Evaluation of subtilisin cleavage specificity for RNase A peptide bonds by high-performance liquid chromatography and mass spectrometric analysis.
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Biomedical subjects
Publications and source records attributed to J V Johnson.
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BACKGROUND: Organic nitrates are widely used in the treatment of chronic heart failure (CHF). No information, however, is available regarding their effect in patients already treated with ACE inhibitors. METHODS AND RESULTS: In a randomized, double-blind, crossover design, we studied the effects of high-dose (50 to 100 mg) transdermal nitroglycerin (NTG) and placebo given daily for 12 hours in 29 patients with CHF (NYHA functional classes II to III). Exercise time (4 hours after patch application) showed a progressive improvement during NTG administration, with an increase of 38+/-35 seconds (9+/-7%) at the end of the first month (P=NS), 76+/-28 seconds (16+/-6%) at the end of the second month (P=0.01), and 117+/-34 seconds (27+/-6%) at the end of the third month (P=0.003). No significant change was seen during placebo administration (12+/-20, 5+/-26, and 19+/-28 seconds, all P=NS). Exercise time 8 hours after NTG application measured at 3 months was also significantly longer, with a difference of 87+/-28 seconds (P=0.006), but not with placebo (23+/-36 seconds, P=0.53). Assessment of quality of life and need for additional diuretics or hospitalizations for CHF failed to demonstrate a significant difference between the 2 treatment periods. In contrast, NTG decreased left ventricular end-diastolic (-2.1+/-0.1%, P<0.05) and end-systolic (-3.2+/-1.3%, P<0.05) dimensions and augmented LV fractional shortening (24.7+/-10.5%, P<0.03). The effect of placebo on these parameters was not statistically significant. CONCLUSION: High-dose nitrate therapy significantly improves exercise tolerance and left ventricular size and systolic function in patients with chronic, mild to moderate CHF already treated with ACE inhibitors. These findings support the role of organic nitrates as an adjunctive therapy to ACE inhibitors in patients with chronic CHF.
OBJECTIVES: The purpose of this study was to identify factors associated with acute low back injury among municipal employees of a large city. METHODS: For each of 200 injured case patients, 2 coworker controls were randomly selected, the first matched on gender, job, and department and the second matched on gender and job classification. In-person interviews were conducted to collect data on demographics, work history, work characteristics, work injuries, back pain, psychosocial and work organization, health behaviors, and anthropometric and ergonomic factors related to the job. Psychosocial work organization variables were examined with factor analysis techniques; an aggregate value for job strain was entered into the final model. Risk factors were examined via multivariate logistic regression techniques. RESULTS: High job strain was the most important factor affecting back injury (odds ratio [OR] = 2.12, 95% confidence interval [CI] = 1.28, 3.52), and it showed a significant dose-response effect. Body mass index (OR = 1.54, 95% CI = 1.08, 2.18) and a work movement index (twisting, extended reaching, and stooping) (OR = 1.42, 95% CI = 0.97, 2.08) were also significant factors. CONCLUSIONS: Results suggest that increasing workers' control over their jobs reduces levels of job strain. Ergonomic strategies and worksite health promotion may help reduce other risk factors.
An 11-year-old boy was evaluated for a maxillary lesion that had been increasing in size over a six-month period. Intraoral examination revealed a firm ulcerated lesion on the maxillary posterior alveolus, which was displacing teeth. The lesion was painful and easily bled during mastication. An incisional biopsy of the lesion resulted in the diagnosis of peripheral giant cell granuloma. The patient was taken to the operating room for excision of the lesion and extraction of involved teeth. The patient was followed for a period of six months with no recurrence.
Measures of family stability, sociocultural background, and emotional ties to parents in medical students (N = 589, mean age = 22 years) predicted their social support measures, assessed 23 to 39 years later (mean age = 56 years). Father's education and family's involvement in church were positively associated with group participation (number of group memberships), whereas parental loss between the ages of 11 and 20 was negatively associated with group participation; perceived emotional closeness to parents was positively associated with social closeness (number of close contacts providing emotional and instrumental support). Thus, group participation and social closeness were influenced by distinctly different childhood factors.
OBJECTIVES: The combination of high psychological job demands and low decision latitude (high job strain) has been associated with an increased risk of coronary heart disease. It has been proposed that this may also be the case for low social support at work. The aim of this study was to analyse the relations between these psychosocial factors and incidence of myocardial infarction. METHODS: Associations between psychosocial work characteristics and incidence of myocardial infarction was investigated through a population based case-control study. The study base comprised employed men and women in five Swedish counties during the years 1976-84. Cases of first myocardial infarction were identified from hospital discharge registers and death records from outside hospital, controls were selected through a random sample, and psychosocial work environment was assessed through a job exposure matrix on the basis of the occupation in the 1970 and 1975 censuses. RESULTS: An increased incidence of myocardial infarction was found for men and women in occupations characterised by low decision latitude. For men this increase was seen primarily in combination with high psychological demands (high job strain) and low social support at work. Younger men (30-54 years of age) in occupations with both high job strain and low social support at work had a relative risk of 1.79 (95% confidence interval (95% CI) 1.22 to 2.65) compared with subjects in low strain and high social support jobs after controlling for age, county of residence, and socioeconomic group. CONCLUSIONS: Our results indicate that jobs characterised by low decision latitude, high job strain, or low social support at work may be associated with an increased risk of acute myocardial infarction. If these associations are causal they may be of substantial importance from the point of view of workers' health.
OBJECTIVES: This study examined the role of decision latitude and job strain in the etiology of a first myocardial infarction. METHODS: Eligible case patients were all full-time working men 45 to 64 years of age who suffered a first myocardial infarction during the period January 1992 to January 1993 in the greater Stockholm region. Referents were selected from the general population. Participation rates were 82% (case patients) and 75% (referents). RESULTS: Both inferred and self-reported low decision latitude were associated with increased risk of a first myocardial infarction, although this association was weakened after adjustment for social class. A decrease in inferred decision latitude during the 10 years preceding the myocardial infarction was associated with increased risk after all adjustments, including chest pain and social class. The combination of high self-reported demands and low self-reported decision latitude was an independent predictor of risk after all adjustments. CONCLUSIONS: Both negative change in inferred decision latitude and self-reported job strain are important risk indicators in men less than 55 years of age and in blue-collar workers.
We assessed the relation between symptoms and cardiac arrhythmias in 110 consecutive pregnant patients without evidence of heart disease referred for evaluation of palpitations, dizziness, and syncope (study group) and in 52 consecutive patients referred for evaluation of an asymptomatic functional precordial murmur (control group). Both groups had a high incidence of arrhythmias on Holter monitoring with atrial premature complexes (APCs) of 56% in the study group and 58% in the control group, > 100 APCs in 7% and 4% of the patients, respectively, and isolated ventricular premature complexes (VPCs) in 59% and 50%, respectively. The number of isolated VPCs was higher and > 50 VPCs/hour were seen in more patients in the study group (3,235 +/- 6,397 vs 678 +/- 3,358 beats/24 hours p < 0.05 and 22% vs 2% p = 0.03). Similarly, the incidence of multifocal VPCs was higher in the study patients (12% vs 2%, p < 0.05). There was no correlation between the incidence of both VPCs or APCs and symptoms, and only 10% of symptomatic episodes were accompanied by the presence of arrhythmias. Repeated Holter monitoring 6 weeks postpartum in 9 women with multiple premature contractions during pregnancy (9,073 +/- 9,210/24 hours) showed a substantial reduction to 1,345 +/- 1,997/24 hours (p < 0.05). Thus, this study confirms an increased incidence of arrhythmias during normal pregnancy. These arrhythmias consist mostly of APCs and VPCs. The number of simple and multifocal VPCs is higher in patients presenting with symptoms of palpitations, dizziness, or syncope; however, there is no correlation between the incidence of arrhythmias and symptoms, and only 10% of symptomatic episodes were accompanied by the presence of arrhythmias.
PURPOSE: This article shows the usefulness of the mandibular symphysis as a source of bone graft for the reconstruction of the orbital floor. PATIENTS AND METHODS: A retrospective study was conducted on 16 patients who had isolated blowout fractures (n = 10) or orbital floor defects (n = 6) reconstructed with mandibular symphyseal bone grafts. Symphyseal bone grafts were used when the defects were less than 2 cm in diameter. Patients were examined at recall visits for any evidence of unsuccessful reconstruction by checking extraocular movements, and evidence of diplopia or enophthalmous. RESULTS: During a mean follow-up of 12 months (range, 9 to 36 months), patients had no postoperative complaints. There were no instances of infection at the surgical sites, and none of the grafts were extruded or lost. There was good restoration of the orbital floor, with no clinical evidence of enophthalmous or diplopia. Extraocular movements were intact in all patients. CONCLUSION: The mandibular symphysis is a readily available source of autogenous bone that can be harvested with minimal morbidity. Its contour is suitable for use in orbital floor reconstruction. It merits consideration when autogenous bone grafts are considered for orbital floor defects less than 2 cm in diameter.
There is considerable international interest in Japanese production management (JPM), known in the West as "lean production." Advocates of this new form of management argue that it improves both economic productivity and health. In Japan, however, the relationship between JPM and sudden death due to cardiovascular and cerebrovascular disease has been an important topic of debate since the 1970s. Japanese have named these types of deaths karoshi, which means "death from overwork." In North America and Western Europe a number of studies have demonstrated a significant relationship between high job strain (high production demands and low levels of control and social support) and cardiovascular disease. This article reviews the elements of JPM and examines their potential health consequences. The authors present an overview of karoshi, discuss its possible connections to specific ideological and organizational characteristics of JPM, and suggest the job strain mechanism as a possible pathway between karoshi and JPM. They conclude by discussing the need for comparative research that examines the health effects of work organization and management methods cross-culturally.
We sought to evaluate two common fluids placed in the pelvis after pelvic surgery for their ability to remain in the pelvis for a time thought adequate for prevention of adhesions. Thirteen patients undergoing operative laparoscopy were randomized to receive 250 ml 32% dextran 70 (Hyskon), 250 ml lactated Ringer's solution, or no fluid (control) at the end of surgery. Serial transvaginal ultrasonograms were obtained at 1 hr, 3 hr, 6 hr, 24 hr, 96 hr (4 days), and 168 hr (7 days) after surgery. Patients were asked about side effects of fluid instillation. The volume of lactated Ringer's solution declined rapidly after instillation, with no significant difference from control at 24 hr (12 ml versus 7 ml). The volume of Hyskon did not decline rapidly by 24 hr and remained higher than the volume in controls or those receiving lactated Ringer's solution (188 ml, P = 0.003). Although the volume of Hyskon remained higher than that of lactated Ringer's solution or fluid volume in control patients by days 4 and 7, this difference did not reach statistical significance (45 ml versus 7 ml and 14 ml respectively, P = 0.39, on day 4). Patients in all groups noted abdominal pain. One patient who received Hyskon developed severe vulvar edema and another developed dyspnea. We conclude that the volume of Hyskon in the peritoneal cavity after laparoscopy does not decline as rapidly as does that of lactated Ringer's solution; however, significant side effects may limit its usefulness. Transvaginal ultrasonography is useful in monitoring fluids placed in the pelvis for prevention of adhesions.
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OBJECTIVES: This study sought to examine the vasodilatory response of the renal circulation to endothelial stimulation in patients with chronic heart failure. BACKGROUND: Renal blood flow is often reduced in patients with chronic congestive heart failure and may lead to deterioration of renal function. Stimulation of renal endothelium has been shown to cause renal vasodilation in animals and in isolated human renal artery. The vasoregulatory role of the renal endothelium in patients with heart failure has not been evaluated. METHODS: Renal vasodilatory effect of endothelial stimulation with acetylcholine was assessed and compared with that of endothelial independent vasodilation with nitroglycerin. Both drugs were infused into the main renal artery. Renal artery cross-sectional area was measured with intravascular ultrasound and renal blood flow velocity with the aid of an intravascular Doppler technique. RESULTS: Both drugs caused a significant and comparable increase in renal artery cross-sectional area (maximal increase [mean +/- SE] 14 +/- 5% with acetylcholine, 15 +/- 5% with nitroglycerin; both changes < 0.05 vs. baseline). Acetylcholine also caused a significant reduction in renal vascular resistance (maximal reduction 55+/- 6%) and increase in renal blood flow (maximal increase 136 +/- 54%). In contrast, nitroglycerin administration showed no significant effect on renal vascular resistance and blood flow. CONCLUSIONS: Stimulation of endothelium-derived nitric oxide with acetylcholine results in a significant vasodilatory effect on both conductance and resistance renal blood vessels and leads to a marked reduction in renal vascular resistance and enhancement of renal blood blow. Nitroglycerin, an exogenous nitric oxide donor, caused a selective vasodilatory effect on renal conductance but not on resistance blood vessels and failed to increase renal blood flow. These data suggest the possibility that stimulation of endogenous nitric oxide production in the kidney could be used as a therapeutic target for enhancement of renal flow in patients with heart failure.
Disposition of citrus flavonoids was evaluated after single oral doses of pure compounds (500 mg naringin and 500 mg hesperidin) and after multiple doses of combined grapefruit juice and orange juice and of once-daily grapefruit. Cumulative urinary recovery indicated low bioavailability ( < 25%) of naringin and hesperidin. The aglycones naringenin and hesperitin were detected in urine and plasma by positive chemical ionization-collisionally activated dissociation tandem mass spectrometry (PCI-CAD MS/MS). After juice administration, PCI-CAD MS/MS detected naringenin, hesperitin, and four related flavanones, tentatively identified as monomethoxy and dimethoxy derivatives. These methoxyflavanones appear to be absorbed from juice. Absorbed citrus flavanones may undergo glucuronidation before urinary excretion.
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In this article, the authors discuss the ongoing tension between etiologically oriented research--particularly that focused on the demand-control model--and the need to conceptually expand the work stress field to include gender and class-specific exposure contexts. Epidemiological research on the effects of low levels of work control is critically reviewed, and new methods of long-term psychosocial work-exposure assessment are presented. The process of conceptually expanding the demand-control model is discussed with respect to including other important variables, such as work-related social support, and specifying the nature of the gendered work process that involves developing new concepts and measures of the invisible and emotional labor often performed by women.
OBJECTIVES: This study examined the effect of cumulative exposure to work organization--psychological demands, work control, and social support on prospectively measured cardiovascular disease mortality risk. METHODS: The source population was a national sample of 12517 subjects selected from the Swedish male population by Statistics Sweden in annual surveys between 1977 and 1981. Over a 14-year follow-up period, 521 deaths from cardiovascular disease were identified. A nested case-control design was used. Work environment exposure scores were assigned to cases and controls by linking lifetime job histories with a job exposure matrix. RESULTS: Conditional logistic regression analysis was used in examining cardiovascular mortality risk in relation to work exposure after adjustment for age, year last employed, smoking, exercise, education, social class, nationality, and physical job demands. In the final multi-variable analysis, workers with low work control had a relative risk of 1.83 (95% confidence interval [CI] = 1.19, 2.82) for cardiovascular mortality. Workers with combined exposure to low control and low support had a relative risk of 2.62 (95% CI=1.22, 5.61). CONCLUSIONS: These results indicate that long-term exposure to low work control is a risk factor for cardiovascular disease mortality.
OBJECTIVES: This study was designed to determine the effect of oral hydralazine on the development of nitrate tolerance in patients with chronic congestive heart failure. BACKGROUND: Early development of nitrate tolerance with either continuous administration of intravenous or topical nitrate preparations or frequent dosing of oral nitrates leads to significant attenuation of nitrate-mediated hemodynamic and anti-ischemic effects. In recent animal experiments, prevention of nitroglycerin-induced hemodynamic tolerance with a concomitant use of hydralazine was demonstrated. This finding may have important clinical relevance. METHODS: Twenty-eight patients with chronic heart failure due to left ventricular systolic dysfunction were randomized to receive either a continuous infusion (24 h) of nitroglycerin alone (group I, 14 patients) or concomitantly with oral hydralazine (75 mg four times a day [group II, 14 patients]). The effect of nitroglycerin in each group was evaluated by analysis of variance for repeated measures. The power of the analysis to detect a 5.4-mm Hg (20%) change in mean pulmonary artery wedge pressure was 90%. RESULTS: Baseline hemodynamic variables as well as the initial hemodynamic response to nitroglycerin were comparable in both groups. Compared with the initial response to nitroglycerin, a significant attenuation of effect was found in group I at 24 h in mean (+/- SE) pulmonary artery pressure (27 +/- 4% vs. 10 +/- 3%, p < 0.05) and mean pulmonary artery wedge pressure (40 +/- 4% vs. 16 +/- 4%, p < 0.05). In group II, conversely, oral hydralazine prevented nitroglycerin-induced hemodynamic tolerance and resulted in a persistent effect on mean pulmonary artery and wedge pressures throughout the study period (31 +/- 3% vs. 27 +/- 4%, p = 0.13 and 37 +/- 4% vs. 34 +/- 6%, p = 0.40, respectively). In addition, the initial effect on blood pressure was attenuated at 24 h in group I (5 +/- 2% vs. 12 +/- 3%, p < 0.05) but not in group II (15 +/- 3% vs. 17 +/- 2%, p = 0.46). CONCLUSIONS: In patients with chronic heart failure due to left ventricular systolic dysfunction, the concomitant use of oral hydralazine prevents early development of nitrate tolerance and results in a persistent nitrate-mediated hemodynamic effect on systemic and pulmonary artery and left ventricular filling pressures. These data may support the concurrent use of hydralazine in patients with heart failure treated with organic nitrates.