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Biomedical subjects

Stephen K Tyring

Publications and source records attributed to Stephen K Tyring.

At least 109 records · Page 6Linked to original sources

A review of antibiotics in dermatology.

BACKGROUND: Since the early 1930s when antibiotics were first introduced, they have revolutionized the way physicians treat infections. Skin conditions from acne to leprosy, which were once shunned by society, are now easily treated with oral antibiotics. OBJECTIVE: Antibiotics are chemicals derived from bacteria and fungi that uniquely have antibacterial action. The most notable example is penicillin, which is derived from a mold. With hundreds of antibiotics available to the practicing physician, improper use of these drugs has become widespread and expensive and has spawned resistant strains. For the dermatologist, antibiotics are vital weapons in the drug armamentarium for treating various skin conditions. CONCLUSION: This review explores the newest and most common oral, parenteral, and topical antibiotics used in dermatology, their indications, adverse effects, dosage, and spectrum of activity. Furthermore, systemic antibacterial prophylaxis and vaccines pertinent to dermatology are discussed. The penicillins, cephalosporins, tetracyclines, macrolides, fluoroquinolones, sulfonamides, aminoglycosides, lincosamides, folate inhibitors, and a new synthetic class of drugs, the oxazolidinones, are reviewed. These antibiotics are used to treat a variety of organisms.

Anti-Bacterial Agents↗

Genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) in ethnic populations in Texas; a report of a novel MTHFR polymorphic site, G1793A.

The importance of hyperhomocysteinemia, birth defects, and vascular diseases has been the subject of intense investigations. The polymorphic MTHFR mutations (C677T and A1298C) cause mild hyperhomocysteinemia, especially in homozygotes for C677T, but also in compound heterozygotes for C677T/A1298C. The subject of this report is the frequency of the polymorphic mutations in the MTHFR gene C677T, C1298A, and newly discovered mutation G1793A, as well as the association with MTRR polymorphic site A66G in different ethnic groups. Four ethnic groups were studied: African-Americans, Caucasians, Hispanics, and Ashkenazi Jews. There are statistically significant differences in the frequency of these alleles in the different populations studied, which impacts compound heterozygosity for such alleles in these populations. DNA samples obtained from the blood of healthy individuals of African-Americans, Hispanics, and Caucasians from south Texas were analyzed and compared to those obtained from Ashkenazi Jewish individuals. The polymorphic site, the G1793A allele, is least frequent among Ashkenazi individuals, 1.3%, compared to 6.9% among Caucasians (P = 0.001), 5.8% among Hispanics (P = 0.012), and 3.1% among African-Americans. The MTRR polymorphic site shows the lowest allele frequency among Hispanics, 28.6%, compared to 34% among African-Americans, 43.1% among Ashkenazi Jews (P = 0.002), and 54.4% among Caucasians (P < 0.0001). Statistically significant differences in allele frequencies of C677T and C1298A polymorphisms were also observed in these populations. Compound heterozygosity for multiple polymorphic alleles may play a role in birth defects and vascular diseases.

Alleles↗

Interleukin-10 induces transcription of the early promoter of human papillomavirus type 16 (HPV16) through the 5'-segment of the upstream regulatory region (URR).

The effects of various proinflammatory cytokines on the transcription of human papillomaviruses (HPVs) have been demonstrated. On the other hand, the role of anti-inflammatory cytokines has not been elaborated, despite the fact that levels of interleukin-10 (IL-10) have been found significantly elevated in cervical dysplasias or carcinomas as well as in the cervix of HIV-positive individuals. These conditions are also associated with elevated viral transcription. Thus, the impact of IL-10 on HPV transcription might be important in pathogenesis of cervical lesions in both immunocompetent or immunosuppressed individuals. In this paper we describe the effects of IL-10 on the transcription of HPV type 16. We found that treatment of HPV 16-positive cervical carcinoma cells with IL-10 increased mRNA levels of the E7 early gene at the level of transcription. Similarly, IL-10 significantly and dose-dependently induced the transcription from the HPV early promoter in a reporter system. Employing deletion mutants we determined that this induction is mapped to the 5' segment of the URR. Transient transfection of an antisense-STAT3-expression vector abolished IL-10-induced reporter activity as well as HPV 16 E7 expression. This suggests that STAT3 either directly binds to the URR and stimulates transcription or affects expression and/or binding of transcription factors that bind to the 5'-region. Our findings suggest a mechanism by which--in addition to its immunosuppressive effects--IL-10 might enhance persistence and progression of HPV-related lesions under conditions (e.g. dysplastic progression, HIV infection) when the cytokine expression in the cervical microenvironment changes.

5' Flanking Region↗

Herpes simplex viruses 1 and 2.

An increased understanding of the pathogenesis and transmission of HSV infections and the development of sensitive type-specific diagnostic tests have helped develop effective prophylactic and therapeutic antiviral drug regimens. Effective medications have been available for quite some time, but the most optimal regimens are still under investigation. Advances in the treatment of atypical presentations of HSV infection (such as the use of cidofovir gel for the treatment of acyclovir-resistant HSV) are promising. Newer treatments, such as resiquimod, actually may alter the course of HSV infection, reducing the severity and frequency of recurrences. Vaccines are being explored as preventive and therapeutic measures against HSV.

Herpes Genitalis↗

Human herpesvirus 8.

Human herpesvirus 8 (HHV 8), also known as Kaposi's sarcoma-associated herpesvirus (KSHV) is a g2 herpesvirus and the most recently identified human tumor virus. HHV 8 has been consistently implicated in the pathogenesis of all clinical variants of Kaposi's sarcoma, as well as in the plasma cell variant of multicentric Castleman's disease and primary effusion lymphomas. Pathogenicity of the virus is increased in the host who is immunosuppressed, either iatrogenically or through H1V-1 infection. The HHV 8 genome contains several homologues of cellular genes that regulate cell growth and differentiation, and the exact mechanisms of the virus' oncogenicity using molecular piracy are still being investigated and elucidated. In this article, the authors review the epidemiology, transmission, clinical manifestations, and molecular genetics of HHV 8 infection and provide a summary of the current treatment modalities available to the clinician.

Herpesvirus 8, Human↗

Rubella.

Rubella is still a public health concern in this country. With the great numbers of immigrants welcomed in the United States also comes the risk of diseases that are little known or thought to be of little concern. Obviously, there is a need for continued vaccination of citizens, not only at approximately 1 year of age and school age but also in terms of continued screening for and immunization of susceptible women of childbearing age. Policies need to be developed to address the issue of rubella infection and susceptibility in areas where there is a high population density of people from countries that may not have such strict immunization practices. Vaccination at workplaces that employ high numbers of foreign-born workers or that involve a close working environment, education of workers and health care professionals in the recognition of rubella and its potentially devastating effects, and continued surveillance for and reporting of cases in high-risk areas may be of benefit.

Humans↗

A review of the dermatologic manifestations of poxvirus infections.

Physicians need to be familiar with the presentation of poxvirus infections. The poxvirus infections that are common, such as MCV, are rarely serious; however, physicians need to understand them because they can be bothersome to patients and require reassurance and, if available, treatment. The more rare poxvirus infections, such as variola, need to be recognized because they are generally serious. It is important to consider that these infections can suggest underlying systemic disease, as in the case of severe, recalcitrant MCV infection, which may be indicative of HIV infection or another immunocompromised state.

Humans↗

Cytomegalovirus infections.

Over the past two decades, there has been an escalation in the number of patients undergoing immunosuppressive therapy following solid organ or bone marrow transplantation, as well as a dramatic increase in the incidence of AIDS. As a result, human cytomegalovirus (HCMV)--once considered a neonatal disease--has captured great interest and importance as a major pathogen in both immunocompromised and immunocompetent patients. Like other members of herpesviridae family, HCMV establishes latency in myeloid lineage cells with potential for reactivation. The natural history of HCMV infection can be divided into primary infection, latency, and reinfection. This review article briefly discusses the molecular pathogenesis of HCMV, then focuses on the clinical picture of this disease, with emphasis on the skin pathology. Diagnostic methods and treatments are also discussed.

Cytomegalovirus↗

The cutaneous manifestations of viral hepatitis.

Viral hepatitis is a common disease with significant morbidity and mortality that is found throughout the world. It is a known cause of acute and chronic liver disease. Because the disease can be asymptomatic in its acute stages, the diagnosis is often missed. This article reviews the extrahepatic manifestations of the disease, in particular the visible cutaneous lesions, which offer clues to the diagnosis of viral hepatitis. Familiarity with the most common skin lesions associated with each type of hepatitis virus will be useful in identifying previously undiagnosed individuals. This article serves as a review of the most widely published associations between skin diseases and specific subtypes of viral hepatitis.

Hepatitis, Viral, Human↗

The cutaneous manifestations of HIV infection.

Dermatologic disease is extremely common and varied in HIV-infected patients. While some cutaneous findings are nearly exclusive to HIV-seropositive individuals, many are found in the general population. However, HIV-infected individuals often have an increased prevalence or severity, atypical presentations, or difficulty with treatment of the disease. Immune reconstitution with HAART significantly reduces the prevalence of many dermatologic diseases, but also has associated cutaneous side effects. Correct and early diagnosis of skin disease in HIV-infected individuals allows for early management and improved quality of life. Because dermatologic manifestations may be the first clue of HIV infection, offering HIV testing to affected individuals can lead to early diagnosis and treatment of HIV infection and, ideally, a decrease in disease progression and transmission.

AIDS-Related Opportunistic Infections↗

Cutaneous manifestations of Epstein-Barr virus infection.

The most common cutaneous manifestations of EBV include IM, OHL, and cutaneous lymphoproliferative disorders. Infectious mononucleosis is a self-limited manifestation of acute EBV infection. The transient rash that occurs quite commonly in patients with IM who have received antibiotic therapy is an erythematous, maculopapular eruption, usually located on the trunk and upper extremities. Oral hairy leukoplakia occurs in immunosuppressed HIV-positive and HIV-negative individuals. In HIV-positive individuals, it serves as an indicator of disease severity and rapid progression to AIDS. The presence of OHL in an individual should prompt the clinician to perform a through history-taking and investigation of immune status. Cutaneous lymphoproliferative disorders associated with EBV occur in individuals with congenital or acquired immunodeficiency syndromes.

Epstein-Barr Virus Infections↗

Human papillomavirus: a review.

Human papillomavirus infection remains a great source of morbidity and mortality. Progress in understanding the structure of HPV and its pathogenesis has led to a wide variety of possible new treatment modalities to combat HPV-related disease. Most HPV infections (whether high risk or low risk) resolve without any medical intervention. Persistent or progressive disease, however, remains difficult to treat. Although currently available therapies have proved efficacious and tolerable in the treatment of nongenital and genital warts, no single therapy is uniformly effective in eradicating persistent HPV infection. Cytodestructive methods, such as cryotherapy, remain the primary treatment modality for nongenital warts. Immune response modifiers, such as imiquimod, currently show the greatest promise in treating HPV-induced anogenital lesions, both with respect to complete response and in preventing recurrence. Human papillomavirus infection is one of the most common sexually transmitted diseases in the world, and cervical cancer still causes significant morbidity and mortality. Pap smear tests have greatly reduced the incidence and mortality of cervical cancer in developed countries. Additional research will focus on primary and secondary prevention strategies. Vaccines against high-risk HPV types are promising modalities currently under investigation to prevent HPV infections and possibly to treat them.

Condylomata Acuminata↗

Update on Kaposi's sarcoma and other HHV8 associated diseases. Part 1: epidemiology, environmental predispositions, clinical manifestations, and therapy.

Kaposi's sarcoma (KS) is a mesenchymal tumour involving blood and lymphatic vessels. Only recently has the pathogenesis of this extraordinary neoplasm been elucidated. Viral oncogenesis and cytokine-induced growth together with some state of immunocompromise represent important conditions for this tumour to develop. In 1994, a novel virus was discovered and termed human herpesvirus 8 (HHV8), also known as Kaposi's sarcoma-associated herpes virus, which can be found in all types of KS, whether related to HIV or not. In the era of highly active antiretroviral therapy (HAART), the incidence of AIDS-KS has considerably declined, probably due to enhanced immune reconstitution and anti-HHV8-specific immune responses. If HAART is able to prevent spreading of KS, local therapy of KS may become an essential component of patient management. Part 1 of the review covers the epidemiology, environmental predispositions, clinical manifestations, and therapy of KS. Newer treatments such as pegylated liposomal anthracyclines and experimental strategies are discussed. We also present rationales and graduated treatment algorithms for local and systemic therapy in patients with KS to appropriately meet the challenges of this extraordinary neoplasm. Part 2, to be published next month, will summarise recent insights in the pathogenesis of KS and will discuss other HHV8-related diseases such as Castleman's disease and primary effusion lymphoma.

AIDS-Related Opportunistic Infections↗

Update on Kaposi's sarcoma and other HHV8 associated diseases. Part 2: pathogenesis, Castleman's disease, and pleural effusion lymphoma.

The pathogenesis of Kaposi's sarcoma (KS) is better understood since the identification of the novel human herpesvirus 8 (HHV8), which can be found in all forms of KS. Viral oncogenesis and cytokine-induced growth, as well as some states of immunocompromise, contribute to its development. Several virally encoded genes--eg, bcl-2, interleukin 6, cyclin D, G-protein-coupled receptor, and interferon regulatory factor--provide key functions on cellular proliferation and survival. Growth promotion of KS is further stimulated by various proinflammatory cytokines and growth factors such as tumour necrosis factor a, interleukin 6, basic fibroblast growth factor, and vascular endothelial growth factor, resulting in a hyperplastic polyclonal lesion with predominant spindle cells derived from lymphoid endothelia. HHV8 has recently been discovered to escape HLA-class-I-restricted antigen presentation to cytotoxic T lymphocytes by increasing endocytosis of MHC class I chains from the cell surface, thus enabling latent infection and immune escape in primary and chronic infection. Multicentric Castleman's disease is a rare lymphoproliferative disorder of the plasma cell type, which has been reported in both HIV-seropositive and HIV-seronegative patients, and which frequently contains HHV8 DNA. Pleural effusion lymphoma, or body-cavity-based lymphoma, belongs to the group of non-Hodgkin B-cell lymphomas characterised by pleural, pericardial, or peritoneal lymphomatous effusions in the absence of a solid tumour mass. Pleural effusion lymphoma has an intermediate immunophenotype lacking B or T lymphocyte antigens and also belongs to the diseases associated with HHV8.

Castleman Disease↗

CD4+ T lymphocytopenia with disseminated HPV.

BACKGROUND: There have been several reports of HIV-negative patients with chronic idiopathic CD4+ T lymphocytopenia, the diagnostic criteria for which are: depressed numbers of circulating T lymphocytes (less than 300/ micro l or less than 20%) on more than one occasion; no laboratory evidence of HIV-1 or HIV-2 infection; and the absence of any defined immunodeficiency or therapy associated with depressed levels of CD4+ T lymphocytes. METHODS: We report a patient with disseminated human papillomavirus infection associated with idiopathic CD4+ T-cell lymphocytopenia. A 50-year-old woman presented to the dermatology clinic with a 10-year history of widespread verrucae involving the skin and the cervix. RESULTS: Biopsy from the arm revealed a common wart. PCR analysis performed from the paraffin-embedded block was strongly positive for HPV type 2. Other HPV types (including EV-associated HPV 5, 8, 14, 15, 17) were not found. Further laboratory work up revealed T-cell lymphocytopenia, with an absolute CD4 count of 21. HIV tests were repeatedly negative. She was treated with interferon A 8 million units SQ three times per week with partial improvement. The patient underwent a hysterectomy for cervical dysplasia and a vulvectomy for vulvar intraepithelial neoplasia. She developed small-cell lung carcinoma and died. CONCLUSIONS: The diagnosis of idiopathic CD4+ T-cell lymphocytopenia should be considered in any patient with widespread viral, fungal, or mycobacterial infection whose HIV test is negative, and appropriate evaluation of the absolute CD4+ counts should be performed.

Carcinoma, Small Cell↗

Antiviral agents: Non-antiretroviral [correction of Nonantiviral] drugs.

The current arsenal of antiviral agents available to the practitioner is expanding rapidly, such that by the time this article goes to press, new drugs may have already been added. Although the majority of approved drugs have been developed for use in only a few viral infections (eg, HIV, herpesviruses, and papillomavirus), discoveries made in the development of these drugs may lead to antiviral agents effective against other viruses. In addition, new uses for the currently available drugs are under evaluation. This review of antiviral agents discusses the treatments available for viral infections such as herpes simplex virus, varicella zoster virus, cytomegalovirus, human papillomavirus, chronic viral hepatitis, and others.

2-Aminopurine↗

Treatment of anogenital warts with imiquimod 5% cream followed by surgical excision of residual lesions.

Cytodestructive or surgical therapy for patients with anogenital warts is frequently associated with recurrence. In February 1997, the US Food and Drug Administration approved imiquimod as a 5% cream for the treatment of anogenital warts. Activity of the drug results primarily from interferon alfa and other cytokine induction in the skin. These cytokines stimulate several other aspects of the innate immune response. In addition, imiquimod stimulates acquired immunity, in particular the cellular arm that is important for control of viral infections and tumors. Published studies indicate that imiquimod results in complete clearance of warts in more than 50% of patients. Residual warts can be surgically excised. Our long-term follow-up (ie, 2 to 7 years) of patients who had a 16-week course of imiquimod cream with subsequent removal of remaining warts showed a much lower rate of recurrence in comparison with those patients who were treated with surgery alone. Therefore, treatment with imiquimod followed by excision of residual lesions may provide long-term clearance of anogenital warts in those patients in whom imiquimod monotherapy is insufficient.

Adjuvants, Immunologic↗