Meghane - your thoughts please!

moonie_57February 14, 2009

Our 20 month old Golden had a seizure last monday night, followed by more Tuesday night. That night he had them approximately every 3 to 4 hours throughout the night, then another one around noon the next day at the Vets office, for a total of 8 seizures. Wednesday night we took him to Virginia to ICU and he had one more not long after we left him. He then went 24 hours and we have brought him home and so far no more.

When we left the emergency care unit in Va., the doctor there recommended we not start him on phenobarb because he's so young and could go a long period without having anymore seizures. We were uncomfortable with that advice but decided we'd discuss it with our Vet. I called and she definitely wanted him on the phenobarb so we started it last night.

I don't have many questions concerning his seizures or even if we should have started the phenobarb, but would like to know your take on it. But, I do have questions regarding his behavior. He is just acting so strange. He won't eat his dog food so I'm having to cook chicken and rice for him. I mixed that with some of his kibble and he spit the kibble out and ate the rest. He acts like his has forgotten all his manners, wanting to take food out of our hands or off the table, and trying to get in the trash. When he first came home (Thursday night) we're not even sure if he knew his name or was aware of who we were. At that point it had been 36 hours since he had been given any kind of meds(phenobarb and valium). He has seemed somewhat better about his name and recognizing us, but he's just a different dog. He was always sort of a "human hog" wanting all the attention and butting his way in when one of the other dogs were getting attention. Now, he doesn't give it any notice. He also is acting like he's unsure on how to maneuver the steps. Almost like he isn't sure how to work his legs to go up and down... mostly down. Also, it seems he can't get in the car by himself. DH has to put him in. He doesn't know to move out of your way when underfoot. You know how it is with several dogs and working around the house. They're always doing that fancy footwork to stay out of the way. He doesn't even respond when you tell him to move. It's like he's clueless to how life used to be.

About a month ago, we decided he was a big boy and didn't have to sleep in the crate anymore. There was a couple of times after that I have tried to put him in and of course he barked like crazy to get out. Now since he's been home, we've been crating him and he sleeps through the night, not one bark. It's just odd behavior to me after being allowed to sleep free with the other two dogs.

I realize that he has been through quite a lot over this last week but we never really got a definitive answer on if this is totally normal behavior.

If you could give your thoughts on this, it would be greatly appreciated.

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I just wanted to make a few more comments on Quincy's behavior.

Had already mentioned his loss of manners and it continues. He is constantly nosing at my hands when I'm in the kitchen, hoping I'm holding something to eat. This is behavior none of the dogs are allowed but its hard to reprimand him for it when I don't know if he knows better.

Another odd thing... with 3 dogs Quincy has always believed himself to be #1. He should get the first treat, he should be brushed first, leashed first, petted first, etc. But he is keeping to himself, spending most of the time in his crate in the bedroom. We haven't seen him laying with the other dogs at all. And our cats seem to be avoiding him although he hasn't shown them the least bit of notice. All of this keeping to himself and being separated from the rest of the family is so out of character.

Usually if we drop something, he's quick to scramble over to make sure it isn't something edible. But, when I'm handing feeding him and drop a bite, he doesn't even seem to be aware. I have to tap the floor for him to notice it.

He is also trying to push his way out the front door when people are going in or out. A definite no-no in this house.

Just a reminder... he has been home about 50 hours now, and on his 3rd phenobarb at home, half of a 64.8 mg.

    Bookmark   February 14, 2009 at 7:34PM
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Phenobarb can do lots of things besides suppress seizures. One thing is that it can cause a dull mental state, ataxia (drunk-like walking, difficulty balancing). It can also increase appetite and thirst, so dogs who would normally NEVER try to grab food suddenly can't help themselves. They also have to go potty more often than normal, due to the increased intake. I think what you are seeing is related to the phenobarb.

Lots of dogs at Quincy's age have one or 2 seizure episodes and then never again. The side effects of phenobarb are such that I wouldn't have started him on meds yet either. My own Ana had a really bad seizure at about 18 months, but never had another one. We never gave her any anti-seizure meds. Phenobarb is also very hard on their liver, and with a typical Golden life span, 14 years is a LONG time to be on phenobarb- I doubt his liver would last that long, and that's definitely an organ you need! I'm in agreement with the ER doc- hold off on phenobarb and see if he has another episode. He may never. If he does though, then he may need phenobarb. Potassium bromide (KBr) can sometimes be added so you can reduce the dose of phenobarb and therefore the negative side effects and still control seizures. Some dogs do well on KBr alone, with much less negative side effects. I'm sure your regular vet was concerned with the number of seizures Quincy had and is thinking that he is a typical age to start with idiopathic epilepsy, which is why she started him on the phenobarb. I am just more reluctant to start a life-long medication with so many negative side effects until I am sure it is needed.

This is from the Plumb's Veterinary Drug Handbook about Phenobarb:
Prescriber Highlights
Barbiturate used primarily as an antiseizure medication; also used as a sedative agent
Contraindications: Known hypersensitivity, severe liver disease, nephritis or severe respiratory depression (large doses)
Caution: hypovolemia, anemia, borderline hypoadrenal function, or cardiac or respiratory disease; use with caution in cats (sensitive to respiratory depression)
Adverse Effects: Dogs: anxiety/agitation or lethargy (when initiating treatment). Profound depression, (even at low doses) is possible. Sedation, ataxia, polydipsia, polyuria, polyphagia can be seen at moderate to high serum levels. Increase in liver enzymes possible, but overt hepatotoxicity relatively uncommon. Rare: anemia, thrombocytopenia or neutropenia. Cats: ataxia, lethargy, polyphagia/weight gain and polydipsia/polyuria. Rare: immune-mediated reactions and bone marrow hypoplasia
When administering IV, give SLOWLY; do not give SC or perivascularly (very irritating)
Drug Interactions; drug-lab interactions
C-IV controlled substance

While barbiturates are generally considered CNS depressants, they can invoke all levels of CNS mood alteration from paradoxical excitement to deep coma and death. While the exact mechanisms for the CNS effects caused by barbiturates are unknown, they have been shown to inhibit the release of acetylcholine, norepinephrine, and glutamate. The barbiturates also have effects on GABA and pentobarbital has been shown to be GABA-mimetic. At high anesthetic doses, barbiturates have been demonstrated to inhibit the uptake of calcium at nerve endings.

The degree of depression produced is dependent on the dosage, route of administration, pharmacokinetics of the drug, and species treated. Additionally, effects may be altered by the age, physical condition of the patient, or the concurrent use of other drugs. The barbiturates depress the sensory cortex, lessen motor activity, and produce sedation at low dosages. Some barbiturates such as phenobarbital are useful as anticonvulsants because they tend to have sufficient motor activity depression, without causing excessive sedation. In humans, it has been shown that barbiturates reduce the rapid-eye movement (REM) stage of sleep. Barbiturates have no true intrinsic analgesic activity.

In most species, barbiturates cause a dose-dependent respiratory depression, but in some species they can cause slight respiratory stimulation. At sedative/hypnotic doses, respiratory depression is similar to that during normal physiologic sleep. As doses increase, the medullary respiratory center is progressively depressed with resultant decreases in rate, depth, and volume. Respiratory arrest may occur at 4 times lower the dose that will cause cardiac arrest. These drugs must be used very cautiously in cats' as they are particularly sensitive to the respiratory depressant effects of barbiturates.

Besides the cardiac arresting effects of the barbiturates at euthanatizing dosages, the barbiturates have other cardiovascular effects. In the dog, pentobarbital has been demonstrated to cause tachycardia, decreased myocardial contractility and stroke volume, and decreased mean arterial pressure and total peripheral resistance.

The barbiturates cause reduced tone and motility of the intestinal musculature, probably secondary to its central depressant action. The thiobarbiturates (thiamylal, thiopental) may, after initial depression, cause an increase in both tone and motility of the intestinal musculature. However, these effects do not appear to have much clinical significance. Administration of barbiturates reduces the sensitivity of the motor endplate to acetylcholine, thereby slightly relaxing skeletal muscle. Because the musculature is not completely relaxed, other skeletal muscle relaxants may be necessary for surgical procedures.

There is no direct effect on the kidney by the barbiturates, but severe renal impairment may occur secondary to hypotensive effects in overdose situations. Liver function is not directly affected when used acutely, but hepatic microsomal enzyme induction is well documented with extended barbiturate (especially phenobarbital) administration. Although barbiturates reduce oxygen consumption of all tissues, no change in metabolic rate is measurable when given at sedative dosages. Basal metabolic rates may be reduced with resultant decreases in body temperature when barbiturates are given at anesthetic doses.

Although some now believe that bromide salts are now the treatment of first choice for treating epilepsy in dogs, most still choose phenobarbital for dogs because of its favorable pharmacokinetic profile, relative safety, efficacy, low cost, and ability to treat epilepsy at sub-hypnotic doses. Phenobarbital is still widely considered the drug of first choice for treating epilepsy in cats. It is also occasionally used as an oral sedative agent in both species. Because it has a slightly longer onset of action, it is used principally in the treatment of status epilepticus in dogs, cats and horses to prevent the recurrence of seizures after they have been halted with either a benzodiazepine or short-acting barbiturate. Phenobarbital may also useful in controlling excessive feline vocalization while riding in automobiles.

In cattle, the microsomal enzyme stimulating properties of phenobarbital has been suggested for its use in speeding the detoxification of organochlorine (chlorinated hydrocarbon) insecticide poisoning. Additionally, phenobarbital has been used in the treatment and prevention of neonatal hyperbilirubinemia in human infants. It is unknown if hyperbilirubinemia is effectively treated in veterinary patients with phenobarbital.

The pharmacokinetics of phenobarbital have been thoroughly studied in humans and studied in a more limited fashion in dogs, cats and horses. Phenobarbital is slowly absorbed from the GI tract. Bioavailabilities range from 70-90% in humans, approximately 90% in dogs and absorption is practically complete in adult horses. Peak levels occur in 4-8 hours after oral dosing in dogs, and in 8-12 hours in humans.

Phenobarbital is widely distributed throughout the body, but because of its lower lipid solubility, it does not distribute as rapidly as most other barbiturates into the CNS. The amount of phenobarbital bound to plasma proteins has been reported to be 40-50%. The reported apparent volumes of distribution are approximately: Horse 0.8 L/kg; Foals 0.86 L/kg; Dogs 0.75 L/kg.

The drug is metabolized in the liver primarily by hydroxylated oxidation to p-hydroxyphenobarbital. Sulfate and glucuronide conjugates are also formed. The elimination half-lives reported in humans range from 2-6 days; in dogs from 12-125 hours with an average of approximately 2 days. Because of its ability to induce the hepatic enzymes used to metabolize itself, (and other drugs), elimination half-lives may decrease with time with concomitant reductions in serum levels. Some dogs may have half lives of less than 24 hours and may require 3 times daily dosing for maximal control. Elimination half-lives of 34-43 hours have been reported in cats. Elimination half-lives in horses are considerably shorter with values reported of approximately 13 hours in foals and 18 hours in adult horses. Phenobarbital will induce hepatic microsomal enzymes and it can be expected that elimination half-lives will decrease with time. Approximately 25% of a dose is excreted unchanged by the kidney. Alkalinizing the urine and/or substantially increasing urine flow, will increase excretion rates. Anuric or oliguric patients may accumulate unmetabolized drug and dosage adjustments may need to be made in these patients.

Changes in diet, body weight, and body composition may alter the pharmacokinetics of phenobarbital in dogs and necessitate dosage adjustment.

Use cautiously in patients who are hypovolemic, anemic, have borderline hypoadrenal function, or cardiac or respiratory disease. Large doses are contraindicated in patients with nephritis or severe respiratory dysfunction. Barbiturates are contraindicated in patients with severe liver disease or who have demonstrated previous hypersensitivity reactions to them.

When administering IV, give slowly (not more than 60 mg/minute). Too rapid IV administration may cause respiratory depression. Commercially available injectable preparations (excluding the sterile powder) must not be administered subcutaneously or perivascularly as significant tissue irritation and possible necrosis may result. Applications of moist heat and local infiltration of 0.5% procaine HCl solution have been recommended to treat these reactions.

Reproductive/Nursing Safety
In humans, the FDA categorizes this drug as category D for use during pregnancy (There is evidence of human fetal risk, but the potential benefits from the use of the drug in pregnant women may be acceptable despite its potential risks.) In a separate system evaluating the safety of drugs in canine and feline pregnancy (Papich 1989), this drug is categorized as in class: B (Safe for use if used cautiously. Studies in laboratory animals may have uncovered some risk, but these drugs appear to be safe in dogs and cats or these drugs are safe if they are not administered when the animal is near term.) Phenobarbital has been associated with rare congenital defects and bleeding problems in newborns, but may be safer than other anticonvulsants.

Exercise caution when administering to the nursing mother, since small amounts are excreted in maternal milk. Drowsiness in nursing offspring has been reported.

Adverse Effects/Warnings
Dogs may exhibit increased symptoms of anxiety/agitation or lethargy when initiating therapy. These effects are generally transitory in nature. Occasionally dogs will exhibit profound depression at lower dosage ranges (and plasma levels). Polydipsia, polyuria, and polyphagia are also quite commonly displayed at moderate to high serum levels and may falsely infer a diagnosis of Cushing's disease; these signs are usually controlled by limiting intake of both food and water. Sedation and/or ataxia often become significant concerns as serum levels reach the higher ends of the therapeutic range. Rarely, anemia, thrombocytopenia or neutropenia may occur which is reversible if detected early. Increases in liver enzymes are well described for phenobarbital in dogs and are not necessarily indicative of liver dysfunction, but if serum ALT or ALP are greater than 4-5 times the upper limit of normal or if any elevation of AST and GGT are noted it should raise concern. Phenobarbital should generally be discontinued if any increases in serum bilirubin, total serum bile acids or hypoalbumenemia are seen. Frank hepatic failure is uncommon and is usually associated with higher serum levels (>30-40 mcg/ml).

Phenobarbital may also rarely cause superficial necrolytic dermatitis (SND) in dogs associated with changes in hepatocytes (severe parenchymal collapse with glycogen-laden hepatocytes and moderate fibrosis sharply demarcated by nodules of normal hepatic parenchyma) distinct from that seen with phenobarbital hepatotoxicity

Cats may develop ataxia, persistent sedation and lethargy, polyphagia/weight gain, and polydipsia/polyuria. Rarely immune-mediated reactions and bone marrow hypoplasia (thrombocytopenia, neutropenia) may be seen. Cats, unlike dogs, apparently do not have the issues of increased liver enzymes. Very high dosages (10-40 mg/kg/day have caused coagulopathies in cats.

Although there is much less information regarding its use in horses (and in particular foals), it would be generally expected that adverse effects would mirror those seen in other species.

Treatment of phenobarbital overdose consists of removal of ingested product from the gut if appropriate and offering respiratory and cardiovascular support. Activated charcoal has been demonstrated to be of considerable benefit in enhancing the clearance of phenobarbital, even when the drug was administered parenterally. Charcoal acts as a "sink" for the drug to diffuse from the vasculature back into the gut. Forced alkaline diuresis can also be of substantial benefit in augmenting the elimination of phenobarbital in patients with normal renal function. Peritoneal dialysis or hemodialysis may be helpful in severe intoxications or in anuric patients.

Drug Interactions
The following drugs may increase the effect of phenobarbital: Other CNS depressants (narcotics, phenothiazines, antihistamines, etc), valproic acid, and chloramphenicol.

Phenobarbital may decrease the effect of the following drugs: oral anticoagulants, chloramphenicol, corticosteroids, doxycycline, beta-blockers (e.g., propranolol), quinidine, theophylline, & metronidazole. Pentobarbital with furosemide may cause or increase postural hypotension. Barbiturates may affect the metabolism of phenytoin; monitoring of blood levels may be indicated.

Rifampin may induce hepatic microsomal enzymes and reduce the half-life and effect of phenobarbital.

Phenobarbital may decrease the absorption of griseofulvin if given concurrently.

Drug/Lab Interactions
Barbiturates may cause increased retention of bromosulfophthalein (BSP; sulfobromophthalein) and give falsely elevated results. It is recommended that barbiturates not be administered within the 24 hours before BSP retention tests; or if they must, (e.g., for seizure control) the results be interpreted accordingly.

Phenobarbital can alter thyroid testing. Decreased total and free T4, normal T3, and either normal or increased TSH have been reported. It has been suggested to wait at least 4 weeks after discontinuing phenobarbital to perform thyroid testing.

In some dogs, phenobarbital may cause false positive low dose dexamethasone suppression test, by increasing the clearance of dexamethasone. Phenobarbital apparently has no effect either on ACTH stimulation tests or on the hormonal equilibrium of the adrenal axis.

    Bookmark   February 15, 2009 at 11:48AM
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Thanks for taking the time to respond, Meghane.

From what I understand, starting phenobarb is for life. Would it be too late to take him off it in 2 weeks, when we go to his 2 week checkup? Would he have to be weened off after such a short period on it?

    Bookmark   February 15, 2009 at 2:58PM
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Depending upon if you brought from a BYB or a reputable breeder, the simple answer is that the dog is a purebred, purebreds in gen have lots of issues, Keep in mind that even the best breeders who breed the best dogs only sell those that don't make the cut, they keep there best animals for breeding.

With such a young dog having all this you may need to see a specialist, and I hope that everything works out good.

    Bookmark   February 15, 2009 at 6:42PM
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I'd call the vet and ask the best way to wean off phenobarb. Everyone has different opinions.

If the screening bloodwork was normal, there is rarely a reason to do any further investigation into the cause of seizures in a young dog. The things that wouldn't show up on labwork are things like brain tumors and other unlikely causes in such a young animal. I always offer people a specialist, but tell them that 99.9% of the time, no cause of seizures will be found, and that would be after spending thousands of dollars for MRI and other advanced imaging. So I don't push the specialist as long as everything else is normal.

Also being a purebreed dog has nothing to do with seizures. And it isn't his food either.

    Bookmark   February 16, 2009 at 4:12PM
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There are several reasons for dogs to have seizures other than epilepsy. Below is an excellent link on some of those reasons. Many of these tests can be done by your GP other tests may require the expertise of a veterinary neurologist.
Type in Veterinary Neurology ( in your state) you may be lucky and have one close to you. Other possibilities for seizures should always be ruled out before epilepsy is ruled in.

Here is a link that might be useful: Reasons for seizures in dogs

    Bookmark   February 17, 2009 at 7:35PM
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Cindyxeus is right- epilepsy is a diagnosis of exclusion. You exclude all other causes of seizures and are left with the diagnosis of idiopathic epilepsy (which translates to seizures and we don't know why). I always do a CBC, chemistry panel, urinalysis, and T4 for all new seizure patients to rule out metabolic, infectious, inflammatory, and endocrine causes of seizures. In a young dog with a normal PE, I pretty much stop there. In older pets (over 6 years) I get more worried about brain tumors and other degenerative type diseases, but in a young dog those are unlikely. Also if the patient is not normal between seizures, other diseases are more likely (not idiopathic epilepsy).

    Bookmark   February 18, 2009 at 8:32AM
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I know labs have been bred to have very low pain and to be calm,cam calm,, Goldens are pretty close to them, with such a young dog, I'd bet the linage is to blame.

Whatever the issue I hope its something they can treat. If I am right then its like being born with autism, the dog will always be prone to getting Epilepsy, you can control it but its just part of the package

    Bookmark   February 18, 2009 at 8:42AM
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I'm happy to report that Quincy is finally himself... 100%! He is still on the low dosage of pheno but we have an appt with the vet Wednesday. I'm going to discuss with her about whether he really should be on any meds at this point. Also, I'm going to find out exactly what kind of tests were done.

Thanks for all the help. :)

    Bookmark   February 20, 2009 at 7:55PM
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Let us know how he does at the vet's on Wednesday. Some dogs are out of sorts for a while when starting phenobarb, then get over it. Glad Quincy is back to his normal self!

    Bookmark   February 22, 2009 at 12:30PM
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Just wanted to let you know that Quincy went back to the vet's today. I won't know about his bloodwork until tomorrow.

My biggest concern was about having him on the phenobarb. She stated the reason she feels he should be on it is because of the way he was clustering and each one getting worse. Hubs and I are discussing putting him on the potassium bromide and weaning him off the pheno. At this point we are unsure.

    Bookmark   February 25, 2009 at 7:51PM
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Moonie, good luck with Quincy.


    Bookmark   February 25, 2009 at 8:39PM
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Good luck too.

    Bookmark   February 28, 2009 at 12:57PM
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I hope everything went well at the vet's office. Any more seizures? I certainly understand the vet's concern about the severity of Quincy's first seizures. However it doesn't necessarily mean that he will ever have a seizure again.

Ana's only seizure lasted 12 minutes, and she was in that post-ictal haze for a good hour afterwards. It was quite a bad seizure- she actually turned blue for a few minutes. And in her post-ictal haze she was VERY aggressive which is totally out of character for her. It took us a half hour to catch her and get her into the car to go to the emergency vet, and I had to grab her with our comforter because she was trying to attack us. Of course by the time we got to the vets, she was pretty much over it. Got the blood work results and took her home. I was worried about her having another seizure too, but am glad I didn't start her on meds right away since she never did have another one. We got lucky. I hope you do too with Quincy.

    Bookmark   March 1, 2009 at 11:15AM
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It's 23 months later since I first posted about Quincy's seizures. Unfortunately, we had to put him to sleep Thursday morning. His seizures became more and more frequent, once to twice a week. He was in bad shape thursday morning. We are just devastated.

    Bookmark   January 29, 2011 at 7:58PM
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spedigrees z4VT

I am so sorry to read this. From what I understand it is hard to predict the path that seizures will take. Sometimes they never reoccur and sometimes they worsen. I'm so sorry that Quincy's was a worst case scenerio. My sincere condolences on your loss. Very sad.

    Bookmark   January 29, 2011 at 8:07PM
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I'm so sorry to hear about Quicy's passing. I had hoped that no news was good news.

(((Moonie_57 and Quincy)))

    Bookmark   January 29, 2011 at 9:25PM
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It's a story I was hoping would have a happy ending. I'm sorry you lost Quincy.

    Bookmark   January 30, 2011 at 2:27AM
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I'm so sorry for your loss. From your posts above, Quincy sounds like a wonderful dog and you did everything you could for him.

    Bookmark   January 30, 2011 at 11:10AM
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I'm so sorry to hear about Quincy. My thoughts are with you during this difficult time.

    Bookmark   January 31, 2011 at 9:18PM
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I'm so sorry about your Quincy. Special thoughts for you Moonie. I had a huskie/st. bernard mix that had seizures but not bad. I lost him in 96 and he was twelve when he died. Can't remember what meds I gave him. Then before that I had a little corgi mix that had them, too.

    Bookmark   February 3, 2011 at 1:06AM
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20 months later and i had Quincy on my mind the last couple of days and came to read this post again. It's silly, but for some reason I don't want this post to get cycled out.

There is some very useful info here for someone else that may come along.

    Bookmark   September 27, 2012 at 1:47PM
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Just thinking about Quincy again.

I saw on the 1st page of posts that someone had a dog that was seizing. Useful info from Meghane here.

We now have Maxwell who is almost as big a goofball as Quincy was. Still miss that boy every day, though!

    Bookmark   March 27, 2013 at 7:27PM
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