Retraction of the paper (MMR) vaccine and an autism-like disorder

The Lancet has finally retracted, more than 10 years after it first published, a paper that linked MMR vaccine and an autism-like disorder. This original paper led to a huge health concern amongst parents and shows how misinformation in medicine can not only affect health care but also have long term scientific consequences.

Following the judgment of the UK General Medical Council’s Fitness to Practise Panel on Jan 28, 2010, it has become clear that several elements of the 1998 paper by Wakefield et al 1 are incorrect, contrary to the findings of an earlier investigation. 2 In particular, the claims in the original paper that children were “consecutively referred” and that investigations were “approved” by the local ethics committee have been proven to be false. Therefore we fully retract this paper from the published….

Retraction—Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children

See also BMJ - Why did the Lancet take so long? | Reflections on investigating Wakefield

Vitamin A and Hirschsprung disease

This recent Development paper identifies a potential non-genetic risk for Hirschsprung disease. During development neural crest cells migrate into the developing gastrointestinal tract wall forming the enteric nervous system required for smoth muscle peristaltic contractility. In Hirschsprung disease  failure of neural crest cell migration leaves sections of the bowel without neurons (aganglionic). Excess retinoic acid though has also been identified as a teratogenic factor.

Hirschsprung disease is a serious disorder of enteric nervous system (ENS) development caused by the failure of ENS precursor migration into the distal bowel. We now demonstrate that retinoic acid (RA) is crucial for GDNF-induced ENS precursor migration, cell polarization and lamellipodia formation, and that vitamin A depletion causes distal bowel aganglionosis in serum retinol-binding-protein-deficient (Rbp4(-/-)) mice. Ret heterozygosity increases the incidence and severity of distal bowel aganglionosis induced by vitamin A deficiency in Rbp4(-/-) animals. Furthermore, RA reduces phosphatase and tensin homolog (Pten) accumulation in migrating cells, whereas Pten overexpression slows ENS precursor migration. Collectively, these data support the hypothesis that vitamin A deficiency is a non-genetic risk factor that increases Hirschsprung disease penetrance and expressivity, suggesting that some cases of Hirschsprung disease might be preventable by optimizing maternal nutrition.

Vitamin A facilitates enteric nervous system precursor migration by reducing Pten accumulation. Fu M, Sato Y, Lyons-Warren A, Zhang B, Kane MA, Napoli JL, Heuckeroth RO. Development. 2010 Feb;137(4):631-40. PMID: 20110328

(More? UNSW Embryology – Gastrointestinal Tract Abnormalities | Neural Crest Abnormalities)

Pregnancy Changes in Patients with Multiple Sclerosis

Pregnancy has been previously associated with the reduced activity of multiple sclerosis (MS) in patients. This recent PLOS One paper has initially attempted to identify at the molecular level the potential changes that occur during pregnancy that could lead to this disease reducing effect.

Results showed an altered expression of 347 transcripts in non-pregnant MS patients with respect to non-pregnant healthy controls. Complementary changes in expression, occurring during pregnancy, reverted the previous imbalance particularly for seven inflammation-related transcripts, i.e. SOCS2, TNFAIP3, NR4A2, CXCR4, POLR2J, FAM49B, and STAG3L1.

Gilli F, Lindberg RLP, Valentino P, Marnetto F, Malucchi S, et al. (2010) Learning from Nature: Pregnancy Changes the Expression of Inflammation-Related Genes in Patients with Multiple Sclerosis. PLoS ONE 5(1): e8962. doi:10.1371/journal.pone.0008962

Effectiveness of Common Household Cleaning Agents in Reducing the Viability of Human Influenza A/H1N1

Some viruses and their associated infection hyperthermia are known teratogens. This recent PLOS One paper studied the actions of commercially available cleaning agents with some common household cleaning agents for viral inactivation and found that both had similar results. This would be useful information in the case of an Influenza pandemic, such as that seen with the  Human Influenza A/H1N1 virus.

Active ingredients in a number of the cleaning agents, wipes, and tissues tested were able to rapidly render influenza virus nonviable, as determined by plaque assay. Commercially available wipes with a claimed antiviral or antibacterial effect killed or reduced virus infectivity, while nonmicrobiocidal wipes and those containing only low concentrations (<5%) of surfactants showed lower anti-influenza activity. Importantly, however, our findings indicate that it is possible to use common, low-technology agents such as 1% bleach, 10% malt vinegar, or 0.01% washing-up liquid to rapidly and completely inactivate influenza virus. Thus, in the context of the ongoing pandemic, and especially in low-resource settings, the public does not need to source specialized cleaning products, but can rapidly disinfect potentially contaminated surfaces with agents readily available in most homes.

Greatorex JS, Page RF, Curran MD, Digard P, Enstone JE, et al. (2010) Effectiveness of Common Household Cleaning Agents in Reducing the Viability of Human Influenza A/H1N1. PLoS ONE 5(2): e8987. doi:10.1371/journal.pone.0008987

(More? UNSW Embryology - Abnormal Development – Viral Infection | Abnormal Development – Maternal Hyperthermia)

Abnormal Development – Illegal Drugs – Cocaine

This recent PNAS paper uses a nonhuman primate model of fetal brain development in combination with non-invasive PET and MRI analysis. The study shows that in addition to the known effects of cocaine on placental circulation there was also a detectable direct pharmacological effect to the developing fetal brain.

Cocaine use during pregnancy is deleterious to the newborn child, in part via its disruption of placental blood flow. However, the extent to which cocaine can affect the function of the fetal primate brain is still an unresolved question. Here we used PET and MRI and show that in third-trimester pregnant nonhuman primates, cocaine at doses typically used by drug abusers significantly increased brain glucose metabolism to the same extent in the mother as in the fetus (∼100%). Inasmuch as brain glucose metabolism is a sensitive marker of brain function, the current findings provide evidence that cocaine use by a pregnant mother will also affect the function of the fetal brain. We are also unique in showing that cocaine’s effects in brain glucose metabolism differed in pregnant (increased) and nonpregnant (decreased) animals, which suggests that the psychoactive effects of cocaine are influenced by the state of pregnancy. Our findings have clinical implications because they imply that the adverse effects of prenatal cocaine exposure to the newborn child include not only cocaine’s deleterious effects to the placental circulation, but also cocaine’s direct pharmacological effect to the developing fetal brain.

Cocaine is pharmacologically active in the nonhuman primate fetal brain. Benveniste H, Fowler JS, Rooney WD, Scharf BA, Backus WW, Izrailtyan I, Knudsen GM, Hasselbalch SG, Volkow ND. Proc Natl Acad Sci U S A. 2010 Jan 4. [Epub ahead of print] PMID: 20080687

More? UNSW Embryology – Abnormal Development – Illegal Drugs | Neural System Development

Meeting – Controversies in Cryopreservation of Stem Cells, Reproductive Cells, Tissue and Organs (CRYO)

Controversies in Cryopreservation of Stem Cells, Reproductive Cells, Tissue and Organs (CRYO)
Palacio de Congresos, Valencia, Spain, April 22-25, 2010

Scientific Program

(More? UNSW Embryology – Stem Cells)

Teratology – Thalidomide

The UK government has announced additional Support for Thalidomide Survivors

Mr Speaker, I am pleased to report to the House that the government will now fund a £20m, three-year pilot scheme to meet health needs of Thalidomide survivors in a more personalised way.  Funding for this has been found from existing Departmental central contingency budgets.

(More? UNSW Embryology Abnormal Development – Thalidomide)

Womens Health Issues – Cervical Cancer

70% of cervical cancer cases are caused by Human papillomavirus and a new vaccine has been recently developed for Types 6, 11, 16, and 18. In Australia (2006) approval was given to add this vaccination to the Australian vaccination program. In a recent study published in PNAS of a mouse model of HPV-associated cancer, the estrogen receptor alpha (ERalpha) was also required for cancer development and the blocking with estrogen receptor antagonists were effective in treating and/or preventing cervical cancer in these mice.

Prevention and treatment of cervical cancer in mice using estrogen receptor antagonists. Chung SH, Lambert PF. Proc Natl Acad Sci U S A. 2009 Nov 9. [Epub ahead of print] PMID: 19901334

“These data are consistent with the observation in women that long-term use of oral contraceptives or multiple pregnancies significantly increases the risk for cervical cancer in HPV-positive women. In the present study, we examined whether drugs that interfere with the function of ERalpha are effective in treating and/or preventing cervical cancer in mice. We provide evidence that a complete ER antagonist, ICI 182,780 (ICI), as well as a selective ER modulator, raloxifene, efficiently clear cancer and its precursor lesions in both the cervix and the vagina.”

(More? UNSW Embryology – Womens Health Issues | Medline Plus)

Genome sequencing, from $20 million to $4,400 in 3 years

Human Genome Sequencing Using Unchained Base Reads on Self-Assembling DNA Nanoarrays. Drmanac R, Sparks AB, Callow MJ, Halpern AL, Burns NL, Kermani BG, Carnevali P, Nazarenko I, Nilsen GB, Yeung G, Dahl F, Fernandez A, Staker B, Pant KP, Baccash J, Borcherding AP, Brownley A, Cedeno R, Chen L, Chernikoff D, Cheung A, Chirita R, Curson B, Ebert JC, Hacker CR, Hartlage R, Hauser B, Huang S, Jiang Y, Karpinchyk V, Koenig M, Kong C, Landers T, Le C, Liu J, McBride CE, Morenzoni M, Morey RE, Mutch K, Perazich H, Perry K, Peters BA, Peterson J, Pethiyagoda CL, Pothuraju K, Richter C, Rosenbaum AM, Roy S, Shafto J, Sharanhovich U, Shannon KW, Sheppy CG, Sun M, Thakuria JV, Tran A, Vu D, Zaranek AW, Wu X, Drmanac S, Oliphant AR, Banyai WC, Martin B, Ballinger DG, Church GM, Reid CA. Science. 2009 Nov 5. [Epub ahead of print]PMID: 19892942

“Genome sequencing of large numbers of individuals promises to advance the understanding, treatment, and prevention of human diseases, among other applications. We describe a genome sequencing platform that achieves efficient imaging and low reagent consumption with combinatorial probe anchor ligation (cPAL) chemistry to independently assay each base from patterned nanoarrays of self-assembling DNA nanoballs (DNBs). We sequenced three human genomes with this platform, generating an average of 45- to 87-fold coverage per genome and identifying 3.2 to 4.5 million sequence variants per genome. Validation of one genome data set demonstrates a sequence accuracy of about 1 false variant per 100 kilobases. The high-accuracy, affordable cost of $4,400 for sequencing consumables and scalability of this platform enable complete human genome sequencing for the detection of rare variants in large-scale genetic studies.”

Meeting – Cardiac Problems in Pregnancy Feb 26-28, 2010 Valencia, Spain

The First International Meeting on Cardiac Problems in Pregnancy

The goal of “The First International Meeting on Cardiac Problems in Pregnancy” (CPP) is to advance the knowledge and expertise of health care professionals around the globe by exchange of information, development of collaborative research both basic and clinical and establishing guidelines for the management of various cardiovascular conditions during pregnancy and the post partial period.  The CPP Meeting is the first of it’s kind and unique in the collaborative nature, thus ensuring an enriching and informative meeting, which is sure to be enhanced by the beautiful backdrop of Valencia, Spain.

Topics: Physiologic Changes During Normal Pregnancy and the Puerperium, Cardiac Evaluation During Pregnancy, Cardiovascular Imaging in the Pregnant Patient, Congenital Heart Disease and Pregnancy, Valvular Disease and Pregnancy, Pregnancy in the Patients with Artificial Heart Valve, Myocarditis and Pregnancy, Peripartum cardiomyopathy, Hypertrophic Cardiomyopathy and Pregnancy, Pericardial Disorders and Pregnancy, Coronary Artery Disease in the Childbearing Age, Acute Myocardial Infarction and Pregnancy, Cardiac Arrhythmias and pregnancy, Pulmonary Hypertension and Pregnancy, Infective Endocarditis and Pregnancy, Vascular Dissections and Aneurysms During Pregnancy, Marfan Syndrome and Pregnancy, Thromboembolic Disease in Pregnancy, Takayasu’s Arteritis and Pregnancy, Amniotic Fluid Embolism, Hypertension During Pregnancy, Cardiac Surgery During Pregnancy, Analgesia and Anesthesia During Pregnancy, Cardiopulmonary Resuscitation of Pregnant Women, Pregnancy After cardiac Transplantation, Drugs in Pregnancy and Lactation, Diagnosis and Management of Fetal Heart Disease