A New Laser Cytophone Device Able to Find and Destroy Cancer Cells in the Blood ?

In vivo liquid biopsy using Cytophone platform for photoacoustic detection of circulating tumor cells in patients with melanoma

Cancer cells can spread to other parts of the body through the blood. And now, researchers have developed a new kind of laser that can find and zap those tumor cells from the outside of the skin, LiveScience reports, medicalxpress reports and medicaldaily reports.

Abstract

Most cancer deaths arise from metastases as a result of circulating tumor cells (CTCs) spreading from the primary tumor to vital organs. Despite progress in cancer prognosis, the role of CTCs in early disease diagnosis is unclear because of the low sensitivity of CTC assays. We demonstrate the high sensitivity of the Cytophone technology using an in vivo photoacoustic flow cytometry platform with a high pulse rate laser and focused ultrasound transducers for label-free detection of melanin-bearing CTCs in patients with melanoma. The transcutaneous delivery of laser pulses via intact skin to a blood vessel results in the generation of acoustic waves from CTCs, which are amplified by vapor nanobubbles around intrinsic melanin nanoclusters. The time-resolved detection of acoustic waves using fast signal processing algorithms makes photoacoustic data tolerant to skin pigmentation and motion. No CTC-associated signals within established thresholds were identified in 19 healthy volunteers, but 27 of 28 patients with melanoma displayed signals consistent with single, clustered, and likely rolling CTCs. The detection limit ranged down to 1 CTC/liter of blood, which is ~1000 times better than in preexisting assays. The Cytophone could detect individual CTCs at a concentration of ≥1 CTC/ml in 20 s and could also identify clots and CTC-clot emboli. The in vivo results were verified with six ex vivo methods. These data suggest the potential of in vivo blood testing with the Cytophone for early melanoma screening, assessment of disease recurrence, and monitoring of the physical destruction of CTCs through real-time CTC counting.

Environmental Chemicals and Autism

A Scoping Review of the Human and Animal Research, 2019

The Endocrine Disruption Exchange newest scoping review finds that 152 environmental chemicals have been investigated in humans or animals for their association with autism. TEDX highlight the need for systematic review of lead, PCBs, and chlorpyrifos.

Abstract

Background
Estimates of autism prevalence have increased dramatically over the past two decades. Evidence suggests environmental factors may contribute to the etiology of the disorder.

Objectives
This scoping review aimed to identify and categorize primary research and reviews on the association between prenatal and early postnatal exposure to environmental chemicals and the development of autism in epidemiological studies and rodent models of autism.

Methods
PubMed was searched through 8 February 2018. Included studies assessed exposure to environmental chemicals prior to 2 months of age in humans or 14 d in rodents. Rodent studies were considered relevant if they included at least one measurement of reciprocal social communicative behavior or repetitive and stereotyped behavior. Study details are presented in interactive displays using Tableau Public.

Results
The search returned 21,603 unique studies, of which 54 epidemiological studies, 46 experimental rodent studies, and 50 reviews were deemed relevant, covering 152 chemical exposures. The most frequently studied exposures in humans were particulate matter (n=14), mercury (n=14), nonspecific air pollution (n=10), and lead (n=10). In rodent studies, the most frequently studied exposures were chlorpyrifos (n=9), mercury (n=6), and lead (n=4).

Discussion
Although research is growing rapidly, wide variability exists in study design and conduct, exposures investigated, and outcomes assessed. Conclusions focus on recommendations to guide development of best practices in epidemiology and toxicology, including greater harmonization across these fields of research to more quickly and efficiently identify chemicals of concern. In particular, we recommend chlorpyrifos, lead, and polychlorinated biphenyls (PCBs) be systematically reviewed in order to assess their relationship with the development of autism. There is a pressing need to move forward quickly and efficiently to understand environmental influences on autism in order to answer current regulatory questions and inform treatment and prevention efforts.

The effects of an EDCs cocktail of BPA + DES + NP

Analysis of individual and combined estrogenic effects of bisphenol, nonylphenol and diethylstilbestrol in immature rats with mathematical models

2019 Study Abstract

Background
Traditional toxicological studies focus on individual compounds. However, this single-compound approach neglects the fact that the mixture exposed to human may act additively or synergistically to induce greater toxicity than the single compounds exposure due to their similarities in the mode of action and targets. Mixture effects can occur even when all mixture components are present at levels that individually do not produce observable effects. So the individual chemical effect thresholds do not necessarily protect against combination effects, an understanding of the rules governing the interactive effects in mixtures is needed. The aim of the study was to test and analyze the individual and combined estrogenic effects of a mixture of three endocrine disrupting chemicals (EDCs), bisphenol A (BPA), nonylphenol (NP) and diethylstilbestrol (DES) in immature rats with mathematical models.

Method
In the present study, the data of individual estrogenic effects of BPA, NP and DES were obtained in uterotrophic bioassay respectively, the reference points for BPA, NP and DES were derived from the dose-response ralationship by using the traditional no observed adverse effect (NOAEL) or lowest observed adverse effect level (LOAEL) methods, and the benchmark dose (BMD) method. Then LOAEL values and the benchmark dose lower confidence limit (BMDL10) of single EDCs as the dose design basis for the study of the combined action pattern. Mixed prediction models, the 3 × 2 factorial design model and the concentration addition (CA) model, were employed to analyze the combined estrogenic effect of the three EDCs.

Results
From the dose-response relationship of estrogenic effects of BPA, NP and DES in the model of the prepuberty rats, the BMDL10(NOAEL) of the estrogenic effects of BPA, NP and DES were 90(120) mg/kg body weight, 6 mg/kg body weight and 0.10(0.25) μg/kg body weight, and the LOAEL of the the estrogenic effects of three EDCs were 240 mg/kg body weight, 15 mg/kg body weight and 0.50 μg/kg body weight, respectively. At BMDL10 doses based on the CA concept and the factorial analysis, the mode of combined effects of the three EDCs were dose addition. Mixtures in LOAEL doses, NP and DES combined effects on rat uterine/body weight ratio indicates antagonistic based on the CA concept but additive based on the factorial analysis. Combined effects of other mixtures are all additive by using the two models.

Conclusion
Our results showed that CA model provide more accurate results than the factorial analysis, the mode of combined effects of the three EDCs were dose addition, except mixtures in LOAEL doses, NP and DES combined effects indicates antagonistic effects based on the CA model but additive based on the factorial analysis. In particular, BPA and NP produced combination effects that are larger than the effect of each mixture component applied separately at BMDL doses, which show that additivity is important in the assessment of chemicals with estrogenic effects. The use of BMDL as point of departure in risk assessment may lead to underestimation of risk, and a more balanced approach should be considered in risk assessment.

References

  • Full study (free access) : Analysis of individual and combined estrogenic effects of bisphenol, nonylphenol and diethylstilbestrol in immature rats with mathematical models, Environmental health and preventive medicine, NCBI PubMed PMC6515622, 2019 May 13.
  • Image credit Helena Yankovska.
DES DiEthylStilbestrol Resources

The James Lind Library’s Introduction to Fair Tests of Treatments

JLL Book of Essays, About Fair Tests, May 2019

Introduction

At various times in our lives and to varying levels of intensity, we all use, provide or pay for health and social care. As we decide what to do, take, offer or buy, we need evidence that is reliable, robust and trustworthy about different options. Even before James Lind’s experiment comparing possible treatments for scurvy on HMS Salisbury people had recognised that getting this evidence requires strenuous efforts to reduce bias –but that achieving this is often not straightforward. This book of essays from the James Lind Library is our attempt to illustrate some of the challenges encountered and how to overcome them.

We will take you on a journey through the sometimes stormy waters of why treatments need to be tested, rather than being based on assumptions that “it must work” before the treatment has even been tried, or based on impressions after it has been used a few times, through to the need for fair tests comparing alternative treatment options. We will show why genuine uncertainties must be identified and addressed, and how research to find the most effective and appropriate treatments need to build on research to identify the most effective and appropriate methods for doing that research. We will navigate through the reasons why comparisons need to be fair at the outset, and then kept fair as the treatments being tested are given;outcomes are measured;and results are analysed, reported, and combined in systematic reviews of all the relevant, trustworthy evidence.

We have not cluttered the chapters with references to all the source material on which we have drawn. For that level of detail, please follow the links to the fuller essays on the James Lind Library website. Instead, where we know of reviews of methodology research which are relevant to a topic, we have listed these at the end of each chapter.

By the end of the book, we hope that you will recognise how, to bring benefits of research to patients and the public, systematic reviews of fair tests are needed to provide key elements of the knowledge needed to inform decisions about health and social care, while taking into account other important factors, such as values, preferences, needs, resources and priorities. We also hope that, as you finish the book, you will share the sense of enlightenment, education and enjoyment that we have gained from preparing it.

Finally, we dedicate this book to England’s National Institute for Health Research. Without the Institute’s 16-year-long support for the James Lind Initiative, the home of the James Lind Library during that time, neither the Library nor these essays would have been possible. And we also wish to acknowledge the role the Institute plays in recognising the vital contribution of research to the delivery of health and social care that is effective and efficient, and the Institute’s leadership in ensuring that the research itself is effective, efficient and reliable, with minimal waste.

Abstract

1.3 Why treatment comparisons must be fair

Untrustworthy treatment comparisons are those in which biases, or the play of chance, or both result in misleading estimates of the effects of treatments. Fair treatment comparisons avoid biases and reduce the effects of the play of chance.

It is not only failure to test theories about treatments in practice that has caused preventable tragedies. They have also occurred because the tests used to assess the effects of treatments have been unreliable and misleading. In the 1950s, theory and poorly controlled tests yielded unreliable evidence suggesting that diethylstilboestrol (DES) helped pregnant women who had previously had miscarriages and stillbirths. Although fair tests suggested that DES was useless, theory and unreliable evidence, together with aggressive marketing, led to DES being prescribed to millions of pregnant women over the next few decades. The consequences were disastrous for the women and their children, who experienced infertility and cancers as a result. The lesson is that a treatment that has not been reliably shown to be useful should not be promoted.

Problems resulting from inadequate tests of treatments continue to occur. Again, because of unreliable evidence and aggressive marketing, millions of women were persuaded to use hormone replacement therapy (HRT). It was claimed that, not only could it reduce unpleasant menopausal symptoms, but also the chances of having heart attacks and strokes. When these claims were assessed in fair tests, the results showed that in women over 60, far from reducing the risks of heart attacks and strokes, HRT increases the risks of these life-threatening conditions, as well as having other undesirable effects.These examples of the need for fair tests of treatments are a few of many that illustrate how treatments can do more harm than good. Improved general knowledge about fair tests of treatments is needed so that –laced with a healthy dose of scepticism –we can all assess claims about the effects of treatments more critically. That way, we will all become more able to judge which treatments are likely to do more good than harm.

DES DiEthylStilbestrol Resources

Dealing with strategies used by industry to influence scientific evidence

Commercial interests, transparency, and independence: a call for submissions

Help the move towards independence from commercial interests

A decade ago the US Institute of Medicine (IOM) issued a landmark report on conflicts of interest in research, medical education, and practice.1 Highlighting benefits of collaborations between physicians, researchers, and companies to develop new products that can improve health, the report also raised substantial concerns that extensive financial ties could unduly influence professional judgments. It concluded these financial conflicts of interest could jeopardise the integrity of science, the objectivity of education, the quality of care, and public trust in medicine. The report recommended more research on conflicts of interest, improvements in transparency, and greater independence from industry.

Today we announce plans for a stream of BMJ content to revisit these concerns and ask you to join us. A key aim is to identify and respond to commercial influences on health and healthcare, to understand under what circumstances involvement with industry is truly necessary. Where it is not necessary, we want to forge a new independence from those who make and sell products, to strengthen trust in how evidence is produced and disseminated, and to drive more rational and safer use of drugs, devices, diagnoses, and data in the public interest.

Key Points

  • Problematic relationships
  • The BMJ’s response so far
  • Call for submissions

Read

Primodos Drug Cover-Up : Marie Lyon Talks, 2017

Marie Lyon, Chair of the ACDHPT, on Primodos pregnancy testing drug evidence

Hundreds of UK families have been battling for compensation over claims hormone-based drug ‘Primodos’ led to severe birth defects.

Reference : nzherald, 7:00 AM, 20 Mar 2017.

More information

  • All our posts tagged primodos. More than 60 videos ref primodos.
  • Studies :
    • Read and/or download the full study (free access) Oral hormone pregnancy tests and the risks of congenital malformations: a systematic review and meta-analysis, F1000Research, First published 31 Oct 2018, 7:1725, DOI:10.12688/f1000research.16758.1.
    • Read and/or download the full study (free access) The Primodos components Norethisterone acetate and Ethinyl estradiol induce developmental abnormalities in zebrafsh embryos, nature, Published 13 Feb 2018, DOI:10.1038/s41598-018-21318-9.
  • To read some real stories told by the Primodos victims, see this post comment section.

Primodos Drug Cover-Up : Hannah Bardell MP Talks, 2017

Hannah Bardell MP on dual use of Primodos

Primodos used in one country as an abortive and in another as a pregnancy test “beggars belief”.

Reference : Sky News Tonight, 8:48 PM, 21 Mar 2017.

More information

  • All our posts tagged primodos. More than 60 videos ref primodos.
  • Studies :
    • Read and/or download the full study (free access) Oral hormone pregnancy tests and the risks of congenital malformations: a systematic review and meta-analysis, F1000Research, First published 31 Oct 2018, 7:1725, DOI:10.12688/f1000research.16758.1.
    • Read and/or download the full study (free access) The Primodos components Norethisterone acetate and Ethinyl estradiol induce developmental abnormalities in zebrafsh embryos, nature, Published 13 Feb 2018, DOI:10.1038/s41598-018-21318-9.
  • To read some real stories told by the Primodos victims, see this post comment section.

Primodos Drug Cover-Up : Prof. John Abraham Talks, 2017

Medicines expert: We need parliament to help Primodos investigation

Medicines expert Professor John Abraham said Parliament might need to get involved to help release thousands of documents on Primodos.

Reference : Sky News Tonight, 8:41 PM, 21 March 2017.

More information

  • All our posts tagged primodos. More than 60 videos ref primodos.
  • Studies :
    • Read and/or download the full study (free access) Oral hormone pregnancy tests and the risks of congenital malformations: a systematic review and meta-analysis, F1000Research, First published 31 Oct 2018, 7:1725, DOI:10.12688/f1000research.16758.1.
    • Read and/or download the full study (free access) The Primodos components Norethisterone acetate and Ethinyl estradiol induce developmental abnormalities in zebrafsh embryos, nature, Published 13 Feb 2018, DOI:10.1038/s41598-018-21318-9.
  • To read some real stories told by the Primodos victims, see this post comment section.

IMMDS Review listens to Professor John Abraham about Primodos

Independent Medicines and Medical Devices Safety Review Oral Hearing, 27th November 2018

The Independent Medicines and Medical Devices Safety Review is Chaired by Baroness Julia Cumberlege CBE DL.

In February 2018, the Secretary of State for Health and Social Care, the Rt Hon Jeremy Hunt MP, announced a review into how the health system responds to reports from patients about harmful side effects from medicines and medical devices. The announcement in the House of Commons follows patient-led campaigns on the use of the hormone pregnancy test Primodos, anti-epileptic drug sodium valproate and surgical mesh.

About Primodos

  • Read and/or download the full study (free access) Oral hormone pregnancy tests and the risks of congenital malformations: a systematic review and meta-analysis, F1000Research, First published 31 Oct 2018, 7:1725, DOI:10.12688/f1000research.16758.1.
  • Read and/or download the full study (free access) The Primodos components Norethisterone acetate and Ethinyl estradiol induce developmental abnormalities in zebrafsh embryos, nature, Published 13 Feb 2018, DOI:10.1038/s41598-018-21318-9.
  • To read some real stories told by the Primodos victims, go to this post comment section.  Read our posts tagged primodos.

IMMDS Review listens to Dr Jesse Olszynko-Gryn about Primodos

Independent Medicines and Medical Devices Safety Review Oral Hearing, 26th November 2018

The Independent Medicines and Medical Devices Safety Review is Chaired by Baroness Julia Cumberlege CBE DL.

In February 2018, the Secretary of State for Health and Social Care, the Rt Hon Jeremy Hunt MP, announced a review into how the health system responds to reports from patients about harmful side effects from medicines and medical devices. The announcement in the House of Commons follows patient-led campaigns on the use of the hormone pregnancy test Primodos, anti-epileptic drug sodium valproate and surgical mesh.

About Primodos

  • Read and/or download the full study (free access) Oral hormone pregnancy tests and the risks of congenital malformations: a systematic review and meta-analysis, F1000Research, First published 31 Oct 2018, 7:1725, DOI:10.12688/f1000research.16758.1.
  • Read and/or download the full study (free access) The Primodos components Norethisterone acetate and Ethinyl estradiol induce developmental abnormalities in zebrafsh embryos, nature, Published 13 Feb 2018, DOI:10.1038/s41598-018-21318-9.
  • To read some real stories told by the Primodos victims, go to this post comment section.  Read our posts tagged primodos.