Urinary B-cell-activating factor of the tumour necrosis factor family (BAFF) in systemic lupus erythematosus.

INTRODUCTION: We examined the clinical relevance of urinary concentrations of B-cell-activating factor of the tumour necrosis factor family (BAFF) and a proliferation-inducing ligand (APRIL) in systemic lupus erythematosus (SLE). METHODS: We quantified urinary BAFF (uBAFF) by enzyme-linked immunosorbent assay in 85 SLE, 28 primary Sjögren syndrome (pSS), 40 immunoglobulin A nephropathy (IgAN) patients and 36 healthy controls (HCs). Urinary APRIL (uAPRIL) and monocyte chemoattractant protein 1 (uMCP-1) were also quantified. Overall and renal SLE disease activity were assessed using the Systemic Lupus Erythematosus Disease Activity Index 2000. RESULTS: uBAFF was detected in 12% (10/85) of SLE patients, but was undetectable in HCs, IgAN and pSS patients. uBAFF was detectable in 28% (5/18) of SLE patients with active nephritis vs 5/67 (7%) of those without ( p = 0.03), and uBAFF was significantly higher in active renal patients ( p = 0.02) and more likely to be detected in patients with persistently active renal disease. In comparison, uAPRIL and uMCP-1 were detected in 32% (25/77) and 46% (22/48) of SLE patients, respectively. While no difference in proportion of samples with detectable uAPRIL was observed between SLE, HCs and IgAN patients, both uAPRIL and uMCP-1 were significantly detectable in higher proportions of patients with active renal disease. CONCLUSIONS: uBAFF was detectable in a small but a significant proportion of SLE patients but not in other groups tested, and was higher in SLE patients with active renal disease.

Design and methods of the REMOVAL-HD study: a tRial Evaluating Mid cut-Off Value membrane clearance of Albumin and Light chains in HaemoDialysis patients.

BACKGROUND: Removal of uraemic toxins is inadequate using current dialysis strategies. A new class of dialysis membranes have been developed that allow clearance of larger middle molecules. The REMOVAL-HD study (a tRial Evaluating Mid cut-Off Value membrane clearance of Albumin and Light chains in HaemoDialysis patients) will address safety, efficacy and the impact on patient-centred outcomes with the use of a mid cut-off (MCO) dialyser in a chronic haemodialysis (HD) population. METHODS: REMOVAL-HD is an open label, prospective, non-randomised, single-arm, multi-centre device study in 85 chronic HD participants. All visits will be conducted during regular HD sessions and participants will undergo a 1 month wash-in period using a standardised high flux dialyser, 6 months of intervention with a MCO dialyser and 1 month of wash-out using a high flux dialyser. The primary endpoint is change in pre-dialysis concentrations of serum albumin, with secondary endpoints including the efficacy of clearance of free light chains and ß-2 microglobulin, and patient-centred outcomes including quality of life, symptom burden, functional status, nutritional status, hospitalisation and death. DISCUSSION: MCO dialysers are a novel form of HD membrane. The REMOVAL-HD study is a pivotal study designed to monitor the immediate and medium-term effects following exposure to this dialyser. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry Number (ANZCTRN) 12616000804482 . Date of registration - 21/06/2016.

A prospective randomized open-label study of single injection versus continuous adductor canal block for postoperative analgesia after total knee arthroplasty.

AIMS: Adductor canal block (ACB) has emerged as an alternative to femoral nerve block (FNB) for analgesia after total knee arthroplasty (TKA). The optimal duration of maintenance of the ACB is still questionable. The purpose of this study was to compare the analgesic benefits and physiotherapy (PT) outcomes of single-shot ACB to two different regimens of infusion of the continuous ACB, 24-hour and 48-hour infusion. PATIENTS AND METHODS: This was a prospective, randomized, unblinded study. A total of 159 American Society of Anesthesiologists (ASA) physical status I to III patients scheduled for primary TKA were randomized to one of three study groups. Three patients did not complete the study, leaving 156 patients for final analysis. Group A (n = 53) was the single-shot group (16 female patients and 37 male patients with a mean age of 63.9 years (sd 9.6)), group B (n = 51) was the 24-hour infusion group (22 female patients and 29 male patients with a mean age of 66.5 years (sd 8.5)), and group C (n = 52) was the 48-hour infusion group (18 female patients and 34 male patients with a mean age of 62.2 years (sd 8.7)). Pain scores, opioid requirements, PT test results, and patient-reported outcome instruments were compared between the three groups. RESULTS: The proportion of patients reporting severe pain, defined as a pain score of between 7 and 10, on postoperative day number 2 (POD 2) were 21% for the single-shot group, 14% for the 24-hour block group, and 12% for the 48-hour block group (p = 0.05). Cumulative opioid requirements after 48 hours were similar between the groups. Functional outcomes were similar in all three groups in POD 1 and POD 2. CONCLUSION: There was no clear benefit of the 24-hour or 48-hour infusions over the single-shot ACB for the primary endpoint of the study. Otherwise, there were marginal benefits for keeping the indwelling catheter for 48 hours in terms of reducing the number of patients with moderate pain and improving the quality of pain management. However, all three groups had similar opioid usage, length of hospital stay, and functional outcomes. Further studies with larger sample sizes are needed to confirm these findings. Cite this article: Bone Joint J 2019;101-B:340-347.

The laterodorsal tegmentum contributes to behavioral sensitization to amphetamine.

A critical event in the development of behavioral sensitization is a transient increase in excitatory drive to dopamine neurons of the ventral tegmental area (VTA). This is likely to be due, in part, to the ability of drugs of abuse to produce long-term potentiation, expressed as increased AMPA receptor transmission, at excitatory synapses onto VTA dopamine neurons. We investigated the role of the laterodorsal tegmentum (LDT) in behavioral sensitization because LDT neurons provide an important source of excitatory drive to VTA dopamine neurons, through mixed glutamate and cholinergic inputs. To test the role of the LDT in amphetamine sensitization, ibotenic acid or sham lesions of the LDT were performed 1 week before the first of six daily amphetamine injections. When challenged with amphetamine 13 days after the last injection, sham rats expressed sensitization of stereotypy and post-stereotypy locomotor hyperactivity, whereas the latter was attenuated by ibotenic acid lesions of the LDT. To determine whether plasticity occurs in the LDT during amphetamine sensitization, we used a previously developed microdialysis assay in which increased ability of AMPA to activate a pathway serves as a marker for long-term potentiation. Two days after discontinuing repeated saline or amphetamine injections, the responsiveness of LDT-VTA neurons to AMPA was determined by microinjecting AMPA (0.4 nmol) into the LDT and measuring glutamate efflux in the ipsilateral VTA. Glutamate efflux was transiently increased in both groups but a delayed group difference was apparent with relatively higher glutamate efflux in amphetamine rats 30-60 min after AMPA injection. In parallel experiments, dopamine efflux in the nucleus accumbens (NAc) following intra-LDT AMPA declined in saline rats but remained relatively stable in amphetamine rats. Both results suggest relatively greater excitability of the LDT-VTA-NAc pathway after repeated amphetamine treatment. Our results provide the first evidence that neuronal plasticity in the LDT contributes to behavioral sensitization.

Dietary fat and postmenopausal breast cancer.

BACKGROUND: Although the results of animal studies and cross-cultural comparisons generally support a role for dietary fat in the etiology of breast cancer, results of analytic epidemiology studies are equivocal. PURPOSE: The association between dietary fat and subsequent breast cancer was examined in a cohort of 34,388 postmenopausal women from Iowa. METHODS: Dietary habits were assessed by a food-frequency questionnaire mailed in January 1986. Through December 31, 1989, 459 incident cases of breast cancer occurred in this cohort. Proportional hazards regression was used to examine the dietary fat-breast cancer association while adjusting for potential confounders. The effects on this association of four analytic approaches to adjustment for energy intake were also considered. RESULTS: After adjustment for known determinants of breast cancer, a modest positive association of total fat intake with risk of breast cancer was seen. Polyunsaturated fat intake was also positively associated with breast cancer (relative risk from lowest to highest intake, 1.0, 1.25, 1.31, and 1.49; P for trend = .052). Different approaches to adjustment for energy intake, however, provided different impressions of the dietary fat-breast cancer association. One method, involving categorization of crude fat intake and inclusion of total energy intake in regression analysis, gave relative risk estimates from low to high fat intake of 1.0, 1.17, 1.25, and 1.38 (P for trend = .18). Another method, based on categorization of fat intake residuals in which the variation in fat due to total energy intake was removed, gave corresponding estimates of 1.0, 1.24, 1.30, and 1.16 (P for trend = .29). The former suggests increasing breast cancer risk with increasing fat intake; the latter suggests no association. CONCLUSIONS: These results are consistent with other cohort studies that have shown a weak association or no association between dietary fat and breast cancer. They are also consistent with studies suggesting that fat intake is a determinant of breast cancer, particularly after accounting for inaccuracies in dietary assessment. The effects of different energy-adjustment methods may account in part for the varying interpretations of four previous cohort studies of dietary fat and breast cancer. IMPLICATIONS: Further work is needed to clarify not only the nature of the dietary fat-breast cancer association, but also the impact of different analytic methods used in the investigation of diet-disease associations.

Unitary construct of generalized cognitive ability underlying BACS performance across psychotic disorders and in their first-degree relatives.

Despite robust evidence of neurocognitive dysfunction in psychotic patients, the degree of similarity in cognitive architecture across psychotic disorders and among their respective first-degree relatives is not well delineated. The present study examined the latent factor structure of the Brief Assessment of Cognition in Schizophrenia (BACS) neuropsychological battery. Analyses were conducted on 783 psychosis spectrum probands (schizophrenia, schizoaffective, psychotic bipolar), 887 of their first-degree relatives, and 396 non-psychiatric controls from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) consortium. Exploratory factor analysis of BACS subtest scores indicated a single-factor solution that was similar across all groups and provided the best overall data fit in confirmatory analyses. Correlations between the standard BACS composite score and the sum of subscale scores weighted by their loadings on this unitary factor were very high in all groups (r≥.99). Thus, the BACS assesses a similar unitary cognitive construct in probands with different psychotic disorders, in their first-degree relatives, and in healthy controls, and this factor is well measured by the test's standard composite score.

Cost-effectiveness of platelet glycoprotein IIb/IIIa inhibition with eptifibatide in patients with non-ST-elevation acute coronary syndromes.

BACKGROUND: In the PURSUIT trial, eptifibatide significantly reduced the 30-day incidence of death and myocardial infarction relative to placebo in 9461 patients with an acute coronary syndrome (unstable angina or non-Q-wave myocardial infarction). METHODS AND RESULTS: We conducted a 2-part prospective economic substudy of the 3522 US patients enrolled in PURSUIT: (1) an empirical intention-to-treat comparison of medical costs (hospital plus physician) up to 6 months after hospitalization and (2) a lifetime cost-effectiveness analysis. The base-case cost-effectiveness ratio was expressed as the 1996 US dollars required to add 1 life-year with eptifibatide therapy. The 2 treatment arms had equivalent resource consumption and medical costs (exclusive of the cost of the eptifibatide regimen) during the index (enrollment) hospitalization (P=0.78) and up to 6 months afterward (P=0.60). The average wholesale price of the eptifibatide regimen was $1217, but a typical hospital discounted price was $1014. The estimated life expectancy from randomization in the US patients was 15.96 years for eptifibatide and 15.85 years for placebo, an incremental difference of 0.111. The incremental cost-effectiveness ratio for eptifibatide therapy in US PURSUIT patients was $16 491 per year of life saved. This result was robust through a wide range of sensitivity analyses. The cost-utility ratio for eptifibatide (using time trade-off defined utilities) was $19 693 per added quality-adjusted life-year. CONCLUSIONS: Based on the results observed in the US PURSUIT patients, the routine addition of eptifibatide to standard care for non-ST-elevation acute coronary syndrome patients is economically attractive by conventional standards.

Ergonovine maleate testing during cardiac catheterization: a 10-year perspective in 3,447 patients without significant coronary artery disease or Prinzmetal's variant angina.

The utility of ergonovine testing for coronary artery spasm was assessed in 3,447 patients with angiographically insignificant (less than 50% diameter stenosis) or no coronary artery disease. No patients clinically had Prinzmetal's variant angina. Overall, 4% had a positive ergonovine test result, defined by spasm causing greater than or equal to 75% focal stenosis. Complications related to ergonovine use occurred in 11 patients (0.03%). In a training sample of 1,136 patients (studied between 1980 and 1984), two independent predictors of spasm were found by using multivariate analysis: the amount of visible coronary artery disease on the coronary angiogram (p less than 0.0001) and a smoking history (p = 0.001). A model to predict spasm based on these variables was validated in a test group of 2,311 patients who received ergonovine from 1985 to 1989. This model allowed the identification of a subset of 400 patients in the validation sample who had a 10% positive test rate compared with a 2% positive test rate in the remaining patients. These results should permit clinicians who use provocative testing in the catheterization laboratory to reserve testing for the subset of this group of patients most likely to have abnormal findings.

Predicting the risk of abrupt vessel closure after angioplasty in an individual patient.

OBJECTIVES: We proposed to examine the relation between angiographic morphologic characteristics and abrupt closure after coronary angioplasty and to develop an empirically based risk stratification system. BACKGROUND: Certain lesion morphologic characteristics are associated with higher rates of abrupt closure after coronary angioplasty. Previous approaches have been limited by relatively small sample sizes and an inability to combine multiple characteristics to predict risk in an individual patient. METHODS: Lesion morphology was determined for 779 lesions in 658 patients undergoing an elective first angioplasty. Abrupt closure occurred in 63 lesions (8.1%). Variables associated with abrupt closure were identified by univariate and stepwise multiple logistic regression analysis, and internal validity was assessed by use of bootstrapping. An empirically based scoring system was developed by assigning different weights to each predictive characteristic and was then validated. RESULTS: Almost all lesion characteristics previously labeled "adverse" were associated with an increased risk of abrupt closure, but only total occlusion, location at a branch point, increasing lesion length, evidence for thrombus and right coronary artery location were statistically significant independent predictors. Despite the large sample size, the study was underpowered to detect even a 50% increase in risk with many characteristics. Using a scoring system, we assigned each lesion a specific risk of abrupt closure. The distribution of risk was broad, with 20% of patients having < or = 2.5% risk and 25% having > 10% risk. Internal validation techniques revealed that when 10% of patients were randomly eliminated from the sample in multiple iterations, the risk estimates varied, again pointing to the need for a larger sample. CONCLUSIONS: Empirically based weighting of lesion characteristics could quantify the risk of abrupt closure for individual patients, but a very large sample will be required to understand the interplay of complex lesion characteristics in altering expected outcomes.

Restenosis after coronary angioplasty: an overview.

Despite substantial basic and clinical efforts to address the problem of restenosis after percutaneous coronary intervention, effective preventive therapies have not yet been developed. Nevertheless, the accumulated information has provided much insight into the process of restenosis in addition to allowing standards to be developed for adequate clinical trials. The pathophysiology of restenosis increasingly appears to be distinct from that of primary atherosclerosis. Restenosis involves elastic recoil, incorporation of thrombus into the lesion and fibrocellular proliferation in varying degrees in different patients. Lack of an animal model that satisfactorily mimics restenosis is a major impediment to further understanding of the process. Clinical studies are hampered by difficulties in finding a single unifying definition of restenosis and by variable methods of reporting follow-up. Reporting of clinical outcomes of all patients in angiographic substudies would allow a more satisfactory interpretation of the results of clinical trials. Current noninvasive test results are not accurate enough to substitute for angiographic and clinical outcome data in intervention trials. In the majority of observational studies, only diabetes and unstable angina have emerged as consistently associated with restenosis; whereas most of the standard risk factors for atherosclerosis have a less consistent relation. Disappointingly, the new atherectomy and laser technologies have not affected restenosis rates. The one possible exception is coronary stenting, as a result of the larger luminal diameter achieved by the placement of the stent. In conclusion, although substantial continued effort is necessary to explore the basic aspects of cellular proliferation and mechanical alteration of atherosclerotic vessels, attention to the principles of clinical trials and observation are required to detect the impact of risk factors and interventions on the multifactorial problem of restenosis. Adequate sample sizes, collection of clinical and angiographic outcomes and factorial study designs hold promise for unraveling this important limitation of percutaneous intervention.

Prefrontal cortical modulation of acetylcholine release in posterior parietal cortex.

Attentional processing is a crucial early stage in cognition and is subject to "top-down" regulation by prefrontal cortex (PFC). Top-down regulation involves modification of input processing in cortical and subcortical areas, including the posterior parietal cortex (PPC). Cortical cholinergic inputs, originating from the basal forebrain cholinergic system, have been demonstrated to mediate important aspects of attentional processing. The present study investigated the ability of cholinergic and glutamatergic transmission within PFC to regulate acetylcholine (ACh) release in PPC. The first set of experiments demonstrated increases in ACh efflux in PPC following AMPA administration into the PFC. These increases were antagonized by co-administration of the AMPA receptor antagonist DNQX into the PFC. The second set of experiments demonstrated that administration of carbachol, but not nicotine, into the PFC also increased ACh efflux in PPC. The effects of carbachol were attenuated by co-administration (into PFC) of a muscarinic antagonist (atropine) and partially attenuated by the nicotine antagonist mecamylamine and DNQX. Perfusion of carbachol, nicotine, or AMPA into the PPC did not affect PFC ACh efflux, suggesting that these cortical interactions are not bi-directional. These studies demonstrate the capacity of the PFC to regulate ACh release in the PPC via glutamatergic and cholinergic prefrontal mechanisms. Prefrontal regulation of ACh release elsewhere in the cortex is hypothesized to contribute to the cognitive optimization of input processing.

Staphylococcus aureus collagen adhesin contributes to the pathogenesis of osteomyelitis.

To evaluate the role of the Staphylococcus aureus collagen-binding adhesin (Cna) in bone and joint infection, we generated a cna mutant in S. aureus UAMS-1, a strain that was originally isolated from the bone of a patient suffering from osteomyelitis. The mutant (UAMS-237) was unable to bind collagen but bound fibronectin at levels comparable to UAMS-1. The relative virulence of UAMS-1 and UAMS-237 was assessed using a murine model of acute hematogenous osteomyelitis. Specifically, 10(8) colony-forming units (cfu) were introduced into the bloodstream of NIH-Swiss mice via tail-vein injection. After 2 weeks, the left hind limb was harvested and examined histologically for evidence of osteomyelitis and septic arthritis. Osteomyelitis developed in 14 of 20 mice (70%) infected with UAMS-1, but only 1 of 20 (5%) infected with UAMS-237 (p < 0.001). In contrast, septic arthritis was observed in 12 of 20 mice (60%) infected with UAMS-1 and 14 of 20 (70%) infected with UAMS-237 (p < 0.75). These results indicate that Cna is not required to establish joint infection, but does make an important contribution to the ability of S. aureus to establish infection in bone through hematogenous spread.

Behavioral approach to nondyskinetic dopamine antagonists: identification of seroquel.

A great need exists for antipsychotic drugs which will not induce extrapyramidal symptoms (EPS) and tardive dyskinesias (TDs). These side effects are deemed to be a consequence of nonselective blockade of nigrostriatal and mesolimbic dopamine D2 receptors. Nondyskinetic clozapine (1) is a low-potency D2 dopamine receptor antagonist which appears to act selectively in the mesolimbic area. In this work dopamine antagonism was assessed in two mouse behavioral assays: antagonism of apomorphine-induced climbing and antagonism of apomorphine-induced disruption of swimming. The potential for the liability of dyskinesias was determined in haloperidol-sensitized Cebus monkeys. Initial examination of a few close cogeners of 1 enhanced confidence in the Cebus model as a predictor of dyskinetic potential. Considering dibenzazepines, 2 was not dyskinetic whereas 2a was dyskinetic. Among dibenzodiazepines, 1 did not induce dyskinesias whereas its N-2-(2-hydroxyethoxy)ethyl analogue 3 was dyskinetic. The emergence of such distinctions presented an opportunity. Thus, aromatic and N-substituted analogues of 6-(piperazin-1-yl)-11H-dibenz[b,e]azepines and 11-(piperazin-1-yl)dibenzo[b,f][1,4]thiazepines and -oxazepines were prepared and evaluated. 11-(4-[2-(2-Hydroxyethoxy)ethyl]piperazin-1-yl)dibenzo[b,f][1,4]thiazepine (23) was found to be an apomorphine antagonist comparable to clozapine. It was essentially nondyskinetic in the Cebus model. With 23 as a platform, a number of N-substituted analogues were found to be good apomorphine antagonists but all were dyskinetic.

Systemic and intra-accumbens administration of amphetamine differentially affects cortical acetylcholine release.

The present experiments tested the hypothesis that the amphetamine-induced increase in dopamine release in the nucleus accumbens represents a necessary and sufficient component of the ability of systemically administered amphetamine to stimulate cortical acetylcholine release. The effects of systemic or intra-accumbens administration of amphetamine on accumbens dopamine release and cortical acetylcholine release were assessed simultaneously in awake animals equipped with dialysis probes inserted into the shell of the nucleus accumbens and the medial prefrontal cortex. Additionally, the ability of intra-accumbens administration of dopamine D(1) and D(2) receptor antagonists to attenuate the effects of systemic amphetamine on cortical acetylcholine was tested. The effects of all treatments were assessed in interaction with a stimulus-induced activation of cortical acetylcholine release to account for the possibility that the demonstration of the trans-synaptic effects of accumbens dopamine requires pre-activation of basal forebrain circuits. Systemic amphetamine resulted in increases in basal cortical acetylcholine and accumbens dopamine efflux. Intra-accumbens administration of amphetamine substantially increased accumbens dopamine efflux, but did not significantly affect cortical acetylcholine efflux. Furthermore, intra-accumbens administration of sulpiride or SCH 23390 did not attenuate the systemic amphetamine-induced increase in cortical acetylcholine efflux. Collectively, the present data suggest that increases in accumbens dopamine release are neither sufficient nor necessary for the effects of systemically administered amphetamine on cortical acetylcholine release. The systemic amphetamine-induced increase in cortical acetylcholine may be mediated via multiple, parallel pathways and may not be attributable to a single afferent pathway of the basal forebrain.

Long-term outcome following successful reopening of abrupt closure after coronary angioplasty.

Abrupt closure after coronary angioplasty is often successfully treated by repeat dilation. Long-term follow-up, including 6-month repeat catheterization and 12-month clinical evaluation, was obtained in 1,056 patients treated with acute (n = 335) or elective (n = 721) coronary angioplasty to evaluate the long-term impact of successful reopening of abrupt closure. Abrupt closure occurred in 13.5% of patients and was successfully reopened in 58%. Adverse outcomes including restenosis, death, bypass surgery, myocardial infarction and repeat angioplasty were compared between patients with successfully treated abrupt closure and those with successful procedures (residual diameter stenosis < or = 50%) without abrupt closure. For patients with acute angioplasty, the restenosis rates (> 50% diameter stenosis at follow-up) were 64% for those with successfully treated abrupt closure versus 36% for those with successful procedures without abrupt closure (p < 0.01). In addition, subsequent myocardial infarction (12 vs 3%; p = 0.01) and repeat angioplasty (21 vs 10%; p = 0.03) were more frequent in the group with abrupt closure. For patients with elective angioplasty, restenosis was 43% in those with successfully treated abrupt closure versus 45% in those without abrupt closure (p = NS). Subsequent death and myocardial infarction were more frequent in patients with abrupt closure (death: 12 vs 3% [p < 0.01]; myocardial infarction: 13 vs 3% [p < 0.01]). Long-term adverse events are increased in patients with successfully treated abrupt closure compared to those with successful procedures without abrupt closure.

Long-term survival benefits of coronary artery bypass grafting and percutaneous transluminal angioplasty in patients with coronary artery disease.

The purpose of this study was to evaluate long-term survival benefits of bypass surgery and angioplasty versus medical therapy in 9263 patients at Duke University Medical Center between 1984 and 1990 with coronary artery disease confirmed by cardiac catheterization to involve one, two, or three vessels. Clinical data were prospectively entered into an established cardiovascular database, and annual follow-up was 97% complete for a mean interval of 5.3 years and a maximal interval of 10 years. Outcomes were analyzed with the Coronary Artery Surgery Study "method A" to define patient groups treated by medicine (n = 2449), angioplasty (n = 2924), or bypass surgery (n = 3890). Differences among treatment groups in baseline characteristics were adjusted by Cox proportional hazard models. The anatomic severity of coronary artery stenosis best defined survival benefit from bypass surgery and angioplasty versus medical treatment. One or both interventional treatments provided better long-term survival than did medical treatment for all levels of disease severity. All patients with single-vessel disease, except those with at least 95% proximal left anterior descending stenosis, benefited from angioplasty versus bypass. All patients with three-vessel disease and those two-vessel patients with > or = 95% proximal left anterior descending stenosis benefited from bypass surgery versus angioplasty. All other patients with two-vessel disease and those with > or = 95% proximal left anterior descending stenosis only had similar survival with either interventional treatment. The absolute survival benefit was greatest for patients with severe three-vessel disease treated with bypass surgery.

The change in serum protein concentration in response to the stress of total joint surgery: a comparison of older versus younger patients.

OBJECTIVE: To investigate whether the physiological response to surgery-induced stress, as measured by changes in serum secretory proteins, is more profound on older than in younger total joint arthroplasty patients. DESIGN: Retrospective study. SETTING: A 267-bed teaching hospital. PARTICIPANTS: A total of 220 ambulatory patients with normal admission serum albumin levels, of whom 106 were 65 years of age or older (mean age 73.3 +/- 6.2 years) and 114 less than age 65 (mean age 48.8 +/- 12.2 years). METHODS: Serum albumin and transferrin levels obtained at admission an on the fifth and tenth postoperative days were compared in the two age groups. RESULTS: In both age groups, admission serum albumins were significantly higher than on the corresponding postoperative Day 5 levels (40.4 +/- 3.7 g/L vs 25.0 +/- 3.3 g/L, P < .0001 and 39.5 +/- 2.5 g/L vs 23.9 +/- 3.1 g/L, P < .001 in older and younger patients, respectively). The drop in the serum concentration of albumin by postoperative Day 5 in the older patients was not significantly different from that of the younger patients (a drop of 15.6 +/- 3.3 g/L in older vs 15.4 +/- 4.4 g/L for the younger, P = .740). Among the 64 patients who remained in the hospital 10 days subsequent to surgery, the average postoperative Day 10 serum albumin concentration was significantly lower in the older patients when compared with the younger (26.2 vs 29.1 g/L P = .016). Similar results were obtained for serum transferrin. CONCLUSIONS: Subsequent to elective arthroplasty, the magnitude of change in serum albumin and transferrin concentrations is similar in older compared with younger, patients, suggesting that this stress response to surgery is nor age dependent. In contrast, the rate of recovery of the serum protein concentrations to preoperative levels may be slower in the older patients. However, this issue needs to be investigated further.

Left ventricular function in hospitalized geriatric patients.

Left ventricular ejection fraction was measured by gated wall motion in 62 patients, 75 years old or older, admitted to a Geriatric Acute Assessment Ward. From this group, 42 patients not taking digitalis or other cardioactive medication were selected for analysis. Thirty of them had clinically identifiable heart disease, whereas 12 did not. Resting left ventricular ejection fractions in the 12 patients without clinically identifiable heart disease averaged 0.60 +/- 0.09. None had an ejection fraction below 0.50. In the 30 patients with clinically identifiable heart disease, mean ejection fraction was 0.49 +/- 0.15 (range 0.17-0.84), P less than 0.01. In the patients with heart disease, reduction of ejection fraction was correlated with either cardiac enlargement or congestive heart failure. Neither age nor electrocardiographic abnormalities added to the strength of this correlation. Fifty-eight per cent of patients with congestive heart failure had ejection fractions greater than or equal to 0.40, suggesting that congestive heart failure in this age group is frequently related to diastolic left ventricular dysfunction unaccompanied by major systolic dysfunction. The prognosis of patients with congestive heart failure and ejection fractions above 0.35 was significantly better than of patients with congestive heart failure and ejection fractions below 0.35. From these data and other data available in the literature, it is proposed that the lower limit for ejection fraction be 0.50 for patients 75 years old or older. Congestive heart failure in patients 75 years old or older appears to be associated with relatively higher ejection fractions or even with ejection fractions within the normal range. In these patients, digitalis may not be indicated, and short term-prognosis is relatively favorable.

Repeated pretreatment with amphetamine sensitizes increases in cortical acetylcholine release.

RATIONALE: Previous studies on the attentional effects of repeated psychostimulant administration in rats suggested the possibility that these effects are mediated via increases in the efficacy of psychostimulants to stimulate cortical acetylcholine (ACh) release. Furthermore, neurochemical data have raised the possibility that increases in nucleus accumbens (NAC) dopamine (DA) release trans-synaptically increase the excitability of basal forebrain corticopetal cholinergic projections, thereby supporting speculations about relationships between the effects of repeated psychostimulant administration on NAC DA and cortical ACh release. OBJECTIVES: To determine whether repeated exposure to amphetamine would potentiate the stimulating effects of the drug on cortical ACh and NAC DA efflux. METHODS: Rats were implanted with microdialysis guide cannula in the medial prefrontal cortex and the shell region of the ipsilateral NAC. Amphetamine (2.0 mg/kg i.p.) or saline (0.9%) was administered every other day for 10 days, for a total of five injections. ACh and DA efflux and locomotor activity were measured on the day of the first and last injections of this pretreatment regimen. All animals were retested following a challenge dose of amphetamine (2.0 mg/kg i.p.) given 10 and 19 days after the last pretreatment injection. RESULTS: The initial injections of amphetamine stimulated ACh and DA efflux and locomotor behavior in both groups. The pretreatment with amphetamine potentiated the ability of the drug to stimulate cortical ACh efflux on day 19 of the withdrawal period. The pretreatment with amphetamine also increased the effects of the challenge dose on motoric activity on day 10. Pretreatment with amphetamine did not result in a significant augmentation of the amphetamine-induced increase in DA efflux in the NAC. CONCLUSIONS: Pretreatment with amphetamine sensitizes the ability of amphetamine to stimulate cortical ACh efflux. These results support the hypothesis that sensitized release of cortical ACh mediated the previously observed hyperattentional impairments in amphetamine pretreated rats. Sensitized cortical ACh release following repeated exposure to psychostimulants may mediate the overprocessing of addictive drug-related stimuli, thus contributing to repeated compulsive addictive drug use.

Environmental bacteriology in the unidirectional (horizontal) operating room.

The continuing attempts to reduce bacterial contamination through clean air systems have been of special interest to surgeons dealing in joint replacement surgery. Although the definitive relationship between airborne contamination and surgical infections is not universally agreed on, there is little question that clean air systems reduce bacterial contamination of the surgical wound at the time of operation. This report reviews the history of surgical infections, presents statistical data that show the reduction of bacterial contamination by a clear air system, and suggests a pragmatic attitude regarding airborne bacterial contamination of surgical wounds.