Friday, February 19, 2010

APROVEITE QUE O FINAL DE SEMANA ESTÁ CHEGANDO...E VENHA COMIGO.

Se você ainda não foi dá tempo..
Apreveite o fianl de semana e venha conferir mais desses cantinhos que nos proporcionam alegrias e confraternização entre os poetas...

AGRADEÇO A SUA COMPANHIA...
AGRADEÇO A TODOS QUE LÁ DEIXARAM SEUS DEPOIMENTOS.
MUITO LINDO..GOSTEI..
SERAM TRAZIDOS PARA A CURIOSA..


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PARA AS LINDAS MULHERES UM SELO...

Wednesday, February 17, 2010

Ash Wednesday



Today is Ash Wednesday. My Dad went to church with me this morning. I go to a Catholic School. We go to mass every day before school. This morning, my Dad came too! And we got our ashes. It's the beginning of Lent. Papi Rene told use not to look at it as a sad time. Or even a time to give up stuff. But a time to do better. To do nice things for people. And make a better effort to pray and meditate every day.

I decided to practice every day for an hour. And to help my Dad and abuelitas more. I'm also going to volunteer at church. I think that would be a good deed to do.

I was happy to get my ashes today. It was weird to see so many people at church. You never see that many people there. But it was nice to see them worshipping. :) C

The Case of the Missing Retrovirus

In October 2009, a team led by Vincent C. Lombardi of the Whittemore Peterson Institute reported the presence of a recently discovered virus, XMRV, in 67% of the blood samples from 101 American patients with chronic fatigue syndrome (CFS). XMRV had previously been linked to some cases of prostate cancer.

This sparked intense interest amongst many people and much discussion. But in January this year, Erlwein et al reported that they did not find any evidence of XMRV in the blood of 186 British CFS patients (my post).

Now, a second British study has appeared, and the results are also negative. The paper is Groom et al's Absence of xenotropic murine leukaemia virus-related virus in UK patients with chronic fatigue syndrome. They found no XMRV in 170 British CFS patients or 395 healthy controls. VirologyBlog has an excellent summary of the latest paper.

In order to help people interested in this topic, I've put together a quick summary of all the data on XMRV infection in humans. If I've left anything out or made any mistakes, let me know in the comments. I'll try to keep this list up to date with every new publication - because there are sure to be plenty more.

Overall, the most striking thing about these results is the national differences. XMRV has been detected in 67% of American CFS patients, in 10-25% of American prostate cancer cases, and in 3-4% of healthy Americans. By contrast, in Germany, Britain and Ireland, it's only been detected in 2 Germans, out of a grand total of 1,300 or so European people who have been tested so far using a variety of methods. The situation elsewhere is unclear; one study claimed to detect XMRV in 1.5% of healthy Japanese blood donors but this is unpublished, and the methodology is unclear.

Other than that, it's not clear what's going on here, and it seems to me that it would be premature to conclude anything about XMRV and CFS (or, indeed, cancer) at this stage.

*

Last Updated: 06 July 2010
Please let me know if I have omitted any data (published or unpublished)

Published Papers
- CFS

1. Lombardi et al 2009
  • Patients: "CDC Fukuda Criteria and the 2003 Canadian Consensus Criteria... presenting with severe disability... their diagnosis of CFS is based upon prolonged disabling fatigue ... cognitive deficits and reproducible immunological abnormalities ... impaired exercise performance with extremely low VO2 max measured on stress testing."
  • Origin: USA
  • Method A: PCR of DNA from PBMCs
  • Result: 68 of 101 patients (67%), 8 of 218 controls (3.7%)
  • Method B: PBMC reactivity to anti-MLVp30Gag antibodies
  • Result: 19 of 30 patients (63%), 0 of 16 controls (0%)
  • Method C: Plasma immunoreactivity to SFFV-Env
  • Result: 9 out of 18 patients with XMRV, 0 out of 7 controls
2. Erlwein et al 2010
  • Patients: CDC Fukeda criteria "markedly unwell. Few were working, and 19% were members of patient support groups for CFS/ME... The levels of fatigue in this sample were high ... as were levels of disability"
  • Origin: London, UK
  • Method: PCR of DNA from whole blood
  • Result: 0 out of 186 patients (0%)
3. Groom et al 2010
  • Patients: CDC Fukeda criteria
  • Origin: Bristol, Dorset, London, Birmingham, Norfolk and Epsom, UK
  • Method A: PCR of gDNA from PBMCs
  • Result: 0 of 48 patients (0%)
  • Method B: PCR of gDNA, cDNA, or both from PBMCs
  • Result: 0 out of 142 patients (0%), and 157 controls (0%)
  • Method C: Serum immunoreactivity to XMRV
  • Result: 1 out of 160 patients; 25 out of 395 controls; but positives were not considered specific to XMRV, as they also reacted to and neutralized other viruses.
4. Switzer et al 2010 "CDC study"
  • Patients: Recruited by random population telephone screening and symptom quizzing (unlike other studies). CDC Fukeda 1994 criteria (but also referred to in the abstract as the "revised" 1994 CDC criteria) and symptoms not better accounted for by medical illness or "current psychiatric disorders considered exclusionary for CFS, which included current melancholic depression, current or lifetime bipolar disorder or psychosis, substance abuse within 2 years and eating disorders within 5 years".
  • Origin: Wichita, Kansas, USA and Georgia, USA.
  • Method A: Western blotting serology for anti-XMRV antibodies in plasma
  • Result: 0 of 51 patients (0%) and 0 of 53 controls (0%)
  • Method B: ELISA serology for anti-XMRV gag and pol antibodies in plasma, performed by RKI.
  • Result: 0 of 51 patients (0%) and 0 of 53 controls (0%)
  • Method C: PCR of DNA from PBMCs or whole blood for XMRV gag and pol
  • Result: 0 of 50 patients (0%) and 0 of 97 controls (0%)
  • Method D: PCR of DNA for XMRV gag, performed by BSRI.
  • Result: 0 of 50 patients (0%) and 0 of 56 controls (0%)
5. van Kuppeveld et al 2010 "Dutch study"
  • Patients: Oxford Criteria
  • Origin: Netherlands. Recruited and samples taken 1991-1992
  • Method: PCR of cDNA from PBMCs for XMRV integrase and gag
  • Result: 0 of 32 patients (0%), 0 of 43 controls (0%)
Published Papers - Prostate Cancer

6. Urisman et al 2006
  • Patients: Familial Prostate Cancer
  • Origin: Cleveland, USA
  • Method: PCR on prostate cell DNA
  • Result: 9 of 86 (10.4%); associated with R462Q QQ genotype
7. Schlaberg et al 2009
  • Patients: Prostate Cancer
  • Origin: Columbia University Medical Center, USA
  • Method A: PCR on prostate cell DNA
  • Results: 14/223 prostate cancer patients (6.2%), 2/101 non-cancer prostate controls (2.0%). Not associated with R462Q QQ genotype.
  • Method B: XMRV protein expression (cell reactivity to anti-XMRV serum)
  • Results: XMRV protein expression in 54/223 (23%) cases with prostate cancer and in 4/101 (4%) controls. Not associated with R462Q QQ genotype.
8. Hohn et al 2009
  • Patients: Prostate Cancer
  • Origin: Berlin, Germany
  • Method: PCR on prostate cell DNA
  • Result: 0 out of 589 (0%)
  • Method: Serum immunoreactivity to XMRV proteins (gp70 and Gag)
  • Result: 0 out of 146 patients, 0 out of 5 controls (0%)
9. Fischer et al 2008
  • Patients: Non-familial Prostate Cancer
  • Origin: Hamburg, Germany
  • Method: PCR of prostate cell RNA
  • Results: 1/105 patients (0.95%), 1/70 healthy controls (1.42%).
Unpublished Data

10. D'Arcy et al 2008
  • Patients: Prostrate Cancer
  • Origin: Dublin, Ireland
  • Method A: PCR of prostate cell RNA
  • Results: 0 out of 9 (7 R462Q QQ genotype, 2 others) (0%)
  • Notes: Unpublished data presented at a conference.
11. Furata et al 2009
  • Patients: n/a
  • Origin: Japan
  • Method: "antibodies [to XMRV]"
  • Result: 5/300 controls (healthy blood donors) (1.5%)
  • Note: Unpublished data presented at a conference - I can't access the abstract and am relying on Erlwein et al's summary. In the light of Groom et al, we really need to know whether the antibodies were truly specific to XMRV.
12. "The Harvey Alter NIH/FDA Paper"
  • Patients: CFS?
  • Origin: ?
  • Method: ?
  • Result: "We (FDA & NIH) have independently confirmed the Lombardi group findings." according to a conference presentation by Harvey Alter: see here.
  • Notes: Rumored as of 5th July 2010 to be about to appear in PNAS.
13. Qui et al 2010
  • Patients: n/a
  • Origin: U.S. blood donors
  • Method: Blood immunoreactivity to XMRV env, gag, and p15E.
  • Result: "reactivity to all 3 antigens in a low proportion (~0.1%) of US blood donors." n=?
  • Notes: Conference presentation given at the 17th Conference on Retroviruses and Opportunistic Infections 2010.
ResearchBlogging.orgHarriet Groom, et al. (2010). Absence of xenotropic murine leukaemia virus-related virus in UK patients with chronic fatigue syndrome Retrovirology

The Case of the Missing Retrovirus

In October 2009, a team led by Vincent C. Lombardi of the Whittemore Peterson Institute reported the presence of a recently discovered virus, XMRV, in 67% of the blood samples from 101 American patients with chronic fatigue syndrome (CFS). XMRV had previously been linked to some cases of prostate cancer.

This sparked intense interest amongst many people and much discussion. But in January this year, Erlwein et al reported that they did not find any evidence of XMRV in the blood of 186 British CFS patients (my post).

Now, a second British study has appeared, and the results are also negative. The paper is Groom et al's Absence of xenotropic murine leukaemia virus-related virus in UK patients with chronic fatigue syndrome. They found no XMRV in 170 British CFS patients or 395 healthy controls. VirologyBlog has an excellent summary of the latest paper.

In order to help people interested in this topic, I've put together a quick summary of all the data on XMRV infection in humans. If I've left anything out or made any mistakes, let me know in the comments. I'll try to keep this list up to date with every new publication - because there are sure to be plenty more.

Overall, the most striking thing about these results is the national differences. XMRV has been detected in 67% of American CFS patients, in 10-25% of American prostate cancer cases, and in 3-4% of healthy Americans. By contrast, in Germany, Britain and Ireland, it's only been detected in 2 Germans, out of a grand total of 1,300 or so European people who have been tested so far using a variety of methods. The situation elsewhere is unclear; one study claimed to detect XMRV in 1.5% of healthy Japanese blood donors but this is unpublished, and the methodology is unclear.

Other than that, it's not clear what's going on here, and it seems to me that it would be premature to conclude anything about XMRV and CFS (or, indeed, cancer) at this stage.

*

Last Updated: 06 July 2010
Please let me know if I have omitted any data (published or unpublished)

Published Papers
- CFS

1. Lombardi et al 2009
  • Patients: "CDC Fukuda Criteria and the 2003 Canadian Consensus Criteria... presenting with severe disability... their diagnosis of CFS is based upon prolonged disabling fatigue ... cognitive deficits and reproducible immunological abnormalities ... impaired exercise performance with extremely low VO2 max measured on stress testing."
  • Origin: USA
  • Method A: PCR of DNA from PBMCs
  • Result: 68 of 101 patients (67%), 8 of 218 controls (3.7%)
  • Method B: PBMC reactivity to anti-MLVp30Gag antibodies
  • Result: 19 of 30 patients (63%), 0 of 16 controls (0%)
  • Method C: Plasma immunoreactivity to SFFV-Env
  • Result: 9 out of 18 patients with XMRV, 0 out of 7 controls
2. Erlwein et al 2010
  • Patients: CDC Fukeda criteria "markedly unwell. Few were working, and 19% were members of patient support groups for CFS/ME... The levels of fatigue in this sample were high ... as were levels of disability"
  • Origin: London, UK
  • Method: PCR of DNA from whole blood
  • Result: 0 out of 186 patients (0%)
3. Groom et al 2010
  • Patients: CDC Fukeda criteria
  • Origin: Bristol, Dorset, London, Birmingham, Norfolk and Epsom, UK
  • Method A: PCR of gDNA from PBMCs
  • Result: 0 of 48 patients (0%)
  • Method B: PCR of gDNA, cDNA, or both from PBMCs
  • Result: 0 out of 142 patients (0%), and 157 controls (0%)
  • Method C: Serum immunoreactivity to XMRV
  • Result: 1 out of 160 patients; 25 out of 395 controls; but positives were not considered specific to XMRV, as they also reacted to and neutralized other viruses.
4. Switzer et al 2010 "CDC study"
  • Patients: Recruited by random population telephone screening and symptom quizzing (unlike other studies). CDC Fukeda 1994 criteria (but also referred to in the abstract as the "revised" 1994 CDC criteria) and symptoms not better accounted for by medical illness or "current psychiatric disorders considered exclusionary for CFS, which included current melancholic depression, current or lifetime bipolar disorder or psychosis, substance abuse within 2 years and eating disorders within 5 years".
  • Origin: Wichita, Kansas, USA and Georgia, USA.
  • Method A: Western blotting serology for anti-XMRV antibodies in plasma
  • Result: 0 of 51 patients (0%) and 0 of 53 controls (0%)
  • Method B: ELISA serology for anti-XMRV gag and pol antibodies in plasma, performed by RKI.
  • Result: 0 of 51 patients (0%) and 0 of 53 controls (0%)
  • Method C: PCR of DNA from PBMCs or whole blood for XMRV gag and pol
  • Result: 0 of 50 patients (0%) and 0 of 97 controls (0%)
  • Method D: PCR of DNA for XMRV gag, performed by BSRI.
  • Result: 0 of 50 patients (0%) and 0 of 56 controls (0%)
5. van Kuppeveld et al 2010 "Dutch study"
  • Patients: Oxford Criteria
  • Origin: Netherlands. Recruited and samples taken 1991-1992
  • Method: PCR of cDNA from PBMCs for XMRV integrase and gag
  • Result: 0 of 32 patients (0%), 0 of 43 controls (0%)
Published Papers - Prostate Cancer

6. Urisman et al 2006
  • Patients: Familial Prostate Cancer
  • Origin: Cleveland, USA
  • Method: PCR on prostate cell DNA
  • Result: 9 of 86 (10.4%); associated with R462Q QQ genotype
7. Schlaberg et al 2009
  • Patients: Prostate Cancer
  • Origin: Columbia University Medical Center, USA
  • Method A: PCR on prostate cell DNA
  • Results: 14/223 prostate cancer patients (6.2%), 2/101 non-cancer prostate controls (2.0%). Not associated with R462Q QQ genotype.
  • Method B: XMRV protein expression (cell reactivity to anti-XMRV serum)
  • Results: XMRV protein expression in 54/223 (23%) cases with prostate cancer and in 4/101 (4%) controls. Not associated with R462Q QQ genotype.
8. Hohn et al 2009
  • Patients: Prostate Cancer
  • Origin: Berlin, Germany
  • Method: PCR on prostate cell DNA
  • Result: 0 out of 589 (0%)
  • Method: Serum immunoreactivity to XMRV proteins (gp70 and Gag)
  • Result: 0 out of 146 patients, 0 out of 5 controls (0%)
9. Fischer et al 2008
  • Patients: Non-familial Prostate Cancer
  • Origin: Hamburg, Germany
  • Method: PCR of prostate cell RNA
  • Results: 1/105 patients (0.95%), 1/70 healthy controls (1.42%).
Unpublished Data

10. D'Arcy et al 2008
  • Patients: Prostrate Cancer
  • Origin: Dublin, Ireland
  • Method A: PCR of prostate cell RNA
  • Results: 0 out of 9 (7 R462Q QQ genotype, 2 others) (0%)
  • Notes: Unpublished data presented at a conference.
11. Furata et al 2009
  • Patients: n/a
  • Origin: Japan
  • Method: "antibodies [to XMRV]"
  • Result: 5/300 controls (healthy blood donors) (1.5%)
  • Note: Unpublished data presented at a conference - I can't access the abstract and am relying on Erlwein et al's summary. In the light of Groom et al, we really need to know whether the antibodies were truly specific to XMRV.
12. "The Harvey Alter NIH/FDA Paper"
  • Patients: CFS?
  • Origin: ?
  • Method: ?
  • Result: "We (FDA & NIH) have independently confirmed the Lombardi group findings." according to a conference presentation by Harvey Alter: see here.
  • Notes: Rumored as of 5th July 2010 to be about to appear in PNAS.
13. Qui et al 2010
  • Patients: n/a
  • Origin: U.S. blood donors
  • Method: Blood immunoreactivity to XMRV env, gag, and p15E.
  • Result: "reactivity to all 3 antigens in a low proportion (~0.1%) of US blood donors." n=?
  • Notes: Conference presentation given at the 17th Conference on Retroviruses and Opportunistic Infections 2010.
ResearchBlogging.orgHarriet Groom, et al. (2010). Absence of xenotropic murine leukaemia virus-related virus in UK patients with chronic fatigue syndrome Retrovirology

VAMOS VIAJAR!!!!!RUMO A PORTUGAL!!!!!

VOO LIBERADO...HORA DE PARTIR..
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AGRADEÇO A SUA COMPANHIA...


ESTOU NA SEGUNDA FASE DO CONCURSO.. VENHA COMIGO:
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2º concurso de Poesia EMBARQUE NETA MAGIA E VAMOS COMIGO.SERÁ UM PRAZER VIAJAR NESTE MUNDO ENCANTADO DA POESIA.

VAMOS ATÉ PORTUGAL.
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Tuesday, February 16, 2010

CHEGOU O DIA..VAMOS VOAR...


ESTOU NA SEGUNDA FASE DO CONCURSO.. VENHA COMIGO:
UMA PROMOÇÃO DO OLHAR DIRETO http://olhardireito.blogspot.com/
2º concurso de Poesia EMBARQUE NETA MAGIA E VAMOS COMIGO.SERÁ UM PRAZER VIAJAR NESTE MUNDO ENCANTADO DA POESIA.

VAMOS ATÉ PORTUGAL.
http://nihilsubsolenovum.files.wordpress.com/2009/02/imagem_aviao.jpg?w=211&h=140
HORÁRIO DO VOO COM SAÍDA AQUI NA CURIOSA.
SERÁ MAIS TARDE..MAS AVISAREI...
AGORA É SÓ CONFIRMAR A VIAGEM... SEGUNDO O CHICO, O AVIÃO PARTE MAIS TARDE..

CHEGOU A HORA DA PARTIDA...VAMOS
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DSM-V: Change We Can Believe In?

So the draft of DSM-V is out.

If, as everyone says, the Diagnostic and Statistical Manual is the Bible of Psychiatry, I'm not sure why it gets heavily edited once every ten years or so. Perhaps the previous versions are a kind of Old Testament, and only the current one represents the New Revelation from the gods of the mind?

Mind Hacks has an excellent summary of the proposed changes. Bear in mind that the book won't be released until 2013. Some of the headlines:
  • Asperger's Syndrome is out - everyone's going to have an "autistic spectrum disorder" now.
  • Personality Disorders are out - kind of. In their place, there's 5 Personality Disorder Types, each of which you can have to varying degrees, and also 6 Personality Traits, each of which you can have to varying degrees.
  • Hypoactive Sexual Desire Disorder - the disease which failed-antidepressant-turned-aphrodisiac flibanserin is supposed to treat - is out, to be replaced by Sexual Interest and Arousal Disorder.
  • Binge Eating Disorder, Hypersexuality Disorder, and Gambling Addiction are in. Having Fun is not a disorder yet, but that's on the agenda for DSM-VI.
More important, at least in theory, are the Structural, Cross-Cutting, and General Classification Issues. This is where the grand changes to the whole diagnostic approach happen. But it turns out they're pretty modest. First up, the Axis system, by which most disorders were "Axis I", personality disorders which were "Axis II", and other medical illnesses "Axis III", is to be abolished - everything will be on a single Axis from now on. This will have little, if any, practical effect, but will presumably make it easier on whoever it is that has to draw up the contents page of the book.

Excitingly, "dimensional assessments" have been added... but only in a limited way. Some people have long argued that having categorical diagnoses - "schizophrenia", "bipolar disorder", "major depression" etc. - is a mistake, since it forces psychiatrists to pigeon-hole people, and that we should stop thinking in terms of diagnoses and just focus on symptoms: if someone's depressed, say, then treat them for depression, but don't diagnose them with "major depressive disorder".

DSM-V hasn't gone this far - the categorical diagnoses remain in most cases (the exception is Personality Disorders, see above). However, new dimensional assessments have been proposed, which are intended to complement the diagnoses, and some of them will be "cross-cutting" i.e. not tied to one particular diagnosis. See for example here for a cross-cutting questionnaire designed to assess common anxiety, depression and substance abuse symptoms.

Finally, the concept of "mental disorder" is being redefined. In DSM-V a mental disorder is (drumroll)...
A. A behavioral or psychological syndrome or pattern that occurs in an individual

B. The consequences of which are clinically significant distress (e.g., a painful symptom) or disability (i.e., impairment in one or more important areas of functioning)

C. Must not be merely an expectable response to common stressors and losses...

D. That reflects an underlying psychobiological dysfunction

E. That is not primarily a result of social deviance or conflicts with society
The main change here is that now it's all about "psychobiological dysfunction", whereas in DSM-IV, it was about "behavioral, psychological, or biological dysfunction". Hmm. I am not sure what this means, if anything.

But read on, and we find something rather remarkable...
J. When considering whether to add a mental/psychiatric condition to the nomenclature, or delete a mental/psychiatric condition from the nomenclature, potential benefits (for example, provide better patient care, stimulate new research) should outweigh potential harms (for example, hurt particular individuals, be subject to misuse)
This all sounds very nice and sensible. Diagnoses should be helpful, not harmful, right?

No. Diagnoses should be true. The whole point of the DSM is that it's supposed to be an accurate list of the mental diseases that people can suffer from. The diagnoses are in there because they are, in some sense, real, objectively-existing disorders, or at least because the American Psychiatric Association thinks that they are.

This seemingly-innocuous paragraph seems to be an admission that, in fact, disorders are added or subtracted for reasons which have little to do with whether they really, objectively exist or not. This is what's apparently happened in the case of Temper Dysregulation Disorder with Dysphoria (TDDD), a new childhood disorder.

TDDD has been proposed in order to reduce the number of children being diagnosed with pediatric bipolar disorder. The LA Times quote a psychiatrist on the DSM-V team:
The diagnosis of bipolar [in children] "is being given, we believe, too frequently," said Dr. David Shaffer, a member of the work group on disorders in childhood and adolescence. In reality, when such children are tracked into adulthood, very few of them turn out to be bipolar, he said.
And the DSM-V website has a lengthy rationale for TDDD, to the same effect.

Now, many people agree that pediatric bipolar is being over-diagnosed. As I've written before, pediatric bipolar was considered to be a vanishingly rare disease until about 10 years ago, it still is pretty much everywhere outside the USA.

So we can all sympathize with the sentiment behind TDDD - but this is fighting fire with fire. Is the only way to stop kids getting one diagnosis, to give them another one? Should we really be creating diagnoses for more or less "strategic" purposes? When the time comes for DSM-VI, and the fashion for "pediatric bipolar" has receded, will TDDD get deleted as no longer necessary? What will happen to all the "TDDD" kids then?

Can't we just decide to diagnose people less? Apparently, that would be a rather too radical change...