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The development of computed tomography (CT) has enabled emphysema to be assessed noninvasively. Objective quantification of lung density correlates well with lung function in patients with chronic obstructive pulmonary disease and has been shown to be a sensitive tool for monitoring disease progression. In order to determine the clinical impact of changes seen on high-resolution computed tomography (HRCT), the relationship between the objective quantification of emphysema on HRCT, lung function and health status in 111 patients with alpha1-antitrypsin deficiency was examined (PiZ). The degree of HRCT scan abnormality correlated well (p<0.001 for all comparisons) with forced expiratory volume in one second (r = -0.60- -0.75), specific airway conductance (r = -0.67-0.76), residual volume/total lung capacity (r = 0.46-0.58) and transfer factor of the lung for carbon monoxide (r = -0.64- -0.81). In addition, the CT scans correlated (p<0.001) with health status as assessed by the St. George's Respiratory Questionnaire (SGRQ total: r = -0.38-0.50) and the Short-Form health survey (e.g. physical functioning: r = -0.39-0.54). In summary, other workers have shown high-resolution computed tomography to be a sensitive indicator of disease progression. This study confirms the relationship between high-resolution computed tomography and lung physiology, and suggests the relationship is even stronger in patients with predominantly lower zone pan-lobular emphysema than in usual chronic obstructive pulmonary disease. High-resolution computed tomography also relates to patients disability and impairment as defined by health status questionnaires and, therefore, should be considered as an alternative outcome measure particularly in alpha1-antitrypsin deficiency.

There are little data describing noncellular changes in bronchial inflammation during exacerbations of chronic bronchitis. The relationship between sputum colour and airway inflammation at presentation has been assessed during an exacerbation in patients with chronic bronchitis and a primary care diagnosis of chronic obstructive pulmonary disease. Sputum myeloperoxidase, neutrophil elastase, leukotriene B4 (LTB4), interleukin-8 (IL-8), sol:serum albumin ratio and serum C-reactive protein were measured in patients presenting with an exacerbation and mucoid (n = 27) or purulent sputum (n = 42). Mucoid exacerbations were associated with little bronchial or systemic inflammation at presentation, and sputum bacteriology was similar to that obtained in the stable state. Purulent exacerbations were associated with marked bronchial and systemic inflammation (p < 0.025 for all features) and positive sputum cultures (90%). Resolution was related to a significant reduction in LTB4 (p < 0.01), but no change in IL-8, suggesting that LTB4 may be more important in neutrophil recruitment in these mild, purulent exacerbations. In the stable state, IL-8 remained higher in patients who had experienced a purulent exacerbation (2p < 0.02). The presented results indicate that exacerbations of chronic bronchitis, defined by sputum colour, differ in the degree of bronchial and systemic inflammation. Purulent exacerbations are related to bacterial infection, and are associated with increased neutrophilic inflammation and increased leukotriene B4 concentrations.

Background: Airway inflammation, with recruitment of neutrophils to the airway lumen, results in purulent secretions and a variety of potential adverse consequences for patients with chronic bronchitis and bronchiectasis. We hypothesised that gradations of sputum colour would correlate directly with the myeloperoxidase content of sputum and with various other indicators of the activity and consequences of bronchial diseases., Methods: To test this hypothesis, we quantified sputum colour by reference to a sensitive nine point colour chart and correlated this assessment with indices of a number of inflammatory mediators in sputum., Results: The results indicate that standardised visual measurements of sputum colour correlated strongly with myeloperoxidase, interleukin 8, leucocyte elastase (both activity and total quantity), sputum volume, protein leak, and secretory leucocyte proteinase inhibitor (p<0.001 for all). In addition, there was a strong direct correlation between leucocyte elastase and both myeloperoxidase (p<0.003) and sputum volume (p<0.001), but a strong negative correlation with secretory leucocyte proteinase inhibitor (p<0.001)., Conclusions: These results indicate that sputum colour graded visually relates to the activity of the underlying markers of bronchial inflammation. The results of this simple visual analysis of sputum provides guidance concerning underlying inflammation and its damaging potential. It also provides a useful scientific tool for improving the monitoring of chronic airways diseases and response to treatment.

Resting lung function is only weakly related to health status in chronic obstructive pulmonary disease, reflecting the multifactorial causes of impairment and the heterogeneous nature of the condition. The current study examined whether density mask analysis of high-resolution computed tomography (HRCT) or exercise capacity were better surrogates for health status in a well-defined, homogeneous group of patients with alpha(1)-antitrypsin deficiency (PiZ). Twenty-nine patients with predominantly lower zone emphysema on HRCT were studied. Exercise was assessed by incremental treadmill (V O(2) peak) and shuttle walking tests (ISWT) and health status by the St. George's Respiratory Questionnaire (SGRQ) and SF-36. Although lower zone expiratory HRCT was related to exercise capacity (rho = -0.64 and -0.63 for V O(2) peak and ISWT, respectively, p < 0.001), multiple regression analysis suggested that FEV(1) was a marginally better predictor (rho = -0.64 and -0.65, p < 0.001). HRCT also related significantly to health status (rho = -0.37 for SGRQ activity, p < 0.05), although again FEV(1) showed a stronger relationship (rho = -0.43, p = 0.01). However, exercise capacity was the best predictor of health status with the ISWT accounting for up to 55% of the variability seen in SGRQ total and up to 53% of the SF-36 domain scores (physical functioning). Although both HRCT and lung function relate to health status, exercise capacity is the best predictor of patients disability in these patients with predominantly lower zone emphysema.

Background: The purpose of this study was to quantitate the effect of surgeons with added qualifications in general vascular surgery on aortic and peripheral vascular surgery performed in a community hospital., Methods: We performed a retrospective study covering a 22-year period and comparing indications, procedures, and results of surgeons who had added qualifications in general vascular surgery with those of board certified general and thoracic surgeons in a private hospital. In Period I (1975-1982), there were 702 vascular procedures all performed by thoracic (65%) and general (35%) surgeons. In Period II (1982-1997), there were 2590 vascular procedures performed by vascular surgeons (73%), general surgeons (7%), and thoracic surgeons (20%). A further comparison was done to examine the results of surgeons with added qualifications in general vascular surgery with board certified general and thoracic surgeons within Period II., Results: The volume and frequency of different types of vascular surgery changed significantly from Period I to Period II with lower extremity prosthetic reconstructions decreasing from 12% to 8.2% and autogenous lower extremity bypasses increasing from 15% to 36%. The percentage of distal reconstructions increased significantly from 27% of the total vascular surgeries in Period I to 44.3% in Period II. In Period II, vascular surgeons operated on older patients, had decreased mortality, decreased length of stay, and performed more distal bypasses than board certified general and thoracic surgeons., Conclusions: The development of vascular surgery as a separate specialty appears to have had a beneficial effect on the types of vascular surgery and the results when compared in a contemporaneous or retrospective fashion.

The therapeutic effect of a nutritional supplement consisting of a combination of glucosamine hydrochloride (FCHG49), purified sodium chondroitin sulfate (TRH122), and manganese ascorbate (GCM)3 was investigated in the rat model of collagen-induced autoimmune arthritis (CIA). The GCM compound was mixed with a palatable nutritional paste (Nutri-cal [NC]). Oral administration of the NC/GCM compound was initiated in 26 rats 10 days before immunization and continued until the day of sacrifice. One group of 12 control rats was given no oral agents; a second group of 12 control rats received NC only. Evaluations included arthritis index (AI) scoring by three independent evaluators, histologic index (HI) scoring of lesions, T-cell proliferation, and serological studies for antibody classes and subclasses. Both the AI and HI criteria showed a statistically significant reduction in the prevalence of CIA in rats pretreated with the NC/GCM (54%) compared to the combined control groups (96%, chi2 analysis P = 0.001). Rats fed the NC/GCM also exhibited a significant decrease in the severity of autoimmune arthritis in both the AI and HI compared to control Group 2 (immunized-NC) (chi2 analysis P < 0.05). Histological studies verified the decreased incidence of arthritis in the NC/GCM group compared to control Group 2. GCM treatment failed to alter T-cell proliferation and antibody production to bovine type-II collagen, indicating that its effects are not due to alteration of the antigen-specific immune response.

Myocarditis offers a unique opportunity to study the factors contributing to its transition from a viral infection to an autoimmune disease. In this article, we review recent studies on the role of nitric oxide (NO), gamma interferon (IFN-gamma) and interleukin 12 (IL-12) in the progression from early (viral) to late (autoimmune) phases of myocarditis induced by Coxsackievirus B3 (CB3) in highly susceptible (A.CA) and moderately susceptible (B10.M) mice. NO plays a paradoxical role, being protective in early stages but detrimental later in the course of disease. Treatment with antibody to IFN-gamma reduced early disease, but had little effect on the severity of cardiac lesions at later times. Treatment with recombinant (r) IL-12 significantly reduced the autoimmune cardiac lesions in moderately susceptible B10.M mice, but had no measurable effect in highly susceptible A.CA animals. These studies provide evidence that the profile of inflammatory mediators produced early in the course of viral infection determines the later development of autoimmune disease.

Background: Patients with more frequent exacerbations of chronic obstructive pulmonary disease (COPD) may have increased bronchial inflammation. Airway inflammation was measured in patients who had been thoroughly investigated with full pulmonary function testing, thoracic HRCT scanning, and sputum microbiology to examine further the relationship between exacerbation frequency and bronchial inflammation., Methods: Airway inflammation (spontaneous sputum sol phase myeloperoxidase (MPO), elastase, leukotriene (LT)B(4), interleukin (IL)-8, secretory leukoprotenase inhibitor (SLPI), protein leakage) and serum levels of C reactive protein (CRP) were compared in 40 patients with stable, smoking related COPD, divided into those with frequent (> or =3/year) or infrequent (< or =2/year) exacerbations according to the number of primary care consultations during the preceding year. The comparisons were repeated after excluding eight otherwise clinically indistinguishable patients who had tubular bronchiectasis on the HRCT scan., Results: Patients with frequent (n=12) and infrequent (n=28) exacerbations were indistinguishable in terms of their clinical, pulmonary function, and sputum characteristics, CRP concentrations, and all of their bronchial inflammatory parameters (p>0.05). The patients without evidence of tubular bronchiectasis (n=32) were equally well matched but the sputum concentrations of SLPI were significantly lower in the frequent exacerbators (n=8) in this subset analysis (p<0.05)., Conclusions: There are several clinical features that directly influence bronchial inflammation in COPD. When these were carefully controlled for, patients with more frequent reported exacerbations had lower sputum concentrations of SLPI. This important antiproteinase is also known to possess antibacterial and antiviral activity. Further studies are required into the nature of recurrent exacerbations and, in particular, the regulation and role of SLPI in affected individuals.

Objectives: This study was designed to examine whether myocarditis induced in a mouse model can be effectively suppressed by nasal administration of cardiac myosin (CM)., Background: Myocarditis in humans often follows viral infection and is accompanied by evidence of an autoimmune response to CM. Treatment has been hampered by the fact that measures undertaken to reduce the autoimmune response often enhance the viral infection. Delivery of antigen via nasal route has been shown to induce antigen-specific tolerance and suppress certain autoimmune diseases in animal models., Methods: Myocarditis was induced in A/J mice by two subcutaneous injections of CM emulsified in complete Freund's adjuvant. Nasal instillation of CM (200 microg/mouse) or vehicle buffer was carried out three days before the first subcutaneous injection (day -3). The effect of nasal instillation of CM on cardiac histopathology, cytokine production by splenocytes, and antibody response was examined three weeks after the first subcutaneous injection (day 21)., Results: Nasal administration of CM effectively reduced the severity of myocarditis. Consistent with the histological findings, the levels of interleukin-2 (IL-2), tumor necrosis factor-alpha, and IL-1beta produced by splenocytes in response to CM were significantly decreased. In addition, the serum levels of IgE and IgG1 anti-myosin antibodies were suppressed. However, the levels of transforming growth factor-beta (TGF-beta) and CM-specific IgA antibodies were not affected., Conclusions: Taken together, our results do not support active suppression through upregulation of TGF-beta, IL-4, and IL-10 as a mechanism of tolerance, but favor anergy or deletion of both Th1 and Th2 autoreactive T cells.

Unlabelled: Conduction abnormalities and arrhythmias may occur in patients following secundum atrial septal defect (ASD) closure using the Amplatzer septal occluder (ASO). Therefore, the aim of this study was to prospectively perform ambulatory ECG monitoring to assess the electrocardiographic effects of transcatheter closure (TCC) of ASD using the ASO device. From 5/97 to 3/99, 41 patients with secundum ASD, underwent TCC using the ASO device at a median age of 9.2[emsp4 ]y. (0.5-87[emsp4 ]y.) and median weight of 34[emsp4 ]kg (5. 6-88[emsp4 ]kg.). Ambulatory Holter monitoring was performed pre- and immediately post TCC. Holter analysis included heart rate (HR), ECG intervals, supraventricular ectopy (SVE), ventricular ectopy (VE), and AV block. No change in baseline rhythm was noted in 37 patients (90%). Changes in AV conduction occurred in 3 patients (7%), including intermittent second degree AV block type II, and complete AV dissociation post closure. SVE was noted in 26 patients (63%) post closure, ranging from 5-2207 supraventricular premature beats (SVPB), including 9 patients (23%) with non-sustained supraventricular tachycardia (SVT), 3 of whom had short runs of SVT prior to closure. A significant increase in post-closure number of SVPB per hour (p=0.047) was noted. No significant difference was noted in PR interval, ventricular premature beats per hour, or QRS duration., Conclusions: Based on ambulatory ECG analysis, TCC of ASD with the ASO device is associated with an acute increase in SVE and a small risk of AV conduction abnormalities, including complete heart block. Long term follow-up studies will be necessary to determine late arrhythmia prevalence and relative frequency compared with standard surgical ASD repair.

Hydroxyapatite (HA) middle ear prostheses have gained popularity as an alternative to human autografts and homografts. This study reports on 3 HA prostheses types: total ossicular chain prostheses, used for grafting the stapes footplate to the tympanic membrane; partial ossicular chain prostheses, used for grafting the stapes superstructure to the tympanic membrane; and Kartush incus struts (Smith & Nephew Richards Inc), used for grafting the stapes superstructure to the undersurface of the malleus. This single-surgeon study of 33 consecutive cases revealed a statistically significant difference in mean postoperative air-bone gap and airbone gap closure between incus struts (14/26 dB) or partial (22/11 dB) or total (25/10 dB) ossicular chain prostheses (t test: P<0.05). Prognostic risk factors graded by the Middle Ear Risk Index indicate a tendency for worse postoperative hearing with increasing Middle Ear Risk Index. This study supports the use of HA ossicular prostheses and, in particular, the use of the malleus for ossicular chain construction.

Purpose: Viable bacteria are often isolated from airway secretions in clinically stable patients with chronic bronchitis. We hypothesized that the number of organisms and bacterial species might be important modulators of airway inflammation., Subjects and Methods: We performed quantitative sputum cultures in 160 stable patients [55 with chronic obstructive pulmonary disease (COPD) and normal serum alpha(1)-antitrypsin levels, 62 with COPD and severe alpha(1)-antitrypsin deficiency (PiZ), and 43 with idiopathic bronchiectasis]. The results were related to several indicators of the mechanisms and severity of airway inflammation., Results: Airway bacterial load correlated with sputum myeloperoxidase level, an indirect measure of neutrophil activation and number (r = 0.50, P<0. 001); sputum neutrophil chemoattractants [interleukin-8 level (r = 0. 68, P<0.001) and leukotriene B4 level (r = 0.53, P<0.001)]; sputum leukocyte elastase activity (r = 0.55, P<0.001); and albumin leakage from serum to sputum (r = 0.26, P<0.01). Markers of inflammation increased at bacterial loads of 10(6) to 10(7) colony-forming units per milliliter, and increased progressively with increasing bacterial load. For example, the median (interquartile range) sputum myeloperoxidase level was 0.3 U/mL (0.1 to 0.5 U/mL) for patients who were not colonized or who had mixed normal oropharyngeal flora alone; 0.5 U/mL (0.2 to 0.7 U/mL) for patients with 10(5) to 10(6) colony-forming units per milliliter (P = 0.07); 0.5 U/mL (0.3 to 1.2 U/mL) for patients with 10(6) to 10(7) colony-forming units per milliliter (P<0.01); 0.7 U/mL (0.3 to 1.2 U/mL) for patients with 10(7) to 10(8) colony-forming units per milliliter (P <0.005); and 2.4 U/mL (0.7 to 4.8 U/mL) for patients with 10(8) or greater colony-forming units per milliliter (P<0.0001). The bacterial species influenced airway inflammation; for example, sputum myeloperoxidase activity was greater (P<0.005) in patients colonized with Pseudomonas aeruginosa [median 32 U/mL (interquartile range, 20 to 65 U/mL)] than those colonized with nontypeable Hemophilus influenzae [4 U/mL (2 to 31 U/mL)], which in turn was greater (P = 0.01) than among those colonized with Moraxella catarrhalis [1.1 U/mL (0.6 to 1.8 U/mL)]. We did not find a relation between bacterial load and lung function., Conclusions: The bacterial load and species contribute to airway inflammation in patients with stable chronic bronchitis. Further studies are required to determine the consequences of bacterial colonization on patient morbidity and decline in lung function.

Background: Chronic obstructive pulmonary disease (COPD) is common although often poorly characterised, particularly in primary care. However, application of guidelines to the management of such patients needs a clear understanding of the phenotype. In particular, the British guidelines for the management of COPD recommend that the diagnosis is based on appropriate symptoms and evidence of airflow obstruction as determined by a forced expiratory volume in one second (FEV(1)) of <80% of the predicted value and an FEV(1)/VC ratio of <70%., Methods: A study was undertaken of 110 patients aged 40-80 years who had presented to their general practitioner with an acute exacerbation of COPD. The episode was treated at home and, when patients had recovered to the stable state (two months later), they were characterised by full lung function tests and a high resolution computed tomographic (HRCT) scan of the chest., Results: There was a wide range of impairment of FEV(1) which was in the normal range (>/=80%) in 30%, mildly impaired (60-79%) in 18%, moderately impaired (40-59%) in 33%, and severely impaired (<40%) in 19% of patients. A reduced FEV(1)/VC ratio was present in all patients with an FEV(1) of <80% predicted but also in 41% of those with an FEV(1) of >/=80% predicted. Only 5% of patients had a substantial bronchodilator response suggesting a diagnosis of asthma. Emphysema was present in 51% of patients and confined to the upper lobes in most (73% of these patients). HRCT evidence of bronchiectasis was noted in 29% of patients and was predominantly tubular; most (81%) were current or ex-smokers. A solitary pulmonary nodule was seen on 9% of scans and unsuspected lung malignancy was diagnosed in two patients., Conclusions: This study confirms that COPD in primary care is a heterogeneous condition. Some patients do not fulfil the proposed diagnostic criteria with FEV(1) of >/=80% predicted but they may nevertheless have airflow obstruction. Bronchiectasis is common in this group of patients, as is unsuspected malignancy. These findings should be considered when developing recommendations for the investigation and management of COPD in the community.

A 41 year old woman presented with community acquired pneumonia (CAP) which failed to resolve following treatment with amoxycillin and cefaclor prior to referral. Quantitative culture of sputum revealed a pure growth of Haemophilus parainfluenzae and, following antibiotic susceptibility testing of the isolate, ciprofloxacin was prescribed resulting in resolution of the infection. Immunological investigations showed that the patient had a high titre of H parainfluenzae specific IgM. The combination of a pure growth of H parainfluenzae, a response to appropriate antimicrobial therapy, and the presence of a specific antibody response indicated that this organism had a pathogenic role in the patient's pneumonia and should be considered in the differential diagnosis of CAP.

The development of the duplex scanner has made the diagnosis of carotid arterial disease easy to those trained in its interpretation. The difficulty lies in the ability to define the patient population most likely to benefit from early diagnosis and treatment. All patients referred to the vascular laboratories at two major hospitals for evaluation of neurologic symptoms were entered into the study. The indications for the study, comorbid conditions, and medications were tabulated and compared with the results of the carotid duplex scan. The purpose was to see whether there was a relationship between the severity of carotid arterial disease and symptoms. A total of 5,807 carotid duplex scans were performed on 5,001 patients. There were 525 patients (11%) with an internal carotid artery stenosis of >70 per cent and 252 patients (5%) with an occlusion of the internal carotid artery. In addition, there were a group of 139 patients with severe bilateral carotid disease. Bruit and a history of known carotid disease were the only indications that were statistically related to severe carotid arterial disease. Smoking, diabetes, peripheral vascular disease, cardiac conditions, and hyperlipidemia were also statistically related to patients with significant carotid disease. This study indicates that the classic indications for carotid duplex scans such as transient ischemic attack, amaurosis fugax, and dizziness have no correlation with the severity of the disease.

Study Objectives: To stratify COPD patients presenting with an acute exacerbation on the basis of sputum color and to relate this to the isolation and viable numbers of bacteria recovered on culture., Design: Open, longitudinal study of sputum characteristics and acute-phase proteins., Setting: Patients presenting to primary-care physicians in the United Kingdom. Patients were followed up as outpatients in specialist clinic., Patients: One hundred twenty-one patients with acute exacerbations of COPD were assessed together with a single sputum sample on the day of presentation (89 of whom produced a satisfactory sputum sample for analysis). One hundred nine patients were assessed 2 months later when they had returned to their stable clinical state., Interventions: The expectoration of green, purulent sputum was taken as the primary indication for antibiotic therapy, whereas white or clear sputum was not considered representative of a bacterial episode and the need for antibiotic therapy., Results: A positive bacterial culture was obtained from 84% of patients sputum if it was purulent on presentation compared with only 38% if it was mucoid (p < 0.0001). When restudied in the stable clinical state, the incidence of a positive bacterial culture was similar for both groups (38% and 41%, respectively). C-reactive protein concentrations were significantly raised (p < 0.0001) if the sputum was purulent (median, 4.5 mg/L; interquartile range [IQR], 6. 2 to 35.8). In the stable clinical state, sputum color improved significantly in the group who presented with purulent sputum from a median color number of 4.0 (IQR, 4.0 to 5.0) to 3.0 (IQR, 2.0 to 4. 0; p < 0.0001), and this was associated with a fall in median C-reactive protein level to 2.7 mg/L (IQR, 1.0 to 6.6; p < 0.0001)., Conclusions: The presence of green (purulent) sputum was 94.4% sensitive and 77.0% specific for the yield of a high bacterial load and indicates a clear subset of patient episodes identified at presentation that is likely to benefit most from antibiotic therapy. All patients who produced white (mucoid) sputum during the acute exacerbation improved without antibiotic therapy, and sputum characteristics remained the same even when the patients had returned to their stable clinical state.

Degradation of extracellular matrix components is central to many pathological features of chronic destructive lung disorders. Desmosine and isodesmosine are elastin-derived cross-linked amino acids whose urine levels are considered representative of elastin breakdown. The aim of this study was to apply a novel methodology, based on high-performance capillary electrophoresis, to the quantification of desmosine and isodesmosine in 11 patients with stable chronic obstructive pulmonary disease (COPD), 10 with an exacerbation of COPD, nine with alpha1-antitrypsin deficiency, 13 with bronchiectasis, and 11 adults with cystic fibrosis, in comparison to 24 controls. It was found that, in patients with stable COPD, urinary desmosine levels were higher than in controls (p=0.03), but lower than in COPD subjects with an exacerbation (p< or =0.05). The highest desmosine levels were found in subjects with alpha1-antitrypsin deficiency, bronchiectasis and cystic fibrosis (p<0.001 versus stable COPD). In a short-term longitudinal study, five stable COPD patients showed a constant rate of desmosine excretion (mean coefficient of variation <8% over three consecutive days). In conclusion, the present method is simple and suitable for the determination of elastin-derived cross-linked amino acid excretion in urine, giving results similar to those obtained using other separation methods. In addition, evidence is presented that urinary desmosine excretion is increased in conditions characterized by airway inflammation, such as exacerbations of chronic obstructive pulmonary disease, bronchiectasis and cystic fibrosis. Results obtained in subjects with alphal-antitrypsin deficiency suggest that this method might be used to evaluate the putative efficacy of replacement therapy.

Airways inflammation in chronic bronchitis is thought predominantly to be a direct consequence of neutrophil recruitment and release of elastase in response to factors such as cigarette smoke. The aims of this study were to assess the role of smoking and determine whether the serum elastase inhibitor alpha1-antitrypsin (alpha1AT) influenced the process. Airways inflammation was compared between patients with chronic obstructive bronchitis with (n=39) and without (n=42) severe alpha1AT deficiency. The authors assessed the sputum concentration of the neutrophil chemoattractants interleukin-8 (IL-8) and leukotriene (LT)B4, myeloperoxidase (MPO) as a marker of neutrophil influx, neutrophil elastase activity and its natural inhibitors, alpha1AT and secretory leukoprotease inhibitor (SLPI). Finally serum alpha1AT was measured to determine the degree of protein leakage (sputum sol serum alpha1AT ratio). Compared to current smokers, the exsmokers had a lower concentration of the chemoattractant IL-8 (p<0.05) and a lower MPO concentration, although this failed to reach conventional statistical significance (p=0.06). Patients with alpha1AT deficiency had greater inflammation in the larger airways with increased LTB4 (p<0.005), MPO (p<0.001), neutrophil elastase activity (p<0.01), protein leak (p<0.001), and were found to have a lower anti-proteinase screen with both reduced sputum alpha1AT (p<0.001) and SLPI concentrations (p<0.05). The reduction in sputum interleukin-8 levels in exsmokers may decrease neutrophil influx and thus explain the slower rate of neutrophil mediated progression of lung disease compared to subjects who continue to smoke. Patients with alpha1-antitrypsin deficiency had greater inflammation suggesting that alpha1-antitrypsin plays an important role in protecting the larger airways from the inflammatory effects of elastase activity and may explain their more rapid progression of disease.

Neutrophil elastase is capable of generating many of the features of chronic bronchial disease. In patients with COPD, airways inflammation with neutrophil recruitment and elastase release is positively correlated with colonizing bacterial load in the stable clinical state (p < 0.0005). In addition, alpha(1)-antitrypsin deficiency is associated with a greater neutrophil load, higher elastase activity, leukotriene-B(4) concentration, and serum protein leak than matched patients without deficiency (p < 0.005). These data confirm an effect of bronchial colonization on airways inflammation in COPD and indicate the role of alpha(1)-antitrypsin in its modulation.

Objective: To determine prevalence of enteric zoonotic organisms in cats in north-central Colorado., Design: Prospective study., Sample Population: Serum and fecal samples from 87 cats with diarrhea, 106 cats without diarrhea, and 12 cats for which fecal consistency was unknown., Procedures: Samples were obtained from client-owned cats and cats at a humane society shelter. Serum was assayed for feline leukemia virus antigen and antibodies against feline immunodeficiency virus, IgM antibodies against Toxoplasma gondii, and IgG antibodies against T gondii and Cryptosporidium parvum. Microscopic examination of unstained feces was performed after centrifugation in a zinc sulfate solution, thin fecal smears were stained with acid fast stain and examined for C parvum, and bacteriologic culture of feces was used to detect aerobic and anaerobic bacteria., Results: Enteric zoonotic organisms were detected in feces from 27 of 206 (13.1%) cats and included C parvum (5.4%), Giardia spp (2.4%). Toxocara cati (3.9%), Salmonella enterica serotype Typhimurium (1.0%), and Campylobacter jejuni (1.0%); each organism was detected in samples from cats with and without diarrhea. Although differences between groups were not significant, a higher proportion of shelter cats (18.2%) had enteric zoonotic organisms than client-owned cats (10.1%)., Conclusions and Clinical Relevance: Enteric zoonotic organisms were detected in feces of 13.1% of cats, suggesting that cats, particularly those in homes of immunocompromised humans, should be evaluated for enteric zoonotic organisms.

Neutrophils recruited to the airways in chronic obstructive pulmonary disease (COPD) are thought to mediate tissue destruction. Neutrophil recruitment is increased during bacterial exacerbations. The inflammatory process was studied in patients with an acute exacerbation of COPD in order to ascertain the role of leukotriene B4 (LTB4). The sputum of eight subjects with a bacterial exacerbation of COPD was analysed for neutrophil products (myeloperoxidase, elastase) and chemoattractants (interleukin-8 (IL-8) and LTB4). The contribution of LTB4 to the chemotactic activity of the sputum sol phase was determined using the LTB4 receptor antagonist LY293111. The concentrations of the serum acute phase proteins alpha1-proteinase inhibitor, alpha1-antichymotrypsin and C-reactive protein were measured. All patients received appropriate broad-spectrum antibiotic treatment for 7-14 days. Initially, the sputum myeloperoxidase activity was high, indicating neutrophil influx; this was associated with high levels of IL-8 and LTB4. All these concentrations fell with treatment (p<0.01). The chemotactic activity of the sputum was raised on presentation and fell with treatment (p<0.01). LTB4 contributed approximately 30% of the total chemotactic activity on presentation; this diminished with therapy. All acute phase proteins were raised on presentation and fell with therapy (p<0.01). These findings suggest that leukotriene B4 contributes to neutrophil influx into the airway in chronic obstructive pulmonary disease and may influence disease progression.

Haemophilus parainfluenzae is often isolated from the sputa of patients with chronic obstructive lung disease. We have investigated the immune response to this organism in patients with chronic bronchitis (n = 3) and bronchiectasis (n = 10) and in healthy controls (n = 9). Outer membrane proteins (OMPs) of H. parainfluenzae were purified for use in enzyme-linked immunosorbent and immunoblot assays. Whole-cell H. parainfluenzae preparations were used to adsorb antibodies from serum samples, which were subsequently immunoblot assayed to investigate the antibody response to surface-exposed epitopes. Levels of H. parainfluenzae-specific immunoglobulin G (IgG), but not IgA or IgM, were increased in the sera of patients with chronic obstructive lung disease compared to levels in control subjects. The species specificity of the antibody response was confirmed, although a degree of cross-reactivity with H. influenzae antigens was observed. IgA and IgG specific for OMPs of H. parainfluenzae were demonstrated to be present in the sputa and sera of five patients with chronic obstructive lung disease. Variation in the pattern and intensity of antigen recognition was observed among patients and among immunoglobulin classes. OMPs of approximately 36, 22, and 15 kDa were confirmed to possess epitopes exposed on the surface of intact H. parainfluenzae. We have demonstrated the presence of a species-specific systemic immune response to H. parainfluenzae in colonized patients. A specific antibody response was also observed in sputum, and the antigen specificity of these responses in patients with chronic obstructive lung disease was investigated for the first time. The presence of a specific immune response suggests that H. parainfluenzae may have a pathogenic role in patients with chronic obstructive lung disease.

Patients with homozygous (PiZ) alpha(1)-antitrypsin (AAT) deficiency have not only low baseline serum AAT levels (approximately 10 to 15% normal) but also an attenuated acute phase response. They are susceptible to the development of premature emphysema but may also be particularly susceptible to lung damage during bacterial exacerbations when there will be a significant neutrophil influx. The purposes of the present study were to assess the inflammatory nature of acute bacterial exacerbations of chronic obstructive pulmonary disease (COPD) in subjects with AAT deficiency, to compare this with COPD patients without deficiency, and to monitor the inflammatory process and its resolution following appropriate antibacterial therapy. At the start of the exacerbation, patients with AAT deficiency had lower sputum AAT (p < 0.001) and secretory leukoprotease inhibitor (SLPI; p = 0.02) with higher elastase activity (p = 0.02) compared with COPD patients without deficiency. Both groups had a comparable acute phase response as assessed by C-reactive protein (CRP) but the AAT-deficient patients had a minimal rise in serum AAT (to < 6 microM). After treatment with antibiotics, in patients with AAT deficiency, there were significant changes in many sputum proteins including a rise in SLPI levels, and a reduction in myeloperoxidase (MPO) and elastase activity (p < 0. 005 for all measures); the sputum chemoattractants interleukin-8 (IL-8) and leukotriene B(4) (LTB(4)) fell (p < 0.01), and protein leak (sputum/serum albumin ratio) became lower (p < 0.01). The changes were rapid and within 3 d of the commencement of antibiotic therapy the biochemical markers had decreased significantly, but took a variable time thereafter to return to baseline values. In conclusion, patients with AAT deficiency had evidence of increased elastase activity at the start of the exacerbation when compared with nondeficient COPD patients which probably reflects a deficient antiproteinase screen (lower sputum AAT and SLPI). The increased bronchial inflammation at presentation resolved rapidly with 14 d of antibiotic therapy.

The in vitro activities of erythromycin, azithromycin, and clarithromycin against 178 clinical isolates from the lower respiratory tract of patients with chronic obstructive pulmonary disease were determined by an agar dilution method. The plates were incubated in air alone or in 5% carbon dioxide. The MICs measured in air alone were lower for most isolates than those measured in 5% carbon dioxide, illustrating the "pH effect" of incubation in carbon dioxide. Testing of isolates in 5% carbon dioxide on pH-adjusted medium (pH 8.4) resulted in MICs of one or two doubling dilutions lower than those obtained on agar with a neutral pH. A bioassay of the three agents incubated in air and in 5% carbon dioxide resulted in a significant loss of activity of all three agents in the carbon dioxide-enriched atmosphere. However, this loss-of-activity effect was significantly reduced when the bioassay medium was adjusted to pH 8.4 prior to incubation in 5% carbon dioxide.

The aim of this study was to assess health-related quality of life (QoL) in elderly subjects with a diagnostic label of asthma from a general practice population, and to determine the main contributory factors. Sixty people aged > or =70 yrs with a primary care diagnostic label of asthma, and 43 control subjects were recruited. Assessment of bronchodilator response, and oral steroid trials were conducted where possible. The main outcome measures were QoL scores for the Short Form (SF)-36 and the St George's Respiratory Questionnaire (SGRQ). In the asthma group, 29 subjects demonstrated a significant airway response to bronchodilators or steroids. Mean SF-36 scores were significantly worse in the total asthma group for components of physical function, physical role limitation, and general health, although psychological scores were similar. QoL remained worse than controls in those subjects with a significant bronchodilator response. Dyspnoea and depression accounted for 61% of the variance in the SGRQ, but forced expiratory volume in one second was not an independent variable. Quality of life is impaired in elderly people with a diagnosis of asthma, including those with demonstrable airway variability. Many older subjects with asthma note a variety of symptoms, highlighting the need for further research into the adequacy and efficacy of their treatment.

Background: Osteomyelitis in the diabetic foot is a difficult problem with multiple etiologies. The effects of peripheral vascular disease, neuropathy, and repetitive trauma all interact to produce complex lesions with exposed bone, surrounding cellulitis, and gangrenous changes., Methods: We performed a retrospective study over a 14-year period at a community hospital looking at osteomyelitis in the diabetic foot. We looked at the contributing factors, organisms involved, most common locations, physical findings, and surgical procedures necessary to treat this condition. The purpose of the study was to determine the incidence and effect of peripheral vascular disease in diabetic patients with foot ulcers., Results: There were a total of 150 patients requiring 278 hospitalizations over the 14-year period who represented 14% of all diabetic admissions. A total of 438 surgical procedures were necessary in these patients, with the most common being debridement (39%) and toe amputation (19%). There were 6 deaths (4%) in this series, and leg amputation was necessary in 21 patients (14%). A vascular bypass was necessary for healing and limb salvage in 36 patients (24%). Most of the bypasses (85%) were with autogenous tissue to the distal leg in order to limit the extent of amputation and to preserve a functional limb., Conclusion: Ischemia is often a contributing factor in the diabetic foot ulcer that must be recognized and treated to avoid prolonged hospitalization, spreading infection, and unnecessary amputation.

The increasing use of CT for the evaluation of blunt abdominal trauma has diagnosed undetected pneumothoraces in many patients. We performed a retrospective study at a major trauma center to determine the incidence of occult pneumothorax in the trauma patient. All trauma patients (3121) admitted to a Level I trauma center over a 51-month period were reviewed to determine the incidence of pneumothorax and occult pneumothorax, the method of diagnosis, and treatment. All major trauma patients received a chest X-ray (CXR), whereas 842 patients (27%) underwent an abdominal CT scan. In the 172 patients diagnosed with pneumothorax, 157 abdominal CT scans were performed and 143 were positive for pneumothorax. CXR revealed 49 right-sided pneumothoraces and 58 left-sided pneumothoraces in 95 patients. Abdominal CT scans diagnosed 73 right pneumothoraces and 90 left pneumothoraces in 143 patients. There were 67 patients (71 thoraces) who were seen to have a pneumothorax on abdominal CT scan not seen on admission CXR. This represents 2.2 per cent of all trauma patients and 7.9 per cent of patients with abdominal CT scans. In looking at just trauma patients with pneumothorax, the CT scan was responsible for diagnosing 39 per cent of the patients with a pneumothorax. The occult pneumothorax is being diagnosed more frequently as methods of evaluating and diagnosing trauma patients become more sensitive.

Compared with adults patients (n = 309) receiving implantable cardioverter-defibrillators at the same institution, pediatric patients (n = 11) exhibited a trend toward lower defibrillation thresholds. At follow-up of 29 +/- 17 months, the incidence of recurrent arrhythmias was similar, but lead revisions and device infections were more common in the pediatric patients.

Previously we showed that autoimmune myocarditis could be induced in mice by immunization with purified murine cardiac myosin (MCM). In this study, we found that identical disease could also be induced in genetically susceptible mice by immunization with porcine cardiac myosin (PCM). The cardiac lesions induced by both antigens were characterized by extensive infiltration of the myocardium accompanied by myocyte necrosis. A novel finding was the presence of multinucleated giant cells and eosinophils in the cardiac infiltrates, in addition to a mixture of mononuclear cells and polymorphonuclear cells described previously. Immunohistochemical staining demonstrated that the mononuclear cells consisted predominantly of macrophages, CD4+ T cells and, to a lesser extent, CD8+ T cells and B cells. In addition, increased cardiac expression of adhesion molecules E-selectin, vascular cell adhesion molecule-1 (VCAM-1) and intercellular cell adhesion molecule-1 (ICAM-1) were demonstrated in mice that developed myocarditis as compared with those that did not develop disease upon immunization with either PCM or MCM. The levels of TNFalpha detected in spleen cell culture supernatant were found to be higher in mice that developed myocarditis than in those that did not develop the disease. Mice immunized with PCM generated T cells and B cells reactive not only with PCM but also with MCM, and vice versa. In addition, the serum levels of IgG1 anti-MCM antibodies produced in mice immunized with PCM as well as MCM were found to correlate positively with the development of myocarditis. Such a detailed characterization of the murine model of autoimmune myocarditis induced by PCM or MCM allowed us to compare the disease process induced by homologous self and foreign antigens.

The activities of six new fluoroquinolones (moxifloxacin, grepafloxacin, gatifloxacin, trovafloxacin, clinafloxacin, and levofloxacin) compared with those of sparfloxacin and ciprofloxacin with or without reserpine (20 microg/ml) were determined for 19 Streptococcus pneumoniae isolates, 5 Haemophilus sp. isolates, and 10 Pseudomonas aeruginosa isolates with decreased susceptibility to ciprofloxacin from patients with clinically confirmed lower respiratory tract infections. Based upon the MICs at which 50% of isolates were inhibited (MIC50s) and MIC90s, the most active agent was clinafloxacin, followed by (in order of decreasing activity) trovafloxacin, moxifloxacin, gatifloxacin, sparfloxacin, and grepafloxacin. Except for clinafloxacin (and gatifloxacin and trovafloxacin for H. influenzae), none of the new agents had improved activities compared with that of ciprofloxacin for P. aeruginosa and H. influenzae. A variable reserpine effect was observed for ciprofloxacin and S. pneumoniae; however, for 9 of 19 (47%) isolates the MIC of ciprofloxacin was decreased by at least fourfold, suggesting the presence of an efflux pump contributing to the resistance phenotype. The laboratory parC (Ser79) mutant strain of S. pneumoniae required eightfold more ciprofloxacin for inhibition than the wild-type strain, but there was no change in the MIC of sparfloxacin and only a 1-dilution increase in the MICs of the other agents. For efflux pump mutant S. pneumoniae the activities of all the newer agents, except for levofloxacin, were reduced. Except for clinafloxacin, all second-step laboratory mutants required at least 2 microg of all fluoroquinolones per ml for inhibition.

Background: IgG subclass deficiency is often associated with recurrent pulmonary infections. The prevalence of deficiency in a large well characterised group of patients with bronchiectasis has not previously been established., Methods: Serum IgG subclass concentrations in 89 patients with bronchiectasis were compared with those obtained from a group of 82 age and sex matched normal healthy controls. Sputum IgG subclass concentrations were also assessed in 44 of the patients. Albumin was measured as a marker of protein transudation from plasma to determine the degree of local IgG subclass production., Results: The serum concentrations of IgG1, IgG2 and IgG3 were increased in the patients compared with the control group whereas IgG4 concentrations were not. There was an overall incidence of deficiency of 1% for subclasses 1-3 and 5% for subclass 4 in patients with bronchiectasis based on observed concentrations being below the lower limit of the control group range. The concentrations of IgG subclasses in sputum were partly dependent upon the degree of inflammation as assessed by the macroscopic appearance of purulence. A comparison of the ratio of sputum:serum subclass concentration and sputum:serum albumin, however, revealed that all of the subclasses were present at greater concentrations than could be accounted for by transudation alone., Conclusions: A new normal control range for serum IgG subclasses has been established and from this range it was found that IgG subclass deficiency in a group of unselected patients with bronchiectasis was comparatively rare. A significant degree of local IgG production was also suggested in the lungs of these patients.

Background: Cisapride is a prokinetic agent that facilitates gastrointestinal motility and is widely used for the treatment of gastroesophageal reflux disease (GERD) in adults and children. However, reports of ventricular proarrhythmia have been noted in patients taking cisapride, particularly in conjunction with other drugs that may inhibit hepatic metabolism of cisapride via the cytochrome P450 3A4 system., Objective: We designed a prospective, blinded study to evaluate the effect of cisapride on ventricular repolarization in children with GERD., Methods: We analyzed the electrocardiograms (ECGs) from 35 children (age 0.4 to 18 years, mean 5.2 years) including measurement of the resting QT interval (QTc), JT interval (JTc), as well as QT and JT interlead dispersion markers. Data from these patients were compared with ECGs from a control group of 1000 normal children., Results: Eleven (31%) of 35 patients receiving cisapride had a prolonged QTc (> or = 450 ms). The JTc was prolonged > or = 360 ms in 16 of 35 patients (46%). The mean QTc in the cisapride group was 428 +/- 35 ms and mean JTc was 336 +/- 35 ms. An increased QT or JT dispersion (> 70 ms) was seen in only 3 of 35 children. Of the 11 children with QTc prolongation, 2 had documented torsades de pointes ventricular tachycardia. Both patients were taking cisapride concomitantly with a macrolide antibiotic. All other patients were treated with either cisapride alone or in conjunction with other GERD agents, such as ranitidine or omeprazole., Conclusions: Cisapride may cause prolongation of ventricular repolarization in children. There does not appear to be increased heterogeneity of repolarization or delayed depolarization in this small sample. The proarrhythmia may be exacerbated by medications that inhibit cytochrome P450 3A4 hepatic metabolism, overdosage, or mechanisms that result in decreased serum clearance. ECG intervals should be monitored in children maintained on cisapride, particularly when used in combination with other known QT-prolonging medications.

Persistent polymorphonuclear neutrophil (PMN) recruitment to airway is thought to be an important component of continuing inflammation and progression of chronic destructive lung diseases. Although chemoattractants are required for the PMN to migrate, the nature of the chemoattractants in the airways has not yet been clarified. We therefore investigated the contribution of interleukin-8 (IL-8) and leukotriene-B4 (LTB4) to the chemotactic activity of lung secretions by inhibiting their activity using a monoclonal antibody to IL-8 and an LTB4 receptor antagonist (LY293111 sodium). Fifty-nine sputum samples obtained from 19 patients with bronchiectasis were studied. In preliminary studies the chemotactic responses to IL-8 and LTB4 were found to be additive, and we were able to remove their contribution independently with the appropriate antibody and antagonist. The chemotactic activity of the secretions was related to the macroscopic appearance (mucoid, mucopurulent, and purulent), and this appeared to be related to an increase in IL-8 contribution. Chemotactic activity was reduced by antibiotic therapy and again that seemed to relate to a reduction in the IL-8 contribution. The contributions of LTB4 were similar among the three types of sputum in varying clinical states. These data suggest that LTB4 and IL-8 are important chemotactic factors in lung secretions from such patients, although IL-8 appears to play a more important role during acute exacerbations. These results may be useful in determining therapeutic strategies for chronic destructive lung diseases in the future.

Junctional tachycardias comprise several arrhythmia types with differing mechanisms, principally involving the region of the atrioventricular (A-V) junction. Neonatal radiofrequency catheter ablation has typically been reserved for life-threatening, drug-refractory cases due to the unique concerns regarding patient size and development. We performed radiofrequency catheter ablation on two neonates with incessant, rapid junctional tachycardias and hemodynamic compromise after failing conventional medical therapy. This report describes 2 neonates who underwent emergent radiofrequency catheter ablation, and compares these two patients to a larger pediatric catheter ablation patient cohort. Both neonates had an acutely successful outcome and were able to be discharged within a week of the ablation procedure. Fluoroscopy time and total procedure time were shorter in these two patients than in the course of the average pediatric catheter ablation. Though long-term developmental consequences of neonatal catheter ablation are yet unknown, in unique extreme situations, radiofrequency catheter ablation can be performed in neonates, as in older children and adults, without excessive acute morbidity.

Following surgery for tetralogy of Fallot (TOF), children may develop late onset ventricular arrhythmias. Many patients have both depolarization and repolarization abnormalities, including right bundle branch block (RBBB) and QT prolongation. The goal of this study was to improve prospective risk-assessment screening for late onset sudden death. Resting ECG markers including QRS duration, QTc, JTc, and interlead QT and JT dispersion were statistically analyzed to identify those patients at risk for ventricular arrhythmias and sudden cardiac death. To determine predictive markers for future development of arrhythmia, we examined 101 resting ECGs in patients (age 12 +/- 6 years) with postoperative TOF and RBBB, 14 of whom developed late ventricular tachycardia (VT) or sudden death. These ECGs were also compared with an additional control group of 1000 age- and gender-matched normal ECGs. The mean QRS (+/- SD) in the VT group was 0.18 +/- 0.02 seconds versus 0.14 +/- 0.02 seconds in the non-VT group (P < 0.01). QTc and JTc in the VT group was 0.53 +/- 0.05 seconds and 0.33 +/- 0.03 seconds compared with 0.50 +/- 0.03 seconds and 0.32 +/- 0.03 seconds in the non-VT group (P = NS). There was no increase in QT dispersion among TOF patients with VT or sudden death compared with control patients or TOF patients without VT, although JT dispersion was more common in the TOF groups. A prolonged QRS duration in postoperative TOF with RBBB is more predictive than QTc, JTc, or dispersion indexes for identifying vulnerability to ventricular arrhythmias in this population, while retaining high specificity. The combination of both QRS prolongation and increased JT dispersion had very good positive and negative predictive values. These results suggest that arrhythmogenesis in children following TOF surgery might involve depolarization in addition to repolarization abnormalities. Prospective identification of high-risk children may be accomplished using these ECG criteria.

The objective was to develop an enzyme-linked immunosorbent assay (ELISA) for the detection of Cryptosporidium parvum IgG in the serum of cats. The ELISA was an indirect ELISA using soluble C. parvum oocyst antigens and a peroxidase-labeled anti-feline IgG secondary antibody. Sera from cats with Toxocara felis, Giardia spp., Aelurostrongylus abstrusus, Isospora felis, Isospora rivolta, Toxoplasma gondii, or Taenia spp. infections were assayed in specificity studies. Following optimization, the ELISA and fecal examination for oocysts were performed on samples from 170 client-owned or humane society source cats and 1 cat inoculated orally with C. parvum oocysts. Cryptosporidium parvum oocysts were detected in feces (4/170; 2.4%), and C. parvum IgG was detected in serum (26/170; 15.3%) from naturally exposed cats. The seroprevalence data suggest that some cats in the geographical area studied were exposed to C. parvum, but persistent oocyst shedding was less common. The ELISA is not useful for predicting oocyst shedding in individual cats.

The gluteal compartment syndrome is a rare, often unrecognized condition which, left untreated, can lead to renal failure, sepsis, and death. The etiology, physiology, and manifestations are similar to those seen in the more common and readily recognized compartment syndromes of the lower leg and forearm. The large gluteal muscle mass confined by the fascia lata of the thigh and tensor fascia lata can, under the right conditions, produce muscle necrosis, acidosis, elevations of creatinine phosphokinase, and ultimately renal failure. A gluteal compartment syndrome most commonly occurs in individuals with an altered mental status due to drugs or alcohol who remain in one position for an extended period of time. This prolonged compression leads to muscle damage, edema, and a full-blown compartment syndrome. Due to its anatomic location and rarity, diagnosis is missed or delayed, resulting in significant morbidity and possible mortality. The mainstay of treatment consists of fasciotomy and debridement.

The duplex scan has become the definitive test in the diagnosis of carotid arterial disease. Its significance, however, has been diminished its extensive use for inappropriate indications. We performed a retrospective study over a four year period at two major hospitals to evaluate the different indications for carotid duplex scans. Symptoms which prompted the test, associated diseases, the type of physician ordering the test, and demographic data were recorded on all patients. Statistical analysis was used to indicate which symptoms and associated diseases were significant in predicting carotid disease. A total of 4,764 scans were reviewed. There were 4,289 studies (90%) which were negative for disease requiring surgery. There were a total of 12 indications for the carotid duplex scan in this study; the most common indications were dizziness, (20%) transient ischemic attack symptoms (19%) and a bruit (16%). Vascular surgeons (28%), Internal Medicine physicians (27%) and Family practice physicians (15%) ordered the duplex scan most frequently, but 39% of the positive scans were ordered by vascular surgeons. A history of seizures, confusion, stroke and as a preoperative evaluation all had a very low yield and should not be used as an indication for a duplex scan. However, a long smoking history, a history of known carotid disease, and peripheral vascular disease all had a statistical correlation with an abnormal duplex scan. The use of the duplex scan to rule out carotid arterial disease for patients with vague, uncommon symptoms is inappropriate and wasteful.

Background: It has been taught that most deep venous thromboses (DVT) begin in the deep veins of the calf and propagate proximally. The duplex ultrasound scan, with its noninvasive characteristics and accuracy, has brought this premise into question. The purpose of this study was to determine the pattern and distribution of acute DVT as well as the different types of thrombi., Methods: We performed a retrospective review of all duplex scans ordered for a diagnosis of acute lower extremite DVT at a 200-bed hospital over a 5-year period., Results: There were 3,585 examinations performed on 2,654 patients. There were 461 patients (17.4%) with a venous thrombosis. Four types of venous thrombosis were identified: an isolated thrombosis in one venous segment (34%), a thrombosis extending over two or more contiguous segments (52%), multiple thromboses in noncontiguous segments (8%), and bilateral thrombi in different locations (6%)., Conclusion: Calf vein thrombi represented 24% of all DVT. Thrombi in the major veins of the thigh and popliteal space without calf involvement were present in 49% of all DVT. The data in this paper indicate that most significant deep venous thromboses do not begin in the calf but instead arise in the proximal thigh or groin.

Fucosidosis was detected in a family of English Springer Spaniels in the United States. To our knowledge, these are the first reported cases of this disease in American-bred dogs. Affected and carrier status of dogs were determined by measuring the activity of the enzyme alpha-L-fucosidase in plasma and in leukocytes. Fucosidosis results in neurologic signs, particularly changes in behavior, in adolescent and adult dogs. Late onset of signs may result in misdiagnosis as a primary behavior problem or acquired neurologic disease. Fucosidosis is inherited in an autosomal recessive manner, and carrier dogs are clinically normal. Thus, the abnormal gene can become widespread in a population before homozygous-affected dogs are produced.

Myocarditis is an important cause of heart failure among adolescents and young adults. A remarkable observation is the discrepancy between the limited overt evidence of myocyte injury and the global impairment of left ventricular function. This discrepancy has stimulated suggestions that immunological mechanisms contribute to cardiac damage. We have developed two murine models of myocarditis, one elicited by cardiotropic Coxsackie B3 (CB3) virus infection and the other by cardiac myosin immunization, to better analyze the pathogenetic mechanisms responsible for immune-mediated heart-muscle disease. Both virus infection and myosin immunization produce myocardial inflammation and elicit heart-reactive antibodies which bind to the myocardium in vivo and which recognize the cardiac myosin heavy chain. Each model offers unique advantages. The virus-induced disease more closely resembles human myocarditis; myosin immunization isolates the autoimmune components of the disease since no virus infection is involved. We have also distinguished strains of mice resistant to autoimmune myocarditis (such as B10.A) from those susceptible to the autoimmune phase of disease (such as A.CA and A/J). Mice from a resistant strain to virus-or myosin-induced autoimmune heart disease develop myocardial inflammation and myosin antibodies if co-treated with tumor necrosis factor (TNF)-alpha or interleukin (IL)-1 when infected or immunized. Thus, cytokines can modulate the outcome of cardiotropic virus infection and enhance its autoimmune sequela. We also found that blocking IL-1 receptor inhibits autoimmune myocarditis in genetically susceptible mice.

The purpose of the present study was to determine whether components of silicone breast implants [silicon (polydimethylsiloxane) oil, silicone gel, and octamethylcyclotetrasiloxane (D4)] potentiate the antibody response to bovine serum albumin (BSA) in mice. Seventy A/J mice were divided into seven groups which received the following: group I--phosphate buffer solution (PBS); group II--20 centistoke (cs) silicone oil; group III--50% silicone gel homogenized in silicone oil; group IV--incomplete Freunds' adjuvant (IFA); group V--IFA mixed with an equal volume of silicone oil; group VI--D4; and group VII--IFA mixed with an equal volume of DA. Each 0.1 mL of treatment material(s) was mixed or emulsified with an equal 0.1-mL volume of 250 micrograms/mL BSA in PBS solution. Antibodies to BSA were measured using an enzyme-linked immunosorbent assay. Our study demonstrates for the first time that both D4 and the silicone gel potentiate antibody production to BSA in mice. Histopathologic evaluation of the injection sites reveals granulomas for mice injected with IFA and D4 preparations. Whether D4 or silicone gel acts as an adjuvant against self-antigens has yet to be determined.

We have developed two models of myocarditis in mice. The first is produced by infection with Coxsackievirus B3; the second results from immunization with cardiac myosin. Both forms of myocarditis occur in the same genetically predisposed strains. Genetically resistant mice can be rendered susceptible to myocarditis by co-treatment with cytokines IL-1 or TNF. Moreover, the disease is inhibited by administration of an antagonist of IL-1. These models will be useful for clarifying outstanding issues related to human myocarditis or dilated cardiomyopathy.

Nitric oxide (NO) is a radical molecule that not only serves as a vasodilator and neurotransmitter but also acts as a cytotoxic effector molecule of the immune system. The inducible enzyme making NO, inducible NO synthase (iNOS), is transcriptionally activated by IFN-gamma and TNF-alpha, cytokines which are produced during viral infection. We show that iNOS is induced in mice infected with the Coxsackie B3 virus. Macrophages expressing iNOS are identified in the hearts and spleens of infected animals with an antibody raised against iNOS. Infected mice have increased titers of virus and a higher mortality when fed NOS inhibitors. Thus, viral infection induces iNOS in vivo, and NO inhibits viral replication. NO is a novel, nonspecific immune defense against viruses in vivo.