JerMa88/BMC_Gastroenterology_Peer_Reviews huggingface dataset:
Review for 10.1186/1471-230X-8-28 (2008)

Reviewer's report
Title:Unexplained Chest/Epigastric Pain in Patients with Normal Endoscopy as a
Predictor for Ischemic Heart Disease and Mortality: A Danish 10-Year Cohort
Study
Version: 3Date:20 November 2007
Reviewer: Jan Gunnar JH Hatlebakk
Reviewer's report:
General
-------------------------------------------------------------------------------
Major Compulsory Revisions (that the author must respond to before a decision
on publication can be reached)
None.
-------------------------------------------------------------------------------
Minor Essential Revisions (such as missing labels on figures, or the wrong use of
a term, which the author can be trusted to correct)
Page 12: The follow-up is hardly "complete", as discussed by the authors later.
Only in-patient hospital diagnoses are included, the way I read the text. Were
diagnoses from outpatient clinics included? To what extent could IHD be treated
by private specialists?
Figure 1 is illogical, since the authors argue that chest and epigastric pain can
not be meaningfully discerned. In this figure the two pain locations are separated,
given specific diagnoses, and then again lumped together. Should be omitted.
-------------------------------------------------------------------------------
Discretionary Revisions (which the author can choose to ignore)
None.
What next?: Accept after discretionary revisions
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests.
Review for 10.1186/1471-230X-8-28 (2008)

Reviewer's report
Title:Unexplained Chest/Epigastric Pain in Patients with Normal Endoscopy as a
Predictor for Ischemic Heart Disease and Mortality: A Danish 10-Year Cohort
Study
Version: 6Date:9 April 2008
Reviewer: Noel Bairey Merz
Reviewer's report:
The manuscript is overall responsive to the prior review. The authors did not fully
respond to the first query, e.g. they did not clarify if they selected the symptom
constellation by fitting it to the outcome data and if they did this, it should be
described as a limitation and proposed to be tested in a secondary population. If
the selected their symptoms a priori this is not a problem.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interests.
Review for 10.1186/1471-230X-8-28 (2008)

Reviewer's report
Title:Unexplained Chest/Epigastric Pain in Patients with Normal Endoscopy as a
Predictor for Ischemic Heart Disease and Mortality: A Danish 10-Year Cohort
Study
Version: 6Date:2 May 2008
Reviewer: Jan Gunnar JH Hatlebakk
Reviewer's report:
The responses to my queries are satisfactory.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I have no competing interests.
Review for 10.1186/1471-230X-8-33 (2008)

Reviewer's report
Title:Epigenetic mechanisms involved in differential MDR1 mRNA expression
between gastric and colon cancer cell lines and rationales for clinical
chemotherapy
Version: 1Date:29 July 2007
Reviewer: Jing-Yuan FANG
Reviewer's report:
General
-------------------------------------------------------------------------------
Major Compulsory Revisions (that the author must respond to before a decision
on publication can be reached)
Specific points:
1. Why does authors did not assay the methylation of the promoter or/and exon 1
using the bisulfite modification and sequencing ( mapping ) ? Because the result
from mapping contains all of data from the MSP and restriction endonuclease
digestion as well as direct sequencing for MSP products. The primers design
problem? Please explain the reason.
2.Please add some publications published from 2002~2007, in References.
-------------------------------------------------------------------------
Minor Essential Revisions (such as missing labels on figures, or the wrong use of
a term, which the author can be trusted to correct)
-------------------------------------------------------------------------------
Discretionary Revisions (which the author can choose to ignore)
What next?: Accept after discretionary revisions
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests.
Review for 10.1186/1471-230X-8-33 (2008)

Reviewer's report
Title:Epigenetic mechanisms involved in differential MDR1 mRNA expression
between gastric and colon cancer cell lines and rationales for clinical
chemotherapy
Version: 2Date:19 March 2008
Reviewer: Jing-Yuan FANG
Reviewer's report:
Dear Sir,
Thanks for your email! I think that the revision version is fine,I do not have any
suggestion. Thank you!
Best,
Jing-Yuan FANG
What next?: Accept without revision
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interest.
Review for 10.1186/1471-230X-8-33 (2008)

Reviewer's report
Title:Epigenetic mechanisms involved in differential MDR1 mRNA expression
between gastric and colon cancer cell lines and rationales for clinical
chemotherapy
Version: 2Date:28 March 2008
Reviewer: Masakazu Yashiro
Reviewer's report:
Major Compulsory Revisions
The authors have not answered our points sufficiently. This paper is
not recommended for publication in this form.
Major Comments:
Authors’ reply is insufficient for request. Authors show few
additional data. While the revised manuscript is improved, its
conclusions are speculative and not supported by the experiments shown.
Minor Comments:
1. Determined quantity of PgP protein in cancer cells and its
correlation with expression mRNA of MDR1 might be required, because
results of isotopic PCR are different from real-time RT-PCR.
2. Examination of methylation status by bisulfite treatment is
necessary. Direct sequencing of promoter region with or without
bisulfite treatment might be useful to examine the methylation status
at in gastric and colon cancer cell lines.
3. In inhibition assay using 5-AC and TSA, functional effect of
them should be clarified for example, in chemo-sensitivity assay or
Pgp protein expression assay.
4. If authors insist on rationale of clinical chemotherapy
described in title and as they also described in discussion, they
should examine effect of other drugs commonly used for gastric and
colon cancer such as 5-FU, irinotecan, and oxaliplatin.
Review for 10.1186/1471-230X-8-33 (2008)

Reviewer's report
Title:Epigenetic mechanisms involved in differential MDR1 mRNA expression
between gastric and colon cancer cell lines and rationales for clinical
chemotherapy
Version: 4Date:23 May 2008
Reviewer: Masakazu Yashiro
Reviewer's report:
Discretionary Revisions
The authors added new experimental data in response to the reviewers’
comments. They provided evidence of DNA methylation status by bisulfate DNA
sequencing assay. Authors demonstrated that methylation status by
quantification PCR-based methylation analysis were completely matched with the
results obtained by bisulfite DNA sequencing assay. They suggested that
complete methylation in the extended MS1 site was responsible for increased
MDR1 mRNA expression by the treatment with 5AC. In addition, MS1 site
derived from exon1 of MDR1 promoter has shown to be more important with
respect to gene expression than MS2 site from intron 1 of MDR1 promoter. This
DNA sequencing studies revised the manuscript extensively.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Review for 10.1186/1471-230X-8-32 (2008)

Reviewer's report
Title:Hosptial-acquired invasive pulmonary aspergillosis in patients with hepatic
failure
Version: 3Date:19 November 2007
Reviewer: saad nseir
Reviewer's report:
General
-------------------------------------------------------------------------------
Major Compulsory Revisions (that the author must respond to before a decision
on publication can be reached)
In this revised version, authors have convincingly addressed most of my
comments. However, substantial English editing is still needed. In addition, some
clarifications would be helpful.
1. In their comments, authors stated that TBLB was performed in 7 patients and
PPLB in 2 patients. However, in the revised manuscript, they stated that stated
that TBLB was performed in 8 patients and PPLB in 4 patients. Please clarify.
2. In their comments, authors stated that complications (one pneumothorax and 2
haemoptysis) occurred in 3 patients after lung biopsy. This should be added to
the manuscript.
3. 9 of 12 (75%) biopsies performed for suspicion of IPA confirmed this
diagnosis. This rate is impressive and should be commented in discussion
section.
4. Results section is rather lengthy and should be shortened. Some of the results
could be presented in a table.
5. Pages should be numbered and modifications should be highlighted.
-------------------------------------------------------------------------------
Minor Essential Revisions (such as missing labels on figures, or the wrong use of
a term, which the author can be trusted to correct)
-------------------------------------------------------------------------------
Discretionary Revisions (which the author can choose to ignore)
What next?: Unable to decide on acceptance or rejection until the authors have
responded to the major compulsory revisions
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Not suitable for publication unless extensively edited
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests
Review for 10.1186/1471-230X-8-32 (2008)

Reviewer's report
Title:Hospital-acquired invasive pulmonary aspergillosis in patients with hepatic
failure
Version: 3Date:10 March 2008
Reviewer: Freedom Nkhululeko N Gumedze
Reviewer's report:
- Minor Essential Revisions
1. Page 3: Methods and materials: Correct spelling for brief.
2. Page 6: Results: It is unclear whether the figures in brackets
(22-51) represents a range or confidence interval.
3. Page 7: Results: Be consistent report the range as from 4 to 11 and
not 1~16.
4. Page 11: Table 1: Include standard deviations for the means of Age
and MELD scoring.
5. The notation “Mean ± SEM” is used thoughout the manuscript and
should be changed. The interval resulting from the expression represents
a 68% confidence interval for the true mean if the variable under
consideration is Normally distributed, but is not of any particular
interest, even when the Normality assumption is justified. The
convention “Mean (SD)” or “Mean (SEM)” is preferable.
What next?: Accept after minor essential revisions
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I declare that I have no competing interests.
Review for 10.1186/1471-230X-8-32 (2008)

Reviewer's report
Title:Hospital-acquired invasive pulmonary aspergillosis in patients with hepatic
failure
Version: 4Date:13 May 2008
Reviewer: saad nseir
Reviewer's report:
Authors have convincingly addressed all of my comments
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests
Review for 10.1186/1471-230X-8-31 (2008)

Reviewer's report
Title:Caustic ingestion in adults: the role of endoscopic classification in
predicting outcome
Version: 1Date:19 January 2008
Reviewer: Menachem Gross
Reviewer's report:
Dear Editor,
Comments to Authors Ã#Â¢Ã#Â#Ã#Â# Manuscript Title: Caustic ingestion in
adults: the role of endoscopic classification in predicting outcome
The authors have provided a well written and interesting original study on the role
of endoscopic classification in predicting outcome of caustic ingestion in adults.
However, after careful consideration of the manuscript, I think that there are few
weak points:
1. In the abstract, the authors should describe more relevant results in the result
section.
2. In the methods, the authors should define how they evaluate the amount of
ingested substance.
3. In the results section page 8: "One patients committed twice suicide with
different corrosive substance in three month" Ã#Â¢Ã#Â#Ã#Â# should be change
to "One patient committed suicide two times with different corrosive substance in
three month".
4. In the result section page 9: "The results of EGD indicated that the largest
group of patients sustained grade 3b mucosal injuries (n = 82, 30.03%)"
Ã#Â¢Ã#Â#Ã#Â# should be change to "The results of EGD in this study showed
that grade 3b injuries was the most common caustic injury (n = 82, 30.03%),
followedÃ#Â¢Ã#Â#Ã#Â¦".
5. Generally, the topic is interesting but the message is not new enough.
Menachem Gross, MD
What next?: Reject because scientifically unsound
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests
Review for 10.1186/1471-230X-8-31 (2008)

Reviewer's report
Title:Caustic ingestion in adults: the role of endoscopic classification in
predicting outcome
Version: 1Date:22 January 2008
Reviewer: Jan-Werner W Poley
Reviewer's report:
General:
interesting series, one of the largest published, on caustic ingestions of interest
to anyone dealing with these kind of patients.
Major Revisions:
Introduction:
* please provide references with regards to both the protective effect of "eschar
formation" and the presumed pyloric spasm as a reaction to large amounts of
caustic substances
Methods:
* Please explain why this period was chosen
* please state whether the used 6 pt scale was used prospectively or
retrospectively based on reports and images/footage from the endoscopies
* Was nasogastric, nasojejunal or parenteral feeding used in these patients
Results
* Please explain or hypothesize why there was an age difference in distribution of
mucosal injury and, if this was used to adjust the data, how this affected
outcome.
* Please provide information on differences between the acid and alkali group
with regards to outcome on the chosen parameters.
* The subject of surgery is briefly touched upon. Please provide more information
on patients that went for surgery and their outcome.
* 66 patients had a stricture. 21 patients were dilated endoscopically (how and
how often and were any complications seen). 24 patients had a
gastrojejunostomy. Was this because of a gastric outlet or duodenal obstruction
and what was the timing of surgery (mortality 3/24!). How were the remaining
patients treated?
Discussion
* compared to some other series, especially those with a high percentage of
acidic intoxications, there is a marked difference with regards to severity of
mucosal damage (quite severe) and mortality (relatively low). Please comment
on this.
* the only significant difference between IIa and IIb was hospital stay. Do the
authors consider differentiating between IIa and IIb useful and reliable?
* especially since the difference betweeen IIIa and IIIb seems to be very
important clinically.
* please explain why patients with IIIb burns should be considered surgical
candidates. What was the outcome in patients that went for surgery and patients
that didn't? What were the characteristics of these patients?
I think one should be very careful to make these kind of recommendations based
on retrospective data.
Minor revisions:
Results:
* the amount of substance taken is sometimes very hard or impossible to
ascertain. Please mention this in the discussion (or results if available).
What next?: Unable to decide on acceptance or rejection until the authors have
responded to the major compulsory revisions
Level of interest: An article of limited interest
Quality of written English: Needs some language corrections before being
published
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interests
Review for 10.1186/1471-230X-8-31 (2008)

Reviewer's report
Title:Caustic ingestion in adults: the role of endoscopic classification in
predicting outcome
Version: 1Date:6 February 2008
Reviewer: Showkat Zargar
Reviewer's report:
The authors describe a retrospective analysis of 273 adult patients with caustic
injury in terms of clinical and endoscopic findings, and short-term and long-term
clinical outcomes in relation to endoscopic findings. The present study shows
that endoscopic classification of burns can be used to predict accurately the
short-term and long-term complications, clinical outcome and provide opportunity
to guide appropriate treatment. Although the study has been well conducted with
valid conclusions, but I would like to authors respond to the following points
Major points
1. The authors should state the complications, if any, encountered because of
upper gastrointestinal endoscopy.
2. Abstract needs to be written
a. Introduction needs to be shortened.
b. Results can be improved by adding more data
a. Conclusions made are inconsistent with observations of the study. Authors
concluded that â##patients with grade 3b burns on endoscopy merit surgical
exploration. The extent of tissue destruction depends on the physical form, type,
and concentration of caustic agent, premorbid state of the tissue, contact
duration, and amount of substance ingested. Indications, mucosal injuryâ##.
There is no data available in the manuscript on these conclusions.
b. I understand conclusions can be â##Upper endoscopy is safe, reliable and
sufficient for evaluation of extent and severity of mucosal injury after caustic
ingestion. It accurately predicts the immediate and long-term complications, and
guides appropriate therapyâ##
Minor points
1. Type of fiberoptic endoscopy used i.e., outer diameter of endoscope used
2. Was entire upper gastrointestinal tract inspected during endoscopy especially
in patients with grade III burns?
Level of interest
An article of importance in its field
Quality of written English
Needs some language corrections before being published
Statistical review
No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests
I have no competing interests
Review for 10.1186/1471-230X-8-31 (2008)

Reviewer's report
Title:Caustic ingestion in adults: the role of endoscopic classification in
predicting outcome
Version: 2Date:22 May 2008
Reviewer: Showkat Zargar
Reviewer's report:
I evaluated revised version along with point-to-point responses to the points
raised by me and I am satisfied with the responses.
Review for 10.1186/1471-230X-8-31 (2008)

Reviewer's report
Title:Caustic ingestion in adults: the role of endoscopic classification in
predicting outcome
Version: 2Date:26 May 2008
Reviewer: Jan-Werner W Poley
Reviewer's report:
I feel that most of the items touched upon in my previous review have been
clarified although the actual text could still use some editing.
Level of interest: An article of limited interest
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interests
Review for 10.1186/1471-230X-8-30 (2008)

Reviewer's report
Title:Evaluation of the Birmingham IBS Symptom Questionnaire.
Version: 1Date:14 March 2008
Reviewer: Lloyd Sutherland
Reviewer's report:
Discretionary changes
1. Community (population based) sample rather than a referral based sample
2. Well written, concise review of the literature
3. The authors might want to consider placing a copyright symbol on the
questionnaire, not for monetary gain but to control the use of the questionnaire.
Minor essential revisions
1. Questions in the questionnaire use a 4 week passage of time whilst the
second questionnaire was sent out within 10 days. Given the fact that the authors
state in the Background that trials should have a duration of 2-3 months, co the
authors think that the difference in time might have altered the acceptability of the
questionnaire.
2. In future trials would the authors recommend using both the IBS Symptom
questionnaire and the IBS-QOL questionnaire.
3. How was the random sample created?
4. Did the questionnaire perform well in both genders?
What next?: Accept without revision
Level of interest: An article of outstanding merit and interest in its field
Quality of written English: Acceptable
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I declare that I have no competing interests.
Review for 10.1186/1471-230X-8-30 (2008)

Reviewer's report
Title:Evaluation of the Birmingham IBS Symptom Questionnaire.
Version: 1Date:31 March 2008
Reviewer: Pali Hungin
Reviewer's report:
This is a timely paper in an important area. IBS is a reletively common problem
but we have few means of assessing patients' symptoms even though specific
diagnostic criteria have been laid out in successive Rome consensus reports.
This research, relying on a postal questionnaire to IBS sufferers, describes the
characteristics of a Likert-based symptom questionnaire. It is cross evaluatated
against a QoL questionaire.
The approach used is very reasonable and the results as described indicate the
instrument to be reliable.
However, is is likely to be effective in the clinical setting? A few important points
arise: the subjects consisted of both those with Rome II confirmed IBS and those
with a previous diagnosis (and thus presumably no Rome II confirmation). I am
not sure if the same results might have been obtained from each of these groups.
Including those with a clinical diagnosis is a pragmatic approach but the chief
symptoms evaluated are very much Rome II orientated.
Also, whereas some of the questions were relatively descriptive (eg "loose,
mushy or water bowel motions")others rely entirely on the subjects's own
intrepretation (eg "diarrhoea" or "constipation"). There has to be a question mark
about the clinical reliability of responses to such questions - a case in point is the
differentiation in two different questions between hard bowel motion and
constipation - in practice many patients would regard the former as constipation
whereas most clinicians would relate constipation with infrequent stool. Previous
research has shown disconect between patients' own intrepretations and a Rome
based evaluation.
The paper woulod be strenghtened by including interviews, or, by an explanation
of how the difficulties above are overcome overcome in commending this
questionnaire. The risk is that the instrument itself may have scored very well (it
has!) but that it does not describe accurately what the patient's problems actually
are in the real life situation. Also, other factors such as bloating or tiredness did
not appear in the symptom evaluation questionaaire even though they are
regareded as part if IBS. Does this matter here?
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interests.
Review for 10.1186/1471-230X-8-30 (2008)

Reviewer's report
Title:Evaluation of the Birmingham IBS Symptom Questionnaire.
Version: 1Date:9 April 2008
Reviewer: Yasuhiro Sagami
Reviewer's report:
1. Major compulsory revision
In this manuscript, 15% of all samples were unable to work for health reasons. Is
this sample appropriate for the diagnosis of only IBS? Could not they work for
only exacerbation of IBS? I just guess that they had not only IBS but also other
severe diseases occurring severe abdominal symptoms.
Authors have to present more details of the group unable to work in the
manuscript. If not presented, authors must describe the limitation (about
samples) of the research in discussion of the manuscript.
2. Minor essential revision
In Rome # criteria, IBS patients have chronic and frequent abdominal pain /
discomfort that has a relief by defecation and an onset associated change in
frequency or form of stool. Therefore, the relation between abdominal pain and
status of defecation is the key of clinical evaluation in IBS. However, there is no
analysis about the relation between abdominal pain and defecation.
Authors should describe why there were no question and factor analysis about
the relation between abdominal pain and defecation.
3. Discretionary revision
Different numbers were presented in abstract (534 persons) and manuscript (533
persons) at the total mailed persons in this research.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests.
Review for 10.1186/1471-230X-8-30 (2008)

Reviewer's report
Title:Evaluation of the Birmingham IBS Symptom Questionnaire.
Version: 2Date:2 June 2008
Reviewer: Pali Hungin
Reviewer's report:
I do not feel that the alterations/additions made deal with my essential difficulties
with this paper. However, on re-reading it in its new format I am happy to suggest
that it should be accepted.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
As before
Review for 10.1186/1471-230X-8-30 (2008)

Reviewer's report
Title:Evaluation of the Birmingham IBS Symptom Questionnaire.
Version: 2Date:4 June 2008
Reviewer: Yasuhiro Sagami
Reviewer's report:
I have just read the author's response and revised manuscript. I understood the
author's answers for my questions.
I think that this manuscript is acceptable without second revision.
Yasuhiro Sagami M.D.
Dept. of Psychosomatic Medicine,
Tohoku University Hospital,
Sendai, Japan.
sagami@mail.tains.tohoku.ac.jp
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests.
Review for 10.1186/1471-230X-8-29 (2008)

Reviewer's report
Title:A Wilson protein expression, copper excretion and sweat production in
sweat glands of Wilson disease patients and controls
Version: 1Date:18 March 2008
Reviewer: Marc Solioz
Reviewer's report:
The paper by Schaefer et al. describes analysis of the expression of the Wilson
copper ATPase in skin of normal and LEC rats as well as in human skin biopsies.
It was found that the Wilson protein is expressed in human and rat sweat gland
epithelia. Copper was measured in sweat and found to be not significantly
different in controls and Wilson patients. It was also described that Wilson
disease patients had lower sweat production, which was partially reversed by
treatment or transplantation.
The expression of Wilson protein in sweat glands in controls and a lack of
expression in the LEC rats is convincingly demonstrated. There was no
correlation between Wilson protein expression and copper in sweat. Given the
methodology at hand, it is unfortunate that the authors did not look at copper in
sweat of brindled mice to determine if the Menkes copper-ATPase is responsible
for sweat copper. The conclusion that treatment of Wilson disease or
transplantation reverses the reduced sweat volume accompanying the disease is
based a single observation each, which is hardly convincing.
Major points:
Various and differing data points have been excluded from the plots of Figs. 2 to
4. There is no rationale for this.
Minor comments:
Throughout: 30 min, not 30min
Various places: penicillamine, trientine, zinc, etc. are not capitalized in English.
pg. 3, line 30: Correct grammar and spelling...by pilocarpin induced
ionotopheresis...
pg. 7, line 9: Wilson patient...was, not patients...were - this was a single case.
pg. 8, line 11: ...Menkes protein as copper-ATPase...correct grammar.
Fig. 1. The micrographs are missing scales in the pictures (fold magnification
does not account for the size of reproduction).
Fig. 3 and 4: Express sweat volumes in ul/min, not ul/30 min.
Fig. 5A and B. The axis are labeled with "Wilson patients", but in fact it was one
patient. Figures 5A and B are not justified. These five values can be described in
the text.
What next?: Accept after minor essential revisions
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests.
Review for 10.1186/1471-230X-8-29 (2008)

Reviewer's report
Title:A Wilson protein expression, copper excretion and sweat production in
sweat glands of Wilson disease patients and controls
Version: 2Date:2 May 2008
Reviewer: Marc Solioz
Reviewer's report:
The ms has been improved substantially and can in my opinion be published in
the present form.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests.
Review for 10.1186/1471-230X-8-29 (2008)

Reviewer's report
Title:A Wilson protein expression, copper excretion and sweat production in
sweat glands of Wilson disease patients and controls
Version: 2Date:13 May 2008
Reviewer: Rajendra Prasad
Reviewer's report:
The authors have responded to the questions raised in the manuscript
satisfactory.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I declare that I have no competing interests.
Review for 10.1186/1471-230X-8-27 (2008)

Reviewer's report
Title:Association between PPARGC1A polymorphisms and the occurrence of
nonalcoholic fatty liver disease (NAFLD)
Version: 1Date:3 February 2008
Reviewer: Brian N Finck
Reviewer's report:
Minor Essential Revisions:
The conclusion made in last sentence of the abstract is too strong. No evidence
that these SNPs alter PGC-1a expression or activity is presented. Also, if activity
is altered, would increasing or decreasing PGC-1a be beneficial.
The proper name is "peroxisome proliferator-activated receptor".
Discretionary Revisions:
A more in depth introduction of PGC-1a is warranted for readers that are not
familiar with the topic. Much is known about the metabolic effects of PGC-1a in
the liver and at least some of these should be listed.
It would be helpful to provide additional information regarding the location of the
SNPs of significance. Are the SNPs coding, non-coding, or in the promoter?
Although this could be determined with some effort by the reader, it would aid
readability to provide the information in the text.
What next?: Accept after minor essential revisions
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Needs some language corrections before being
published
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interests.
Review for 10.1186/1471-230X-8-27 (2008)

Reviewer's report
Title:Association between PPARGC1A polymorphisms and the occurrence of
nonalcoholic fatty liver disease (NAFLD)
Version: 1Date:12 February 2008
Reviewer: Hakan Bozkaya
Reviewer's report:
This is an interesting polymorpism study reporting frequent occurance of a
PPARGC1A polymorphism in NAFLD patient. Study design is satisfactory and
the study is well conducted. However, the number of the patients is too small for
a polymorphism study although p value for the polymorphism is small. This
should be stated. On the other hand study is informative and gives another clue
for the genetic tendency for the development of NAFLD.
Review for 10.1186/1471-230X-8-27 (2008)

Reviewer's report
Title:Association between PPARGC1A polymorphisms and the occurrence of
nonalcoholic fatty liver disease (NAFLD)
Version: 2Date:1 May 2008
Reviewer: Anna Baranova
Reviewer's report:
This is re-review of the paper Association between PPARGC1A polymorphisms
and the occurrence of nonalcoholic fatty liver disease (NAFLD) by Yoneda and
co-authors.
the re-reviewed paper much improved after revision. nevertheless, it still requires
Minor Essential Revisions. Particularly, all new additions of the paper has not
been proof-read for the point of view of teh grammar and style. as an example,
three different added sentences start from word "And", which is not acceptebale
in English. Added paragraph also contain "Jargon" expressions, e.g. "expression
lower in the liver of the TT group"
and "p value for the polymorphism is small"
Real-time PCR experiments shall be performed at least in triplicates, but I guess
this is too late to fix :-(
RT-PCR section in Methods shall at least mention that sample were liver
biopsies.
Secondly, Authors
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Needs some language corrections before being
published
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I declare that I have no competing interests.
Review for 10.1186/1471-230X-8-26 (2008)

Reviewer's report
Title:Rifaximin for maintenance therapy in antibiotic-dependent pouchitis
Version: 1Date:26 December 2007
Reviewer: Ayman S Abdelrazeq
Reviewer's report:
Thank you for the opportunity to re-review this manuscript. The manuscript is of
interest I have listed few comments
Major Compulsory Revisions
1-It will be very useful to present your pouchitis management algorithm.
2- When would you use a single vs. combination therapy to induce remission?
Minor Essential Revisions
1- A reference is required to support your statement that many patients
experience only one acute episode of pouchitis.
2- Your group has reported that the use of NSAID is an independent risk factor
for chronic pouchitis. Yet you have asked your patients who are on regular
NSAIDs to stop using these drugs for the duration of study ONLY, please clarify.
What next?: Accept after minor essential revisions
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
'I declare that I have no competing interests'
Review for 10.1186/1471-230X-8-26 (2008)

Reviewer's report
Title:Rifaximin for maintenance therapy in antibiotic-dependent pouchitis
Version: 1Date:27 December 2007
Reviewer: Darrell S Pardi
Reviewer's report:
This is a straight-forward study of rifaximin for maintenance of remission in
antibiotic-dependent pouchitis, and the manuscript is well written. I have a few
comments/questions:
Major Compulsory Revisions
1) Given that this is basically a time-to-recurrence study, it would seem that the
construction of survival curves with Kaplan-Meier analyses would be most
appropriate, rather than the proportion of subjects in remission at various points
in time.
2) The dose of rifaximin used in this study seems too low, particularly given the
unimpressive results published recently with 400 mg TID in active pouchitis
(Issacs Inflamm Bowel Dis 2007). The authors should justify the selection of this
dose, and also incorporate this newer reference into their discussion. The low
dose of rifaximin should also be acknowledged as a potential limitation of the
present study. For example, it is not clear if the 35% relapse rate by 3 months
was due to rifaximin being a suboptimal drug for these patients, or if the dose
was simply too low. The authors did attempt to analyze the maintenance dose of
rifaximin as a predictor of maintenance of remission and found it to be
non-significant, but the majority of patients in each group only got 200 mg per
day, and 73% of the relapsers discontinued medication within 2 months.
3) The choice of 3 months maintenance also needs to be justified. In other recent
studies (eg the VSL #3 studies), the duration of follow up was longer. This issue
is particularly important given the decreasing rates of maintenance that you
report after 6 and 12 months. It is not clear if these decreasing rates are due to
insufficient follow up or loss of efficacy.
Minor Essential Revisions
1) Patients routinely using NSAID were asked to stop. Was there any wash-out
period between stopping NSAIDs and inclusion in the study? This issue is
important since your group has reported that discontinuation of NSAIDs in
regular users may lead to significant improvement in PDAI.
2) Your results wold be more useful if you could provide some comparative data
(from the literature or from your own practice) on maintenance rates with other
medications (like ciprofloxacin).
What next?: Unable to decide on acceptance or rejection until the authors have
responded to the major compulsory revisions
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I helped develop and am participating in a study of rifaximin in C. difficile colitis.
As part of that work, I have served as a consultant to Salix (makers of rifaximin).
I have also collaborated with the first author on several pouchitis projects.
I believe I have been able to give a fair assessment of this manuscript despite
these potential conflicts.
Review for 10.1186/1471-230X-8-26 (2008)

Reviewer's report
Title:Rifaximin for maintenance therapy in antibiotic-dependent pouchitis
Version: 2Date:24 March 2008
Reviewer: Darrell S Pardi
Reviewer's report:
The authors have satisfactorily addressed my comments. The only additional
comment I have is in reference to the figure they have submitted in response to
Reviewer #1. Therein, they suggest that secondary causes of pouch symptoms
be excluded if a patient does not respond to a 4 week course of dual antibiotics
(or after not responding to a total of 8 weeks of therapy). I think that is too long to
let a patient go before evaluating for secondary causes, especially given the fact
that most patients with pouchitis respond well to antibiotics. Thus, i would
suggest that they move "Exclusion of secondary causes" up a few lines, before
the "cipro + metronidazole...." line.
What next?: Accept after discretionary revisions
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I have previously performed consulting work for Salix, and am currently
participating in a clinical trial using rifaximin for the treatment of C. difficile
infection.
Review for 10.1186/1471-230X-8-25 (2008)

Reviewer's report
Title:Quality of health care and patient satisfaction in liver disease: the
development and first results of the QUOTE-Liver questionnaire
Version: 2Date:9 March 2008
Reviewer: Giovanni Apolone
Reviewer's report:
I have reviewed the revised version of the manuscript, together with the
document where authors has provided a response to all reviewers.
All together, answers to our comments and modifications introduced in the new
version of the paper have greatly improved its quality that now is more in line with
my expectations and with the standards of the Journals.
Major Compulsory Revisions
The title should include words that better than now ackowledge the preliminary
althoug promising nature of evidence. I would suggest to introduce the term
“preliminary” instead of “first results”
Minor Essential Revisions
My principal concerns was about the preliminary nature of data available, the
lack of some testabout the questiionaire responsiveness/capability to detect
changes and the consequent over-interpretation of current results. While other
more technical requests/comments were very well addressed, questioned or
satisfied, I still believe that currently available results do not support the “full
validity” of the questionnaire.
Thus I reccommend that this fact should be better underscored/acknowledged in
the manuscrip, mainly in the Title, Abstract and Discussion.
An additional critical issue is the utilization of non-validated external criteria and
the lack of information about the responsiveness of the new questionnaire. It is
hard to me understand as a measure intended to be used to monitor the effect of
health care interventions (i.e, an outcome) may be used without information
about its capability to detect change over time in the same group receiving a
given intervention, or changes between groups receiving different interventions.
The fact that authors had not planned this evalaution is an explanation for the
lack of information but it is still a major problem for an evaluative tool.
This limitation should be more clearly stated whereever appropriate in the paper.
What next?: Accept after minor essential revisions
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests
Review for 10.1186/1471-230X-8-25 (2008)

Reviewer's report
Title:Quality of health care and patient satisfaction in liver disease: the
development and first results of the QUOTE-Liver questionnaire
Version: 2Date:20 March 2008
Reviewer: Ann A Jacoby
Reviewer's report:
I thank the authors for addressing the points I raised in my previous report. No
further comments.
What next?: Accept without revision
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests.
Review for 10.1186/1471-230X-8-25 (2008)

Reviewer's report
Title:Quality of health care and patient satisfaction in liver disease: the
development and preliminary results of the QUOTE-Liver questionnaire
Version: 3Date:20 May 2008
Reviewer: Andrew M Garratt
Reviewer's report:
The authors have done a good job of responding to my comments. The paper is
now acceptable for publication.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests.
Review for 10.1186/1471-230X-8-24 (2008)

Reviewer's report
Title:The pro-apoptotic K-Ras 4A proto-oncoprotein does not affect
tumorigenesis in the ApcMin/+ mouse small intestine
Version: 1Date:3 January 2008
Reviewer: Sylvie Robine
Reviewer's report:
The ratio of Kras 4A/ Kras 4B splicing variants is frequently altered in intestinal
tumours. The authors want to study the effect of K-Ras 4A splicing variant
deficiency in intestinal tumorigenesis without affecting the transcription of the
K-Ras 4B splicing variant.
To this purpose, they use mice deficient for the K-Ras 4A splicing variant in an
APC Min/+ background. The APC Min/+ mice develop spontaneously a high
number of intestinal tumours.
They expect to accelerate tumorigenesis in absence of the K-Ras 4A splicing
variant. But, in fact, they show that in absence of K-Ras 4A, there is no effect on
tumorigenesis driven by the mutation of APC, as shown by unaffected mouse
survival and unmodified tumour number and size.
One comment: The authors show that in WT intestinal epithelium and in APC
Min/+ normal intestinal epithelium, the K-Ras4A/ K-Ras4B ratio is about 50% and
is comparable between WT and APC Min/+ mice. It would be interesting to show
what is the K-Ras 4A/ 4B ratio in tumours arising spontaneously in the APC
Min/+ mice. Evaluation of proliferation and apoptosis as well as tumour grading
could be performed in order to better characterize the tumours in both genetic
backgrounds.
What next?: Accept after minor essential revisions
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
'I declare that I have no competing interests'
Review for 10.1186/1471-230X-8-24 (2008)

Reviewer's report
Title:The pro-apoptotic K-Ras 4A proto-oncoprotein does not affect
tumorigenesis in the ApcMin/+ mouse small intestine
Version: 1Date:7 February 2008
Reviewer: Onno Kranenburg
Reviewer's report:
In the present manuscript Patek et al have examined the role of the Kras4A
splice variant in intestinal tumor development driven by heterozygous loss of
APC. This group previously reported that the 4A/4B ratio is altered in favor of 4B
in CRC. Based on this observation they formed the hypothesis that alteration of
the 4A/4B ratio may affect tumor formation. The study is based on the use of the
tmï##4A mouse that lacks the 4A splice variant and that was previously
generated in the same lab. By crossing these mice with the well known APC-Min
mouse they show that loss of 4A has no effect on tumor development and
survival.
The paper is well written, the data are clear and convey a simple message that is
well explained.
I have one suggestion for improving the current manuscript. Given the
differences in 4A and 4B with respect to stimulation of cell proliferation, motility,
invasion and apoptosis induction it would be interesting to see whether the
proliferation-apoptosis ratio is altered in APC-Min versus APC-Min/tmdelta4A
tumors by immunohistochemistry for markers of apoptosis (e.g. activated
caspase 3) and proliferation (e.g. Ki67). Likewise, it would be informative to
analyze tissue sections by histochemistry to assess whether the 2 types of
tumors differ in their ability to invade the underlying submucosa.
What next?: Accept after minor essential revisions
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests
Review for 10.1186/1471-230X-8-24 (2008)

Reviewer's report
Title:The pro-apoptotic K-Ras 4A proto-oncoprotein does not affect
tumorigenesis in the ApcMin/+ mouse small intestine
Version: 2Date:23 April 2008
Reviewer: Onno Kranenburg
Reviewer's report:
The authors have answered the issues raised and, to my opinion, the manuscript
is acceptable for publication in BMC Gastroenterology.