Therapeutic management of triglycerides: an international perspective.

Current recommendations from various international expert committees generally concur in their definitions of borderline and high triglyceride levels, with small but important differences between recommendations in the definition of normal levels. However, population-based data on triglyceride levels are poorly developed in most countries, making difficult any international comparisons of prevalences of hypertriglyceridemia using the new definitions. However, it is probable that there should be considerable differences in the prevalence of hypertriglyceridemia, probably due to a mixture of genetic and environmental influences. The management of hypertriglyceridemia must continue to emphasize the detection and correction of secondary causes, even though the specific secondary causes may vary between countries. Dietary and exercise interventions must deal with local customs and resources, including striking international differences in alcohol consumption. Pharmacologic therapies will likely increase in use if they follow the trends in countries with available data. Although various drugs are available, nicotinic acid and fibric acid derivatives remain the drugs of choice. Considerably more research is needed to describe these international differences in etiology, prevalence and management practices of hypertriglyceridemia.


Epidemiology of triglycerides: a view from Framingham.

New analyses from the Framingham Heart Study are presented showing that men and women who have high triglyceride levels (> 1.7 mmol/liter) and a low high-density lipoprotein (HDL) level (< 1.03 mmol/liter) run a significantly higher rate of coronary artery disease and can be identified, and that this risk group (high triglyceride-low HDL) is, independently of the major risk factors (including low HDL), related to occurrence of coronary artery disease. Further, this trait appears to be common in our society, producing twice as many cases of coronary artery disease during the 14 years of the Framingham study as the next highest disease-producing lipid abnormality. This trait of high triglyceride-low HDL is associated in the medical literature with increased insulin resistance, higher blood sugars (within the normal range), higher uric acid levels, hypertension, and centrally mediated obesity. Because total cholesterol in people with these traits may be less than or just slightly greater than 5.2 mmol/liter, they are missed or neglected by most cholesterol screening programs.


Effect of coronary angioplasty on late potentials one to two weeks after acute myocardial infarction.

In survivors of acute myocardial infarction (AMI), the restoration of anterograde flow in the infarct artery, even if accomplished beyond the time for myocardial salvage, may reduce the frequency of subsequent arrhythmic events and sudden death. Twelve subjects (8 men and 4 women, aged 39 to 69 years) with a first AMI, signal-averaged electrocardiographic late potentials, and an occluded infarct artery were prospectively identified. Seven (group I) had successful coronary angioplasty 6 to 15 days after AMI, and 5 (group II) were managed conservatively. Follow-up signal-averaged electrocardiography was performed 3 to 7 months later. From baseline to follow-up, the 7 group I subjects had a significant change in QRS duration (117 +/- 13 [mean + SD] to 102 +/- 10 ms), root-mean-square voltage (10.4 +/- 4.7 to 31.0 +/- 7.6 microV), and low-amplitude signal duration (47.5 +/- 8.5 to 32.4 +/- 5.2 ms) (p < or = 0.05 for all 3 variables). No group I patient had a late potential at follow-up. In contrast, the 5 group II patients showed no change in QRS duration or low-amplitude signal duration from baseline to follow-up, and all 5 had a late potential at follow-up. At follow-up, the root-mean-square voltage was significantly greater and the low-amplitude signal and QRS durations significantly less in group I than in group II (p < 0.05 for all 3 variables). Thus, in our patients, the mechanical restoration of anterograde perfusion in an occluded infarct artery 1 to 2 weeks after AMI caused the resolution of signal-averaged electrocardiographic late potentials.


Percutaneous transluminal coronary angioplasty without on-site surgical facilities.

Percutaneous transluminal coronary angioplasty (PTCA) is associated with a low risk of serious complications, the most important of which is acute coronary occlusion needing emergency surgery. There is a consensus among many cardiologists and cardiac surgeons that all PTCA procedures need on-site surgical backup. A task force report on PTCA by the American College of Cardiology/American Heart Association mandates the presence of an on-site cardiovascular surgical team. Since 1981, we have performed PTCA without the benefit of on-site surgery but with backup surgery provided at a regional cardiac surgical center located 6 kilometers away. Up to the end of 1991, 762 patients have undergone 847 PTCAs. Most patients had 1-vessel angioplasty (94.6%). The primary success rate since 1981 was 76%, and from January 1990 to December 1991 it was 87% (n = 313). Complications included death in 7 patients (0.9%), myocardial infarction in 16 (2.1%) and emergency surgery in 12 (1.6%). Surgical backup was provided on a next available operating room basis. The average time from decision to transfer to onset of surgery was 164 minutes (range 75 to 320). All patients survived surgery, but 42% developed a new Q-wave myocardial infarction. These patients were followed up until the end of 1991, and are all alive. The results are similar to those reported from centers with and without on-site surgery. With careful selection of patients and a formal, coordinated plan for backup surgery, PTCA can be safely performed without on-site surgery.


Results of coronary angioplasty using the transluminal extraction catheter.

To assess the procedural results after coronary angioplasty using the transluminal extraction catheter (TEC) in patients with complex lesion anatomy, experience with 51 patients undergoing this procedure was reviewed. One or more adverse lesion morphologic features were present in 45 patients (88%) and > or = 2 adverse features were present in 38 (74%). Procedural success (< 50% final diameter stenosis and the absence of major complications) was obtained in 42 patients (82%); major complications occurred in 7 patients (death, 3; Q-wave myocardial infarction, 4; emergency bypass operation, 2). Distal embolization was noted in 5 patients with thrombus-containing saphenous vein graft stenoses. Only lesion thrombus correlated with an unsuccessful outcome. After TEC use, diameter stenosis was reduced from 76 +/- 13 to 50 +/- 22% (p < 0.001). Adjunct balloon angioplasty was used in 44 procedures (86%), further reducing the diameter stenosis to 32 +/- 22% (p < 0.001 compared with post-TEC). High-frequency intracoronary ultrasound was performed in 11 patients after TEC use. Plaque fissuring was present in all lesions and intraluminal dissection was noted in 4 (36%). Residual plaque after TEC use was found in virtually all lesions. During the 5.2 +/- 2.8-month follow-up period, 17 patients (40%) developed recurrent symptoms. Coronary bypass surgery was performed in 4 patients and repeat coronary angioplasty was required in 3. In addition, 3 patients died from cardiac causes. It is concluded that coronary angioplasty using the TEC may be a useful alternative to balloon angioplasty in patients with complex coronary anatomy, although distal embolization may still occur in thrombus-containing saphenous vein graft lesions.


Clinical success, complications and restenosis rates with excimer laser coronary angioplasty. The Percutaneous Excimer Laser Coronary Angioplasty Registry.

The role of excimer laser angioplasty in treating complex coronary artery disease remains uncertain. A randomized trial comparing this new technology with balloon angioplasty cannot be designed until systematic analysis identifies the lesion types that are likely to benefit from treatment with excimer laser angioplasty. In a cohort of 764 patients who had 858 coronary stenoses treated with excimer laser-facilitated angioplasty, relative risk analysis was used to examine acute success, complications and restenosis rates, and the results were compared with those of balloon angioplasty to identify the lesion types that show the greatest benefit with the new treatment. Clinical success was achieved in 657 patients (86%), as indicated by < or = 50% residual stenosis and no in-hospital complication. A major in-hospital complication (death, bypass surgery, or Q-wave or non-Q-wave myocardial infarction) occurred in 58 patients (7.6%). Follow-up angiography was obtained in 70% of eligible patients. Combining angiographic and noninvasive restenosis rates yielded an overall restenosis rate of 46%. Relative risk analysis showed that major complications occurred frequently in lesions at an arterial bifurcation (odds ratio [OR] 5.96 [2.76, 12.6]; p = 0.001). However, certain complex lesions that are difficult to treat with balloon angioplasty (saphenous vein graft lesions, lesions > 10 mm, ostial lesions, calcified stenoses, total occlusions and unsuccessful balloon dilatations), analyzed together as a group, had lower complication rates by univariate (OR 0.59 [0.35, 1.00]; p = 0.051) and multivariate logistic regression (p = 0.006) analyses.(ABSTRACT TRUNCATED AT 250 WORDS)


Prediction of risk for hemodynamic compromise during percutaneous transluminal coronary angioplasty.

The availability of circulatory support devices has increased the importance of accurately identifying patients at risk for hemodynamic compromise during percutaneous transluminal coronary angioplasty (PTCA). Accordingly, prospective evaluation of 3 criteria to predict hemodynamic compromise (defined as a decrease in systolic blood pressure > or = 20 to < 90 mm Hg during balloon inflation) in 157 patients (group A) undergoing PTCA was performed. Left ventricular ejection fraction < 35% had a sensitivity of 13% and a specificity of 95%. Greater than 50% of the myocardium at risk was associated with a sensitivity of 31% and a specificity of 85%. The angiographer's assessment of high risk for hemodynamic compromise had the highest sensitivity of 56% and a specificity of 86%. The clinical and angiographic characteristics of these patients were reviewed to identify risk factors retrospectively. Multivariate analysis of 28 variables identified multivessel disease, diffuse disease, myocardium at risk, and stenosis before PTCA as independent predictors of hemodynamic compromise. With use of this analysis, a 13-point weighted scoring system was created based on the regression of coefficients of the variables. Defining high risk for hemodynamic compromise as a risk score > or = 4, the sensitivity of this criterion in group A patients was 81% and the specificity was 74%. The scoring system was then prospectively applied to 61 consecutive patients (group B) undergoing PTCA. In using a risk score > or = 4 to define high risk, this scoring system had a sensitivity of 92% and a specificity of 92%.(ABSTRACT TRUNCATED AT 250 WORDS)


Classification of morphologic effects of percutaneous transluminal coronary angioplasty assessed by intravascular ultrasound.

The aim of this study was the assessment and classification of the morphologic effects of percutaneous transluminal angioplasty (PTCA) by intravascular ultrasound (IU). Fifty-eight patients were examined immediately after PTCA with a 4.8Fr, 20 MHz rotational tip IU system. In 10 patients (17%), IU images could not be analyzed due to failure of the imaging system or poor image quality. In 48 patients (83%; 40 men and 8 women, aged 55 +/- 9 years), IU images of 48 PTCA segments, as well as 41 distal and 44 proximal sites, were analyzed. The left anterior descending artery was studied in 30 patients, the right coronary artery in 17 and the left main coronary artery in 1. Calcium was present in 32 of 48 PTCA segments (67%). Plaque morphology was concentric in 18 patients (38%) and eccentric in 30 (62%). Seven distinct morphologic patterns were observed. In concentric plaques, plaque compression without significant wall alterations (type 1) was found in 2 patients (4%), superficial tears within the plaque (type 2) in 1 (2%) and deep tears (type 3) in 8 (17%). Deep tearing associated with submedial or subintimal dissection (type 4) was found in 2 patients (4%). Dissection between plaque and vessel wall without noticeable intimal tearing (type 5) was the most common morphology (n = 15; 31%) and occurred in concentric and eccentric plaques. In eccentric plaques, no significant tearing of the plaque (type 6) was found in 6 patients (13%), and tearing of the plaque close to its base with dissection (type 7) in 14 (29%).(ABSTRACT TRUNCATED AT 250 WORDS)


Comparison of painful and painless left ventricular dysfunction recorded during ambulatory ventricular function monitoring in angina pectoris secondary to coronary artery disease.

Left ventricular (LV) function and the electrocardiogram of 55 patients with coronary artery disease and angina were monitored for a mean of 3.2 +/- 1.9 hours with an ambulatory LV function monitor. During the monitoring interval, patients performed daily activities such as sitting, walking, climbing stairs, and eating. Sixty episodes of transient reduction in ejection fraction of > 5% lasting > 60 seconds were observed in 24 patients; 13 episodes were associated with typical angina, but 47 were asymptomatic. Asymptomatic episodes had a shorter duration of ventricular dysfunction (116 +/- 49 vs 189 +/- 113 seconds; p < 0.05), and smaller increases in relative end-diastolic and end-systolic volumes (end-diastolic 0.9 +/- 5.4% vs 4.6 +/- 4.9% [p < 0.05], and end-systolic 21 +/- 11% vs 35 +/- 20% [p < 0.05]) than did symptomatic ones. When a subset of patients with both symptomatic and asymptomatic episodes were analyzed, similar results were observed: in asymptomatic episodes, duration was shorter (82 +/- 31 vs 200 +/- 110 seconds; p < 0.005), ejection fraction decrease was smaller (-7.3 +/- 2.6% vs -11.0 +/- 4.7%; p < 0.05), and end-systolic volume increase was smaller (23 +/- 12% vs 37 +/- 19%; p < 0.05). The data suggest that asymptomatic transient LV dysfunction is less severe and of shorter duration in patients with angina pectoris.


Variable location of accessory pathways associated with the permanent form of junctional reciprocating tachycardia and confirmation with radiofrequency ablation.

Permanent junctional reciprocating tachycardia (PJRT) occurs primarily in young patients and causes nearly incessant tachycardia that is frequently refractory to pharmacologic treatment. Previous nonpharmacologic therapy has included surgical or direct-current catheter ablation of either the His bundle or the accessory pathway. The accessory pathway in PJRT has been described as having retrograde and anterograde decremental conduction properties, and is typically identified in the posteroseptal location. This report describes radiofrequency catheter ablation of accessory pathways in 8 patients with PJRT. All ablations were successful and without adverse effects. Accessory pathway potentials were detected just before atrial activation in 6 of 8 patients. A new finding was that 5 of the 8 pathway locations, as identified by the site of successful ablation, were not in the typical posteroseptal region. In 1 patient it was located in the right posteroseptal region, 2 were in the right atrial freewall, 1 was in the right anterior septum and 1 was in the left posterior region just outside of the septal region. In conclusion, radiofrequency catheter ablation can be a highly effective and safe method for treatment of young patients with PJRT. Because the accessory pathways can be located outside of the posteroseptal region, careful mapping of both the right and left atrioventricular groove may be necessary for successful ablation.


Detection of left anterior descending coronary artery disease in patients with left bundle branch block.

The detection of coronary artery disease is difficult if a patient has electrocardiographic evidence of left bundle branch block (BBB). Septal blood flow may be reduced in patients with left BBB, despite no angiographic evidence of left anterior descending (LAD) coronary artery disease. We have developed a new method of quantification of Thallium-201 single-photon emission computed tomographic (SPECT) images with the aim of better separating patients with left BBB and LAD disease from those with left BBB alone. The study cohort comprised 8 normal subjects (group I) and 20 patients with left BBB and chest pain who underwent thallium-201 SPECT imaging and coronary angiography. Eight patients (group II) had < or = 50% LAD stenosis, and 12 (group III) had > or = 70% LAD stenosis. Septal abnormality scores on the second short-axis slice from the base were computed, based on comparison of each subject's short-axis circumferential profile with a normal reference curve. This followed a procedure in which each profile was scaled to minimize differences in its absolute level in relation to the reference curve. Septal abnormality scores on stress images were 0.8 +/- 22 for group I, 27 +/- 43 for group II, and 165 +/- 67 for group III (p = 0.15 for group I vs II, and p < 0.0001 between groups I and III, and II and III).(ABSTRACT TRUNCATED AT 250 WORDS)


Comparison of sustained-release formulations of nicardipine and verapamil for mild to moderate systemic hypertension.

In this double-blind, parallel, multicenter study, sustained-release (SR) preparations of 2 calcium antagonists, nicardipine and verapamil, were compared for the treatment of mild to moderate systemic hypertension. Two hundred eighteen patients with supine diastolic blood pressures (BP) 95 to 114 mm Hg were randomly assigned to receive nicardipine-SR 45 mg twice daily (n = 73), nicardipine-SR 60 mg twice daily (n = 73) or verapamil-SR 240 mg once daily in the morning (n = 72). All 3 regimens significantly reduced supine and sitting systolic and diastolic BPs compared with baseline values (p < 0.005). The efficacy of drugs became apparent after 2 weeks of therapy, and was sustained throughout the 12-week study. Reductions in sitting diastolic BP and supine and sitting systolic BPs were statistically greater with nicardipine-SR 60 mg twice daily compared with verapamil, and nicardipine-SR 45 mg twice daily was equivalent to verapamil. Asthenia and constipation occurred more frequently in patients treated with verapamil (9.7 and 11.1%, respectively, compared with 6.8 and 4.1% in either nicardipine group). Adverse events reported more frequently with nicardipine were headache (17.8% with nicardipine-SR 60 mg and 15.1% with nicardipine-SR 45 mg vs 13.9% with verapamil) and edema (15.1% in the nicardipine-SR 60 mg group, 8.2% with nicardipine-SR 45 mg vs 4.2% with verapamil). Verapamil, but not nicardipine, produced significant reductions in heart rate. SR preparations of calcium antagonists offer options for effective monotherapy of systemic hypertension. Side-effect profiles differ and may affect choice of therapy.


Comparison of different methods for assessing sympathovagal balance in chronic congestive heart failure secondary to coronary artery disease.

Twenty-five patients (aged 62 +/- 2 years) with stable, moderate to severe ischemic congestive heart failure (CHF) (New York Heart Association class II/III: 15/10; ejection fraction 21.6 +/- 2%; and peak oxygen uptake 13.6 +/- 0.7 ml/kg/min) were studied to evaluate the ability of different methods to characterize autonomic tone in chronic CHF. Sympathovagal balance was assessed by: (1) heart rate variability in the time domain, assessed by the SD of RR intervals; (2) heart rate variability in the frequency domain, assessed by low- (0.03 to 0.14 Hz) and high- (0.18 to 0.40 Hz) frequency components of heart rate variability by autoregressive power spectral analysis; (3) 24-hour, daytime and nighttime heart rate; (4) submaximal heart rate during upright bicycle exercise, with respiratory gas analysis to obtain peak oxygen uptake; and (5) radiolabeled norepinephrine spillover. These methods did not correlate, with the exception of day and nighttime heart rate (r = 0.74; p < 0.001) and the expected inverse correlation between low and high frequency (r = -0.92; p < 0.001). No method correlated significantly with peak oxygen uptake, exercise tolerance or ejection fraction. After 8 weeks of physical training at home, all methods showed improvement in autonomic balance: increases in SD of RR intervals (+21%; p < 0.02) and high frequency (+41%; p < 0.007), and decreases in low frequency (-19%; p < 0.002), low-/high-frequency ratio (-48%; p < 0.03), norepinephrine spillover (-28.9%; p < 0.03), 24-hour heart rate (-2.7%; p < 0.005) and submaximal heart rate (-10.8%; p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)


Noninvasive detection of left ventricular diastolic dysfunction using M-mode echocardiography to assess left ventricular posterior wall kinetics in hypertrophic cardiomyopathy.

In patients with hypertrophic cardiomyopathy (HC), it is difficult to determine the severity of left ventricular (LV) diastolic dysfunction. Three different patterns of LV posterior wall motion were found by M-mode echocardiography in patients with HC, and the use of these patterns is proposed as a new noninvasive index of the severity of LV diastolic dysfunction. M-mode echocardiograms were recorded prospectively from 35 patients with HC, and the posterior wall motion pattern in late systole and early diastole was classified into the following 3 types: (1) normal motion (n = 9); (2) flat motion--flat motion from late systole to early diastole, followed by rapid backward movement (n = 13); and (3) downward motion--slow backward movement from late systole (n = 13). There were no differences in the severity or type of hypertrophy, LV systolic function and pulsed Doppler indexes of LV filling among these 3 groups. However, LV end-diastolic pressure was increased in the groups with flat (15 +/- 6 mm Hg) and downward (16 +/- 9 mm Hg) motion. Furthermore, the maximal rate of decrease in LV pressure (normal 1,450 +/- 300, flat 1,250 +/- 300 and downward 860 +/- 80 mm Hg/s) and the time constant of LV pressure reduction (normal 60 +/- 15, flat 70 +/- 25 and downward 101 +/- 34 ms) showed a stepwise deterioration from the normal to the flat and then to the downward motion groups.(ABSTRACT TRUNCATED AT 250 WORDS)


Magnetic resonance imaging in right ventricular dysplasia.

Fifteen patients with right ventricular dysplasia were investigated by T1-weighted spin- and gradient-echo pulse sequences, using a protocol that enabled both a subjective analysis of myocardial signal intensity and a quantitative/qualitative analysis of right and left ventricular function. In 8 patients, 3 investigators independently recognized abnormally hyperintense areas in the anatomic sites usually affected by the disease. In 7 of these patients, these areas showed an overlap with a-dyskinetic areas imaged by both magnetic resonance imaging (MRI) and echocardiography. In 1 patient who underwent a cardiac transplant, MRI of the explanted heart showed an excellent correlation between the distribution of the lesions and the in vivo/in vitro features. The data were compared with those from an equivalent sample of patients affected by dilated cardiomyopathy. In the latter patients, no focal hyperintensities were attributed to any anatomic sites in the right ventricule, and no focal a-dyskinetic foci were observed. Furthermore, the 2 groups of patients were significantly different in regard to dimensional and functional quantitative parameters. The results suggest that MRI is useful in integrating echocardiographic data and can be helpful in diagnosing this disease in late stages.


Maxepa versus bezafibrate in hyperlipidemic cardiac transplant recipients.

Accelerated coronary artery disease is the most serious obstacle to long-term survival in cardiac transplant recipients. Lipid abnormalities are found frequently in these patients, and there is growing evidence that even minimally increased levels of cholesterol and triglycerides contribute to the development of accelerated coronary artery disease. However, the optimal lipid-lowering therapy after cardiac transplantation has not been defined. In an open, randomized study, the efficacy and safety of bezafibrate (400 mg/day) and fish oil (Maxepa) (10 g/day) for 3 months were compared in 87 cardiac transplant recipients with serum total cholesterol > 6.5 or triglycerides > 2.8 mmol/liter, or both. After 1 month, bezafibrate reduced total cholesterol by 13%, low-density lipoprotein cholesterol by 20% and apolipoprotein B by 13%. It also increased apolipoprotein A1 and high-density lipoprotein cholesterol by 12 and 20%, respectively, and significantly reduced fibrinogen at 3 months. Maxepa had no significant effect on these variables, but was as effective as bezafibrate in reducing triglycerides (36 and 31%, respectively). Both drugs increased lipoprotein (a) to a similar extent, and bezafibrate significantly increased serum creatinine. These results suggest that bezafibrate has better lipid-, apolipoprotein- and hemostatic modifying properties than does Maxepa, but its potentially adverse effect on renal function needs further investigation.


Bone densitometry in patients with multiple myeloma.

We performed dual-energy x-ray absorptiometry in 10 selected patients with aggressive multiple myeloma in whom substantial tumor mass reduction was achieved after high-dose chemoradiotherapy followed by autologous blood stem cell transplantation. In most cases, bone mineral density (BMD) of the spine was initially low (Mean Z score: -2.69, SEM 0.76) and dramatically increased after treatment (mean increase 16.4%; 7.7% with 95% confidence interval 2.2 to 12.2, excluding one patient whose spine BMD increased by 94.8%). In contrast, skeletal roentgenograms, computed tomographic scans, and magnetic resonance imaging did not reveal any significant improvement of patients' bone lesions. In patients with multiple myeloma, bone densitometry could be a useful way to assess the efficacy of treatment on bone status.


Prognostic significance of elevated serum beta 2-microglobulin levels in adult acute lymphocytic leukemia.

Elevated serum beta-2 microglobulin (beta 2M) levels are associated with poor prognosis in several lymphoproliferative disorders including multiple myeloma and lymphoma. Their prognostic relevance in acute lymphocytic leukemia (ALL) is unknown. We analyzed the associations of serum beta 2M levels at diagnosis with pretreatment characteristics and with prognosis in adult ALL. One hundred fifty-nine adults with newly diagnosed ALL were investigated. Serum beta 2M levels were determined at diagnosis, on fresh peripheral blood samples, using a radioimmunoassay, the Pharmacia beta 2 Micro RIA (Pharmacia Diagnostics, Uppsala, Sweden). Statistical correlations were assessed by standard methods, and further independent prognostic value of serum beta 2M was determined by multivariate analysis. Patients with beta 2M levels of 4.0 mg/L or above had a lower complete response rate (61% versus 80%; p = 0.02), a significantly worse survival (p < 0.01), and a significantly higher association with development of central nervous system (CNS) leukemia (p < 0.01). High beta 2M levels were more common among patients with older age, with elevated creatinine, bilirubin, and alkaline phosphatase levels, with low albumin levels, and with B-cell disease. Multivariate analysis for survival indicated the beta 2M level to be an independent prognostic variable (after adjusting for pretreatment creatinine level and age). The evaluation of beta 2M levels within low- and high-risk groups for CNS disease suggested an association of elevated beta 2M levels with a worse incidence of CNS disease in the high-risk patients. Monitoring serum beta 2M levels may provide significant prognostic information in adults with ALL and should be included in their pretreatment evaluation. Its importance in childhood ALL requires investigation.


Diabetic cutaneous microangiopathy.

To determine a potential relationship between skin blood flow changes and the duration of diabetes and the presence of other microvascular complications. Skin blood flow was measured by laser Doppler techniques at the finger and toe pulps, areas of predominant arteriovenous anastomotic (AVA) flow, and on the finger and toe dorsums, which have a greater nutritive microvascular contribution, in 83 diabetic patients and 39 nondiabetic control subjects. The average duration of diabetes was 14 +/- 1 years. Thirty-four patients had retinopathy. Eighteen patients had proteinuria. Forty patients had definite signs and symptoms of neuropathy, whereas 11 had no detectable neuropathy. There was little difference between diabetic and nondiabetic skin blood flow at normal body temperatures. However, at an elevated skin temperature of 44 degrees C, significant reductions in skin blood flow versus control were demonstrated in the diabetic group. Skin blood flow at finger and toe dorsums showed a decrease as a function of the duration of diabetes. In contrast, there was little, if any, relationship between the duration of diabetes and skin blood flow at the finger and toe pulps. Diabetic patients with retinopathy had significantly lower blood flow at both finger and toe dorsums than those without retinopathy. Even excluding patients with recent onset of diabetes from the analysis, flows at finger (18.6 +/- 2.0 mL/min/100 g) and toe dorsums (11.2 +/- 1.4 mL/min/100 g) in the patients with retinopathy were significantly lower than in diabetic patients without retinopathy [finger: 28.6 +/- 2.7 mL/min/100 g (p < 0.01) and toe: 15.1 +/- 1.5 mL/min/100 g (p < 0.05)]. The presence of proteinuria was also associated with lower blood flow at the toe dorsum. There were no differences between patients with or without clinical diabetic neuropathy. At finger and toe pulps, there were no significant differences between diabetic patients with or without retinopathy, proteinuria, or neuropathy. There appears to be a diabetic cutaneous microangiopathy that coexists with diabetic retinal and renal microvascular disease. This process is expressed primarily at sites of nutritive microvasculature. The ability to use the skin as a model for diabetic microangiopathy would have great practical importance, both experimentally and in clinical practice.


Pulmonary function in systemic lupus erythematosus is related to distinct clinical, serologic, and nailfold capillary patterns.

The purpose of this study was to investigate whether systemic lupus erythematosus (SLE) patients with interstitial lung disease represent a particular subset of patients characterized by the presence of clinical, serologic, and nailfold capillary patterns overlapping scleroderma. In 57 consecutive patients with SLE, a standardized detailed history was obtained and a physical examination performed, directed at signs and symptoms of connective tissue diseases, in particular scleroderma. Additionally, pulmonary function testing, chest radiography, radionuclide transit studies of the esophagus, nailfold capillary microscopy, and detailed serologic studies directed at the antigenic specificities of antinuclear antibodies were performed. Patients were divided into three groups based on the results of pulmonary function testing, i.e., normal lung function, restriction, or isolated impairment of diffusion. Clinical, serologic, and nailfold capillary microscopic findings were compared among these three groups. Twenty patients had normal lung function, 19 had restrictive lung function loss, and 9 had an isolated impairment of the diffusing capacity (T1,CO). Patients with obstructive lung disease (n = 9) were excluded from analysis. Sclerodermatous changes of the hands were associated with a restrictive lung function pattern. Interstitial changes on chest radiograph were associated with isolated impairment of T1,CO. Nailfold capillary abnormalities correlated with decreased T1,CO and Dm, the component of T1,CO representing the diffusing capacity of the alveolocapillary membrane. Antibodies to U1-RNA were associated with restrictive lung function and decreased T1,CO. We conclude that interstitial lung disease is present in a subset of SLE patients characterized by an increased prevalence of scleroderma traits and anti-(U1)RNA antibodies. Microvascular changes may contribute to the development of interstitial lung disease in SLE as well as in scleroderma.


Transforming growth factor beta within fibrotic scleroderma lungs.

Since transforming growth factor beta (TGF beta) has been implicated as an important mediator of pulmonary fibrosis, we measured TGF beta protein and gene expression in alveolar epithelial lining fluid (ELF) of fibrotic scleroderma lungs sampled by bronchoalveolar lavage (BAL). TGF beta protein was qualitatively examined by Western blot analysis, and quantitatively by radioreceptor assays. Gene expression was evaluated in BAL mononuclear cells by Northern blot analysis with quantification of relative gene expression by densitometric analysis of the autoradiograms. Normal and scleroderma subjects had a 24-kd protein that comigrated with defined human TGF beta 1 and immunoreacted with anti-TGF beta antibody. The normal population had a significantly higher average TGF beta concentration (705 pM) compared with the scleroderma subjects (177 pM). The TGF beta 1 gene was expressed in amounts that did not significantly differ between the scleroderma and normal groups. On an individual subject basis, the TGF beta concentration variability did not correlate with variations in BAL cellularity or TGF beta 1 gene expression within the recovered mononuclear cells. It is concluded that both normal and fibrotic lungs have TGF beta 1 present at the alveolar epithelial surface. However, in the fibrotic scleroderma lungs, TGF beta protein content and gene expression were not increased at the alveolar epithelial surface. The simultaneous analysis of TGF beta protein content, gene expression, and cellular constituents within individual ELF specimens showed that the cellular components of the ELF do not appear to be major determinants of TGF beta protein concentration at the alveolar epithelial surface.


Prevalence and prognosis of chronic obstructive pulmonary disease among 5,839 consecutive patients with acute myocardial infarction. SPRINT Study Group.

The purpose of this study was to report the prevalence and the clinical significance of clinically recognized chronic obstructive pulmonary disease (COPD) during acute myocardial infarction. During 1981 to 1983, a secondary prevention study with nifedipine (SPRINT) was conducted in Israel among 2,276 survivors of acute myocardial infarction. During the study, demographic, historical, and medical data were collected on special forms for all patients with diagnosed acute myocardial infarction in 13 hospitals (the SPRINT Registry, n = 5,839). Mortality follow-up was completed for 99% of hospital survivors for a mean follow-up of 5.5 years (range: 4.5 to 7 years). The prevalence of COPD was 7% (406 of 5,839). The latter rate increased significantly in men (7.6%), smokers (9.7%), and older patients (70 years or older, 10.0%). Patients with COPD exhibited a complicated hospital course with an in-hospital mortality rate of 23.9%. Subsequent mortality rates in survivors at 1 and 5 years were 12.3% and 35.9%, respectively. Rates at the same time periods in patients without COPD were 17.2%, 9.2%, and 26.9% (p < 0.005 for in-hospital and 5 years). In a multivariate analysis that included age, gender, and history of myocardial infarction and congestive heart failure, COPD was not independently associated with either in-hospital or postdischarge excess fatality rates. In this large cohort of consecutive patients with myocardial infarction, the prevalence of COPD was 7% and higher among smokers, men, and elderly patients. Although in-hospital and postdischarge mortality rates were higher among patients with COPD, this condition did not independently increase either the risk of early death or the risk of long-term mortality among survivors of acute myocardial infarction.


Bone mineral density and abstention-induced changes in bone and mineral metabolism in noncirrhotic male alcoholics.

Abuse of alcohol may derange bone metabolism and cause osteoporosis. Due to confounding factors associated with alcohol abuse, however, the effect of alcohol itself on bone loss remains obscure. The influence of alcohol intake on bone and mineral metabolism is rather well known, but how the metabolism normalizes during withdrawal has rarely been investigated. The aims of the present study were to evaluate the alcohol-induced changes of bone and mineral metabolism and their recovery during abstention, and to reassess any possible link between alcohol abuse and osteoporosis. We studied 27 non-cirrhotic male alcoholics hospitalized for 2 weeks for withdrawal. For comparison, three groups of control subjects were examined. Serum and urinary parameters of bone and mineral metabolism as well as intestinal absorption of calcium were determined at the beginning and end of the treatment period. Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry at four axial sites (lumbar spine, femoral neck, Ward's triangle, trochanter). On admission, bone formation in the alcoholics was reduced as reflected by decreased serum levels of osteocalcin (-28%; p < 0.05) and procollagen I carboxyterminal propeptide (-17%; p < 0.05). Both parameters normalized within 2 weeks of abstention (p < 0.0001 and p < 0.01, respectively). Urinary hydroxyproline, a parameter of bone resorption, was at the control level on admission and increased slightly during abstention (p < 0.05). Serum ionized calcium increased by 3% (p < 0.0001) during withdrawal. Concomitantly, serum free fatty acids (FFA) decreased by 38% (p < 0.001), and there existed an inverse correlation (r = -0.50, p < 0.05) between changes in ionized calcium and FFA. Serum levels of intact parathyroid hormone and vitamin D metabolites were similar in patients and controls throughout the whole observation period. Intestinal absorption of calcium measured by stable strontium was 37% higher in alcoholics than in controls (p < 0.001); it decreased to nearly normal toward the end of the treatment period. Mean axial BMD did not differ between patients and controls at any of the four measurement sites. However, BMD decreased parallel with duration of drinking history in the alcoholics at all axial sites (p < 0.05 to < 0.01, analysis of covariance with age and weight as covariates). Decreased bone formation, which is uncoupled from ongoing bone resorption, recovers completely during 2 weeks of abstention. In the absence of confounding factors, the central BMD is normal in noncirrhotic male alcoholics, although the negative effect of alcohol on BMD is evident when duration of excessive drinking is taken into account.


Coagulation, fibrinolytic, and inhibitory proteins in acute myocardial infarction and angina pectoris.

The role of thrombus formation in the pathogenesis of acute myocardial infarction (AMI) and unstable angina pectoris has been well established. However, comprehensive and systematic studies of the blood coagulation, fibrinolytic, and inhibitory proteins are not available in patients with these conditions. Fourteen patients with AMI, 10 patients with angina pectoris, and 32 normal volunteers were studied. Plasma antigen concentrations and/or activities of high-molecular-weight kininogen (HMWK), fibrinogen, fibronectin, plasminogen, D-dimer, tissue plasminogen activator (t-PA), alpha 2-antiplasmin, alpha 2-macroglobulin, alpha 1-antitrypsin, protein C, total and free protein S, antithrombin III (AT-III), von Willebrand factor (vWF), factors (F) XII, XI, IX, VIII, VII, X, V, II, and XIII, and plasma antiplasmin activity were measured using appropriate functional or immunologic assays. The AMI group showed a significant reduction in F XII activity, F XII activity-to-concentration ratio, and HMWK concentration. In addition, the AMI patients exhibited a significant elevation of plasma F XI activity, F IX concentration, and F IX activity, and vWF, fibrinogen, D-dimer, and t-PA concentrations. This was associated with significant reductions in F V, F II, and AT-III activity-to-concentration ratio. Many of the changes observed in AMI patients were also present in patients with angina pectoris. Furthermore, the latter group exhibited an elevation of F VIII activity, alpha 2-macroglobulin activity, and alpha 1-antitrypsin concentration and a significant reduction of antiplasmin activity despite a normal alpha 2-antiplasmin concentration. The observed reduction of the plasma F XII activity-to-antigen concentration ratio combined with a reduced HMWK concentration suggests intrinsic pathway activation, while the elevation of the D-dimer concentration indicates thrombin generation and fibrin formation and degradation in the AMI group. The latter changes were also present in patients with angina pectoris. Both AMI and angina groups showed several other abnormalities of the coagulation, fibrinolytic, and inhibitory systems. The results suggest the presence of a prothrombotic state associated with the activation of coagulation and fibrinolytic systems in patients with acute myocardial ischemia or infarction.


Plasma lipoprotein (a) protein concentration and coronary artery disease in black patients compared with white patients.

This study examines the relation between lipoprotein (a) protein levels and other lipid parameters and coronary artery disease in white and black patients. Plasma lipoprotein (a) protein levels were measured prior to coronary angiography in a population of 127 white and 111 black patients. Each angiogram was given a total coronary artery disease score based on the number and severity of atherosclerotic coronary lesions. White and black patients exhibited no differences in total plasma cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. Black patients had higher lipoprotein (a) protein levels than white patients (8.6 versus 4.0 mg/dL; p < 0.0001). The extent and severity of coronary artery disease was the same in white and black patients. White and black patients with coronary artery disease had higher lipoprotein (a) levels than patients without coronary lesions (4.37 versus 1.99 mg/dL, p = 0.027 for white; 9.23 versus 6.87 mg/dL, p = 0.072 for black). In both groups of patients, there was a weak but significant positive correlation between lipoprotein (a) protein levels and coronary artery disease score. Lipoprotein (a) is higher in patients with coronary artery disease. Black patients have higher plasma lipoprotein (a) protein levels than white patients and a comparable degree of coronary artery disease. It follows that the cardiovascular pathogenicity of lipoprotein (a) is not significantly greater in black patients despite higher lipoprotein (a) levels.


Value of functional status as a predictor of mortality: results of a prospective study.

To assess the value of functional status questions in predicting mortality, we conducted a 4-year prospective longitudinal follow-up study of functionally impaired community-dwelling elderly persons. A total of 282 elderly (aged 64 years or older) patients of 76 community-based physicians who were UCLA clinical faculty members were assessed at baseline and at an average of 51 months later using scales from the Functional Status Questionnaire. By the end of the study, 24% of the sample had died. By means of a multivariate model, the following baseline characteristics were independently predictive of death: greater dysfunction on a scale of intermediate activities of daily living, male gender, living alone, white race, better quality of social interactions, and age. Initial baseline functional measures were also predictive of follow-up health status perceptions. The assessment of information on physical functioning and the quality of social interactions provides prognostic information regarding mortality. Furthermore, of the independent predictors of death identified in this sample, only functional impairment and living alone are remediable. Whether improving functional status can reduce the risk of mortality remains to be determined.


Paroxysmal nocturnal hemoglobinuria as a marker for clonal myelopathy.

Paroxysmal nocturnal hemoglobinuria (PNH) is recognized as a clonal disorder manifested as increased sensitivity of marrow cells to complement. Case reports have associated this condition with leukemia, myelodysplasia, and myeloproliferative disorders. We identified 47 patients with PNH from 1976 to 1990. In 9 of the 47 patients, PNH was associated with another clonal myelopathy. Five patients had PNH and a myelodysplastic syndrome, and four had PNH and agnogenic myeloid metaplasia. PNH preceded the development of myelodysplastic syndrome but occurred after the development of agnogenic myeloid metaplasia. This is the largest series of PNH and other clonal myelopathies. We suggest that the PNH defect may represent a second manifestation of a single stem cell disorder.


Antineutrophil cytoplasmic antibodies: a still-growing class of autoantibodies in inflammatory disorders.

Antineutrophil cytoplasmic antibodies (ANCA) have been described as sensitive and specific markers for active Wegener's granulomatosis (WG). ANCA in WG produce a characteristic cytoplasmic staining pattern of neutrophils (c-ANCA) and are directed against proteinase 3 (Pr3), a serine protease from the azurophilic granules. c-ANCA, more or less equivalent to anti-Pr3, occur in more than 90% of patients with extended WG, in 75% of patients with limited WG without renal involvement, and in some 40% to 50% of patients with vasculitic overlap syndromes suggestive of WG such as microscopic polyarteritis. The presence of c-ANCA is highly specific for those diseases (greater than 98%). Changes of levels of c-ANCA precede disease activity and may be used as guidelines for treatment. Antibodies producing a perinuclear staining of ethanol-fixed neutrophils (p-ANCA) occur in a wide range of diseases. They are directed against different cytoplasmic constituents of neutrophils. Among those, antibodies to myeloperoxidase are found in patients with idiopathic crescentic glomerulonephritis, the Churg-Strauss syndrome, polyarteritis nodosa with visceral involvement, and vasculitic overlap syndromes. Their specificity for this group of necrotizing vasculitides is high (94% to 99%), although they may occur in patients with hydralazine-induced glomerulonephritis, anti-glomerular basement membrane disease, and possibly in some patients with idiopathic systemic lupus erythematosus. Antibodies to leukocyte elastase are incidentally found in patients with vasculitic disorders, whereas lactoferrin antibodies are detected in patients with primary sclerosing cholangitis with or without ulcerative colitis and in rheumatoid arthritis. Their diagnostic significance awaits further studies. p-ANCA of undefined specificity may distinguish ulcerative colitis (sensitivity of 75%) from Crohn's disease (sensitivity of 20%). p-ANCA also occur in autoimmune liver diseases: in 75% of patients with chronic active hepatitis, in 60% to 85% of those with primary sclerosing cholangitis, and in about 30% of patients with primary biliary cirrhosis. Finally, p-ANCA are detected in chronic arthritides and in some 5% of healthy controls. Assessment of their diagnostic value has to await further characterization of the antigens involved, allowing the development of antigen-specific assays.


Interventricular septal rupture complicating acute myocardial infarction: from pathophysiologic features to the role of invasive and noninvasive diagnostic modalities in current management.

Rupture of the interventricular septum is a serious complication of acute myocardial infarction, accounting for 5% of deaths due to acute infarction. The septal perforation most frequently occurs during the first week after the infarction. The majority of these patients present with at least two-vessel coronary artery disease, and most cases have a total occlusion of the infarct-related artery. The degree of associated right ventricular damage is clinically important. Unpredictable hemodynamic deterioration can rapidly develop in 80% of the patients, and mortality with medical therapy alone exceeds 90%. Because the preoperative hemodynamic status of these patients appears to be a major determinant for survival, accurate diagnosis, urgent management, and early operative correction are necessary to avoid a catastrophic clinical outcome. Traditionally, diagnostic procedures included first, the insertion of a pulmonary artery catheter for recording of pressures, sequential oximetry, and calculation of the shunt's magnitude and the cardiac output followed by left ventriculography and coronary arteriography for angiographic demonstration of the shunt and the coronary anatomy. Currently, optimal utilization of color flow Doppler and two-dimensional and transesophageal echocardiography offers a significant clinical advantage and can be used to shorten the time spent on diagnosis, evaluation, and management prior to the urgent surgical repair. The elimination of time-consuming diagnostic tests can contribute to further improvement in the survival rate.


Role of antibodies to tubulointerstitial nephritis antigen in human anti-tubular basement membrane nephritis associated with membranous nephropathy.

We report three patients, from two unrelated families, with anti-tubular basement membrane (TBM) antibody nephritis associated with membranous nephropathy. This rare disorder is characterized by nephrotic syndrome, tubular dysfunction, and progression to renal failure. Direct immunofluorescent studies in these patients revealed linear IgG deposition along the proximal TBM, while circulating antibodies reacting with proximal TBM but not with glomerular basement membrane were identified by indirect immunofluorescence. Sera from all three patients reacted by enzyme-linked immunosorbent assay and Western immunoblotting with purified 58-kd tubulointerstitial nephritis (TIN) antigen isolated from TBM. Additional reactivity with a 175-kd component, which may be a higher-molecular-weight form of TIN antigen, was observed by immunoblotting. Since recurrent Fanconi syndrome was seen after transplantation in one patient, anti-TBM antibodies were removed by plasmapheresis prior to kidney transplantation in the other two patients. Neither patient has clinical evidence of recurrent anti-TBM nephritis in the allograft despite the posttransplantation reappearance of anti-TBM antibodies in the serum of one patient. Serologic and molecular HLA class I and class II polymorphism analysis has identified the presence of both HLA-B7 and -DRw8 antigens in two unrelated affected individuals (0.3% expected frequency in the white population). We conclude that sera from patients with anti-TBM nephritis associated with membranous nephropathy react with 58-kd TIN antigen previously implicated in the pathogenesis of primary anti-TBM nephritis. This rare autoimmune disorder may be HLA associated with B7 and/or DRw8, providing susceptibility to the disease. Further investigation is needed to understand the pathogenesis of recurrent anti-TBM nephritis in the renal allograft.


Trisomy 12 in pediatric granulosa-stromal cell tumors. Demonstration by a modified method of fluorescence in situ hybridization on paraffin-embedded material.

The use of fluorescence in situ hybridization (FISH) to detect chromosomal abnormalities has many applications. Use of FISH on archival, paraffin-embedded material has been limited to microscopic sections. We have carried out FISH on preparations of disaggregated nuclei obtained from paraffin-embedded tissue to evaluate chromosome 12 copy number in granulosa-stromal cell neoplasms occurring in infants, children, and adolescents. Trisomy 12 was detected in the majority of cells from three of four juvenile granulosa cell tumors (three ovarian and one testicular) and one malignant granulosa cell tumor. Tetrasomy 12 was observed in a case of ovarian thecoma.


Identification of monoclonal B-cell populations by rapid cycle polymerase chain reaction. A practical screening method for the detection of immunoglobulin gene rearrangements.

Alternatives to Southern blot hybridization for gene rearrangement analysis are being studied because of the time, labor, cost, and radioisotopes required for this technique. We have utilized a rapid, hot air, thermocycling polymerase chain reaction (PCR) system to examine various lymphoproliferative disorders for immunoglobulin heavy chain (IgH) gene rearrangements. This unique system amplifies DNA from 10 microliters samples placed in glass capillary tubes, over a total cycle time of about 30 minutes. Amplified bands are easily visualized on ethidium bromide-stained agarose gels. Forty-one monoclonal B-cell proliferations, 27 reactive lymphoid hyperplasias, 17 T-cell lymphomas and 3 cases of Hodgkin's disease were studied. All 88 cases were fully characterized by morphologic, immunophenotypic, and genotypic (Southern blot) analyses. Each case was separately evaluated by PCR with two primer pairs: 1) IgH variable region (VH) and IgH joining region (JH) and 2) bcl-2 and JH. Thirty-four of 41 monoclonal B-cell proliferations revealed a distinct band (within an expected base pair range) with 1 or both primer combinations supporting B-cell monoclonality; the other 7 cases were considered false negatives. The 47 entities without IgH gene rearrangements detectable by Southern analysis demonstrated no amplified product or a smear of amplified DNA with no distinct band. The overall specificity of PCR was 100%, and the sensitivity was 83% when directly compared with Southern blot analysis. Although its sensitivity is currently less than optimal, PCR is a rapid and practical screening method for the detection of IgH gene rearrangements. If a positive result is obtained no further analysis is required; however, if there is a negative result, standard Southern blot analysis should be performed to definitively exclude the presence of a monoclonal B-cell population in the sample.


An ultrastructural analysis of tumor-promoting phorbol diester-induced degranulation of human basophils.

Release reactions stimulated in human basophils by a variety of secretagogues show biochemical and morphologic differences as well as similarities. Biochemical differences include those of rate, amount, and order of mediator release, as well as mediator type released or generated. Morphologic diversity of release reactions includes prototypic anaphylactic degranulation (AND), or piecemeal degranulation (PMD), and a continuum of anatomic release comprised of PMD followed by AND that is seen when human basophils are stimulated by the bacterial peptide, formyl methionyl leucyl phenylalanine (FMLP). AND is characterized by extrusion of membrane-free granules through multiple plasma membrane pores; PMD is characterized by partially to completely empty, nonfused granule containers in the cytoplasm of basophils. AND is further characterized by diminished-to-absent granules and reduced cytoplasmic vesicles at peak histamine release intervals; PMD does not show decreases in numbers of granules, and cytoplasmic vesicles are plentiful. Smooth membrane-bound vesicles with granule particles and vesicles that appear empty comprise this organelle population. PMD is the single most evident activation change present in basophils that traffic into tissues in multiple diseases in vivo. In this study, we examined the ultrastructural kinetic morphology associated with stimulation of human basophils with tetradecanoyl phorbol acetate (TPA)--a tumor-promoting phorbol diester known to elicit histamine (but not LTC4) release. Partially purified human basophils were prepared for electron microscopy and examined either after control incubations in buffer alone or at 0 time, 1, 2, 5, 10, 30, and 45 minutes after TPA stimulation. Standard morphology and ultrastructural quantitation of vesicles and granules and contents of vesicles or alteration of granules was done and compared with previous ultrastructural kinetic analyses of human basophil release reactions stimulated by different triggers. Like biochemical studies that have determined that TPA is a unique secretogogue for human basophils, the morphology stimulated by TPA and associated with histamine release was also unique. For example, very minor images of AND were evident. Far greater amounts of PMD were imaged. PMD was associated with approximately 50% alteration of cytoplasmic granules by 45 minutes after TPA stimulation. This evidence of empty granules was associated with, and preceded by, a rapid, extensive, and sustained increase in particle-containing cytoplasmic vesicles, as compared with buffer controls (P < 0.001 for each TPA stimulation time compared with unstimulated basophils). In addition, previously undescribed interactions of releasing granules and their overlying plasma membranes characterized TPA-stimulated cells.(ABSTRACT TRUNCATED AT 400 WORDS)


High-resolution analyses of two different classes of tumor cells in situ tagged with alternative histochemical marker genes.

To evaluate interactions of two different tumor cell classes during the establishment of micrometastases at the single-cell level, two different BALB/c 3T3 tumor cell derivatives were established that harbor different histochemical marker genes: bacterial lacZ in a EJ-Harvey ras transformant (abbreviated LZEJ cells) and human placental alkaline phosphatase (ALP) gene in a human c-sis transformant (APSI cells). Several different histochemical staining methods were evaluated, using the distinctiveness of lacZ and ALP gene activities, for identification of these cell classes singly or together in the lung after their intravenous injection into nude mice. LZEJ and APSI cells could readily be distinguished from each other after co-injection by using specific and sequential staining protocols of whole organs or sections; staining of host organ cells was minimized. Co-injection of the two tumor cell classes resulted in similar numbers of homogeneous microfoci in lungs of LZEJ or APSI cells within minutes after injection that persisted for several hours before clearance of most of them. Furthermore, a significant percentage of foci could be identified containing both classes of tumor cells on whole-organ or section evaluations; these cohabiting foci resisted clearance from lungs. Therefore, use of two different histochemical marker genes to tag different classes of tumor cells provides a powerful approach for determining their in situ co-localization, cooperation, or interference with the establishment and development of micrometastases, as well as an opportunity to evaluate gene regulation in situ at the single-cell level.


Immunohistochemical analysis of p53 expression in malignant lymphomas.

p53 is a tumor suppressor gene that commonly undergoes mutations in human tumors, including lymphomas. Because p53 mutations are not restricted to a single locus, immunohistochemistry is useful to detect p53 expression and correlate this finding with lymphoma phenotype. Cryostat sections from 125 cases of lymphoma were analyzed for p53 expression using three different monoclonal antibodies (pAb 421, 1801, 240) which react with human cellular p53 and a common conformational epitope on mutant p53. A control antibody (pAb 246) reacts only with wild type p53 of murine origin and was negative in all cases. Tissue from 29 cases of lymphoid hyperplasia, including six from human immunodeficiency virus-positive (HIV+) patients, were negative for p53. p53 was predominantly localized in nuclei of high-grade lymphomas, including 14 of 46 cases of B cell immunoblastic lymphomas and two of five T cell immunoblastic lymphomas. p53 expression was relatively common in lymphomas from HIV+ patients, and unusual in intermediate and low-grade lymphomas of follicular center cell type. Low-grade lymphoma of small lymphocytic type disclosed p53+ large cells (paraimmunoblasts) that may play a role in tumor progression in this lymphoma subtype. p53 was also strongly expressed in the nuclei of Reed Sternberg cells from 19 of 37 cases of Hodgkin's disease, including six cases of mixed cellularity, and 13 cases of nodular sclerosing type. Immunohistochemical staining is a rapid method to identify p53 expression in lymphomas.


Transient disruptions of aortic endothelial cell plasma membranes.

Cells of gut, skin, and muscle frequently suffer transient survivable plasma membrane disruptions ("wounds") under physiological conditions, but it is not known whether endothelial cells of the aorta, which are constantly exposed to hemodynamically generated mechanical forces, similarly are injured in vivo. We have used serum albumin as a molecular probe for identifying endothelial cells of the rat aorta that incurred and survived transient plasma membrane wounds in vivo. Such wounded endothelial cells were in fact observed in the aortas of all rats examined. However, the percentage of wounded cells in the total aortic endothelial population varied remarkably between individuals ranging from 1.4% to 17.9% with a mean of 6.5% (+/- 4.6% SD). Wounded endothelial cells were heterogeneously distributed, being found in distinct clusters often in the shape of streaks aligned with the long axis of the vessel, or in the shape of partial or complete rims surrounding bifurcation openings, such as the ostia of the intercostal arteries. Physical exercise (running) did not increase the frequency of aortic endothelial cell membrane wounding, nor did spontaneous hypertension. Surprisingly, 80% of mitotic endothelial cell figures were identified as wounded. This article identified a previously unrecognized form of endothelial cell injury, survivable disruptions of the plasma membrane, and shows that injury to the endothelial cells of the normal aorta is far more commonplace than previously suspected. Plasma membrane wounding of endothelial cells could be linked to the initiation of atherosclerosis.


Peripheral T-cell lymphomas of the intestine.

Twenty-seven cases of primary peripheral T-cell lymphomas of the intestine (PTLI) were investigated. Seven patients had histories of malabsorption. The most frequent symptoms at presentation were weight loss, abdominal pain, and acute abdomen. The jejunum was the most common site of lymphoma and multifocal disease was found in 72% of the cases. Twenty-two patients (92%) presented with localized disease confined to the intestine and abdominal lymph nodes, only two patients had generalized disease. According to the pattern of lymphoma infiltration and the morphology of the uninvolved small intestinal mucosa, 21 cases were separated histologically into three categories; 1) enteropathy-associated T-cell lymphoma (EATCL, n = 9) showing predominant intramucosal lymphoma spread and villous atrophy of uninvolved mucosa with high density of intraepithelial lymphocytes (IEL), 2) EATCL-like lymphoma without enteropathy (EATCL-LLWE, n = 5) but with an infiltration pattern similar to EATCL, and 3) T-cell lymphoma without features of EATCL (Non-EATCL, n = 7). Distinctive features of EATCL were the high incidence of malabsorption states, multifocal intestinal disease in all cases, and the high frequency of intestinal recurrences. On frozen sections four of eight PTLI showed the phenotype CD3+ CD4- CD8- HML-1+, which is also expressed on a small subset of normal IEL. The morphologic and immunomorphologic findings suggest that the majority of PTLI is derived from mucosal T lymphocytes. This derivation may be responsible for certain biologic features, such as the preferential spread to and relapse of PTLI at small intestinal sites.


Induction of fatty streak-like lesions in vitro using a culture model system simulating arterial intima.

In this study a two-compartment culture model of arterial intima was used for the in vitro induction of fatty streaklike lesions. The apparatus consisted of upper and lower compartments separated by a human amnion membrane stretched between them. Human umbilical vein endothelial cells (HUVECs) were cultured to confluence on the stromal surface of the amnion membrane. Maximal migration of blood mononuclear cells (MCs) through the HUVEC monolayer in response to a f-Met-Leu-Phe gradient was observed at 10(-8) mol/l; the migration was 3.29 times greater than that observed under the condition of random migration (control). In the study of MC transformation into lipid-laden cells in the amnion membrane (foam cell formation in 'arterial intima'), 10(6) MCs were incubated, in the presence of freshly prepared low-density lipoprotein (LDL; 100 microgram/ml). The lipid loading of MCs was time dependent. After 12 hours' incubation, 39% of the MCs that migrated into the amnion membrane contained a small number of lipid droplets, whereas the remaining 61% showed no lipid droplets. Only 1.7% of the cells contained a high number of lipid droplets in the cytoplasm and took on the appearance of foam cells. With time, the number of lipid-laden cells and the amounts of intracytoplasmic lipid droplets gradually increased. At 72 hours after incubation, 65.4% of the MCs were loaded with lipid droplets, and 20.9% of them, an eightfold increase over 12 hours of incubation, showed a foamy cell appearance. Because MCs consist of 70% monocytes and 30% lymphocytes, about 93% of the monocytes were filled with lipid after a 72-hour incubation. Ultrastructural examination showed that lipid-laden cells took on macrophage characteristics, such as wide and heterogeneous cytoplasm, indented nuclei, and abundant lysosomes. A minority of the MCs in the amnion were considered lymphocytes; they had scanty cytoplasm, round nuclei with abundant heterochromatin, no lysosomes, and no lipid vacuoles. In conclusion, the formation of an in vitro fatty streaklike lesion is demonstrated, and this is reminiscent of in vivo human atherogenesis.


Isolation and characterization of granuloma initiation factor.

A soluble component that transfers granulomatous tissue reaction was fractionated from Schistosoma mansoni egg-induced hepatic granulomas (SMHG) by Sephacryl S-300 column chromatography. The fractions separately bound to inert, Affi-Gel agarose beads were inoculated subcutaneously in naive mice. The low molecular weight fraction, consisting of proteins 23 kd, 20 kd, and 16 kd, produced organized granulomas 6 to 7 weeks after inoculation. This fraction was further purified by high-pressure liquid chromatography (HPLC) gel filtration and gave three fractions eluting at retention times of 44, 46, and 48 minutes. Each fraction contained all low-molecular-weight proteins in varying amounts and induced skin granulomas when inoculated subcutaneously. Amino acid sequence of the major 20-kd protein showed 11 N-terminal residues identical to those of cyclophilin. Antisera raised to the protein with retention time of 46 minutes, reacted with cells in the granulomas but not surrounding liver tissue as detected by immunofluorescence microscopy. The findings indicate a low molecular weight soluble fraction of SMHG can induce new granuloma formation when injected in an immobilized form into skin of naive mice. The results suggest granuloma initiation factor is a homolog of the cyclophilin gene family.


Immunohistochemical and histopathologic correlates of Alzheimer's disease-associated Alz-50 immunoreactivity quantified in homogenates of cerebral tissue.

Alz-50 is a monoclonal antibody that immunoreacts with neurofibrillary tangles and neurites in brains with Alzheimer's disease (AD). In addition, the levels of Alz-50 immunoreactivity in brain, measured by either enzyme-linked immunosorbent assay or ALZ-enzyme-linked immunosorbant assay (EIA), are increased in AD relative to age-matched controls. The current study compares the distribution and extent of Alz-50 immunostaining with quantified levels of Alz-50 immunoreactivity measured in adjacent frozen blocks of tissue by ALZ-EIA. The brain tissue studied was obtained from individuals with AD, AD + Down's syndrome (AD + DN), Parkinson's disease with dementia (PD), or AD + PD, and from nondemented aged controls. In AD, AD + DN, and AD + PD, there were significantly higher densities of Alz-50-immunoreactive (AFI) neurons, more abundant diffuse AFI neurites, and higher ALZ-EIA values than in aged controls. In PD, the overall mean density of AFI neurons was significantly lower than in AD and AD + DN, but AFI neurites were as abundant as they were in brains with an AD diagnosis. However, PD was readily distinguished from AD and AD + DN by significantly lower mean ALZ-EIA values, and significantly lower densities of neurofilament-immuno-reactive AD lesions. Multiple-regression analysis demonstrated significant correlations between ALZ-EIA levels and the severity of AD lesions, and the density of AFI neurites, but not with the density of AFI neurons. Therefore, ALZ-EIA levels may represent only a portion of the Alz-50 immunoreactivity detectable by immunohistochemical staining.


Programmed cell death in heterokaryons. A study of the transfer of apoptosis between nuclei.

Thymocytes undergoing apoptosis induced by dexamethasone showed nuclear refractivity changes under Nomarski optics that correlated precisely with internucleosomal DNA degradation and was prevented by cycloheximide. When heterokaryons between thymocytes and 9L or NIH3T3 cells were examined, 99.75% of the nuclei in heterokaryons followed the original and distinct fate characteristic of the parental cells. Thymocyte nuclei proceeded to undergo apoptotic cell death, whereas the 9L and NIH3T3 nuclei in the heterokaryons did not show the morphologic changes of apoptosis or any DNA cleavage on gels, and remained viable and mitotic. Cycloheximide prevented the induction of apoptosis in thymocyte nuclei in the heterokaryons. An excess of up to seven thymocyte nuclei undergoing programmed cell death in a heterokaryon did not detectably damage the 9L nucleus, and an excess of six 9L nuclei did not protect the thymocyte nucleus from apoptosis. The proposed model stating that programmed cell death results from de novo synthesis of death-causing gene products is difficult to reconcile with these findings. A cell-type-specific activity, present in thymocyte nuclei before induction of apoptosis with corticosteroids and unable to diffuse between nuclei, appears to be responsible for DNA fragmentation. These results also show that nuclear disintegration is the trigger of thymocyte death and not a consequence of cell death due to another mechanism.


Changes in thickness and anionic sites of the glomerular basement membrane after subtotal nephrectomy in the rat.

Rats progressively develop proteinuria and glomerular sclerosis with age. These physiologic and histologic changes are accelerated by subtotal renal mass ablation. Alterations in the glomerular basement membrane (GBM), such as thickening and decreased anionic site density, occur during senescence. This study examines the ultrastructural alterations of the GBM affecting remnant glomeruli. Six week-old male Wistar rats underwent a subtotal nephrectomy (70%) and were compared with sham operated rats. Rats were fed a standard diet, and physiologic measurements were performed every 3 weeks. Rats were killed 6 and 12 weeks after surgery. Anionic sites were labeled by polyethyleneimine perfusion before killing. Kidneys were processed for light and electron microscopy. Nephrectomized rats had higher protein-uria than the controls and developed glomerular sclerosis. The GBM of nephrectomized rats were significantly thinner and anionic sites were less numerous 12 weeks after nephrectomy, especially in the lamina densa (LD) of the GBM. The number and distribution of anionic sites were similar to those observed in sham operated rats killed 6 weeks after surgery. These results indicate that glomerular sclerosis and GBM thickening are unrelated phenomena. They also suggest that the number and density of anionic sites in LD are not a prominent factor for increasing proteinuria after subtotal nephrectomy.


Ultrastructural analysis of contractile cell development in lung microvessels in hyperoxic pulmonary hypertension. Fibroblasts and intermediate cells selectively reorganize nonmuscular segments.

The current study traces the development of contractile cells in the nonmuscular segments of rat lung microvessels in hyperoxic pulmonary hypertension. New intimal cells first develop into a well-defined layer beneath the endothelium and internal to an elastic lamina. Ultrastructurally, these cells are found to be 1) fibroblasts recruited to the vessel wall from the interstitium and 2) intermediate cells, a population of preexisting vascular cells (structurally between a smooth muscle cell and a pericyte). Early in hyperoxia (days 3 through 7), interstitial fibroblasts migrate and align around the smallest vessels in which an elastic lamina is either absent or fragmentary. These cells then are incorporated into the vessel wall by tropoelastin secretion and the formation of an elastic lamina along their abluminal margin. After day 7, the new mural fibroblasts acquire the features of contractile cells, namely a basal lamina, extensive microfilaments, and dense bodies. In other vessels, as early as day 3 of hyperoxia, intermediate cells within the vessel intima begin to acquire the additional filaments and dense bodies of contractile cells. As hyperoxia continues, each cell pathway gives rise to vessels with distinct intimal or medial layers of contractile cells. In this way, thick-walled 'newly muscularized' vessel segments form adjacent to the capillary bed.


The occupational hazard of human immunodeficiency virus and hepatitis B virus infection. I. Perceived risks and preventive measures adopted by anaesthetists: a postal survey.

We have conducted a postal survey of members of the Association of Anaesthetists to ascertain perceived risks and preventive measures adopted with regard to the occupational hazard of Human Immunodeficiency Virus and Hepatitis B Virus infection. Despite recognition of the infection risk and the adoption of appropriate measures when managing known infected patients, the majority of anaesthetists have not implemented simple precautions in their daily routine work. Less than 16% of respondents routinely wear gloves and more than one in three still resheath needles. It would appear that the recommendations of the Association with regard to universal safety precautions have not been implemented by the majority of its members.


The occupational hazard of human immunodeficiency virus and hepatitis B virus infection. II. Effect of grade, age, sex and region of employment on perceived risks and preventive measures adopted by anaesthetists.

The effect of grade, age, sex and region of employment on the attitude of anaesthetists to the possible risk of Human Immunodeficiency Virus (HIV) and Hepatitis B Virus (HBV) infection and the measures adopted to minimise the risk were assessed. As a group, anaesthetists in training were more concerned than consultants about the risk of HIV or HBV infection and, as a consequence, were more likely to adopt protective measures. A similar variation was seen with age, younger anaesthetists being more concerned about the risk of infection and adopting preventive measures in greater numbers than their older colleagues. The sex of the anaesthetist had minimal effect on their attitude. Despite the marked variation in the incidence of both HIV and HBV, the attitude of anaesthetists to the risk of infection and the numbers adopting simple preventive measures did not vary significantly on a regional basis throughout the country. However, there was a significant inter-regional variation in the availability and uptake of HBV immunisation (p < 0.01) and knowledge of the existence of local policy guidelines for the management of known HIV or HBV positive patients (p < 0.01).


Estimation of tidal volume from the reservoir bag. A laboratory study.

The accuracy of 21 anaesthetists in estimating tidal volumes from reservoir bag movements was assessed using a model lung apparatus. The breathing system configuration (Mapleson A or D), the grade of anaesthetist, and the years of anaesthetic experience had no effect on accuracy. Greater precision of tidal volume estimation was observed with larger tidal volumes and lower fresh gas flows. The mean systematic error of 18 of the 21 anaesthetists was greater than zero, indicating a general tendency to overestimate tidal volume. This study therefore strengthens the view that clinical observations should be supplemented with information from continuous monitoring devices.


Anaesthesia for myocardial revascularisation. A comparison of fentanyl/propofol with fentanyl/enflurane.

We studied the effects on myocardial performance and metabolism of fentanyl/propofol and fentanyl/enflurane anaesthesia in 20 patients before coronary artery bypass grafting. Anaesthesia was induced with fentanyl 20 micrograms.kg-1 and pancuronium 0.15 mg.kg-1. Patients received, by random allocation, either propofol by infusion, 6 mg.kg-1.h-1 reduced by half after 10 min then adjusted as necessary (mean rate 2.8 mg.kg-1.h-1), or enflurane 0.8% inspired concentration for 10 min reduced to 0.6% and adjusted as required (mean 0.7%). Measurements were made before induction, after tracheal intubation, after skin incision and after sternotomy. There were no significant differences between the groups in any haemodynamic variables during the study. Following intubation both groups showed a rise in heart rate (p < 0.01) and cardiac index (p < 0.05). Systemic vascular resistance decreased after intubation (p < 0.05) then returned to baseline during surgery; stroke index was unchanged after intubation but was reduced during surgery (p < 0.01) as systemic vascular resistance increased. Regional and global coronary blood flow were maintained in both groups, as were myocardial oxygen consumption and lactate extraction ratio. However, lactate production did occur in one patient receiving enflurane and Holter monitoring confirmed ischaemia. One patient receiving propofol showed lactate production not accompanied by any ECG changes. This study suggests that propofol may be a suitable alternative to enflurane as an adjunct to opioids in anaesthesia for coronary artery bypass grafting.


Vital capacity breath technique for rapid anaesthetic induction: comparison of sevoflurane and isoflurane.

This study compares vital capacity rapid inhalational induction of anaesthesia with sevoflurane and isoflurane. Forty-six volunteers undergoing the procedure had one of the two agents: 25 had sevoflurane and 21 isoflurane. Subjects were unpremedicated and breathed approximately 1.7 MAC equivalents of either vapour. There were no significant differences in the patients' monitored cardiovascular, respiratory, and electrocardiographic variables. The mean time for induction of anaesthesia with sevoflurane (120 s) was significantly shorter than with isoflurane (145 s), reflecting its higher blood-gas solubility. There were fewer induction complications in the sevoflurane group. Subjects in the sevoflurane group found the induction of anaesthesia more pleasant and were more willing to undergo it again compared to subjects in the isoflurane group. We conclude that sevoflurane is superior to isoflurane in vital capacity rapid inhalational induction of anaesthesia, particularly in instances where premedication should be avoided.


Upper oesophageal sphincter pressure during inhalational anaesthesia.

Upper oesophageal sphincter pressure was recorded with a Dent sleeve in 30 patients breathing nitrous oxide, oxygen and halothane. Twenty-three patients, after thiopentone induction, received suxamethonium and had their trachea intubated either before (group A, n = 11), or after (group B, n = 11), a study period of inhalational anaesthesia. Group C (n = 8) received an inhalational induction. Mean (SD) sphincter pressure after loss of consciousness was 8 (7) mmHg (group A), 6 (5) mmHg (group B) and 24 (13) mmHg (group C) increasing to 19 (7) mmHg in group A immediately after intubation. With an end-tidal halothane concentration of 1.5%, mean sphincter pressure in group B, 16 (7) mmHg, was significantly lower than in group A, 45 (21) mmHg (p < 0.001) and group C, 27 (14) mmHg (p < 0.05). Halothane had no dose-related effect on sphincter pressure. Insertion of a laryngeal mask in group C (n = 7) had no significant effect on sphincter pressure. Induction and maintenance of anaesthesia with halothane, unlike thiopentone or suxamethonium, maintained a degree of upper oesophageal sphincter tone, although three patients in this study had sphincter pressures of less than 10 mmHg and would therefore have been at risk of regurgitation in the presence of gastro-oesophageal reflux.


Peri-operative liver graft function: monitoring using the relationship between blood glucose and oxygen consumption during anaesthesia.

The purpose of our study was to test the hypothesis that the quotient between plasma glucose and whole body oxygen consumption (VO2) as a 'metabolic index' is a sensitive indicator of early graft function. Arterial levels of glucose and oxygen consumption were determined in 100 consecutive patients during orthotopic liver transplantation performed without anhepatic veno-venous bypass. Patients were divided into survivors with no obvious problems related to graft function and those with primary nonfunction of the graft. The neohepatic increase in VO2 was significantly higher in survivors (112 +/- 4 vs 88 +/- 11 ml.min-1.m-2; p < 0.05), whereas blood glucose levels after reperfusion were higher (352 +/- 18 vs. 287 +/- 36 mg dl-1) in those with primary non-function of the graft. The calculated metabolic index was also higher (4.02 +/- 0.93 vs 2.67 +/- 0.45, p < 0.05) in patients with primary nonfunction of the graft. Our principal conclusion was that 92% of normal functioning liver grafts could be classified correctly by the metabolic index immediately after reperfusion, whereas glucose levels and VO2 alone classified only 67% and 70% of normal functioning liver grafts correctly.


Comparison of digital blood pressure, plethysmography, and the modified Allen's test as means of evaluating the collateral circulation to the hand.

The collateral circulation to the hand was evaluated on 70 hands of healthy volunteers. Comparisons were made between the results of the modified Allen's test alone and the Allen's test combined with either plethysmography or digital blood pressure. The modified Allen's test requires patient cooperation and the results can be subjective. Plethysmography does not require patient cooperation and produces a signal that varies directly with flow; however, this is not a quantifiable signal. Digital blood pressure (measured by the 2300 Finapres noninvasive blood pressure monitor, Ohmeda, Englewood, CO, USA) also requires no patient cooperation. The values produced are of clinical value and reproducible. Both the plethysmograph and digital blood pressure monitors were able to demonstrate the dominant arterial vessel of the hand. The digital blood pressure monitor produces an objective recordable numerical value, an accepted clinical parameter, and it does not require patient cooperation. The use of a digital blood pressure monitor may prove to be an acceptable alternative to the traditional Allen's test.


Erythropoietin in a patient following multiple trauma.

We report on a Jehovah's Witness who had severe blood loss following major trauma. The problems of her management without blood transfusion, and with the use of recombinant human erythropoietin therapy for severe anaemia, are described.


Cimetidine-dobutamine interaction?

The report describes a patient during induction of anaesthesia for coronary artery by-pass grafting, in whom the infusion of dobutamine at a rate of 5 micrograms.kg-1.min-1 resulted in unanticipated severe hypertension. The exaggerated response may be attributed to cimetidine--dobutamine interaction.


The Laerdal pocket mask: effects of increasing supplementary oxygen flow.

To determine the effect of increasing supplementary oxygen flow during ventilation with the Laerdal pocket mask 24 subjects ventilated a modified recording mannikin for four 90 s periods using the mask with oxygen flows of 5 l, 10 l, 15 l and 20 l.min-1. Oxygen concentration increased and carbon dioxide concentration decreased with increasing oxygen flow. Tidal volume also increased with oxygen flow. The delivered oxygen concentrations were lower than previously reported at all four rates; however, mask function improved with increasing flow up to 20 l.


Pre-oxygenation: the Hudson mask as an alternative technique.

The use of a simple oxygen facemask (Hudson) with high oxygen inflow (48 l.min-1) was investigated as a technique for pre-oxygenation, comparing it with the Magill system (oxygen flow: 100 ml.kg-1.min-1). One hundred and thirty-eight patients scheduled for elective gynaecological and orthopaedic surgery were studied: group 1, Hudson mask and group 2, Magill system (ASA 1-2, n = 107); group 3, Hudson mask and group 4, Magill system (ASA 3, n = 30). Pre-oxygenation was assessed by measuring the times to 97%, 95% and 93% arterial desaturation (finger pulse oximetry) following 3 min of pre-oxygenation. The times taken to achieve these end-points in all the study groups suggest that the Hudson mask offers an alternative technique for pre-oxygenation.


Influence of hearing of 22 G Whitacre and 22 G Quincke needles.

Audiograms were performed pre-operatively and 2 days postoperatively in 48 patients given spinal anaesthesia for transurethral resection of the prostate. Hearing levels were examined at 1000 Hz and below. Either 22 G standard design (Quincke) needles (n = 25) or 22 G pencil-point design (Whitacre) needles (n = 23) were used. Hearing loss of 10 dB or more at two or more frequencies were observed in six of 25 patients in the Quincke group and in two of 23 patients in the Whitacre group. The mean hearing level was more reduced in the Quincke group. The shape of the tip of the spinal needle seems to be of some importance to the effects on hearing level that may occur after spinal anaesthesia.


Baroreflex control of heart rate during high thoracic epidural anaesthesia. A randomised clinical trial on anaesthetised humans.

Baroreflex control of heart rate after cardiac sympathectomy induced by thoracic epidural anaesthesia was evaluated in 30 patients who were randomly assigned to group 1 (bupivacaine 0.25%), group 2 (bupivacaine 0.5%) or group 3 (control). Plasma volume expanders were given to equalize preload conditions, as assessed using transoesophageal echocardiography. All measurements were made under general anaesthesia. Baroreflex sensitivity was determined from the heart rate response to phenylephrine and nitroglycerin. There was no difference in cardiac slowing in response to phenylephrine between the three groups. Baroreflex sensitivity, measured as cardiac acceleration in response to nitroglycerin, was significantly lower (p < 0.01) in groups 1 and 2 (1.8 and 1.5 ms.mmHg-1 respectively) compared with group 3 (3.5 ms.mmHg-1) with no differences between the two bupivacaine concentrations. The results suggest that baroreflex-mediated response to decreases in arterial pressure is dependent on the integrity of the sympathetic nervous system.


Use of adrenaline in obstetric analgesia.

A questionnaire on the use of adrenaline in obstetric analgesia was completed by 87 obstetric anaesthetists: 71% of consultants in teaching hospitals were prepared to use adrenaline mixed with local anaesthetics compared with 33% of consultants in district hospitals; they had a similar duration of obstetric anaesthetic experience. Test doses containing adrenaline were not commonly used in labour, but were more often used prior to elective Caesarean section. Adrenaline was used with either lignocaine or bupivacaine; few consultants used both solutions. Contraindications to the use of adrenaline in the nonuser group were in decreasing order of rank: neurological damage, pregnancy-induced hypertension, stenotic valvular heart disease, sickle cell disease or trait of fetal distress. Overall, the contraindications related to the systemic absorption of adrenaline were most common.


An evaluation of a combined spinal/epidural needle set utilising a 26-gauge, pencil point spinal needle for caesarean section.

We have conducted a prospective study into the ease of use and incidence of postdural puncture headache with the 'Portex' combined spinal/epidural set. The pack contains a 16-gauge Tuohy needle of standard 8 cm shaft length with a matching 26-gauge pencil point spinal needle. The study included 150 consecutive combined spinal/epidural anaesthetics for lower segment Caesarean section. Eighty-eight percent of the cases fulfilled the criteria as technically perfect, i.e. cerebrospinal fluid obtained at the first attempt after identifying the epidural space. There were two cases of significant postdural puncture headache requiring blood patch due to puncture by the 26-gauge spinal needle giving an incidence of 1.3%. This compares favourably with previously reported rates in obstetric patients.


Modified parallel 'Lack' breathing system for use in dental anaesthesia.

A twin-tube breathing system for inhalational anaesthesia in dental surgery is described. The system is a modification of a parallel Mapleson 'A' breathing system and is suitable for use with continuous flow anaesthetic machines. Resistance to airflow has been evaluated and is within the recommended ranges at all flows likely to be experienced in normal clinical conditions. The system is suitable for children and adults, easy to use and efficient. The expiratory valve is located remote from the face and the system is suitable for scavenging by active, assisted or passive systems.


The Gulf war: anaesthetic experience at 32 Field Hospital Department of Anaesthesia and Resuscitation.

The organisation and the workload of the anaesthetic department of a Field Hospital deployed during the Gulf war were described. Suggestions are made as to how the problems encountered might be overcome in the future.


Application of a trochoidal electron monochromator/mass spectrometer system to the study of environmental chemicals.

A trochoidal electron monochromator has been interfaced to a mass spectrometer to perform electron capture negative ion mass spectrometric (ECNIMS) analyses of environmentally relevant chemicals. The kinetic energy of the electron beam can be varied from 0.025 to 30 eV under computer control. No reagent gas is used to moderate the electron energies. An electron energy spread of +/- 0.1 to +/- 0.4 eV full width at half-maximum (fwhm) can readily be obtained at a transmitted current of 2 x 10(-6) A, improving to +/- 0.07 eV at 5 x 10(-7) A. Comparisons of ECNI results from the electron monochromator/mass spectrometer system with those from a standard instrument that uses a moderating gas show similar spectra for heptachlor but not for the s-triazine herbicides, as for example, atrazine. This compound shows numerous adduct ions by standard ECNIMS that are eliminated by using the electron monochromator to generate the mass spectra. Isomeric tetrachlorodibenzo-p-dioxins show distinct differences in the electron energies needed to produce the maximum amount of parent and fragment anions. Multiple resonance states resulting in stable radical anions (M.-) are easily observed for nitrobenzene and for polycyclic aromatic hydrocarbons. Ionic products of dissociative electron capture invariably occur from several resonance states.


High-resolution determination of 147Pm in urine using dynamic ion-exchange chromatography.

A procedure has been developed for measuring 147Pm in bioassay samples, based on the separation and preconcentration of 147Pm from the urine matrix by adsorption onto a conventional cation-exchange column with final separation and purification by HPLC using dynamic ion-exchange chromatography. The concentration of 147Pm is determined by collecting the appropriate HPLC fraction and measuring the 147Pm by liquid scintillation counting. The limit of detection is 0.1 Bq (3 fg) 147Pm based on a 500-mL sample of urine and a counting time of 30 min with a background of 100 cpm. Ten samples can be processed in 1.5-2 days.


Use of spherical targets to minimize effects of neutron scattering by hydrogen in neutron capture prompt gamma-ray activation analysis.

For hydrogenous targets that are thinner than they are wide, element sensitivities (counts.s-1.mg-1) for determining concentrations of elements by neutron capture prompt gamma-ray activation analysis (PGAA) are enhanced relative to sensitivities obtained from measurements on nonhydrogenous materials. These enhancements are caused mainly by elastic neutron scattering by H, which changes the average neutron fluence rate within the matrix. The magnitude of the effect depends on the macroscopic scattering and absorption cross sections and on the size, shape, and orientation of the target with respect to the neutron beam. Sensitivities increase linearly with H density for thin targets of constant size and shape and also vary with target shape. Theoretical work was shown that element sensitivities for hydrogenous targets in the form of spheres are least affected by neutron scattering. Methods were devised for creating solid spheres and for containing liquids in spherical shapes. Element sensitivities were determined for spheres and disks of several hydrogenous materials. For H, B, Cl, K, Br, and Cd, sensitivities for spheres were found to be less affected by neutron scattering. Exceptions were Sm and Gd sensitivities measured in liquids contained in quartz globes.


Data-processing method to reduce error coefficients for membrane-based analytical systems. 1. Amperometric-based sensor evaluated for quantification of oxygen.

This paper describes the use of a predictive, curve-fitting method to reduce the effects of experimental variables on results obtained with membrane-based devices. Multipoint data from the transient regions of responses are used with suitable models and curve-fitting methods to predict the signal that would be measured for the system at equilibrium. The resulting equilibrium response usually is much less dependent on experimental variables than the transient responses used to predict it. The approach is evaluated for the membrane-based amperometric electrode for oxygen. Current vs time data are used to predict the equilibrium current expected when oxygen concentrations are the same on both sides of the membrane. Predicted equilibrium currents vary linearly with oxygen concentration. Relative to the more common steady-state method, the sensitivity of the predictive method is about 5-fold higher, the measurement time is about 17-fold shorter and the dependencies on membrane thickness and stirring rate are 125- and 8-fold lower, respectively. Pooled standard deviations (n = 40) correspond to uncertainties in oxygen concentration of about 0.009 mmol L-1.


Acrylamide polymerization kinetics in gel electrophoresis capillaries. A Raman microprobe study.

The formation of 3.5% T, 3.3% C cross-linked polyacrylamide is monitored in 75-microns-i.d. electrophoresis capillaries by Raman microprobe spectroscopy. The disappearance of the acrylamide 1292-cm-1 band is followed with 60-s time resolution for 30 min, and 2-4 min resolution for up to 10 h. Polymerization is 98% complete in 1.5 h and greater than 99% complete after 2 h. In the 900-1700-cm-1 region no bands attributable to cross-linking are observable. Reaction in the capillary follows second-order kinetics. The reaction is faster in the bulk system because heat dissipation is not sufficient to maintain a constant temperature.


Quantification of the degradation products of sevoflurane in two CO2 absorbants during low-flow anesthesia in surgical patients.

Sevoflurane, a new inhalational anesthetic agent has been shown to produce degradation products upon interaction with CO2 absorbants. Quantification of these sevoflurane degradation products during low-flow or closed circuit anesthesia in patients has not been well evaluated. The production of sevoflurane degradation products was evaluated using a low-flow anesthetic technique in patients receiving sevoflurane anesthesia in excess of 3 h. Sevoflurane anesthesia was administered to 16 patients using a circle absorption system with O2 flow of 500 ml/min and average N2O flow of 273 ml/min. Preoperative and postoperative hepatic and renal function studies were performed. Gas samples were obtained from the inhalation and exhalation limbs of the anesthetic circuit for degradation product analysis and analyzed by gas chromatography/mass spectrometry for four degradation products. The first eight patients received sevoflurane anesthesia using soda lime, and the following eight patients received anesthesia using baralyme as the CO2 absorbant. CO2 absorbant temperatures were measured during anesthesia. Of the degradation products analyzed, only one compound [fluoromethyl-2, 2-difluoro-1-(trifluoromethyl) vinyl ether], designated compound A, was detectable. Concentrations of compound A increased during the first 4 h of anesthesia with soda lime and baralyme and declined between 4 and 5 h when baralyme was used. Mean maximum inhalation concentration of compound A using baralyme was 20.28 +/- 8.6 ppm (mean +/- SEM) compared to 8.16 +/- 2.67 ppm obtained with soda lime, a difference that did not reach statistical significance. A single patient achieved a maximal concentration of 60.78 ppm during low-flow anesthesia with baralyme. Exhalation concentrations of compound A were less than inhalation concentrations, suggesting patient uptake.(ABSTRACT TRUNCATED AT 250 WORDS)