Dissenting Diagnosis

Voices of Conscience from the Medical Profession

dissenting diagnosis book cover image
Dissenting Diagnosis,
Voices of Conscience from the Medical Profession, by Dr Arun Gadre and Dr Abhay Shukla.

Complaints about the state of medical care are increasing in today s India; whether it s unnecessary investigations, botched operations or expensive, sometimes even harmful, medication. But while the unease is widespread, few outside the profession understand the extent to which the medical system is being distorted.

Dr Arun Gadre and Dr Abhay Shukla have gathered evidence from seventy-eight practising doctors, in both the private and public medical sectors, to expose the ways in which vulnerable patients are exploited by a system that promotes unscrupulous medical practices. At a time when the medical sector is growing rapidly, especially in urban areas, with the proliferation of multi-specialty hospitals and the adoption of ever-more sophisticated technologies, rational and ethical medical care is becoming increasingly rare. Honest doctors feel under siege, professional bodies meant to regulate the medical sector fail to do so, and the influence of the powerful pharmaceutical industry becomes even more pervasive.

Drawing on the frank and courageous statements of these seventy-eight doctors dismayed at the state of their profession, Dissenting Diagnosis lays bare the corruption afflicting the medical sector in India and sets out solutions for a healthier future.

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  • Read How Pharmaceutical Companies Entice Doctors Into Prescribing Expensive Medication, the Caravan, 16 April 2016.
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Perinatal Exposure to DES Increases the Susceptibility to Develop Mammary Gland Lesions after Estrogen Replacement Therapy

Hormones and Cancer, April 2017, Volume 8, Issue 2, pp 78–89

2017 Study Abstract

The development of the mammary gland is a hormone-regulated event.

Several factors can dysregulate its growth and make the gland more susceptible to cellular transformation.

Among these factors, perinatal exposure to xenoestrogens and hormone replacement therapy has been associated with increased risk of developing breast cancer.

Perinatal Exposure to Bisphenol A or Diethylstilbestrol Increases the Susceptibility to Develop Mammary Gland Lesions After Estrogen Replacement Therapy in Middle-Aged Rats, US National Library of Medicine National Institutes of Health, Hormones and Cancer, April 2017, Volume 8, Issue 2, pp 78–89, NCBI PubMed PMID: 28078498, 2017 Apr 8.

Here, we assessed the effects induced by estrogen replacement therapy (ERT) in ovariectomized (OVX) middle-aged rats and whether perinatal exposure to diethylstilbestrol (DES) or bisphenol A (BPA) modified these effects in the mammary gland.

Pregnant rats were orally exposed to vehicle, 5 μg DES/kg/day, or 0.5 or 50 μg BPA/kg/day from gestational day 9 until weaning. Then, 12-month-old offspring were OVX and treated with 17β-estradiol for 3 months.

Morphological changes and the percentage of epithelial cells that proliferated or expressed estrogen receptor alpha (ESR1) and progesterone receptor (PR) were analyzed in mammary gland samples of 15-month-old animals.

ERT induced lobuloalveolar hyperplasia and ductal cysts in the mammary gland of middle-aged rats, associated with a higher proliferation index of epithelial cells.

Perinatal exposure to DES followed by ERT increased the number of cysts and induced the formation of fibroadenoma and ductal carcinoma in situ, without modifying the expression of ESR1 or PR.

Also, after 3 months of ERT, BPA-exposed rats had a higher incidence of ductal hyperplasia and atypical lobular hyperplasia than animals under ERT alone.

In conclusion, perinatal exposure to xenoestrogens increases the susceptibility of the mammary gland to develop cysts and hyperplastic lesions when confronted with ERT later in life.

More DES DiEthylStilbestrol Resources

Mothers need to limit their consumption of added sugars when breastfeeding

From mother to baby: ‘Secondhand sugars’ can pass through breast milk

A new study by researchers at the Keck School of Medicine of USC indicates that a “secondhand sugar” – derived from a mom’s diet – is passed from mother to infant through breast milk.

Even a small amount of fructose – a sweetener linked to health issues ranging from obesity to diabetes – in breast milk is associated with increases in a baby’s body weight.

2017 Study Abstract

Fructose in Breast Milk Is Positively Associated with Infant Body Composition at 6 Months of Age, Nutrients, doi:10.3390/nu9020146, 16 February 2017.

From mother to baby: ‘Secondhand sugars’ can pass through breast milk, news.usc.edu, MARCH 2, 2017.

Cake credit waferboard.

Dietary sugars have been shown to promote excess adiposity among children and adults; however, no study has examined fructose in human milk and its effects on body composition during infancy.

Twenty-five mother–infant dyads attended clinical visits to the Oklahoma Health Sciences Center at 1 and 6 months of infant age. Infants were exclusively breastfed for 6 months and sugars in breast milk (i.e., fructose, glucose, lactose) were measured by Liquid chromatography-mass spectrometry (LC-MS/MS) and glucose oxidase. Infant body composition was assessed using dual-energy X-ray absorptiometry at 1 and 6 months. Multiple linear regression was used to examine associations between breast milk sugars and infant body composition at 6 months of age. Fructose, glucose, and lactose were present in breast milk and stable across visits (means = 6.7 μg/mL, 255.2 μg/mL, and 7.6 g/dL, respectively).

Despite its very low concentration, fructose was the only sugar significantly associated with infant body composition. A 1-μg/mL higher breast milk fructose was associated with a 257 g higher body weight (p = 0.02), 170 g higher lean mass (p = 0.01), 131 g higher fat mass (p = 0.05), and 5 g higher bone mineral content (p = 0.03).

Conclusion

Overall, this study suggests a novel mechanism by which infants may be inadvertently exposed to fructose through breast milk, before sugar sweetened beverages and other fructose-containing foods are introduced to the infant diet.

This work also opens the door for interventions aimed towards decreased consumption of added sugars while lactating.

Future work should be performed with larger samples with longer follow-up (>6 months) in order to establish whether the relationships observed between fructose exposure and infant growth meaningfully impact the development of obesity phenotypes in later childhood and to investigative the mechanism of such an effect at very low levels of fructose.

In conclusion, we provide preliminary evidence that fructose is present in breast milk and may be transmitted to the infant, impacting growth and body composition by 6 months of age.

Can non-daytime shifts and physically demanding jobs decrease women’s fertility?

Indeed : heavy lifting, shift work could affect women’s fertility

Women who lift heavy loads at work may experience decreased fertility, and the effect appears stronger among overweight or obese women and older women, according to a new study from Harvard T.H. Chan School of Public Health.

Working non-daytime work schedules may also decrease fertility, the researchers found. 

2017 Study Abstract

Objectives
To explore whether work schedules and physically demanding work were associated with markers of ovarian reserve and response.

Methods
This analysis included women (n=473 and n=313 for ovarian reserve and ovarian response analysis, respectively) enrolled in a prospective cohort study of couples presenting to an academic fertility centre (2004–2015). Information on occupational factors was collected on a take-home questionnaire, and reproductive outcomes were abstracted from electronic medical records. Generalised linear models and generalised linear mixed models were used to evaluate the associations.

Occupational factors and markers of ovarian reserve and response among women at a fertility centre, BMJ, dx.doi.org/10.1136/oemed-2016-103953, 6 February 2017.

Results
Women who reported lifting or moving heavy objects at work had 1.0 fewer total oocytes (p=0.08), 1.4 fewer mature oocytes (p=0.007) and 0.7 fewer antral follicles (p=0.06) compared with women who reported never lifting or moving heavy objects at work. The inverse association between heavy lifting and oocyte yield was stronger in women >37 years and with a Body Mass Index ≥25 kg/m2. Women who worked evening/night/rotating shifts had 2.3 (p<0.001) fewer mature oocytes, on average, compared with women who worked day-only shifts. None of the occupational exposures were associated with day 3 follicle-stimulating hormone or peak oestradiol levels.

Conclusions
Women working non-daytime shifts and those with physically demanding jobs had fewer mature oocytes retrieved after controlled ovarian hyperstimulation. Our results provide insight into possible mechanisms linking these occupational exposures with decreased fecundity.

Mother’s diet in pregnancy may have lasting effects for offspring

Visualizing Changes in Cdkn1c Expression Links Early-Life Adversity to Imprint Mis-regulation in Adults

A poor diet during pregnancy can cause biological changes that last throughout life, according to research from Imperial College London.

The study Visualizing Changes in Cdkn1c Expression Links Early-Life Adversity to Imprint Mis-regulation in Adults, published this week in the journal Cell Reports, showed that when pregnant mice were fed a diet deficient in protein this interfered with the expression of genes within the embryo that are known to be important for healthy growth.

The impact of adversity, such as a poor diet in early life, and whether this might cause lasting effects has long intrigued scientists. There have been suggestions that the children of women pregnant during famines, for example, may suffer harmful effects later in life. This new study offers a new way to visualise such effects and possible ways to counter these.

The researchers, at the Medical Research Council London Institute of Medical Sciences (MRC LMS), developed novel imaging techniques that enabled them to visualise genes as they were switched “on” or “off” in mouse embryos as they grew. This enabled the team to see exactly where alterations in response to maternal diet were happening and, crucially when during pregnancy key changes took place.

Understanding how genes are controlled and kept “on” or “off” is a relatively new field of science known as “epigenetics”. This is the first time such epigenetic effects have been visualised during development in this way, using a simple but powerful bioluminescent imaging approach.

The team attached enzymes from fireflies (luciferase) or bacteria (beta-galactosidase) onto the gene they were studying, and watched how this produced a glow as the gene was turned “on” in mice.

The research focused on a group of genes called “imprinted” genes, and on one in particular known as Cdkn1c. Imprinted genes are intriguing because although a copy of the gene is inherited from each parent, as usual, only one of these copies is active. The other copy is kept idle, or “silenced”. In the case of Cdkn1c, only the copy inherited from the mother is active.

Using their new visualising technique, the team showed that if a mouse carried the copy of the gene from the father, which is “silenced”, then it could not be seen. If they used either diet or drugs to re-activate it, they were able to see the gene glow. The researchers expect that this new way to “see” when imprinted genes are active or silent will prove valuable for many other scientists who are investigating epigenetic effects in our bodies.

Imprinted genes

Dr Mathew Van de Pette, a lead author based at the MRC LMS, said:

“There are around 100 imprinted genes, about 0.4% of the total in the genome, and most appear to have their greatest impact during pregnancy.
The pattern by which imprinted genes are ‘set’ in early life plays an important part in the development of healthy offspring. If a gene is ‘miss-set’ then problems may occur later.
We found that mice fed a low protein diet in pregnancy produced offspring in which the father’s copy of the gene became active and stayed that way. This demonstrates a clear link between early life adversity and later life outcomes.”

Professor Amanda Fisher, who led the study and is director of the MRC LMS, said:

“We were surprised that this change in diet permanently affected the expression of this imprinted gene.
Our work suggests there may be a window of vulnerability when diet can indeed have an effect, and that once these genes are set, they’re set for life.
The good news is that we’ve also shown that it’s possible to avoid this with a normal diet.”

Kate Wighton, Imperial College London newssummary, 03 February 2017.

Are your new generation breast implants, in fact, poisoning you?

Destiny rides again: the reappearance of silicone gel-filled breast implant toxicity

2017 Study Abstract

Background
Twenty-five years ago attorneys representing ailing women in class action litigation against silicone breast implant manufacturers made the procedural error of defining silicone-induced toxicity in the courtroom before it was properly studied in the exam room. This aberrant methodology perverted the proper research process, rendered verification of any real disease elusive, and cemented the groundwork for a repeat public health crisis potentially affecting two million women in the USA who possess new silicone gel devices inserted over the past 10 years.

Destiny rides again: the reappearance of silicone gel-filled breast implant toxicity, SAGE Publications, doi/full/10.1177/0961203317690241, January 29, 2017.

Image credit Sergio Moraes.

Patients and methods
Six women, previously well, aged 27 to 53 (mean 42), were recipients of the new generations of cohesive silicone gel-filled breast implants approved for general use by the Food and Drug Administration (FDA) since December of 2006. They averaged seven years of total implantation time, and none experienced implant rupture.

Results
All six became ill on average 3.5 years from the time of implantation. By seven years the women manifested multiple types of skin rashes, polyarthritis, fatigue, protracted AM stiffness, myalgias, headaches, photosensitivity, hair loss, paresthesias, tinnitus, lymphadenopathy, chest pain, cognitive dysfunction, dry eyes, skin pigment changes, itching, muscle twitching, dizziness, nausea, easy bruising, and odor and smell sensitivity. Three of the four who were explanted noted improvement and/or resolution of at least 50% of their total disease manifestations.

Conclusions
These six women are representative of over 70,000 other breast implant recipients who, over the past three years, have had their new silicone devices permanently removed because of alleged gel-induced toxicity. The recurrence of this public health crisis has been fueled by manufacturers’ research fraud, FDA ineptness, faulty informed consent, patient abandonment, proprietary manufacturing secrecy, misleading advertising, physician indifference, aberrant research methodology, and lax Congressional oversight.

Download the full study PDF.

Impact of prenatal exposure to diethylstilbestrol (DES) on psychological outcome

A national survey of DES daughters and unexposed controls

2017 Study Abstract

To explore whether prenatal exposure to diethylstilbestrol (DES) is associated with increased risk of poor psychological outcome independently of the occurrence of major somatic complications related to DES exposure.

Data on health outcome were collected in women prenatally exposed to DES (n = 2566) and unexposed women (n = 2967) recruited in a French national survey.

Women prenatally exposed to DES were 1.7 times more likely to have consulted a mental health specialist compared to unexposed women (adjusted odds ratio = 1.69, 95% confidence interval 1.47-1.96), independently of demographic characteristics, poor gynecological or obstetrical outcome, or history of cancer.

Impact of prenatal exposure to diethylstilbestrol (DES) on psychological outcome: a national survey of DES daughters and unexposed controls, US National Library of Medicine National Institutes of Health, Archives of women’s mental health, NCBI PubMed PMID: 28064340, 2017 Jan 7.

Image credit Alessandra.

Frequency of consultation with a mental health specialist in persons with a history of gynecological complications or cancer was comparable in women prenatally exposed to DES and unexposed women.

Findings regarding psychological outcome obtained in the high-risk group of women prenatally exposed to DES may contribute to improving identification of psychological needs of all women presenting with gynecological abnormalities.

More DES DiEthylStilbestrol Resources

Link between early menstruation and early menopause

Starting periods at a young age is linked to early menopause

Women are more likely to go through menopause early if they started menstruating before their 12th birthday.

This is the conclusion of the largest study of its kind, involving 50,000 postmenopausal women in the UK, Australia, Japan and Scandinavia.

2017 Study Abstract

STUDY QUESTION
Are parity and the timing of menarche associated with premature and early natural menopause?

SUMMARY ANSWER
Early menarche (≤11 years) is a risk factor for both premature menopause (final menstrual period, FMP

WHAT IS KNOWN ALREADY
Women with either premature or early menopause face an increased risk of chronic conditions in later life and of early death. Findings from some studies suggest that early menarche and nulliparity are associated with early menopause, however overall the evidence is mixed. Much of the evidence for a direct relationship is hampered by a lack of comparability across studies, failure to adjust for confounding factors and inadequate statistical power.

Early menarche, nulliparity and the risk for premature and early natural menopause, Oxford University Press, doi.org/10.1093/humrep/dew350, 25 January 2017.

Image credit Texas.713.

STUDY DESIGN, SIZE, DURATION
This pooled study comprises 51 450 postmenopausal women from nine observational studies in the UK, Scandinavia, Australia and Japan that contribute to the International collaboration for a Life course Approach to reproductive health and Chronic disease Events (InterLACE).

PARTICIPANTS/MATERIALS, SETTING, METHODS
Age at menarche (categorized as ≤11, 12, 13, 14 and 15 or more years) and parity (categorized as no children, one child and two or more children) were exposures of interest. Age at FMP was confirmed by at least 12 months of cessation of menses where this was not the result of an intervention (such as surgical menopause due to bilateral oophorectomy or hysterectomy) and categorized as premature menopause (FMP before age 40), early menopause (FMP 40–44 years), 45–49 years, 50–51 years, 52–53 years and 54 or more years. We used multivariate multinomial logistic regression models to estimate relative risk ratio (RRR) and 95% CI for associations between menarche, parity and age at FMP adjusting for within-study correlation.

MAIN RESULTS AND THE ROLE OF CHANCE
The median age at FMP was 50 years (interquartile range 48–53 years), with 2% of the women experiencing premature menopause and 7.6% early menopause. Women with early menarche (≤11 years, compared with 12–13 years) were at higher risk of premature menopause (RRR 1.80, 95% CI 1.53–2.12) and early menopause (1.31, 1.19–1.44). Nulliparity was associated with increased risk of premature menopause (2.26, 1.84–2.77) and early menopause (1.32, 1.09–1.59). Women having early menarche and nulliparity were at over 5-fold increased risk of premature menopause (5.64, 4.04–7.87) and 2-fold increased risk of early menopause (2.16, 1.48–3.15) compared with women who had menarche at ≥12 years and two or more children.

LIMITATIONS, REASONS FOR CAUTION
Most of the studies (except the birth cohorts) relied on retrospectively reported age at menarche, which may have led to some degree of recall bias.

WIDER IMPLICATIONS OF THE FINDINGS
Our findings support early monitoring of women with early menarche, especially those who have no children, for preventive health interventions aimed at mitigating the risk of adverse health outcomes associated with early menopause.

STUDY FUNDING/COMPETING INTEREST(S)
InterLACE project is funded by the Australian National Health and Medical Research Council project grant (APP1027196). G.D.M. is supported by Australian Research Council Future Fellowship (FT120100812). There are no competing interests.

High body mass index during pregnancy not associated with a long term risk of obesity in offspring

High Pregnancy BMI Not Linked to Offspring BMI

This new study looked at whether increased body mass index (BMI) in mothers while pregnant was causally associated with excess weight in offspring during childhood and adolescence. It also examined whether this effect was over and above the expected contribution of genes to being overweight.

2017 Study Abstract

Background

It has been suggested that greater maternal adiposity during pregnancy affects lifelong risk of offspring fatness via intrauterine mechanisms. Our aim was to use Mendelian randomisation (MR) to investigate the causal effect of intrauterine exposure to greater maternal body mass index (BMI) on offspring BMI and fat mass from childhood to early adulthood.

Methods and Findings

Using Genetic Variation to Explore the Causal Effect of Maternal Pregnancy Adiposity on Future Offspring Adiposity: A Mendelian Randomisation Study, PLOS one, dx.doi.org/10.1371/journal.pmed.1002221, January 24, 2017.

Image credit remon rijper.

We used maternal genetic variants as instrumental variables (IVs) to test the causal effect of maternal BMI in pregnancy on offspring fatness (BMI and dual-energy X-ray absorptiometry [DXA] determined fat mass index [FMI]) in a MR approach. This was investigated, with repeat measurements, from ages 7 to 18 in the Avon Longitudinal Study of Parents and Children (ALSPAC; n = 2,521 to 3,720 for different ages). We then sought to replicate findings with results for BMI at age 6 in Generation R (n = 2,337 for replication sample; n = 6,057 for total pooled sample).

In confounder-adjusted multivariable regression in ALSPAC, a 1 standard deviation (SD, equivalent of 3.7 kg/m2) increase in maternal BMI was associated with a 0.25 SD (95% CI 0.21–0.29) increase in offspring BMI at age 7, with similar results at later ages and when FMI was used as the outcome.

A weighted genetic risk score was generated from 32 genetic variants robustly associated with BMI (minimum F-statistic = 45 in ALSPAC). The MR results using this genetic risk score as an IV in ALSPAC were close to the null at all ages (e.g., 0.04 SD (95% CI -0.21–0.30) at age 7 and 0.03 SD (95% CI -0.26–0.32) at age 18 per SD increase in maternal BMI), which was similar when a 97 variant generic risk score was used in ALSPAC.

When findings from age 7 in ALSPAC were meta-analysed with those from age 6 in Generation R, the pooled confounder-adjusted multivariable regression association was 0.22 SD (95% CI 0.19–0.25) per SD increase in maternal BMI and the pooled MR effect (pooling the 97 variant score results from ALSPAC with the 32 variant score results from Generation R) was 0.05 SD (95%CI -0.11–0.21) per SD increase in maternal BMI (p-value for difference between the two results = 0.05). A number of sensitivity analyses exploring violation of the MR results supported our main findings. However, power was limited for some of the sensitivity tests and further studies with relevant data on maternal, offspring, and paternal genotype are required to obtain more precise (and unbiased) causal estimates.

Conclusions

Our findings provide little evidence to support a strong causal intrauterine effect of incrementally greater maternal BMI resulting in greater offspring adiposity.

14 Filles Distilbène, telles qu’elles sont…

3’35 pour “parler” autrement du DES…

Vidéo publiée le 13 janvier 2017 par la chaine Association Réseau DES FRANCE DISTILBENE.

Une série de portraits de femmes touchées, traversées, abîmées par le Distilbène DES.

“Je veux que chaque femme touchée par le DES dans le monde puisse s’y retrouver : française, américaine, australienne, hollandaise, africaine, allemande… Je veux que ce témoignage muet soit entendu dans toutes les langues par toutes les cultures. Je souhaite qu’il permette aux femmes qui y participeront de déposer quelque chose derrière la caméra et de repartir plus légères et fières du courage qu’elles ont eu à le faire. Je veux que la gravité et la beauté de ces visages sans mots résonnent puissamment aux oreilles des lobby, dans les couloirs de la commission européenne, dans l’antichambre des tribunaux où se rejoue David contre Goliath à chaque procès de ‘fille DES’ “

Laetitia Dormoy, créatrice du projet.
Sources : la chronique de Marie Darrieussecq.

Le Distilbène DES, en savoir plus