Disseminated cryptococcal infection in immunocompromised patients,
such as those with HIV, used to be quite common. We have seen and reported a series of patients with cryptococcal meningitis and HIV in the late nineties of the last
century, before the availability of effective HRT. The prognosis used
to be universally poor. Some of our patients were likely to be
immunocompetant since they did not have HIV. These patients...
Disseminated cryptococcal infection in immunocompromised patients,
such as those with HIV, used to be quite common. We have seen and reported a series of patients with cryptococcal meningitis and HIV in the late nineties of the last
century, before the availability of effective HRT. The prognosis used
to be universally poor. Some of our patients were likely to be
immunocompetant since they did not have HIV. These patients mostly had disseminated tuberculosis or diabetes. Some of them did recover
from the cryptococcosis, until they returned for follow up.
With the availability of effective HRT for HIV, now the main factor for
disseminated mycosis will be diabetes, as in the case report.
The authors need to be complemented for the effective management in this case.
I read with great interest the thought provoking article by Chong et
al.[1] about the potential
association between hypokalaemia and excessive green tea intake with or
without concomitant medications. I would like to highlight the findings
from an Indian animal study on rats [2] which found that green tea extract
(GTE) in both high and low doses has significant diuretic activity with
increased urinary sodium (Na+) excreti...
I read with great interest the thought provoking article by Chong et
al.[1] about the potential
association between hypokalaemia and excessive green tea intake with or
without concomitant medications. I would like to highlight the findings
from an Indian animal study on rats [2] which found that green tea extract
(GTE) in both high and low doses has significant diuretic activity with
increased urinary sodium (Na+) excretion but without causing significant
urinary potassium (K+)loss. In fact when it was combined with
hydrochlorothiazide (HCT), a thiazide diuretic, GTE significantly reduced
urinary potassium loss compared to treatment with HCT alone. The authors
argued that this might be due to the angiotensin converting enzyme (ACE)
inhibition effect of GTE leading to a reduction in aldosterone activity
and increased potassium retention.
The findings from this animal study are relevant given that patient 1
in Chong et al.'s case report who was on bendroflumethiazide had
asymptomatic mild
hypokalaemia which was only picked up by routine
screening despite taking similar excessive amounts of green tea to his
wife (Patient 2) who was not on a diuretic. It is possible that the reason
why his serum potassium level was not significantly different from his
wife's was because of the reduced renal K+ loss due to a combination of
bendroflumethiazide and green tea.
The mechanism by which green tea might induce hypokalaemia is clearly
complex. Chong et al. give a very important warning for patients who are
prescribed medications that can lower serum potassium about this risk. I
think doctors who prescribe potassium lowering medications also need to be
aware of the potential potassium sparing effect of green tea from thiazide
diuretic induced hypokalaemia demonstrated in the Indian animal study.
Obviously larger controlled studies are required to further clarify
whether there is a causal relationship between excessive green tea intake
and hypokalaemia.
References
1. Chong SJK, Howard KA, Knox C. Hypokalaemia and drinking green tea: a
literature review and report of 2 cases, BMJ Case Reports 2016:published
online 16 Feb 2016, doi:10.1136/bcr-2016-214425
2.Chakraborty M, Kamath JV, Bhattacharjee A. Potential Interaction of
Green Tea Extract with Hydrochlorothiazide on Diuretic Activity in Rats,
International Scholarly Research Notices, vol. 2014, Article ID 273908, 5
pages, 2014. doi:10.1155/2014/273908
I wish to draw attention to the following misdescription in my
orginal letter (dated 28th Nov 2015). I had incorrectly stated that
Amoxicillin was a fluoroquinolone. I had assumed that since Hong et al
(2005) found a significant association between the use of this antibiotice
and dental fluorosis that it must be a fluoroquinolone antibiotic. I was
unaware that the letter had been published in the B...
I wish to draw attention to the following misdescription in my
orginal letter (dated 28th Nov 2015). I had incorrectly stated that
Amoxicillin was a fluoroquinolone. I had assumed that since Hong et al
(2005) found a significant association between the use of this antibiotice
and dental fluorosis that it must be a fluoroquinolone antibiotic. I was
unaware that the letter had been published in the BMJ until yesterday and
feel that to safeguard the integrity of scientific debate and promote
constructive dialogue among the scientific community it is important to
correct this for the record. I have corrected my letter and in doing do
have explained how amolicillin enhances fluoride toxicity.
Yours sincerely
Declan Waugh
A case of misdiagnosis: chronic fluoride intoxication?
Lugg et al (2015) reported a case study of a 16 year old girl who
presented with signs of chronic joint pain, dizziness and non-specific
abdominal pains after consuming 3 cups per day of imported herbal green
tea (as tea bags) for a period of 3 months [1]. There are a number of
interesting points not addressed in the case study which physicians may
not be aware of that are of clinical significance.
Firstly, the description of the ailments which the subject presented with
strongly suggest chronic fluoride intoxication. Hallanger et al (2007)
reported that the clinical features associated with fluoride intoxication
resulting from habitual tea consumption can include joint pain and
gastrointestinal complaints and that fluoride toxicity is often overlooked
by clinicians [2]. Despite the publication of a large number of reports
addressing fluoride intoxication from habitual tea drinking [3] many
health care professionals remain unaware of the risk of fluoride
intoxication from tea and lack an understanding of the pathophysiology of
fluoride toxicosis. The United States National Academy, National Research
Council (2006) reported that excessive intake of fluoride will manifest
itself in a musculoskeletal disease with associated symptoms including
chronic joint pain and arthritic symptoms [4]. However, perhaps one the
most detailed explanations of the pathophysiology of fluoride toxicosis is
provided by Professor Alexander V. Akleyev [5]. In addition to
musculoskeletal disorders, Akleyev reported that stage 2 fluorosis, the
following symptoms are observed: subatrophic and atrophic rhinitis,
pharyngitis, laryngitis, chronic conjunctivitis, retinal degeneration with
visual impairment, hearing loss, increasing impairment of bronchial
patency, and pulmonary insufficiency; mycrodial dystrophy with reduced
contractility, chronic gastritis mainly with the reduction of secretory
and acid forming function of the stomach, and chronic hepatitis with
persistent liver failure; distinct astheno-vegetative syndrome, toxic
polyneuritis and decrease in glucocorticoid function of adrenal cortex;
and microhematuria and proteinura [4]. Kessabi et al (1986) also reported
that acute hepatitis and degeneration in the liver develop following
chronic fluoride intake [6]. Other studies have also found that fluoride
toxicosis can induce hepatotoxicity and oxidative stress in humans [7-8]
and animals [9].
In the case study described by Lugg and associates [1], the fluoride
concentration in the tea samples ingested by the patient are unknown, as
they were not tested. Chan et al (2013) reported high fluoride levels in
tea infusions in the United Kingdom including green tea leaves which were
found to contained up to 6.67mg/L when made with deionized water [10]. The
European Food Safety Authority (EFSA) have reported that drinking just 2
cups of tea per day (with a fluoride content of 5mg/l), combined with an
average consumption of fluoridated drinking water and use of fluoridated
tap water in the preparation of food, but excluding all other sources
(including solid foods, toothpaste and dental products), would provide a
daily dietary intake of 6 mg per day [11]. The EFSA have established
daily recommended intake levels (AI) and Tolerable Upper Intake Levels
(ULs) for fluoride. For an adult female the AI is 2.9mg per day while the
UL is 7mg per day [11-12]. Birmingham is the largest city in the England
with artificially fluoridated water. Thus, the patient having consumed 3
cups of tea per day, is likely to have exceeded the recommended UL for
fluoride, thereby increasing the risk of chronic fluoride intoxication.
Secondly, Lugg and associates noted that the condition of the subject
worsened following prescribing of amoxicillin [1]. While amoxicillin is
not a fluoroquinolone, which like ciprofloxacin can significantly
contribute to daily fluoride intake [13], amoxicillin has nevertheless
been found to enhance the toxicity of fluoride [14]. The mechanism by
which this appears to occur is by the ability of amoxicillin to increase
cell permeability [15-16], thereby enhancing the absorption and activity
of fluoride. This would perhaps explain why Hong et al (2005) reported
that amoxicillin significantly increased the risk of fluorosis in children
when compared with those who never used amoxicillin during the first year
of life [17]. Thus, it is likely that administration of amoxicillin
resulted in further contributing to chronic fluoride intoxication of the
subject and a worsening of her condition.
Thirdly, on cessation of the herbal tea and treatment with intravenous
fluids and N-acetylcysteine, her condition resolved [1]. N-acetylcysteine
is known to protect against fluoride-induced oxidative damage [18].
Overall, the evidence indicates the symptoms reported may be due fluoride
toxicosis caused by high fluoride intake from tea, combined with other
fluoride sources such as fluoridated drinking water and potentiated by the
use of certain medications. There is a need for healthcare workers to be
aware of the pathophysiology of fluoride toxicosis as well as dietary
fluoride sources, particularly among habitual tea drinkers in communities
with artificially fluoridated drinking water. Urinary or blood fluoride
levels should be routinely monitored in patients with musculoskeletal and
gastrointestinal disorders. Fasting serum fluoride concentrations ranging
from 2.5 - 8.0 ?M/L can result in chronic fluoride intoxication and stage
I and stage II skeletal fluorosis [19].
[1] Lugg ST, Menezes DB, Gompertz S. Chinese green tea and acute
hepatitis: a rare yet recurring theme. BMJ Case Rep 2015, doi:10.1136/ bcr
-2014-208534
[2] Hallanger-Johnson JE, Kearns AE, Doran PM, Khoo TK., Wermers RA.
Fluoride-related bone disease associated with habitual tea consumption.
Mayo Clinic Proceedings 2007;82(6):719-24.
[3] Yi J, Cao J. Tea and fluorosis. Journal of Fluorine Chemistry, 2008,
129: 76-81.
[4] National Research Council, Review of Fluoride in Drinking Water, U.S.
National Research Council 2006.
[5] Neurological Disorders of Non-Radiation Nature, Fluorosis, In
Chronic Radiation Syndrome, Alexander V. Akleyev, Spriner-Verlag Berlin
Heidelberg 2014. ISBN 978-3-642-45116-4
[6] Kessabi M, Hamliri A. Experimental fluorosis in sheep: Alleviating
effects of aluminum. Vet. Hum. Toxicol., 1986, 28: 300-304.
[7] Michael M, Barot VV, Chinoy NJ. Investigations of Soft Tissue
Functions In Fluorotic Individuals of North Gujarat. Fluoride 1996, Vol.29
No.2 63-71.
[8] Medvedeva VN. Characteristics of the course of chronic hepatitis in
workers coming in contact with flourine compounds. Gigiena Truda;
Professional'nye Zabolevaniia, Jan 1985. pg 24-6
[9] AL-Harbia MS, Hamzaa RZ, Dwarya AA. Ameliorative effect of selenium
and curcumin on sodium fluoride induced hepatotoxicity and oxidative
stress in male mice. J Chem Pharma Res, 2014, 6(4):984-998.
[10] Chan L, Mehra A, Saikat S, Lynch P. Human exposure assessment of
fluoride from tea (Camellia sinensis L.) Food Res Internat. 2013; 51: 564-
570.
[11] European Food Safety Authority, Scientific Opinion on Dietary
Reference Values for fluoride, EFSA Panel on Dietetic Products, Nutrition,
and Allergies: EFSA Journal. 2013;11(8):3332.
[12] European Food Safety Authority, Scientific Opinion of the Panel on
Dietetic Products, Nutrition, and Allergies (NDA) on the tolerable upper
intake level of fluoride. The EFSA Journal. 2005, 192, 1-65.
[13] Pradhan KM, Arora NK, Jena A, Susheela AK, Bhan MK. Safety of
ciprofloxacin therapy in children: magnetic resonance images, body fluid
levels of fluoride and linear growth. Acta Paediatr. 1995, 84:555-560.
[14]Sahlberg C, Pavlic A, Ess A, Lukinmaa PL, Salmela E, Alaluusua S.
Combined effect of amoxicillin and sodium fluoride on the structure of
developing mouse enamel in vitro. Arch Oral Biol. 2013 Sep;58(9):1155-64.
doi:10.1016/j.archoralbio.2013.03.007. Epub 2013 Apr 17.
[15]Novo DJ, Perlmutter NG, Hunt RH, Shapiro HM. Multiparameter Flow
Cytometric Analysis of Antibiotic Effects on Membrane Potential, Membrane
Permeability, and Bacterial Counts of Staphylococcus aureus and
Micrococcus luteus. Antimicrobial Agents and Chemotherapy. 2000;44(4):827-
834.
[16] Khargharia S, Chakraborty AK., Bhattacharyya A, Manda T K.
Disposition Kinetic of Amoxicillin in Healthy and Nephropathic Goats with
Immunological and Residual Level in Blood and Tissues. J Drug Metab
Toxicol S5:003. doi:10.4172/2157-7609.S5-003
[17] Hong L, Levy SM, Warren JJ, Dawson DV, Bergus GR, Wefel JS.
Association of Amoxicillin Use During Early Childhood With Developmental
Tooth Enamel Defects, Arch Pediatr Adolesc Med. 2005;159:943-948, 995-996.
[18] Paw?owska-G?ral K, Kurzeja E, Stec M. N-acetylcysteine protects
against fluoride-induced oxidative damage in primary rat hepatocytes.
Toxicology in Vitro, December 2013, Volume 27, Issue 8, Pages 2279-2282.
doi:10.1016/j.tiv.2013.09.019
[19] Xiang QY, Chen LS, Chen XD., Wang CS, et al. Serum Fluoride And
Skeletal Fluorosis In Two Villages In Jiangsu Province, China. 178
Fluoride 2005;38(3):178-184
There are several methods of measuring intracranial pressure (ICP).
These include insertion of an ICP 'bolt' into brain parenchyma or
subdurally through a small burr hole, direct placement of a pressure
monitor under the dura following a craniotomy/craniectomy, or insertion of
a drainage catheter into the ventricles allowing direct transduction of
cerebrospinal fluid (CSF) pressure. The later is known as an external
vent...
There are several methods of measuring intracranial pressure (ICP).
These include insertion of an ICP 'bolt' into brain parenchyma or
subdurally through a small burr hole, direct placement of a pressure
monitor under the dura following a craniotomy/craniectomy, or insertion of
a drainage catheter into the ventricles allowing direct transduction of
cerebrospinal fluid (CSF) pressure. The later is known as an external
ventricular drain, a term often used synonymously with ventriculostomy.
The high infection rates associated with ICP measurement that Lewis cites
(Lozier et al, 2002) refer to ventriculostomy catheters and not ICP bolts
or subdural monitors. The case study describes an "ICP bolt placed over
the left frontal lobe", from this description it is not possible to
ascertain the exact monitor used but it does not appear to describe an
intraventricular catheter. Therefore, in the context of the case; it may
be prudent to note that intraparenchymal or subdural ICP monitoring is
recognised as having far lower infection rates and does not allow CSF
drainage or sampling.
Although Tetanus has become a rare disease in most of the developed
countries it had been quite common disease with high mortality in the
developing countries like India. We have seen a variety of presenting
symptoms in patients who ultimately were diagnosed as Tetanus. Now of
course it is rare to find a patient developing Tetanus because of the
universal immunization against the same. The authors are right in
expressin...
Although Tetanus has become a rare disease in most of the developed
countries it had been quite common disease with high mortality in the
developing countries like India. We have seen a variety of presenting
symptoms in patients who ultimately were diagnosed as Tetanus. Now of
course it is rare to find a patient developing Tetanus because of the
universal immunization against the same. The authors are right in
expressing the concern in suspecting the diagnosis of Tetanus in this
patient. A high index of suspession is needed to think of the possibility
and start the management early to have the best prognosis
The photo above the caption "Ramaria rufescens" is clearly not in the genus Ramaria, the "coral fungi". A quick Google search of the name would have revealed this. As an amateur mycologist, I find it hard to believe that this article received peer review by anyone with professional training in mycology.
In trans sccaphoid perilunate dislocation as shown on the
radiographs the lunate is not dorsaly dislocated.the lunate stays in its
place the peri lunate carpal bones are dorsaly displaced.
Many thanks go the authors for reporting this very interesting
finding.
A minor comment, please:
Figure 1, although it is somewhat blurred and dark, the MRI sequence
it contains seems be to the "T2 FLAIR" one, not the T1 with Gadolinium, as
the manuscript reads. Therefore, the lesions it demonstrates are the non-
suppressed hyper-intensities from the T2-weighted film (which is not
shown).
Many thanks go the authors for reporting this very interesting
finding.
A minor comment, please:
Figure 1, although it is somewhat blurred and dark, the MRI sequence
it contains seems be to the "T2 FLAIR" one, not the T1 with Gadolinium, as
the manuscript reads. Therefore, the lesions it demonstrates are the non-
suppressed hyper-intensities from the T2-weighted film (which is not
shown).
Wilson's disease is known to directly affect parathyroid function
resulting in hypoparathyroidism. In a patient with rickets, one would
expect secondary hypoparathyroidism. Moreover, this patient likely
suffered from vitamin D resistant rickets due to renal calcium and
phosphate wasting. Were PTH and serum vitamin D levels assayed in this
instance?
Wilson's disease is known to directly affect parathyroid function
resulting in hypoparathyroidism. In a patient with rickets, one would
expect secondary hypoparathyroidism. Moreover, this patient likely
suffered from vitamin D resistant rickets due to renal calcium and
phosphate wasting. Were PTH and serum vitamin D levels assayed in this
instance?
Disseminated cryptococcal infection in immunocompromised patients, such as those with HIV, used to be quite common. We have seen and reported a series of patients with cryptococcal meningitis and HIV in the late nineties of the last century, before the availability of effective HRT. The prognosis used to be universally poor. Some of our patients were likely to be immunocompetant since they did not have HIV. These patients...
I read with great interest the thought provoking article by Chong et al.[1] about the potential association between hypokalaemia and excessive green tea intake with or without concomitant medications. I would like to highlight the findings from an Indian animal study on rats [2] which found that green tea extract (GTE) in both high and low doses has significant diuretic activity with increased urinary sodium (Na+) excreti...
Thank you for this interesting report. Please check for skeletal fluorosis also given amount of tea consumed per day over so many years.
Thank you
Conflict of Interest:
None declared
Dear Editor,
I wish to draw attention to the following misdescription in my orginal letter (dated 28th Nov 2015). I had incorrectly stated that Amoxicillin was a fluoroquinolone. I had assumed that since Hong et al (2005) found a significant association between the use of this antibiotice and dental fluorosis that it must be a fluoroquinolone antibiotic. I was unaware that the letter had been published in the B...
There are several methods of measuring intracranial pressure (ICP). These include insertion of an ICP 'bolt' into brain parenchyma or subdurally through a small burr hole, direct placement of a pressure monitor under the dura following a craniotomy/craniectomy, or insertion of a drainage catheter into the ventricles allowing direct transduction of cerebrospinal fluid (CSF) pressure. The later is known as an external vent...
Although Tetanus has become a rare disease in most of the developed countries it had been quite common disease with high mortality in the developing countries like India. We have seen a variety of presenting symptoms in patients who ultimately were diagnosed as Tetanus. Now of course it is rare to find a patient developing Tetanus because of the universal immunization against the same. The authors are right in expressin...
Conflict of Interest:
None declared
In trans sccaphoid perilunate dislocation as shown on the radiographs the lunate is not dorsaly dislocated.the lunate stays in its place the peri lunate carpal bones are dorsaly displaced.
Conflict of Interest:
None declared
Many thanks go the authors for reporting this very interesting finding.
A minor comment, please:
Figure 1, although it is somewhat blurred and dark, the MRI sequence it contains seems be to the "T2 FLAIR" one, not the T1 with Gadolinium, as the manuscript reads. Therefore, the lesions it demonstrates are the non- suppressed hyper-intensities from the T2-weighted film (which is not shown).
Th...
Sir,
Wilson's disease is known to directly affect parathyroid function resulting in hypoparathyroidism. In a patient with rickets, one would expect secondary hypoparathyroidism. Moreover, this patient likely suffered from vitamin D resistant rickets due to renal calcium and phosphate wasting. Were PTH and serum vitamin D levels assayed in this instance?
Yours sincerely,
Kushal Naha, MD
...Pages