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Biomedical subjects

M H Goldschmidt

Publications and source records attributed to M H Goldschmidt.

At least 19 recordsLinked to original sources

A comparative review of melanocytic neoplasms.

Melanoma is a devastating disease frequently encountered within both veterinary and human medicine. Molecular changes linked with neoplastic transformation of melanocytes include mutations in genes that encode proteins intrinsic to the regulatory pathways of two tumor suppressor proteins (retinoblastoma protein and p53), proto-oncogene mutation to oncogenes, altered expression of epithelial cadherin and CD44 adhesion molecules, and upregulation of angiogenic factors and other growth factors. Histologic evaluation of the primary mass is the most common means of diagnosis, with cytology used more frequently to document metastasis. Melanoma's highly variable histologic and cytologic patterns can make diagnosis by either method problematic. Adherent epithelioid morphology, including signet ring forms, and nonadherent round and spindle forms are recognized, with pigmentation an inconsistent finding. The site of the tumor, the thickness of the primary tumor or depth of invasion, and the number of mitotic figures per high-power field or per millimeter are used histologically to predict biologic behavior, whereas site and degree of pleomorphism are typically used for cytologic preparations. Diagnosis of amelanotic melanoma can be aided by ancillary diagnostic techniques. Tumor cells are usually positive for vimentin, S100, neuron-specific enolase, and Melan-A, and negative for cytokeratin. Melan-A as a positive marker is not as sensitive as the others are but is likely more specific. Monoclonal antibodies to human melanosome-specific antigens 1 and 5 cross-react with canine antigens for a combined sensitivity rate of 83%. Mouse monoclonal antibody IBF9 specifically recognizes canine melanoma antigen and also has good sensitivity. Serologic markers, including cytokines, cell adhesion molecules, and melanoma-inhibitory activity, are being investigated as potential sentinels of melanoma. Currently, there is no single diagnostic technique capable of differentiating benign from malignant melanocytic neoplasms or predicting survival time.

Animals↗

Factors associated with Army obstetricians-gynecologists' practice of HIV prevention education during routine gynecologic care.

The authors evaluate obstetricians-gynecologists' (OB-GYNs') anxiety about clinical uncertainty and patient, physician, and organizational factors associated with their selection of HIV-related educational activities for high-risk and low-risk written case simulations. A total of 117 U.S. Army OB-GYNs completed a mailed, anonymous questionnaire. Overall, informants were much less likely to educate in response to the low-risk simulation; however, more informants who were anxious about uncertainty were more likely to do so in a model that included supportive institutional policies, willingness to educate despite patient barriers, and comfort with the topic. OB-GYNs were more likely to educate in response to the high-risk simulation given greater willingness to discuss HIV despite organizational barriers, supportive policies, and comfort. Findings suggest a need to better understand the role that anxiety about uncertainty plays in HIV prevention and the need to promote organizational policies that support and remove barriers to clinically based education.

Anxiety↗

Piloleiomyosarcoma in seven ferrets.

In each of seven ferrets (Mustela putorius furo) with leiomyosarcoma, a single dermal mass was identified and biopsied. Each mass consisted of a well-demarcated but nonencapsulated proliferation of large spindle- to strap-shaped cells arranged in interwoven bundles. The cells resembled the smooth muscle cells of the adjacent arrector pili muscles, but with marked nuclear pleomorphism. Immunohistochemical staining for smooth muscle actin, desmin, and vimentin was positive and staining for myoglobin and cytokeratin was negative. Follow-up on three of the ferrets indicates that the prognosis is good following complete surgical excision.

Animals↗

Anemia, splenomegaly, and increased osmotic fragility of erythrocytes in Abyssinian and Somali cats.

OBJECTIVE: To determine clinical and clinicopathologic features of a chronic intermittent severe hemolytic anemia characterized by erythrocyte osmotic fragility in Abyssinian and Somali cats. DESIGN: Case series. ANIMALS: 13 Abyssinian and 5 Somali cats. PROCEDURES: History, pedigree information, and results of routine laboratory tests, special erythrocyte studies, and histologic evaluation of splenic and hepatic specimens were analyzed. RESULTS: Age at which clinical signs of anemia were first apparent ranged from 6 months to 5 years. Ten cats had splenomegaly. Most often, the PCV was between 15 and 25%, but it was as low as 5% at some times. The anemia was characterized by macrocytosis and mild to moderate reticulocytosis, but no poikilocytosis. Hyperglobulinemia, lymphocytosis, mild hyperbilirubinemia, and high hepatic enzyme activities were common findings. Results of Coombs tests and tests for infectious diseases were negative. The erythrocytic osmotic fragility was high in affected cats (mean osmotic fragility, 0.66 to 0.78%), compared with healthy cats (0.48 to 0.58). No specific membrane protein abnormality, erythrocyte enzyme deficiency, or hemoglobinopathy was identified. Histologic evaluation of splenic and hepatic specimens revealed extramedullary hematopoiesis and hemosiderosis. Four of the 5 Somali cats were closely related. CONCLUSIONS AND CLINICAL RELEVANCE: On the basis of results of pedigree analyses, the apparent breed predilection, and the exclusion of other known causes of anemia in cats, we believe that the hemolytic anemia in these cats was likely a result of a novel hereditary erythrocyte defect. A genetic predisposition to immune-mediated destruction of erythrocytes could not be ruled out.

Anemia, Hemolytic, Autoimmune↗

Eosinophilic dermatitis with edema in nine dogs, compared with eosinophilic cellulitis in humans.

A unique eosinophilic dermatitis with edema in dogs is characterized by extremely erythematous coalescing macules and plaques with associated edema, and is similar to eosinophilic cellulitis (Wells' syndrome) in humans. Histopathologic features include a profound eosinophilic dermal infiltrate, focal areas of collagen fiber degeneration surrounded by eosinophils (flame figures), dilated vessels, and dermal edema. Etiopathogenesis is unknown, but a hypersensitivity reaction to medications, arthropod bites, or other foreign antigens is suspected.

Animals↗

Glutaraldehyde-induced esophageal injury. Histologic study of laboratory rats.

RATIONALE AND OBJECTIVES: A patient was encountered with a long esophageal stricture that may have been caused by glutaraldehyde-contaminated endoscopic equipment. An in vivo study of laboratory rats was performed to determine the effect of glutaraldehyde exposure on the esophagus. METHODS: Ten laboratory rats were divided into five groups that received daily gavage of the esophagus with either 3.2% glutaraldehyde solution (treated rats) or 1 mL of normal saline (control rats) for varying durations. After the rats were killed, histologic sections from the esophagus were reviewed in a blind fashion. The degree of inflammatory infiltrate at the gastroesophageal junction was quantified as mild, moderate, or marked. RESULTS: Histologic examination revealed greater neutrophilic infiltration in the submucosa of the gastroesophageal junction in three of four glutaraldehyde-treated rats compared with controls. Treated rats also had evidence of segmental esophageal vasculitis not seen in any of the controls. Both controls and treated rats had areas of myositis and myonecrosis within the esophagus. CONCLUSION: Exposure to glutaraldehyde has a toxic effect on the rat esophagus. Glutaraldehyde-induced esophageal injury should therefore be considered in patients who develop esophagitis or esophageal strictures after upper endoscopy.

Animals↗

Dominantly inherited epidermal acantholysis in dogs, simulating human benign familial chronic pemphigus (Hailey-Hailey disease).

We report on dominantly inherited epidermal acantholysis in three dogs, a sire and two female offspring. The skin lesions were characterized by hairless, hypertrophic plaques. Histopathologically, these lesions showed epidermal hyperplasia with individual enlargement of keratinocytes, extensive acantholysis and minimal dyskeratosis. Ultrastructural analysis revealed that attachment plaques of desmosomes were still intact while some tonofilaments were detached from them in early lesions; there were well-developed microvilli at dissociated cell surfaces. The data imply that these animals have undergone a process similar to human benign familial chronic pemphigus (BFCP). Immunohistochemical examination revealed that staining for E-cadherin and actin variably remained in dissociated keratinocytes. Focal intracellular staining for desmosomal glycoproteins and desmosomal proteins were observed within the dissociated keratinocytes. This dominantly inherited acantholytic disease in dogs could be a useful animal model for investigating the pathogenesis of BFCP in humans.

Acantholysis↗

Feline atopic dermatitis. A model for Langerhans cell participation in disease pathogenesis.

Atopic dermatitis is a disorder characterized by cutaneous exanthemata as a consequence of exaggerated eczematous reactions to topical and systemic allergens. Langerhans cells, expressing CD1a and HLA-DR, and dermal dendritic cells, expressing HLA-DR, are known to be potent antigen-presenting cells and are thought to play an important role in the pathogenesis of atopic dermatitis. The immunophenotype of lesional skin in atopic dermatitis in humans involves increased numbers of CD1a+/MHC class II+ dendritic cells in addition to activated T cells, mast cells, and macrophages. To establish feline skin as a model for the study of human atopic dermatitis, and to elucidate the role of dendritic cells in feline atopic dermatitis, we investigated the presence of CD1a+ cells and MHC class II+ cells in the epidermis and dermis of lesional feline skin and in skin of healthy control animals. Immunohistochemistry revealed that MHC class II+ epidermal dendritic cells were CD1a+ in normal feline skin and significantly increased numbers of CD1a+ cells and MHC class II+ cells were present in the epidermis and dermis of lesional skin. These data provide the first correlative documentation of CD1a expression by feline dendritic cells containing Birbeck granules, and indicate the utility of feline skin in the study of human cutaneous atopy.

Animals↗

Serum alpha 1-antitrypsin concentration in dogs with panniculitis.

OBJECTIVE: To measure serum alpha 1-antitrypsin (alpha 1AT) concentration in dogs with histologically confirmed panniculitis to determine whether serum deficiency could cause or exacerbate panniculitis in dogs. DESIGN: Cross-sectional, descriptive study. ANIMALS: 9 dogs (5 with multiple lesions and 4 with solitary lesions). PROCEDURE: Serum samples were obtained by means of cephalic or jugular venipuncture and frozen at -20 C until assayed. Serum alpha 1AT concentration was measured by means of radial gel immunodiffusion. RESULTS: In all dogs, serum alpha 1AT concentration was within the previously established reference range. CLINICAL IMPLICATIONS: In the small number of-dogs studied, panniculitis was not associated with serum alpha 1AT deficiency.

Adipose Tissue↗

Perturbation in connexin 43 and connexin 26 gap-junction expression in mouse skin hyperplasia and neoplasia.

To examine the possible role of gap junctions in mouse skin tumor progression, we generated a panel of mouse skin tissue samples exhibiting normal, hyperplastic, or neoplastic changes and characterized the expression of the gap-junction genes connexin 43 (Cx43) and connexin 26 (Cx26) by in situ hybridization and immunohistochemical analyses. In normal skin, these two gap junction genes were differentially expressed; Cx43 was found predominantly in the less differentiated lower spinous layers, whereas Cx26 was found in terminally differentiating upper spinous and granular layers. In hyperplastic epidermis exhibiting an expansion of the differentiated upper layer, i.e., epidermis with a thickened granular layer or in which the granular layer was replaced with keratinocytes exhibiting tricholemmal differentiation, expression of Cx43 and Cx26 remained segregated in the lower and upper spinous layers, respectively. However, in papillomas, Cx26 was localized in the lower but not upper spinous layer, an expression pattern identical to that of Cx43. In addition, the overall expression levels of both Cx43 and Cx26 appeared to be greatly elevated in the papillomas. It is interesting that such marked alteration in the pattern of Cx26 expression occurred within the context of hyperplastic changes histologically identical to those seen in the nonpapillomous hyperplasias. Interestingly, in neoplastic skin lesions containing a squamous cell carcinoma, Cx43 and Cx26 expression was extinguished. Moreover, expression of Cx43 was also significantly reduced in adjacent apparently nonneoplastic tissues. Overall, these observations show that perturbations in gap-junction gene expression are associated with skin hyperplasia and neoplasia. Such findings suggest a possible role for gap junctions in the malignant conversion of mouse epidermal cells.

Animals↗

Comparison of fibrosarcomas that developed at vaccination sites and at nonvaccination sites in cats: 239 cases (1991-1992).

Questionnaires were sent to veterinarians who had submitted a fibrosarcoma from a cat to the surgical pathology services of the veterinary schools of the University of Pennsylvania and Tufts University between Jan 1, 1991 and June 30, 1992. Questionnaire items included signalment, FeLV and feline immunodeficiency virus status, site of sarcoma, vaccination site, vaccines used, treatment, biologic behavior of the tumor, and final outcome. Data were analyzed, using Student's t-test for continuous data, chi 2 test for categoric data, and log-rank test for survival estimates. Comparing results for cats with vaccination-site (VS) tumors and nonvaccination-site (NVS) tumors, we determined that VS tumors developed in younger cats and were larger than NVS tumors. Although VS sarcomas were biologically aggressive and redeveloped more often than NVS sarcomas, metastasis was not detected, and cats with VS tumors survived longer than cats with NVS tumors. Vaccination-site sarcomas developed in cats after injection of many types of vaccines, administered singularly or in combination. Of the cats in the VS group administered a single vaccine, 37% were given rabies, 33% were given feline viral rhinotracheitis/calicivirus/panleukopenia virus, and 30% were given FeLV vaccines. Cats with VS tumors were more likely to have received FeLV vaccine and less likely to have received rabies vaccine than those with NVS tumors. Although vaccines produced by certain manufacturers were used most often in cats with VS and NVS sarcomas, it was believed that this probably represented marketing practices and brand popularity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗

Comparative histopathology of pemphigus foliaceus and superficial folliculitis in the dog.

A comparative histopathologic study of 50 cases of pemphigus foliaceus and 47 cases of superficial folliculitis in the dog was undertaken to identify those histopathologic features important in differentiating these diseases. All cases were diagnosed by the Surgical Pathology Service of the Laboratory of Pathology of the University of Pennsylvania, School of Veterinary Medicine, between January 1986 and March 1991. These cases were followed clinically to determine the accuracy of the initial histopathologic diagnosis. Data were analyzed by Fisher's exact test for discrete data and the Mann-Whitney U-test for continuous data. A probability of < 0.05 was considered statistically significant. The following breeds were affected with pemphigus foliaceus: Akita, Brittany Spaniel, Chow Chow, Collie, Dachshund, Doberman Pinscher, English Cocker Spaniel, English Setter, Golden Retriever, Siberian Husky, Laborador Retriever, Miniature Schnauzer, Old English Sheepdog, Scottish Terrier, Chinese Shar Pei, Spitz, Shetland Sheep Dog, Weimeraner, and West Highland White Terrier. An increased risk of developing pemphigus foliaceus was noted in the Akita (OR = 37.8), English Springer Spaniel (OR = 20.7), Chow Chow (OR = 12.3), Chinese Shar Pei (OR = 7.9), and Collie (OR = 3.9). Pemphigus foliaceus had a higher average density of acantholytic cells (226 +/- 22.9) than superficial folliculitis (11.8 +/- 4.6), and acantholytic cells were 183 times more likely to be present in pemphigus foliaceus. The presence of rafts of acantholytic cells occurred in pemphigus foliaceus (23/50) more often than superficial folliculitis (1/47). Recornification and reformation of pustules were, respectively, 13.4 and 3.6 times more likely to occur in pemphigus foliaceus.(ABSTRACT TRUNCATED AT 250 WORDS)

Acantholysis↗

Cutaneous lymphosarcoma and leukemia in a cat.

A cat with cutaneous lymphosarcoma and leukemia, similar to Sézary syndrome in human beings, had initial clinical signs that included pruritus and exfoliative dermatosis, associated with weight loss and lymphadenopathy. Dermatopathologic findings and ultrastructural morphologic features of the circulating cells and cellular infiltrate were consistent with Sézary cells. Cutaneous lymphosarcoma and leukemia should be considered in cats with chronic pruritic exfoliative dermatoses.

Animals↗

Postvaccinal sarcomas in the cat: epidemiology and electron probe microanalytical identification of aluminum.

An increase in fibrosarcomas in a biopsy population of cats in the Pennsylvania area appears to be related to the increased vaccination of cats following enactment of a mandatory rabies vaccination law. The majority of fibrosarcomas arose in sites routinely used by veterinarians for vaccination, and 42 of 198 tumors were surrounded by lymphocytes and macrophages containing foreign material identical to that previously described in postvaccinal inflammatory injection site reactions. Some of the vaccines used have aluminum-based adjuvants, and macrophages surrounding three tumors contained aluminum oxide identified by electron probe microanalysis and imaged by energy-filtered electron microscopy. Persistence of inflammatory and immunological reactions associated with aluminum may predispose the cat to a derangement of its fibrous connective tissue repair response, leading to neoplasia.

Aluminum↗

Body conformation, diet, and risk of breast cancer in pet dogs: a case-control study.

Canine and human breast cancer share several important clinical and histologic features. A case-control study of nutritional factors and canine breast cancer was conducted at the Veterinary Hospital of the University of Pennsylvania in 1984-1987 by interviewing owners of 150 pet dogs diagnosed with breast cancer, owners of 147 cancer control dogs, and owners of 131 noncancer control dogs. The risk of breast cancer was significantly reduced in dogs spayed at or before 2.5 years of age. Neither a high-fat diet nor obesity 1 year before diagnosis increased the risk of breast cancer according to multiple logistic regression analysis. However, the risk of breast cancer among spayed dogs was significantly reduced in dogs that had been thin at 9-12 months of age (odds ratio (OR) = 0.04 (95% confidence interval (CI) 0.004-0.4) and OR = 0.04 (95% CI 0.004-0.5) for cases vs. cancer controls and cases vs. noncancer controls, respectively, after adjustment for age at spay). Among intact dogs, the risk associated with being thin at 9-12 months of age was reduced, but not significantly so (OR = 0.60 (95% CI 0.2-1.9) and OR = 0.51 (95% CI 0.2-1.4) for the two comparisons, respectively). Results of this study suggest that nutritional factors operating early in life may be of etiologic importance in canine breast cancer.

Adenocarcinoma↗

Testicular feminization in a cat.

Testicular feminization, caused by an inherited defect of the androgen receptor, was diagnosed in a domestic cat. Individuals affected with this syndrome are genetic males that have testes but fail to undergo masculinization because the internal and external genitalia cannot respond to androgens. The affected cat had the external appearance of a sexually normal female, but during surgery for ovariohysterectomy, only 2 abdominal gonads were found. Müllerian (uterus) or wolffian (epididymides) derivatives were not present. Only testicular tissue was found in histologic sections of the gonad. A normal male chromosome constitution (38,XY) was found in karyotypes prepared from lymphocyte cultures. High affinity binding of dihydrotestosterone was undetectable in fibroblasts cultured from genital skin of the affected cat, indicating that the cytosolic androgen receptor was nonfunctional. Pedigree analysis indicates that this is an X-linked disorder in cats, as it is in other mammals. Accurate diagnosis and genetic counseling are advocated to reduce the prevalence of the disorder.

Androgen-Insensitivity Syndrome↗