Late humoral rejection in a cardiac transplant recipient treated with the anti-CD20 monoclonal antibody rituximab.

Humoral or vascular rejection results from a B cell-mediated production of immunoglobulin (Ig) G antibody against a transplanted organ, producing immune complex deposition on the vascular endothelium, activation of the complement cascade, generation of endothelial dysfunction, and regional ischemic injury. Antibody-mediated rejection, which may be accompanied by hemodynamic compromise, is associated with reduced long-term graft survival. Patients believed to be at an increased risk of developing humoral rejection include women, particularly those with high levels of panel reactive antibodies, cytomegalovirus seropositivity, and positive cross matches, and subjects with prior sensitization to OKT3. Treatment options for humoral rejection include plasmapheresis to lower the circulating immunoglobulin levels followed by high-dose cyclophosphamide to reduce the B-cell population. Other modalities include total lymphoid irradiation, photophoresis, splenectomy, and, for treatment failures, retransplantation. Rituximab is a chimeric humanized monoclonal antibody directed against the pan B-cell surface molecule, CD20. It is approved for the treatment of low-grade B-cell non-Hodgkin's lymphoma. It has also been used successfully for the treatment of posttransplant B-cell lymphoproliferative disease. We report a case of late humoral rejection successfully treated with rituximab.

Canine thyroid neoplasms: epidemiologic features.

A retrospective study of medical records from twelve veterinary university hospitals-clinics yielded 144 dogs with a confirmed diagnosis of a thyroid neoplasm (25 adenomas and 119 carcinomas). Forty-five of these dogs had additional primary neoplasms. As in man, associated tumors suggested the inherited multiple endocrine adenomatosis, type 1, and a possible syndrome of thyroid and chemoreceptor lesions. Although the female preponderance of human thyroid cancer was not seen in dogs, females showed a much sharper increase in risk with advancing age than did males. Three breeds (beagle, boxer, and golden retriever) had a significantly greater risk for thyroid carcinoma than did all dogs combined, whereas miniature and toy poodles had a low risk. The function of thyroiditis in the origin of thyroid cancer, as suggested by reports of thyroid carcinoma in people with Hashimoto's disease, may be clarified by follow-up studies of beagles which are prone to Hashimoto-type thyroiditis.

Excess of seminomas observed in Vietnam service U.S. military working dogs.

During the Vietnam War, US military working dogs served with their companion dog handlers in close proximity, sharing common exposures to war-related activity, many zoonotic infectious agents, chemical pesticides, phenoxy herbicides, and extensive use of therapeutic drugs. To gain insight into the effects of the Vietnam experience, we investigated the occurrence of neoplasms in military working dogs based on standard necropsy examination by the Armed Forces Institute of Pathology. We observed that these dogs experienced significant elevated risks for testicular seminoma and, independently, testicular dysfunction. Experimental evidence shows testicular dysfunction and impaired spermatogenesis in laboratory animals exposed to phenoxy herbicides, dioxin, or tetracycline, and antibiotic used extensively in military working dogs in Vietnam. Because an unexplained significant decrease in sperm quality in Vietnam veterans has been observed by the Centers for Disease Control, further research is warranted if we are to clarify military service in Vietnam as a risk factor for testicular dysfunction. The testis should be made a priority site in the study of Vietnam experience-related cancers.

Case-control study of canine malignant lymphoma: positive association with dog owner's use of 2,4-dichlorophenoxyacetic acid herbicides.

A hospital-based case-control study of companion dogs examined the risk of developing canine malignant lymphoma associated with the use of chemicals in and about the home. Information from a self-administered owner questionnaire and/or a telephone interview of about 491 cases, 466 nontumor controls, and 479 tumor controls indicated that owners in households with dogs that developed malignant lymphoma applied 2,4-dichlorophenoxyacetic acid (2,4-D) herbicides to their lawn and/or employed commercial lawn care companies to treat their yard significantly more frequently than control owners (odds ratio = 1.3). In addition, the risk of canine malignant lymphoma rose to a twofold excess with four or more yearly owner applications of 2,4-D. The findings in this study are consistent with occupational studies in humans, which have reported modest associations between agricultural exposure to 2,4-D and increased risk of non-Hodgkin's lymphoma, the histology and epidemiology of which are similar to those of canine malignant lymphoma. The present study suggests that human health implications of 2,4-D exposure in the home environment should receive further investigation.

Epidemiological features of canine renal neoplasms.

A retrospective study of medical records from 13 veterinary university hospitals and clinics yielded 73 cases of confirmed primary neoplasms of the kidney and renal pelvis. Analysis of the 34 cases of renal carcinoma revealed no evidence of familial (breed) predisposition, but an excess risk was identified in males, especially during middle life. The morphological and epidemiological features of canine renal carcinoma are similar to those of renal carcinoma in humans. The dog may be a suitable model for further research into the causes of this cancer.

Hormone-dependent neoplasms of the canine perianal gland.

The epidemiological features of 472 dogs with microscopically confirmed neoplasms of the perianal gland are described. These general characteristics suggest etiological factors similar to those responsible for hormone-related neoplasms occurring in human beings. Perianal gland tumors appear to be androgen dependent. Male dogs show a 5.6-fold-increased risk compared with females; endogenous estrogens offer protection and the use of estrogenic hormones is conventional therapy for the benign lesion. Both sexes of the cocker spaniel breed show excessively high risk, suggesting that this dog family may be a model for genetic studies that could be relevant to familial aggregations of hormone-related tumors in men and women. Adrenocortical hormones may play a role in the development of the tumor in female dogs. Research into alterations of the biochemical pathways of steroidogenesis in affected female dogs may provide clues to similar conditions in humans.

Comparability of national death index plus and standard procedures for determining causes of death in epidemiologic studies.

PURPOSE: To determine whether causes of death obtained through National Death Index (NDI) Plus are comparable to those obtained by requesting death certificates from state vital statistics offices and having deaths coded by contractor nosologists. METHODS: The authors compared underlying cause of death codes obtained from NDI Plus with those assigned by contractor nosologists for a sample of 250 known decedents. RESULTS: The underlying cause of death codes differed for 18 (7%) of 249 successful matches. Independent coding by an expert National Center for Health Statistics (NCHS) nosologist trainer revealed that seven of these had an NDI Plus code that matched the code provided by the NCHS nosologist and a contractor nosologist code that did not match the NCHS nosologist code, seven had a contractor nosologist code that matched the NCHS nosologist code and an NDI Plus code that did not match the NCHS nosologist code, and four had both an NDI Plus and a contractor nosologist code that did not match the NCHS nosologist code. The level of disagreement with the NCHS nosologist and the organ systems involved were similar for NDI Plus and the contractor nosologist. CONCLUSIONS: The authors report that NDI Plus provides comparable information within a substantially shorter time period for most states and, for known decedents, at about half the cost of standard procedures.

Epidemiology and toxicology of arsenic poisoning in domestic animals.

Arsenic poisoning is one of the more important causes of heavy metal poisoning in domestic animals. Two species--dogs and cattle--are intoxicated more frequently than other animals; yet sporadic instances of poisoning have been observed in cats, horses, and pigs. Cases observed by veterinary clinicians are either peracute, acute, or chronic intoxications. Frequently the initial and only indication that a severe problem exists with peracute poisoning in a cattle herd is dead animals. Chronic intoxications are also observed in cattle. Acute intoxication is the most common form of arsenic poisoning observed and documented in the dog. Also intoxicated dogs were younger, i.e., 2-6 months of age. Arsenic is a severe alimentary tract irritant in domestic animals, and treatment in most instances consists mainly of symptomatic and supportive treatment. The source of intoxication, when it can be determined, is usually dips, sprays, powders, or vegetation contaminated by pesticides containing arsenic.

Mortality patterns among US veterinarians, 1947-1977: an expanded study.

Causes of death among 5016 white male veterinarians identified from obituary listings in the Journal of the American Veterinary Medical Association were compared to a distribution based on the general US population. Proportions of deaths were significantly elevated for cancers of the lymphatic and haematopoietic system, colon, brain, and skin. Fewer deaths were observed than expected for cancers of the stomach and lung. Although socio-economic and methodological factors may be involved, the patterns suggest that sunlight exposure is responsible for the excess of skin cancer among veterinarians whose practices are not exclusively limited to small animals, and ionizing radiation exposure contributes to the excess of leukaemia among veterinarians practising during years when diagnostic radiology became widely used. Mortality was also high for motor vehicle accidents and suicides, but low for diseases of the respiratory system.

Canine biliary carcinoma: epidemiological comparisons with man.

A retrospective study of abstracted data representing 1.1 million hospital examinations of dogs at veterinary university teaching facilities identified 77 with bile duct carcinoma. Using the hospital population, based on patient years at risk, as the expected frequency of particular zoographic characteristics, there was a suggestion of a familial (breed) predisposition in Labrador retrievers and limited evidence of a sex differential. Because mongrel dogs displayed about the same frequency of bile duct cancer as all breeds combined, other causal factors, besides genetics, are implied. A possible association was detected between canine cholangiocarcinoma and host infection by canine hookworms and/or whipworms. Human infection from hookworms (Necator americanus) and whipworms (Trichuris trichiura) is common in the southern rural areas of the U.S.A. (e.g. Appalachia), and tropical and sub-tropical countries of Africa, Central and South America, where there have been unexplained high rates reported for human biliary cancer. It is possible that the presence of these blood-letting nematodes, like a number of other parasites (ascarids, flukes and protozoa), may be related to the occurrence of human cholangiocarcinoma.

Effects of ear type and weather on the hospital prevalence of canine otitis externa.

A retrospective study of 8975 dogs seen at 15 university veterinary medical teaching hospitals in North America (1975 to 1978) found that dogs with pendulous ears and heavy ear canal hair had significantly (P less than 0.01) more otitis externa than dogs with other ear types. Dogs with erect ears, regardless of the amount of ear canal hair, had less risk (P less than 0.01) of the disease than mongrel dogs. Direct evidence is available for the first time showing that monthly variations in ambient temperature, rainfall and relative humidity explain, to a large extent, the monthly variations in the hospital prevalence of canine otitis externa in different geographic regions.

Epidemiological features of 5009 cases of equine cryptorchism.

Data from 16 North American veterinary university teaching facilities, 5009 cryptorchid horses, were analysed using relative risk methodology. In five breeds (Thoroughbred, Standardbred, Morgan, Tennessee Walking horse and Arabian), cryptorchism was diagnosed significantly (P less than 0.05) less frequently than expected by their representation in the hospital population. Three breeds, (Percheron, American Saddle horse and American Quarterhorse), plus ponies (as a group) and crossbred horses were significantly over-represented within the series. The over-representation of Quarter-horses was evident at each veterinary teaching facility. Other developmental defects and testicular tumours diagnosed in cryptorchid horses were presented. Analysis of the frequency of diagnosis of second anomalies among cryptorchids showed testicular hypoplasia to occur significantly more often, and inguinal and umbilical hernias less often, than expected (P less than 0.05).

Epizootiologic features of canine hydrocephalus.

In a retrospective study of hydrocephalus (of congenital origin) diagnosed in 564 dogs, 11 breeds (including 8 "toy" breeds) were identified as being a significantly high risk. An inverse relationship between risk and body size was detected. The smaller the dam at maturity, either in height at the shoulder or body weight, the greater the risk of hydrocephalus in the offspring.

Patent ductus arteriosus in the dog: a retrospective study of radiographic, epidemiologic, and clinical findings.

Twenty-seven cases of patent ductus arteriosus (PDA) in the dog, which were confirmed by cardiac catheterization, surgical exploration, or at necropsy, were reviewed. A machinery murmur, electrocardiographic evidence of left ventricular enlargement, and radiographic evidence of cardiomegaly with an aortic and a pulmonary artery dilatation were consistent features. Surgical repair was successful in 65% of the dogs. The postoperative radiographic and electrocardiographic changes are described. A concomitant congenital defect was present in 2 dogs. The epidemiologic features of 532 dogs identified as having PDA and submitted to the National Cancer Institute's Veterinary Medical Data Program were reviewed. Miniature and Toy Poodles, Pomeranians, and Shetland Sheepdogs were identified as being at high risk for PDA. An excess of females over males was noticed.

Castration for treatment of perianal gland neoplasms in the dog.

Neoplasms of the perianal gland are common in the dog, particularly the male. Adenomas of the gland develop about 4.5 times more often than do carcinomas of the gland. The adenoma is hormone dependent; thus, castration without excision of the tumor has been successful in promoting regression without recurrence. Microscopic examination of the testes from dogs with perianal gland neoplasms has revealed 1 in 10 with tubular atrophy and 1 in 3 with testicular neoplasia. Interstitial cell tumors have been seen more often than other cell types of testis tumors.

Risk factors associated with canine heartworm infection.

Risk factors associated with canine heartworm infection were determined by screening medical records from the Veterinary Medical Data Program of June 1964--May 1976. Data represented were from 14 colleges and schools of veterinary medicine in the United States and Canada. A total of 3,655 dogs were infected. Intact male dogs 4 to 7 years old and of the larger hound breeds had the highest relative risk, whereas dogs of smaller breeds, those less than 2 years old, spayed females, and castrated males were at least risk.

Juvenile renal disease in Doberman Pinscher dogs.

Renal failure was diagnosed in 22 young Doberman Pinscher dogs. The clinical findings were anorexia, weight loss, vomiting, lethargy, polydipsia, polyuria, and dehydration. Laboratory findings were azotemia, hyperphosphatemia, lymphopenia, nonregenerative anemia, hypercholesterolemia, and proteinuria. The kidneys were characterized pathologically by glomerular sclerosis, cystic glomerular atrophy, tubular dilatation, tubular atrophy, mononuclear interstitial inflammation, interstitial fibrosis, interstitial mineralization, and hyperplasia of the collecting duct epithelium.

Hospital incidence of hypospadias in dogs in North America.

A review of medical records from 17 North American university veterinary medical teaching hospitals identified 66 dogs with hypospadias. Males predominated (15:1) and cryptorchidism was the most commonly diagnosed second anomaly, often associated with intersexuality. Fifteen cases, diagnosed at 10 different university hospitals, were Boston terriers, strongly suggesting that this breed has a familial predisposition for hypospadias. Male mongrels, as a group, were seen in approximately the same proportion as their representation in the hospital population, suggesting other components in the aetiology of the condition. If maternal histories are obtained as new cases are identified, a better understanding of the factors associated with the aetiology of the condition may be possible.

Epidemiological features of feline mammary carcinoma.

An epidemiological survey involving 132 cats with mammary neoplasia, seen at 15 North American veterinary medical teaching hospitals, was conducted. The ratio of malignant to benign tumours was 9:1. There were 113 cases of carcinomas of all types (including two males), with adenocarcinoma being the predominant cell-type. Relative risk analysis indicated that the Siamese breed had twice the risk (P less than 0.01) of developing mammary carcinoma compared to all breeds combined. The age at diagnosis in Siamese females tended to be younger than in other breeds. Comparison of clinical and pathological features of breast cancer suggests that the cat is an appropriate surrogate for the experimental study of human breast cancer. The apparent lack of oestrogen dependency in feline breast cancer also suggests that the cat may be especially suited for evaluating therapeutic regimens for breast cancers that do not respond to hormonal manipulation.

A cohort study of the effects of Vietnam service on testicular pathology of U.S. military working dogs.

Using histopathologic diagnoses made on necropsy material from 3,024 military working dogs (MWDs) who died from 1968 to 1973, we analyzed the effect of military service in the Republic of Vietnam on testicular pathology. Among 1,048 MWDs that died in Vietnam and had no reported developmental risk factors for testicular disease, significant excesses of testicular hemorrhage, epididymitis/orchitis, sperm granuloma, testicular degeneration, and seminoma were evident. Among 126 MWDs with prior Vietnam service who died at other duty stations outside Vietnam from 1968 to 1973, significant excesses of testicular degeneration and seminoma were likewise evident. Among 136 MWDs with prior Vietnam service that later died from 1974 to 1980, seminoma continued to be diagnosed in significant excess. In each instance, the odds ratio for the association between Vietnam service and seminoma was 2.0 or greater. Analysis of ever service by Corps Tactical Zones showed significant excesses of seminoma with each Corps area of service compared to Vietnam-era MWDs, but risk was highest in I Corps, particularly at Da Nang Port and Da Nang Air Base. This finding with respect to I Corps is consistent with certain human studies in Vietnam veterans and points to the need for further investigation of possible environmental exposures, particularly those associated to a greater extent with service in I Corps.