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9 October 2006
I.
WHAT'S NEW?
Ongoing Trials with Target e*CRF®
II.
QUIZ - (Fill In The Blanks)
Probiotics
III. HISTORY OF MEDICINE
Leukemia
IV. PSYCHIATRY
Polymorphism and Disease Response
V. MUSCULAR DYSTROPHY
Mouse Models of Disease Show Very Promising Results
VI. OPHTHALMOLOGY
Ranibizumab For The Treatment of Age-Related
Macular Degeneration
VII. GASTROENTEROLOGY
Baclofen Works in Pediatric Patients
VIII. FDA
Zolinza Approved For Cutaneous T-cell lymphoma
IX.
Ongoing
Trials with Target e*CRF®
Target e*CRF®, Target Health's proprietary EDC system is now being used in
studies all over the world in areas such as Oncology, Ophthalmology,
Rheumatology, Cardiology, Dermatology, Metabolism, Oral Care, Women's Health,
Pediatrics, Wound Healing, Diagnostics and Public Health. Release of the next
version of Target e*CRF® is planned for this quarter. Based on conversations
with several of our clients and companies who got a sneak preview, we
have redesigned the software to eliminate the need for any advanced
programming skills, virtually all of application development can be done
with experienced Sr. CRAs and clinical data managers. Companies will not
need to hire any new people to run a web trial and costs will come down even
more.
For more information about
Target Health, please contact Dr.
Jules T. Mitchel.
Probiotics
Probiotics are small 1) ___ that
help maintain the natural balance of microflora in the intestines. The normal
human 2) ___ tract contains about 400 types of bacteria that reduce the growth
of 3) ___ bacteria and promote a healthy digestive system. The largest group of
probiotic bacteria in the intestine is 4) ___ acid bacteria, of which Lactobacillus
acidophilus, found in yogurt, is the best known. Yeast is also a probiotic
substance. Probiotics are available as dietary supplements. In most
circumstances, people use probiotics to prevent diarrhea caused by 5) ___.
Antibiotics kill "good" (beneficial) bacteria along with the bacteria
that cause illness. A decrease in beneficial bacteria may lead to 6) ___.
Taking probiotic supplements (as capsules, powder, or liquid extract) may help
replace the lost beneficial bacteria and thus help prevent diarrhea. A decrease
in beneficial bacteria may also lead to development of other infections, such
as 7) ___ and urinary tract infections. Probiotics are considered safe because
they are bacteria that already are part of the 8) ___digestive system.
ANSWERS: 1) organisms; 2) digestive; 3) harmful;
4) lactic; 5) antibiotics; 6) diarrhea; 7) yeast; 8) normal
III. HISTORY OF MEDICINE
Leukemia
The first fact description of a
case of leukemia in the medical literature dates to 1827, when a French
physician named Velpeau described a 63-year-old florist who developed an
illness characterized by fever, weakness, urinary stones, and substantial
enlargement of the liver and spleen. Velpeau noted that the blood of this
patient had a consistency "like gruel", and speculated that the
appearance of the blood was due to white corpuscles. In 1845, a series of
patients who died with enlarged spleens and changes in the "colors and
consistencies of their blood" was reported by the Edinburgh-based
pathologist, J.H. Bennett; who used the term "leucocythemia" to
describe this pathological condition. The term "leukemia" was
coined by Rudolf Virchow, the renowned German pathologist, in 1856. As a
pioneer in the use of the light microscope in pathology, Virchow was the first
to describe the abnormal excess of white blood cells in patients with the
clinical syndrome described by Velpeau and Bennett. As Virchow was uncertain of
the cause of the white blood cell excess, he used the purely descriptive term
"leukemia" (Greek: "white blood") to refer to the
condition. Further advances in the understanding of acute myeloid leukemia
occurred rapidly with the development of new technology. In 1877, Paul Ehrlich
developed a technique of staining blood films which allowed him to describe in
detail normal and abnormal white blood cells. Wilhelm Ebstein introduced the
term "acute leukemia" in 1889 to differentiate rapidly progressive
and fatal leukemias from the more indolent chronic leukemias. The term
"myeloid" was coined by Neumann in 1869, as he was the first to
recognize that white blood cells were made in the bone marrow (Greek: myelos)
as opposed to the spleen. The technique of bone marrow examination to diagnose
leukemia was first described in 1879 by Mosler. Finally, in 1900 the
myeloblast, which is the malignant cell in AML, was characterized by Naegeli,
who divided the leukemias into myeloid and lymphocytic. Edited
by Alexander Hays.
Polymorphism and Disease
Response
Polymorphisms in
the serotonin transporter gene (5-HTT) may influence antidepressant response to
selective serotonin reuptake inhibitors (SSRIs). The norepinephrine transporter
(NET) is the analogous target for norepinephrine reuptake inhibitors (NRIs). As
a result, a study published in the Journal of the American Medical Association
(2006;296:1609-1618), was performed to determine
whether antidepressant responses to SSRIs or NRIs are associated with genetic
polymorphisms of the corresponding monoamine transporters. The investigation
was a 6-week naturalistic treatment study with blinded outcome evaluation of 241
Korean inpatients and outpatients with major depression at an academic
psychiatry service. Treatments with an SSRI (n = 136)included
fluoxetine (Prozac) or sertraline (Zoloft) or an NRI (n = 105) nortriptyline
(Pamelor, Aventyl) antidepressant. Adherence was assessed by measuring plasma
concentration at 4 weeks. Patients were genotyped for s/l polymorphisms in
5-HTT promoter region (5-HTTLPR), 5-HTT intron 2 s/l variation,
and NET G1287A variation of exon 9. The main outcome measures were an SSRI and
NRI response (defined as ³ 50% decrease in Hamilton Rating Scale for Depression
score at 6 weeks). Results showed that an NRI response was associated with the
NET G1287A polymorphism (odds ratio [OR], 7.54; P<.001). An SSRI response
was associated with the 5-HTT intron 2 s/l variation (OR, 20.11; P<.001).
The 5-HTTLPR was also associated with an SSRI response (OR, 3.34; P = .006). In
contrast to studies in white patients, the favorable allele for SSRI response
was S 5-HTTLPR. The S 5-HTTLPR was associated also with NRI response (OR, 3.73
P = .01). The NET polymorphism was not associated with an SSRI response. The
NET G1287A GG genotype (56% of the population) was associated with better
response to the NRI (83.3% than to SSRI (58.7%) (OR, 3.52; P = .006). Some genotype
combinations were associated with high rates of antidepressant response and
others with low rates of response. It was concluded that monoamine transporter
gene polymorphisms were associated with response to antidepressants with
homologous monoamine transporter targets and that combinations of polymorphisms
were informative for response and nonresponse. The authors added that
confirmation of these preliminary findings would permit refined pharmacogenetic
selection of antidepressant treatment
Mouse Models of Disease Show
Very Promising Results
According to an
article published online in Nature Medicine (September 17, 2006; PMID
16980968), it has been demonstrated, for the first time, that a single drug can
rebuild damaged muscle in two strains of mice that develop diseases comparable
to two human forms of muscular dystrophy. For the study, trichostatin A (TSA),
an inhibitor of the enzyme deacetylase, was tested in two mouse models of
muscular dystrophy (MD): one that naturally develops a disease similar to
Duchenne MD in humans, the other genetically altered to develop a form of
dystrophy similar to the human limb-girdle MD. Results showed that at 45 to 90
days of age, the muscles of the MD mice showed much fibrous tissue and infiltration
of inflammatory cells. Unlike healthy mice, the mice with MD were unable to
either run on a treadmill or swim. MD mice given TSA daily for two to three
months, however, were virtually indistinguishable from healthy mice, and
biophysical studies showed virtually no difference between the muscle strength
of the mice with MD given the deacetylase inhibitor and healthy mice. According
to the authors, this is the first example of using a drug to counteract
muscular dystrophy in mouse models. The authors added that before such drugs
can be tested in people, further studies are needed to determine how long the
drug works and if it works in larger animals with bigger muscles, such as dogs.
Ranibizumab For The Treatment
of Age-Related Macular Degeneration
According to an article
published in the New England Journal of Medicine (2006;355:1419-1431),
Ranibizumab, a recombinant, humanized, monoclonal antibody Fab that neutralizes
all active forms of vascular endothelial growth factor A, has been evaluated
for the treatment of neovascular age-related macular degeneration. The
investigation was a multicenter, 2-year, double-blind, sham-controlled study.
Patients with age-related macular degeneration with either minimally classic or
occult (with no classic lesions) choroidal neovascularization, were randomly
assigned to receive 24 monthly intravitreal injections of ranibizumab (either
0.3 mg or 0.5 mg) or sham injections. The primary end point was the proportion
of patients losing fewer than 15 letters from baseline visual acuity at 12
months. The study enrolled 716 patients. Results showed that at 12 months,
94.5% of the group given 0.3 mg of ranibizumab and 94.6% of those given 0.5 mg
lost fewer than 15 letters, as compared with 62.2% of patients receiving sham
injections (P<0.001 for both comparisons). Visual acuity improved by 15 or
more letters in 24.8% of the 0.3-mg group and 33.8% of the 0.5-mg group, as
compared with 5.0% of the sham-injection group (P<0.001 for both doses).
Mean increases in visual acuity were 6.5 letters in the 0.3-mg group and 7.2
letters in the 0.5-mg group, as compared with a decrease of 10.4 letters in the
sham-injection group (P<0.001 for both comparisons). The benefit in visual
acuity was maintained at 24 months. During 24 months, presumed endophthalmitis
was identified in five patients (1.0%) and serious uveitis in six patients
(1.3%) given ranibizumab. It was concluded that intravitreal administration of
ranibizumab for 2 years prevented vision loss and improved mean visual acuity,
with low rates of serious adverse events, in patients with minimally classic or
occult (with no classic lesions) choroidal neovascularization secondary to
age-related macular degeneration.
Baclofen
Works in Pediatric Patients
Baclofen, a
gamma-amino-butyric-acid B receptor agonist, is currently indicated for the
alleviation of signs and symptoms of spasticity resulting from multiple
sclerosis, particularly for the relief of flexor spasms and concomitant pain,
clonus, and muscular rigidity. A recent study, published in The Journal of
Pediatrics (2006;149:468-474),was performed to
evaluate the effects of baclofen on transient lower esophageal sphincter
relaxation (TLESR), gastroesophageal reflux (GER), and gastric emptying (GE) in
children with GER disease. For the investigation, the efficacy of 0.5 mg/kg
baclofen was evaluated in a randomized, double-blinded, placebo-controlled
trial in 30 children. Patients were intubated with a manometric/pH assembly and
given 250 mL of cow’s milk. Esophageal motility and pH were then measured for 2
hours (control period). Baclofen or placebo was then administered, and 1 hour
later 250 mL of milk was given again and measurements performed for another 2
hours (test period). The GE rate was measured by the 13C octanoate breath test.
Results showed that, in comparison with placebo, baclofen significantly reduced
the incidence of TLESR (mean, 7.3 vs 3.6; P < .05) and acid GER (mean 4.2 vs
1.7; P < .05) during the test period. Baclofen also significantly
accelerated the GE rate 61 minutes vs 114 minutes; P < .05). Baclofen had no
effect on the swallowing rate, pattern of esophageal peristalsis, or lower
esophageal sphincter pressure.
TARGET HEALTH excels in
Regulatory Affairs and works closely with many of its clients performing all
FDA submissions. TARGET HEALTH receives daily updates of new developments at
FDA. Each week, highlights of what is going on at FDA are shared to assure that
new information is expeditiously made available.
Zolinza Approved For
Cutaneous T-cell lymphoma
Cutaneous T-cell lymphoma
(CTCL) is a term that was created in 1979 to describe a group of
lymphoproliferative disorders characterized by localization of neoplastic T
lymphocytes to the skin. When the term was first coined, it most often referred
to mycosis fungoides/Sézary syndrome, the most common CTCL. More recently,
however, the many entities that comprise the CTCLs have been found to differ
widely in biologic course, histologic appearance, and in some cases,
immunologic and cytogenetic features and in their response to appropriate
treatment. The skin is the second most common extranodal site for lymphoma;
gastrointestinal sites are first. Of all primary cutaneous lymphomas, 65% are
of the T-cell type. The most common immunophenotype is CD4-positive. The FDA
has approved Zolinza (vorinostat) capsules for the treatment of cutaneous
T-cell lymphoma (CTCL), to be used when the disease persists, gets worse, or
comes back during or after treatment with other medicines. Zolinza was approved
as part of FDA's Orphan Drug program, which offers companies financial
incentives to develop medications for diseases affecting fewer than 200,000
American patients a year. Every year in the
For more information about our
expertise in Regulatory Affairs, please contact Dr. Jules T. Mitchel or Dr. Glen Park.
TARGET HEALTH INC. (www.targethealth.com)
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and device development. Areas of expertise include Regulatory Affairs,
comprising, but not limited to, IND, IDE, NDA, PMA and 510(k) submissions,
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