(Complimentary Newsletter from Target Health Inc.)
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17 April 2006
I.
WHAT'S NEW?
Regulatory
Affairs Consulting
II. QUIZ
(Fill In The Blanks)
Accessory
Olfactory System vs. Main Olfactory System
III.
HISTORY OF MEDICINE
Polycythemia
Vera: Plethora, from Prehistory to Present
IV. ONCOLOGY
Device For the Detection of Oral Cancers
V. BASIC SCIENCE
How the Kaposi's Sarcoma Herpesvirus (KSHV) Enters the Cell
VI. WOMEN'S HEALTH
Breast Cancer Estrogen-Receptor (ER) Status and Adjuvant Chemotherapy
VII. EPIDEMIOLOGY
Clinical Utility of Determining Metabolic Syndrome
VIII. FDA
ReNu MoistureLoc® Contact Lens Recall
IX. Target Health Inc.
Regulatory
Affairs Consulting
Target Health is pleased
to announce that one of its clients received clearance of a 510(k) in the area
of male reproductive health. Vanessa Hays, JD took the lead on the project. The
project had a 3rd party review as well as a fee reduction as a small business
Target Health is also pleased to announce that Mary Shatzoff has joined Target
Health as Senior Manager Regulatory Affairs. Mary has over 10 years
experience in the regulatory area and comes to us from Sanofi-Aventis. Mary
will report directly to Dr. Glen Park, Sr. Director of Clinical and Regulatory
Affairs. We now represent 19 companies at FDA. For more information, please contact Dr.
Jules T. Mitchel.
Accessory Olfactory System
vs. Main Olfactory System
During
perception, information is acquired by sensory systems through primary sensory
organs and transmitted to specific brain regions for further processing. The sensory
system that plays a critical role in processing 1) ___ signals, or pheromones,
that are transmitted between members of the same species, is the 2) ___
olfactory system. It is separate from the main olfactory system, which is
involved in the sense of smell. The other olfactory pathway, which is prominent
in many vertebrate species, begins with receptors 3) ___ in the vomeronasal 4)
___ (VNO), and follows a multisynaptic route to subcortical 5) ___ regions that
include the amygdala and parts of the 6) ___. The VNO projection pathway has
been shown to be critical for a number of psychological and 7) ___ functions.
One is in gender dimorphic processing of 8) ___. Research is proceeding to
understand how pheromones are processed, and to identify where in the brain,
changes associated with pheromone exposure occur, and to define factors that
may contribute to between- and within-individual responses.
Answers: 1) chemical;
2) accessory; 3) neurons; 4) organ; 5) brain; 6) hypothalamus; 7)
neuroendocrine; 8) pheromones
Polycythemia Vera:
Plethora, from Prehistory to Present
The term polycythemia
(literally, "many blood cell disease") and its obsolete synonym,
erythremia, postdate Robert Hooke's 17th century discovery of cells. However,
the concept of a clinically problematic excess of blood was formulated in
antiquity. Observation of plethoric patients by clinicians of the Hippocratic
school informed the classical humoral framework that dominated theoretical
constructs of human disease for more than a thousand years. In the golden era
of disease description at the end of the 19th century, the idiopathic entity
polycythemia rubra vera (PRV) was first described and distinguished from
secondary and relative polycythemia (red cell excess not caused by a primary
bone marrow disorder, and artifactual red cell excess caused by plasma volume
contraction, respectively).
Device For the Detection of
Oral Cancers
The American
Cancer Society (ACS) estimated last year that about 20,000 Americans were
diagnosed and 5,000 died from various oral cancers. Because developing tumors
in the mouth are often easily visible, public health officials have long
advocated early detection of oral cancer. But determining whether a suspicious
sore is benign or potentially cancerous has remained scientifically
problematic. A major reason is looks alone can be deceiving. According to an
article published in the Journal of Biomedical Optics (2006;11: 024006), there
is a new optical device that allows dentists to visualize, in a completely new
way, whether a patient might have a developing oral cancer. The device, called
a Visually Enhanced Lesion Scope (VELScope), is a simple, hand-held device
which emits a cone of blue light into the mouth. Upon excitation, normal oral
tissue emits a pale green fluorescence, while potentially early tumor, or
dysplastic, cells appear dark green to black. When testing the device in 44
people, an oral tumor could be distinguished correctly in all but one instance.
According to the authors, since the natural fluorescence of the mouth is
invisible to the naked eye, the VELScope literally brings this natural
fluorescence to light, helping dentists to determine whether or not to perform
a biopsy. The project started with a crude, light-emitting box and a pair of
goggles that their group had previously cobbled together to visualize skin
cancer. Over time, the box-and-goggles concept was refined and integrated into
one device. For the study, 50 tissue sites from 44 people were evaluated. All
sites were biopsied, and pathologists classified seven as normal, 11 as severe
dysplasia, and 33 biopsies were oral squamous cell carcinoma. Reading the
fluorescence patterns of the 50 sites, the group correctly identified all of
the normal biopsies, 10 of the severe dysplasias, and all of the cancers. These
numbers translated to 100% specificity and 98% sensitivity. Sensitivity refers
to how well a test correctly identifies people who have a disease (true
positives), while specificity characterizes the ability of a test to correctly
identify those who are well (true negatives).
How the Kaposi's Sarcoma
Herpesvirus (KSHV) Enters the Cell
Kaposi's sarcoma
(KS) is a major cancer associated with HIV/AIDS, and it typically manifests as
multiple purple-hued skin lesions. Although less common in the United States
now than early in the AIDS pandemic, KS is still the most common cancer
associated with HIV infection. Prior to the AIDS pandemic, it was an obscure
disease. First identified as a multi-pigmented skin disease by a Hungarian
doctor named Moritz Kaposi in 1872, it was considered to be quite rare -- a
medical curiosity usually found in particular populations such as older Italian
men, transplant patients and young men in certain parts of sub-Saharan Africa.
But then at the dawn of the AIDS pandemic in the early 1980s, the small purplish
KS skin lesions began appearing on the bodies of young American men, many of
whom went on to develop opportunistic infections. A critical human cell surface
molecule has been identified which is involved in infection by Kaposi's sarcoma
herpesvirus (KSHV), the virus that causes KS and certain forms of lymphoma. In
an article published in the journal Science (March 31, 2006DOI:
10.1126/science.1120878), it is described how the molecule xCT is a major
gateway that KSHV uses to enter human cells. The molecule may also play a role
in the development of Kaposi's sarcoma and other syndromes associated with the
virus. The natural function of xCT in the body is to transport molecules,
necessary for protecting against stress, into cells. When cells are stressed,
they express more xCT on their surfaces. This sort of stress can also be caused
by KSHV itself which suggests that the virus may facilitate its own infectivity
and dissemination in the body by inducing a physiological state that results in
increased numbers of its own receptor. According to the authors, the discovery
may lead to new avenues for treating KSHV, and should enable other
investigators to determine whether levels of xCT determine disease severity. It
also will allow researchers to study whether the expression of xCT on cells
varies among different groups of people and whether these variations are
genetic or environmental. Note: An illustration of KSHV entering a cell can be
found at the NIH
website.
Breast Cancer
Estrogen-Receptor (ER) Status and Adjuvant Chemotherapy
Breast cancer
estrogen-receptor (ER) status is useful in predicting benefit from endocrine
therapy. However, it is not known if ER status also helps predict which
patients benefit from advances in adjuvant chemotherapy. As a result, a study
published in the Journal of the American Medical Association
(2006;295:1658-1667), was performed to compare differences in benefits from adjuvant
chemotherapy achieved by patients with ER-negative vs ER-positive tumors. For
the study, clinical trial data from the Cancer and Leukemia Group B and US
Breast Cancer Intergroup were analyzed. Randomized trials were evaluated
comparing 1) 3 regimens of cyclophosphamide, doxorubicin, and fluorouracil; 2)
3 doses of doxorubicin concurrent with cyclophosphamide, with or without
subsequent paclitaxel; 3) sequential doxorubicin, paclitaxel, and
cyclophosphamide with concurrent doxorubicin and cyclophosphamide followed by
paclitaxel. A total of 6644 node-positive breast cancer patients received
adjuvant treatment. The main outcome measures were disease-free status and
overall survival. Results showed that for ER-negative tumors, chemotherapy
improvements reduced the relative risk of recurrence by 21%, 25%, and 23% in
the 3 studies, respectively, and 55% comparing the lowest dose in the first
study with biweekly cycles in the third study. Corresponding relative risk
reductions for ER-positive tumors treated with tamoxifen were 9%, 12%, and 8%
in the 3 studies, and 26% overall. The overall mortality rate reductions
associated with chemotherapy improvements were 55% and 23% among ER-negative
and ER-positive patients, respectively. All individual ER-negative comparisons
and no ER-positive comparisons were statistically significant. Absolute
benefits due to chemotherapy were greater for patients with ER-negative
compared with ER-positive tumors: 22.8% more ER-negative patients survived to 5
years disease-free if receiving chemotherapy vs. 7.0% for ER-positive patients.
The corresponding improvements for overall survival were 16.7% vs 4.0%.
According to the authors, among patients with node-positive tumors, ER-negative
breast cancer, biweekly doxorubicin/cyclophosphamide plus paclitaxel lowers the
rate of recurrence and death by more than 50% in comparison with low-dose
cyclophosphamide, doxorubicin, and fluorouracil.
Clinical Utility of
Determining Metabolic Syndrome
According to an article published
in the British Medical Journal (2006;332:878-882), a prospective cohort study
was performed to determine if the presence of the metabolic syndrome increases
the risk of subsequent total and cardiovascular mortality, taking into account
established risk factors for cardiovascular disease. Study participants
included a community based sample of 2,322 men followed since 1970 for a
maximum of 32.7 years. The main outcome measures were the relations of the
metabolic syndrome to subsequent total and cardiovascular mortality. Metabolic
Syndrome was defined by the national cholesterol education program (NCEP) of
the US National Heart, Lung, and Blood Institute or criteria of the World
Health Organization (WHO). Results showed that when adding the metabolic syndrome
to models with established risk factors for cardiovascular disease (smoking,
diabetes, hypertension, and serum cholesterol) at age 50, it significantly
predicted total and cardiovascular mortality (Cox proportional hazard ratios
1.36 and 1.59, respectively). The metabolic syndrome added prognostic
information to that of the established risk factors for cardiovascular disease
(likelihood ratio tests, P < 0.0001 for both outcomes). Similar results were
obtained in a subsample without diabetes or manifest cardiovascular disease.
According to the authors, if confirmed, the study results may indicate clinical
value in diagnosing the metabolic syndrome.
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.
ReNu MoistureLoc® Contact Lens Recall
FDA is continuing to work closely with
the Centers for Disease Control and Prevention (CDC) and Bausch & Lomb to
investigate the source of Fusarium keratitis eye infections. The agency
supports Bausch & Lomb's decision to voluntarily withdraw ReNu MoistureLoc®
contact lens solution from the market until the agencies have had a chance to
conclude their investigation. FDA started its investigation of the Bausch &
Lomb manufacturing plant on March 22, 2006, and will continue inspections of
the Greenville, SC manufacturing plant and other facilities through next week.
While the investigation continues, FDA will work with CDC to identify and
confirm cases of Fusarium keratitis reported by state health departments
and from FDA Medwatch reports. FDA and CDC are advising consumers to take
precautions to reduce their risk for Fusarium keratitis through
preventive practices for contact lens wearers that include:
1.
Wash hands
with soap and water, and dry (lint-free method) before handling lenses.
2.
Wear and
replace lenses according to the schedule prescribed by the doctor.
4.
5.
Remove the
lenses and consult your doctor immediately if you experience symptoms such as
redness, pain, tearing, increased light sensitivity, blurry vision, discharge
or swelling.
For more information about our expertise in Regulatory
Affairs, please contact Dr.
Jules T. Mitchel or Dr. Glen
Park.
IX. TARGET HEALTH
TARGET HEALTH INC. (www.targethealth.com)
is a full service e*CRO with fulltime staff dedicated to all aspects of drug
and device development. Areas of expertise include Regulatory Affairs,
comprising, but not limited to, IND, IDE, NDA, PMA and 510(k) submissions,
execution of Clinical Trials, Project Management, Biostatistics and Data
Management, Web Trials, utilizing Target e*CRF™, our proprietary Internet-based
Clinical Trial System, and Medical Writing. TARGET HEALTH's Pharmaceutical
Advisory Dream Team (PADT) assists companies in strategic planning from Discovery
to Market Launch. Let us help you on your next project.
TARGET HEALTH INC.
261 Madison Avenue
24th Floor
New York, NY 10016
Phone: (212) 681-2100; Fax (212) 681-2105
Target Health
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www.targethealth.com
Dr. Jules T. Mitchel,
President
Ms Joyce Hays, CEO
©2006 Target Health Inc. All rights reserved