An interesting recent article by Sheehan et al. in your journal investigated whether the MIB-1 (Ki-67) labelling index in astrocytoma tissue cores – designed to replicate unrepresentative biopsies – could provide valuable information concerning tumor grade. The authors studied
134 cases of glioma and found that Ki-67 may be used to exclude low-grade astrocytoma, but cannot be used to distinguish between gli...
An interesting recent article by Sheehan et al. in your journal investigated whether the MIB-1 (Ki-67) labelling index in astrocytoma tissue cores – designed to replicate unrepresentative biopsies – could provide valuable information concerning tumor grade. The authors studied
134 cases of glioma and found that Ki-67 may be used to exclude low-grade astrocytoma, but cannot be used to distinguish between glioblastoma multiforme and anaplastic astrocytoma. They found that a MIB-1 staining count greater than 3.07% practically excludes low-grade astrocytoma,
although any MIB-1 count below that threshold cannot exclude anaplastic astrocytoma or glioblastoma multiforme.[1] This is of paramount importance since both anaplastic astrocytoma and glioblastoma multiforme require different therapeutic approach and carry diverse prognosis from low-grade
astrocytoma.
Our ongoing research deals with the usefulness of functional brain tumor imaging by single-photon emission computed tomography (SPECT). We currently investigate the imaging properties of technetium-99m-Tetrofosmin
(99mTc-TF), a lipophilic diphosphine routinely used for myocardial perfusion imaging that also displays tumor-seeking properties. We found that 99mTc-TF SPECT can reliably distinguish glioma recurrence from radiation necrosis and neoplastic from non-neoplastic intracranial
hemorrhage.[2,3] We also evaluated the relationship between glioma proliferation (as expressed by Ki-67) and the uptake of 99mTc-TF. We performed brain SPECT within a week prior to glioma surgical excision and then assessed the tumoral tracer uptake visually as well as semiquantitatively, by a method of lesion-to-normal uptake ratio calculation described elsewhere.[3,4] Statistical analysis verified that
the intensity of 99mTc-TF uptake displayed a linear strong positive correlation with Ki-67 expression.[4]
Since tumor immunostaining requires direct tissue sampling, a functional (metabolic) imaging technique to provide before surgery a non-invasive estimate of glioma proliferative potential, would be of particular clinical and prognostic value. In view of the unambiguously solid correlation between 99mTc-TF uptake and cellular proliferation in our series, we believe that 99mTc-TF brain SPECT could provide substantial additive information preoperatively to optimize patient management and
treatment. For example, it could guide tissue sampling biopsy towards the tumor region displaying maximal tracer uptake activity. We consider this initial evidence as strong enough to substantiate further research regarding the clinical utility of this imaging modality.
References 1. Sheehan KM, Burke M, Heffernan J, et al. Unrepresentative Astrocytoma biopsy sampling is partly overcome by assessment of the MIB-1 labeled growth fraction. J Clin Pathol. 2007;5: [Epub ahead of print].
2. Alexiou GA, Fotopoulos AD, Papadopoulos A, et al. Evaluation of brain tumor recurrence by 99mTc-Tetrofosmin SPECT – A prospective pilot study. Ann Nucl Med (in press; DOI: 10.1007/s12149-007-0027-x).
3. Alexiou GA, Bokharhii JA, Kyritsis AP, et al. Tc-99m Tetrofosmin SPECT for the differentiation of a cerebellar hemorrhage mimicking a brain metastasis from a renal cell carcinoma. J Neurooncol 2006;78:207-8.
4. Alexiou GA, Tsiouris S, Goussia A, et al. Evaluation of glioma proliferation by 99mTc-Tetrofosmin. Neurooncol (in press)
HPV (Human Papilloma Virus) is known to be related to cancers for a long time. However it was only recently that breakthrough has been made to introduce vaccines that can prevent HPV infection. The reason for this is that HPV infections are rarely, if ever, immediately ife-threatening.
Vaccination has always focused towards preventing causes of immediate death or disability.
HPV (Human Papilloma Virus) is known to be related to cancers for a long time. However it was only recently that breakthrough has been made to introduce vaccines that can prevent HPV infection. The reason for this is that HPV infections are rarely, if ever, immediately ife-threatening.
Vaccination has always focused towards preventing causes of immediate death or disability.
The importance of HPV vaccination has not been recognised either by healthcare providers or recipients as most of the HPV infections are silent but at least 50 percent(1) of sexually active men and women acquire genital HPV infection at some point in their lives. By age 50, at least 80
percent of women will have acquired genital HPV infection, manifest or otherwise.
The study conducted by Professor Margaret Stanley has dealt with HPV as aetiology, primarily of cervical cancer. However, HPV is also known to have a role in the causation of colorectal cancers, bladder cancers and head and neck cancers. In a study(2) conducted by National Cancer
Institute, NIH, Bethesda, Maryland, it was seen that more than 50% of patients with colorectal cancers were positive for HPV DNA, where as the controls were negative for the same. This implies that even though HPV cannot be designated as the causative factor in colorectal cancers, it does increase the risk of development of these cancers. Further, more than one-third of patients who were positive had the HPV 16 subgroup.
Though the protection provided by the vaccine is not 100%, the study has still proved a 70% efficacy of the vaccine. Vaccines that are part of the British National Vaccination Schedule vary in their efficacy. For example, the influenza vaccine(1) is only 50%- 60% effective in preventing influenza-related hospitalization or pneumonia in adults > 65 years, but it is still strongly advocated since it decreases a substantial amount of morbidity and burden of disease in the general population.
Cancer Prevention is a very important part of healthcare provided by the NHS (National Health Service) in the United Kingdom (UK). There are organised, active cancer screening programmes(3) for the prevention of colon cancer, cervical cancer and breast cancer. HPV vaccination along with screening programmes can effectively be part of a multi-modal approach to cancer prevention and treatment if introduced as a part of the British National Vaccination Schedule in the UK.
There is the question of cost-effectiveness in introducing HPV vaccination in the British National Vaccination schedule as its role is less important in males than in females. However, there have been studies which show that HPV has a role in causation of male genital warts,
carcinoma in situ and invasive carcinoma of the penis(4). In addition, as the study by Professor Margaret Stanley suggests, vaccination of young boys would help in establishing herd immunity, thus helping to prevent
cervical cancer. Hence, though the significance of HPV vaccination is lesser in males due to the lower incidence of penile cancer, vaccination is still important in males in preventing penile cancer and cervical cancer.
Since, at present there is no effective treatment for HPV infection except for removal of warts and excision of tissue damaged by the virus where possible, in my opinion HPV infections is better dealt with before it infects the body, than after.
References:
1. Centre for Disease Control and Prevention,Sexually Transmitted Diseases.
2. Clinical Cancer Research Vol. 11, 2862-2867, April 15, 2005
3. www.cancerscreening.nhs.uk
4. International Journal of Cancer, 2005 Sep 10;116(4):606-16.
Persistent enteroviral infection in gastric tissue is found in a high percentage of cfs-patients by Chia & Chia (Sept. 13, 2007) while histological changes are not specifically addressed in this paper. A comparison between cfs - and non-cfs enterovirus positive patients with
regard to local inflammatory reaction would be of interest, though, as the lack of a proper inflammatory response to infectious agents...
Persistent enteroviral infection in gastric tissue is found in a high percentage of cfs-patients by Chia & Chia (Sept. 13, 2007) while histological changes are not specifically addressed in this paper. A comparison between cfs - and non-cfs enterovirus positive patients with
regard to local inflammatory reaction would be of interest, though, as the lack of a proper inflammatory response to infectious agents is a common finding in postinfectious fatigue syndrome, and the symptoms are easily dismissed as psychosomatic.
Among the comparatively few that later develop cfs or myalgic encephalomyelitis (me) that see a doctor during the initial stages of a triggering infection, a lack of adequate inflammatory response is frequently seen not only with respect to fever and enlarged lymph nodes, but also to SR, CRP and white cell count, even in the presence of ongoing
infection verified otherwise. An exception to the rule are cases that present with low grade fever and enlarged lymph nodes, that may persist for months and years despite no other evidence of ongoing infection. Cfs/me is for instance rarely diagnosed following meningitis, whereas it may be triggered by what is perceived as a mild encephalitis - although these conditions almost invariably coexist.
During the Cumberland epidemic, white cell count was in the lower normal range (Wallis, 1957). During the Los Angeles epidemic in 1934 that ran parallel to a polio epidemic, patients failed to present changes in cerebrospinal fluid and the epidemic was known as atypical polio (Hyde, 1992). Only rarely do patients with polio develop cfs/me. The postpolio syndrome is postponed by several decades. Why?
Epidemics that presented with similar features as the Cumberland and Los Angeles epidemics were included in the proposed designation benign myalgic encephalomyelitis in 1956 although the –itis was difficult to establish as such. Variability with respect to findings in cerebrospinal
fluid (Ramsay, 1986) strengthened the notion that viral infections were crucial in initiating this condition when agents were not identified. These findings do not, however, preclude the notion that cfs/me is an erratic expression or a forme fruste of the classical inflammatory reaction and, albeit harmful, may be perceived as a type of general
reaction mode to various inflammatory agents, in keeping with vast clinical experience.
References 1. Chia JKS and Chia AY. Chronic fatigue syndrome is associated with chronic enterovirus infection of the stomach. J Clin Pathol 2007; 0:1-6 (online)
2. Wallis, AL. An investigation into an unusual disease seen in epidemic and sporadic form in a general practice in Cumberland in 1955 and subsequent years. University of Edinburgh 1957, M.D. Thesis.
3. Hyde, BM (ed). The clinical and scientific basis of myalgic encephalomyelitis chronic fatigue syndrome. Ottawa 1992, The Nightingale Research Foundation
4. Ramsay, AM. Postivral fatigue syndrome The saga of Royal Free disease. London 1986, Gower Medical Publishing
The TMPRSS2-ERG has been described in several prostate cancer patients' cohorts. The article by Ashish et al. describes the frequency of this fusion in another patient cohort. It further demonstrates that the frequency of TMPRSS2-ERG is increased in moderate to poorly differentiated tumors. We would like to congratulate the authors on their interesting study and advocate that more work still has to be carrie...
The TMPRSS2-ERG has been described in several prostate cancer patients' cohorts. The article by Ashish et al. describes the frequency of this fusion in another patient cohort. It further demonstrates that the frequency of TMPRSS2-ERG is increased in moderate to poorly differentiated tumors. We would like to congratulate the authors on their interesting study and advocate that more work still has to be carried out to investigate and characterize the true frequency and association of TMPRSS2-ERG gene fusion in prostate cancer. Earlier reports have generated conflicting results about the association of the TMPRSS2-ERG with Gleason score. It has been demonstrated earlier that the rate of fusion positive tumours is actually lower in the poorly differentiated tumours.1 This latest finding was confirmed by our own study (data not published). These results should be further confirmed in larger and multiple cohorts as we investigate the TMPRSS2-ERG gene fusion as a biomarker of aggressive prostate cancer.
References: 1. Tu et al Modern Pathology (2007) 20, 921-928
Intracavitatory metastases may either be left-sided, as documented
in a recent case report1, or right-sided, as documented in two previous
case reports2,3, both cases in the latter two reports2,3
characterised by symptomatic right-sided cardiac failure attributable, in
the second of the two cases to the fact that tumour cells originating from
the right intracavitatory...
Intracavitatory metastases may either be left-sided, as documented
in a recent case report1, or right-sided, as documented in two previous
case reports2,3, both cases in the latter two reports2,3
characterised by symptomatic right-sided cardiac failure attributable, in
the second of the two cases to the fact that tumour cells originating from
the right intracavitatory secondary deposit had been seeded into the
pulmonary circulation3(fig. 4), mimicking pulmonary thromboembolism. The tumour itself was composed of papillary glandular epithelium with vesicular nuclei charcterised by moderate mitotic activity.
What also distinguished the intracavitatory deposit in the latter case was
that no primary tumour could be identified, even after an extensive post-
mortem examination. This was contrary to the expectation that cardiac
metastases are typically associated with an identifiable primary tumour,
as was the case in 56 out of 57 patients with cardiac metastases
documented in one necropsy study4. Arguably, as well, the seeding of
tumour deposits from the right intracavitatory tumour deposit to the
pulmonary circulation was an example of what might be better termed
"tertiary" dissemination, given the fact that it originated from an
identifiable secondary deposit, via a haematogenous route unique to the
site of that secondary deposit, rather than being an example of secondary
dissemination from an unknown primary. This implies that, in that
particular instance, the heart itself was the sole site of secondary
dissemination from the unknown primary. For the heart to be the "only
target of metastases" is distintly unusual, having been documentd in only
10 out of 662 cases in one series, all ten of those cases having an
identifiable primary site of origin of the cardiac metastases5.
Oscar M Jolobe
References
(1) Gupta K., Joshi K., Aggarwal AN., Vaiphei K
Asymptomatic polypoidal intracavitatory cardiac metastases from pulmonary
adenocarcinoma
Journal of Clinical Pathology 2008:61:142
(2) Hull HK., Usmani O
Intracavity right ventricular metastasis
Lancet 2006:367:424
(3) Jolobe OMP
Cor pulmonale: variation on a theme
Postgraduate Medical Journal 2001:77:675-77: correction of erratum in
Postgraduated Medical Journal 2002:78:62
(4) Metastatic and invasive tumours involving the heart in a geriatric
population: a necropsy study
Virchows Archiv A Pathological Anatomy and Pathology 1991:419:183-9
(5) Bussani R., De-Giorgio F., Abbate A., Ailvestri F
Cardiac metastases
Journal of Clinical Pathology 2007:60:27-34
We read with interest the paper by Borgquist et al (2008),
published recently in Journal of Clinical Pathology1. In their article
the authors aimed to investigate the impact of ERbeta expression on breast
cancer outcome using a cohort of 512 tumours represented in tissue
microarray (TMA). Since the discovery of ERbeta over a decade ago, this
has been the goal of many research groups. However pr...
We read with interest the paper by Borgquist et al (2008),
published recently in Journal of Clinical Pathology1. In their article
the authors aimed to investigate the impact of ERbeta expression on breast
cancer outcome using a cohort of 512 tumours represented in tissue
microarray (TMA). Since the discovery of ERbeta over a decade ago, this
has been the goal of many research groups. However progress in this area
has been impeded by the lack of a consensus in terms of choice of primary
antibody and cut-off value used to determine ERbets postivity2,3.
Additionally, we know that ERbeta exists as 5 isoforms (ERbeta1-5), each
formed by alternative splicing of the last coding exon4,5, which has
further complicated interpretation of immunohistochemical studies.
Comparative studies have been conducted to help determine the most
suitable antibody for a number of applications and of these, 2 reliable
antibodies have emerged for immunohistochemistry: 14C8 (AbCam, Cambridge,
UK), located in the N-terminus of the ERbeta peptide and which detects
most isoforms of ERbeta and PPG5/10 (Serotec, Oxford, UK) which is
specific for ERbeta12,6,7. We routinely use both these antibodies in
our immunohistochemical studies. Borgquist et al1 used a different
antibody, EMR02 (Novocastra, Newcastle-upon-Tyne), which is claimed
through epitope mapping studies to show specific reactivity to a 17-amino
acid sequence present in the C-terminus of full length wild type ERbeta
and which is absent in ERbeta2/ERbetacx 8. While Borgquist et al1 show
immunohistochemical and Western blot analysis of ERbeta in a panel of
breast cell lines we find it remarkable that they showed no staining of
their breast TMAs especially as all the survival data presented in the
paper was obtained from these. Using cell lines to validate antibodies is
certainly a step in the right direction but it is insufficient as tissue
characteristics and processing protocols will almost certainly differ
substantially from those used in cell lines and these may alter antibody
specificity and sensitivity.
In addition, the authors used a very low cut off value to define
ERbeta positivity (1%) and with such a value we find it surprising that
the percentage of ERbeta positive tumours was only 50% - substantially
less than in many previous studies6,9-12. We believe this could
indicate an issue with antibody specificity and suggest this be confirmed
through peptide absorption studies.
Finally, as part of or on-going programme to understand the
significance of ERbeta in breast carcinogenesis, when EMR02 antibody
became available, we compared its efficacy to the well-validated 14C8 and
PPG5/10 antibodies which we use routinely. As illustrated in Figure 1, we
were unable to achieve robust and consistent staining using EMR02, while
TMA and full sections of breast carcinoma were clearly stained with 14C8
and PPG5/10.
Figure 1 - Serial sections of TMAs (top panel) and full sections (bottom panel) of breast carcinomas stained with EMR02 (a, d), 14C8 (b, e) and PPG5/10 (c, f). Consistent staining was only observed for 14C8 and PPG5/10 with EMR02 unable to detect the protein.
There still remains a great deal of controversy and indeed suspicion
surrounding the potential importance of ERbeta in breast cancer. We
believe to a large extent this is due to the use of poorly validated
antibodies which have poisoned the field somewhat. We urge all scientists,
clinicians and journals to be aware of the need for carefully validated
studies to help eliminate these controversies which, more than a decade
on, still continue to cloud ERbeta.
Valerie Speirs
References
1. Borgquist S, Holm C, Stendahl M, et al. Oestrogen receptors alpha and
beta show different associations to clinicopathological parameters and
their co-expression might predict a better response to endocrine treatment
in breast cancer. J Clin Pathol 2008;61:197-3.
2. Carder PJ, Murphy CE, Dervan P, et al. A multi-centre investigation
towards reaching a consensus on the immunohistochemical detection of
ERbeta in archival formalin-fixed paraffin embedded human breast tissue.
Breast Cancer Res Treat 2005;92:287-93.
3. Shaaban AM, Speirs V. Estrogen receptor beta - which one and where
should we draw the line? Hum Pathol 2006;37:498.
4. Moore JT, McKee DD, Slentz-Kesler K, et al. Cloning and
characterization of human estrogen receptor beta isoforms. Biochem Biophys
Res Commun 1998;247:75-8.
5. Poola I, Abraham J, Baldwin K, et al. Estrogen receptors beta4 and
beta5 are full length functionally distinct ERbeta isoforms: cloning from
human ovary and functional characterization. Endocrine 2005;27:227-38.
6. Skliris GP, Parkes AT, Limer JL, et al. Evaluation of seven oestrogen
receptor beta antibodies for immunohistochemistry, western blotting, and
flow cytometry in human breast tissue. J Pathol 2002;197:155-62.
7. Weitsman GE, Skliris G, Ung K, et al. Assessment of multiple different
estrogen receptor-beta antibodies for their ability to immunoprecipitate
under chromatin immunoprecipitation conditions. Breast Cancer Res Treat
2006;100:23-31.
8. Rees ML, Marshall I, McIntosh GG, et al. Wild-type estrogen receptor
beta expression in normal and neoplastic paraffin-embedded tissues. Hybrid
Hybridomics 2004;23:11-8.
9. Saunders PT, Millar MR, Williams K, et al. Expression of oestrogen
receptor beta (ERbeta1) protein in human breast cancer biopsies. Br J
Cancer 2002;86:250-6.
10. Shaaban AM, O'Neill PA, Davies MP, et al. Declining estrogen receptor-
beta expression defines malignant progression of human breast neoplasia.
Am J Surg Pathol 2003;27:1502-12.
11. Fuqua SA, Schiff R, Parra I, et al. Estrogen receptor beta protein in
human breast cancer: correlation with clinical tumour parameters. Cancer
Res 2003;63:2343-39.
12. Nakopoulou L, Lazaris AC, Panayotopoulou, et al. The favourable
prognostic value of oestrogen receptor beta immunohistochemical expression
in breast cancer. J Clin Path 2004;57:523-28.
Letter to the Editor - Sputum sampling, storage and recovery: accuracy and sensitivity for Mycobacterium tuberculosis
Dear Editor,
The recent article by Pye et al. discusses the recovery of bacteria
from sputum specimen samples stored at different temperatures (1). This
article highlights sample handling, storage and transport, from the field
to the clinical laboratory. This may be important in the fiel...
Letter to the Editor - Sputum sampling, storage and recovery: accuracy and sensitivity for Mycobacterium tuberculosis
Dear Editor,
The recent article by Pye et al. discusses the recovery of bacteria
from sputum specimen samples stored at different temperatures (1). This
article highlights sample handling, storage and transport, from the field
to the clinical laboratory. This may be important in the field collection
and identification of highly contagious and epidemiologically important
microbes like Mycobacterium tuberculosis (MTB). Indeed, Tansuphasiri et
al. found that positive cultures of MTB decreased significantly when
stored at room temperature for 5 days compared with cultures from fresh
specimens (2). Conversely, storage of MTB at low temperatures (-20 0C) for
2 months also increased bacterial lysis and decreased recovery (3). To
date, research supports the use of molecular methods (e.g. polymerase
chain reaction) the sensitive detection of small sample sizes of sputum
collection bacterial (i.e. MTB) (4), and the shipping of sampling from
rural, isolated areas for accurate molecular diagnosis is preferred
methodology over sputum smears (5).
Kenneth Hoekstra Assistant Professor
Western States Chiropractic College
References
1. A Pye, S L Hill, P Bharadwa, and R A Stockley Effect of storage
and postage on recovery and quantitation of bacteria in sputum samples J
Clin Pathol 2008; 61: 352-354
2. Tansuphasiri U, Chinrat B, Rienthong S.Evaluation of culture and
PCR-based assay for detection of Mycobacterium tuberculosis from sputum
collected and stored on filter paper. Southeast Asian J Trop Med Public
Health. 2001 Dec;32(4):844-55.
3. Pathak D, Chakravorty S, Hanif M, Tyagi JS. Lysis of tubercle
bacilli in fresh and stored sputum specimens: implications for diagnosing
tuberculosis in stored and paucibacillary specimens by PCR. BMC Microbiol.
2007 Sep 4;7:83.
4. Guio H, Okayama H, Ashino Y, Saitoh H, Xiao P, Miki M, Yoshihara
N, Nakanowatari S, Hattori T.
Method for efficient storage and transportation of sputum specimens for
molecular testing of tuberculosis.
Int J Tuberc Lung Dis. 2006 Aug;10(8):906-10.
5. Tansuphasiri U, Boonrat P, Rienthong S.Direct identification of
Mycobacterium tuberculosis from sputum on Ziehl-Neelsen acid fast stained
slides by use of silica-based filter combined with polymerase chain
reaction assay. J Med Assoc Thai. 2004 Feb;87(2):180-9.
In the context of clinically suspected non-thyroidal illness(NTI) the
advice to retest patients with raised levels of thyroid stimulating
hormone(TSH)(1) may extend even to those in whom TSH levels are in the
range 20-32.4 mIU/L(2). In one study, over a period averaging 88
days(Standard Error ie SE=34), seven such subjects, with mean baseline TSH
of 32.4 mIU/L(SE=3.6), experienced a spontaneous fall in...
In the context of clinically suspected non-thyroidal illness(NTI) the
advice to retest patients with raised levels of thyroid stimulating
hormone(TSH)(1) may extend even to those in whom TSH levels are in the
range 20-32.4 mIU/L(2). In one study, over a period averaging 88
days(Standard Error ie SE=34), seven such subjects, with mean baseline TSH
of 32.4 mIU/L(SE=3.6), experienced a spontaneous fall in that parameter to
levels averaging 12.3 mIU/L(SE=3.7)as a result of recovery from NTI. In
two of those subjects, both of whom tested negative for antimicrosomal
antibodies, TSH fell to 2.1 mIU/L, and 2.3 mIU/L, respectively. In the
other five, all of whom were antibody positive, TSH levels fell to 9.9,
10.1, 11.5, 21.7, and 28.5 mIU/L,respectively. In order to check whether
or not patients tested for TSH have significant but clinically unsuspected
NTI it might even be advisable to test for the acute phase marker, C
reactive protein(CRP). This was the strategy followed in one study so as
to check if patients with suspected hypoferritinaemia might have spurious
"normalisation" of their serum ferrtin levels attributable to an acute
phase response. In that study 10.2% and 44% of patients in primary care
and in secondary care, respectively, had elevated CRP levels(3). Where
necessary, TSH levels also need to be interpreted in the context of
advanced age, given the recent analysis of the age-specific distribution
of TSH levels in 14,376 subjects who were not only disease-free, but also
tested negative for thyroid antibodies. In that analysis the 95%
confidence limits for TSH yielded the range 6.17-10.85 mIU/L in patients
aged 80 or more(4). One interpretation of these findings was that the age-
related shift in the reference range "could either facilitate or be a
consequence of healthy aging"(4). This view resonated with the findings in
a cohort of 599 subjects 37 of whom had overt hypothyroidism, the latter
characterised by the association of subnormal levels of free thyroxine and
TSH levels in the range 4.86-33.0 mIU/L. The enrollment age was 85, and
the mean follow up was 3.7 years(standard deviation 1.4). Over that
period, in spite of non-treatment, these overtly hypothyroid participants
showed a significant trend towards the lowest mortality rates when
compared with the rest of the cohort(Cox regression, P for trend=0.03).
Furthermore, increasing baseline levels of TSH were not associated with an
accelerated increase in phsical disability, cognitive decline, or
depressive symptoms(5). Accordingly, in primary care best practice is to
take account of NTI, using clinical criteria, and, possibly, CRP as well,
and to take cognisance of advanced age.
Oscar M Jolobe Retired Geriatrician
References
(1) Smellie WSA., Vanderpump MPJ., Fraser WD., Bowley R., Shaw N
Best Practice in primary care pathology; review 11
Journal of Clinical Pathology 2008:61:410-18
(2)Spencer C ., Elgen A., Shen D et al
Specificity of sensitive assays of thyrotropin(TSH) used to screen for
thyroid disease in hoispitalised patients
Clinical Chemistry 1987:33:1391-6
(3) O'Broin S., Kelleher B., Balfe A., mCMahon C
Evaluation of serum transferrin receptor assays in a centralised iron
screening service
Clinical and Laboratory Haematology 2005:27:190-4
(4) Surks MI., Hollowell JG
Age-specific distribution of serum thyrotropin and antithyroid antibodies
in the U.S. population: Implications for the prevalence of subclinical
hypothyroidism
Journal of Clinical Endocrinology and Metabolism 2007:92:4575-82
(5) Gussekloo J., van Exel E., de Craen AJM et al
Throid status, disability and cognitive function, and survival in old age
Journal of the American Medical association 2004:292:2591-9
I was interested to read the article by Zheng and colleagues in the
July 2007 edition of the Journal of Clinical Pathology 1, wherein the
authors describe detection of Jamestown Canyon virus in human tissue
samples. I write to urge caution as I fear that a simple unfortunate error
has been made.
Jamestown Canyon virus is a bunyavirus belonging to the ‘California
serogroup’, an enveloped, sing...
I was interested to read the article by Zheng and colleagues in the
July 2007 edition of the Journal of Clinical Pathology 1, wherein the
authors describe detection of Jamestown Canyon virus in human tissue
samples. I write to urge caution as I fear that a simple unfortunate error
has been made.
Jamestown Canyon virus is a bunyavirus belonging to the ‘California
serogroup’, an enveloped, single stranded RNA virus. It is an arthropod-
borne virus found predominantly in northern America 2,3. It is not, as
Zheng et al suggest, “a family of polyoma viruses”. I suspect that the
authors have confused this virus (often abbreviated to JCV) with the more
widely known JC polyomavirus, which is named for the initials of a patient
suffering from progressive multifocal leukoencephalopathy 4. Indeed, the
article seems to describe JC polyomavirus throughout rather than Jamestown
Canyon virus.
In order to avoid ongoing confusion, I would suggest that the article
be withdrawn and republished with suitable amendments.
James J Clayton
References
1. Zheng H, Murai Y, Hong M, Nakanishi Y, Nomoto K, Masuda S,
Tsuneyama K, Takano Y. Jamestown Canyon virus detection in human tissue
specimens. J Clin Pathol. 2007; 60:787-93.
2. Grimstad PR, Shabino CL, Calisher CH, Waldman RJ. A case of
encephalitis in a human associated with a serologic rise to Jamestown
Canyon virus. Am J Trop Med Hyg. 1982; 31:1238-44.
3. Mayo D, Karabatsos N, Scarano FJ, Brennan T, Buck D, Fiorentino T,
Mennone J, Tran S. Jamestown Canyon virus: seroprevalence in Connecticut.
Emerg Infect Dis. 2001; 7:911-2.
4. Padgett BL, Walker DL, ZuRhein GM, Eckroade RJ, Dessel BH.
Cultivation of papova-like virus from human brain with progressive
multifocal leucoencephalopathy. Lancet. 1971; 1(7712):1257-60.
I fully endorse the recommendations of Reddy and co-workers
concerning management of potential Brucella isolates and those staff
potentially exposed 1. The authors highlight that clinical information may
not always suggest potential brucellosis, especially if time has elapsed
since exposure, thus suspicion may not be raised. The authors then proceed
to describe four blood culture isolates obtained from patien...
I fully endorse the recommendations of Reddy and co-workers
concerning management of potential Brucella isolates and those staff
potentially exposed 1. The authors highlight that clinical information may
not always suggest potential brucellosis, especially if time has elapsed
since exposure, thus suspicion may not be raised. The authors then proceed
to describe four blood culture isolates obtained from patients with travel
histories to endemic regions. Although recovery of Brucella from blood
cultures taken from patients with undulant fever is the typical text book
scenario, readers should be aware that brucellae may result in focal
lesions affecting nearly every organ 2. Unusual sources for isolation of
brucellae are typified by the recent recovery of a Brucella-like organism
from a breast implant 3.
The importance of non-blood samples for diagnosis of brucellosis must
also be stressed. Where there is a suitable degree of clinical suspicion,
bone marrow is the sample of choice for isolation. This is further
substantiated by the recent findings of Mantur and co-workers who
undertook a comparative study of Brucella recovery from various specimens.
During these investigations, recovery was only achieved from 45.6% of
blood cultures whereas 82.5% of bone marrow biopsies yielded growth 4.
Although the United Kingdom is officially Brucella-free, I would like to draw the attention of medical colleagues to
recent human infections with marine mammal-associated brucellae. A paper
by Sohn et al described two patients with neurological disease attributed
to infection with strains of Brucella derived from marine mammals 5.
Brucella was isolated following surgical intervention although only one
patient was positive serologically. A further infection initially
mistaken as B. suis, was reported from New Zealand 6. Previously,
laboratory-acquired infection with a similar strain had been described 7.
Serological and cultural evidence suggests that brucellosis is very
widespread in a range of cetaceans, pinipeds around the coasts of the
British Isles and elsewhere, and there is similar evidence that otters
located inland are also infected 8.
Finally, regarding the application of PCR to identify Brucella in
clinical material as used in case 4, this provides a useful diagnostic
tool, negating the need to handle large quantities of this highly
infectious microbe. Indeed, this has proven particularly valuable to
confirm infection in patients, and household contacts with potential
shared exposures 9. Molecular diagnostics have now evolved to offer
equivalent discriminatory power to more traditional identification
methods, however, cultivation and classical microbiological biotyping
remain the gold standard, underscoring the need for precise
recommendations for reduction of laboratory exposure, or appropriate
management of exposed individuals, as outlined in the afore mentioned
article.
Sally J Cutler
References:
1.Reddy S, Manuel R, Sheridan E, et al., Brucellosis in United
Kingdom - a risk to laboratory workers? Recommendations for prevention and
management of laboratory exposure. Journal of Clinical Pathology,
2008:jcp.2007.053108.
2.Al Dahouk S, Nockler K, Hensel A, et al., Human brucellosis in a
nonendemic country: a report from Germany, 2002 and 2003. Eur J Clin
Microbiol Infect Dis, 2005;24:450-6.
3.De BK, Stauffer L, Koylass MS, et al., Novel Brucella Strain (BO1)
Associated with a Prosthetic Breast Implant Infection. Journal of Clinical
Microbiolology 2008;46:43-49.
4.Mantur BG, Mulimani MS, Bidari LH, et al., Bacteremia is as
unpredictable as clinical manifestations in human brucellosis. Int J
Infect Dis, 2008;12:303-7.
5.Sohn AH, Probert WS, Glaser CA, et al., Human neurobrucellosis with
intracerebral granuloma caused by a marine mammal Brucella spp. Emerging
Infectious Diseases, 2003;9:485-488.
6.McDonald WL, Jamaludin R, Mackereth G, et al., Characterization of a
Brucella sp. Strain as a Marine-Mammal Type despite Isolation from a
Patient with Spinal Osteomyelitis in New Zealand. Journal of Clinical
Microbiolology, 2006;44:4363-4370.
7.Brew SD, Perrett LL, Stack JA, et al., Human exposure to Brucella
recovered from a sea mammal. Veterinary Record, 1999;144:483.
8.Foster G, MacMillan AP, Godfroid J, et al., A review of Brucella sp.
infection of sea mammals with particular emphasis on isolates from
Scotland. Vet Microbiol, 2002;90:563-80.
9.Mendoza-Nunez M, Mulder M, Franco MP, et al., Brucellosis in Household
Members of Brucella Patients Residing in a Large Urban Setting in Peru. Am
J Trop Med Hyg, 2008;78:595-598.
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