Sights:The scorching heat, the pickets, the helicopter, the blank stares of bus loads of apprehensive People’s Liberation Army soldiers surrounded by Beijing’s irate mothers and fathers, the water tankers, the chuandan (pamphlets), the handwritten messages on the school noticeboard, real tears, fleeing, panic, emptiness, dry tears, bloated bodies. How many more?
Tastes: Dry, salty and bitter.
Time:Central Beijing –3.45pm Saturday June 3, 1989, the first time I heard the traumatising sounds of teargas canisters exploding all around me, gunfire. A wave of spine-chilling panic and astonishment shuddered through the maddened crowd.
“Look at what the People’s Liberation Army are using against the people”, said my local friend.
I was standing near Zhongnanhai, the Communist Party of China and central government’s seat of power. Nine hours later from the safety of my dormitory my eyes were fixed on the horizon where a menacing, murky pall of orange hung over downtown Beijing. June 4, 1989, one month, two weeks, six days since the popular student-led ‘nothing to my name’ [Read more at: http://wp.me/p15Yzr-19] demonstrations began in Tiananmen Square. All was eerily quiet in the immediate vicinity, but we knew, the rumour machine knew, and it wasn’t long before the first of the bloated purples would be carried back to the campus. No wailing, just lifeless silence.
The most dramatic and formative event of my life, all permanently etched in my mind as if it was yesterday.
“You missed Woodstock” said my brother upon my return home.
In August 1969, forty-nine years ago this Summer, during the height of the Vietnam War, and a year after the assassinations of Dr. Martin Luther King and Robert Kennedy, a 450,000-strong hippie commune established itself at the Woodstock Music and Art Fair to hear rock legends the Rolling Stones’ “You Can’t Always Get What You Want” “Gimmie Shelter” and a feast of other rock bands belt out some of the most powerful rock music ever written. Braving rain, mud, heat, cold, poor sanitation, and food shortages it was just another typical rock concert they were all going to. None of them had come in search of a huge historical turning point, they just wanted to listen to what is still the most powerful rock music ever made. As it rained and rained the calmness and undisturbed feeling of the gathering grabbed the attention of the world’s media who gazed in grudging admiration at the 450,000 [the same as the number of American soldiers at the time fighting the Vietnam War] number spectacle.
People turned to each other and said “Can you believe this?”
It wasn’t a rebellion, rather the people doing as they pleased for the happiness of it, enjoying the freedom. Towards the end of the Fair when much of the crowd had already left, Jimi Hendrix, intoxicated by the mood, took to the stage: “No to the Vietnam War, No to racism...” and then came his 4 and a half minute rendition of the American National Anthem the “Star Spangled Banner“…. the culmination of a new patriotic counter culture that was questioning the direction of American society.
American journalist and educator Max Lerner summed up Woodstock as:
“a turning point in the consciousness generations have of each other and of themselves“.
People who were there spread out across America and the world to relate stories of an ideal and perfect time and place called Woodstock, where for three days everyone lived in harmony and everything was for the best in size and spirit surpassed all fantasies. They find themselves part of history.
Woodstock was proof that America was still big enough to contradict itself on a huge scale, and to stand up in the best possible spectacle against its worst excesses.
“We have kneeled down too long and are getting up to stretch our legs” (Anonymous 89er)
I recall the heady weeks leading up to June 4, 1989 as vividly as if it was yesterday: a passionate flowering of student idealism, mingling with the students, exchanging stories, philosophising about the differences between capitalism and socialism, how energetic, so full of life they were. Their thirst for information, their frustrations with the harsh restrictions of life, their optimism for the future, the music, the sense of intellectual excitement, a free-spirited atmosphere, more debates, pasting their manifestos on campus boards across Beijing, the marching, the banners, the hunger strikes, the city at a complete standstill, the enormous public compassion and understanding, being in Tiananmen Square staring at the statue of the lady in white and realising this was their rebellion not mine. The cry was for reform. An entire nation was about to blossom, but then came the cruel response, and with it the death of hope, romanticism and idealism in China.
China’s Woodstock? Yes, flattery indeed. The bands didn’t play on.
In the intervening time the Zhongnanhai Establishment still advocates the same lamentable verdict in relation to the events of June 4, 1989...
… Modern China’s enduring transformational pain. 遗忘症节快乐!
As the ‘International Year of the Child’ draws to a close we find it disturbing that the plight of millions of children working in slave labour conditions has received minimal publicity. The following is the story of some of them.
Like many other ill informed travelers – knowing a little but not enough – I had a certain impression of South America, a land of rhythmic music, colour, gaiety and an almost permanent fiesta. – Yes, I knew there was great poverty, but there isn’t a country to-day without it.
Among the many places in South America I visited Bogotá, the capital city of Colombia, with a population of 5,000,000 (five million) people, at an altitude of 8,612 feet, lies almost permanently in a drifting web of clouds, fortress like. Beneath the clouds, however, lies a cosmopolitan city of amazing contrasts both in people and ways of life. The clever modern architecture blends graciously with the old, unbelievable wealth – mostly gained from great mineral resources, and illicit wealth, which is not spoken of, fueled by the drug trade and illegal emerald racketeering.
If the wealth and prosperity of a country portrays itself in the way it treats its underprivileged children – then Bogotá should bow its head in shame.
In Bogotá one sees the sickening contrast of the ultimate in opulence next door to the most desperate poverty – I speak of the slum dwellings on the slopes of the Andes “Resotration” which sprawl down the hillsides overlooking the city’s northern shopping centre. These dwellings are make from stolen bricks, cardboard, sheets of plastic, pieces of wood and disused petrol drums – anything that substitutes for four walls – at any moment the bulldozer can come, sent at a whim by a local landowner or government official. When the rains come they are more often than not washed away.
Bewildered prematurely aged women in the squatter settlements migrate from slow starvation in the countryside, like so many desperate ‘Dick Whittingtons’, hopeful that the city can offer more than their rural life. They bear too many children: In Bogotá the infant mortality rate is said to be 60 per 1,000 live births, while many of those born will die of disease, malnutrition and lack of medicine. For example, last August, in just one Bogotá maternity clinic a lack of medicine resulted in the deaths of 93 babies. Girls, with poor young mothers facing intense peer pressure from husbands and relatives desiring the survival of sons over daughters, are particularly at risk. Moreover, a cultural inclination for the dilution of milk bottles, which invariably are contaminated, over breast-feeding further fuels the risk of malnutrition and disease.
Volunteer workers find that the most common objections to birth control are social ones, not religious, deriving from the male’s excessive concern with ‘machismo’. From this wretched background the wandering homeless urchins street children – the gamines[in Espanola pronounced (gah MEE nays)] are bred, left to fend for themselves on the pitiless streets of Bogotá.
[Blog Note: In 1978, according to Page 272 of “Gamines: how to adopt from Latin America” [by Jean Nelson-Erichsen and Heino R. Erichsen (1981)], there were 130,000 gamines were living on the streets of Colombia’s cities.]
The children, as young as six years old, are sent out onto the streets by their mother or father or whatever where they compete with the vultures in their daily quest for food among the city’s refuse bins. Ill clad in their torn shirts and pants – often with no shoes, sometimes straw slippers, they form packs, sleeping on quiet streets, in doorways, in local parks and under bridges. It is a well know fact that they can strip a car down to the chassis in five minutes flat. They are fast on their feet, so fast the police seldom catch them – more often than not the police turn a blind eye. Girls of thirteen become prostitutes, their faces reflecting the hopelessness of their lives. Even children earning ₤1 per week down the treacherous coal mines are considered lucky.
Three years ago, when the Pope visited Bogotá the government sent military trucks on to the streets to pick up the gamines, keeping them in the mountains until His Holiness had left, for fear that he would see them or that their plight would be brought to his attention.
To walk on the streets of Bogotá wear even a wrist watch is not just hazardous, it’s crazy. The gamines would pull it off your arm, and if it didn’t come your wrist would be at stake. The same fate applies to handbags or any kind of jewellery.
The Casa de las Menores is a kind of remand home where boys picked up from the streets were sent. They may have committed some small crime or be guilty of the crime of illegitimacy and abandonment, unwanted orphans without any identification papers. Many boys are crammed into limited accommodation, and, certainly in the past, gruesome offences have been committed by the stronger against the weaker.
I heard of a Christmas party given by some social workers for these children. When the children saw the food they went crazy, knocked over the tables and ate like animals. They paid for this misdemeanour by being flogged with thongs by the wardens who accompanied them.
I have been told that the authorities are doing “something” – but “something” is not enough. There are now a number of volunteer projects in motion – Colombian and American teenagers are dynamic in the work that they do for these waifs – but it is only the tip of the iceberg. A complete change in social attitudes is not only necessary but vital if the smouldering discontent is not to erupt into a volcano of violence that the lethargic authorities will be unable to control.
And what of us safely ensconced in the faraway ‘developed’ worlds of Europe and America? What responsibility do our affluent societies bear for the prevalence and maltreatment of Bogotá’s disposable street children? It is clear to me that with Columbia’s drug trafficking cartels seeking to cash in on growing demand in our world for the highly addictive cocaine, more and more the true cost, the victims, of such demand will be the Gamines, the throwaway children.
This article was posted in the Irish Women’s Political Association (WPA) Journal No 14, Winter 1979. It was written by my late mother Kathryn O’Reillyhttp://wp.me/p15Yzr-k7 (or Catherine O’Reilly as attributed by the journal’s editor) who had recently returned from an extraordinary journey to Ecuador, Colombia and Venezuela as guests of great personal friends the British Ambassador to Ecuador (John and Jenny Hickman) and the British Ambassador to Venezuela (Jock and Molly Taylor).
During International Year of the Child in 1979 many problems relating to children—slavery, abuse, prostitution, homelessness – which thus far had been rejected out of hand or blatantly ignored by municipal governments throughout Latin America were given an international airing. In her own small, yet determined, way my mother, Kathryn O’Reilly, had hoped her article would draw the attention of Irish women to the wrongful practices of the Bogotá authorities with respect to addressing the plight of the gamines. International pressure, with Unicef actively assisting in the exposure of nationally embarrassing child maltreatment issues, moved previously complacent national government and city authorities in Latin America to start taking steps, albeit piecemeal, to address child protection issues, particularly with respect to homeless street children.
Despite the nature of this article about the vicious cycle of poverty, desertion, abuse, neglect and children’s lack of access to basic amenities that breeds the gamines, the sight of which left an indelible mark on my mother’s psyche, she considered Colombia a wonderful and fascinating country. In Bogotá she met many inspirational local NGO volunteers and thus had a first-hand knowledge of their outstanding efforts to resolve the many complex, multidimensional, problems that every developing country with limited resources faces – which are mainly the result of a rapid increase in urban populations without the housing and service provisions that such growth demands. For my mother the best things about Colombia were its natural beauty and the warm welcoming attitude of Colombians towards visitors. In fact, given half the chance she wouldn’t have hesitated to go back!
Update: April 2018
If you would like to sponsor a homeless child in Bogotá check out the NGO
“Fr. Javier De Nicolo, a dedicated Salesian missionary, visionary and human rights activist, passed away on March 22, 2016 at the age of 88. He dedicated his life to saving the young people that no one else wanted to help – children living on the streets of Bogota, Colombia. As in the likeness of the founder of the Salesians, St. John “Don” Bosco, Fr. Javier De Nicolo was devoted to helping homeless youth that others refused to approach – many of whom had severe social problems and drug addictions. Fr. Javier De Nicolo developed a system of mutual trust and respect, which became the foundation of success for his street children program. He joined in the activities of the children, sharing in their experiences and even sharing a little bit of money with them. Once respect was established, he invited them into his community where they would be provided with showers, clean clothes, meals and a warm bed. The children were able to come and go as they wished, but most chose to stay. Through various additional steps, the children were introduced to basic education and skills training, and were given the opportunity of a promising future. Fr. Javier’s generosity, dedication and hard work is something that every Salesian missionary strives to accomplish. He gave those children who had nothing and needed everything the chance to live a life of dignity, joy and empowerment. In his more than 50 years of service, Fr. Javier was a faithful disciple of both Jesus and Don Bosco, allowing thousands of children to benefit from his generous heart. May he now rest peacefully. http://www.salesianmissions.org”
Ballyhanna Man – Early Evidence of Hereditary Multiple Exostoses
He occupies pride of place in a specially constructed case at Donegal Museum in Letterkenny, in far-flung rugged North West Ireland, and was a key focus of the Ballyhanna Research Project funded by Ireland’s National Roads Authority (NRA) and involving cross-border collaboration between Queen’s University Belfast and the Institute of Technology in Sligo.
Dating at least 600 years, from 1100-1400, ‘Ballyhanna Man’ was one of 1,200 skeletal remains found by archaeologists around a buried church less than a mile south of Ballyshannon, on the banks of the River Erne, in 2006.
And what makes him so interesting is that he is the first intact case of Hereditary Multiple Exostoses (HME) / Diaphyseal Aclasis to have emerged in Irish archaeology and one of the very few in the world.
Research (which is ongoing) evidence so far indicates he was about a young adult of about 25 years old when he died (typical of the mortality rate of the other non-HME male remains excavated at the burial site). Projecting bony lumps were evident on the upper and lower limbs: Two bones on each lower leg were fused together, and he was knock kneed. His arms were bow-shaped, with the left arm noticeably shorter.
Ballyhanna Man’s condition would have meant he suffered from pain and was very much disabled, and it’s unlikely he would have survived to such an age without some form of support. He appears to have been afforded the same Christian burial as other remains. Regarding his quality of life, given he would have had HME since childhood, who knows?
Given the congenital nature of HME, osteoarchaeologists are working to establish family ties between Ballyhanna Man among the other remains. The remains of a second, man, young to middle aged adult in his late 30’s to 40’s, exhibiting lumps that would have been less obvious than those which afflicted Ballyhanna Man, were also excavated in the same burial ground. According to researchers radiocarbon dating indicates he died several hundred years before Ballyhanna Man, which may point to the HME gene existing within the group for a considerable period of time.
The hope is that in future advancements in genetics and DNA research will provide evidence regarding how HME has evolved.
In addition to the two skeletal remains uncovered by archaeologists at Ballyhanna, two skeletal remains with indications of HME were uncovered by archaeologists in Dublin: The remains of a young to middle-aged female were excavated from a medieval cemetery on St. Stephen’s Street, while a young adult male, dating back to later early Christian era, was exhumed in Kilshane.
In the study of ancient diseases that is paleopathology four of the 16 known cases of HME are specific to Ireland, and a further three cases specific to England (the remaining nine ancient cases of HME are located in Jordan, Zimbabwe, Peru, Sweden, Poland and Canada). As such, is living on an isolated island in any way significant in the context of a higher HME prevalence in the UK and Ireland?
The purpose of this composition (updated March, 2019) is to provide a focal point of support and information for family members and persons living in Ireland and beyond who have Hereditary Multiple Exostoses (HME) in order to encourage them to share their experiences so that people in general will have a clearer understanding of this rare condition and how challenging affected lives can be.
What are the chances of transmitting HME to your children?
Pre-Implantation Genetic Diagnosis (PGD): Karyomapping and MALBAC
Traditional Chinese Medicine (TCM)
Omega-3 Krill Oil
Prognosis – The Good News
HME in Ireland
HME and Autism / Asperger Syndrome linkage?
HME and animals?
Dorsal Foot Exostosis
Is that a bunion or exostosis protruding from your foot?
Orthopaedic / Neurological Consultant / Surgeon HME Know-how in Ireland
Support resources for HME patients and their families
HME and Me
I recall being about nine years old, maybe younger, when I first noticed the large tender lump protruding from my left shoulder blade like a Rhino horn. I soon became very self-conscious as bone protrusions multiplied to cover my legs (femur, tibia, and fibula), arms (humerus, radius, and ulna), shoulder blades, hands, feet, ribs, and pelvis, particularly around the shoulder, elbow, wrist, knee, and ankle joints. My height was affected, as was the shape of my arms (bow-shaped, my left arm is shorter than my right) and legs (my knees won’t bend all the way), with structural impairment to my left elbow and hand. I knew I was different to all my other friends, and with such low self-esteem I certainly felt that way. I hated going to school. I just wanted to seclude myself. As a consequence I was shy and introverted as a child. I wore long sleeve shirts and explained away the bow-like curvature of my left arm by faking how it had been broken. I loved sports, but was unable to participate like other kids my age, while almost nobody, except my mother, knew of the constant 24*7*365 daily pain, the cause of which medical practitioners in the 1970s and 1980s were at a loss to deduce.
The surgery started in earnest when I was 13 years old and by the time I was 27 years old 48 of the more irritating lumps had been hacked, sawed, and chiseled off. The leading orthopedic surgeons in Ireland at the time Messrs. Gerry “Gold Fingers” Brady, John Varian, and Jimmy Sheehan all had a go on me in both Saint Michael’s Private Hospital, in Dun Laoghaire, and the Mount Carmel Hospital, over in Churchtown (Dublin), while I have been also referred to orthopedic consultants, ENT consultants, neurologists (medical interns in tow) and Traditional Chinese Medicine (TCM) practitioners in Liverpool (UK), Seoul (Korea), Singapore, Malaysia, Hong Kong and mainland China.
In 1990, following an operation to remove a lump from my pelvis, I recall the surgeon’s reassuring words “That’s it, no more operations, the bony lumps wouldn’t grow again“, and that I could now get on with my life. I was 27 years old and I’d gone through more operations, physiotherapy, and recovery periods and overcome more obstacles than anyone should ever have to go through in their entire life. So get on with my life I certainly tried to do, and did.
However, despite leading as active a life as I could, the ever present twinge, spasm, ache, and clicking sound, which I guess only a person with HME can truly identify with, continued and in 2008 I was referred to neurologist Mr. Chris Pidgeon at Dublin‘s Beaumount Hospital. He advised surgery on compressed cervical vertabra caused by atypical spinal curvature on the basis that if I didn’t have such surgery sooner rather than laternerve damage and dysfunction would gradually lead to acute lack of sensation on the left side of my body. At around the same time one of China‘s leading ENT experts, Professor Pu Xing Kuan (JiangSu Province Hospital, Department of Oto-Rhino-Laryngology -卜行宽, 江苏省人民医院耳鼻咽喉科卜行宽主任医师) postulated a connection between the bony growths and troubling hearing and balance challenges.
New medical knowledge gleaned through advances in scientific research indicate that intermittent fatigue, poor coordination and short concentration span troubles I have always tried to come to grips with are neurological motor disorder symptoms associated with HME, and not just a figment of my imagination.
By and large living with HME has been a largely silent battle marked by good and bad days. While the bad days don’t define me, they do seem to be happening more often than I care to admit. I would describe a good day as a day when things are manageable, when the level of needling pain is at least two levels below my average. Regardless, in spite of the challenges that come with the territory, I will never let HME beat me.
What is Hereditary Multiple Exostoses?
The condition was first alluded to in 1786 by John Hunter, the prominent, yet controversial, Scottish surgeon and anatomist, infamously known for taking possession of 2.31 metres tall Irish giant Charles Byrne’s corpse contrary to Byrne’s clear deathbed request. It would take a further 90 years for the term ‘multiple exostoses’ to first surface, as conceived in 1876 by the venerated German physician Rudolf Virchow. What is more, the first reference to Hereditary Multiple Exostoses (HME) in American medical literature only happened in 1915 when the Boston surgeon Albert Ehrenfried wrote of “Multiple cartilaginous exostoses—hereditary derforming chorodysplasia: A brief report on a little know (sic) disease”.
Hereditary Multiple Exostoses (HME) is one of the numerous synonyms [along with: Bessel-Hagen Syndrome;Chondral Osteogenic Dysplasia of Direction;Chondral Osteoma;Deforming Chondrodysplasia; Diaphyseal Aclasis (multiple hereditary); Dyschondroplasia;Exostosing Disease; Exostotic Dysplasia;Exostosis Multiplex;EXT; Hereditary Deforming Chondrodysplasia;Hereditary Multiple Osteochondromas;Multiple Cartilaginous Exostoses;Multiple Congenital Osteochondromata;Multiple Exostoses;Multiple Hereditary Exostoses (MHE); Multiple Hereditary Osteochondromatosis (MHO); Multiple Osseous Exostoses;Multiple Osteochondromas (MO – which is the term designated by the World Health Organisation (WHO)); Multiple Osteomatoses; Osteochondromatosis; and Osteogenic Disease] is a very rare bone disease in which multiple benign bony cartilage-capped outgrowths (or exostoses /osteochondromas) thatare atypical in size, position and number grow in areas of active bone development, or open growth plates, in children.
Regarding HME’s origins scientists have linked it with chromosomal mutations in three genes: EXT1, which maps to Chromosome 8q24.1; EXT2 which maps to Chromosome 11p13; and EXT3 which maps to the short arm of Chromosome 19 (though its precise location is still unclear). It seems the majority of HME cases have either HME EXT1 or HME EXT2 mutations, while a small proportion of HME cases are linked to the EXT3 gene.
Approximately 50% of people with HME are diagnosed by the time they are three years old
5% of newborns that carry an HME gene show some signs at birth
Though not present at birth, 96% of all cases with HME will show noticeable signs by the time they are 12 years old
Approximately 70% of people with HME have an exostosis or bone abnormality around the knee
Six is the number of exostoses the average person affected with HME will typically develop during his or her life
Most often affected are long tubular bones, while in 10% of cases the small bones of the hands and feet are also affected, the scapula only in 1% of patients. The spine is involved only in 2%, but it can lead to cord compression.
While HME currently has no cure, the good news is that a cure may not be far away!
FANTASTIC NEWS FROM MARCH 2018
Update March 2018: MHE Research Foundation in collaboration with Clementia Pharmaceuticals is has announced recruitment for the trialing in Australia, Belgium, Canada, France, Italy, Japan, Portugal, Spain, The Netherlands, Turkey, United Kingdom and United States ) of (once daily pill) the efficacy and safety ClementiaPalovarotene, as a potential treatment of HME in children.
Research moves toward the first drug treatment for Hereditary Multiple Exostoses
Prevalence and geographical reach
Curiously, the research also points to much higher prevalence rates amongst island populations with geographically restricted movement, such as Guam, which has about 100 HME cases per 100,000 people.
Be that as it may, taking for granted that Ballyhanna Man, and the two age-old skeletal remains discovered in Dublin, proved HME’s existence in Ireland over 600 years ago one would be inclined to think that given its hereditary nature the prevalence of HME among their future ascendants on the island would be relatively high. In actuality, secondary research and interactions with orthopaedic surgeons and online support groups undertaken by myself suggest there may be less than 100 cases on the island of Ireland (April, 2018).
Geographically, while the primary HME clusters are to be found in Europe, North America, and Australia, HME is a global disease with people impaired by the condition living in China, India, South East Asia, South America and Africa.
Chloe B tells the story behind the scars
An exotosis is a benign rounded or sharp bone growth at the metaphyseal areas of the long bones. Exostoses start, and continue, growing, for the duration of a child’s development around the growth centres of bones that are near the ends of the bones, which is why lumps tend to grow, or fuse, near the joints. When a person has achieved full skeletal growth, the exostoses are expected to stop growing, which is not to say their tenderness also stops. This last point is quite contentious, as previously less painful exostoses can become very tender with the wear and tear of age. Moreover, exostoses can also return to the same places from where lumps have been previously extracted, and they may be more painful. Many members of online HME support communities highlight increasingly chronic pain experienced in later life.
What is an Osteochondroma?
Chronic, not contagious
What complications are caused by HME?
HME can be particularly troublesome. Because the exostoses grow around areas of active bone growth, they disrupt the normal growth process, leading to defective growth that causes nerve compression, inequality of limb length and irritation of adjoining soft tissue, such as skin, nerves, tendons, muscles, and blood vessels. Such is their sensitivity, these cartilage-capped lumps can cause chronic pain, clicking sounds, and numbness until they are surgically removed. Accidentally bumping them against something solid can be particularly painful.
Exostoses that grow near the ends of long bones may limit the normal range of motion of the joints upon which they encroach. Consequently, people with HME may have a shorter stature than average, with studies of HME patients showing the final height in men typically averaging 170 cm (66 in), while the average height in women is about 160 cm (62 in). Moreover, differential rates of growth between a child’s legs or arms can result in disparities in leg or arm length sometimes reaching 2 cm (1 in) or more. Leg length disparity can result in hip pain and difficulties with walking caused by a slanting of the pelvis.
HME patients may also have bowed arms or legs. Often, the forearm will bow out, or the legs can grow to be “knock-kneed“. While function is usually fairly normal, the bowing can be very troublesome.
Another complication caused by HME is stiffness, particularly in the hands, elbows and hips usually because the lumps block their natural movement.
The most alarming potential HME complication is also one of the rarest, typically occurring after skeletal growth has finished. In less than 1% of cases the benign exostoses can become a cancerous tumor called Chondrosarcoma. Such Chondrosarcoma cases are usually in the 20’s to 50’s age range. Growth and soreness are two key warning signs that a benign tumor has become malignant. If a person with HME notices after they have stopped growingthat an exostosis is getting larger or painful he or she should consult their doctor right away. Chondrosarcoma while uncommon (arising in0.5% to 3% of HME patients) is still something people who have Hereditary Multiple Exostoses must know about. An unnoticed bone malignancy always presents a risk of metastasis (the spreading of cancerous cells elsewhere in the body), which is one of the most dangerous complications of any cancer (For more on Chondrosarcoma check out this YouTube video explanation from Dr. Christopher R. Beauchamp, M.D., Orthopedic Oncology and Adult Reconstruction Surgery, Mayo Clinic ).
Hereditary Multiple Exostoses (HME) [Multiple Hereditary Exostoses (MHE), Hereditary Multiple Osteochondromas, Multiple Exostoses, Exostosis Multiplex, Multiple Osseous Exostoses, Multiple Cartilaginous Exostoses], or Diaphyseal aclasisis a condition that is passed by the genes of the affected parent to their children. If one parent has the condition, there is a 50% likelihood that any child could also develop Hereditary Multiple Exostoses (HME).
As is my own situation, in 10% to 20% of HME cases a person can develop multiple exostoses with no family history of HME. In medical terms this is referred to as a de novo or “spontaneous mutation” indicating a genetic problem arose in that person without being inherited from a parent. Moreover, my two brothers, who are both in their 60s, did not inherit this condition.
HME has a 96% penetrance, which means that if the disease is indeed transmitted to a child, he or she will have a 96% chance of actually manifesting the disease, and 4% chance of having the disease but never manifesting it.
While males who have the HME gene tend to exhibit more obvious and severe symptoms than females, and are therefore more likely to be diagnosed with HME, males and females are equally likely to inherit HME.
Straight talking exostoses boy Mikey spells it out in black and white
What are the chances of transmitting HME to your children?
A person with HME has a 50% chance of transmitting this condition to his or her children. Male and female are equally likely to be affected. In other words, if it is assumed that four children are produced, and one parent is a carrier and exhibits the disease, the statistical expectation is for two children to be normal and two children to inherit this disease. This does not mean that children will necessarily be affected; it does mean that each child has a 50:50 chance of inheriting the disorder.
Pre-Implantation Genetic Diagnosis: Karyomapping and MALBAC
For individuals with HME who are considering starting a family, recent scientific developments in pre-implantation genetic screening and diagnosis (PGS & PGD) and pre-natal diagnosis can detect the exostoses gene from embryo samples and help select normal embryos. [Note: For further information about PGS refer to the ‘Research’ section below].
In February 2015, confirming the significance of pre-implantation genetic diagnosis with respect to detecting the exostoses gene the Cork Fertility Centre , stated:
“We do provide PGD service for Multiple Exostoses patients based on Karyomapping technic, which can do the same job as MALBAC. Karyomapping can detect the exostoses gene from embryo samples and at the same time obtain the information of chromosome status. ” (Source: Cork Fertility Centre email to author of this blog piece, dated 15th February, 2015).
The Beacon CARE Fertility centre in Sandyford, Dublin, also provides pre-implantation genetic testing services.
FANTASTIC NEWS FROM SEPTEMBER 2014
“Hereditary Multiple Exostoses patients can now expect their offspring to be free from their disorders”
Beijing (Peking) University, Sep.24, 2014: On September 19, 2014, the first in vitro fertilization (IVF) baby with pre-implantation genomic screening based on MALBAC was born in the Beijing University Third Hospital, Beijing, China. MALBAC is a newly developed whole genome amplification method, allowing for the precise selection of embryos in the IVF process when combined with next generation sequencing. This event brings the good news to patients with monogenic diseases around the world that they can now expect their off springs free from their disorders.
In this case, the husband suffers from Hereditary Multiple Exostoses, an autosomal dominant hereditary disorder, which is characterized by multiple bony spurs or lumps on the bones at an early age. There is a frame-shift point mutation at the EXT2 gene of this patient, which has a 50% chance of transmitting this disorder to his children. To avoid this risk, a normal embryo free from the husband’s disease allele was selected by Dr. Jie Qiao’s group at Beijing University Third Hospital using the MALBAC technique that was developed by Sunney Xie’s lab.
Total 18 embryos at blastocyst stage were obtained from the couple during IVF cycle, and a few cells were biopsied from each of the day 5 or day 6 embryo. Genomic DNAs of the obtained cells were amplified evenly and accurately with the MALBAC method for the whole genome sequencing analyses. Combined with the targeted PCR and next generation sequencing techniques, all the numerical and structural chromosome abnormalities and the mutated allele of the genetic disease were accurately detected with low depth sequencing data (0.1X). The team identified three embryos with neither the inherited mutated allele nor chromosome copy number abnormalities from these 18 embryos, and finally chose one healthy embryo to transfer back to the wife. The embryo implanted successfully, grew normally, and later the amniotic fluid cells from the baby were isolated and analyzed as free of aneuploidy and mutated allele. Now the baby was born successfully, with 4.03 kg of weight and 53 cm of length. Umbilical cord blood genome detection confirmed the baby is free of the mutated allele.
Pre-implantation genetic diagnosis (PGD) is a technique that helps selecting normal embryos to transfer into uterine using IVF. It is an early prenatal diagnosis technology to obtain a healthy offspring by avoiding the genetic diseases.
Currently, the widely used PGD technologies are fluorescence in situ hybridization (FISH), polymerase chain reaction (PCR), and comparative genomic hybridization (Array-CGH) and single-nucleotide polymorphism (SNP-array)… it has been highly desirable, but has not yet been reported to simultaneously detect monogenic point mutations and chromosome abnormalities. MALBAC allows for simultaneous circumvention of point mutations and chromosome abnormalities with high accuracy. Furthermore, the procedure developed by the team has used low depth sequencing, allowing low cost and fast PGD.
MALBAC, a powerful single cell whole genome amplification method, which was first developed and reported by Sunney Xie’s lab in 2012, is the key technique in this project. Since MALBAC use linear instead of exponential amplification, it is much more accurate and uniform than the traditional DOP-PCR and MDA methods. So MALBAC can be used to analyze the genomes of rare and limited materials. At the end of 2013, Sunney Xie’s lab cooperated with Jie Qiao’s team and Fuchou Tang’s lab and demonstrated the proof of principle of using MALBAC for PGD in IVF, which was published in Cell.
The project is done with the support from the Ministry of Science and Technology, Beijing Municipal Science and Technology Commission, the National Natural Science Foundation of China, and 985 project of Peking University. The project is accomplished under the cooperation of the three partners: Jie Qiao’s team in Peking University Third Hospital, Sunney Xie’s lab and Fuchou Tang’s lab in Biological dynamic Optical Imaging Center (BIOPIC) of Beijing University.
Ruby Page explains what it’s like to live with HME
Some people with HME never need any treatment. They learn to counterbalance the abnormality or reduced range of motion so they can perform as normally as possible. When abnormality does occur it often develops so slowly that the patient can adjust to it well, while others may require surgical treatment to provide relief.
Surgery (bear in mind modern medicine has really advanced with ongoing technological breakthroughs!), physiotherapy and pain management are currently the only options available to HME patients, and while success varies from patient to patient many continue to struggle with pain, fatigue and mobility problems throughout their lives.
It is not unusual for patients with Hereditary Multiple Exostoses (HME) [Multiple Hereditary Exostoses (MHE), Hereditary Multiple Osteochondromas, Multiple Exostoses, Exostosis Multiplex, Multiple Osseous Exostoses, Osteocartilaginous Exostoses, Multiple Cartilaginous Exostoses], or Diaphyseal aclasis to undergo numerous surgical procedures throughout their lives to remove painful or deforming exostoses, correct limb length discrepancies or improve range of motion.
HME Presentation by Dr. Dror Paley, Paley Limb Lengthening Institute, St. Mary’s Hospital, West Palm Beach, Florida
If an exostoses is painful, pressuring an important structure, visibly unsightly, or is easily knocked, it can be removed by surgical methods. Excision itself is usually a fairly straightforward procedure, some are removed without necessitating an overnight stay in hospital. Once removed, however, as previously mentioned, exostoses can reappear (about 20% – 50% of the time), although they are may not grow to the same extent as before.
When an exostosis causes a growth deformity, such as bowing, sometimes simply cutting off the lumps at an early stage will let the bone straighten itself out and adapt as the child grows. However, some bowing is so acute that not only must the lumps be removed, but also the bone must be straightened. This can be done either by cutting the bone, remodeling it and then holding it in place while it mends or, if the child is still developing, by altering the rate of growth on one side of the growth plate.
There are a number of options available and an orthopedic doctor should be able to advise accordingly.
Moses Ndiritu’s story – Every day gets harder
Managing the severe pain associated with HME can be very disheartening, and there are all sorts of opinions regarding treatment. Below are several different approaches to pain management, notwithstanding that fact that in distinguishing which pain medicine provides the most effective relief it is important for each HME patient (or parent / guardian in the case of children) to do their own research before any new treatments are commenced. While a proposed treatment may sound beneficial, there are also some potential negative side effects that a HME patient may suffer from. Always be aware of both the pros and cons of any treatment before deciding whether it is the right approach to controlling specific pain, and preferably use the therapy in a controlled environment.
1. Medical Marijuana?
While the MHE Research Foundation does not support the use of Medical Marijuana, HME is one of a defined number of conditions with symptoms or ailments that advocates claim can treated with Medical Marijuana. Stockbroker and HME patient Irvin Rosenfeld, from Fort Lauderdale, Florida, has been issued with 12 daily government-supplied marijuana cigarettes for more than 30 years. The longest surviving patient to be assigned to the federal medical marijuana, Mr. Rosenfield claims he would not be alive if he hadn’t been issued with marijuana cigarettes for the treatment of his HME condition.
For more on Irvin Rosenfeld (http://irvinrosenfeld.com/), refer to the YouTube video ‘Medical Marijuana – Multiple Exostoses (Irvin Rosenfeld)’ below.
In Canada, Saskatoon high school student Michael Wileniec says high-grade medical marijuana is the only drug that eases his chronic pain, noting in a January 2015 newspaper interview, he had already “…tried conventional prescription drugs, from Tylenol 3 to morphine, but didn’t like how they clouded his mind“.
For more about Michael Wileniec and his usage of Medical Marijuana to help alleviate HME related pain refer to:
Having lived in China for a number of years I have had the benefit of trying out traditional acupuncture, electroacupuncture, and tuina acupressure, the needle free alternative to acupuncture. These Traditional Chinese Medicine treatments are effective paint controls, although I found the relief to be short lived, meaning that once treatment concluded the soreness would soon return. For specific HME patient feedback regarding the effectiveness of such Traditional Chinese Medicine practices, including qigong read the “Comments” https://nialljoreilly.com/2012/04/28/hereditary-multiple-exostoses-ireland/#comments section located at the bottom of this post.
Learning to Love Myself and My Scars From Multiple Hereditary Exostoses
3. Omega-3 Krill Oil?
Having endured an agonising winter of 2013 / 2014, to the point where even a walk of 20 metres could be a harrowing exercise -the degree of tenderness contingent on the prevailing weather- my introduction to the benefits of Omega-3Krill Oil, which the Journal of Lipid Research claims is 48 times more potent than fish oil, was simply a business-driven fluke. Yet, while there are no research studies to back me up, I have found exceptional relief (reduced pain, inflammation, functional impairment, stiffness) since the summer of 2014 when I started taking Omega-3Krill Oil in capsule (500 mg per day) and more recently in syrup format. In fact, of late, since finishing the bottle of Omega-3Krill Oil (300 ml) syrup in late January (2015), once again I can now feel both bone and joint pain levels starting to give me a hard time.
The Omega-3 Krill Oil capsule and syrup products I used are from CleanMarine (http://www.cleanmarine.ie/), who also produce a Krill Oil syrup for kids.
Advocates of homeopathy for HME contend that surgical excision of exostoses does not remove the cause of HME, as it cannot guarantee further exostoses from forming. Homeopathists aim to treat the patient (not HME) by strengthening his/her immune system to remove the disease and prevent recurrence.
FANTASTIC NEWS FROM NOVEMBER 2017!
“Preclinical study demonstrates promising treatment for rare bone disease
Data supports clinical investigations of palovarotene to treat multiple hereditary exostoses”
La Jolla, Calif., November 20, 2017 – Researchers at Sanford Burnham Prebys Medical Discovery Institute (SBP) have led a preclinical study demonstrating that the drug palovarotene suppresses the formation of bony tumors (osteochondromas) in models of multiple hereditary exostoses (MHE). The research, published in the Journal of Bone and Mineral Research, is an important step toward an effective pharmacological treatment for MHE, a rare genetic condition that affects about 1 in 50,000 people worldwide.
MHE (also known as multiple osteochondromas, or MO) is an inherited genetic disorder in which multiple benign bone tumors covered with cartilage grow at active areas of bone growth. The condition is caused by mutations in two genes: EXT1 and EXT2. Individuals with these mutations develop painful, debilitating tumors, often repeatedly during their childhood and adolescence. Surgery and pain management are currently the only treatment options for MHE patients.
“Our study shows that palovarotene is a remarkably potent inhibitor of osteochondromas, says Yu Yamaguchi, M.D., Ph.D., professor at SBP. “In our mouse model of MHE, we were able to reduce bone tumors by more than 90 percent, which is a significant improvement over the previous drugs we have tested in the same mouse model.”
“Especially promising is that palovarotene has been tested for toxicity and side effects in humans and has been shown to be well tolerated,” says Yamaguchi. “This means that time line for getting the drug to the clinic for MHE may be shortened.”
Clementia Pharmaceuticals licensed palovarotene from Roche Pharmaceuticals, which previously investigated the compound as a possible treatment for chronic pulmonary disease and evaluated its safety in more than 800 healthy volunteers and patients. Clementia Pharmaceuticals is planning to initiate a Phase 2/3 clinical trial in 2018 for patients with MHE.
“This is first time we are seeing a clear path toward a therapy that will improve the lives of MHE patients and their families,” says Sarah Ziegler, vice-president of the MHE Research Foundation. “The long awaited first clinical trial for a drug to treat MHE is now a reality. This breakthrough comes after years of working with medical professionals and scientists like Dr. Yamaguchi to achieve something we have all been desperately striving for, for many years.”
Through gene mapping studies scientists, as previously noted, have linked HME with mutations in three genes: EXT1, which maps to Chromosome 8q24.1; EXT2 which maps to Chromosome 11p13; and EXT3 which maps to the short arm of Chromosome 19 (though its precise location is still unclear).
Continuing research of the HME genes will likely establish an accurate prevalence for each of the three gene types, thus providing greater insight into the growth of cells, which is really what HME is all about. With such rapid advances in science, particularly in terms of gene mapping, it not inconceivable that such as understanding will sooner rather than later provide the knowledge leading to a tangible treatment for HME.
Recently, Chinese scientists, supported by the Ministry of Science and Technology, have also started conducting extensive research into HME. One such research paper published in 2014 concluded that in China:
“HME starts earlier and becomes more severe and extensive with each successive generation in members of the pedigree analyzed”
[For more about HME in China refer to ‘10. Instances of Hereditary Multiple Exostoses (HME) in China, from 1990 – 2013′ in the research segment at the bottom of this blog.
As it stands, gene mapping can serve as a basis for testing children at risk with HME and the information gleaned from such testing will hopefully lead to the prevention of the development of exostoses and their associated complications. There is good reason for optimism: the day when our doctors are equipped to undertake such testing is near.
Multiple Hereditary Osteochondromatosis (MHO)* – Suzie’s Story
*Multiple Hereditary Osteochondromatosis is the official World Health Organisation term for HME / MHE
HME in Ireland
Osteochondroma… this is My story
HME and Autism / Asperger Syndrome Linkage?
Heparan Sulphate and MHE – Dr. Yu Yamaguchi. Many parents of children with MHE / HME / MHO frequently observe autism and Asperger Syndrome like social issues in their children
“….“The bumps themselves are not so much a problem, what tends to cause the issue in children or even in adults is if [the bumps] are causing deformity,” explains Dr. Carmen Brauer, an orthopediatric surgeon with the Alberta Children’s Hospital. “Bone lengthening in the upper extremity is fairly rare compared to the lower extremity, and here at the Alberta Children’s Hospital we hadn’t done any lengthening of the upper extremity,” Dr. Brauer says. A team was assembled to perform the first procedure on Dunbar last June. His bone was cut and a device was implanted to apply tension over time to help the bone to grow. “We slowly distract and the bone then heals under the tension we’re applying. By doing that we can lengthen the bone up to a millimeter a day,” Dr. Brauer explains…….” Source / read more and view the Video: http://globalnews.ca/news/907083/bone-lengthening-surgery-saves-calgary-boy-from-disability/
Dorsal Foot Exostosis
Dorsal foot exostosis is a bony growth on the dorsum (top) of the foot. It can occur where the first metatarsal joint meets the big toe, causing the toe to lose its ability to bend. This is also known as Hallux rigidus (inability to move the joint) or Hallux limitus (limited movement of the big toe). Acute or chronic pain on the top of the foot happens in the morning and as the day progresses, more so the longer a person is standing. Metatarsal Cuneiform Exostoses crop up in the midfoot area, where the first metatarsal shaft meets the cuneiform, while a forefoot version of Haglund’s Deformity is where the throat line of the shoe meeting the foot causes pressure and rubbing which results in the fleshy area behind the toes..
Is that a Bunion or an Exostosis protruding from your foot?
– “A large exostosis was the source of a bunion deformity in a 60-year-old woman. Its unusual clinical and radiographic features were suggestive of a bizarre parosteal osteochondromatous proliferation. However, histologic features were most consistent with a benign osteocartilaginous exostosis…..” Source / read more: http://www.ncbi.nlm.nih.gov/pubmed/11482512
Orthopaedic / Neurological Consultant / Surgeon HME Know-how in Ireland
Unfortunately GPs / HSE in Ireland have little or no knowledge of HME. Best to have a GP refer you to an orthopedic consultant specialising in the specific area that causes most discomfort. No one consultant will cover all areas affected by HME. Below is what I would consider to be the best orthopaedic surgeon team in Ireland. These guys are very well grounded, they know the score and have the know-how when it comes to dealing with HME. Typically, the first consultant you engage with should take the lead in calling in other orthopaedic specialists either to verify a particular prognosis or to advise on specific areas beyond his area of expertise.
Mr. Hannan Mullett (Shoulder), Blackrock Clinic, Beaumont Hospital, Sports Surgery Clinic, Cappagh National Orthopedic Hospital
Mr. Philip P. Grieve (Elbow, Hand, and Wrist), Blackrock Clinic
Mr. Alan Liang (Foot and Ankle), Blackrock Clinic
Mr. Fintan Doyle (Hip and knee), Blackrock Clinic
Mr. Eoin Fenton (Neurosurgery, Spine), Blackrock Clinic
Dr. Sean Connelly (Neurophysiology), Blackrock Clinic
Tip: Make sure you have health insurance. MRIs at Blackrock Clinic should be fully covered by VHI, but not CTs. CTs are fully covered by VHI at the Affidea clinics. For x-rays public hospitals have walk in services, which cost about €50.00, rather than €100.00 + in the private hospitals
Useful Support Resources for HME patients and their families
– This support group offers a German translation of The MHE and Me Handbook
Hereditary Multiple Exostoses (HME) and Mehttp://wp.me/p15Yzr-Mr – Despite evidence of HME occurring in 4 ancient Irish skeletal remains (“Ballyhanna Man“) of only 16 ancient skeletal remains worldwide diagnosed with HME bone growth disorder, Ireland doesn’t have an HME information support group, hence this blog.
National Center for Biotechnology Information (NCBI) http://www.ncbi.nlm.nih.gov/sites/ga?disorder=multiple%20hereditary%20exostoses – Up to date website with detailed information on Hereditary Multiple Exostoses (HME). Includes: * Links to introductory material about Multiple Hereditary Exostoses and genetics. * NCBI Book sections and chapters about Multiple Hereditary Exostoses and genetics. * Recent scientific articles about Multiple Hereditary Exostoses. * Links to resources for screening, genetic testing, and directories of specialists.
PAPER – Cervical spinal cord compression in hereditary multiple exostoses Abstract– Spinal cord compression is an extremely serious complication of hereditary multiple exostoses (HME). A case of HME with compression of the cervical spinal cord is reported. Complete recovery following surgery was achieved. A review of the relevant literature revealed 51 previous cases of HME with cord/cauda equina compression. Most patients were under 30 years of age with more men affected than women. The family history was positive in 60%. The cervical and thoracic areas were predominantly affected, with the symptoms usually developing slowly. Recovery following surgery is to be expected in the majority of cases. In patients with HME and suffering from neurological symptoms, the possibility of spinal cord compression should be considered. Prompt diagnosis and surgical excision provide the best prognosis. Source / read more: http://www.ncbi.nlm.nih.gov/pubmed/9006779
ONGOING RESEARCH – Call for participants – Gene Mutations and Orthopaedic Symptoms Correlation of Multiple Hereditary Exostoses: Multicentre Project.
PAPER (Chinese)- Ultrastructural features of hereditary multiple osteochondroma cartilage cap in children Abstract –目的观察儿童遗传性多发性骨软骨瘤（hereditary multiple exostoses, HME）软骨帽的超微结构，为儿童HME超微病理诊断提供可靠依据。方法实验组：切除18例HME患儿肋骨瘤体分离软骨帽；对照组：15例胸廓发育畸形患儿手术矫正切除的肋软骨；分别取其纵、横切面应用扫描电镜和透射电镜观察。结果对照组：冷冻断裂的软骨组织内见少量软骨细胞位于软骨陷窝内，软骨组织表面可见大量散乱、稀疏的胶原纤维；软骨细胞数量不多，细胞表面有少量短小的微绒毛，细胞核形状不规则，细胞质内可见到粗面内质网呈条索样分散在细胞质内，线粒体较小，糖原颗粒呈簇状分布。实验组：冷冻断裂的软骨组织内见大量不规则的软骨陷窝，每个软骨陷窝内均含有软骨细胞，细胞表面有丰富的细胞突起；软骨组织内见大量瘤样细胞增生，聚集分布，细胞核较大，细胞质内可见圆形或椭圆形的线粒体及扩张的粗面内质网；瘤细胞间可见毛细血管，其附近可见明显增多的软骨细胞，软骨细胞体积较对照组增大。结论儿童HME软骨帽的超微结构改变（细胞形态及细胞内部细胞器），不同于正常软骨细胞，可能与儿童HME的遗传、发病、发展、转归因素密切相关。 Source / read more: http://www.cjcep.com/oa/darticle.aspx?type=view&id=201302014
PAPER – Multiple osteochondromas in the archaeological record: a global review Abstract
…The paper undertakes the ﬁrst synthesis study of the 16 known cases of the condition that have been identiﬁed in the international palaeopathological record. It also includes information derived from two newly discovered cases of the disease in two adult male individuals recovered from the Medieval cemetery at Ballyhanna, Co. Donegal, Ireland. Source / read more: http://www.qub.ac.uk/sites/Ballyhanna/FileStore/Filetoupload,216459,en.pdf
7. PAPER – Hereditary Multiple Exostoses: A Current Understanding of Clinical and Genetic Advances…Recent advances in understanding the molecular and genetic basis of this condition not only offer hope for patients and families with HME, but also offer clues to the underlying basis for the formation of the human musculoskeletal system… Source / read more: http://upoj.org/site/files/v14/v14_09.pdf
“In medicine and (clinical) genetics preimplantation genetic diagnosis (PGD or PIGD) (also known as embryo screening) refers to procedures that are performed on embryos prior to implantation, sometimes even on oocytes prior to fertilization. PGD is considered another way to prenatal diagnosis. Its main advantage is that it avoids selective pregnancy termination as the method makes it highly likely that the baby will be free of the disease under consideration. PGD thus is an adjunct to assisted reproductive technology, and requires in vitro fertilization (IVF) [Note: IVF costs around €4,000, with fertility drugs, if required, costing up to €3,000] to obtain oocytes or embryos for evaluation.
PGD is also now being performed in a disease called Hereditary multiple exostoses (MHE / MO / HME)..
The term preimplantation genetic screening (PGS) is used to denote procedures that do not look for a specific disease but use PGD techniques to identify embryos at risk. PGD is a poorly chosen phrase because, in medicine, to “diagnose” means to identify an illness or determine its cause. An oocyte or early-stage embryo has no symptoms of disease. They are not ill. Rather, they may have a genetic condition that could lead to disease. To “screen” means to test for anatomical, physiological, or genetic conditions in the absence of symptoms of disease. So both PGD and PGS should be referred to as types of embryo screening….” Source / read more: http://library.everyonehealthy.com/library/furthertest/In%20Vitro%20Fertilization%20With%20Preimplantation%20Genetic%20Diagnosis
9. NEW RESEARCH: How gene mutations lead to the abnormal bone growth that is Hereditary Multiple Exostoses (MHE)?
In humans, MHE is caused by a mutation in one of two genes, Ext1 or Ext2. Together, these genes encode an enzyme necessary to produce heparan sulfate—a long sugar chain that facilitates cell signals that direct bone cell growth and proliferation. But when these genes were inactivated in mice just as they are in human MHE patients, the mice failed to develop the symptoms of MHE. This had scientists scratching their heads.
Enter Dr. Yamaguchi and his colleagues, who took a different approach. Instead of knocking out the Ext1 gene in the whole mouse, they targeted the gene only in bone cells. Moreover, they deleted the gene in only a small fraction of these cells. Surprisingly, this minimalistic approach led to a mouse with all the physical manifestations of MHE, such as bony protrusions, short stature and other skeletal deformities.
The new mouse model answered some long-standing questions about MHE. Scientists had gone back and forth on whether the abnormal growths observed in MHE are true tumors or just malformations of the bone. In this study, the protrusions were made up of two cell types. A minority were mutant cells lacking Ext1, but, amazingly, most were normal bone cells. True tumors, in the strictest sense, arise from the proliferation of mutant cells only. Hence, MHE bone protrusions must result from a different – though still very serious – type of growth.
“I have been waiting 13 years for this breakthrough,” said Sarah Ziegler, vice president of The MHE Research Foundation, which has provided seed funding for Dr. Yamaguchi’s research. “My son had more than a 100 of these tumors and has gone through 15 surgeries. When your child has such a debilitating condition, and you know there’s nothing you can do, it’s petrifying. Now we have hope.”
While this study takes MHE research a giant step forward, more questions remain. For one, it is still unknown how a few mutant bone cells can convince normal cells to divide and proliferate abnormally. Researchers hope that this MHE model will help solve that mystery, as well as provide leads for new treatments.
“This new mouse system also provides a platform for screening potential drugs that inhibit bone growths in MHE,” Dr. Yamaguchi explained. “We are currently developing chemical inhibitors to block their formation.”
10. Instances of Hereditary Multiple Exostoses (HME) in China, from 1990 – 2013
“...Hereditary multiple exostoses (HME) are an autosomal dominant skeletal disease with wide variations in clinical manifestations among different ethnic groups. This study investigated the epidemiology, clinical presentations, pathogenetic features and treatment strategies of HME in mainland China. We searched and reviewed the related cases published since 1990 by searching electronic databases, namely SinoMed database, Wanfang database, CNKI, Web of Science and PubMed as well as Google search engines. A total of 1051 cases of HME (male-to-female ratio 1.5:1) were investigated and the diagnosis was made in 83% before the age of 10 years. Approximately 96% patients had a family history. Long bones, ribs, scapula and pelvis were the frequently affected sites. Most patients were asymptomatic with multiple palpable masses. Common complications included angular deformities, impingement on neighbouring tissues and impaired articular function. Chondrosarcomas transformation occurred in 2% Chinese cases. Among the cases examined, about 18% had mutations in EXT1 and 28% in EXT2. Frameshift, nonsense and missense mutations represented the majority of HME-causing mutations. Diagnosis of HME was made based on the clinical presentations and radiological documentations. Most patients needed no treatment. Surgical treatment was often directed to remove symptomatic exostoses, particularly those of suspected malignancy degeneration, and correction of skeletal deformities. This study shows some variance from current literature regarding other ethnic populations and may provide valuable baseline assessment of the natural history of HME in mainland China.”
– Source: Guo XL, Deng Y, Liu HG, Clinical characteristics of hereditary multiple exostoses: a retrospective study of mainland chinese cases in recent 23 years. J Huazhong Univ Sci Technolog Med Sci. 2014; 34(1):42-50 – See more at: http://www.cancerindex.org/geneweb//X0205.htm
11. The following links http://www.cancerindex.org/geneweb//X0205.htm provides a detailed overview of ongoing HME-related research worldwide. A lot of research is now being conducted on mainland China with conclusions (as per the attached) highlighting that:
– “HME starts earlier and becomes more severe and extensive with each successive generation in members of the pedigree analyzed. A splicing mutation, IVS5+1G>A, of EXT1, first identified in Chinese population, may be responsible for HME in the studied pedigree. EXT1 and EXT2 mutation rates may be different between the Chinese and Western populations – See more at: http://www.cancerindex.org/geneweb//X0205.htm#sthash.JRl5abuL.dpuf“
12. Hereditary Multiple Exostoses: New Insights into Pathogenesis, Clinical Complications, and Potential Treatments (June 2017)
“Hereditary multiple exostoses (HME) is a complex musculoskeletal pediatric disorder characterized by osteochondromas that form next to the growth plates of many skeletal elements, including long bones, ribs, and vertebrae. Due to its intricacies and unresolved issues, HME continues to pose major challenges to both clinicians and biomedical researchers. The purpose of this review is to describe and analyze recent advances in this field and point to possible targets and strategies for future biologically based therapeutic intervention.
Most HME cases are linked to loss-of-function mutations in EXT1 or EXT2 that encode glycosyltransferases responsible for heparan sulfate (HS) synthesis, leading to HS deficiency. Recent genomic inquiries have extended those findings but have yet to provide a definitive genotype-phenotype correlation. Clinical studies emphasize that in addition to the well-known skeletal problems caused by osteochondromas, HME patients can experience, and suffer from, other symptoms and health complications such as chronic pain and nerve impingement. Laboratory work has produced novel insights into alterations in cellular and molecular mechanisms instigated by HS deficiency and subtending onset and growth of osteochondroma and how such changes could be targeted toward therapeutic ends. HME is a rare and orphan disease and, as such, is being studied only by a handful of clinical and basic investigators. Despite this limitation, significant advances have been made in the last few years, and the future bodes well for deciphering more thoroughly its pathogenesis and, in turn, identifying the most effective treatment for osteochondroma prevention.”
Source / Author: https://www.ncbi.nlm.nih.gov/pubmed/284664532017 Translational Research Program in Pediatric Orthopaedics, Abramson Research Center, 902D, Division of Orthopaedic Surgery, Department of Surgery, The Children’s Hospital of Philadelphia, Philadelphia, PA, 19104, USA. firstname.lastname@example.org.
Dedicated to ‘Our Lady Of The Immaculate Conception’ (formerly known as the Church of the Saviour), Hangzhou’s Cathedral of Santa Maria Immaculate, which I attend, has long been
Address: 415 North Zhongshan Road, Hangzhou. 天主教堂 中山北路415号
Bus #s: 11, 28, 38
Tel #: 0571-85101503
English Mass Schedule: Saturday 18.30 hrs
Chinese Mass Schedule: Sunday 06.30 hrs, 09.00 hrs, 19.00 hrs
considered one of the most serenely beautiful churches in China. Remarkable is the wonderful quality of silence experienced within, given that bustling Zhongshan Road is only a very short distance away. Known simply as Tiānzhǔ Táng (天主堂), the three naves Catholic Church sporting a conspicuous baroque facade is the only Catholic Church currently in service within the city of Hangzhou. Indoors, the three naves (or one nave and two aisles) are separated by two rows of columns running longitudinally down the granite tiled flooring to the sanctuary of the main altar and apse area which is adorned by a large, eye-catching, fresco depicting Christ watching over his Hangzhou flock by way of bright rays of light beaming through clouds of darkness over the West Lake. Striking in its simplicity the fresco based on typical western artistic styles was painted by local Hangzhou artists. Natural light, beaming through stain-glass windows of saints, brightens the inside and the aisles on either side of main aisle lead down to side-altars worshiping statues of St. Peter and St. Paul. Placed at intervals along the side walls of the outer naves are plaques depicting the Stations Of The Cross, and there is also one confessional booth.
History of the Hangzhou Catholic Church of Our Lady of the Immaculate Conception
It will be difficult to find anyone locally who knows much about its history. Here’s what I found out. Likely inspired by the baroque designed Chiesa del Gesu Jesuit church in Rome, which was the model for many Jesuit churches, the first Catholic Church of Our Lady Of The Immaculate Conception in Hangzhou was built in 1661 by Italian Jesuit pastor, missionary, cartographer, and historian, Martino Martini (Wei Kuang Guo / 卫匡国).
It had taken two years to construct and was hardly built when on June 6thMartino Martini died from cholera in Hangzhou. He is buried in the Dafangjing Jesuit Cemetery (大方井卫匡国等公墓) on the north side of Beigao Feng (北高峰). It seems that twenty years later Martino Martini’s body was discovered in a relatively unblemished state, whereupon it became a venerable object of cult-like worship, not only for Christians. In 1877, in a bid to put an end to what it perceived to be idolisation, the Catholic Church hierarchy had Martini’s body reburied.
As the leading China geographer of the 18th Century, Martino Martini is celebrated as the first to undertake the study of Chinese history and geography with meticulous scientific impartiality. Added acclaim in China and beyond alludes to Martino Martini’s unique awareness of Chinese culture and profound understanding of all things Chinese as being the bedrock from which modern sinology has developed. During the reign of the Qing Emperor Kangxi, in 1691 an anti-catholic drive coordinated by Zhang Penghe (张鹏翮), the Confucian governor of Zhejiang Province, resulted in the practice of Catholicism being outlawed throughout Zhejiang. The Italian Jesuit Prospero Intorcetta, who had already lived in Hangzhou for 13 years, was expelled for staying in Hangzhou without authorisation, publishing books, circulating pamphlets throughout Zhejiang, and baptising over 1,000 people. Governor Zhang subsequently took over the Church of Our Lady Of The Immaculate Conception ordering all its books to be burned and printing woodcuts destroyed.
The following year, under pressure from Jesuits and Manchu Prince Songgotu, Zhang Penghe in an apparent about turn commanded that the Church of Our Lady Of The Immaculate Conception be completely repaired. However, Zhang continued to arrest and persecute Catholics, while several churches in Hangzhou, Haining and Jiaxing which didn’t have residing priests were confiscated.
In late 1692 the Catholic Church of Our Lady Of The Immaculate Conception in Hangzhou was badly damaged by a fire, remaining in a state of disrepair until 1699 when Emperor Kangxi himself passed by the church. After one of his ministers had inspected the interior Kangxi granted 200 silver taels to complete the restoration. Two characters “敕建” (chi jian) – meaning “built by order of the emperor” – were inscribed on to the gate.
In 1730 Kangxi’s son Emperor Yongzheng proscribed Catholicism and Catholic Church of Our Lady Of The Immaculate Conception was converted into the Tao Buddhist temple of the Celestial Empress, Tian Hou Gong (天后宫). The characters “敕建” were chiseled off the gate. It was not until 1848 that it became a working Catholic church again when a group of Dutch, French and English Lazarists took it over.
Further disruption occurred during the Cultural Revolution when all religious activities ceased. For a period of 12 years the main church hall was divided into 10 small cells for imprisoning criminals, while the other church buildings were also divided up as residences. On December 12th 1982 Mass was once again celebrated at the re-opened church, while by 1986 all remaining families who had lived there during the Cultural Revolution had been relocated to new residences.
The Catholic Church of Our Lady Of The Immaculate Conception is now listed as an historic site under the protection of the Municipal Government of Hangzhou.
Chinese Catholic Patriotic Association (CCPA)
Prior to the founding of the People’s Republic of China in 1949 the Catholic Church in China was under the control of foreign missionaries, and some Church organisations opposed communist rule. In 1957 the secular Chinese Catholic Patriotic Association (CCPA) was set up to organise the Catholic Church in China under government patronage. It no longer recognised the authoritative role of the Pope as the leader of Chinese Catholics, and in the appointment of new bishops. The Vatican immediately declared the Chinese Catholic Patriotic Association incompatible with Catholic doctrine and since then there have been no formal diplomatic links between the Vatican and Beijing. An underground Catholic Church said to number millions of Chinese Catholics still remains faithful to the Bishop of Rome.
Today’s Mass at Catholic Church of Our Lady of the Immaculate Conception
The Catholic Church of Our Lady Of The Immaculate Conception in Hangzhou is always filled to capacity for the 9.00 a.m.. Clear evidence of the growing appetite for spiritual values among mainland China’s officially atheist population, the worshipers represent a broad spectrum of men and women, young and old, all in thoughtful concentration. This church has a genuine feel to it and, given the unremitting pressures of daily life that abound in rapidly changing China, it is wonderful to observe and experience the congregation’s deep sense of spiritualism and respect for each other. Streaming out of the church after the conclusion of Mass all appear at peace within, assured.
On the face of it, given that in spite of everything this is a Chinese Catholic Patriotic Association-operated church, this could be a Mass typical of any Catholic Church the world over. The choir sings the usual hymns (the acoustics are very good), while the benches at the foot of the left side-aisle hold a very energetic group of hearing impaired parishioners using sign language to communicate, their smiling facial expressions and fast-moving hands corresponding with every spoken word. There is holy water, a lively confessional, and communion, while the Our Father is prayed most fervently with hands raised high. When it comes to offering each other the sign of peace there is that spontaneous outpouring of goodness and togetherness which typifies Catholic Church communities everywhere. The genuine sincerity is palpable.
If you did not have a chance to experience the serenity of a place like this you’d probably leave China thinking that in the rush to keep up with what is termed as “progress” everyone is only concerned with their own material well-being. As witnessed by the outpouring of compassion following the apocalyptic Sichuan Earthquake, and now today in the Catholic Church of Our Lady Of The Immaculate Conception in Hangzhou such a thought would be entirely mistaken. I cannot visually / vocally see or hear any difference between this and Mass back in Ireland, expect for noticing that no offering was collected. I guess the official Catholic Church in China doesn’t have a problem with funding!
The most recent renovation of Catholic Church of Our Lady Of The Immaculate Conception in Hangzhou was completed in 2012, and while the demolition of the front wall may have been designed to present a church that is more conspicuously open, the appearance of security camera above the nave ensures that worshipers are always under the watchful eye of the Party.
English Mass Saturday 18:30 hrs
An English Mass, which is celebrated at 6.30 p.m. on Saturday evening, is typically attended by a colourful mix of Hangzhou’s foreign community from Africa, Asia, South America and Europe. The English mass pamphlet refers to the Pope (in a spiritual capacity) – indeed the wall of an office just inside the entrance gate hosts a large photo of the late Pope John Paul II.
Roman Catholic Archdiocese of Hangzhou / Hangchow
The archdiocese of Hangzhou, which at the time had less than 30,000 practising Catholics has not had a Vatican appointed bishop since 1956 following the death of Archbishop Jean Joseph Georges Deymier (梅占魁). In June 2000, The Chinese Catholic Patriotic Association appointed (now 91 years old) Matthew Cao Xiang-de (曹緗德) (a.ka. Cao Yude) as bishop, an appointment that prompted the Vatican to invoke canon 1382: “Both the Bishop who, without a pontifical mandate, consecrates a person a Bishop, and the one who receives the consecration from him, incur a ´latae sententiae´ excommunication reserved to the Apostolic See.”. Source: Latae sententiae
Previous Archbishops of Hangzhou, Matthias Wu Guo-huan (吳國煥) (1958–1987), John Zhu Feng-qing (朱峰青) (1988 – 1997) also had no papal mandate.