Do microscopic abnormalities at resection margins correlate with increased anastomotic recurrence in Crohn's disease?

The relationship between histologic changes at resection margins and anastomotic recurrence was evaluated in patients with Crohn's disease. Pathology and medical records from 1960 to 1977 identified 100 patients who met the following criteria: 1) no prior surgery for Crohn's disease, 2) small bowel or small bowel and colonic resection with anastomosis done for Crohn's disease at the Cleveland Clinic, and 3) resection margins available for microscopic analysis. The following histologic features of the margins were evaluated: edema, inflammation, lymphoid aggregates, pyloric metaplasia, fibrosis, cryptitis and crypt abscesses, ulcers, granulomas, villous shortening, mucin depletion, neuronal hyperplasia, and transmural inflammation. Additionally, margins were categorized as histologically normal, showing nonspecific changes, showing changes suggestive of Crohn's disease, and showing changes diagnostic for Crohn's disease. Anastomotic recurrence occurred in 50 patients after an average follow-up period of 11.5 years. Cumulative recurrence-free rates for the four margin categories were not significantly different. Anastomotic recurrence was not associated with any clinical or histologic feature or combination of features.     

The oxidative metabolism of circulating phagocytes in ankylosing spondylitis: determination by whole blood chemiluminescence

OBJECTIVE: Superoxide anion radicals within the human body are regarded as a major cause of inflammation. However, their role in the pathogenesis of ankylosing spondylitis (AS) has not been well identified. This study aimed at investigating the relation between AS and the oxidative metabolism of phagocytes in whole blood. METHODS: 24 patients with classic AS were examined to determine their clinical status; complete blood count, erythrocyte sedimentation rate (ESR), and C reactive protein (CRP) were determined, and levels of the superoxide anion radicals in the patients with AS and 21 healthy subjects were assessed by the ultraweak chemiluminescence method. Subsequently, the relation between this disease and phagocytes was examined by using N-formyl-methionyl-leucyl-phenylalanine (fMLP) and phorbol-12-myristate-13-acetate (PMA) stimulants. RESULTS: In clinical assessments, patients with AS had abnormally raised serum CRP (>10 mg/l) and ESR (>15 mm/1st h) levels. In contrast with healthy subjects, patients with AS had significantly increased rates of superoxide anion radical production in their whole blood either in the resting state or with either fMLP or PMA stimulation. In addition, chemiluminescence maximum light intensity was significantly higher in patients with AS than in healthy subjects after fMLP or PMA stimulation. CONCLUSIONS: Our results suggest that the phagocytes of patients with AS are partly activated in the resting state, and are sensitive to fMLP or PMA stimulation. The priming of phagocytes in the bloodstream is likely to be a causative factor in the onset of AS.     

Regulation by the antioxidants ascorbate, cysteine, and dapsone of the increased extracellular and intracellular generation of reactive oxidants by activated phagocytes from cigarette smokers

The bimodal pattern of N-formyl-methionyl-leucyl-phenylalanine (FMLP)-activated luminol-enhanced chemiluminescence with distinct early (occurring within 1 min) extracellular and late intracellular oxidative responses was compared in polymorphonuclear leukocytes (PMNL) from asymptomatic cigarette smokers and nonsmoking control subjects. Relative to control PMNL, the PMNL from smokers were hyperreactive to FMLP stimulation with increased generation of both extracellular (p less than 0.025) and intracellular (p less than 0.025) reactive oxidants. Smokers' PMNL also showed increased PMNL-activated superoxide generation and increased apparent receptors for FMLP. The water-soluble antioxidants ascorbate and cysteine (2.5 X 10(-5) M to 2.5 X 10(-4) M) selectively neutralized the extracellular activity of PMNL-derived reactive oxidants. The lipid-soluble antioxidant dapsone (1.25 to 30 micrograms/ml), on the other hand, inhibited both the extracellular and intracellular FMLP-activated chemiluminescence responses in PMNL from smokers and nonsmoking control subjects. Regulation of the increased extracellular and intracellular membrane-associated oxidative responses in PMNL from cigarette smokers is probably an important function of water-soluble and lipid-soluble antioxidants in vivo.     

Predictors of neutrophilic airway inflammation in young smokers with asthma

Introduction: Asthma is one of the most widespread chronic diseases worldwide. In spite of numerous detrimental effects on asthma, smoking is common among asthma patients. These smoking-induced aggravations of asthma may be attributed to changes in airway inflammation, which is characterized by a higher degree of neutrophilic inflammation than in non-smokers. A state of neutrophilic inflammation may lead to increased steroid resistance and an accelerated loss of lung function owing to tissue destruction. The aim of this study was to elucidate predictors of neutrophilic inflammation in young asthmatic smokers not on steroid treatment, including analysis of tobacco history and bacterial colonization. Methods: In a cross-sectional study, 52 steroid-free, current smokers with asthma were examined with induced sputum, fractional exhaled nitric oxide (FeNO), lung function, ACQ6 score, mannitol and methacholine challenge. A sample from the sputum induction was taken for bacterial analysis using 16S gene PCR technique and sequencing. Results: Using one-way analysis of variance and binary and linear regression models, only age and ACQ6 score were found to be significant predictors for airway neutrophilia. The investigation also included analysis for effect of pack years, current tobacco consumption, body mass index, lung function, FeNO; methacholine and mannitol responsiveness, atopy, gender, asthma history and presence of bacteria. The most common potentially pathogenic bacteria found were Streptococcus spp., Haemophilus spp. and Mycoplasma spp. Conclusion: In this study, no tobacco-related predictors of airway neutrophilia were found, indicating that in the younger years of asthma patients who smoke, the amount of tobacco smoked in life does not influence the degree of neutrophilia. Conversely, for asthmatic smokers, neutrophilia may be induced when a certain threshold of tobacco consumption is reached.     

Alveolar fenestrae in smokers. Relationship with light microscopic and functional abnormalities

We studied 12 smokers' lungs with scanning electron microscopy in order to analyze the distribution and size of alveolar fenestrae and their relationship to the average distance between alveolar walls (Lm) and lung function. Alveolar fenestrae in areas near terminal airways (respiratory bronchioles and alveolar ducts) were consistently larger than fenestrae far from airways (alveoli). Fenestrae in near areas increased in size as Lm increased (r = 0.845, p less than 0.001), whereas no correlation between Lm and fenestrae size in far areas was found (r = 0.281, NS). The overall area of fenestrae (near and far) correlated significantly with FEV1 (r = -0.745, p less than 0.01), MMEF (r = -0.752, p less than 0.01), and PL90 (r = -0.804, p less than 0.05). However, when subdivided into near and far, only fenestrae near the small airways showed a significant correlation with function. These findings suggest that in smokers with mild to moderate emphysema, destruction affects preferentially the areas around the terminal airways (near areas), and these changes, although small, might play an important role in the lung function.     

Elevated whole blood chemiluminescence in patients with systemic sclerosis

OBJECTIVE: Systemic sclerosis (SSc) is accompanied by oxidative stress that in turn may accelerate endothelium degeneration and thus disease progression. We tested whether phagocytes from SSc patients release more reactive oxygen species (ROS) and whether this release correlates with some clinical parameters. METHODS: ROS production by blood phagocytes was measured with the luminol enhanced whole blood chemiluminescence (CL). Resting and N-formyl-methionyl-leucyl-phenylalanine -induced CL (fMLP-induced CL) was measured in 30 patients with SSc and 30 healthy controls matched as to age, sex, and level of cigarette smoking. RESULTS: Resting CL and fMLP-induced CL calculated per 10(4) phagocytes present in the assayed blood sample were higher in patients with systemic sclerosis than in healthy controls (median; range, 0.88; 0.47-1.39 vs. 0.73; 0.13-1.07 aU/10(4)p and 621; 293-3522 vs. 411; 289-810 aUxs/10(4)p, p<0.02). Patients treated with cyclophosphamide and/or prednisone for 11; 3-168 months did not differ in respect to CL from those that never received the medications. Similarly, no significant differences were found between patients with limited and diffuse SSc. Resting CL correlated (p<0.05) with clinically manifested interstitial lung disease (r=0.59), single breath carbon monoxide diffusing capacity (r= -0.56) and serum autoantibodies titre (r= 0.43). CONCLUSIONS: Blood phagocytes from patients with systemic sclerosis, especially from those with interstitial lung disease, generate elevated amounts of ROS as assessed with CL. This confirms the presence of systemic oxidative stress in SSc patients.     

Resting and activated endothelial cells are increased in the peripheral blood of cancer patients

Circulating endothelial cells (CECs) were enumerated in 20 healthy controls and 76 newly diagnosed cancer patients by means of 4-color flow cytometry. In breast cancer (n = 46) and lymphoma (n = 30) patients, both resting and activated CECs were increased by 5-fold (P <.0008 vs control). CECs significantly correlated with plasma levels of vascular cell adhesion molecule-1 and vascular endothelial growth factor. Resting and activated CECs were similar to healthy controls in 7 lymphoma patients achieving complete remission after chemotherapy, and activated CECs were found to decrease in 13 breast cancer patients evaluated before and 24 hours after quadrantectomy. (Blood. 2001;97:3658-3661)     

Risk of myocardial infarction in young female smokers

OBJECTIVES—To determine the extent of risk of myocardial infarction from cigarette smoking in young women, and to examine the relation of smoking with other putative risk factors.
DESIGN—Community based case control study.
SETTING—England, Scotland, and Wales.
PATIENTS—Women (n = 448) between 16 and 44 years old with a diagnosis of incident myocardial infarction between 1 October 1993 and 16 October 1995. Controls (n = 1728) were age and general practice matched women without a diagnosis of myocardial infarction.
OUTCOMES MEASURES—Odds ratios for risk of myocardial infarction associated with smoking and other risk factors.
RESULTS—Odds ratios for myocardial infarction in smokers versus non-smokers showed a strong dose response, from 2.47 (95% confidence interval (CI) 1.12 to 5.45) in smokers of 1-5 cigarettes per day to 74.6 (95% CI 33.0 to 169) in smokers of  40 cigarettes per day. There was no interaction of smoking with use of oral contraceptives, but there were additive risks with other clinical risk factors such as hypertension and diabetes. It is estimated that if all women aged 16-44 years were able to stop smoking, 400 cases of myocardial infarction per annum (of whom 112 would die) would be prevented.
CONCLUSIONS—In young women the risk of myocardial infarction from smoking was considerable, and heavy smokers with other risk factors were especially at risk.


Keywords: myocardial infarction; smoking; risk factors     

Cardiac abnormalities in young women with anorexia nervosa.

OBJECTIVE--To identify the characteristics of cardiac involvement in the self-induced starvation phase of anorexia nervosa. METHODS--Doppler echocardiographic indices of left ventricular geometry, function, and filling were examined in 21 white women (mean (SD) 22 (5) years) with anorexia nervosa according to the DSMIII (Diagnostic and Statistical Manual of Mental Disorders) criteria, 19 women (23 (2) years) of normal weight, and 22 constitutionally thin women (21 (4) years) with body mass index < 20. RESULTS--13 patients (62%) had abnormalities of mitral valve motion compared with one normal weight woman and two thin women (p < 0.001) v both control groups). Left ventricular chamber dimension and mass were significantly less in women with anorexia nervosa than in either the women of normal weight or the thin women, even after standardisation for body size or after controlling for blood pressure. There were no substantial changes in left ventricular shape. Midwall shortening as a percentage of the values predicted from end systolic stress was significantly lower in the starving patients than in women of normal weight: when endocardial shortening was used as the index this difference was overestimated. The cardiac index was also significantly reduced in anorexia nervosa because of a low stroke index and heart rate. The total peripheral resistance was significantly higher in starving patients than in both control groups. The left atrial dimension was significantly smaller in anorexia than in the women of normal weight and the thin women, independently of body size. The transmitral flow velocity E/A ratio was significantly higher in anorexia than in both the control groups because of the reduction of peak velocity A. When data from all three groups were pooled the flow velocity E/A ratio was inversely related to left atrial dimension (r = -0.43, p < 0.0001) and cardiac output (r = -0.64, p < 0.0001) independently of body size. CONCLUSIONS--Anorexia nervosa caused demonstrable abnormalities of mitral valve motion and reduced left ventricular mass and filling associated with systolic dysfunction.     

Urological abnormalities in young women with severe constipation.

Anorectal and urodynamic studies were carried out in 10 young women with severe constipation and the results compared with those obtained in controls. The lowest volumes that provoked a desire to defecate (constipated 200 +/- 50 v controls 110 +/- 10 [mean +/- SEM] ml: p less than 0.05), and a desire to micturate (constipated 560 +/- 40 v controls 295 +/- 15 [mean +/- SEM] ml: p less than 0.001), were significantly greater in constipated patients compared with controls. The maximum tolerable rectal volume (380 +/- 30 v 290 +/- 20 [mean +/- SEM] ml: p less than 0.05) and the bladder capacity (720 +/- 50 v 540 +/- 10 [mean +/- SEM] ml: p less than 0.001) were also increased in the constipated subjects compared with controls. Electromyographic studies show failure of relaxation of the external anal sphincter (EAS) on attempted defecation in all 10 patients; and eight of these patients actually contracted their EAS when they strained to defecate, causing a functional outlet obstruction. Urodynamic studies showed normal urinary flow rates, normal detrusor pressures and normal radiology during voiding. Thus, these studies suggest that constipated patients have an increase in capacity and a reduction in sensitivity in the urinary bladder as well as in the rectum, but showed no evidence of obstruction to urine flow.     

Vascular abnormalities in asymptomatic, healthy young adult smokers without other major cardiovascular risk factors: the Bogalusa Heart Study

Cigarette smoking, an established cardiovascular (CV) disease risk factor, is known to impair pulsatile arterial function in middle-aged and older adults. However, information is scant in healthy young adults for whom smoking is the only CV risk factor, at current guidelines. Nonsmokers (n = 145) and smokers (n = 142) aged on average 36 years were selected for not having obesity, hypertension, dyslipidemia, diabetes, or clinically manifest CV disease. Pulsatile arterial function was measured in terms of large artery compliance (C1), small artery compliance (C2), and systemic vascular resistance (SVR) by noninvasively recorded radial artery waveforms. Smokers versus nonsmokers had significantly lower measures of adiposity and LDL-cholesterol; and higher systolic blood pressure and triglycerides. In addition, smokers versus nonsmokers had lower C2 (5.09 v 6.63 mL/mm Hg x 100, P = .0009) and higher SVR (1399.0 v 1325.5 dyn . sec . cm(-5), P = .006), after adjustment for race, sex, and age. Decreases in C2 (P for trend = .001) and increases in SVR (P for trend = .01) were noted with increasing years of smoking. Multivariate analysis revealed that duration of smoking was associated adversely with C2 (P = .004), independent of race, sex, age, systolic and diastolic blood pressures, HDL-cholesterol, triglycerides, glucose, and insulin. The odds of having adverse C2 (bottom 10 percentile) and SVR (top 10 percentile) were, respectively, 2.9 (P = .01) and 2.6 (P = .07) times higher in smokers versus nonsmokers. The observed deleterious effects of cigarette smoking on arterial wall dynamics in otherwise healthy young adults underscore the need for aggressive early prevention and intervention strategies to control smoking behavior.     

Altered regulation of the myocardial microcirculation in young smokers

Smoking is known to affect microcirculatory function in a middle-aged population. However, the effects of smoking on myocardial perfusion in young smokers have not been studied. Myocardial perfusion was measured in 15 smokers (24 +/- 2 years) and 15 nonsmokers (24 +/- 3 years) using positron emission tomography. Myocardial perfusion was measured at rest, during cold stress and during dipyridamole. Resting myocardial blood flow was similar in the two groups. The well-described correlation between rate-pressure product and myocardial blood flow was present only in the nonsmokers (r(2) = 0.61, p < 0.001). Myocardial blood flow corrected for the rate-pressure product declined during cold by 20% in the smokers [1.11 +/- 0.28 vs. 0.92 +/- 0.20 ml x g(-1) x min(-1) (p = 0.012)], but remained unchanged in nonsmokers [1.11 +/- 0.25 vs. 1.09 +/- 0.30 ml x g(-1) x min(-1) (p = NS)]. Dipyridamole-induced hyperemia was similar in the two groups [2.23 +/- 0.78 vs. 2.42 +/- 0.65 ml x g(-1) x min(-1) (p = NS)]. In conclusion, smoking induces abnormalities in myocardial microcirculatory regulation in young otherwise healthy smokers. The coronary flow reserve, however, is not significantly altered.     

Predictive value of whole blood chemiluminescence in patients with alcoholic hepatitis

Recent reports suggest that ethanol metabolism leads to reactive oxygen intermediates that may be responsible for the lesions observed in alcoholic hepatitis. This study investigated the production of reactive oxygen intermediates in peripheral blood phagocytes of patients with alcoholic hepatitis and attempts to evaluate its predictive value. Using a luminol-dependent chemiluminescence method, reactive oxygen intermediate production was measured directly within microamounts of whole blood, both in the absence (basal chemiluminescence production) and in the presence of phagocyte-stimulating agents including latex, zymosan, phorbol myristate acetate and N-formyl-methionyl-leucyl-phenylalanine. Thirty patients with well-documented and histologically proven alcoholic hepatitis were studied. Pugh's and Child's classification, Orrego's composite clinical and laboratory index and Maddrey's discriminant function were used to assess the prognosis of the liver disease. Patients were followed up monthly for 6 mo. Results were compared with those obtained in 17 patients with nonalcoholic liver disease and in 78 normal control subjects. Basal chemiluminescence production was significantly higher in patients with alcoholic hepatitis than in those with nonalcoholic liver disease and in normal subjects (p less than 0.001). Chemiluminescence responses to latex, zymosan and phorbol myristate acetate were significantly lower in alcoholic hepatitis patients than in normal subjects (p less than 0.001); however, when compared with nonalcoholic liver disease patients, these responses were significantly decreased only in the presence of zymosan (p less than 0.05). Both basal chemiluminescence production (p less than 0.001) and zymosan-induced chemiluminescence responses (p less than 0.02) were closely related to alcoholic hepatitis prognosis indices (i.e., Pugh's and Child's classification, Orrego's composite clinical and laboratory index and Maddrey's discriminant function.(ABSTRACT TRUNCATED AT 250 WORDS)     

Parallel renal and extremity blood supply abnormalities in nonmodulation: responses to ACE inhibition

The aim of this work was to ascertain, in nonmodulating essential hypertension, whether the abnormality in the renal blood supply is extended to the extremities and showed a similar response to ACE inhibition and whether these abnormalities could be identified in normotensive offspring of hypertensives, as non-modulation is a familial process with genetic underpinnings. We measured forearm vascular blood flow (FBF) and forearm vascular resistance (FVR) by plethysmography and urinary albumin excretion in 20 normotensive without family story of hypertension (NT: 25+/-9 years), 10 modulating offspring of hypertensive parents (MHO: 25+/-6 years), 10 nonmodulating offspring of hypertensive parents (NMHO: 26+/-5 years), 12 modulating essential hypertensives (MHT: 34+/-5 years), and 11 nonmodulating essential hypertensives (NMHT: 32+/-4 years). Measurements were repeated in hypertensives after 3-month treatment with ramipril (5 mg daily). Nonmodulating individuals showed lower maximum FBF (NMHT: 41.96+/-3.3 mL/100 g per minute and NMHO: 35.6+/-9.0 mL/100 g per minute) than modulating subjects (MHT: 57.5+/-10.0 mL/100 g per minute and MHO: 51.8+/-7.0 mL/100 g per minute; P<0.003). Likewise, all nonmodulating subjects showed higher minimum FVR (NMHT: 2.5+/-0.2 AU; NMO: 2.8+/-0.5 AU) than modulating individuals (MHT: 1.9+/-0.5 AU; MHO, 1.8+/-0.3AU; P<0.025). Urinary albumin excretion was higher in NMHT and NMHO than MHT, MHO, and NT (P<0.05). Ramipril increased maximum FBF to 53.8+/-8.0 mL/100 g per minute and reduced minimum FVR to 1.9+/-0.5 AU in NMHT (P<0.01). Likewise, ramipril increased effective renal plasma flow and reduced renal vascular resistance and urinary albumin excretion only in NMHT (P<0.05). These results have shown an early involvement of the peripheral circulation in association with increased urinary albumin excretion not only in essential hypertensives but also in NMHO. The effectiveness of ramipril in reducing minimum FVR and urinary albumin excretion in NMHT also suggests a common mechanism.