bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of oral prednisolone on the bronchoprotective effect of formoterol in patients with persistent asthma
Authors: Grootendorst D.C. , Sterk P.J. , Heijerman H.G.M.
Published: July 2002

Tolerance to the bronchoprotective effects by long-acting β2‐agonists (LAB) in patients with asthma is not prevented by inhaled corticosteroids (ICS). This study examined whether oral prednisolone can restore the bronchoprotective effects of formoterol in 24 patients with persistent asthma already treated with ICS (at least 800 μg budesonide·day−1or equivalent) and LAB, using a parallel-group design.

During a 2‐week run-in period and during the study, patients used formoterol 12 μg twice daily by Turbuhaler®, instead of their own LAB. At baseline and at the end of 7‐days treatment with oral placebo or prednisolone (30 mg·day−1), provocative concentration of histamine causing a 20% fall in forced expiratory volume in one second (PC20histamine) was measured on two separate days after randomized single-dose inhalation of placebo (postP) or formoterol (postF). In addition, PC20postF was measured 24 h after starting oral treatment. The protective effect by formoterol at baseline and during treatment was calculated as the difference between the logs of PC20postP and PC20postF.

The mean±sem in doubling dose (DD) bronchoprotective effect at baseline was 0.8±0.4 DD in the placebo group and 1.0±0.4 DD in the prednisolone group. At the end of the treatment period, the protective effect changed to 1.0±0.5 DD and 0.8±0.6 DD in the placebo and prednisolone treated groups, respectively. This change was not different between the groups (p>0.4).

In conclusion, the bronchoprotective effect by formoterol is not influenced by 1 week prednisolone treatment in patients with asthma who are using regular inhaled corticosteroids and long-acting β2‐agonists. These findings indicate that tolerance to long-acting β2‐agonists cannot be restored by oral steroid therapy.
Significance of lymphocytosis in bronchoalveolar lavage in suspected ocular sarcoidosis
Authors: Takahashi T. , Azuma A. , Abe S. , Kawanami O. , Ohara K. , Kudoh S.
Published: July 2002

Ocular sarcoidosis is frequent in Japan, but in many cases the condition remains undiagnosed in patients with suspected ocular sarcoidosis. Bronchoalveolar lavage (BAL) was performed in order to study the clinical implications of lymphocytosis of BAL fluid in such patients with characteristic ocular manifestations.

The subjects included in this study were 39 patients with suspected ocular sarcoidosis. The patients were divided into four types based on high-resolution computed tomography (HRCT) findings; no lung involvement (HRCT-0), bilateral hilar lymphadenopathy (BHL) without lung involvement (HRCT-I), lung involvement and BHL (HRCT-II), and lung involvement and no BHL (HRCT-III). Transbronchial lung biopsy (TBLB) and BAL were conducted after examining serum angiotensin-converting enzyme and serum lysozyme values, skin test for purified protein derivative chest radiograph, HRCT, and gallium scintigram.

Twenty patients were histologically diagnosed as having sarcoidosis, and 19 patients remained undiagnosed. Granuloma was identified by TBLB in 19 of 20 patients in type HRCT-II but in only one of 19 patients in types HRCT-0 and HRCT-I (p<0.0001). Lymphocytosis in BAL (>15%) was identified in all patients who showed lung field involvement (type HRCT-II) and in 16 of 19 patients without lung field involvement (types HRCT-0 and HRCT-I). There were 10 patients whose only relevant findings were lymphocytosis in BAL. Among these 10 patients, an increased CD4+/CD8+ ratio (>3.5) in BAL was seen in 60%.

The authors conclude that high-resolution computed tomography results yield the same degree of diagnostic accuracy as transbronchial lung biopsy in ocular sarcoidosis suspects. However, bronchoalveolar lavage revealed significant lymphocytosis in patients with negative high-resolution computed tomography results. It should be kept in mind that a diagnostic group of patients with sarcoidosis who manifest ocular involvement and lymphocytosis in bronchoalveolar lavage exists.
Serum surfactant proteins‐A and ‐D as biomarkers in idiopathic pulmonary fibrosis
Authors: Greene K.E. , King T.E. , Kuroki Y. , Bucher-Bartelson B. , Hunninghake G.W. , Newman L.S. , Nagae H. , Mason R.J.
Published: July 2002

Idiopathic pulmonary fibrosis (IPF) has a high mortality rate, and current therapies are only marginally effective. A serum biomarker that predicts clinical outcome would be useful to stage disease, indicate prognosis and the need for aggressive therapy, and help stratify patients for clinical trials.

The goals of this study were to determine whether serum levels of surfactant protein‐A (SP‐A) or surfactant protein‐D (SP‐D) would distinguish between IPF and other types of interstitial lung disease and whether serum SP‐A or SP‐D levels predict outcome in patients with IPF.

The authors found that serum SP‐A and SP‐D levels were significantly elevated in patients with IPF and systemic sclerosis compared to sarcoidosis, beryllium disease and normal controls, and that SP‐D correlated with radiographic abnormalities in patients with IPF. In addition, the authors found that both serum SP‐A and SP‐D levels were highly predictive of survival in patients with IPF.

This is the largest North American data set of surfactant protein measurements in idiopathic pulmonary fibrosis and the first report using multivariate analysis comparing serum surfactant proteins‐A and ‐D to other commonly measured predictors of survival in idiopathic pulmonary fibrosis. Based on these results, the authors propose that serum surfactant proteins may prove to be useful biomarkers in patients with idiopathic pulmonary fibrosis.
Management of lower respiratory tract infections by French general practitioners: the AIR II study
Authors: Raherison C. , Peray P. , Poirier R. , Romand P. , Grignet J-P. , Arsac P. , Taytard A. , Daures J-P.
Published: July 2002

The Analyse Infections Respiratoires (AIR) II study is a prospective, multicentre survey of the management of lower respiratory tract infections in patients aged 15–65 yrs by general practitioners (GPs) in France.

To obtain real-time data recording, practitioners were required to submit an anonymous copy of their drug prescriptions. They were then interviewed over the telephone about the patients' sociodemographic data, signs and symptoms, as well as their presumptive diagnosis and the investigations they had decided upon.

GPs (n=3,144) reported 5,469 evaluable cases. Pneumonia accounted for 9.6% of diagnoses, acute exacerbations of chronic bronchitis 14.9% and acute bronchitis 72.5%. The symptomatology covered an extremely wide range of clinical features, which, although statistically different in terms of incidence, overlapped to a large extent across diagnoses. By contrast, hospitalization, investigations or referral to a specialist were much more prevalent in pneumonia, although still very infrequent in general terms (0.5, 1.2 and 10.8%, respectively). Antibiotics were prescribed in 96.5% of patients, with minor differences between diagnoses. However, other medications such as nonsteroid, anti-inflammatory drugs, steroids, nonspecific antitussives and bronchial liquefiers accounted for two-thirds of the prescriptions.

This study demonstrates the lower respiratory tract infections encountered by general practitioners are usually mild. However, antibiotic prescription was more systematic than in previous studies and the prescription of nonspecific symptomatic treatments was twice as frequent. General practitioners did not perform additional examinations or refer on a regular basis. There was a high prescription rate for symptomatic treatment.
Bronchial bacterial colonization in patients with resectable lung carcinoma
Authors: Ioanas M. , Angrill J. , Baldo X. , Arancibia F. , Gonzalez J. , Bauer T. , Canalis E. , Torres A.
Published: July 2002

The pattern and clinical implications of bronchial bacterial colonization have been widely investigated in patients with chronic lung disease, particularly chronic obstructive pulmonary disease. The main aim of this study was to determine the frequency and risk factors for bronchial colonization in lung cancer patients who have undergone surgical resection.

Forty-one patients with resectable lung cancer (22 (54%) active smokers, 52±23 pack-yrs) with a mean forced expiratory volume in one second of 80±16% predicted, were studied with bilateral protected specimen brush and lung tissue biopsy during the surgical procedure. Quantitative bacterial culture, susceptibility tests and histological examination of samples were performed.

Bronchial colonization with ⩾1 potential pathogenic micro-organism was found in 17 of 41 (41%) patients. The most frequent strains isolated were:Haemophilus influenzae(35%),Streptococcus pneumoniae(13%) andPseudomonasspp. (9%). The risk factors for bronchial colonization were central location of the tumour (odds ratio (OR)=9.2, confidence interval (CI) 95%=2.1–39.6, p=0.003) and increased body mass index (OR=1.6, CI 95%=1.2–2.2, p=0.005). The frequency of postoperative infectious pulmonary complications was low (five cases (12%)) and no relationship was observed with bronchial colonization.

Patients with resectable lung carcinoma had a high rate of bronchial colonization (41%), mainly with potential pathogenic microorganisms. The independent risk factors for colonization in these patients were central location of the tumour and a high body mass index.
Pharmacodynamic steady state of tiotropium in patients with chronic obstructive pulmonary disease
Authors: van Noord J.A. , Smeets J.J. , Custers F.L.J. , Korducki L. , Cornelissen P.J.G.
Published: July 2002

Tiotropium (Spiriva®) is a new once-daily inhaled anticholinergic that has its effect through prolonged muscarinic (M)3receptor antagonism. It has a clinically documented, long duration of action with once-daily dosing in chronic obstructive pulmonary disease (COPD). A single-centre, double-blind, ipratropium-controlled study was conducted in order to characterize the onset of pharmacodynamic steady state of tiotropium in patients with COPD. Thirty-one patients (25 male, six female) with a mean age of 62 yrs and a mean forced expiratory volume in one second (FEV1) of 1.13 L (38% of predicted) were randomly assigned to receive either tiotropium 18 µg once-daily from a dry-powder inhaler (HandiHaler®, 20 patients), or ipratropium 40 µg four-times daily from a pressurized metered-dose inhaler (11 patients) for a period of 1 week. FEV1and forced vital capacity (FVC) were measured 1 h prior to, and just before inhalation (mean value of the two measurements on test-day 1 was the baseline value, while on all other test days it was the trough value), and 0.5, 1, 2, 3, 4, 5, and 6 h after inhalation of the morning dose of the study drug (one capsule and two puffs) on days 1, 2, 3, and 8.

Trough FEV1following 8 days of tiotropium was 0.19 L (18%) above baseline. Approximately 90% of this increase was achieved within 24 h of the first dose (0.17 L, 16%). Trough FVC increased 0.67 L (27%) on test-day 8. Approximately 70% of the improvement was observed after two tiotropium doses (0.47 L, 19%). Achievement of FVC steady state was delayed compared to FEV1. Ipratropium performed typically with an onset of action within 30 min, a peak response between 1–2 h postdosing and a duration of action of ∼4 h. It was concluded that forced expiratory volume in one second steady state with tiotropium is reached within 48 h, while continued improvements in forced vital capacity can be expected over or beyond the first week of therapy. The continued increases in forced vital capacity beyond 48 h suggests that maintenance bronchodilator therapy is required to achieve maximal changes in hyperinflation.
Haemorrhagic hypersensitivity pneumonitis due to naphthylene-1,5-diisocyanate
Authors: Merget R. , Marczynski B. , Chen Z. , Remberger K. , Raulf-Heimsoth M. , Willroth P.O. , Baur X.
Published: July 2002

Symptoms of hypersensitivity pneumonitis and massive pulmonary haemorrhage occurred in a 24-yr-old male shortly after occupational exposure to naphthylene-1,5-diisocyanate (NDI).

The present examination was performed ∼1-yr after the initial life-threatening haemoptysis and following an uneventful recovery after resection of the middle lobe, which had been identified bronchoscopically as the bleeding source. Histological re-examination of the lung was compatible with hypersensitivity pneumonitis.

After a chamber challenge with NDI (5 parts per billion (ppb) for 10 min, 10 ppb for 110 min), rales were heard in both lungs, and a fall in vital capacity and partial pressure of arterial oxygen as well as a rise in body temperature were documented. Isocyanate-specific immunoglobulin-G antibodies could not be detected in the patient's serum, possibly due to the long period without exposure to isocyanates.

The authors conclude that naphthylene-1,5-diisocyanate may cause immunological pulmonary haemorrhage. The underlying disease is consistent with hypersensitivity pneumonitis and may be triggered by low concentrations of the diisocyanate.
Respiratory viral infections as promoters of allergic sensitization and asthma in animal models
Authors: Schwarze J. , Gelfand E.W.
Published: July 2002

Respiratory virus infections can trigger exacerbations of asthma and may also contribute to allergic sensitization to aeroallergens and the development of asthma. Conversely, atopy may predispose to more severe virus-induced airway disease. The animal models reviewed in this article support the hypothesis that respiratory virus infections can promote allergic sensitization and the development of asthma. Respiratory viruses can prevent induction of tolerance and enhance sensitization to inhaled allergens resulting in increased airway inflammation and airway hyperresponsiveness.

Probable mechanisms involved in this enhanced sensitization are increased permeability of the airway mucosa to allergens and recruitment of dendritic cells to the respiratory epithelium during acute infection. Factors involved in augmenting the consequences of allergic airway sensitization appear to be T-cells, especially CD8+ T-cells as regulators of this process, interleukin-5 as a pivotal cytokine for eosinophilic airway inflammation and eosinophils themselves as effector cells triggering airway hyperresponsiveness. Depending on the timing of allergen exposure, respiratory virus infections which elicit a significant type 1 T-helper cell cytokine response may also downregulate allergic sensitization.

Respiratory virus infections in animals previously sensitized to aeroallergens result in prolonged increases in inflammation and airway responsiveness, indicating that critical interactions between immune responses to allergen sensitization and the responses to infection can lead to more severe disease.

Taken together, animal models have proved valuable in generating a number of plausible pathogenetic concepts, and can be used to address a host of unresolved questions regarding the immunology of respiratory virus infections, allergic sensitization and asthma.
Role of persistent infection in the control and severity of asthma: focus onChlamydia pneumoniae
Authors: von Hertzen L.C.
Published: July 2002

Conventional risk factors have been unable to explain most of the substantial increase in the prevalence of asthma observed in many countries during the last few decades. Much attention has been directed at the “hygiene hypothesis”, the apparent inverse relationship between intense systemic childhood infections and the subsequent development of asthma and atopy. However, it is not only the absence or scarcity of infections, but the prolonged presence of certain microorganisms in the lungs that may be involved in the development of asthma.

Accumulating evidence suggests thatChlamydia pneumoniae, an intracellular ubiquitous pathogen with an innate propensity to persist and cause chronic infections, may be associated with asthma. This microorganism can achieve a state of “latency” in which it is viable but dormant and does not multiply. During this state, however, chlamydia continues to synthesize the “stress” protein, a 60‐kDa heat shock protein (hsp60). This protein is able to elicit a strong host inflammatory response at sites of its production and appears to be involved in tissue injury and scarring processes.

As inflammation has been found to be present in almost all asthmatics, whatever the severity and aetiology of the disease, inhaled glucocorticoids now have an established position in the treatment of early stages. However, corticosteroids negatively affect many aspects of cell-mediated immunity and favour the shift from a T‐helper‐1‐type response towards a T‐helper‐2‐type response. Corticosteroids may thus severely deteriorate the host's ability to eradicate an intracellular pathogen, such asChlamydia pneumoniae, which requires a properly functioning cell-mediated (T‐helper‐1‐type) immune response to be cleared. These drugs are also able to reactivate persistent Chlamydia to an active growth phase, which, by increasing the production of pro-inflammatory cytokines at the site of infection, can further amplify inflammation in the airways of patients with asthma.
Bedside methodsversusdual energy X‐ray absorptiometry for body composition measurement in COPD
Authors: Steiner M.C. , Barton R.L. , Singh S.J. , Morgan M.D.L.
Published: July 2002

The measurement of body composition is of value in the nutritional assessment of patients with chronic obstructive pulmonary disease (COPD). The purpose of the present study was to compare two bedside methods for the measurement of body composition using dual energy X‐ray absorptiometry (DEXA) as a reference method.

Fat-free mass (FFM) was measured using DEXA, bioelectric impedance analysis (BIA) and skinfold anthropometry (SFA) in a cohort of 85 COPD patients accepted for pulmonary rehabilitation. Patients whose body mass index was >30 were excluded.

Relative to DEXA, BIA underestimated FFM, whereas it was overestimated by SFA. There was a systematic increase in bias with mean FFM for both DEXAversusBIA and DEXAversusSFA, but this was almost eliminated when results were expressed as FFM index. Significant sex differences in the bias of BIA and SFA measurements of FFM were found. Forty-two (49.4%) patients were identified as nutritionally depleted using DEXA. Compared to DEXA, the sensitivity for detecting nutritional depletion was 86 and 74% for BIA and SFA, respectively, and the specificity 88 and 98%, respectively.

There are significant intermethod differences in the measurement of body composition in chronic obstructive pulmonary disease patients. The choice of measurement method will have implications for nutritional assessment in chronic obstructive pulmonary disease.
Dose-related effects of formoterol on airway responsiveness to adenosine 5′‐monophosphate and histamine
Authors: Ketchell R.I. , Jensen M.W. , Spina D. , O'Connor B.J.
Published: July 2002

Inhaled short-acting β2‐agonists provide greater protection against airway responsiveness (AR) to the mast-cell stimulus, adenosine 5′‐monophosphate (AMP), than to histamine, a direct spasmogen. Both terbutaline and albuterol exhibit this mast-cell stabilizing property in a dose-dependent manner. A single dose of the long-acting β2‐agonist formoterol has also been reported to have a mast cell-stabilizing effect, whereas salmeterol has not. To explore the dose-related actions of the long-acting β2‐agonist formoterol on AR, the authors compared the acute effects of three doses of formoterol and terbutaline on AR to AMP and histamine.

In a double-blind, randomized, placebo-controlled, cross-over study, 25 mild, steroid naive, asthmatic subjects attended on 10 occasions. At each visit, subjects inhaled either a single dose of terbutaline (500 µg), formoterol (6, 12 or 24 µg) or a matched placebo, administeredviaTurbuhaler®, 30 min prior to challenge with both AMP and histamine.

Each dose of β2‐agonist reduced AR to AMP and histamine. The bronchoprotective effects of formoterol (6 µg) and terbutaline (500 µg) were similar in magnitude in reducing AR to histamine (mean±sd: 3.6±0.3 and 3.1±0.3 doubling doses (DD)) and AR to AMP (3.5±0.5 and 3.3±0.4 DD, respectively). Overall, formoterol reduced AR to both spasmogens in a dose-dependent manner. In addition, formoterol (12 and 24 µg) provided a significantly greater protective effect against AMP than against histamine challenge. It decreased AR by 5.7±0.6 and 6.3±0.7 DD against AMP and 4.3±0.4 and 4.8±0.43 DD against histamine, respectively.

The results of this study indirectly demonstrated anin vivodose-dependent mast-cell stabilizing effect of formoterol, in addition to functional antagonism on airway smooth muscle. This property of β2‐agonists may have clinical benefits in asthma management.
A randomized trial of nocturnal oxygen therapy in chronic obstructive pulmonary disease patients
Authors: Chaouat A , Weitzenblum E , Kessler R , Charpentier C , Enrhart M , Schott R , Levi-Valensi P , Zielinski J , Delaunois L , Cornudella R , Moutinho dos Santos J
Published: July 2002

The beneficial effects of nocturnal oxygen therapy (NOT) in chronic obstructive pulmonary disease (COPD) patients with mild-to-moderate daytime hypoxaemia (arterial oxygen tension (Pa,O2) in the range 7.4-9.2 kPa (56-69 mmHg)) and exhibiting sleep-related oxygen desaturation remains controversial. The effectiveness of NOT in that category of COPD patients was studied. The end points included pulmonary haemodynamic effects after 2 yrs of follow-up, survival and requirement for long-term oxygen therapy (LTOT). Seventy-six patients could be randomized, 41 were allocated to NOT and 35 to no NOT (control). The goal of NOT was to achieve an arterial oxygen saturation of >90% throughout the night. All these patients underwent polysomnography to exclude an associated obstructive sleep apnoea syndrome. The two groups exhibited an identical meansD daytime Pa,O2 of 8.4+/-0.4 kPa (63+/-3 mmHg) at baseline. Twenty-two patients (12 in the NOT group and 10 in the control group, p=0.98) required LTOT during the whole follow-up (35+/-14 months). Sixteen patients died, nine in the NOT group and seven in the control group (p=0.84). Forty-six patients were able to undergo pulmonary haemodynamic re-evaluation after 2 yrs, 24 in the NOT and 22 in the control group. In the control group, mean resting pulmonary artery pressure increased from 19.8+/-5.6 to 20.5+6.5 mmHg, which was not different from the change in mean pulmonary artery pressure in the NOT group, from 18.3+/-4.7 to 19.5+/-5.3 mmHg (p= 0.79). Nocturnal oxygen therapy did not modify the evolution of pulmonary haemodynamics and did not allow delay in the prescription of long-term oxygen therapy. No effect of NOT on survival was observed, but the small number of deaths precluded any firm conclusion. These results suggest that the prescription of nocturnal oxygen therapy in isolation is probably not justified in chronic obstructive pulmonary disease patients.
Effect of cromolyn on adenosine-induced airway microvascular leakage in sensitized rats
Authors: Tamaoki J , Yamawaki I , Taira M , Nagano Y , Nakata J , Nagai A
Published: July 2002

Inhalation of adenosine causes bronchoconstriction in asthmatic subjects, but the effect of this purine nucleotide on airway vascular permeability is unknown. In order to determine whether adenosine produces airway microvascular leakage and, if so, to examine the effect of cromolyn (sodium cromoglycate (SCG)) on this extravasation of Evans blue was measured in the airways of ovalbumin-sensitized Brown Norway rats. Inhaled adenosine caused microvascular leakage in sensitized but not in non-sensitized rats, and the response was abolished by capsaicin pretreatment or the tachykinin neurokinin-1 receptor antagonist FK888. Adenosine-induced vascular leakage became apparent in nonsensitized rats when treated with phosphoramidon, and airway neutral endopeptidase activity was lower in sensitized than in non-sensitized animals. The extravasation induced by adenosine in sensitized rats was dose dependently inhibited by SCG aerosols, SCG likewise inhibited microvascular responses to substance P, but had no effect on those to platelet-activating factor. These results suggest that: 1) adenosine induces airway microvascular leakage in sensitized rats through stimulation of neurokinin-1 receptors; 2) this effect is associated with a sensitization-induced decrease in neutral endopeptidase activity; and 3) sodium cromoglycate inhibits adenosine-induced extravasation, presumably via functional antagonism of tachykinins.
Cigarette smoke exposure causes constriction of rat lung
Authors: Wright JL , Sun JP , Churg A
Published: July 2002

Cigarette smoke is known to cause acute increases in airway resistance, but the mechanisms behind this effect are unknown. Lung explants were utilized to examine the constrictive effects of acute cigarette smoke exposure on bronchioles from rats in vitro that had or had not been previously exposed to cigarette smoke in vivo. It was found that smoke induced a small but consistent degree of contraction of the airways in vitro, which could be reduced by an endothelin receptor antagonist in the animals which had had no previous smoke exposure in vivo, and reduced by the oxidant scavengers superoxide dismutase or catalase in the animals with previous smoke exposure. In conclusion, cigarette smoke induces acute small airways constriction through both endothelin release and direct oxidant effects; which mechanisms are operative depends on the prior smoking status.
Haemodynamic response to dynamic exercise after heart-lung transplantation
Authors: Vachiery JL , Niset G , Antoine M , LeClerc JL , Degre S , Estenne M
Published: July 2002

The purpose of this study was to investigate the haemodynamic response to dynamic exercise after heart-lung transplantation (HLT). Nine stable HLT recipients (6 males) were studied 12-55 months after transplantation. While sitting on a cycle ergometer, they first underwent a maximal symptom-limited exercise test (power increment was 10 W x min(-1)) to determine the maximal tolerable workload. On the next day, they performed a second exercise test at 0, 40, 60 and 80% of their predetermined maximal workload (mean+/-sD: 108+/-20 W). Stage duration was 6 min. Respiratory, gas exchange, and haemodynamic measurements were performed at rest, during the last minute of each stage, and after recovery. Haemodynamic variables at rest were within normal limits except heart rate (HR) which was greater and stroke volume index (SVI) which was lower than normal. Peak oxygen consumption was 61+/-8% of predicted. HR showed an initial slow increase followed by a steeper rise, and a delayed return to baseline during the recovery period. SVI and cardiac index (CI) increased at the onset of exercise but did not change significantly at 40-80% of the maximal workload. Pulmonary capillary wedge pressure increased from 4+/-2 mmHg at rest to 14+/-3 mmHg at maximal exercise. It is concluded that during dynamic exercise, heart-lung transplantation recipients demonstrate a chronotropic incompetence, a reduced increase in cardiac index and stroke volume index, and an excessive rise in left ventricular filling pressures. These alterations may contribute to the persistent exercise limitation.
Human herpes virus-8 associated primary effusion lymphoma of the pleural cavity in HIV-negative elderly men
Authors: Ascoli V , Scalzo CC , Danese C , Vacca K , Pistilli A , Lo Coco F
Published: July 2002

Human herpes virus-8 (HHV-8)-associated primary effusion lymphoma (PEL) is an unusual lymphoma confined to the body cavities, which primarily affects human immunodeficiency virus (HIV)-positive men at high risk for Kaposi's sarcoma (KS). We describe two HIV-negative elderly Italian men, who developed pleural HHV-8-positive PEL in association with other diseases (systemic hypertension, colonic carcinoma, chronic obstructive airways disease, dilated cardiomyopathy), but without KS. Thoracic computed tomography revealed unilateral pleural effusion and pleural thickening. Thoracentesis disclosed large lymphoma cells, with no T- or B-cell associated antigens, clonal rearrangement of the immunoglobulin heavy chain gene and the presence of HHV-8 but not Epstein-Barr virus deoxyribonucleic acid sequences. Our cases differ from most pleural effusion lymphomas, in that they are non-acquired immunodeficiency syndrome-related. This highlights the possible human herpes virus-8-associated primary effusion lymphoma risk among elderly human immunodeficiency virus-negative patients, particularly Italians, in whom human herpes virus-8 seroprevalence rates and incidence of classic Kaposi's sarcoma are high.
Investigating accommodation in language proficiency interviews using a new measure of lexical diversity
Authors: Malvern David , Richards Brian
Published: July 2002

Lexical diversity is an important indicator of language learners’ active vocabulary and how it is deployed. Traditionally it has been measured by the Type-Token Ratio (TTR), the ratio of different words to total words used. Unfortunately, TTR is a function of sample size: larger samples of words will give a lower TTR and even commonly used measures derived from TTR which are claimed to be independent of sample size are problematic. To overcome this, the authors have developed an innovative measure of vocabulary diversity, D, based on mathematically modelling how new words are introduced into larger and larger language samples, and have produced software (vocd) to calculate it.

Previous research by the authors into language proficiency interviews (Richards and Malvern, 2000) investigated linguistic and discourse accommodation of teacher-testers using a wide range of student and teacher variables. In a study of teenage learners of French, the aspect of teachers’ language in oral interviews that was most responsive to the ability of their students was lexical diversity. The analysis reported here focuses on this finding in greater depth using the new measure, D. The relationship between D and other measures of foreign language proficiency is investigated, the Ds of students and teachers are compared and the correlations between teachers’ D and students’ proficiency are computed.

Results firstly demonstrate the validity of D as a measure of vocabulary diversity and the effectiveness of vocd as a tool to analyse language data. Secondly, with regard to accommodation processes in oral testing, the two teachers did not finely tune their vocabulary diversity to the proficiency of individual students. Instead, each teacher roughly adjusted his or her language to the ability of the class they examined.
Mannitol in cardioplegia as an oxygen free radical scavenger measured by malondialdehyde
Authors: Larsen M , Webb G , Kennington S , Kelleher N , Sheppard J , Kuo J , Unsworth-White J
Published: July 2002

Oxygen free radicals (OFRs) are associated with ischaemia-reperfusion injury involving many organs, including the heart, which can lead to depressed cardiac function and abnormalities in the cardiac ultrastructure. This is seen upon the release of the aortic crossclamp when the ischaemic myocardium is reperfused in patients undergoing cardiopulmonary bypass (CPB).1 Various studies have shown that by adding OFR scavenging agents or antioxidants to the CPB prime or cardioplegia, cardiac performance improves.2,3 Mannitol is an osmotic diuretic with free radical scavenging properties, which has been shown to reduce the extent of ischaemic injury and improve the function of the myocardium.4,5 This study evaluated how effective mannitol is as an OFR scavenger by administering different concentrations of cardioplegia antegrade into the aortic root, thus maximising its effects directly upon the myocardium rather than being diluted in the CPB prime. Thirty-three patients undergoing primary coronary artery bypass grafting (CABG) were, by double blind random selection, allocated into one of three groups: group 1, a control group (consisting of 11 patients) receiving no mannitol; group 2 (11 patients), receiving a concentration of 4 g/l; and group 3 (11 patients), receiving 8 g/l. Three blood samples were taken directly from the coronary sinus during bypass: the first sample at the start of bypass, just prior to the crossclamp being applied; the second sample just after removal of the crossclamp; and the third sample just prior to termination of bypass. All samples were then centrifuged and the plasma analysed for malondialdehyde (MDA) using high-performance liquid chromatography (HPLC). MDA, an endproduct of lipid peroxidation, causes cellular damage and disruption of cell membranes when tissue antioxidants are exhausted.6 The more MDA produced, the greater the depletion of tissue antioxidants secondary to OFR formation during reperfusion when the aortic crossclamp is removed.7 HPLC is a useful biochemical study; however, it is not a direct indicator of depressed myocardial function, such as an invasive test would be, and this should be borne in mind. Statistically, the results do not show a significant difference among the three groups or among the three samples. However, a trend can be seen, which shows lower levels of MDA in the two groups receiving mannitol and there is an indication of a rise in MDA levels upon the start of reperfusion in the two groups receiving mannitol, but not the control group. It is concluded that further samples would be needed to find a significant difference in MDA concentrations.
Platelet function test HemoSTATUS 2: tool or toy for an optimized management of hemostasis?
Authors: Isgro Frank , Rehn Erik , Kiessling Arndt-H , Kretz Kai-U , Kilian Wolfgang , Saggau W
Published: July 2002

Background: Bleeding after open heart surgery is a common but unintended problem, which is unequivocally related to platelet function. The target of our study was to correlate platelet activation levels and postoperative blood loss as well as the predictive power of measurements focusing on postoperative hemostasis.

Materials and methods: The prospective trial comprised 100 patients (mean age: 64.3 years, 68% male) undergoing cardiac surgery. Platelet activation was measured by the new and modified HemoSTATUS™ test. Blood samples were drawn pre-, intra- and postoperatively. Standard hemostasis tests, including activated clotting time (ACT), partial thromboplastin time (PTT), hemoglobin, platelet count, antithrombin III (AT III) and fibrinogen, were measured according to the clinical routine. Blood loss and consumed blood products were documented up to the 24th hour after the operation.

Results: Platelet activation showed a typical change, with lowest levels after the end of extracorporeal circulation and a restitution to preoperative levels after 24 h. Mean blood loss was 461 ml. Statistical analysis showed neither a correlation to the platelet activation measurements nor to low pre-, intra- or postoperative levels.

Conclusion: The HemoSTATUS platelet function test is not suitable for a reliable monitoring of platelet pathophysiology and patient outcome after extracorporeal circulation. Furthermore, no correlation of preoperative platelet activation and blood loss could be shown.
Factors influencing the change in cerebral hemodynamics in pediatric patients during and after corrective cardiac surgery of congenital heart diseases by means of full-flow cardiopulmonary bypass
Authors: Abdul-Khaliq Hashim , Uhlig Ralph , Böttcher Wolfgang , Ewert Peter , Alexi-Meskishvili Vladimir , Lange Peter E.
Published: July 2002

Background: The pathophysiology of hypoxic -ischemic brain injury in relation to extracorporeal circulation is multifactorial and can be interpreted, in part, as possible alteration in cerebral perfusion and inadequate oxygen delivery to the brain cells. The aim of this study was to evaluate influencing factors on the change in cerebral blood flow velocity (CBFV) patterns determined by transcranial Doppler sonography (TCD) in infants who undergo corrective cardiac surgery by means of full-flow cardio-pulmonary bypass (CPB).

Methods: Included in the study were 67 neonates, infants, and children with a median age of 4 months (0.1-70 months), median weight of 4.8 kg (2.5-18.8 kg), and with cyanotic and noncyanotic congenital heart disease (CHD), who underwent surgical correction of CHD by means of CPB [flow rate 144± 47 ml/kg body weight (BW)] and the alpha-stat strategy. The patients were divided into three groups with respect to the minimum rectal temperature during perfusion: deep hypothermic CPB (< 18°C) n= 18, moderate hypothermic CPB (22-35°C) n= 29, normothermic CPB (36°C) n=20. Continuous determination of mean flow velocity (Vmean) in the middle cerebral artery (MCA) by TCD provided qualitative on-line information on cerebral perfusion. The pulsatility index (PI) was calculated in accordance with the formula: PI = Maximum flow velocity -end -diastolic flow velocity/Mean flow velocity and was used as a parameter for the qualitative assessment of cerebrovascular resistance after the end of CPB.

Results: The Vmean was significantly increased 15 min after cross-clamping in the normothermic group ( p= 0.03) and decreased in the moderate hypothermic group ( p=0.02) and deep hypothermic group ( p= 0.009). The postoperative Vmean values correlated significantly with age ( r= 0.79, p< 0.0001), weight ( r= 0.75, p< 0.0001), bypass time ( r=-0.51, p=0.0006), and minimum rectal temperature ( r= 0.60, p= 0.0001). Mean arterial pressure and hemoglobin concentration, but not pCO2, seem to significantly influence the change in Vmean after the termination of CPB ( r= 0.5, p= 0.001; r= -0.55, p= 0.002, respectively). In comparison with the values at the start of CPB, the Vmeanwas significantly decreased after the end of CPB in the hypothermic and moderate hypothermic groups and still significantly elevated in the normothermic group. The age-independent PI was increased after termination of bypass in all groups ( p<0.05) and still slightly elevated after the end of operation in the hypothermic group ( p= 0.05).

Conclusions: The changes in CBFV patterns before, during, and after the termination of CPB were dependent on age, weight, perfusion pressure, and degree of hypothermia during CPB.
Correspondence of the Functional Independence Measure (FIM) self-care subscale with real-time observations of dementia patients' ADL performance in the home
Authors: Cotter Ellen M , Burgio Louis D , Stevens Alan B , Roth David L , Gitlin Laura N
Published: July 2002

Objective: To determine if caregivers of dementia patients can validly report (a) the level of patient activities of daily living (ADL) dependence and (b) the amount of time they spend providing ADL assistance.

Design: Seven ADLs were assessed through caregiver report using the Functional Independence Measure (FIM) and then videotaped. Videotapes were coded using a computer-assisted data collection system that documented the nature and duration of caregiver assistance provided during ADLs.

Setting: The study took place in the homes of the caregiver–patient dyads.

Subjects: Twenty-one people with dementia and their primary caregivers participated in the study.

Main outcome measures: Data analysis examined (a) the degree to which caregiver-reported FIM scores corresponded to FIM scores derived from the observational data and (b) the extent to which caregivers' estimates of ADL assistance time corresponded to the assistance time observed during ADL interactions.

Results: For all ADLs, caregiver-reported FIM scores were correlated significantly with observation-derived FIM scores ( rs values ranged from 0.620 to 0.909), and means were similar. Assistance durations were also significantly correlated for some ADLs, but means were significantly different, indicating poor correspondence.

Conclusions: Although caregivers of dementia patients can describe the nature of their ADL assistance with reasonable accuracy, they consistently overestimate their ADL assistance time, suggesting that caregiver reports of ADL assistance duration be used with caution. Additionally, the degree to which the assistance provided corresponds to the assistance actually needed needs to be addressed in future studies.
Pain, sedation and morphine metabolism in cancer patients during long-term treatment with sustained-release morphine
Authors: Andersen G , Jensen N-H , Christrup L , Hansen S H , Sjøgren P
Published: July 2002

Background: Morphine-6-glucuronide (M-6-G) and morphine-3-glucuronide (M-3-G) are the two most important metabolites of morphine. Both are pharmacologically active, however, with different effects. M-6-G has been demonstrated capable of inducing anti-nociception and sedation, and M-3-G may induce behavioural excitation and possibly antagonise anti-nociception. Their impact on pharmacodynamics in patients in long-term treatment with oral morphine remains to be settled.

Methods: Forty-two cancer patients treated with oral sustained-release (SR) morphine were assessed for pain, sedation and other side effects related to morphine treatment. Blood samples were analysed for morphine, M-3-G and M-6-G by high-performance liquid chromatography (HPLC).

Results: Significant correlations were found between the daily dose of SR morphine and plasma morphine (M) (r=0.535, P<0.001), plasma M-6-G (r =0.868, P<0.001) and plasma M-3-G (r =0.865, P<0.001). There was no relationship between plasma morphine, M-6-G, M-6-G/M and pain and sedation scores. Seventy-nine percent of the patients suffered from dryness of the mouth, which was the most frequent side effect observed. Patients in this group had higher plasma morphine and M-6-G concentrations than patients who did not suffer from this side effect.

Conclusion: The plasma concentrations of morphine and its metabolites, M-3-G and M-6-G, are significantly correlated to the daily dose of SR morphine. Although M-6-G has analgesic properties, no associations were found between pain and plasma morphine and morphine metabolites. This may be due to the multitudinous factors affecting the dose effect relationship. Patients with dryness of the mouth had higher concentrations of morphine and M-6-G than patients without this side effect.
Daily journal club: an education tool in palliative care
Authors: Mazuryk M , Daeninck P , Neumann C M , Bruera E
Published: July 2002

Journal clubs are a valuable tool for medical education. This paper describes a unique daily journal club format utilized by our palliative care programme and presents the results of a questionnaire sent to trainees exploring satisfaction with its educational value. We reviewed the number and type of articles presented at the journal club over 1 year. A questionnaire was mailed to participating family medicine residents and palliative care fellows. The number of articles presented over 1 year was 252. Pain and symptom control, psychosocial issues and drugs other than opioids were topics accounting for 72% of the presentations. Half were given by attending physician staff, 38% by trainees and 12% by multidisciplinary visitors. Palliative care fellows indicated significantly higher levels of satisfaction than family medicine residents, particularly in the areas of clinical applicability, acceptability of the daily schedule and overall educational value. The increased emphasis on evidence-based practice in palliative care suggests that a journal club could be a useful educational tool. The results from our experience could be applied to other palliative care programmes.
Learning, innovation and regional development: a critical appraisal of recent debates
Authors: MacKinnon Danny , Cumbers Andrew , Chapman Keith
Published: July 2002

A resurgence of interest in the region as a scale of economic organization has been apparent within economic geography over the past decade or so. In view of the apparent shift towards a ‘knowledge-driven economy’, the capacity of regions to support processes of learning and innovation has been identified as a key source of competitive advantage. This paper provides a critical appraisal of recent work on innovation, learning and regional development, situating this within its intellectual context. We argue that, while the focus on knowledge and learning is highly relevant, much of the literature fails to adequately ground its arguments in empirical enquiry and also tends to underemphasize the importance of wider extra-local networks and structures. In conclusion, we offer some directions for further research.
Age distribution of cancer in mice: the incidence turnover at old age
Authors: Pompei Francesco , Polkanov Michael , Wilson Richard
Published: July 2002

We have studied cancer incidence in mice as a function of age in those cohorts where the rodents are allowed to live very close to their full natural lifetime. We find that the incidence rises as a function of age, but then flattens and turns over at an age of about 800 days. This behaviour is similar to that which we observed (Pompei and Wilson, 2001) in the Surveillance, Epidemiology, and End Results (SEER) data where the age distribution of human cancer incidence turns over at about age 80. Although other fits are possible, the three-parameter beta function model fits both the mouse data and the human data well. The beta model implies, and the data do not deny, the interpretation that cancer is not a certainty and mice may also outlive their cancers, although high-dose cohort results suggest cancer might be certain if dose is sufficiently high. Limited data suggest that the cancer age distribution, including the turnover, may be time shifted by dietary restriction.
Dermal exposure assessment of polycyclic aromatic hydrocarbons: in vitro percutaneous penetration from coal dust
Authors: Sartorelli Pietro , Montomoli Loretta , Sisinni Antonietta Gerardina , Bussani Rossana , Cavallo Domenico , Foá Vito
Published: July 2002

To understand the dermal uptake of chemicals bound to soil and dust, information on the neat substance is helpful but does not seem sufficient. Because of its content of polycyclic aromatic hydrocarbons (PAHs) coal is suspected to be carcinogenic. However, experimental carcinogenity studies on coal dust never succeeded in demonstrating a higher incidence of cancer in treated animals. The aim of the study was to assess dermal penetration through human skin of PAHs from coal dust. A sample of coal dust was grinded and sieved, using the particle size of <30 μm. An in vitro static diffusion cell system validated by in vitro/in vivo comparison has been used to study dermal penetration through human skin of PAHs from coal dust compared with their percutaneous absorption as pure compounds. No percutaneous penetration of PAHs was observed in the cells where coal dust was applied, while dermal penetration was demonstrated for PAHs applied in an acetone solution. Results agree with the literature that PAHs are poorly absorbed through the skin from solids. Dermal risk assessment of PAHs should take into account not only the degree and the extent of skin contamination, but also their bioavailability, which is heavily influenced by the physico-chemical characteristics of the matrix.
Evidence from northwest European bogs shows ‘Little Ice Age’ climatic changes driven by variations in solar activity
Authors: Mauquoy Dmitri , van Geel Bas , Blaauw Maarten , van der Plicht Johannes
Published: July 2002

Fluctuations in Holocene atmospheric radiocarbon concentrations have been shown to be due to variations in solar activity. Analyses of both 10Be and 14C nuclides con” rm that production-rate changes during the Holocene were largely modulated by solar activity. Analyses of peat samples from two intact European ombrotrophic bogs show that climatic deteriorations during the ‘Little Ice Age’ are associated with transitions to increasing atmospheric 14C content due to greater 14C production. Both ombrotrophic mires, which are positioned c. 800 km apart, register reactions to globally recorded 14C ‘ fluctuations between ad 1449 and 1464 and an almost identical reaction between ad 1601 and 1604.