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Dosage Form: tablets
To reduce the development of drug-resistant bacteria and maintain the effectiveness of Metronidazole tablets and other antibacterial drugs, Metronidazole tablets should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.
Metronidazole has been shown to be carcinogenic in mice and rats. (See PRECAUTIONS.) Unnecessary use of the drug should be avoided. Its use should be reserved for the conditions described in the INDICATIONS AND USAGE section below.
Metronidazole is an oral synthetic antiprotozoal and antibacterial agent, 1-(β-hydroxyethyl)-2-methyl-5-nitroimidazole. The structural formula is represented below:
Each tablet, for oral administration, contains 250 mg or 500 mg of Metronidazole. In addition, each tablet contains the following inactive ingredients: colloidal silicon dioxide, crospovidone, hydrogenated vegetable oil and microcrystalline cellulose.
Metronidazole – Clinical Pharmacology
Disposition of Metronidazole in the body is similar for both oral and intravenous dosage forms, with an average elimination half-life in healthy humans of eight hours.
The major route of elimination of Metronidazole and its metabolites is via the urine (60 to 80% of the dose), with fecal excretion accounting for 6 to 15% of the dose. The metabolites that appear in the urine result primarily from side-chain oxidation [1-(β-hydroxyethyl)-2-hydroxymethyl-5- nitroimidazole and 2-methyl-5-nitroimidazole-1-yl-acetic acid] and glucuronide conjugation, with unchanged Metronidazole accounting for approximately 20% of the total. Renal clearance of Metronidazole is approximately 10 mL/min/1.73 m2.
Metronidazole is the major component appearing in the plasma, with lesser quantities of the 2-hydroxymethyl metabolite also being present. Less than 20% of the circulating Metronidazole is bound to plasma proteins. Both the parent compound and the metabolite possess in vitro bactericidal activity against most strains of anaerobic bacteria and in vitro trichomonacidal activity.
Metronidazole appears in cerebrospinal fluid, saliva, and human milk in concentrations similar to those found in plasma. Bactericidal concentrations of Metronidazole have also been detected in pus from hepatic abscesses.
Following oral administration, Metronidazole is well absorbed, with peak plasma concentrations occurring between one and two hours after administration. Plasma concentrations of Metronidazole are proportional to the administered dose. Oral administration of 250 mg, 500 mg, or 2,000 mg produced peak plasma concentrations of 6 mcg/mL, 12 mcg/mL, and 40 mcg/mL, respectively. Studies reveal no significant bioavailability differences between males and females; however, because of weight differences, the resulting plasma levels in males are generally lower.
Decreased renal function does not alter the single-dose pharmacokinetics of Metronidazole. However, plasma clearance of Metronidazole is decreased in patients with decreased liver function.
Trichomonas vaginalis, Entamoeba histolytica
Metronidazole possesses direct trichomonacidal and amebacidal activity against T. vaginalis and E. histolytica. The in vitro minimal inhibitory concentration (MIC) for most strains of these organisms is 1 mcg/mL or less.
Metronidazole is active in vitro against most obligate anaerobes but does not appear to possess any clinically relevant activity against facultative anaerobes or obligate aerobes. Against susceptible organisms, Metronidazole is generally bactericidal at concentrations equal to or slightly higher than the minimal inhibitory concentrations. Metronidazole has been shown to have in vitro and clinical activity against the following organisms:
Anaerobic gram-negative bacilli, including:
Bacteroides species including the Bacteroides fragilis group (B. fragilis, B.ovatus , B.distasonis, B. thetaiotaomicron, B. vulgatus)
Anaerobic gram-positive bacilli, including:
Clostridium species and susceptible strains of Eubacterium
Anaerobic gram-positive cocci, including:
Bacteriologic studies should be performed to determine the causative organisms and their susceptibility to Metronidazole; however, the rapid, routine susceptibility testing of individual isolates of anaerobic bacteria is not always practical, and therapy may be started while awaiting these results.
Quantitative methods give the most precise estimates of susceptibility to antibacterial drugs. A standardized agar dilution method and a broth microdilution method are recommended1.
Control strains are recommended for standardized susceptibility testing. Each time the test is performed, one or more of the following strains should be included: Clostridium perfringens ATCC 13124, Bacteroides fragilis ATCC 25285, and Bacteroides thetaiotaomicron ATCC 29741. The mode Metronidazole MICs for those three strains are reported to be 0.25, 0.25, and 0.5 mcg/mL, respectively.
A clinical laboratory is considered under acceptable control if the results of the control strains are within one doubling dilution of the mode MICs reported for Metronidazole.
A bacterial isolate may be considered susceptible if the MIC value for Metronidazole is not more than 16 mcg/mL. An organism is considered resistant if the MIC is greater than 16 mcg/mL. A report of “resistant” from the laboratory indicates that the infecting organism is not likely to respond to therapy.
Indications and Usage for Metronidazole
Metronidazole is indicated for the treatment of symptomatic trichomoniasis in females and males when the presence of the trichomonad has been confirmed by appropriate laboratory procedures (wet smears and/or cultures).
Metronidazole is indicated in the treatment of asymptomatic females when the organism is associated with endocervicitis, cervicitis, or cervical erosion. Since there is evidence that presence of the trichomonad can interfere with accurate assessment of abnormal cytological smears, additional smears should be performed after eradication of the parasite.
Treatment of Asymptomatic Consorts
T. vaginalis infection is a venereal disease. Therefore, asymptomatic sexual partners of treated patients should be treated simultaneously if the organism has been found to be present, in order to prevent reinfection of the partner. The decision as to whether to treat an asymptomatic male partner who has a negative culture or one for whom no culture has been attempted is an individual one. In making this decision, it should be noted that there is evidence that a woman may become reinfected if her consort is not treated. Also, since there can be considerable difficulty in isolating the organism from the asymptomatic male carrier, negative smears and cultures cannot be relied upon in this regard. In any event, the consort should be treated with Metronidazole in cases of reinfection.
Metronidazole is indicated in the treatment of acute intestinal amebiasis (amebic dysentery) and amebic liver abscess.
In amebic liver abscess, Metronidazole therapy does not obviate the need for aspiration or drainage of pus.
Anaerobic Bacterial Infections
Metronidazole is indicated in the treatment of serious infections caused by susceptible anaerobic bacteria. Indicated surgical procedures should be performed in conjunction with Metronidazole therapy. In a mixed aerobic and anaerobic infection, antimicrobials appropriate for the treatment of the aerobic infection should be used in addition to Metronidazole.
In the treatment of most serious anaerobic infections, the intravenous form of Metronidazole is usually administered initially. This may be followed by oral therapy with Metronidazole at the discretion of the physician.
INTRA-ABDOMINAL INFECTIONS, including peritonitis, intra-abdominal abscess, and liver abscess, caused by Bacteroides species including the B. fragilis group (B. fragilis, B. distasonis,B. ovatus, B. thetaiotaomicron, B. vulgatus), Clostridium species, Eubacterium species, Peptococcus niger, and Peptostreptococcus species.
SKIN AND SKIN STRUCTURE INFECTIONS caused by Bacteroides species including the B . fragilis group, Clostridium species, Peptococcus niger, Peptostreptococcus species, and Fusobacterium species.
GYNECOLOGIC INFECTIONS, including endometritis, endomyometritis, tubo-ovarian abscess, and post-surgical vaginal cuff infection, caused by Bacteroides species including the B. fragilis group, Clostridium species, Peptococcus niger, and Peptostreptococcus species.
BACTERIAL SEPTICEMIA caused by Bacteroides species including the B. fragilis group, and Clostridium species.
BONE AND JOINT INFECTIONS, as adjunctive therapy, caused by Bacteroides species including the B. fragilis group.
CENTRAL N E RVOUS SYSTEM (CNS) INFECTIONS, including meningitis and brain abscess, caused by Bacteroides species including the B. fragilis group.
LOWER RESPIRATO RY TRACT INFECTIONS, including pneumonia, empyema, and lung abscess, caused by Bacteroides species including the B. fragilis group.
ENDOCARDITIS caused by Bacteroides species including the B. fragilis group.
To reduce the development of drug-resistant bacteria and maintain the effectiveness of Metronidazole tablets and other antibacterial drugs, Metronidazole tablets should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
Metronidazole is contraindicated in patients with a prior history of hypersensitivity to Metronidazole or other nitroimidazole derivatives.
In patients with trichomoniasis, Metronidazole is contraindicated during the first trimester of pregnancy. (See PRECAUTIONS.)
Convulsive Seizures and Peripheral Neuropathy
Convulsive seizures and peripheral neuropathy, the latter characterized mainly by numbness or paresthesia of an extremity, have been reported in patients treated with Metronidazole. The appearance of abnormal neurologic signs demands the prompt discontinuation of Metronidazole therapy. Metronidazole should be administered with caution to patients with central nervous system diseases.
Patients with severe hepatic disease metabolize Metronidazole slowly, with resultant accumulation of Metronidazole and its metabolites in the plasma. Accordingly, for such patients, doses below those usually recommended should be administered cautiously.
Known or previously unrecognized candidiasis may present more prominent symptoms during therapy with Metronidazole and requires treatment with a candidacidal agent.
Prescribing Metronidazole tablets in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
Information for patients
Alcoholic beverages should be avoided while taking Metronidazole and for at least one day afterward. (See Drug Interactions.)
Patients should be counseled that antibacterial drugs including Metronidazole tablets should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Metronidazole tablets are prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Metronidazole tablets or other antibacterial drugs in the future.
Metronidazole is a nitroimidazole and should be used with caution in patients with evidence of or history of blood dyscrasia. A mild leukopenia has been observed during its administration; however, no persistent hematologic abnormalities attributable to Metronidazole have been observed in clinical studies. Total and differential leukocyte counts are recommended before and after therapy for trichomoniasis and amebiasis, especially if a second course of therapy is necessary, and before and after therapy for anaerobic infections.
Metronidazole has been reported to potentiate the anticoagulant effect of warfarin and other oral coumarin anticoagulants, resulting in a prolongation of prothrombin time. This possible drug interaction should be considered when Metronidazole is prescribed for patients on this type of anticoagulant therapy.
The simultaneous administration of drugs that induce microsomal liver enzymes, such as phenytoin or phenobarbital, may accelerate the elimination of Metronidazole, resulting in reduced plasma levels; impaired clearance of phenytoin has also been reported.
The simultaneous administration of drugs that decrease microsomal liver enzyme activity, such as cimetidine, may prolong the half-life and decrease plasma clearance of Metronidazole. In patients stabilized on relatively high doses of lithium, short-term Metronidazole therapy has been associated with elevation of serum lithium and, in a few cases, signs of lithium toxicity. Serum lithium and serum creatinine levels should be obtained several days after beginning Metronidazole to detect any increase that may precede clinical symptoms of lithium intoxication.
Alcoholic beverages should not be consumed during Metronidazole therapy and for at least one day afterward because abdominal cramps, nausea, vomiting, headaches, and flushing may occur.
Psychotic reactions have been reported in alcoholic patients who are using Metronidazole and disulfiram concurrently. Metronidazole should not be given to patients who have taken disulfiram within the last two weeks.
Drug/laboratory test interactions
Metronidazole may interfere with certain types of determinations of serum chemistry values, such as aspartate aminotransferase (AST, SGOT), alanine aminotransferase (ALT, SGPT), lactate dehydrogenase (LDH), triglycerides, and hexokinase glucose. Values of zero may be observed. All of the assays in which interference has been reported involve enzymatic coupling of the assay to oxidation-reduction of nicotinamide adenine dinucleotide (NAD+ ↔ NADH). Interference is due to the similarity in absorbance peaks of NADH (340 nm) and Metronidazole (322 nm) at pH 7.
Carcinogenesis, mutagenesis, impairment of fertility
Metronidazole has shown evidence of carcinogenic activity in a number of studies involving chronic, oral administration in mice and rats.
Prominent among the effects in the mouse was the promotion of pulmonary tumorigenesis. This has been observed in all six reported studies in that species, including one study in which the animals were dosed on an intermittent schedule (administration during every fourth week only). At very high dose levels (approx. 500 mg/kg/day which is approximately 33 times the most frequently recommended human dose for a 50 kg adult based on mg/kg body weight) there was a statistically significant increase in the incidence of malignant liver tumors in males. Also, the published results of one of the mouse studies indicate an increase in the incidence of malignant lymphomas as well as pulmonary neoplasms associated with lifetime feeding of the drug. All these effects are statistically significant.
Several long-term, oral-dosing studies in the rat have been completed. There were statistically significant increases in the incidence of various neoplasms, particularly in mammary and hepatic tumors, among female rats administered Metronidazole over those noted in the concurrent female control groups.
Two lifetime tumorigenicity studies in hamsters have been performed and reported to be negative.
Although Metronidazole has shown mutagenic activity in a number of in vitro assay systems, studies in mammals (in vivo) have failed to demonstrate a potential for genetic damage.
Fertility studies have been performed in mice at doses up to six times the maximum recommended human dose based on mg/m2 and have revealed no evidence of impaired fertility.
Teratogenic effects-Pregnancy Category B
Metronidazole crosses the placental barrier and enters the fetal circulation rapidly. Reproduction studies have been performed in rats at doses up to five times the human dose and have revealed no evidence of impaired fertility or harm to the fetus due to Metronidazole. No fetotoxicity was observed when Metronidazole was administered orally to pregnant mice at 20 mg/kg/day, approximately one and a half times the most frequently recommended human dose (750 mg/day) based on mg/kg body weight; however, in a single small study where the drug was administered intraperitoneally, some intrauterine deaths were observed. The relationship of these findings to the drug is unknown. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, and because Metronidazole is a carcinogen in rodents, this drug should be used during pregnancy only if clearly needed.
Use of Metronidazole for trichomoniasis during pregnancy should be restricted to those in whom alternative treatment has been inadequate. Use of Metronidazole for trichomoniasis in pregnancy should be carefully evaluated because Metronidazole crosses the placental barrier and its effects on the human fetal organogenesis are not known (see above).
Because of the potential for tumorigenicity, shown for Metronidazole in mouse and rat studies, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Metronidazole is secreted in human milk in concentrations similar to those found in plasma.
Decreased renal function does not alter the single-dose pharmacokinetics of Metronidazole. However, plasma clearance of Metronidazole is decreased in patients with decreased liver function. Therefore, in elderly patients, monitoring of serum levels may be necessary to adjust the Metronidazole dosage accordingly.
Safety and effectiveness in pediatric patients have not been established, except for the treatment of amebiasis.
Two serious adverse reactions reported in patients treated with Metronidazole have been convulsive seizures and peripheral neuropathy, the latter characterized mainly by numbness or paresthesia of an extremity. Since persistent peripheral neuropathy has been reported in some patients receiving prolonged administration of Metronidazole, patients should be specifically warned about these reactions and should be told to stop the drug and report immediately to their physicians if any neurologic symptoms occur.
The most common adverse reactions reported have been referable to the gastrointestinal tract, particularly nausea reported by about 12% of patients, sometimes accompanied by headache, anorexia, and occasionally vomiting; diarrhea; epigastric distress; and abdominal cramping. Constipation has also been reported.
The following reactions have also been reported during treatment with Metronidazole:
A sharp, unpleasant metallic taste is not unusual. Furry tongue, glossitis, and stomatitis have occurred; these may be associated with a sudden overgrowth of Candida which may occur during therapy.
Reversible neutropenia (leukopenia); rarely, reversible thrombocytopenia.
Flattening of the T-wave may be seen in electrocardiographic tracings.
Central Nervous System
Convulsive seizures, peripheral neuropathy, dizziness, vertigo, incoordination, ataxia, confusion, irritability, depression, weakness, and insomnia.
Urticaria, erythematous rash, flushing, nasal congestion, dryness of the mouth (or vagina or vulva), and fever.
Dysuria, cystitis, polyuria, incontinence, and a sense of pelvic pressure. Instances of darkened urine have been reported by approximately one patient in 100,000. Although the pigment which is probably responsible for this phenomenon has not been positively identified, it is almost certainly a metabolite of Metronidazole and seems to have no clinical significance.
Proliferation of Candida in the vagina, dyspareunia, decrease of libido, proctitis, and fleeting joint pains sometimes resembling “serum sickness.” If patients receiving Metronidazole drink alcoholic beverages, they may experience abdominal distress, nausea, vomiting, flushing, or headache. A modification of the taste of alcoholic beverages has also been reported. Rare cases of pancreatitis, which generally abated on withdrawal of the drug, have been reported.
Crohn’s disease patients are known to have an increased incidence of gastrointestinal and certain extraintestinal cancers. There have been some reports in the medical literature of breast and colon cancer in Crohn’s disease patients who have been treated with Metronidazole at high doses for extended periods of time. A cause and effect relationship has not been established. Crohn’s disease is not an approved indication for Metronidazole.
Single oral doses of Metronidazole, up to 15 g, have been reported in suicide attempts and accidental overdoses. Symptoms reported include nausea, vomiting, and ataxia.
Oral Metronidazole has been studied as a radiation sensitizer in the treatment of malignant tumors. Neurotoxic effects, including seizures and peripheral neuropathy, have been reported after 5 to 7 days of doses of 6 to 10.4 g every other day.
There is no specific antidote for Metronidazole overdose; therefore, management of the patient should consist of symptomatic and supportive therapy.
Metronidazole Dosage and Administration
In elderly patients, the pharmacokinetics of Metronidazole may be altered, and, therefore, monitoring of serum levels may be necessary to adjust the Metronidazole dosage accordingly.
In the Female
One-day treatment— two grams of Metronidazole, given either as a single dose or in two divided doses of one gram each given in the same day.
Seven-day course of treatment— 250 mg three times daily for seven consecutive days. There is some indication from controlled comparative studies that cure rates as determined by vaginal smears, signs and symptoms, may be higher after a seven-day course of treatment than after a one-day treatment regimen.
The dosage regimen should be individualized. Single-dose treatment can assure compliance, especially if administered under supervision, in those patients who cannot be relied on to continue the seven-day regimen. A seven-day course of treatment may minimize reinfection by protecting the patient long enough for the sexual contacts to obtain appropriate treatment. Further, some patients may tolerate one treatment regimen better than the other.
Pregnant patients should not be treated during the first trimester. (See CONTRAINDICATIONS.) In pregnant patients in whom alternative treatment has been inadequate, the one-day course of therapy should not be used, as it results in higher serum levels which can reach the fetal circulation (see PRECAUTIONS, Pregnancy).
When repeat courses of the drug are required, it is recommended that an interval of four to six weeks elapse between courses and that the presence of the trichomonad be reconfirmed by appropriate laboratory measures. Total and differential leukocyte counts should be made before and after retreatment.
In the Male
Treatment should be individualized as for the female.
For acute intestinal amebiasis (acute amebic dysentery): 750 mg orally three times daily for 5 to 10 days.
For amebic liver abscess: 500 mg or 750 mg orally three times daily for 5 to 10 days.
35 to 50 mg/kg/24 hours, divided into three doses, orally for 10 days.
Anaerobic Bacterial Infections
In the treatment of most serious anaerobic infections, the intravenous form of Metronidazole is usually administered initially.
The usual adult oral dosage is 7.5 mg/kg every six hours (approx. 500 mg for a 70-kg adult). A maximum of 4 g should not be exceeded during a 24-hour period.
The usual duration of therapy is 7 to 10 days; however, infections of the bone and joint, lower respiratory tract, and endocardium may require longer treatment.
Patients with severe hepatic disease metabolize Metronidazole slowly, with resultant accumulation of Metronidazole and its metabolites in the plasma. Accordingly, for such patients, doses below those usually recommended should be administered cautiously. Close monitoring of plasma Metronidazole levels2 and toxicity is recommended.
The dose of Metronidazole should not be specifically reduced in anuric patients since accumulated metabolites may be rapidly removed by dialysis.
How is Metronidazole Supplied
Metronidazole Tablets USP 250 mg are 11/32״, unscored, round, white to off-white tablets imprinted DAN and 5540 supplied in bottles of 50, 100, 250, 500 and 1000.
Metronidazole Tablets USP 500 mg are 17/32״, scored, round, white to off-white tablets imprinted DAN and 5552 supplied in bottles of 50, 100, 250, 500 and 1000. Dispense in a well-closed, light-resistant container with child-resistant closure.
Store below 86°F (30°C).
Protect from light.
1. Proposed standard: PSM-11-Proposed Reference Dilution Procedure for Antimicrobic Susceptibility Testing of Anaerobic Bacteria, National Committee for Clinical Laboratory Standards; and Sutter, et al.: Collaborative Evaluation of a Proposed Reference Dilution Method of Susceptibility Testing of Anaerobic Bacteria, Antimicrob. Agents Chemother. 16:495-502 (Oct.) 1979; and Tally, et al.: In Vitro Activity of Thienamycin, Antimicrob. Agents Chemother. 14:436-438 (Sept.) 1978.
Ralph, E.D., and Kirby, W.M.M.: Bioassay of Metronidazole With Either Anaerobic or Aerobic Incubation, J. Infect. Dis.132:587-591 (Nov.) 1975; or Gulaid, et al.: Determination of Metronidazole and Its Major Metabolites in Biological Fluids by High Pressure Liquid Chromatography, Br. J. Clin. Pharmacol. 6:430-432, 1978.
This article is used with permission from the author.
Autoimmune Lymphocytic Thyroiditis – The Unknown Epidemic?? © 2005
Written by sinbajé basenjis for the BCOA Bulletin – a quarterly publication of the National breed club
Surveys conducted in the mid 1990’s by the AKC Delegate Committee on Health Research showed thyroid disease to be the number one health concern of major breed clubs, placed ahead of hip dysplasia and epilepsy in breeds with a high incidence of both. Due to this overwhelming concern, thyroid testing, diagnosis and treatment have improved tremendously over the years. However, when compared to fanconi, malabsorption, or PRA, thyroid dysfunction fails to ignite much interest in the basenji breed. The thyroid is treated much like a poor relation, greatly ignored by the breeding masses, despite our ability to test for this hereditary condition early and often. Are we doing the breed a major disservice by not taking thyroid disease in breeding stock more seriously?
What is the exact function of the thyroid and why is proper function so important?
The sole purpose of the thyroid gland is to convert dietary iodine into two thyroid hormones; thyroxine (T4) and triiodothyronine (T3). Once converted, these hormones are dispersed throughout the body where almost every cell depends upon them for regulation of their individual metabolism. This means excessive, sufficient or insufficient thyroid levels affect every metabolic activity of the body to some degree, either positively or negatively.
When thyroid hormones become abnormal, many, if not all, body systems are also affected; skin (hair), immune system (allergies), sex glands (low sex drive and/or infertility) and brain (seizures and/or aberrant behavior such as aggression) to name just a few. Proper thyroid function is needed for proper body function. Too much thyroid hormone, or hyperthyroidism, means metabolism speeds up. Too little thyroid hormone, or hypothyroidism, means metabolism slows down. Hyperthyroidism, while quite common in the cat, is extremely rare in the dog while the opposite is true of hypothyroidism; rare in the cat and common in the dog. Research has shown the most common disease of the canine endocrine system to be primary hypothyroidism.
What exactly is hypothyroidism and how is it diagnosed?
In short, active hypothyroidism (HT) is created when the thyroid gland is no longer efficient at converting iodine into much needed thyroid hormone (T3 and T4) and body systems begin to wane. The most accurate means of diagnosis is made via a series of specific blood tests, with or without correlating symptoms. Symptoms can range from the outwardly obvious – weight gain, lethargy and behavior changes to inwardly subtle – anemia, and sterility and have been shown to take as long as 18 months after the official lab diagnosis to become noticeable. While hypothyroidism can be diagnosed via blood work without supporting symptoms, an influx of symptoms is not always predictive of hypothyroidism, as there are many other conditions with parallel symptoms.
There are three classifications of hypothyroidism: primary, secondary and tertiary with primary being associated with the thyroid gland, secondary with the pituitary gland and tertiary with the hypothalamus. As previously stated, primary hypothyroidism appears to have a high rate of occurrence in the canine with secondary and tertiary being less commonly found. While there are five classes of primary canine hypothyroidism, the two most commonly found are: autoimmune lymphocytic thyroiditis (ALT) and idiopathic follicular atrophy. While hypothyroidism is not a life threatening condition when properly treated, the quality of life for a true hypothyroid animal, especially one not accurately diagnosed and/or treated, can be substandard.
What is Autoimmune Lymphocytic Thyroiditis (ALT)?
Autoimmune Lymphocytic Thyroiditis (ALT) is a hereditary disease that occurs when lymphocytes, or white blood cells associated with the immune system, attack the thyroid gland creating inflammation. The lymphocytes not only attack, they irreversibly destroy healthy thyroid tissue needed to produce thyroxine (T4), the hormone that supports body system metabolism. Without viable tissue, the gland can no longer produce T4 and the dog becomes actively hypothyroid. While ALT is responsible for 50% of all primary hypothyroid cases, active hypothyroidism is not a guaranteed outcome of all ALT diagnosis. The Orthopedic Foundation for Animals (OFA), a national health registry, classifies ALT in two ways: positive advanced or compensative.
- Positive advanced ALT occurs after total eradication of all thyroid tissue and is defined by the following lab results: positive TgAA, low FT4(ed), and high cTSH.
A dog with positive advanced ALT is by all accounts actively hypothyroid and should begin hormone replacement therapy even though clinical (observable) symptoms may take as long as 18 months to support lab work. This lack of symptoms can be deceiving, making some owners unwilling to medicate immediately. This is a mistake.
- Compensative ALT is when inflammation of the thyroid gland is still in the early stages and complete destruction of the gland has not yet occurred. It is defined by the following lab results: positive TgAA, normal FT4(ed), and normal cTSH.
While compensative ALT dogs do have a high probability of progressing to active hypothyroidism, especially when positive T3AA and T4AA are also present, active hypothyroidism does not always occur, making hormone therapy of compensative ALT dogs debatable/controversial in some circles. Retesting compensative dogs semi-annually, to keep abreast of any lab work changes that might indicate a development to active hypothyroidism, and supplementing at that time, is a viable option for those owners who do not feel comfortable medicating.
Canine ALT shows no gender inclination with both sexes being equally at risk. ALT is considered to be hereditary and is believed to be polygenetic with familial tendencies, much like hip dysplasia, though some experts feel it is more autosomally recessive in nature. Therefore, dogs diagnosed with either positive advanced or compensative ALT (or positive TgAA) should be bred carefully, if at all.
What is “idiopathic follicular atrophy hypothyroidism”?
Idiopathic atrophy of the thyroid gland is characterized by the unexplained loss of thyroid cells, which are replaced by fat and/or scar tissue. Once again, the lack of functioning thyroid cells needed to produce thyroxine (T4), is what creates active hypothyroidism. While idiopathic loosely means ‘without cause’, research is beginning to suggest that 50% of diagnosed idiopathic atrophy is more likely a natural progression, or end result, of the heritable autoimmune lymphocytic thyroiditis. This translates to roughly 75% of true thyroid disease being caused in some way by ALT, a hereditary condition. The remaining 25%, those that are truly idiopathic ‘without cause’, appears to be quite rare in young dogs, affecting most dogs in mid-life between the ages of 5 and 9, and is not believed to be hereditary. That said, true idiopathic hypothyroidism should not be considered a “common” condition of a specific breed.
What does FT4(ed), cTSH, TgAA, et al mean – it’s all Greek to me?
T4 (thyroxine) is one of two thyroid hormones used in the regulation of the body’s metabolism. FT4(ed), sometimes seen as FT4D, stands for free thyroxine tested by way of equilibrium dialysis. Free, to mean not bound by carrier protein representing the portion of the T4 hormone that is actually active on a cellular level, as opposed to representing all parts that make up the total T4. Use of the equilibrium dialysis testing method is considered as the ‘gold standard’ due to its lack of interference by T4 autoantibodies (T4AA) as the process of dialysis actually removes said antibodies during testing. The radioimmunoassay (RIA) method of testing can have T4AA interference, which simply means that the interference must be taken into consideration when FT4 (RIA) results are interpreted as T4 levels can be falsely increased or decreased depending on the lab running the test.
cTSH is canine thyroid stimulating hormone. The job of the cTSH is to regulate the production of T4 within the thyroid gland, much like a thermostat regulates whether the furnace should heat up, cool down or stay as it is. When T4 circulation levels drop, the pituitary gland is alerted to the problem and quickly responds by releasing cTSH, which makes its way to the thyroid gland where it attempts to stimulate the gland into producing more thyroxin (T4). In theory, when the T4 level is normal, cTSH is expected to also be normal. When T4 levels are high, cTSH is expected to be low, as there is no need for more T4 in the system and once cTSH production is stopped, its levels decrease. When T4 levels are low, cTSH is expected to be high, as the pituitary gland is hard at work making cTSH needed to encourage the thyroid into increasing its T4 production. While the TSH test in humans has a near 100% rate of accuracy, the canine TSH is less precise with an accuracy rate closer to 85%, meaning that a small percentage of hypothyroid dogs may not show the expected elevation in serum TSH. This low diagnostic sensitivity understandably keeps some testing facilities from incorporating the cTSH into their diagnostic profiles, however increased diagnostic differentiation between those animals who are sick, but have normal functioning thyroids, and those with active hypothyroidism, has been found when cTSH is used along with FT4ed and TgAA.
TgAA is short for thyroglobulin autoantibodies and is believed to be the first indicator of hereditary autoimmune lymphocytic thyroiditis. TgAA can be positive a year or two before clinical signs are noted, which allow breeders to test early and often so that better breeding decisions can be made which will ultimately reduce the prevalence of the disease within the breed. The standard methodology of TgAA testing is via enzyme-linked immunosorbent assays (ELISA). The ELISA test has been compared favorably with thyroid biopsy results, which is to say, when ELISA results have said “positive”, corresponding thyroid biopsy results have also said “positive”. Testing via the ELISA method is considered by some to be the ‘gold standard’ of genetic screening for ALT. Note of interest: It has been recently identified that statistically, significantly higher prevalence of positive TgAA has been found in, amongst several other breeds, the basenji dog.
T3AA/T4AA is T3 and T4 autoantibodies respectively. Autoantibodies are proteins produced by the immune system against its own tissues which are perceived as foreign invaders. Defined as TgAA subclasses, both T3AA/T4AA are considered, along with TgAA, as markers for ALT. While almost all cases of autoimmune lymphocytic thyroiditis will have elevated TgAA levels, less than 20% of these same cases will also have elevated T3AA or T4AA. Since the absence of T3AA/T4AA has a high rate of expectancy (~80%), nothing diagnostic, specifically idiopathic hypothyroidism should ever be inferred by the lack of their presence when FT4ed is low and TgAA is either negative or untested. Human thyroid articles suggest that T3/T4 AA levels, especially T3AA, can be falsely elevated due to interference from lipids (fat) in the serum or blood cell damage due to processing and are therefore not routinely included in human thyroid testing panels. However, T3AA/T4AA testing is important in animal diagnostics, especially when radioimmunassay (RIA) method of testing is used to measure T3 and T4, due to their ability to interfere with (falsely increase) the results. Accurate interpretations of RIA based T3 and T4 results can not be fully established without first knowing whether or not T3/T4 autoantibodies are also present.
Do I understand this right? If my dog is TgAA negative then I’m in the clear?
Unfortunately it is not so simple. If a dog’s TgAA is tested for the first time at the age of five and the TgAA is negative it can not be said, with 100% certainty, that the dog did not, in the proceeding five years, have positive TgAA, and thus hereditary autoimmune lymphocytic thyroiditis. The recommendations for properly screening breeding stock of hereditary autoimmune lymphocytic thyroiditis is to start testing at the age of one. Test annually until the age of five, then every other year until old age. Studies have suggested that a dog tested annually from the age of one who does not acquire the disease by the age of five, has a greater potential of remaining disease free throughout its lifetime. That said, there are cases, albeit rare, where TgAA initially becomes positive beyond the age of five due perhaps to a disruption of the gland structure or thyroid tumor rather than inflammation normally associated with autoimmune lymphocytic thyroiditis.
Isn’t active hypothyroidism the same as autoimmune lymphocytic thyroiditis (positive TgAA)?
No. Autoimmune lymphocytic thyroiditis, or positive TgAA, is merely a classification of thyroid damage; it alone doesn’t tell us whether thyroid function has (yet) been affected. While autoimmune lymphocytic thyroiditis is the major cause (~75%) of active hypothyroidism, many dogs can harbor thyroiditis for years before showing clinical (observable) signs of the disease, if at all. It is believed that 60% or more of viable thyroid tissue needs to be destroyed before lab work begins to reflect thyroid dysfunction. Studies have shown that there is no set rule to the development, or lack of development, of autoimmune lymphocytic thyroiditis as some dogs remain TgAA positive for life and never progress to active hypothyroidism, while others become actively hypothyroid and need hormone supplementation. Some dogs go from positive to negative TgAA and still have enough viable thyroid tissue needed to produce adequate amounts of T4, while other dogs will go from positive to negative TgAA and have no functional tissue left and become actively hypothyroid and in need of supplementation. Regardless of whether the dog does or does not progress to active hypothyroidism the fact remains that if the TgAA is positive the dog has hereditary autoimmune lymphocytic thyroiditis and should not be bred.
What’s the big deal? It’s not like hypothyroidism can kill my dog.
Hypothyroidism that has not been properly diagnosed does have the potential to directly and/or indirectly kill your dog or a dog you have bred. The ultimate consequence of hypothyroidism can result in coma (myxedmatous coma). The immune system does not function correctly as a result, leaving the dog susceptible to infections and blood poisoning. Fatal anaphylactic reactions to spider bites, ingested plant material and/or of unknown origins are common problems in the canine species. Thyroid dysfunction comprises the immune system leaving a dog susceptible to these kinds of deadly allergic reactions.
Puberty, roughly between fifteen and eighteen months of age, is a prime time for basenjis to exhibit aberrant behaviors such as aggression. Many pet owners, too embarrassed to contact their breeders, feeling perhaps they did something wrong in the pups upbringing, choose instead to dump the “problem” dog onto their local animal shelter. On a good day the shelter might contact purebred rescue and have the animal picked up where it will be evaluated and hopefully re-homed. On a bad day the ‘aggressive’ basenji, a breed already labeled as ‘land sharks’ in the animal care profession, has a high probability of being euthanised to make room for a more adoptable dog. The more tenacious owner might keep the aggressor longer, perhaps spending a fair wage on behavior modification training, to no avail, while continuing to live in fear of their highly unpredictable pet. Eventually they too release the dog where death is not always last on the list of probabilities, and thyroid testing is rarely, if ever, first.
While hypothyroidism might not seem like a big deal to breeders when compared to other ills of our breed, it becomes a big deal to the average pet owner, who has the most to lose, financially and emotionally. All breeders should be actively trying to produce the best dogs and should therefore be concerned about thyroid disease. While hypothyroidism is easily treated, and the medication is relatively cheap, the cost of initial diagnosis can run into the high hundreds for those dogs showing symptoms of a number of other possible conditions, using common veterinary practitioners unfamiliar with current thyroid testing protocols. Add to that the life sentence of annual testing, at times semi-annually, and you are looking at serious monetary investments for a disease that can be controlled by breeders through proper screening and culling of breeding stock.
What can I do as a breeder?
The following suggestions for reducing the incidence of hereditary primary hypothyroidism was cited from the International Symposium of Canine Hypothyroidism at the University of California – Davis:
- Keep accurate records of thyroid status, especially parents, siblings and offspring.
Much like hip dysplasia, vertical pedigrees have more information for breeders evaluating gene potential when compared to the more standard horizontal pedigrees. The premise being that a dog that has several affected littermates has a greater potential for carrying the disease than a dog whose maternal grandmother is the only dog affected. Keeping track of all siblings and offspring – even those sold as pets – is crucial in creating these informative vertical pedigrees.
- Expand gene pools by avoiding inbreeding and line breeding.
This is especially true for basenji families with a large number of dogs on thyroid hormone supplementation. The prevalence of familial hypothyroidism has been shown to decrease with each generation when dogs symptomatic for hypothyroidism are removed from breeding.
- Remove TgAA positive dogs from the breeding pool
In order for this to work to its full potential, TgAA must be tested annually from the onset of puberty, around the age of one, to the age of five and then every other year. Breeding of dogs should ideally not take place until after the age of five, with three being the absolute minimum age. If the TgAA has not been tested from the onset, hereditary status is not fully known and care should be taken by way of current testing along with close study of vertical pedigrees of potential sires and dams for risk factors such as numerous hypothyroid siblings/offspring/aunts/uncles.
Is there a time when my dog should/should not be tested?
The blood sample should be taken when the dog is relaxed and otherwise healthy, is not approaching or in a heat cycle, and is not being medicated with the following, due to their ability to falsely decrease T4 levels; steroids, non-steroidal anti-inflammatories, sulfonamides or anti-seizures. If in doubt, including cTSH levels in your testing regime might provide a clear distinction between true hypothyroidism and drug suppression.
A dog whose hypothyroid diagnosis is questionable, but is currently on thyroid replacement therapy, should discontinue medication for at least 6 weeks prior to testing so that the dog’s true thyroid function will not be influenced by the medication.
Tell me again the tests I should be asking for.
Ideally a full thyroid profile – FT4ed, cTSH, TgAA, T3AA & T4AA will show every piece of the puzzle needed for accurate diagnosis: T4/cTSH to show thyroid dysfunction, if any and TgAA/T3AA/T4AA to show hereditary disease, if any. However, doing a full profile, every year from the age of one onwards, on every breeding animal is not cost effective for most breeders. Another approach would be to test only the TgAA during the first four years, adding the full panel at the age of five and then testing every other year from then onwards. Should the TgAA become positive prior to the age of five a full panel is necessary to get a baseline level of the thyroid function. Since relatively few dogs have been shown to have low T4, high cTSH and negative TgAA prior to the age of five, testing TgAA only would be a cost efficient means of hereditary screening.
Where can I get tested?
Diagnosing hypothyroidism solely on total T4 (TT4) blood levels and ambiguous clinical signs, is considered archaic by most experts in the field and yet many local practitioners continue to do just that. Until all veterinarians educate themselves on current testing recommendations, it is suggested that outside laboratories be used for more accurate thyroid screening.
Whether you are interested in testing for OFA certification, or for your own records, the following are approved OFA thyroid testing facilities. Applications for OFA certification, along with their fees, can be found at: (http://ofaweb.offa.org/OFA)
Note: For inclusion to the OFA registry FT4ed, cTSH and TgAA are the only tests needed. However, as stated above, a full thyroid profile should ideally include FT4ed, cTSH, TgAA, T3AA & T4AA. All testing facilities listed below can do a full panel if requested.
Michigan State University
|Veterinary Diagnostic Laboratory
Univ. of Minnesota
|University of California
Veterinary Medical Teaching Hospital
|Texas Veterinary Medical Diagnostic Lab
|Animal Health Laboratory
|Veterinary Diagnostic Lab
University of Minnesota
Lake Success , NY
*only the Lake Success, NY location of Antech has been certified to process
OFA thyroid panels
HEMOPET is another good testing facility that not only offers a wide range of testing and vaccine titration, but also the chance to personally discuss the results and/or treatment needed with the attending veterinarian, Dr. W. Jean Dodds. Being a small, not for profit blood bank, HEMOPET has not applied for OFA accreditation due, in part, to the substantial fee needed for application. Test request forms and instructions can be found at: http://www.itsfortheanimals.com/HEMOPET.HTM
HEMOPET: Dr. W Jean Dodds, DVM
11330 Markon Drive
Garden Grove, CA 92841
Phone: 714/ 891-2022
PLEASE NOTE: Because HEMOPET does not include TgAA in their Thyroid Antibody Profile, or Free T4 by equilibrium dialysis, you must ask for these tests specifically if you are interested in them.
If there were any keys points to remember – what would they be?
There are currently forty-four (44) basenjis registered with the OFA Thyroid registry. Of these, 15.9% have been diagnosed as having hereditary autoimmune lymphocytic thyroiditis. For comparison purposes, percentages for the top three breeds showing the highest prevalence of thyroiditis per the OFA website were: 22.1.4%, 20.3% and 14.6% respectively. MSU shows 12.4% of all basenjis tested as having thyroiditis, with another 7.7% needing to be retested due to questionable (non definitive) results. Basenjis ranked 28 out of 100 breeds represented for prevalence of thyroiditis. Another interesting comparison would be versus the evidence of hip dysplasia in the basenji; per OFA only 2.8% of the 1436 tested had abnormal hips. That’s 2.8% hips versus 15.9% ALT. Ironically, breeders are more concerned with hips than they are thyroids!
Ideally a full thyroid profile – FT4ed, cTSH, TgAA, T3AA & T4AA will show every piece of the puzzle needed for accurate diagnosis. However, TgAA is the first indicator of hereditary autoimmune lymphocytic thyroiditis and can be tested for as early as one year of age.
While autoimmune lymphocytic thyroiditis (positive TgAA) is considered to be hereditary and some experts feel dogs diagnosed with positive TgAA should be removed from the breeding pool, there are those who feel that it is a recessive gene and bred wisely, can be avoided.
~75% of all primary thyroid disease is caused by autoimmune lymphocytic thyroiditis, a hereditary condition while true idiopathic hypothyroidism accounts for roughly 25%. Therefore idiopathic hypothyroidism should not be a “normal” condition in any breed.
Hereditary autoimmune lymphocytic thyroiditis can NOT be definitively ruled out if the dog’s TgAA was initially tested negative at the age of five due to the lack of information in the proceeding five years.
The prevalence of familial hypothyroidism has been shown to decrease with each generation when dogs symptomatic for hypothyroidism are removed from breeding.
Symptoms can take as long as 18 months after lab work supports active hypothyroidism to become noticeable, making blood work crucial for early accurate diagnosis.
All breeders should be actively trying to produce the best dogs and should therefore be concerned about thyroid disease.
Dr. Peter A Graham BVMS, PhD, CertVR, Diplomate ECVCP, MRCVS
Director North Western Laboratories and Cambridge Specialist Laboratory Services, UK
Dr. Graham worked in the thyroid lab at Michigan State University (www.ahdl.msu.edu) for 7 years before moving recently to head two British based laboratories, North Western Laboratories (www.nwlabs.co.uk) and Cambridge Specialist Laboratory Services (www.cslabs.co.uk) and has authored/co-authored numerous peer reviewed articles relating to thyroid function and testing.
Dr. W. Jean Dodds, DVM
Dr. Dodds, is a nationally and internationally recognized authority on blood and immune disorders, thyroid disease and nutrition. Dr. Dodds is the president of Hemopet/Pet Lifeline, the first national nonprofit animal blood bank and greyhound rescue/adoption program serving North America. Hemopet also conducts nonprofit clinical research studies.
Dr. Graham and Dr. Dodds were kind enough to answer any email queries I sent asking for more information/explanation regarding canine hypothyroidism. Dr. Graham and Dr. Dodds also took time out of their busy schedules to personally review my article and offer their insights. For that I am extremely appreciative. Thank you both for your wonderful contributions.
References:Lymphocytic Thyroiditis: Veterinary Clinics Of North America: Small Animal Practice: RF Nachreiner, M Bowman, KR Refsal, PA Graham, A Provencher Bolliger. Vol. 31/No. 5/September 2001
Antech Diagnostic NEWS – November 1998: Dr. W. Jean Dodds, DVM: http://www.antechdiagnostics.com/clients/antechNews/1998/11-98.htm
Antech Diagnositc NEWS – November 2002: Dr. W. Jean Dodds, DVM:
International Symposium Of Canine Hypothyroidism -UC Davis.
A synopsis by Timberline Retrievers LLC – http://www.goldens.com/tip8.html
Canine Hypothyroidism by David Bruyette World Small Animal Veterinary Asssociation–World Congress 2001
Small Animal Clinical – Endocrinology: Thyroid Function and Tests Of Thyroid Function: Evaluation of canine serum thyrotropin (TSH) concentration: comparison of three analytical procedures Marca MC, Loste A, Orden, I et al. Jvet Diagn Invest 2001:13:106-110
The Orthopedic Foundation of Animals – Thyroid information and registry
THE ADVOCATE: News From the Orthopedic Foundations of Animals, a non-proft organization
“Is Hypothyroidism Really The Leading Canine Genetic Disease?” – http://www.offa.org/issue1.pdf
Common Tests to Examine Thyroid Gland Function – The Human Endocrine Web Site
Thyroid Function in Dogs: MSU FAQs:
Titres were first used to determine the need for annual vaccinations. Then, when vaccines moved to triennial schedules, titres did, too. Now there is confusion on how often titres need to be done and how to interpret them.
A titre is a measure of antibody to a particular virus in the blood. It is expressed as a ratio of how many times the blood can be diluted before antibodies are no longer detectable. For example, if blood is diluted twice and antibodies can’t be found, the titre is 1:2. If it can be diluted 2,000 times, the titre is 1:2,000. Laboratories often suggest that titres of 1:20 for distemper and 1:80 for parvovirus are protective.
You would assume that a high titre suggests a dog is protected from disease and a low titre indicates poor immunity, but it is not that straightforward.
When a dog is vaccinated, two main types of cells are produced. Effector cells are the quick-response cells. They manufacture large amounts of antibody but they’re short-lived and die off within weeks after vaccination. Memory cells, in contrast, persist for years but produce only small amounts of antibody. These memory cells provide long-term immunity by standing on guard, ready to create antibodies at a moment’s notice.
While active, effector cells produce a high titre. As they dissipate, the titre falls and stays at a low level because of the contribution by memory cells.
Titres are useful for telling us if a puppy has responded to vaccinations. For example, once a puppy is vaccinated at eight, 11 and 14 weeks of age, a titre test should be done two weeks after the last vaccination. If the titre is high, the pup is protected. A low or non-existent titre indicates that the pup failed to respond and needs additional vaccines.
In the past, titres were done at a year of age to see if vaccines were required at that point. The problem was that if a pup had not responded to the vaccines and was not revaccinated (at 18 weeks in the earlier example), he would be susceptible during the most critical time of his life.
A debate among veterinarians is – how often should titres be done? Some veterinarians do them every three years, coinciding with current vaccine recommendations. Others believe that a positive titre means the dog responded to the vaccine and memory cells are present for the life of the dog. This thinking comes from experience with humans regarding viral vaccines. If this truly is the case (it has not been proven), one titre test showing a response is all that’s needed. This is not a view held by all veterinarians.
This article was published in the June 2007 issue of Dogs In Canada.
This article was published in the August 2007 edition of Dogs In Canada.
If an eye is forced from its socket, the prolapsed state is called “proptosis.” In a flat-faced dog such as a Pug, Shih Tzu or Pekingese, this is not an uncommon eye injury. It is, however, an emergency that needs immediate veterinary attention.
Most cases of proptosis occur as a direct result of head trauma. A blow to the skull or a bite from a larger dog can lever the eye out of its socket.
Occasionally, an owner will accidentally prolapse his dog’s eye through excessive restraint to the head and neck that forcibly pulls the eyelids back. In this case, the eye can be returned to its normal position by pulling the eyelids from behind the eye to in front of it. This immediately allows the eyeball to fall back into place. Obviously, this correction must be done immediately.
If a dog’s eyeball habitually prolapses, a simple surgery can be performed to correct the anatomical anomaly at the root of the problem. The eyelids are sewn partially closed so the opening becomes too small for the eyeball to fit through.
If your dog has a prolapsed eye that can’t be easily returned to its socket, you must get him to your veterinarian as soon as possible. For the best results, the eye should be repositioned within 15 to 30 minutes.
If you want to give your dog’s eye the best chance at survival, you’ll need to perform some first aid before leaving for the hospital. Keep the eye moist with sterile saline, an eye irritating solution, or as a last resort, water (it’s better than nothing). Moisten a pad and bandage it your dog’s eye, or hold it in place with your hand. Keep your dog from rubbing by holding his paws or putting an Elizabethan collar on him.
When you arrive at the clinic, the veterinarian will determine whether your dog’s pupil is responding to light (constricts). If this happens normally, nerve function is still present in the eye (a good sign). If his pupil is constricted (small), it also means the eye has nerve function (since the pupil goes small under painful conditions). If the pupil is dilated and non-reactive, the prognosis for future vision is much poorer. Only 20 per cent of dogs suffering from a prolapse eye regain some functional vision.
A prolapsed eye can be handled in one of two ways – the eyeball is either replaced or removed (enucleation). Unless the eye is severely damaged (nerves and muscles torn, or the eyeball ruptured), the eyeball should be returned to its socket and the eyelids temporarily sewn together to hold it in place.
If the eye is non-functional, immediate enucleation is indicated. The eyeball is removed and the eyelids stitched together permanently. An alternative is to replace the damage glove with a false eyeball (prosthesis). In the latter case, the eye looks almost normal.
Ethan was treated with HCG, 3 injections. Dr Hess thought it would only be effective up to 6 months of age and that he should keep both testicles down after the cartilage ring closes at about 6 months.
Human chorionic gonadotropin (hCG) is a peptide hormone produced in pregnancy, that is made by the embryo soon after conception and later by the syncytiotrophoblast (part of the placenta). Its role is to prevent the disintegration of the corpus luteum of the ovary and thereby maintain progesterone production that is critical for a pregnancy in humans. hCG may have additional functions, for instance it is thought that it affects the immune tolerance of the pregnancy. Early pregnancy testing generally is based on the detection or measurement of hCG. Because hCG is produced also by some kinds of tumor, hCG is an important tumor marker, but it is not known whether this production is a contributing cause or an effect of tumorigenesis.
hCG interacts with the LHCG receptor and promotes the maintenance of the corpus luteum during the beginning of pregnancy causing it to secrete the hormone progesterone. Progesterone enriches the uterus with a thick lining of blood vessels and capillaries so that it can sustain the growing fetus. Due to its highly negative charge hCG may repel the immune cells of the mother, protecting the fetus during the first trimester. It has also been hypothesized that hCG may be a placental link for the development of local maternal immunotolerance. For example, hCG-treated endometrial cells induce an increase in T cell apoptosis (dissolution of T-cells). These results suggest that hCG may be a link in the development of peritrophoblastic immune tolerance and may facilitate the trophoblast invasion which is known to expedite fetal development in the endometrium. It has also been suggested that hCG levels are linked to the severity of morning sickness in pregnant women.
This was posted on Dr. Catherine Marley’s apsobreederslist.
Posted by: “Ronny Junkins”
Mon Nov 12, 2007 5:08 am (PST)
In a previous litter we had a case where the mother ripped
the umbilical cord leaving a severe tear in the puppy’s
stomach. We freaked out and lost the puppy. This situation
happened again yesterday morning however after the last
time I watch the births very carefully. This time we dumped
corn starch on the stomach (as well as the rest of the kitchen)
and that seemed to stop the bleeding. I held her and kept her
warm and still for about a half an hour adding additional starch
as needed. When we were convinced that the bleeding had
stopped we carefully cleaned her off and applied Super Glue
to the wound. After that had dried thoroughly we put the
puppy bach with her mother. I am happy to say that today the
puppy is in great shape.http://www.geocities.com/4dogs.geo/puppies.html
Just wanted to pass on the experience in case anyone might find
Ronny Junkins Jaron’s Lhasas ROM