Article published the Monday 22 November 2010 - Latest update : Monday 22 November 2010
Prosecutors call for prison terms for growth hormone doctors
A man holds a sign that says "aberration, infected hormone, justice flouted" at the courthouse after the first trial AFP By RFI Prosecutors have called for a three-year prison sentence for a biochemist accused of causing the wrongful death of 119 people to whom he administered tainted growth hormones in the 1980s. The months-long appeals trial ends Wednesday against Fernand Dray and other medical staff involved in administering the hormones.
"Professor Dray’s specific fault is an accumulation of imprudence and negligence," said prosecutor Bruno Sturlese, who asked for the maximum sentence for Dray.
The 88-year-old is the former head of a laboratory at the prestigious Pasteur Institute, which manufactured the growth hormone. Dray’s lawyers have called for a dismissal of the charges.
Prosecutors are also calling for six to nine months of prison for paediatrician Elisabeth Mugnier, 61, for involuntary homicide.
The hormone, which was manufactured from the glands from unregulated cadavers, turned out to transmit Creutzfeldt-Jakob (MCJ) disease. It was administered to 1,698 children between 1980 and 1988.
Victims have already received some 31 million euros in damages from the government.
Families of those who took the hormones have been involved in court cases against the manufacturers and administrators for almost 20 years to prove that they acted with the knowledge that the drug was infected.
The judge in the first case against Dray determined there was not enough evidence that he acted knowingly, and he was acquitted in January 2009.
The appeals case ends Wednesday, and a verdict is not expected before the spring.
tags: France - Health/Medicine - Judge - Law - Trial
France - Article published the Monday 04 October 2010 - Latest update : Monday 04 October 2010
Relatives appeal over French growth hormone deaths
Fernand Dray, 88-year-old manager of an Institut Pasteur lab appears in court on October 2010 AFP By RFI Relatives of patients who died after being prescribed growth hormones are appealing a 2009 court ruling which cleared doctors who had prescribed the hormones.
Since the trial’s first hearing in 2008, five patients have died years after taking growth hormones which were infected with the Creutzfeldt-Jakob disease, a degenerative brain disease.
In the 1980s, doctors prescribed growth hormones to 1,698 children who were deemed too small. Two-hundred children have since died and relatives have launched legal action against paediatricians and biologists who allowed the drug to be prescribed.
In January 2009 a French court ruled that the doctors could not have known that the hormones – removed from corpses – were contaminated.
The prosecution is appealing against the court ruling and insists that three of the doctors should be held responsible for the deaths.
On Monday, hundreds of families converged on Paris to witness the trial. Although relatives of the victims hope that French judges will condemn several doctors, many have lost hope.
“I have come today, but without much hope. I am left to take responsibility for this treatment that was given to my son. That’s not enough,” Lea Le Thaeno, mother of Benoît, who died at the age of 28, told the AFP wire service.
More deaths may be expected in coming years as the Creutzfeldt-Jakob disease has an incubation period of over 30 years and may be transmitted to the patient’s children.
tags: France - Health - Justice
Today in France 6 February 2008
Growth hormone victims have their day in court
Article published on the 2008-02-06 Latest update 2008-02-06 10:15 TU
Members of the French association of growth hormone's victims (AVHC) and others in front of the Paris court on 6 February. (Photo: AFP) Seven french doctors and health officials went on trial Wednesday accused of manslaughter and fraud. They allegedly ignored dangers associated with growth hormones taken from the pituitary glands of cadavers that may have been infected with a varient of mad cow. More than 100 children who were given the hormones in the 1980s have since died. Wednesday was the first time victims and their families faced the accused. Sarah Elzas reports on the opening of the four-month long trial.
PPo4-14: Dura Mater-Associated Creutzfeldt-Jakob Disease in Italy
Anna Ladogana,1 Maria Puopolo,1 Loredana Ingrosso,1 Susanna Almonti,1 Vittorio Mellina,1 Giulio Rosati,1 Renato Ortu,2 Orso Bugiani,2 Fabrizio Tagliavini,2 Vincenzo La Bella,2 Federico Piccoli,2 Maria Valeria Saddi,2 Salvatore Bruno Murgia,3 Giorgio Giovanni Bono,3 Salvatore Castellino,3 Paolo Fociani,3 Piero Parchi3 and Maurizio Pocchiari3
1Istituto Superiore di Sanità, Roma; Ospedale Pertini, Roma; Ospedale Civile, Rieti; University of Sassari, Sassari; IRCCS C. Besta Milano; IRCCS C. Besta Milano; 2University of Palermo, Palermo; Ospedale S. Francesco, Nuoro; 3Ospedale di Circolo di Varese e Fondazione Macchi, Varese; Ospedale Civile, Ragusa; Ospedale L. Sacco, Milano; University of Bologna, Bologna; Istituto Superiore di Sanità, Roma
Key words: dura mater, CJD, transmission
During the years 1993 to 2008, 40 suspected CJD cases were reported to the Italian CJD Registry with a previous history of neurosurgery, and in seven of these cases commercial "dura mater" (DM) grafts were clearly stated in the record of the surgical intervention. Of these seven cases, one case did not receive a final diagnosis of CJD, while in six cases a diagnosis of definite or probable iatrogenic DM-associated CJD was made. Further analysis of these iatrogenic CJD patients found a time-and-space cluster for two patients treated on June 1986 within ten days in the same hospital by neurosurgical intervention for traumatic head injury. The six DM-CJD patients were studied for their clinical and diagnostic findings. The DM-CJD patients had a mean incubation time (period between surgery and the onset of the disease) of 178.3 months ranging from 94 to 287 months, and a mean age at onset of 40.5 (range 21–75) years. The median disease duration was 12 (range 3–46) months. Five cases were clinically classified as probable CJD (typical EEG n = 2 and 14-3-3 proteins positive test n = 4) and one case as possible CJD. Three patients were MM homozygous and two were VV at codon 129 of the prion protein gene (PRNP), while in one case the genetic analysis of PRNP was not done. The MRIs showed basal ganglia signal increase in three out of six cases. Three patients underwent necroscopy and were classified as definite, while three cases were finally classified as probable CJD.
also please see the attached pdf file of the ;
International Prion Congress: From agent to disease September 8–11, 2010 Salzburg, Austria Previously published online
WHO Tables on Tissue Infectivity Distribution in Transmissible Spongiform Encephalopathies Updated 2010
MAJOR CATEGORIES OF INFECTIVITY: TABLES IA, IB, IC
The assignment of tissues to high, low, and undetected infectivity categories is based exclusively upon observations of naturally occurring disease, or primary experimental infection by the oral route (in ruminants). The Tables do not include results from disease models using strains of TSE that have been adapted to experimental animals, because passaged strain phenotypes can differ significantly and unpredictably from those of naturally occurring disease. However, for tissues and fluids of exceptional public health interest, such as muscle, intestine, skin, secretions and excretions, experimental results have been indicated in footnotes.
Because the detection of misfolded prion protein (PrPTSE) broadly parallels infectivity titers in various tissues [Beekes et al 1996; Andreoletti et al 2004], PrPTSE testing results are presented in parallel with bioassay data.
Although a given tissue may be positive or negative in different varieties of TSE, the expert group considered a tissue to be potentially infectious even if a positive result occurred in only a single disease. The categorical assignment of tissues will almost certainly undergo further revision as new data accumulate from increasingly sensitive tests.
IA: High-infectivity tissues: CNS tissues that attain a high titer of infectivity in the later stages of all TSEs, and certain tissues that are anatomically associated with the CNS.
IB: Lower-infectivity tissues: peripheral tissues that have tested positive for infectivity and/or PrPTSE in at least one form of TSE.
IC: Tissues with no detectable infectivity: tissues that have been examined for infectivity and/or PrPTSE with negative results.
Data entries are shown as follows
+ Presence of infectivity or PrPTSE
- Absence of detectable infectivity or PrPTSE
NT Not tested
NA Not applicable ?
( ) Limited or preliminary data
[ ] Infectivity or PrPTSE data based exclusively on bioassays in transgenic
(Tg)mice over-expressing the PrP-encoding gene or PrPTSE amplification methods.
A word of caution is offered about tissues in Table IB for which positive results are so far limited to either detection of PrPTSE using amplification techniques (PMCA), or infectivity bioassays in Tg mice that over-express PrP. The amounts of pathological protein or infectious agent detected by these exquisitely sensitive assays may well fall below the threshold of transmissibility for normal animals and humans. WHO Tables on Tissue Infectivity Distribution in Transmissible Spongiform Encephalopathies 5
A good example is illustrated in the studies of urine and feces from deer infected with CWD: bioassays using normal deer as recipient subjects were negative; subsequent bioassays performed in Tg mice were positive. A similar discordance was observed for BSE muscle inoculated into cattle and Tgmice. Until more evidence is compiled showing that positive results in experimental PMCA and Tg mouse assays equate to a risk of transmitting disease under natural conditions, it cannot be assumed that such results imply the existence of a substantial risk to the health of animals or humans.
Considering the succession of updated Tables of the past few years, and the fact that inflammation has been shown to result in PrPTSE deposition in tissues that are not normally involved in TSE pathogenesis, it is evident that as testing continues, more tissues will find their way from Table IC into Table IB (but probably not from either Table IC or IB into Table IA). It is also evident that the data generated to date are far from complete, and that a great deal more work needs to be done if conclusions about the tissue distribution and significance of infectivity in a given TSE are to be based on direct measurements rather than by analogy to other forms of the disease.
Finally, it is critically important to understand that categories of infectivity are not the same as categories of risk, which require consideration not only of the level of infectivity in tissue, but also of the amount of tissue to which a person or animal is exposed, and the route by which infection is transmitted. For example, although the level of tissue infectivity is the most important factor in estimating the risk of transmission by instrument crosscontamination during surgical procedures (e.g., neurosurgery versus general surgery), it will be only one determinant of the risk of transmission by blood transfusions, in which a large amount of low-infectivity blood is administered intravenously, or the risk of transmission by foodstuffs that, irrespective of high or low infectivity, involve a comparatively inefficient oral route of infection.
Table IC: Tissues with no detected infectivity or PrPTSE
Bone NT - NT - - NT NT NT NT NT
Tendon NT - NT - - NT NT NT NT NT
please see full text with tables here ;
WHO Tables on Tissue Infectivity Distribution in Transmissible Spongiform Encephalopathies Updated 2010
also in the references at bottom i saw ;
12. A single positive marrow in multiple transmission attempts from cattle orally dosed with BSE-infected brain [Wells et al., 1999; Wells et al., 2005; Sohn et al., 2009].
Thursday, July 08, 2010
Nosocomial transmission of sporadic Creutzfeldt–Jakob disease: results from a risk-based assessment of surgical interventions Public release date: 8-Jul-2010
Tuesday, May 04, 2010
Review of the Human Pituitary Trust Account and CJD Issue 20 January 2010
Saturday, January 26, 2008
CJD HGH BODY SNATCHERS Saturday, January 26, 2008 CJD HGH BODY SNATCHERS HORMONE DRUGS LED TO CJD DEATH
09:00 - 26 January 2008
Sunday, November 21, 2010
Preclinical Deposition of Pathological Prion Protein in Muscle of Experimentally Infected Primates and potential Iatrogenic TSE there from
Monday, February 01, 2010
Import Alert 57-20 and 84-03 Human Dura Mater and risk factors there from due to Creutzfeldt Jakob Disease (CJD)
Creutzfeldt-Jakob Disease, CJD Support Group for short statured children of the 1970's and 1980's. Recommendations for Unapproved/Unregistered recipiants
Report of a WHO Consultation on Medicinal and other Products in Relation to Human and Animal Transmissible Spongiform Encephalopathies
With the participation of the Office International des Epizooties (OIE)
Geneva, Switzerland 24-26 March 1997
Early cognitive decline in Creutzfeldt-Jakob disease associated with human growth hormone treatment
R J Cordery, M Hall, L Cipolotti, S Al-Sarraj, D G O’Donovan, L Davidson, P Adlard, M N Rossor
Creutzfeldt-Jakob disease 38 years after diagnostic use of human growth hormone
E A Croes, G Roks, G H Jansen, P C G Nijssen, C M van Duijn
J Neurol Neurosurg Psychiatry 2002;72:792-793
A 47 year old man is described who developed pathology proven Creutzfeldt-Jakob disease (CJD) 38 years after receiving a low dose of human derived growth hormone (hGH) as part of a diagnostic procedure. The patient presented with a cerebellar syndrome, which is compatible with iatrogenic CJD. This is the longest incubation period described so far for iatrogenic CJD. Furthermore, this is the first report of CJD after diagnostic use of hGH. Since the patient was one of the first in the world to receive hGH, other cases of iatrogenic CJD can be expected in the coming years.
Prion diseases are potentially transmissible. Human to human transmission was first reported in 1974, when a 55 year old woman was described who developed symptoms of Creutzfeldt-Jakob disease (CJD) 18 months after a corneal transplant.1 Since then, transmission has been reported after stereotactic electroencephalographic (EEG) depth recording, human growth hormone (hGH) and gonadotrophin treatment, and dura mater transplantation.2-5 More than 267 patients with iatrogenic CJD are known today and their number is growing.6 The most important iatrogenic cause of CJD is still contaminated cadaveric hGH. Exposure to contaminated hGH occurred before 1985, when recombinant growth hormone became available. In a recent study, incubation periods in 139 patients with hGH associated CJD were found to range from 5-30 years, with a median of 12 years.6 One of the factors influencing incubation time is genotype on polymorphic codon 129 of the prion protein gene.7 The incubation time is significantly shorter in people who are homozygous for either methionine or valine on this polymorphism.7
We describe the second patient with hGH related CJD in the Netherlands. The patient developed the disease 38 years after hGH injections. To our knowledge, this is the longest incubation period described for any form of iatrogenic CJD. Further-more, our patient was not treated with hGH but only received a low dose as part of a diagnostic procedure.
This patient presented at the age of 47 years with paraesthesia in both arms for six months, difficulty with walking for four weeks, and involuntary movements of mainly the upper extremities of two weeks' duration. He did not notice any change in cognitive function, although his twin sister had noticed minor memory disturbances. There was no family history of neurological disease. During childhood the patient had experienced a growth delay compared with his twin sister and with the average in the Netherlands. When he was 9 years old, a nitrogen retention test with 6 IU hGH over five days was performed to exclude growth hormone deficiency. Since the result was not decisive, a quantitative amino acid test was performed, which measures 30 amino acids during fasting and one, two, and three hours after growth hormone injection. No abnormal amino acid concentrations were found making the diagnosis of primordial dwarfism most likely. Therefore, no treatment with hGH was given.
On neurological examination we found a slight dysarthria without aphasia. Cranial nerve function was normal. Walking was unstable and wide based. During movements of the upper extremities myoclonic jerks were present. Sensation, muscle tone, and strength were normal. Co-ordination was impaired in all four limbs with a disturbed balance. Tendon reflexes were brisk at the arms and increased at the legs with a clonus in the ankle reflex. Plantar responses were both normal. On the mini mental state examination, the patient scored 30/30. Routine laboratory investigation, thyroid function, vitamin concentrations (B-1, B-6, B-12, and E), and copper metabolism were normal. Admission EEG examination showed generalised arrhythmic slow activity with diffuse spikes and spike waves. EEG examination two months later showed a further slowing of the rhythm with bilateral diphasic sharp waves but was not typical for CJD. Cerebral magnetic resonance imaging was normal. Cerebrospinal fluid examination showed 1 cell/3 µl, normal glucose and protein concentrations, and a strongly positive 14-3-3 protein test. The patient was homozygous for methionine on the PRNP codon 129 polymorphism. On clinical grounds, CJD was diagnosed. Within one month the patient's condition deteriorated rapidly and because of severe disturbances in coordination and progressive myoclonus he became bedridden. An eye movement disorder developed with slow saccadic and dysmetric eye movements. Temperature became unstable with peaks of 39°C without an infectious focus, for which a disorder of autoregulation was presumed. Until a very advanced stage, cognitive function was intact. The patient died five months after admission. The diagnosis of CJD was confirmed at necropsy. The brain weighed 990 g and showed clear cortical and cerebellar atrophy. Spongiosis, neuronal loss, and gliosis were found predominantly in the putamen, caudate nucleus, and basotemporal and cerebellar cortex; the cerebellum was the most severely affected of these. Vacuoles ranged from 2-12 µm. No amyloid or Kuru plaques were found. Immunohistochemical staining (3F4 antibody 1:1000, Senetek, USA) was clearly positive for prion protein accumulation in a "synaptic" distribution. Most deposition was found in the stratum moleculare of the cerebellum.
We describe a 47 year old patient who developed pathology proven CJD 38 years after hGH injections. The patient was never treated with hGH but received a small dose as part of a diagnostic procedure. The onset of CJD was signalled by prodromal symptoms of paraesthesia followed by a rapidly progressive ataxia. The disease presentation and course with predominantly cerebellar and eye movement disorders are compatible with iatrogenic CJD caused by hGH treatment.6 8
Growth hormone treatment was first described in 1958 but hGH was not produced on a larger scale from human pituitary glands until the beginning of the 1960s. In the Netherlands growth hormone extraction started in 1963 and was soon centrally coordinated. Until 1979 growth hormone was extracted non-commercially from pituitaries by a pharmaceutical company. In 1971 commercial products also became available. Our patient was one of the first to receive hGH in the Netherlands but the origin of this product was not recorded. A causal relation can therefore not be established with full certainty, but coincidentally receiving growth hormone and developing this very rare disease is unlikely. Since the clinical course in this relatively young patient is in accordance with an iatrogenic cause, we think the probability is high that the hGH injections explain the development of CJD in this patient.
The first Dutch patient with hGH related CJD died in 1990. 9 During several periods from 1963 to 1969 she received intramuscular injections of hGH. During an unknown period the hGH was derived from South America. At age 39, 27 years after starting the treatment, she developed an ataxic gait, slurred speech, sensory disorders, and myoclonus, but her cognitive function remained normal. Postmortem examination of the brain confirmed the diagnosis of CJD.9 Following the identification of this patient, a retrospective study was started to trace all 564 registered hGH recipients who were treated before May 1985. Until January 1995, none of these was suspected of having CJD.10 Since 1993 prospective surveillance for all forms of human prion disease has been carried out in the Netherlands and, apart from the patient described above, a further two patients with iatrogenic CJD have been identified, who developed the disease after dura mater transplantation.11
An incubation period as long as 38 years had never been reported for iatrogenic CJD. Huillard d'Aignaux et al7 studied the incubation period in 55 patients with hGH related CJD in a cohort of 1361 French hGH recipients. The median incubation period was between 9 and 10 years. Under the most pessimistic model, the upper limit of the 95% confidence interval varied between 17 and 20 years. Although the infecting dose cannot be quantified, it can be speculated that the long incubation period in our patient is partly explained by the administration of a limited amount of hGH. This hypothesis is supported by experimental models, in which higher infecting doses usually produce shorter incubation periods.6 Since our patient was one of the first in the world to receive hGH, this case indicates that still more patients with iatrogenic CJD can be expected in the coming years. Another implication of our study is that CJD can develop even after a low dose of hGH. This case once more testifies that worldwide close monitoring of any form of iatrogenic CJD is mandatory.
We are grateful to M Jansen PhD MD for his search for the origin of the growth hormone and P P Taminiau MD. CJD surveillance in the Netherlands is carried out as part of the EU Concerted Action on the Epidemiology of CJD and the the EU Concerted Action on Neuropathology of CJD, both funded through the BIOMED II programme, and is supported by the Dutch Ministry of Health. This surveillance would not have been possible without the cooperation of all Dutch neurologists and geriatricians.
E A Croes, G Roks*, C M van Duijn, Genetic Epidemiology Unit, Department of Epidemiology and Biostatistics, Erasmus University Medical Centre Rotterdam, PO Box 1738, 3000 DR Rotterdam, Netherlands
P C G Nijssen, Department of Neurology, St Elisabeth Hospital, PO Box 90151, 5000 LC Tilburg, Netherlands
G H Jansen, Department of Pathology, University Medical Centre Utrecht, Heidelberglaan 100, 3584 CX Utrecht, Netherlands
*Also the Department of Neurology, St Elisabeth Hospital
Correspondence to: Professor C M van Duijn, Genetic Epidemiology Unit, Department of Epidemiology and Biostatistics, Erasmus University Medical Centre Rotterdam, PO Box 1738, 3000 DR Rotterdam, Netherlands; email@example.com
Received 27 December 2001 In revised form 1 March 2002 Accepted 12 March 2002
Competing interests: none declared
1 Duffy P, Wolf J, Collins G, et al. Possible person-to-person transmission of Creutzfeldt-Jakob disease. N Engl J Med 1974;290:692-3.
2 Bernoulli C, Siegfried J, Baumgartner G, et al. Danger of accidental person-to-person transmission of Creutzfeldt-Jakob disease by surgery. Lancet 1977;i:478-9.
3 Koch TK, Berg BO, De Armond SJ, et al. Creutzfeldt-Jakob disease in a young adult with idiopathic hypopituitarism: possible relation to the administration of cadaveric human growth hormone. N Engl J Med 1985;313:731-3.
4 Cochius JI, Burns RJ, Blumbergs PC, et al. Creutzfeldt-Jakob disease in a recipient of human pituitary-derived gonadotrophin. Aust NZ J Med 1990;20:592-3.
5 Thadani V, Penar PL, Partington J, et al. Creutzfeldt-Jakob disease probably acquired from a cadaveric dura mater graft: case report. J Neurosurg 1988;69:766-9.
6 Brown P, Preece M, Brandel JP, et al. Iatrogenic Creutzfeldt-Jakob disease at the millennium. Neurology 2000;55:1075-81.
7 Huillard d'Aignaux J, Costagliola D, Maccario J, et al. Incubation period of Creutzfeldt-Jakob disease in human growth hormone recipients in France. Neurology 1999;53:1197-201.
8 Billette de Villemeur T, Deslys JP, Pradel A, et al. Creutzfeldt-Jakob disease from contaminated growth hormone extracts in France. Neurology 1996;47:690-5.
9 Roos RA, Wintzen AR, Will RG, et al. Een patiënt met de ziekte van Creutzfeldt-Jakob na behandeling met humaan groeihormoon. Ned Tijdschr Geneeskd 1996;140:1190-3.
10 Wientjens DP, Rikken B, Wit JM, et al. A nationwide cohort study on Creutzfeldt-Jakob disease among human growth hormone recipients. Neuroepidemiology 2000;19:201-5.
11 Croes EA, Jansen GH, Lemstra AF, et al. The first two patients with dura mater associated Creutzfeldt-Jakob disease in the Netherlands. J Neurol 2001;248:877-81.
FULL TEXT AND MORE HERE ;
Possible iatrogenic Creutzfeldt-Jakob Disease in an adult male 50 years after treatment with human chorionic gonadotrophin
Brian Appleby1, Paul Brown2 1Johns Hopkins University School of Medicine, USA; 2CEA/DSV/iMETI/SEPIA, France
Background: Known causes of iatrogenic Creutzfeldt-Jakob disease (iCJD) include cadaverous corneal transplants, dural mater grafts, human growth hormone (hGH), neurosurgical depth electrodes, and neurosurgical instrument contamination. Four cases of iCJD from human gonadotrophin have been described to date, all of whom have been women.
Objectives: To present a case of possible iCJD from human chorionic gonadotrophin (hCG) and review data from four other cases Methods: Case report and descriptive analysis
Results: A 62-year-old Caucasian man developed ataxia that resulted in frequent falls and an initial diagnosis of benign positional vertigo. Further workup including brain magnetic resonance imaging (MRI), electroencephalogram (EEG), and a lumbar puncture were unrevealing. A cerebrospinal 14-3-3 protein analysis was indeterminate. At the end of the third month of his illness, he developed short-term amnesia, disorientation, and confabulation. A repeat EEG showed generalized slowing without evidence of periodic sharp wave complexes and a repeat 14-3-3 analysis was positive. A second brain MRI showed hyperintensity in the basal ganglia on diffusion- weighted images. He died following a four-month illness. Severe vacuolization was noted on microscopic examination and Western blot analyses detected type II prion proteins. Genomic analyses detected a silent polymorphism at codon 117 and valine homozygousity at codon 129 of the prion protein gene. Further review of his medical records revealed a history of cryptorchidism and treatment with hCG as a child in the 1940’s-1950’s.
Discussion: This case report describes a possible case of iCJD from hCG injections and is unique in that the patient was male and the incubation period approached 50 years. His clinical presentation, EEG findings, and codon 129 homozygousity are similar to previously described cases.