This study by Prof Abbas et al of German Pathology Institute is in
the very important domain of transitional medicine, requiring molecular
definition and designation for the lesions or morbid entities previously
held diagnosable on the histopathological basis with or without special
staining. Molecular basis of defining disease as in the case under
consideration of IgG-4 related systemic disease, is to take into account...
This study by Prof Abbas et al of German Pathology Institute is in
the very important domain of transitional medicine, requiring molecular
definition and designation for the lesions or morbid entities previously
held diagnosable on the histopathological basis with or without special
staining. Molecular basis of defining disease as in the case under
consideration of IgG-4 related systemic disease, is to take into account
the molecule(s), like IgG-4 here, so varied histopathological
inflammatory, sclerotic, fibrotic, and phlebitic entities in bone, joint,
pancreas, salivary glands, skin, lymph nodes or else, if present with
serum IgG-4 elevation/ presence of IgG-4 plasma cells, such
lesions/morbidities are being by the researchers labelled as IgG-4
associated inflammatory expression diseases (Kim HJ 2000, Fragoulis GE
2010, Stone JR 2011). As evident in the present study, there may be IgG-4
plasmoinflammatory (mean 55/hpf) Rheumatoid (RF+ve) Synovitis, and IgG-4
plasmoinflammatory Rheumatoid factor negative (RF-ve) Synovitis as also
reported by previous studies above. Likewise in oral including neoplastic
lesions, skin diseases previously defined as allergies like pemphigus,
Salivary sclerotic inflammations; where ever lesion is accompanied by
tumifective inflammatory component and shows serum IgG-4 above normal
levels and/or IgG-4 plasma cells infiltration 5-50 or more cells/hpf, the
diagnostician is bound to tag diagnosis as IgG-4 associate say Rheumatoid
arthritis. As such any anti nuclear, anti cytoplasm or anti membranous
features could not be demonstrated in the IgG-4 or related plasma cells,
which also appeared to be consequence of (B lymphocyte irritation) disease
rather than cause. Hence designations like IgG-4 associated disease may
not be proper in view of the consequent confusion. Better it may be
identified as a common feature in several varied inflammation manifesting
diseases requiring treatment for IgG-4 plasmoinflammation, besides for the
cause and symptoms of the disease. What the authors concluded in this
study appeared to constitute IgG-4 related transition defect (TD) or
transition ambiguity (TA).
Digital mammography represents a potential new and exciting
development in the interface between computers and health care. Your paper
highlights some of the emerging issues which might be expected with new
technology. You have noted the increase in incidence of breast cancer,
together with a large increase in recall rates. Reports from the
radiologists also indicate that between 6% and 10% of tumors are
identified clini...
Digital mammography represents a potential new and exciting
development in the interface between computers and health care. Your paper
highlights some of the emerging issues which might be expected with new
technology. You have noted the increase in incidence of breast cancer,
together with a large increase in recall rates. Reports from the
radiologists also indicate that between 6% and 10% of tumors are
identified clinically following mammography.
The protocol presented by those involved in the screening program
differs in a number of significant aspects from conventional screen film
mammography.
The instructions provided to women attending for screening do not include
any advice regarding using talcum powder. This advice had always
previously been given both in writing and orally to those attending for
mammograms.
All X-rays are reported and scored by two specialist radiologists.
However, the reports, when issued, do not identify the radiologists, nor
is the panel from which they are selected apparent. The Quality Assurance
manual indicates that targets are set for the incidence of breast cancer.
A Standarised Detection Ratio (S.D.R.)is the preferred method for
correcting unit performance. This raises the possibility that the computer
can over-ride the results from the individual radiologists. Such a
mechanism might again contribute to an increase in detection of breast
cancer.
The new digital equipment relies much less on X-ray exposure and has
substituted pressure to compensate for the reduction in the X-ray content.
Is it possible that the increase in pressure on breast tissue might
contribute to the increase in incidence of second round breast cancers
from 4.4 to 5.7/1,000 when the older SFM machine is compared to the newer
FFDM machine, reported by Hambly et al in the American Journal of
Radiology, October 2009.
Is the observed interval tumor rate a result of the reduced
penetration in the new machine, with consequent diminution in accuracy of
detecting mass lesions? Alternatively, is the increased pressure in the
new machine causally related to the number of women who present with mass
lesions following mammography?
Ref:Immunohistochemical assessment for Cdx2 expression in the Barrett metaplasia-dysplasia-adenocarcinoma sequence;
This original study confirms to its cited and previous reports on Cdx2 expression in BO related intestinal metaplasia and its downregulation with the evolution of lesion to dysplasia and adenocarcinoma.[1] A well documented research communication about authors' confirmation and conclusion that the Cdx2 down regulatio...
Ref:Immunohistochemical assessment for Cdx2 expression in the Barrett metaplasia-dysplasia-adenocarcinoma sequence;
This original study confirms to its cited and previous reports on Cdx2 expression in BO related intestinal metaplasia and its downregulation with the evolution of lesion to dysplasia and adenocarcinoma.[1] A well documented research communication about authors' confirmation and conclusion that the Cdx2 down regulation was linear and significant from BO metaplasia to dysplasia to adenocarcinoma, and that the Cdx2 evaluation hence, was a reliable parameter for diagnosing and distinguishing the three entities from one another by IHC score using normal colonic mucosa as control. However, the normal colonic mucosa control mentioned by authors in last paragraph of methods was neither depicted with the tests IHC images which was essential in view of novelty of the study, nor this sole novel aspect of the study was mentioned in their effective conclusion, to say that any case of BO related metaplasia, dysplasia, adenocarcinoma was Cdx2 score-able using normal colonic mucosa as control and finally diagnosable on the basis of IHC score despite inconclusive histopathological evidence.
References:
1. Fitzgerald RC. Molecular basis of Barrett's oesophagus and oesophageal adenocarcinoma Gut 2006;55:1810-1820
This study from multiple centers of repute from UK and Spain
demonstrated cytoplasmic and nuclear expressions of NF-kB/p65, and
established that in good number-ratio of 1:4 or 1:3 cytoexpression was
followed/accompanied by the nuclear expression, besides there were cases
of breast carcinoma negative for nuclear as well as cyto expression of NF-
kB; could imply that p65 expression was consequence rather than being an
esse...
This study from multiple centers of repute from UK and Spain
demonstrated cytoplasmic and nuclear expressions of NF-kB/p65, and
established that in good number-ratio of 1:4 or 1:3 cytoexpression was
followed/accompanied by the nuclear expression, besides there were cases
of breast carcinoma negative for nuclear as well as cyto expression of NF-
kB; could imply that p65 expression was consequence rather than being an
essential component of the etiopathogenic pathway sequence of the breast
carcinogenesis. Further it appeared that this study identified NF-kB
negative ER +ve, NF-kB +ve ER -ve, NF-kb +ve ER +ve, NF-kB -ve ER -ve
subgroups; it could be indicative of remotely coordination of NF-kb and ER
receptors expressions and regulation by EGFR. It may also explain
unexpected result relating to therapy, but only the authors may be in
position to explain what may be the factual position.
Kapoor et al. (1) investigated pseudohyperkalemia in outpatients and
attributed many of the cases to hematological abnormalities or delay in
specimen centrifugation or clotting. Plasma is often recommended as the
preferred specimen in patients with leukocytosis, erythrocytosis or
thrombosis (2). Potassium released from ruptured cells during the clotting
process of serum specimens may result in false...
Kapoor et al. (1) investigated pseudohyperkalemia in outpatients and
attributed many of the cases to hematological abnormalities or delay in
specimen centrifugation or clotting. Plasma is often recommended as the
preferred specimen in patients with leukocytosis, erythrocytosis or
thrombosis (2). Potassium released from ruptured cells during the clotting
process of serum specimens may result in false-positive reporting and
unnecessary therapy (3). Others have reported on a phenomenon known as
reverse pseudohyperkalemia in patients with leukocytosis where potassium
concentrations in plasma specimens exceeded concentrations in serum (4).
We describe a similar case of reverse psuedohyperkalemia. A 87-year-
old man with chronic lymphocytic leukemia (CLL) was treated for the past 2
years as an outpatient. He received cyclophosphamide, vincristine, and
rituximab chemotherapeutic agents as part of his treatment plan. Blood was
collected in serum separator (SST) and EDTA tubes for routine metabolic
and hematology studies. The potassium concentration averaged 3.7 mmol/L on
a Beckman DXC chemistry analyzer (n=11). His white blood cell (WBC) and
platelet counts averaged 306 x 109 cells/L (94-97% lymphocytes) and 95 x
109 platelets/L over this time period. Recently, he was admitted to the
ED. Specimens were collected for metabolic (lithium-heparin specimen with
separator gel) and hematology (EDTA plasma) analyses. The specimens were
transported by pneumatic tube, and time from collection to analysis was
<60 min. The potassium concentration was 7.5 mmol/L; similar results
were obtained on a second analyzer. No hemolysis was observed. The
hematology results supported a known diagnosis of CLL but all other
laboratory data was within normal limits. Pseudohyperkalemia was
investigated. Additional venous blood specimens were collected in lithium-
heparin with a separator gel and a SST tubes. The specimens were
immediately transported to the lab by pneumatic tube (<5 min transport
time), promptly centrifuged (5 min at 3500 rpm) or allowed to clot (30
min; then centrifuged for 5 min at 3500 rpm) and analyzed. The plasma
specimen exhibited significantly higher potassium (7.4 mmol/L)
concentration compared with the serum specimen (3.9 mmol/L). A significant
layer of WBC was evident on the packed erythrocyte layer in the lithium-
heparin tube. No WBC layer was observed in the serum specimen. Four days
later, a similar occurrence (lithium-heparin potassium = 6.4; serum
potassium = 4.2 mmol/L) was observed on the same in-patient.
Some cells, especially malignant ones are susceptible to in-vitro
heparin-induced cell membrane damage during specimen processing resulting
in diffusion of potassium into the supernatant from ruptured leukocytes.
Similar cases in other leukemia patients have been observed in our
laboratory. Both laboratorians and clinicians should be aware of this
phenomenon to minimize false-positive reporting and unnecessary therapy.
1. A K Kapoor, AK, Ravi A, Twomey PJ. Investigation of outpatients
referred to a chemical pathologist with potential pseudohyperkalaemia. J
Clin Pathol 2009; 62:920-923.
2. Ifudu O, Markell MS, Friedman EA. Unrecognized pseudohyperkalemia
as a cause of elevated potassium in patients with renal disease. Am J
Nephrol. 1992;12(1-2):102-4.
3. Sevastos N, Theodossiades G, Savvas SP, Tsilidis K, Efstathiou S,
Archimandritis AJ. Pseudohyperkalemia in patients with increased cellular
components of blood. Am J Med Sci. 2006 Jan;331(1):17-21
4. Abraham B, Fakhar I, Tikaria A, Hocutt L, Marshall J, Swaminathan
S, Bornhorst JA. Reverse pseudohyperkalemia in a leukemic patient. Clin
Chem. 2008 Feb;54(2):449-51.
Editor - The article "Alcohol and unnatural death in the West of
Ireland: a 5-year review" emphasized the need for effective interventions
to reduce mortality due to the alcohol-related road traffic collision
(RTC)[1]. Recently in Ireland, allowable blood alcohol concentration (BAC)
limit of drivers was decreased from 0.8mg/ml to 0.5mg/ml. According to
Ingoldsby and Callagy concluded in their manuscript that legislative...
Editor - The article "Alcohol and unnatural death in the West of
Ireland: a 5-year review" emphasized the need for effective interventions
to reduce mortality due to the alcohol-related road traffic collision
(RTC)[1]. Recently in Ireland, allowable blood alcohol concentration (BAC)
limit of drivers was decreased from 0.8mg/ml to 0.5mg/ml. According to
Ingoldsby and Callagy concluded in their manuscript that legislative
change might not be effective in reducing fatalities because the BACs in
most of fatal drivers exceeded 0.8mg/ml[1]. However, the conclusion seems
to be doubtful.
In Japan, legal limit of BAC in drivers decreased and its effect have been
scientifically validated by us. In 1970, the Japanese government
introduced a law setting the maximum allowable breath alcohol
concentration at 0.25mg/L (BAC of 0.5mg/ml). This law was revised in 1978
to increase penalties for drivers in violation of this law. We analyzed
the BAC of drivers involved in fatal MVCs that occurred between 1986 and
2001[2]. Approximately 10.0 to 13.7% of offenders were drunk drivers with
BAC levels of 0.5mg/ml or more. However, 3.8 to 6.1% of offenders were
drunk drivers with BAC levels below the legal limit (between 0 and
0.5mg/ml). Furthermore, we determined the relative risks of fatal MVCs due
to alcohol-impaired (BAC level greater than 0.25mg/L) driving in Japan[3].
The relative risk of fatality was 5.5 in 1986 and gradually increased to
8.0 by 2001 for alcohol-impaired driving of a four-wheeled vehicle. The
increase in the relative risk indicates that a large number of deaths
could be prevented if drivers refrained from drinking. In June 2002, the
Japanese Government strengthened the Road Traffic Law and decreased the
allowable breath alcohol concentration from 0.25 to 0.15 mg/L (BAC: from
0.5 to 0.3mg/ml). In 2002, the number of drunk driving collisions was
markedly decreased from the previous year (25,440 to 20,328, a 20.1%
decrease). Also, the number of fatal drunk driving collisions was 997 in
2002, a 16.3% decrease from the previous year. In 2002, 8,326 persons died
in MVCs in Japan, the lowest number in the preceding 35 years and a 5.0%
decrease from the previous year. These data reflected the deterrent effect
of the revised law. With the strength of allowable BAC limit, the
awareness in which drunk driving should be prohibited also improved,
subsequently, the number of drunk driving might be decreased. Therefore,
the effect of the revision of the law of drunk driving in Ireland should
be accurately validated with the nationwide statistics of the accidents
and fatalities by drunken-driving.
We agree the proposal that interventions other than driving limit
reduction should be considered to reduce mortality. In Japan, in addition
to reduce the allowable BAC limit of drivers, stricter countermeasures for
drunk driving also contributed to the decrease of alcohol related vehicle
accidents and fatalities. The police responded by implementing the revised
Traffic Law to include stricter regulations and penalties targeting drunk
driving and any environments that enable drunk driving (enacted in 2007).
Furthermore, the police force continues to promote strict regulations.
When a person is arrested for drunk driving, an in-depth investigation is
conducted not only on the driver but also on the other vehicle passengers
and/or persons who provided the alcohol to the driver. It was decided that
the revised Road Traffic Law would also promote the application of the
penal code to fellow passengers who had enabled the drunk driving actions,
or to persons who had provided alcohol to the driver. Recently, the number
of traffic collisions caused by drunk driving has decreased as a result of
the expansion and consolidation of two sets of penal codes, along with the
revision of the Road Traffic Act and establishment of a new penal code. In
2008, there were 6,219 cases of drunk driving-related collisions, less
than one-third of those in 2002[4]. We showed the effective measures to
prevent alcohol-related traffic fatalities in Japan.
We forensic pathologists have to not only determine the actual cause of
death, but contribute to the primary prevention of unnatural deaths.
Further effort might be needed for us to lesser the common alcohol-
associated unnatural deaths.
References
1. Ingolsby H, Callagy G. Alcohol and unnatural deaths in the West of
Ireland: a 5-year review. J clin Pathol 2010;63:900-903.
2. Hitosugi M, Maegawa M, Kido M, et al. Trends in fatal traffic accidents
due to alcohol-impaired driving in Japan, relative to breath alcohol
levels of drivers. Jpn J Occup Med Traumatol 2007;55:234-238, in Japanese
with English abstract.
3. Hitosugi M, Sorimachi Y, Kurosu A, et al. Risk of death due to alcohol-
impaired driving in Japan. Lancet 2003;361:1132.
4. Ministry of Land, Infrastructure, Transport and Tourism in Japan. White
Papers on Ministry of Land, Infrastructure, Transport and Tourism, 2008.
Ministry of Land, Infrastructure, Transport and Tourism in Japan, Tokyo,
2009, in Japanese.
Masahito Hitosugi, MD, PhD, Shogo Tokudome, MD, PhD,
Department of Legal Medicine, Dokkyo Medical University School of Medicine
Mibu, Tochigi 321-0293, Japan
hitosugi@dokkyomed.ac.jp
Dear Drs Kaushik, Fear, Richards, McDermott, Nuwaysir, Kellam,
Harrison, Wilkinson, Tyrrell, Holgate, Kerr, and Editors at JCP,
I hope this note finds you
well. Congratulations to the Physicians and Researchers who completed such
admirable work regarding the possible etiology of the CFS (Chronic Fatigue
Syndrome), as they made the observations that were "consistent with a
complex pathogenesis involving T...
Dear Drs Kaushik, Fear, Richards, McDermott, Nuwaysir, Kellam,
Harrison, Wilkinson, Tyrrell, Holgate, Kerr, and Editors at JCP,
I hope this note finds you
well. Congratulations to the Physicians and Researchers who completed such
admirable work regarding the possible etiology of the CFS (Chronic Fatigue
Syndrome), as they made the observations that were "consistent with a
complex pathogenesis involving T cell activation and abnormalities of
neuronal and
mitochondrial function, possibly as a result of virus infection or
organophosphate exposures."
While the Chronic Fatigue Syndrome (CFS) is considered to be a
multifactoral disease affecting several organ systems, there are many who
believe that
the mitochondria should provide answers to its etiology.
The results of Dr Kaushik et al, to the effect of,
"The involvement of genes from several disparate pathways suggests a
complex pathogenesis involving T cell activation and abnormalities of
neuronal and mitochondrial function"
and "These results suggest possible molecular bases for the
recognized contributions of organophosphate exposure and virus infection"
remind me of another study of Patients, some with malabsorption
syndromes, who seemed to have the most reduced levels of Interferron. If
Interferon levels are severely reduced, then perhaps that would explain a
smoldering virus which wasn't very aggressive, but persistent.
A malabsorption syndrome would very possibly cause reduced Thiamine,
Niacin and other Nutrient levels. I've always thought that one must fill
the Nutritional Tank before much should be expected from the usual and
corrective Metabolic
Pathways.
I was most surprised to recently find what could be described as a
mitochondrial specific toxin found almost everywhere, which is synthesized
by the
Streptomyces griseus strain of bacteria.
Writing in the January 2000, Infection and Immunity, p165, V68, Drs
Paananen and Timonen found that "human blood lymphocytes treated with
small doses
(30 ng/ml ) of pure valinomycin, or high-pressure liquid chromatorgraphy-
pure valinomycin from S. griseus quickly show mitochondrial swelling and
reduced NK cell activity. Larger doses (>100 ng/ml1) induced NK cell
apoptosis within 2 days. Within 2 h, the toxin at 100 ng/ml dramatically
inhibited interleukin-15 (IL-15)- and IL-18-induced granulocyte-
macrophage" and "Here we report that pure commercial valinomycin and high-
pressure liquid chromatography (HPLC)-pure valinomycin from S. griseus
inhibit human NK activity and cytokine production and induce apoptosis of
NK cells at doses 10 to 500 times lower than those previously used. Thus,
a toxin derived from bacteria that are abundant in the environment has the
potential to cause immune suppression."
Since S griseus is ubiquitous, found in both soil and household dust,
the possibility exists that the toxin, valinomycin, could cause or worsen
a CFS
by disrupting mitochondrial function. The Respiratory chain inhibitor,
valinomycin, is a Thiamine triphosphate inhibitor in the mitochondria.
My impression is that fatigue:depression::dementia:psychosis.
Significant deficiencies or blockage of the Thiamine and/or Niacin
Metabolic Pathways
cause severe fatigue and dementia, which is possibly misdiagnosed as
depression and psychosis.
The fact that valinomycin disrupts the mitochondrial Thiamine Pathway
is significant.
Overseas, the CFS is known as the systolic hypotensive syndrome,
which could be how a different toxin, reserpine, presents itself. During
the 1950's,
reserpine was added to chicken and turkey feed to improve productivity,
and could have then entered the Human Food Chain.
In the Article titled "Thiamine Triphosphate Synthesis In Rat Brain
Occurs In Mitochondria, And Is Coupled To The Respiratory Chain," the
Authors Dr
Gangolf et al, comment on how "In animals, thiamine deficiency causes
specific brain lesions, generally attributed to decreased levels of
thiamine
diphosphate (, an essential cofactor in brain energy metabolism.
However, another derivative, thiamine triphosphate , may have a
neuronal
function" and "ThTP synthesis is severely inhibited by respiratory chain
inhibitors such as myxothiazol-" and "ThTP synthesis is impaired by
disruption of
the mitochondria or depolarization of the inner membrane (by protonophores
or valinomycin)-." (Journal of Biological Chemistry, Published on November
11,
2009 as Manuscript M109.054379)
Dr Gangolf et al's Discussion ends with- "Such a mechanism could help
to better understand the events involved in the onset of neurodegenerative
diseases. It is therefore interesting to note that thiamine deficiency has
been shown to exacerbate the pathology of
Alzheimer disease and that there are
dysfunctions of thiamine metabolism in neurodegenerative diseases."
I would suggest that while competitive inhibition of the Thiamine
Pathway could be overcome with higher levels of Thiamine, the valinomycin
toxin mechanism which inhibits ThTP synthesis needs further study
Perhaps the mitochondrial genome needs to be studied separately for
gene expression, since it is always derived from a maternal source.
Best wishes always. Keep up the Good Work.
Cordially,
Joseph W Arabasz MD
Past Division Chairman, Anesthesiology, Cook County Hospital,
Chicago, Illinois
Past Chairman, Respiratory Therapy, Cook County Hospital, Chicago,
Illinois
Diplomate ABA
Mensa
Sigma Xi, The Professional Science Research Society
Of all the prospective candidates for thyroid replacement therapy(1),
even when due account is taken of the improvent in left ventricular
diastolic function attributable to this treatment modality in patients of
mean age 39.9 with subclinical hypothyroidism(SCH)(2), the over 65s with
SCH are probably the ones least likely to be at cardiovascular
disadvantage if they do not receive thyroid replacement t...
Of all the prospective candidates for thyroid replacement therapy(1),
even when due account is taken of the improvent in left ventricular
diastolic function attributable to this treatment modality in patients of
mean age 39.9 with subclinical hypothyroidism(SCH)(2), the over 65s with
SCH are probably the ones least likely to be at cardiovascular
disadvantage if they do not receive thyroid replacement therapy(3)(4). In
a longitudinal study of risk factors for development of cardiovascular
disease(CVD) in 3233 adults aged 65 or more with baseline serum
thyrotropin(TSH) levels(including 496 with SCH characterised by serum TSH
>4.5 mU/l but < 20.0 mU/l) no difference was documented between SCH
and euthyroidism for incident coronary heart disease and CVD death(3).
Likewise, among 427 subjects of mean age 73 with SCH(characterised by mean
TSH 8.1 mU/l) and coexisting type 2 diabetes, there was no relationship
between baseline TSH and cardiovascular mortality(4). Furthermore, on
follow-up of SCH for 5 or more years, this disorder was not additive to
the relatively higher cardiovascular risk attributable solely to type 2
diabetes(4). Finally, in a prospective longitudinal study evaluating
disability in daily life, depressive symptoms, cognitive function, and
mortality in 558 subjects aged 85(including 67 with TSH in the range 4.8
mU/l to 33 mU/l, some of whom were subclinically hypothyroid, and others
overtly hypothyroid), who were followed up for 4 years, all measures of
performance significantly deteriorated with time, but increasing baseline
levels of TSH were not associated with accelerated increase in disability
in activities of daily living, depressive symptoms, or cognitive decline
during follow-up. If anything, "increasing TSH levels at baseline were
associated with a significant(p=0.03) decelerated increase in disability
in instrumental ADLs(activities of daily living". Furthermore, increasing
baseline TSH levels were associated with lower mortality on 4 year follow-
up(5). Accordingly, especially in subjects aged 85 or more with SCH
characterised by TSH < 33 mU/l, there should be no "rush" to initiate
thyroid replacement therapy, because it appears to confer no improvement
in quality of life, and definitely neither cardiovascular benefit nor
survival benefit.
(2) Yazici M., Gorgulu S., Sertbas Y et al
Effects of thyroxin therapy on cardiac function in patients with
subclinical hypothyroidism: index of myocardial performance in the
evaluation of left ventricular function
International Journal of Cardiology 2004;95:135-143
(3)Cappola AR., Fried LP., Arnold AM et al
Thyroid status, cardiovascular risk, and mortality in older adults
JAMA 2006;295:1033-1041
(4)Sathyapalan T., Manuchehri AM., Atkin SL
Subclinical hypothyroidism is associated with reduced all-cause mortality
in patients with type 2 diabetes
Diabetes Care 2010;33:e37
(5)Gussekloo J., van Exel E., de Craen AJM et al
Throid status, disability and cognitive function, and survival in old age
JAMA 2004;292:2591-9
We are astonished by Wiwanitkit's inaccurate remarks regarding the
number of subjects studied and analytical methodology in our study [1].
The data set was of more than sufficient size to be subjected to rigorous
statistical analyses. If Wiwanitkit had bothered to even casually read the
articles he cites [1,2], he should have immediately realised that firstly
the thrust of Lenters-Westra's and Sling...
We are astonished by Wiwanitkit's inaccurate remarks regarding the
number of subjects studied and analytical methodology in our study [1].
The data set was of more than sufficient size to be subjected to rigorous
statistical analyses. If Wiwanitkit had bothered to even casually read the
articles he cites [1,2], he should have immediately realised that firstly
the thrust of Lenters-Westra's and Slingerland's paper was to
highlight poor analytical performance of some HbA1c point-of- care (not
laboratory based) instruments and secondly that laboratory HbA1c analyser
used in our study (Tosoh G7, cation-exchange HPLC) was a reference method
for measurement of HbA1c in study of Lenters-Westra and Slingerland [1,2].
In addition our HbA1c assay, and indeed all our assays, are subject to
stringent internal quality control procedures and external quality
assurance. We had hoped our article would stimulate meaningful debate
rather than inane comment.
Dr Taruna Likhari,
Professor Rousseau Gama
References
1. Likhari T, Gama R. Ethnic differences in glycated haemoglobin
between white subjects and those of South Asian origin with normal glucose
tolerance. J Clin Pathol 2010; 63:278-280
2. Lenters-Westra E, Slingerland RJ. Six of eight hemoglobin A1c point-of-
care instruments do not meet the general accepted analytical performance
criteria. Clin Chem 2010;56:44-52
I read the recent publication by Likhari et al with a great
interest [1]. Likhari et al concluded that "In subjects with similar
fasting and postprandial glycaemia on OGTT, those of South Asian origin
have higher HbA(1c) levels than white subjects. It is speculated that the
higher glycaemia-independent HBA1c levels in people of South Asian origin
could possibly contribute to their increase cardiovas...
I read the recent publication by Likhari et al with a great
interest [1]. Likhari et al concluded that "In subjects with similar
fasting and postprandial glycaemia on OGTT, those of South Asian origin
have higher HbA(1c) levels than white subjects. It is speculated that the
higher glycaemia-independent HBA1c levels in people of South Asian origin
could possibly contribute to their increase cardiovascular risk [1]." I
have some additional concerns on this work. First, the rather few subjects
in this work reduce the value of the research. It is questionable whether
the number of subjects in this work is statisticall acceptable or not.
Second, the concern on the performance of the analyzers for HBA1C should
be raised. In a recent publication, only a few analyzers are acceptable
for precision and accuracy [2].
References
1. Likhari T, Gama R. Ethnic differences in glycated haemoglobin between
white subjects and those of South Asian origin with normal glucose
tolerance. J Clin Pathol 2010; 63:278-280
2. Lenters-Westra E, Slingerland RJ. Six of eight hemoglobin A1c point-of-
care instruments do not meet the general accepted analytical performance
criteria. Clin Chem 2010;56:44-52
This study by Prof Abbas et al of German Pathology Institute is in the very important domain of transitional medicine, requiring molecular definition and designation for the lesions or morbid entities previously held diagnosable on the histopathological basis with or without special staining. Molecular basis of defining disease as in the case under consideration of IgG-4 related systemic disease, is to take into account...
Digital mammography represents a potential new and exciting development in the interface between computers and health care. Your paper highlights some of the emerging issues which might be expected with new technology. You have noted the increase in incidence of breast cancer, together with a large increase in recall rates. Reports from the radiologists also indicate that between 6% and 10% of tumors are identified clini...
This study from multiple centers of repute from UK and Spain demonstrated cytoplasmic and nuclear expressions of NF-kB/p65, and established that in good number-ratio of 1:4 or 1:3 cytoexpression was followed/accompanied by the nuclear expression, besides there were cases of breast carcinoma negative for nuclear as well as cyto expression of NF- kB; could imply that p65 expression was consequence rather than being an esse...
Dear Editor:
Kapoor et al. (1) investigated pseudohyperkalemia in outpatients and attributed many of the cases to hematological abnormalities or delay in specimen centrifugation or clotting. Plasma is often recommended as the preferred specimen in patients with leukocytosis, erythrocytosis or thrombosis (2). Potassium released from ruptured cells during the clotting process of serum specimens may result in false...
Editor - The article "Alcohol and unnatural death in the West of Ireland: a 5-year review" emphasized the need for effective interventions to reduce mortality due to the alcohol-related road traffic collision (RTC)[1]. Recently in Ireland, allowable blood alcohol concentration (BAC) limit of drivers was decreased from 0.8mg/ml to 0.5mg/ml. According to Ingoldsby and Callagy concluded in their manuscript that legislative...
Dear Drs Kaushik, Fear, Richards, McDermott, Nuwaysir, Kellam, Harrison, Wilkinson, Tyrrell, Holgate, Kerr, and Editors at JCP,
I hope this note finds you well. Congratulations to the Physicians and Researchers who completed such admirable work regarding the possible etiology of the CFS (Chronic Fatigue Syndrome), as they made the observations that were "consistent with a complex pathogenesis involving T...
Dear Editor
Of all the prospective candidates for thyroid replacement therapy(1), even when due account is taken of the improvent in left ventricular diastolic function attributable to this treatment modality in patients of mean age 39.9 with subclinical hypothyroidism(SCH)(2), the over 65s with SCH are probably the ones least likely to be at cardiovascular disadvantage if they do not receive thyroid replacement t...
Dear Editor
We are astonished by Wiwanitkit's inaccurate remarks regarding the number of subjects studied and analytical methodology in our study [1]. The data set was of more than sufficient size to be subjected to rigorous statistical analyses. If Wiwanitkit had bothered to even casually read the articles he cites [1,2], he should have immediately realised that firstly the thrust of Lenters-Westra's and Sling...
Dear Editor,
I read the recent publication by Likhari et al with a great interest [1]. Likhari et al concluded that "In subjects with similar fasting and postprandial glycaemia on OGTT, those of South Asian origin have higher HbA(1c) levels than white subjects. It is speculated that the higher glycaemia-independent HBA1c levels in people of South Asian origin could possibly contribute to their increase cardiovas...
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