A pharmacogenetic basis for the safe and effective use of azathioprine and other thiopurine drugs in dermatologic patients.
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Alleles↗
Biomedical subjects
J L Snow
Publications and source records attributed to J L Snow.
Diagnostic immunohistochemistry of cutaneous metastatic breast carcinoma: a statistical analysis of the utility of gross cystic disease fluid protein-15 and estrogen receptor protein.
BACKGROUND: For accurate classification of cutaneous metastatic carcinoma, reliable tumor-specific immunohistochemical markers would be valuable. OBJECTIVE: Our purpose was to analyze the sensitivity, specificity, and positive predictive value of gross cystic disease fluid protein-15 (GCDFP-15) and estrogen receptor protein (ERP) for diagnosing cutaneous metastatic breast carcinoma. METHODS: Tissue sections from 68 consecutive cases of cutaneous metastatic carcinoma were stained for GCDFP-15 and ERP. Hematoxylin-eosin-stained slides and immunostained slides were reviewed in a blinded fashion before retrospective chart review to ascertain the underlying primary tumor type. RESULTS: Of 42 cases of cutaneous metastatic breast carcinoma, 30 were positive for GCDFP-15. Of 41 cases of metastatic breast carcinoma, 30 were positive for ERP. Calculated sensitivity, specificity, and positive predictive value for GCDFP-15 for diagnosing cutaneous metastatic breast carcinoma were 71%, 91%, and 94%, respectively, and 73%, 100%, and 100% for ERP, respectively. Combined values of these indices for both stains were 83%, 91%, and 95%, respectively. CONCLUSION: GCDFP-15 and ERP are valuable markers for cutaneous metastatic breast carcinoma and should be used in combination.
Apolipoproteins↗
Degos syndrome: malignant atrophic papulosis.
Malignant atrophic papulosis is a rare disorder characterized by pathognomonic cutaneous lesions that have been associated with multiple infarctive thrombotic lesions of other viscera, most notably the gastrointestinal tract and the central nervous system. Systemic involvement may develop from weeks to years after the onset of the characteristic cutaneous lesions or, rarely, may precede the cutaneous lesions. However, the existence of patients with a prolonged, purely cutaneous variant of this disease has been increasingly appreciated, and this brings into question the appropriateness of applying the term "malignant" to all patients who have the peculiar characteristic cutaneous lesions of malignant atrophic papulosis. Despite half a century of sporadic investigation, the precise cause of this disease remains unknown, and accurate classification of this entity as a primary vasculopathy or primary coagulopathy has not been possible. Unfortunately, no effective therapy exists for those patients in whom systemic involvement develops.
Adult↗
Malignancy-associated multicentric reticulohistiocytosis: a clinical, histological and immunophenotypic study.
The clinical, histopathological, and immunophenotypic characteristics of four cases of malignancy-associated multicentric reticulohistiocytosis (MMR) and one case each of diffuse cutaneous reticulohistiocytosis (DCR) and isolated reticulohistiocytoma (IR), are reviewed. In all four cases of MMR the cutaneous lesions and joint manifestations were judged to be concurrent with the diagnosis of malignancy. Malignancies observed included one case each of pancreatic adenocarcinoma, squamous cell carcinoma of the lung, metastatic melanoma and intraperitoneal grade 4 mucinous adenocarcinoma of uncertain origin. Histologically, all six cases demonstrated the typical changes of a diffuse histiocytic and multinucleated giant cell infiltrate with ground-glass cytoplasm, predominantly in the upper dermis. Immunohistochemical investigation revealed strong cytoplasmic staining with KP-1 (CD68) in all six cases. Prominent membrane staining was noted with leucocyte common antigen (CD45) in four cases (three MMR and one IR), and CD3 in four cases (three MMR and one IR). Weak membrane staining with Leu 22 (CD43) was noted in two MMR cases. UCHL-1 (CD45RO), L26 (CD20), S-100 and BerH2 stains were all uniformly negative. A prominent number of perilesional factor XIIIa-positive dermal dendrocytes were noted in the single case of IR, in contrast with the other five cases. We conclude that MMR, DCR and IR are histopathologically and immunohistochemically similar. The pattern of immunoreactivity observed is consistent with a monocyte-macrophage origin of the infiltrating tumour cells. We emphasize the paraneoplastic association of multicentric reticulohistiocytosis, which we have observed in four of 13 such cases (31%) evaluated at our institution.
Adult↗
Lymphoma associated with human immunodeficiency virus infection.
OBJECTIVE: To describe lymphoma associated with human immunodeficiency virus (HIV) infection. DESIGN: A review of HIV-related lymphoma and its associated epidemiology, etiopathogenesis, and clinicopathologic characteristics is presented. Major studies of therapeutic regimens for HIV-related lymphoma are discussed. Factors that could contribute to a poor prognosis are summarized. RESULTS: Malignant lymphoma that develops in patients with HIV infection fulfills diagnostic criteria for the acquired immunodeficiency syndrome (AIDS). The incidence is increasing and varies by subtype of lymphoma, age, sex, race, and risk factors. B-cell hyperactivation is thought to contribute to the development of lymphoma. The mechanisms that may show transformed cell hyperproliferation and clonal expansion are HIV itself or other viruses (for example, Epstein-Barr virus), growth factors, aberrant oncogene or tumor-suppressor gene expression, and factors that induce genetic instability or DNA damage or alter host or viral genome repair. Treatment of HIV-related lymphoma is associated with toxicity, infectious complications, low rate of complete response, and brief median survival time. CONCLUSION: Persons with HIV-induced immune dysregulation have a high risk for the development of aggressive non-Hodgkin's lymphoma characterized by histologic evidence of a high-grade malignant process, B-cell phenotype, an unusual extranodal involvement, and a poor prognosis. The potential role of specific viruses, antiviral treatments, and other therapeutic strategies are future areas of investigation.
HIV Infections↗
The role of genetic variation in thiopurine methyltransferase activity and the efficacy and/or side effects of azathioprine therapy in dermatologic patients.
BACKGROUND: Thiopurine methyltransferase (TPMT) is one of three major enzymes involved in the metabolism of azathioprine and its active metabolite 6-mercaptopurine. Thiopurine methyltransferase activity is determined by an allelic polymorphism for either high (TPMTH) or low (TPMTL) enzyme activity. Homozygotes for the low activity allele are known to be at risk for profound myelosuppression with azathioprine. Heterozygotes may be at risk for myelosuppression. Homozygotes for the high activity allele may be inadequately immunosuppressed with conventional, empiric doses of azathioprine. We analyzed TPMT activity in red blood cell (RBC) lysates and determined the TPMT genotypes (based on normal population screening) of 28 dermatologic patients. This information was correlated with the observed efficacy and side effects of azathioprine therapy. OBSERVATIONS: Two patients with TPMT levels of less than 12.5 U/mL RBCs (both TPMTH heterozygotes) experienced leukopenia (white blood count < 4.0 x 10(9)/L) with azathioprine doses around 1.5 mg/kg. A third patient who experienced leukopenia had a TPMT level at the lower end of the homozygous range (15.5 U/mL RBCs) but received the highest dose of azathioprine (2.6 mg/kg) of all patients in this series. Ten patients with TPMT levels of more than 18.5 U/mL RBCs (all TPMTH homozygotes) receiving less than 1.5 mg/kg of azathioprine were judged to have a poor clinical response. In comparison, seven patients with TPMT levels between 12.5 and 18.5 U/mL RBCs (six TPMTH homozygotes and one TPMTH heterozygote) receiving 0.9 to 1.8 mg/kg of azathioprine had a favorable clinical response. Adverse effects of gastrointestinal upset and liver function test abnormalities did not appear to correlate with TPMT activity. CONCLUSION: The TPMTH heterozygotes may be at increased risk for myelosuppression with standard, empiric doses of azathioprine. On the other hand, homozygotes for TPMTH, particularly those with TPMT levels at the upper end of the homozygous range, may have a poor clinical response to azathioprine due to inadequate empiric dosing.
Adult↗
Lipomembranous (membranocystic) changes associated with morphea: a clinicopathologic review of three cases.
Lipomembranous (membranocystic) changes represent a distinctive form of pathology in adipose tissue. Although first described in the rare neurodegenerative disorder now called Nasu-Hakola disease, this change has also been observed in a variety of relatively common inflammatory and noninflammatory dermatoses. We report three cases of morphea associated with marked lipomembranous (membranocystic) changes in the subcutaneous adipose tissue.
Adipose Tissue↗
Hidroacanthoma simplex: an ultrastructural and immunohistochemical study.
A representative case of hidroacanthoma simplex was studied with routine light microscopy, immunohistochemistry, and electron microscopy. Staining with the periodic acid-Schiff reagent and immunostaining with anti-keratin antibodies were useful in demarcating the tumor cells from adjacent normal epithelium. However, antibodies to carcinoembryonic antigen and epithelial membrane antigen did not help us to segregate or identify the neoplastic cells. Electron microscopy revealed tumor cells markedly different in appearance from luminal cells of the acrosyringium. Hidroacanthoma simplex does not appear to be derived from luminal cells of the acrosyringium. We propose criteria for the histologic diagnosis of this benign neoplasm.
Aged↗
Sales: evaluating the return on investment.
In this article, a case study is presented to illustrate the ways in which sales programs have evolved in healthcare organizations over the last few years. The importance of developing a system of tracking sales so revenues can be tied to sales efforts is emphasized.
Accounting↗
The polymerase chain reaction. Applications in dermatology.
Within the space of the last 5 years, application of the revolutionary in vitro method of deoxyribonucleic acid (DNA) amplification known as the polymerase chain reaction (PCR), has become ubiquitous. The rapidly increasing number of clinical and research articles utilizing this technology, both in the dermatologic and general medical literature, requires one to have at least a basic understanding of how the PCR is conducted, what it has to offer, and the potential shortcomings. Such knowledge will hopefully allow a more critical appraisal of an increasingly complex literature. This review aims to describe the methodology and medical applications of this powerful technique with special consideration to the increasing role PCR may have on dermatologic research and practice.
Genetic Diseases, Inborn↗
Sales force can lead to dollars for OH (occupational health) services.
As hospitals enter the 1990s, one of the challenges they will face is finding additional sources of revenue. Occupational Health (OH) programs offer an opportunity for increased dollars--but only for hospitals willing to use sales tactics common to corporate America. In the following article, the author tells how an institution can sell OH services.
Hospitals↗
Occupational health programs can generate new revenue.
A hospital may find an untapped source of revenue by setting up occupational health services. Starting with treatment of workers' compensation cases, an occupational health program may open the door to additional revenue through family practice or group health plans. A preliminary feasibility study of market conditions, operational needs, and potential obstacles is essential to successful program management.
Communication↗
A quantitative study of the optic system of butterflyfishes (family chaetodontidae).
The following measurements were taken on the visual system in 13 species of butterflyfishes (family Chaetodontidae): volume and cell density of the nucleus geniculatus lateralis, nucleus corticalis, and nucleus pretectalis; and width of the stratum opticum-stratum fibrosum et griseum superficiale. Tests for correlations between these components showed that the volumes of the nucleus pretectalis and nucleus corticalis are positively correlated. No significant differences were found when the volumes and cell densities of these parts were compared in two groups of butterflyfishes whose feeding behaviors are different: plankton feeders and coral feeders. A possible spurious positive correlation between the sizes of the nucleus pretectalis, nucleus corticalis, stratum opticum-stratum fibrosum et griseum superficiale and total body length was also demonstrated.
Animals↗
Volume compensation for pulsatile blood pumps.
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Animals↗
Mechanical strain and calcification in blood pumps.
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Animals↗
Bovine aortic and human dura mater valves: a comparative study in artificial hearts in calves.
Thirty-one glutaraldehyde-treated bovine aortic valves (BAVs) and 105 glycerol-treated human dura mater valves (HDVs) were used in 51 various artificial hearts up to 316 days in calves. Multiple valves were implanted in the same animal under different hemodynamic conditions. A comparative study of these valves was performed in terms of blood compatibility and durability with relation to the different hemodynamic environments. Both BAVs and HDVs showed good blood compatibility. The degradation of collagen bundles of the valves began as early as 7 days in BAVs and 13 days in HDVs, and was seen in the hinged portions of the cusps. The fiber separation and resultant void formation were followed with insudation of blood elements and subsequent calcification. Calcification was dystrophic in nature and was encountered in 70.9% of BAVs and 7.6% of HDVs. All 17 BAVs used more than 30 days were calcified; in HDVs the earliest calcified lesion was seen in a 78 day specimen. The pathological changes were more severe in the left side than the right of the total artificial hearts. These results clearly indicated that the HDV is more durable than the glutaraldehyde-treated BAV. It was suggested that degradation of these tissue valves is greatly affected by the degree of hemodynamic stress on the valve cusp. Although glutaraldehyde treatment has increased the durability of tissue valves in general, the structure of the valve tissue also plays an important role in long-term durability.
Animals↗
The dura mater valve: in vitro characteristics and pathological changes after implantation in calves.
Human dura mater valves of various sizes with rigid and flexible stents were tested in an in vitro pulsatile mock circulatory system. A 22-mm flexible stent valve incorporating a new fabrication technique showed almost the same pressure gradient as a 28-mm rigid stent valve. The backflow/stroke volume ratio was about 4% at a net flow of 10 L/min. One hundred and five rigid stent-mounted dura mater valves were used in 51 pump implantations for up to 316 days. Collagen fiber degeneration began three months after implantation. Microscopic and macroscopic calcification of the valve tissue was seen in eight out of 105 valves, giving an overall incidence of 7.6%. The calcified degeneration was dystrophic in nature, not accompanied by cellular reactions, and was seen in the areas of the valve under stress. The degenerative changes were more severe in the left side than in the right side of the total artificial heart. These findings suggest that mechanical damage to the tissue plays an important role in the pathogenesis of calcification.
Animals↗