxial cardiac arrest for 8 min and then resuscitated for 30 min. Significant ERK activation was detected in both cortex and hippocampus following ischemia/reperfusion by immunoblotting. ERK phosphatase activity was reversibly inhibited in cerebral cortex but not affected in hippocampus following ischemia/reperfusion. MEK1/2 was activated in both cerebral cortex and hippocampus following ischemia/reperfusion. Using a specific inhibitor of protein phosphatase 2A (PP2A), okadaic acid (OA), we have identified PP2A to be the major ERK phosphatase that is responsible for regulating ERK activation in ischemic brain tissues. Orthovanadate inhibited ERK phosphatase activity in brain tissues, suggesting that tyrosine phosphatases and dual specificity phosphatases may also contribute to the ERK phosphatase activity in brain tissues. Together, these data implicate ERK phosphatase in the regulation of ERK activation in distinct brain regions following global ischemia.

Bupropion for weight loss: an investigation of efficacy and tolerability in overweight and obese women.

OBJECTIVE: On the basis of the clinical observations that bupropion facilitated weight loss, we investigated the efficacy and tolerability of this drug in overweight and obese adult women. RESEARCH METHODS AND PROCEDURES: A total of 50 overweight and obese (body mass index: 28.0 to 52.6 kg/m(2)) women were included. The core component of the study was a randomized, double-blind, placebo-controlled comparison for 8 weeks. Bupropion or placebo was started at 100 mg/d with gradual dose increase to a maximum of 200 mg twice daily. All subjects were prescribed a 1600 kcal/d balanced diet and compliance was monitored with food diaries. Responders continued the same treatment in a double-blind manner for an additional 16 weeks to a total of 24 weeks. There was additional single-blind follow-up treatment for a total of 2 years. RESULTS: Subjects receiving bupropion achieved greater mean weight loss (last-observation-carried-forward analysis) over the first 8 weeks of the study (p = 0.0001): 4.9% +/- 3.4% (n = 25) for bupropion treatment compared with 1.3% +/- 2.4% (n = 25) for placebo treatment. For those who completed the 8 weeks, the comparison was 6.2% +/- 3.1% (n = 18) vs. 1.6% +/- 2.9% (n = 13), respectively(p = 0.0002), with 12 of 18 of the bupropion subjects (67%) losing over 5% of baseline body weight compared with 2 of 13 in the placebo group (15%; p = 0.0094). In the continuation phase, 14 bupropion responders who completed 24 weeks achieved weight loss of 12.9% +/- 5.6% with fat accounting for 73.5% +/- 3.7% of the weight lost and no change in bone mineral density as assessed by DXA. Bupropion was generally well-tolerated in this sample. DISCUSSION: Bupropion was more effective than placebo in achieving weight loss at 8 weeks in overweight and obese adult women in this preliminary study. Initial responders to bupropion benefited further in the continuation phase.

Caregiver and elder experiences of Cambodian, Vietnamese, Soviet Jewish, and Ukrainian refugees.

Our purpose was to describe and compare Cambodian, Vietnamese, Soviet Jewish, and Ukrainian refugee caregivers and elders on life experiences, health status, and knowledge of available services. Detailed interviews were conducted with 105 female caregivers and 52 elders. Similar patterns emerged across all groups with regard to filial obligation, minimal knowledge of services, impact of immigration, and retention of cultural ties. Findings confirmed the special health and social service needs of refugee families in transition.

Randomized trial of sertraline in patients with unexplained chest pain of noncardiac origin.

BACKGROUND: Between 10% and 30% of patients with symptoms similar to angina and sufficient to justify cardiac catheterization are found to have normal coronary angiograms. Treatment of patients with chest pain with no apparent cardiac cause is a major clinical problem. Our hypothesis was that sertraline would reduce the severity of pain in patients with chest pain of noncardiac origin. METHODS AND RESULTS: This was a single-site, double-blind, placebo-controlled study of the efficacy, tolerability, and safety of sertraline in the treatment of noncardiac chest pain in outpatients. Thirty patients were enrolled in the study. After 1 week of single-blind placebo washout, patients were randomly assigned in a double-blind fashion either to drug or placebo. The Beck Depression Inventory was administered at baseline and at completion of study. Daily pain diaries (visual analogue scale, rating pain on a scale of 1 to 10) were selfadministered and evaluated at baseline and at follow-up visits. Statistical measures were performed with an intention-to-treat approach. Patients who received sertraline over the course of the study showed a statistically significant reduction in pain compared with those who were receiving placebo. CONCLUSIONS: The use of sertraline in patients with noncardiac chest pain produced clinically significant reduction of daily pain. These results suggest the need for further studies of the efficacy and tolerability of sertraline and other selective serotonin reuptake inhibitors in the long-term management of noncardiac chest pain.

Obesity management in primary care: assessment of readiness to change among 284 family practice patients.

BACKGROUND: Most adults in primary care are overweight or obese; two thirds of patients with weight problems have other obesity-related conditions. The study objective was to explore the feasibility of a primary care obesity intervention based on the transtheoretical model (TM) of behavior change and principles of chronic disease (CD) care. METHODS: A prospective study of the initial version of the TM-CD intervention with obese family practice patients (n = 284) yielded cross-sectional data on baseline stage of change for six target behaviors: dietary fat, portion control, vegetable intake, fruit intake, usual physical activity, and planned exercise. The sample consisted of obese patients scheduled for an office visit during times when recruitment and informed consent did not conflict with acute care. RESULTS: Obese patients volunteering for a TM-CD program are in different stages of change for six target behaviors. Preparation was the most frequently reported stage for increased exercise (49%) or activity (34%), decreased dietary fat consumption (44%), and increased portion control (51%). Patients in a particular stage for one behavior were distributed across all five stages for another behavior. Stage of change for five target behaviors was associated with body mass index or waist girth (P < .05) in a manner consistent with stage-of-change theory. CONCLUSIONS: Using the transtheoretical model of behavior change will allow physicians to recognize when obese patients are receptive to specific behavioral interventions.

Quantitative assessment with SPECT imaging of stress injuries of the pars interarticularis and response to bracing.

The evaluation and management of acute spondylolysis remains unclear in part because of outcome data that are primarily subjective. The aim of this study was to evaluate and monitor these patients objectively using quantitative single-photon emission computed tomography (SPECT). Thirty-four patients were so observed clinically between 1987 and 1996 and were studied with an initial and at least one follow-up SPECT scintigram. Initial radiographs and planar bone scans failed to demonstrate the pars lesion in 53 and 19% of the patients, respectively. The average SPECT ratio before brace treatment was 1.45. After treatment, this ratio significantly decreased to 1.27 (p = 0.03). A subset of patients remained symptomatic at follow-up. Their reduction in SPECT ratio averaged only 2.8% as compared with 13% for the remainder of the patients (p = 0.01). Patients diagnosed and braced in the early, more active stage of the condition (with greater intensity on SPECT) had more predictable symptom relief. An initial SPECT ratio of >1.5 was associated with complete symptom resolution after brace treatment. Patients treated with activity restriction only (>3 months) before bracing were more likely to have persistent symptoms and more modest improvement on SPECT (p = 0.01). These data, which use SPECT scintigraphy, support prompt treatment with brace immobilization for acute spondylolysis in children and adolescents.

Suicide precautions in a medical/surgical unit.

A suicide precautions policy and procedure program designed specifically for patients in a medical/surgical unit provides a protected environment and allows for a timely psychiatric evaluation. General principles of crisis intervention guided this suicide policy.

Presentation and management of childhood psychosocial problems.

BACKGROUND: Between 15% and 25% of children who visit primary care physicians have emotional, behavioral, or psychiatric problems that affect their functioning. The majority of these children are treated by primary care physicians. The purpose of this study was to examine the presentation and treatment of children's psychosocial problems in primary care and to investigate ways in which physician management of a problem is related to parent-physician agreement that the problem exists. METHODS: Twenty-six physicians at an ambulatory care center of a community-based, university-affiliated family medicine training program collected data during outpatient visits of 898 children aged 2 to 16 years. The physicians used a checklist to collect data on children's developmental problems, parents' concerns about the psychosocial functioning of their children, whether physicians and parents were in agreement about these concerns, and the parents' influence on physicians' management of the problems. RESULTS: Family physicians and parents agreed that 10% of the children were experiencing psychosocial problems. For 5% of children, physicians recorded emotional or behavioral concerns when parents did not disclose any such concerns. For only 1.8% of children, parents raised psychosocial concerns while physicians did not. Physicians diagnosed and managed psychosocial concerns during both acute-care and well-child visits. When parents and physicians agreed on the presence of pediatric psychosocial problems, referral to a mental health professional was more likely than when they disagreed (60% vs 16%). CONCLUSIONS: Pediatric psychosocial concerns are raised by parents during acute-care and well-child visits. Family physicians identified and managed these problems at rates consistent with past research. Management strategies appeared to differ as a function of agreement between physicians and parents on whether a problem existed.

Dermatitis complicating saphenous nerve injury after arthroscopic debridement of a medial meniscal cyst.

We report the case of a patient who developed hypesthesia in the distribution of the saphenous nerve after an arthroscopic debridement of a medial meniscal cyst. Dermatitis developed in the area of the hypesthesia 3 months later, Both complications responded to symptomatic treatment. A review of the literature confirms the unusual nature of these complications.

Identification of obesity: waistlines or weight? Nutrition, Exercise, and Obesity Research Group.

BACKGROUND: Obesity can be divided into "general" and "central." Since abnormal glucose and lipid metabolism are more strongly associated with central obesity, it may not be adequate to use a general measure, such as a weight-for-height index, to assess for obesity. An index of central obesity, such as the waist-to-hip ratio, might be more appropriate. METHODS: Nurses measured height and weight for the body mass index (BMI = kilograms of mass divided by the square of the height in meters) and girths for the waist-to-hip ratio (WHR) in 414 patients aged 45 years and over. Patients completed an obesity-related questionnaire. RESULTS: Fifty-seven percent of patients had an elevated BMI. Fifty percent of men (95% confidence interval [CI], 46 to 55) and 78% of women (95% CI, 75 to 80) had central obesity based on elevated WHRs. Using an elevated WHR as the standard for central obesity, elevated WHR as the standard for central obesity, elevated BMI had a positive predictive value of only 64% and a negative predictive value of 68% in men. For women, the corresponding positive and negative predictive values were 84% and 31%, respectively. CONCLUSIONS: The data indicate that the practice of using only scales to identify "overweight" patients should be reevaluated since doing so will miss patients at risk. In primary care patients, particularly those 50 years of age and over, weight-for-height indices such as the BMI result in underdiagnosis of central obesity.

Do we practice what we preach? Comparing the patients of faculty and residents.

BACKGROUND AND OBJECTIVES: In academic family practice centers, the distribution of patients between faculty and residents influences the educational milieu. The medical literature has rarely addressed the differential case mix within the ambulatory medical educational setting. The goal of this study was to compare the characteristics of patient visits to resident and faculty physicians in seven community-based, university-affiliated family practice programs. METHODS: Using the National Ambulatory Care Survey instrument and protocol, 98 faculty and resident physicians recorded their ambulatory patient visits for one randomly selected week between July 1991 and June 1992 (n = 1,498). RESULTS: Patients of resident physicians were younger, more likely to be nonwhite (21.7% vs 9.8%, P < .001), and more likely to be reimbursed by Medicaid (34.2% vs 14.3%, P < .001) than patients of faculty physicians. Despite these patient differences, the spectrum of clinical problems was similar. There were minimal differences in the delivery of diagnostic services and therapeutic services. CONCLUSIONS: The patients seen by residents and faculty differ in important demographic characteristics. These differences could adversely affect the education of resident physicians. Academic family practice centers should actively monitor the age/gender/payment profile of resident and faculty patient panels and assign patients to achieve a desirable case mix for resident education. The differential racial distribution of faculty and resident visits suggests an unidentified systematic bias in patient assignment that warrants further investigation.

The relationship among the transtheoretical model of behavioral change, psychological distress, and diet attitudes in obesity: Implications for primary care intervention.

Obesity is prevalent but undertreated in primary care. Family practice volunteer outpatients (N=454) were administered the Stage of Change for Weight (URICA), the Brief Symptom Inventory (BSI), and the Diet Readiness Test (DRT) to assess the relationship between these variables and obesity. The body mass index (BMI) was used to classify obesity revealing 197 patients with elevated BMI's. There was no significant difference between the obese and the nonobese on any of the psychological measures. The obese reported significantly more difficulty setting diet goals and less control over their eating, ate more to emotional situations, and exercised less than the nonobese. The obese sample (46.7%) reported being in the Action stage of change for weight management. Implications for intervention in primary care include targeting attitudes (DRT) and dispelling physician attitudes that obese individuals have increased levels of psychological distress. Addressing Stage of Change for weight management can facilitate tailoring the appropriate intervention when used in concert with the DRT variables.

Does family practice at residency teaching sites reflect community practice?

BACKGROUND: Family medicine has aspired to train residents and conduct research in settings that closely resemble community practice. The purpose of this study was to compare the patient characteristics of the ambulatory teaching centers of a consortium of seven community-based university-affiliated family practice residency programs in northeast Ohio with the National Ambulatory Medical Care Survey (NAMCS) results for family physicians (FPs) and general practitioners (GPs). METHODS: Ninety-eight faculty and resident physicians at the residency training site of the Northeastern Ohio Universities College of Medicine collected data on all ambulatory patient visits (N = 1498) for one randomly chosen week between July 1, 1991, and June 30, 1992. We compared these data with patient visits reported in the 1990 NAMCS for FPs and GPs. RESULTS: The residency training sites saw slightly more children, women, blacks, and Medicare and Medicaid patients. The most common reason for an office visit in both populations was an undifferentiated symptom. Fifteen of the top 20 "reason for visit" codes were identical, as were 14 of the top 20 diagnoses. More preventive and therapeutic services were offered or performed at our residency training sites but fewer diagnostic services were performed. There were fewer consultations requested at our residency training sites but similar hospitalization rates for patients. The mean duration of visit differed by only 1 minute. CONCLUSIONS: The residency training sites of the Northeastern Ohio Universities College of Medicine provide patient care opportunities similar to those found in a national survey of family and general practitioners.

Antigenic stimulation and multiple myeloma. A prospective study.

BACKGROUND: A causal relationship between antigenic conditions and multiple myeloma was suggested by case reports. Although controlled studies identified associations with individual conditions, they failed to give overall support to the hypothesis. Using a prospective cohort representative of the U.S. population, the authors hypothesized that immune-stimulating conditions are a risk factor for multiple myeloma. METHODS: The First National Health and Nutrition Examination Survey cohort of 14,407 persons were interviewed from 1971 to 1975 by the National Center for Health Statistics. Vital status with cause of death and hospitalizations were ascertained from 1982 to 1985 and in 1986. From the initial questionnaire, four risk factors were constructed: allergies (asthma, hives, hay fever, food allergies, and other allergies); autoimmune conditions (arthritis, thyroid disease and/or medication, rheumatic fever, diabetes, pernicious anemia); chronic bacterial conditions (chronic bronchitis or emphysema, chronic cough, tuberculosis, ulcers); and inflammatory conditions (gout, gallstones, recurrent or chronic enteritis, pleurisy). RESULTS: Eighteen multiple myeloma (MM) cases were documented. The rate ratio (RR) of MM increased as the number of reported inflammatory conditions increased (one condition, RR = 2.0, 95% confidence interval [CI] = 1.2-3.3; 2 or more conditions, RR = 4.3, 95% CI = 1.5-12.4). The RR of myeloma also increased (P = 0.0002) with time since start of inflammatory conditions (RR = 1.6 for every 10 years of exposure). When cases were restricted to those with more than five years of follow-up, myeloma risk increased with the number of inflammatory conditions (two conditions, RR = 4.6, 95% CI = 1.5-13.8). CONCLUSIONS: Although the number of cases is small and exposure may be misclassified, the prospective nature of the study design strengthens the results of the study.

Recognition and management of obesity in a family practice setting.

BACKGROUND: Research on the diagnosis and management of obesity in primary care is limited. Our study goals were to describe the rate of obesity in a primary care setting, to identify factors associated with clinically recognized obesity, and to ascertain the level of diet and exercise counseling for obesity. METHODS: Medical records from a private group practice were used for a historical cohort study of 276 patients (aged 40 years and older) who were provided care for a maximum 4.5-year follow-up period. RESULTS: Forty-six percent of the study patients (95 percent confidence interval = 0.43, 0.49) received an obesity diagnosis according to medical record notations. The diagnosis of obesity, in turn, was predicted by body mass index (BMI) quartile (P < 0.001) and a positive family history of cardiovascular disease (P < 0.01). Those patients with a diagnosis of obesity had a higher mean level of subsequent weight and diet counseling (P = 0.0001) but the same level (P = 0.11) of exercise counseling as nonobese patients. Weight and diet counseling was also predicted by diabetes (P = 0.0001) and hypercholesterolemia (P = 0.0003). CONCLUSIONS: The clinical recognition of obesity was not determined by BMI alone. Although weight and diet counseling was initiated for those individuals described as obese, there was a relatively low level of exercise counseling among these patients. Additional research could provide ways of reducing both physician and patient barriers to exercise counseling.

Elapsed time from symptom onset and acute myocardial infarction in a community hospital.

STUDY OBJECTIVE: Previous reports have emphasized that thrombolytic therapy for acute myocardial infarction should be initiated within three or four hours of symptom onset to obtain the best clinical outcomes. However, our clinical impression was that late arrivers, who often do not receive thrombolytic therapy, have a good short-term prognosis. Therefore, we investigated the relationships among the elapsed time from symptom onset, thrombolytic therapy, and short-term prognosis in acute myocardial infarction patients. The research hypothesis was that late arrivers have a better in-hospital prognosis because they have less severe disease that may involve spontaneous thrombolysis. DESIGN: Observational cohort study based on reviewing medical records and emergency department service logs. SETTING: 500-bed teaching hospital with medical school affiliation in northeastern Ohio. TYPE OF PARTICIPANTS: Four hundred consecutive patients with acute infarction confirmed by chest pain and positive ECGs or elevated cardiac enzymes. MEASUREMENTS AND MAIN RESULTS: Patients arriving early (elapsed time less than or equal to 1.5 hours) were more likely to be in Killip class III or IV (P = .04) or to have hypotension (P = .0004); and they experienced twofold increased odds of ventricular tachycardia (P = .007), cardiac arrest (P = .03), or death (P = .01). Patients arriving late (elapsed time greater than 3.5 hours) were more likely to have a history of angina (P = .002) and had a better short-term prognosis. CONCLUSIONS: Time of ED arrival after onset of acute myocardial infarction symptoms distinguishes two patient groups that differ in their risk of in-hospital complications. Late arrivers have better short-term prognoses and less (acutely) severe disease, and may have less need for thrombolytic therapy because of possible spontaneous thrombolysis. Patients with prior angina may need education on seeking care if their symptoms change.

Variation in heart disease mortality across census tracts as a function of overdispersion and social class mixture.

Variation in heart disease (HD) mortality rates across census tracts is greater than expected given binomial error and available explanatory variables. We extended an extra-binomial variation model for rates standardized by the direct method. The overdispersion parameter accounted for 36 per cent of the observed variation in standardized rates. Ignoring overdispersion resulted in a change in an estimate of the effect of social class on HD mortality and substantial underestimation of the error of the estimates of such effects. Ecologic regression on the proportional mixture of social classes within tracts provided an appealing approach to the problem of estimating fixed effects with aggregated data.

Hyperacute T-wave criteria using computer ECG analysis.

Hyperacute T waves (HATWs) have been described as tall-amplitude, primary T-wave abnormalities sometimes seen in the early phases of transmural myocardial infarction. Despite numerous human and animal studies addressing the presence and significance of HATWs, there are no widely held, reliable ECG criteria for their accurate identification. Using a specially designed computer program on a Hewlett-Packard Realm ECG analysis system, we screened 13,393 adult ECGs to identify those having T-wave amplitudes greater than accepted standards (limb leads, greater than 0.5 mV; precordial leads, greater than 1.0 mV). Patients with other known causes of primary and secondary tall T waves were excluded from the study sample. Patients with tall-amplitude T-waves who then developed clinically verifiable myocardial infarction were labeled the HATW group. The HATW group (21) represented 4.1% of the tall T wave group (513) and 0.16% of the entire sample. The remaining patients, who did not meet HATW criteria, were called the early repolarization variant (ERV) group (51). Both groups underwent comparative computer morphology analysis. Nine parameters were statistically significant in discriminating HATWs from early repolarization variants. A combination of J-point position/T-wave amplitude of more than 25%, T-wave amplitude/QRS amplitude of more than 75%, J-point position of more than 0.30 mV, and age of more than 45 years predicted HATWs from a control group with a specificity of 98.0% and a sensitivity of 61.9% and with positive and negative predictive values of 92.9% and 86.2%, respectively. We conclude that HATWs have characterizable discriminating ECG morphology as determined by computer ECG analysis compared with a control group.

Modeling heart disease mortality with census tract rates and social class mixtures.

The relationship between social class and 1980 heart disease (HD) mortality in eight urban U.S. counties was examined by regressing age and sex adjusted census tract specific HD rates (N = 1211) on tract social class characteristics. The regression model indicated that lower middle class residents experienced a HD mortality rate 1.9 (95% CI = 1.3, 2.8) times the rate in the upper middle/middle class, while the working poor experienced a HD rate 4.4 (95% CI = 3.5, 5.7) times the rate in the referent class. Similar class effects were seen for both black and nonblack residents. The crude race effect (1.3 with 95% CI = 1.2, 1.4) was explainable by the concentration of blacks in the lower classes. The methods illustrate the ecologic regression of mixtures of mortality rates on mixtures of exposure in the presence of random tract effects which eliminates some of the problems associated with small denominators or zero rates in some tracts.