VetInfo Digest      August 2000

This Month:

More Precious Than Oil

Mast Cell Tumors

Low Tech Medicine

Baytril Alert

Updates
 

I am sorry that last month's VetInfo Digest said June 2000 in the title.
If  you find that you are missing the July issue, check to see if you have
two different June issues!

There is a medication alert in this month's VetInfo Digest. I was surprised
to get this information since I had tried to find a link between
enrofloxacin and blindness for a subscriber less than a month ago and found
no information on this topic. It is very important to be sure that your
veterinarian reports any drug reactions, so that infrequent problems like
this do get recognized. The phone number for reporting drug reactions to
the FDA is 1-888-FDA-VETS. In addition, drug reactions should be reported
to the manufacturer.

This month, I am going to try a multimedia approach to the information in
the VetInfo Digest. I will be putting pictures of a couple of mast cell
tumors online in the subscriber area. Hopefully, we will be able to do more
of this sort of thing in the future.
 

More Precious Than Oil

While I like inexpensive gasoline like most consumers, I try to keep its
price in perspective. Just to give you some idea of comparative cost of
medicines, by the gallon, take a look at these prices:

cyclosporin liquid      $5.60 per cc    x       3785cc/gal      =       $ 21,196 per gallon
isoflurane anesthesia   $  .21 per cc                           =       $      794
ivermectin injection    $1.05 per cc                            =       $   3,974
eye drops (generic)     $  .94 per cc                           =       $   3,558

These are just a few examples --- and veterinary medications cost less than
human medications, in most cases!
 

Mast Cell Tumors  (mastocytomas)

Mast cells are an odd cell. They originate in the same cell lines as white
blood cells but spend their life in the connective tissues which support
all of the body's organs, making them very widespread in the body tissues.
They contain a chemical arsenal, stored in granules inside the cell. Mast
cells are capable of expelling these granules, which allows the chemicals
they contain to produce effects in the surrounding tissue. The granules may
contain histamine, heparin or enzymes capable of breaking down proteins.
These cells are one of the first lines of defense against foreign invaders
and are therefore more common in tissues susceptible to attack, such as the
ocular tissues and the digestive tract. This is why some people's eyes itch
when they have allergies. When cancer occurs in these cells it may be
referred to as a mast cell tumor or as a mastocytoma.

Approximately 5% of skin tumors in dogs are mastocytomas, but they are the
most common malignant skin tumor in this species, accounting for about 20%
of the total cases of malignant skin tumors. Mastocytomas are not as common
in cats and are frequently benign in cats, so there is a great difference
between the species in this particular tumor type.

Mast cell tumors are noticed by pet owners most commonly when they occur in
the skin. They can occur in other tissues, especially the gastrointestinal
tract. These tumors can occur at almost any age, including a couple of
reports of Siamese kittens with mast cell tumors at 6 to 8 weeks of age.
Despite the wide age range of possible occurrence, most dogs and cats with
mast cell tumors are older middle-aged to geriatric age patients.

Boxers, Boston terriers, Labrador retrievers, English bulldogs, bull
terriers, fox terriers, dachshunds, Staffordshire terriers and Weimaraners
are thought to be predisposed to these tumors. Boxers and Boston terriers
seem especially prone, based on the patient population in our veterinary
practice.

Mast cell tumors are normally single tumors but may vary significantly in
their appearance. Over the years, I have become convinced that it is not
possible to conclusively rule out the possibility of a mast cell tumor
based on the appearance of the tumor, in a dog. In cats, these tumors tend
to be solitary, dark in color and located on the head or neck. In dogs, we
see mast cell tumors that look like skin abrasions and mast cell tumors
that look like solid tumors. We even see an occasional mast cell tumor that
appears to be a lipoma (fatty cell tumor) on our initial examination. Most
mast cell tumors are solitary but some dogs have several tumors in a small
area or two or more tumors widely spread on the body. It is very important
to look carefully for additional tumors whenever mast cell tumors are
suspected to be present, as the presence of widely spread tumors impacts
significantly on the prognosis.

There are some differences between mast cell tumors and other skin tumors.
One sign that a tumor is potentially a mastocytoma is itchiness associated
with the tumor.  Mast cells are the cells that release histamine, the
substance that causes itchiness and irritation associated with allergies,
which is why mastocytomas are often itchy. The release of histamine from
the tumors may make the tissue around the tumor red or swollen, so an
edematous appearance to a skin tumor should cause a strong suspicion of a
mast cell tumor. Some mast cell tumors appear to have a "pin-feather"
appearance, in which hair growth in the tumor looks spiked, similar to the
appearance of new feathers growth in birds.

Most mast cell tumors in dogs occur on the body, the area around the rectum
and scrotum or on the legs. These tumors are seen on toes fairly frequently
and may be more likely to be malignant if they occur on the toes, making
amputation of the affected toe the surgery of choice for mast cell tumors
in this location. Mast cell tumors on cats tend to occur on the head or
neck near the head.

Benign skin tumors are very common in dogs. This makes it hard to decide
whether or not to remove tumors when they appear to be a tumor type that we
would normally expect to be benign, such as a sebaceous adenoma, which is a
very common tumor in dogs that many clients think of as old age
"warts".  The situation is not as hard in cats, since we tend to remove
almost any skin tumor in cats, since skin tumors are not as common in cats
and since there is a higher probability of malignancy with skin tumors in
cats, even though that isn't true of  mast cell tumors.

The histamine release from mast cell tumors can also cause systemic
problems. Gastric ulcers are sometimes seen in patients with mast cell
tumors. Signs of ulcers include decreased appetite, vomiting, vomiting
blood and blood loss through the digestive tract leading to black colored
stools. Some dogs have blood clotting disorders or immune mediated
thrombocytopenia (decreased platelet counts) as secondary side effects of a
mast cell tumor. When any of these signs occur in conjunction with a skin
tumor, suspicion of a mast cell tumor should be very high. Gastric ulcers
not related to the use of medications should always raise the index of
suspicion for mastocytomas, as well. It is prudent to use cimetidine
(Tagamet Ô), famotidine (Pepsid AC Ô), or similar histamine antagonists at
the time of surgery and post-operatively, to counteract the irritation to
the gastrointestinal tract from histamine release during surgery.

Mast cell tumors can itch enough that severe self-inflicted trauma is
sometimes a problem at tumor sites. They can also cause generalized
itchiness that is harder to relate specifically to a tumor. Anti-histamines
can be very helpful in controlling the itchiness, as can corticosteroids
such as prednisone. This can be beneficial at or around the time of
surgery, as manipulation of the tumor may lead to a temporary increase in
itchiness.

There are two ways to evaluate the prognosis for mast cell tumors.  The
first is tumor grade and second is clinical staging. Tumor grade is
determined by examination of the tumor itself and clinical staging is an
evaluation of the whole patient's status.

The most commonly used grading scheme for mast cell tumors uses a three
step grading process.

Grade I tumors contain mast cells that are well differentiated, meaning
they still look like mast cells. Individual cells usually do not show much
evidence of mitosis (splitting into two cells). The tumor is usually
contained in the upper portions of the skin.

Grade II tumors contain mast cells that are more likely to be in the
process of dividing, have invaded into the deeper layers of the skin and
which may have induced edema or cell death in the tissues around them.

Grade III tumors contain cells that no longer are easily identifiable as
mast cells. It is more likely that they will have edema, cell death or even
bleeding (from heparin's effects) in the tissue around the tumor. There is
more cell division.

Grading is a subjective process but pathologists are careful to follow
guidelines in making their analysis. Based on grade, the prognosis for
tumors is as follows:

Grade I tumors, if removed so that there are no tumor cells in the margin
of the tissue that was surgically removed will not recur in approximately
90% of cases. This means that surgery alone is likely to be curative for
this cancer, if it is caught in this stage and the surgery includes a wide
tissue margin. Approximately 35% of mast cell tumors that are removed are
judged to be Grade I tumors by pathologists.

Grade II tumors, if removed with clean surgical margins, are likely to
recur at the same site, or spread to other sites, in about 50% of cases.
Radiation therapy post-operatively is supposed to increase the success rate
for Grade II tumors in Stage I patients (explained later) to about
85%.  Even for Stage II  patients radiation therapy is reported to increase
long term survival significantly. About 45% of mast cell tumors are Grade
II when they are removed.

Grade III tumors represent about 20% of the cases of mast cell tumors
examined by pathologists. These tumors have often spread by the time they
are removed and the long term survival rate, even with radiation or
chemotherapy, is very low. Less than 10% of dogs with Grade III mast cell
tumors live a year after surgical removal, with or without additional
treatment.

Staging usually follows the World Health Organization guidelines. It is
based on examination of the patient rather than the appearance of the
tumor.  An abbreviated explanation of the significance of various stages
follows.
 

Stage I is usually considered to be a single tumor that occurs in the skin
and which has not invaded the local lymph nodes.

Stage II is one tumor in the skin but evidence of invasion of the local
lymph node.

Stage III patients have more than one mast cell tumor in the skin or a mast
cell tumor in other tissues (usually the gastrointestinal tract).  There
may or may not be involvement of the local lymph nodes.

Stage IV patients have obvious metastases of mast cell tumors from the skin
to other tissues or are experiencing a recurrence of a previously removed
mast cell tumor.
 

For mast cell tumors, Stage I and Stage II patients may have a good long
term prognosis with surgical removal, possibly with follow up radiation or
chemotherapy. Stage III and IV patients have a poor prognosis in most cases.

While the pathologist determines the grade of the tumor, your vet or an
oncology specialist,  determines the stage of the illness. This is done by
looking for evidence of spread of the tumor to other areas of the skin or
other areas of the body.  Aspiration from a local lymph node, or removal of
the node for exam, examination of the bone marrow, examination of the white
blood cell layer in a blood tube (the buffy coat), X-rays of the abdomen
(most likely place for the tumor to spread) and ultrasound examination of
the abdomen are all possible tests to help identify the stage of the cancer
in a particular patient.  There is some controversy over the value of buffy
coat smears since mast cells occur in the buffy coat with several other
problems in pets but it is an easy test to run so we still do it. X-rays of
the chest are less useful for mast cell tumors than for other malignant
cancers, since this particular tumor tends not to spread to the chest.

There are some controversies in treatment options for mast cell tumors.
Whether or not to pursue local radiation therapy at the site of the tumor
removal is one area in which the best answer is not always clear. With a
90% success rate for surgical removal alone for Grade I tumors, it is hard
to figure out whether or not to pursue radiation therapy, for instance. For
Grade II tumors, radiation therapy increases the long term survival rate
from about 45% to about 85%, so it is more clearly beneficial in this case.

The biggest problem with radiation is that many people have to travel very
long distances to find an oncology service that offers radiation and the
patient usually has to be hospitalized for several weeks, as it is best for
the oncology staff to manage the effects of radiation therapy, since most
general practitioners are not experienced with this sort of care. For Grade
II, Stage I mast cell tumors, there is little doubt that radiation therapy
is worthwhile, if it can be arranged.

Prednisone was reported to be a chemotherapeutic for mast cell tumors in
one study but this has not been as successful in follow-up studies. At the
present time prednisone is considered to be helpful in extending the time
between surgical removal of mast cell tumors and recurrence of the tumors
in about 20% of patients. This is good enough that most vets would use
prednisone if it didn't have so many side effects. There are vets who
advocate the use of prednisone and vets who feel its use is not justified
when its risks are considered. It does not seem necessary to use prednisone
for Grade I, Stage 1 tumors with good surgical margins but is very tempting
for Stage 2 or 3 tumors.

Chemotherapy using traditional chemotherapy medications has not been very
successful for mast cell tumors. The combination of prednisone and
vinblastine has been the most successful therapy up until recently,
although it is helpful less than half the time in providing long term
success. Recently, though, there have been preliminary reports of success
with CCNU (Lomustine Rx). To the best of my knowledge there are no really
long term reports on this agent but it has been reported to induce
remission in some cases in which other chemotherapeutic protocols are not
working well. Chemotherapy is generally used when the tumor is Grade II or
III and Stage 2 or greater. Even though it has not been highly successful
it offer some hope in these patients.

Dog owners will continue to have to make decisions based on the
pathologist's review of the tumor, the clinical staging of the tumor and
uncertain statistics regarding chemotherapy success for some time.
Utilizing the services of a veterinary oncologist is very helpful when
making these decisions. For cat owners, mast cell tumors do not represent
quite the problem they do for dog owners. In almost all cases surgical
removal will totally resolve the problem in a cat.

Visuals of Mast cell tumors
 
 

Low Tech Medicine

I spend a lot of time on the web site pointing out all the high tech
options for health care in dogs and cats. I do this because I think it is
important for pet owners to know all of their options. In practice, though,
I often take a much more "low tech" approach. This can be important for pet
owners who do not have the financial resources to pursue higher cost
diagnostic procedures or for situations in which it just isn't practical to
pursue those options. Prior to the availability of MRI and CT scans,
ultrasound, scintigraphy and even X-ray machines in veterinary practice,
veterinarians made sound diagnostic decisions using their hands, eyes and
brains and it is still possible to do that today.

The most important low tech procedure is collection of the medical history.
This is especially important in chronic illnesses and skin disorders. I
believe that it is possible to make an accurate diagnosis of a medical
condition, based on the history of the illness and the clinical signs that
can be ascertained during a physical exam in the majority of cases. It is
very hard to be certain of this diagnosis, in many cases, without
supporting lab work, though. When circumstances make doing lab work to
conclusively prove a diagnosis impossible or impractical, going with your
vet's working diagnosis is reasonable.

It is critical that the history taking be done carefully and that the pet
owner and veterinarian work together to get an accurate accounting of the
progression of an illness and any potential contributing factors. It is
equally important not to get so distracted by minute details that the
overall history becomes meaningless. Many pet owners come to the vet with a
pre-formed opinion of the nature or cause of their pet's illness.
Sometimes, they are reluctant to discuss history that doesn't jive with
their presumption or they are so convinced of the cause of an illness that
they miss important clues to alternative diagnoses. A few of my clients are
embarrassed about providing a medical history or are so worried about
taking up my time that they try to abbreviate the history. This can cause
problems, too. Give your vet all the facts that seem relevant and include
the behaviors that seem unusual for your pet, even if they don't sound
especially significant to you. I think it helps a great deal if you write
these down prior to the office visit and then give them to your vet,
because it makes it less likely that you will get so detailed, or so
sidetracked, that your vet will lose track of the symptoms.

Your vet should ask you questions based on the history you provide, in most
instances. These will vary depending on the completeness of the history you
provide and by the condition that the vet suspects. Don't get impatient if
the question seems irrelevant to you. Sometimes it is necessary to figure
out if problems in other body systems are related to the present problem or
if there are contributing factors in the environment. So even though you
are concerned about your pet's apparent ear infection, for example, you vet
may be trying to decide if it is actually a secondary problem due to food
allergies or hypothyroidism and ask questions pertaining to those problems.

Be careful not to mislead your vet. One of the worst situations for
veterinarians is a client who insists that a key part of the history could
not possibly apply to their pet. To give you an example of this, I worked
on a very sore and slightly lame puppy one day. One of the causes of
unexplained joint pain in dogs is exposure to rat or mice poisons
containing warfarin-like toxins. So I asked the owner if there was any
possibility of exposure to these poisons. She adamantly insisted that there
was no conceivable way the puppy could have been exposed and seemed
somewhat angry that I would even ask that question. She absolutely insisted
that the puppy had not left her sight since it was adopted several days
previously. The puppy had no sign of bleeding at this time. Forty-eight
hours later this puppy was bleeding severely and it was obvious that
warfarin toxicity was likely. Although the puppy responded well to
treatment, it was close to death at the point the toxicity became obvious.
The owner was again furious, this time insisting that I should have treated
the puppy for warfarin toxicity on the first visit!

If you write down a list of the symptoms that are worrisome, the number of
times they have occurred, when the very first occurrence of the condition
was (this is especially important for skin diseases), it will help your vet
a great deal.  If you answer the vet's questions as carefully as possible,
it will help even more. If your pet grew up in an another geographic area,
it is important that your vet know that. There are a number of diseases
that only occur in limited geographic areas and won't be looked for without
knowledge of the possibility that they might be present. A good history,
followed by a good examination and perhaps a few more questions about the
course of the illness, can make it possible to provide an accurate diagnosis.

The physical exam is also an important part of the low tech approach to
medicine. A careful clinical exam can often produce clues that may have
gone unnoticed. Something as simple as finding a tick on an exam may
provide a major clue as to the origin of an illness. Enlarged lymph nodes,
palpable thyroid glands in cats, coughing when the trachea is palpated
(handled), heart murmurs, abdominal masses -- many things can be found
simply by looking for them. Last week we had a dog come into the practice
who had severe crusty abrasions on the bridge of its nose, which the owner
felt was due to a lack of response to antibiotics for a bite wound that had
been treated by the usual vet just prior to coming here for vacation. The
sores made me think of discoid lupus or one of the other immune mediated
diseases that affect dogs. As I examined the dog and looked in its mouth, I
saw a bone wedged between the top teeth. Removing the bone led to
resolution of the clinical signs. The dog was apparently rubbing his nose
in an effort to dislodge the bone or relieve discomfort associated with it.
It is very important for veterinarians to do a systematic physical exam of
ill or injured pets, so that problems like this do not get overlooked.

It is very easy for veterinarians to get distracted by the first obvious
problem that they see and to miss other conditions that are more subtle.
Watch your vet perform your pet's yearly physical exam and try to get
accustomed to what a good physical exam entails. Did your vet look in your
pet's mouth, check its eyes, its ears, the heart and lungs, feel the
abdomen, examine the skin, check for lumps, weigh your pet and take its
temperature? Sometimes it is OK to skip some steps on exam but if your pet
is ill, be sure your vet does a complete physical exam.  Asking something
like "did his eyes look OK?",  can serve as a gentle reminder to take a
good look at them.

Sometimes a physical exam can be enhanced by the use of anesthesia. In
cats, it is possible to physically assess the size of the kidneys, the
urinary bladder, or search for lumps in the abdomen with just about as much
precision manually as it is to use X-rays or ultrasound exam. This is
especially true in an anesthetized patient. It is a little more difficult
in many canine patients to assess both kidneys and abdominal masses have
more room to hide in a rottweiler dog than in a Siamese cat, but even in
dogs palpation is an overlooked diagnostic tool. In a large canine patient,
anesthesia is often the difference between finding or missing an abdominal
tumor. I think it is very reasonable to use anesthesia as an adjunct to a
physical exam in some patients, especially those for which X-rays or
ultrasound exam are not available options.

Cystocentesis, or withdrawal of urine through the use of a syringe and
needle, is a pretty low tech procedure that can be very beneficial. It
provides a quick way to get a urine sample from a cat or dog that is good
for bacterial culture and can be examined with the chemistry "multi-stix"
that analyze for glucose, protein, bilirubin, pH and other substances.
Using a refractometer to evaluate urine specific gravity can also be done.
This is a test that can help a great deal in evaluating kidney function and
establishing the possibilty of hyperadrenocorticism, diabetes insipidis and
other conditions with direct effects on the specific gravity of the urine.
Once in a while a patient asks me if obtaining a urine sample prior to
coming in for a visit would be helpful. For many conditions, it is. If your
pet has a urinary tract problem, is drinking more and urinating more, or
just seems very ill, it isn't a bad idea to call and ask your vet if
obtaining a urine sample and bringing it at the time of the exam would be
helpful.

The last low tech technique that really works for me is tincture of time.
It is often possible to make a diagnosis on a second or third visit that
just wasn't apparent on the first one. Sometimes, just reviewing the
history when a client calls to let us know that a problem isn't responding
to treatment is enough to make me see another alternative in diagnosis or
treatment. I am not sure why clients are reluctant to call and let us know
that a treatment is not working, but it happens frequently in our
practice.Don't hesitate to schedule a recheck or to call your vet on the
phone when things are not working well. This is the low tech thing that you
can do to help your vet make a better diagnosis or treatment plan for your pet.
 
 
 

Medication Alert

BaytrilÔ injection (enrofloxacin) is currently difficult to obtain. The
apparent reason for this is the recent discovery that it may cause
blindness when used at the higher end of the dosing scale in cats. This was
reported to veterinarians by Bayer, the manufacturer, in a recent letter.
Prior to 1997 the approved dosage for Baytril in cats was 2.5mg/kg every 12
hours.  Baytril Injection has never been approved for use in cats but was
used in certain circumstances, despite this.

In 1997 the dose for Baytril was changed to 5 to 20mg per day, in a single
dose or divided twice daily, as previously approved. The high end of the
dosing scale is used when once a day dosing is desirable and for bacterial
infections such as Pseudomonas, which are more susceptible to high
concentrations of the medication. The letter from Bayer states that the
problem has occurred approximately 1 in 122,414 cats treated with Baytril.
They further state that the most severe effects were seen in cats treated
at 50mg/kg per day, which is above the approved dosage. There have been no
reports of problems, to date, in cats in which the original approved dosage
of  5mg/kg per day has been used.

At the present time, even though enrofloxacin is beneficial at higher doses
for some infections, it seems advisable to use doses in the lower end of
the range and to keep the dose to 5mg/kg per day.

If your pet experiences a reaction to a medication, or is suspected to have
reacted badly to a medication, it is important that the adverse reaction be
reported. At an incidence rate of 1 in 122,414, it took some time to
recognize the correlation between enrofloxacin and blindness in cats. It is
necessary for all significant reactions to medications to be reported to
pick up problems that occur this infrequently. If your vet seems unsure of
how to report a drug reaction, give him or her this phone
number:  1-888-FDA-VETS. It is the number for veterinarians to report drug
reactions to the FDA. It is also important to report reactions to the
manufacturers. There is usually a phone number in the medication insert
that can be used for this purpose.

Updates

I have started to work on a medication formulary for the subscriber area. I
will try to have a chart of most of the medications used in veterinary
medicine, and their doses, by the end of the year. Then I will work on a
link to a more detailed page for each of these medications over time. I
believe that it is important for pet owners to have access to medication
dosing information as well as information on potential side effects, drug
interactions and similar information. Please remember that there are a
number of published dosages for many medications and that the information
in the package insert may not reflect the most commonly used doses or uses
for a medication, since these tend to change as veterinarians gain more
experience with medications.

We still have some times when we can not correspond with subscribers due to
e-mail address that refuse to work. Please do not hesitate to contact us if
you feel that a question has not been answered in a reasonable length of
time (give me at least three days, though) of if you do not receive the
VetInfo Digest either by post or by e-mail.

If you have a problem getting into the subscriber area it is faster to
contact me at mervet@inna.net than to write to Michal at vetinfo@vetinfo.com.

Lastly, we know that some people subscribe to our site hoping to get
emergency information or to find an answer to a hopeless situation. We are
truly grateful to all of you who have supported our site, but we know that
we can not provide much help in these circumstances. For this reason, and
for any other, we will refund the subscription fee upon request.
 
 

The VetInfo Digest is published by:
TierCom, Inc.
P.O. Box 476
Cobbs Creek, VA 23035.
804-725-5051
fax: 804-725-0149

The opinions expressed in this newsletter are those of
Michael Richards, DVM., author.

Copyright  2000,2001, TierCom, Inc.