Positive-pressure ventilation may be associated with adverse
cardiovascular effects, particularly when using large tidal volumes and /
or high PEEP. The increased intra-thoracic pressure decreases venous
return to the heart with subsequent reduction of cardiac filling, cardiac
output and blood pressure. On the other hand, positive-pressure
ventilation may have beneficial hemodynamic effects. If the pos...
Positive-pressure ventilation may be associated with adverse
cardiovascular effects, particularly when using large tidal volumes and /
or high PEEP. The increased intra-thoracic pressure decreases venous
return to the heart with subsequent reduction of cardiac filling, cardiac
output and blood pressure. On the other hand, positive-pressure
ventilation may have beneficial hemodynamic effects. If the positive
airway pressure is timed to occur during systole and the airway pressure
is released during diastole, cardiac output can sometimes be increased and
the mechanical ventilator can actually function as a partial ventricular
assist device ( as if the ventilator is squeezing the heart when the intra
-thoracic pressure is increased during systole) . Based on clinical
observation, many patients with decompensated heart failure (who were
intubated and ventilated because of acute pulmonary oedema) improved
significantly several hours after mechanical ventilation. Compensatory
tachycardia, ventricular ectopics and gallop rhythm decreased and many
patients showed much better diuretic response. In addition, some patients
with underlying Coronary artery disease - CAD - demonstrated ECG evidence
of improved myocardial ischemia after initiation of positive- pressure
ventilation (nitrates and calcium antagonists were not given to those
patients with borderline B.P for fear of exaggerated ventilator - induced
hypotension). It should be remembered that ventilator-induced hypotension
is a potential complication in volume-depleted patients rather than the
fluid-overloaded patients with heart failure. We can assume that
mechanical ventilator may be particularly useful to patients with
decompensated heart failure as it may augment ventricular contraction,
improve arterial oxygenation and hence myocardial O2 supply and reduce
preload (as a result of increased intra-thoracic pressure and reduced
venous return). Preload reduction not only reduces pulmonary congestive
symptoms but also decreases left ventricular end-diastolic diameter (
L.V.EDD ), L.V wall tension and therefore cardiac work and myocardial O2
demand (the same mode of action of nitrates that may explain the ECG
evidence of improved ischemia in some patients with CAD shortly after
intubation. It is to be remembered that L.V wall tension depends on
L.V.EDD - determined by preload - and intra-ventricular pressure -
determined by after load. Positive - pressure ventilation may also be
beneficial in the clinical setting of acute pulmonary oedema in which up
to 40 – 50 % of the cardiac output may be taken up by the overacting
respiratory muscles of the severely distressed patients. After intubation,
ventilation and sedation (with or without muscle paralysis), mechanical
ventilator provides "rest" to the overacting respiratory muscles and
allows redistribution of the cardiac output from the respiratory muscles
to the heart, brain and kidneys. This may lead to improved coronary blood
flow and myocardial O2 supply which may further enhance myocardial
contractility and reduce myocardial ischemia. In addition, renal blood
flow may also be increased which may explain the enhanced diuretic
response in heart failure patients after intubation and mechanical
ventilation. In conclusion, positive-pressure ventilation may have several
beneficial effects in patients with decompensated heart failure who are
intubated because of acute pulmonary oedema and hypoxemic respiratory
failure. This may include increased cardiac output, improved myocardial
ischemia (due to increased O2 supply and reduced O2 demand) and increased
renal perfusion and diuretic response. Finally, this issue needs more
evaluation using echocardiography (to assess L.V function and regional
wall motion), invasive hemodynamic monitoring (to measure cardiac output,
PCWP and pulmonary artery pressure) as well as biochemical markers of
heart failure such as the recently available B-type natriuretic peptide
that may be of value in assessing the severity of heart failure.
References
1. Pinsky HR. Cardiovascular effects of ventilatory support and withdrawal. Anaesth. Analg 1994; 79: 567 – 576
2. Veisprille A. The pulmonary circulation during mechanical ventilation. Acta Anesthesiol Scand 1990; 34 (Suppl):51-62.
We read with interest the recent article by Wu et al. [1] in which
they investigated a single nucleotide polymorphism at exon 1 of the
transforming growth factor beta1 (TGF-beta1) gene.
While we agree with their assumption that TGF-beta1 is a candidate
gene for COPD association study, we can not understand why they restricted
their study to only one polymorphism in that gene. There a...
We read with interest the recent article by Wu et al. [1] in which
they investigated a single nucleotide polymorphism at exon 1 of the
transforming growth factor beta1 (TGF-beta1) gene.
While we agree with their assumption that TGF-beta1 is a candidate
gene for COPD association study, we can not understand why they restricted
their study to only one polymorphism in that gene. There are several
registered polymorphisms within TGF-beta1 and its promoter [2] that might
be functional and might be associated with COPD. A polymorphism of special
interest is the promoter SNP at -509 C/T that had been shown to be
associated with elevated total IgE [3] and asthma severity [4]. Recently,
Silverman et al. [5] showed that this SNP is associated with the diagnosis
of asthma and may enhance TGF-beta1 gene transcription. Another
interesting SNP is that at codon 25 (Arg25Pro). This SNP had been shown to
be associated with levels of TGF-beta1 production,[6] the development of
lung fibrosis [6] and proliferative diabetic retinopathy.[7]
To our knowledge, the study by Wu et al. [1] is the first study to
search for association between TGF-beta1 polymorphisms and COPD. In our
laboratory, when we examine a gene -for the first time- for disease
association, we search for polymorphisms inside the gene and its promoter.
Then, we compare the genotype and allele frequencies between the patient
and control groups.[8] If a large number of polymorphisms were detected,
we also check the linkage disequilibrium and compare the haplotypes
between the different groups for the common polymorphisms [9]. We found
that haplotype analysis, testing associations using several polymorphisms,
sometimes demonstrates genetic influences that are not detected by the
analysis of single polymorphisms [9].
References
1. Wu L, Chau J, Young RP, Pokorny V, Mills GD, Hopkins R, McLean L,
Black PN. Transforming growth factor-beta1 genotype and susceptibility to
chronic obstructive pulmonary disease. Thorax 2004; 59: 126-9.
2. Watanabe Y, Kinoshita A, Yamada T, Ohta T, Kishino T, Matsumoto N,
Ishikawa M, Niikawa N, Yoshiura K. A catalog of 106 single-nucleotide
polymorphisms (SNPs) and 11 other types of variations in genes for
transforming growth factor-beta1 (TGF-beta1) and its signaling pathway. J
Hum Genet 2002;47: 478-83.
3. Hobbs K, Negri J, Klinnert M, Rosenwasser LJ, Borish L.
Interleukin-10 and transforming growth factor-beta promoter polymorphisms
in allergies and asthma. Am J Respir Crit Care Med 1998;158: 1958-62.
4. Pulleyn LJ, Newton R, Adcock IM, Barnes PJ. TGFbeta1 allele
association with asthma severity. Hum Genet. 2001 Dec;109(6):623-7.
5. Silverman ES, Palmer LJ, Subramaniam V, Hallock A, Mathew S, Vallone J,
Faffe DS, Shikanai T, Raby BA, Weiss ST, Shore SA. Transforming growth
factor-beta1 promoter polymorphism C-509T is associated with asthma. Am J
Respir Crit Care Med 2004; 169: 214-9.
6. Awad MR, El-Gamel A, Hasleton P, Turner DM, Sinnott PJ, Hutchinson
IV. Genotypic variation in the transforming growth factor-beta1 gene:
association with transforming growth factor-beta1 production, fibrotic
lung disease, and graft fibrosis after lung transplantation.
Transplantation 1998; 66: 1014-20.
7. Beranek M, Kankova K, Benes P, Izakovicova-Holla L, Znojil V,
Hajek D, Vlkova E, Vacha J. Polymorphism R25P in the gene encoding
transforming growth factor-beta (TGF-beta1) is a newly identified risk
factor for proliferative diabetic retinopathy. Am J Med Genet 2002; 109:
278-83.
8. Hirano K, Sakamoto T, Uchida Y, Morishima Y, Masuyama K, Ishii Y,
Nomura A, Ohtsuka M, Sekizawa K. Tissue inhibitor of metalloproteinases-2
gene polymorphisms in chronic obstructive pulmonary disease. Eur Respir J
2001; 18: 748-52.
9. Hegab AE, Sakamoto T, Uchida Y, Nomura A, Ishii Y, Morishima Y,
Mochizuki M, Kimura T, Saitoh W, Massoud HH, Massoud HM, Hassanein KM,
Sekizawa K. CLCA1 gene polymorphisms in chronic obstructive pulmonary
disease. J Med Genet 2004; 41: e27.
Malignant mesothelioma (MM) is a rare, highly aggressive tumor,
accounting for less than 1% of all cancer deaths in the world. Although
the association between exposure to asbestos and the development of MM is
commonly accepted, the exact mechanism whereby asbestos induces MM is
unknown. Therefore, we agree with Dr Lange observation that the search
for other agents/factors causing this disease should...
Malignant mesothelioma (MM) is a rare, highly aggressive tumor,
accounting for less than 1% of all cancer deaths in the world. Although
the association between exposure to asbestos and the development of MM is
commonly accepted, the exact mechanism whereby asbestos induces MM is
unknown. Therefore, we agree with Dr Lange observation that the search
for other agents/factors causing this disease should be strengthened.
Our
research group is actually investigating the pathogenesis of MM looking
both at molecular events and environmental factors. We have a manuscript
in press on Thorax showing a possible implication of COX-2 in MM
pathogenesis through the effects on cell cycle regulatory proteins.[1]
Moreover, our group is collaborating with the Regional Mesothelioma
Registry instituted by the Campania Region, and entrusted in convention to
the II University of Naples under the direction of Professor Massimo
Menegozzo. Finally, in collaboration with the SAFU Dept of Regina Elena
Cancer Institute in Rome, we are setting up a canine model of spontaneous
MM Spontaneous canine neoplasms have been considered in the recent years a
valuable and highly underused resource to characterize several tumor types
and to evaluate new experimental therapeutics.[2-4] The advantages of
this model system include: 1. similarities between specific types of
canine and human cancer with regards to histopathological appearence,
biological behavior and response to therapy; 2. significant similarity in
drug metabolism between dogs and humans; 3. pet owners’ willingness to
enter their tumor bearing dogs in humanely conducted clinical trials due
to the absence of a well defined “standard” therapy for many canine
cancers; 4. the compressed life-span of dogs, which allows the completion
of clinical trials in a timely manner;
5. the fact that dogs share the
same environment of their owners but lack their unhealthy habits such as
alcohol consumption and cigarette smoking which act as “confounding” in
many clinical and epidemiological studies;
6. the larger size of dogs
compared to rodents which makes feasible to perform many medical
procedures; 7. novel interventional strategies developed in vitro or in
laboratory animals studies can be tested in dogs affected by cancer,
similar studies might be unacceptable or less feasible in human patients,
especially when a standard, yet only partially effective treatment exists.
In conclusion, defining all the factors involved in mesothelioma
pathogenesis is a very difficult task, that can be accomplished only by a
multidisciplinary approach.
References
1. Baldi A., Santini D., Vasaturo F., Santini M., Vicidomini G., Di
Marino M.P., Esposito V., Groeger A.M., Liuzzi G., Vincenzi B., Tonini G.,
Piccoli M., Baldi F., Scarpa S. Prognostic significance of Cyclooxygenase-
2 (COX-2) and cell cycle inhibitors p21 and p27 expression in human
pleural malignant mesothelioma. Thorax 2004 (in press)
2. MacEwen EG. Spontaneous tumors in dogs and cats: models for the
study of cancer biology and treatment. Cancer Met Rev 1990; 9: 125-136.
3. Hahn KA, Bravo L, Adams WH, Frazier DL. Naturally occurring tumors
in dogs as comparative models for cancer therapy research. In Vivo 1994;
8: 133-144.
4. Vail DM, Mac Ewen EG. Spontaneously occurring tumors of companion
animals as models for human cancer. Cancer Invest 2000; 18: 781-792.
We thank Andreas von Glehn for his interest in our paper, sufficient
that he took resveratrol capsules for his own condition, presumably COPD.[1]
His short course of treatment (9 weeks) highlights the difficulties
in evaluating therapies for the treatment of COPD. COPD is a slowly
progressive inflammatory condition of the lungs and, as such, clinical
trials using lung function measurements a...
We thank Andreas von Glehn for his interest in our paper, sufficient
that he took resveratrol capsules for his own condition, presumably COPD.[1]
His short course of treatment (9 weeks) highlights the difficulties
in evaluating therapies for the treatment of COPD. COPD is a slowly
progressive inflammatory condition of the lungs and, as such, clinical
trials using lung function measurements as endpoints are generally
considered inadequate unless they are in large numbers of patients and of
at least 3 years duration.[2] The length of studies could be shortened if
adequate surrogate markers were available. However, at present there is
debate concerning the usefulness in COPD of most of these markers.[3]
Consequently, it is unsurprising that von Glehn reported that taking
resveratrol for 9 weeks was 'without absolutely any result'. It would have
been interesting to have had a more formal quality of life assessment, as
improvement in patient well-being is a valid end point in COPD.[4]
Although we found that resveratrol effectively inhibited cytokine
release by alveolar macrophages in vitro from patients with COPD, it is
unlikely that oral dosing would have a similar effect. This is because of
the low bioavailibility of resveratrol.[5] Consequently, resveratrol
analogues such as piceatannol are under investigation for improved
bioavailibilty.[6]
Finally, in the present climate of the debatable efficacy of
pharmacotherapy for COPD,[3] we understand the eagerness of von Glehn to
test the benefit of any proposed new treatment for his COPD. However, we
wish to highlight that our study examined the effect of resveratrol on
specific responses by a specific population of inflammatory cells that may
have a role to play in the pathophysiology of COPD. Further studies are
clearly required on the effect of resveratrol on the underlying
inflammation in COPD before considering large scale clinical
investigations. At present we would emphasise that the only intervention
proven to alter disease progression in COPD is smoking cessation.[3] We
recommend this course of action to von Glehn and wish him well for the
future.
References
(1) A von Glehn. Resveratrol/COPD [electronic response to Culpitt et
al. Inhibition by red wine extract, resveratrol, of cytokine release by
alveolar macrophages in COPD] thoraxjnl.com 2004http://thorax.bmjjournals.com/cgi/eletters/58/11/942#153
(2) MJ Leckie, SA Bryan, TT Hansel, PJ Barnes. Novel therapy for
COPD. Exp Opin Invest Drugs 2000; 9: 3-23.
(3) LE Donnelly, DF Rogers. Therapy for chronic obstructive pulmonary
disease in the 21st century. Drugs 2003; 63: 1973-1998.
(4) PW Jones, FH Quirk CM Baveystock. Why quality of life measures
should be used in the treatment of patients with respiratory illness.
Monaldi Arch Chest Dis 1994; 49:79-82.
(5) DM Goldberg, J Yan, GJ Soleas.Absorption of three wine-related
polyphenols in three different matrices by healthy subjects. Clin Biochem
2003; 36:79-87.
(6) T Wieder, A Prokop, B Bagci, F Essmann, D Bernicke, K Schulze-
Osthoff, B Dorken, HG Schmalz, PT Daniel, G Henze. Piceatannol, a
hydroxylated analog of the chemopreventive agent resveratrol, is a potent
inducer of apoptosis in the lymphoma cell line BJAB and in primary,
leukemic lymphoblasts. Leukemia 2001; 15:1735-42
Despite the great advances in critical care medicine, mortality of
ARDS is still high. Protective ventilatory strategy - utilizing lower
tidal volumes - has been used to reduce mortality of ARDS. Both
conventional and protective ventialtory strategies aim to achieve
satisfactory arterial rather than tissue oxygenation.According to
protective strategy, PEEP is used - even with acceptable SPO2...
Despite the great advances in critical care medicine, mortality of
ARDS is still high. Protective ventilatory strategy - utilizing lower
tidal volumes - has been used to reduce mortality of ARDS. Both
conventional and protective ventialtory strategies aim to achieve
satisfactory arterial rather than tissue oxygenation.According to
protective strategy, PEEP is used - even with acceptable SPO2 - to prevent
atelectato-trauma. When SPO2 is low, PEEP is usually set at higher level
to improve arterial oxygenation. In the clinical setting of ARDS, the
severely-injured lungs may be particularlly more vulnerable to damage from
high FIO2 and PEEP than would be otherwise expected. It may be more
appropriate to concenterate more on the tissue oxygenation than on the
arterial oxygenation when dealing with ARDS patients. Tissue oxygenation
can be monitored either directly by measuring whole-body O2 uptake by
calorimetery or indirectly by calculating Oxygen extraction ratio ( 02 ER
= Sao2-Svo2/Sao2 ) where Sao2 is arterial O2 saturation and Svo2 is mixed
venous O2 saturation. Tissue oxygenation can be improved by increasing
oxygen delivery to the tissues - DO2 - and decreasing oxygen uptake -
VO2. Oxygen delivery can be increased not only by improving arterial O2
saturation but also by optimizing hemoglobin level and improving cardiac
output( QT ). DO 2 = 1.34 x Sao2 x Hb x QT. According to previous equation,
it can be concluded than O2 delivery can be maintained - at least
theoretically - by supra-normal cardiac output if Sao2 is relatively
low.Cardiac output may be increased to supra-normal levels by inotropics
such as dobutamine or milrinone. To achieve supra-normal QT, in addition
to inotropics, volume expantion - by colloids - and vasodilators such as
prostacyclin may be used. Prostacyclin is a systemic and pulmonary
vasodilator that can increase cardiac output and counteract the
vasospastic effect of hypoxemia on pulmonary vasculature. In conclusion, i
hypothesize that maintaining adequate tissue oxygenation - by supranormal
cardiac output - may enable us to use more protective ventilatory strategy
(lower levels of PEEP, FIO2 and I:E ratio) and to accept lower levels of
arterial O2 saturation (permissive hypoxemia) with the aim of reducing the
risk of pulmonary O2 toxicity, barotrauma and lung injury that may be
particularlly difficult to diagnose in the clinical setting of ARDS. It is
hoped that this tissue oxygenation - oriented rather than arterial
oxygenation - oriented approach may have a more favourable impact on
mortality of ARDS.
I read with interest the recent article by Green et al. [1] showing
that in acute asthma, activation of leukotriene pathways correlated with
the degree of airflow obstruction, and a reduction in leukotriene levels
was associated with resolution of asthma exacerbation.
However, no analysis was performed on patients categorised as being
in the treatment failure group, which was reported to...
I read with interest the recent article by Green et al. [1] showing
that in acute asthma, activation of leukotriene pathways correlated with
the degree of airflow obstruction, and a reduction in leukotriene levels
was associated with resolution of asthma exacerbation.
However, no analysis was performed on patients categorised as being
in the treatment failure group, which was reported to be as high as 10% of
patients receiving intravenous montelukast.[2]
The importance of this analysis can not be understated as not
everyone with asthma respond to antileukotriene therapy[3,4] and non-
responders have been reported to be as high as 50% in chronic asthma.[5]
It would have been interesting to observe urinary leukotriene LTE4
levels in the treatment failure group as it has been shown that cysteinyl
leukotriene release from leukocytes of responders were higher than non-
responders, which in turn correlated with response to antileukotriene
therapy.[5]
References
1. Green SA, Malice M-P, Tanaka W, Tozzi CA, et al.Increase in
urinary leukotriene LTE4 levels in acute asthma: correlation with airflow
limitation. Thorax 2004;59:100-4.
2. Camargo CA, Smithline HA, Malice M-P, et al. A randomized
controlled trial of intravenous montelukast in acute asthma. Am J Respir
Crit Care Med 2003;167:528-37.
3. Wenzel SE. Antileukotriene drugs in the management of asthma. JAMA
1998;280:2068-9.
4. Drazen JM, Israel E, O’Byrne PM. Treatment of asthma with drugs
modifying the leukotriene pathway. N Engl J Med 1999;340:197-206.
5. Terashima T, Amakawa K, Matsumaru A, et al. Correlation between
cysteinyl leukotriene release from leukocytes and clinical response to a
leukotriene inhibitor. Chest 2002;122:1566-70.
In reviewing the literature on non-asbestos causes of mesothelioma I located the paper by Baldi et al.[1]
This paper provides excellent
evidence supporting a molecular mehanism on the pathology of mesothelioma.
It is mentioned in passing that there may be other causes of mesothelioma
besides asbestos. Certainly this paper suggests the SV40 virus as one of
these other agents/factors. When...
In reviewing the literature on non-asbestos causes of mesothelioma I located the paper by Baldi et al.[1]
This paper provides excellent
evidence supporting a molecular mehanism on the pathology of mesothelioma.
It is mentioned in passing that there may be other causes of mesothelioma
besides asbestos. Certainly this paper suggests the SV40 virus as one of
these other agents/factors. When evaluating the literature, there is no
current list of the other agents/factors identified, besides asbestos,
that have been reported to cause mesothelioma. However, it is commonly
discussed that other agents/factors exist in causing this disease with
most are not able to mention what they are, which I suggest is because no
general list has been published identifying these agents/factors. Table 1 provides a list of these agents/factors along with a reference. Familial
mesothelioma has been reported,[2] which is unrelated to any causative
agent. Mesothelioma has also been indicated to “naturally” occur with a
background level of this disease.[3] It should be mentioned that this
list does not include all references and there is likely other
agents/factors that I missed in my literature search along with others
that have yet to be identified.
Table 1 Agents/Factors reported in causation of mesothelioma
Agent/Factors
Reference
Ionizing radiation
Hoffman et al., 1994
(reference 4)
Beryllium
Ilgren and Wagner,
1991 (reference 5)
Copper
Ilgren and Wagner,
1991 (reference 5)
Nickel
Ilgren and Wagner,
1991 (reference 5)
Rubber
Ilgren and Wagner,
1991 (reference 5)
Glass dust
Ilgren and Wagner,
1991 (reference 5)
MMMF
Health Effects
Institute - Asbestos Research,1991 (reference 6)
Lung infections
Hillerdal and Berg,
1985 (Reference 7)
Dietary
Huncharek, 2002
(Reference 8)
Sugarcane
Das, 1976 (Reference
9)
Zeolite minerals
Dogan, 2003
(Reference 10)
The agents/factors listed exclude SV40 and asbestos. Current
investigations on asbestos caused mesothelioma’s suggest that these are a
result of amphiboles and a dose-response relationship exist.[11] This
indicates that a threshold for amphibole asbestos inducted mesothelioma
exist with a suggested threshold level of 5 fiber-years.[12] It has been
indicated [13] that chrysotile, a serpentine type of asbestos, is not a
causative agent of mesothelioma.
References
1. Baldi A, Groeger AM, Esposito V, Cassandra R, Tonini G, Battista
T, Di Marino MP, Vincenzi B, Santini M, Angelini A, Rossiello R, Baldi F,
Paggi MG. Expression of p21 in SV40 large T antigen positive human pleural
mesothelioma: relationship with survival. Thorax. 2002;57:353-6.
2. Risgerg H, Nickels J, Wagermark J. Familial clustering of
malignant mesothelioma. Cancer. 1980;45:2422-7.
3. Price B, Ware A. Mesothelioma trends in the United States: an
update based on surveillance, epidemiology, and the end results program
data for 1973 through 2003. Am J Epidemiol. 2004;159:107-112.
4. Hoffman J, Mintzer D, Warhol MJ. Malignant mesothelioma following
radiation therapy. Am J Med. 1994;94:379-92.
5. Ilgren EB, Wagner JC. Background incidence of mesothelioma: animal
and human evidence. Regul Toxicol Pharm. 1991;13:133-49.
6. Health Effects Institute - Asbestos Research (1991) Asbestos in
public and commercial buildings: a literature review and synthesis of
current knowledge. Cambridge, MA.
7. Hillerdal G, Berg J. Malignant mesothelioma secondary to chronic
inflammation and old scars. Cancer. 1985;55:1968-72.
8. Huncharek M. Non-asbestos related difuse malignant mesothelioma.
Tumori. 2002;88:1-9.
9. Das PB, Fletcher AG, Deodhare SG. Mesothelioma in an agricultural
community of India: a clinicopathological study. Aust New Zealand Journal
of Surgery. 1976;46:218-226.
10. Dogan AU. Mesothelioma in Cappadocian villages. Indoor-Built
Environ. 2003;12:367-75.
11. Price B, Ware A. Mesothelioma trends in the United States: an
update based on surveillance, epidemiology, and the end results program
data for 1973 through 2003. Am J Epidemiol. 2004;159:107-112.
12. Lange, JH. Has the World Trade Center tragedy established a new
standard for asbestos? Indoor-Built Environ. Editorial. 2001;10: 346-369.
13. Ilgren ED. Coliga fibre: a short fibre, amphibole-free chrysotile
–Part 4: further evidence for a lack of fibrogenic and tumorigenic
activities. Indoor-Built Environ. 2002;11:171-177.
Regarding the article by Culpitt et al.[1] I wish to comment on the use of Resveratrol and the claims made with regard to COPD. I would interested in learning what evidence the authors
have for the claims made. I have, after reading the report and as a patient,
tested Resveratrol for 9 weeks without absolutely any result! There were
no indications of influence on the immune system or
inflammato...
Regarding the article by Culpitt et al.[1] I wish to comment on the use of Resveratrol and the claims made with regard to COPD. I would interested in learning what evidence the authors
have for the claims made. I have, after reading the report and as a patient,
tested Resveratrol for 9 weeks without absolutely any result! There were
no indications of influence on the immune system or
inflammatory system.
The test was done as per: 1. 3 capsulas , 25 mg Resveratrol/capsule) a day for 3 weeks
after that 2. 6 capsulas per day for 3 weeks
and after that 3. 9 capsulas per day for 3 weeks
Measurements were taken with an FEV-meter and an
oxygen-saturation meter for the duration of the test. No effect was measured.
I think it is of vital interest that results as those in this article can be repeated in vivo. Otherwise, valuable and costly scientific work could be lost.
I am looking forward hearing from the authors.
Reference
(1)
SV Culpitt, DF Rogers, PS Fenwick, P Shah, C De Matos, RE K Russell, PJ Barnes, and LE Donnelly. Inhibition by red wine extract, resveratrol, of cytokine release by alveolar macrophages in COPD. Thorax 2003; 58: 942-946.
I thank Mishra and colleagues for their cogent comments about the
potential clinical utility of ELISPOT for diagnosis of tuberculosis
infection in high burden countries, such as India.[1]
The high prevalence of latent tuberculosis infection in Indian adults
[2] means that ELISPOT (as with any test of tuberculosis infection, as
opposed to active disease) cannot be used to routinely ‘rule in’ a...
I thank Mishra and colleagues for their cogent comments about the
potential clinical utility of ELISPOT for diagnosis of tuberculosis
infection in high burden countries, such as India.[1]
The high prevalence of latent tuberculosis infection in Indian adults
[2] means that ELISPOT (as with any test of tuberculosis infection, as
opposed to active disease) cannot be used to routinely ‘rule in’ a
diagnosis of active tuberculosis. However, the high sensitivity of ELISPOT
relative to the tuberculin skin test (TST) means that it could be used
effectively as a ‘rule out’ test in patients with suspected tuberculosis
who do not, in fact, have tuberculosis. Notwithstanding, its main
application in high burden countries will be in vulnerable subgroups who,
once infected with Mycobacterium tuberculosis, are at high risk of
progression to active, often disseminated, tuberculosis: young children,
HIV-infected people and iatrogenically immunosuppressed patients.
We recently prospectively confirmed the clinical utility of ELISPOT
(and its superiority over TST) in the diagnostic evaluation of HIV-
infected children with suspected tuberculosis in a high burden region in
South Africa (Liebeschuetz et al, manuscript submitted). Our experience
with clinical application of ELISPOT to date has shown that it accelerates
diagnosis of tuberculosis in clinically challenging patients with anergic
false negative TST results due to immunosuppressive medication [3] or
leukaemia (Richeldi L, Luppi M, Lalvani A, unpublished observations). The
potential role of ELISPOT for improving diagnosis of tuberculosis in
iatrogenically immunosuppressed patients in India is, understandably, of
particular interest to Mishra and colleagues, and we recognize the need
for large prospective studies. In this regard, with colleagues at
Christian Medical College, Vellore, South India, we have initiated a
prospective evaluation of ELISPOT for early detection of tuberculosis in
renal transplant recipients who suffer very high rates of disseminated
tuberculosis in the first year post-transplant.[4]
Differences in the strength of ELISPOT responses (numbers of
interferon-gamma spot-forming cells) do not precisely discriminate between
patients with active tuberculosis and latently infected healthy contacts.[5] However, our ongoing longitudinal studies, including the one in
Vellore, will assess whether changes in strength of ELISPOT response over
time in latently infected individuals can provide an early marker of
progression to active tuberculosis.
Reference
1. Pravas Pratap Mishra et al. Use of ELISPOT for latent tuberculosis: utility in countries with a high burden of infection [electonic response to Lalvani A,
Spotting latent infection: the path to better tuberculosis control] thoraxjnl.com 2004http://thorax.bmjjournals.com/cgi/eletters/58/11/916#140
1. Lalvani A, Nagvenkar P, Udwadia Z, et al. Enumeration of T cells
specific for RD1-encoded antigens suggests a high prevalence of latent
Mycobacterium tuberculosis infection in healthy urban Indians. J Infect
Dis 2001;183:469-77.
2. Richeldi L, Ewer K, Losi M, Hansell D, Roversi P, Fabbri L and Lalvani
A. Early diagnosis of multidrug resistant tuberculosis. Annals of Internal
Medicine 2004; in press.
3. John GT, Shankar V, Abraham AM, Mukundan U, Thomas PP and Jacob CK.
Risk factors for post-transplant tuberculosis. Kidney Int 2001;60:1148-53.
4. Pathan AA, Wilkinson KA, Klenerman P, et al. Direct ex vivo analysis of
antigen-specific IFN-gamma-secreting CD4 T cells in Mycobacterium
tuberculosis-infected individuals: associations with clinical disease
state and effect of treatment. J Immunol 2001;167:5217-25
Conflict of interest statement AL is a named inventor on patents
relating to T cell-based diagnosis filed by the University of Oxford.
Regulatory approval and commercialisation of ELISPOT is being undertaken
by a spin-out company of the University of Oxford (Oxford Immunotec Ltd),
in which AL has a share of equity.
I was excited by this study which shows a decline in the rate of
decline in lung function in COPD with inhaled steroids. Although small,
this effect could be significant over time, with the potential to delay
the onset of debilitating symptoms with this disease. However, the study
seems to use similar methadology to a recently published study in another
journal which reached the opposite conclusion.[1]...
I was excited by this study which shows a decline in the rate of
decline in lung function in COPD with inhaled steroids. Although small,
this effect could be significant over time, with the potential to delay
the onset of debilitating symptoms with this disease. However, the study
seems to use similar methadology to a recently published study in another
journal which reached the opposite conclusion.[1] Are the authors able to
explain the disparate results?
Reference
(1) Long-Term Effects of Inhaled Corticosteroids on FEV1 in Patients
with Chronic Obstructive Pulmonary Disease: A Meta-Analysis
Kristin B. Highland, Charlie Strange, and John E. Heffner
Annals 2003 138: 969-973.
Dear Editor
Positive-pressure ventilation may be associated with adverse cardiovascular effects, particularly when using large tidal volumes and / or high PEEP. The increased intra-thoracic pressure decreases venous return to the heart with subsequent reduction of cardiac filling, cardiac output and blood pressure. On the other hand, positive-pressure ventilation may have beneficial hemodynamic effects. If the pos...
Dear Editor
We read with interest the recent article by Wu et al. [1] in which they investigated a single nucleotide polymorphism at exon 1 of the transforming growth factor beta1 (TGF-beta1) gene.
While we agree with their assumption that TGF-beta1 is a candidate gene for COPD association study, we can not understand why they restricted their study to only one polymorphism in that gene. There a...
Dear Editor
Malignant mesothelioma (MM) is a rare, highly aggressive tumor, accounting for less than 1% of all cancer deaths in the world. Although the association between exposure to asbestos and the development of MM is commonly accepted, the exact mechanism whereby asbestos induces MM is unknown. Therefore, we agree with Dr Lange observation that the search for other agents/factors causing this disease should...
Dear Editor
We thank Andreas von Glehn for his interest in our paper, sufficient that he took resveratrol capsules for his own condition, presumably COPD.[1]
His short course of treatment (9 weeks) highlights the difficulties in evaluating therapies for the treatment of COPD. COPD is a slowly progressive inflammatory condition of the lungs and, as such, clinical trials using lung function measurements a...
Dear Editor
Despite the great advances in critical care medicine, mortality of ARDS is still high. Protective ventilatory strategy - utilizing lower tidal volumes - has been used to reduce mortality of ARDS. Both conventional and protective ventialtory strategies aim to achieve satisfactory arterial rather than tissue oxygenation.According to protective strategy, PEEP is used - even with acceptable SPO2...
Dear Editor
I read with interest the recent article by Green et al. [1] showing that in acute asthma, activation of leukotriene pathways correlated with the degree of airflow obstruction, and a reduction in leukotriene levels was associated with resolution of asthma exacerbation.
However, no analysis was performed on patients categorised as being in the treatment failure group, which was reported to...
Dear Editor
In reviewing the literature on non-asbestos causes of mesothelioma I located the paper by Baldi et al.[1]
This paper provides excellent evidence supporting a molecular mehanism on the pathology of mesothelioma. It is mentioned in passing that there may be other causes of mesothelioma besides asbestos. Certainly this paper suggests the SV40 virus as one of these other agents/factors. When...
Dear Editor
Regarding the article by Culpitt et al.[1] I wish to comment on the use of Resveratrol and the claims made with regard to COPD. I would interested in learning what evidence the authors have for the claims made. I have, after reading the report and as a patient, tested Resveratrol for 9 weeks without absolutely any result! There were no indications of influence on the immune system or inflammato...
Dear Editor
I thank Mishra and colleagues for their cogent comments about the potential clinical utility of ELISPOT for diagnosis of tuberculosis infection in high burden countries, such as India.[1]
The high prevalence of latent tuberculosis infection in Indian adults [2] means that ELISPOT (as with any test of tuberculosis infection, as opposed to active disease) cannot be used to routinely ‘rule in’ a...
Dear Editor
I was excited by this study which shows a decline in the rate of decline in lung function in COPD with inhaled steroids. Although small, this effect could be significant over time, with the potential to delay the onset of debilitating symptoms with this disease. However, the study seems to use similar methadology to a recently published study in another journal which reached the opposite conclusion.[1]...
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