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Biomedical subjects

Stephen K Tyring

Publications and source records attributed to Stephen K Tyring.

At least 73 records · Page 4Linked to original sources
PubMed2004

Therapy of nontuberculous mycobacterial infections.

Mycobacterial infections are increasing in incidence worldwide, partly as a result of the increase in immunocompromised individuals. They cause a large number of cutaneous infections with a broad array of manifestations. Because of their diverse manifestations and sometimes fastidious nature, infections with mycobacteria are often misdiagnosed, leading to delay in and sometimes failure of therapy. In addition, many mycobacteria display both in vitro and in vivo drug resistance to antimicrobial agents. Early recognition of affected patients, initiation of appropriate antimicrobial therapy based on current guidelines, and tailoring of therapy after susceptibility testing is available are therefore essential to the successful treatment of mycobacterial infections.

Diagnosis, Differential↗
PubMed2004

Treatment and prevention of rickettsial and ehrlichial infections.

Rickettsial and ehrlichial infections are both carried by arthropod vectors. Both Rickettsia and Ehrlichia are small intracellular gram-negative coccobacilli. Clinical manifestations of Rickettsia range from spotted fevers to various forms of typhus. Human ehrlichiosis can present as monocytic ehrlichiosis or granulocytic anaplasmosis. Prevention is by avoidance of the responsible vectors. Therapy is usually with doxycycline, but chloramphenicol can also be used.

Animals↗
PubMed2004

Treatment of protozoan infections.

Protozoan infections can have a variety of different cutaneous manifestations in addition to systemic signs and symptoms of disease. Recognition and diagnosis can be difficult, as additional laboratory tests, in addition to biopsies, may be required. Treatment options for different protozoa vary and resolution of disease may be refractory despite lengthy treatment courses. An overview of cutaneous manifestations, diagnosis, and treatment regimen of amebiasis, leishmaniasis, trypanosomiasis, and toxoplasmosis is outlined in this article.

Amebiasis↗
PubMed2004

Therapy of common superficial fungal infections.

Superficial fungal infections are common, especially onychomycosis, dermatophytoses, and superficial Candida infections. Most superficial fungal infections are treated with topical antifungal agents unless the infection covers an extensive area or is resistant to initial therapy. Onychomycosis often requires systemic therapy with griseofulvin, itraconazole, or terbinafine. The objective of this review is to provide the practicing dermatologist with the recommended available therapy for the treatment of common superficial fungal infections.

Antifungal Agents↗
PubMed2004

Subcutaneous fungal infections.

Subcutaneous mycoses are caused by a variety of mostly tropical organisms, usually when they are implanted into the dermis or the subcutaneous tissue. They rarely disseminate or become systemic. Sporotrichosis, mycetoma, and chromoblastomycosis are more common subcutaneous mycoses than are rhinosporidiosis, zygomycosis, pheohyphomycosis, and lobomycosis.

Antifungal Agents↗
PubMed2004

Therapy of systemic fungal infections.

The incidence of both community-acquired and nosocomial fungal infections has significantly increased over the past several decades. The major factors for this increase are a heightened use of antibiotics, a growing population of the elderly and of immunocompromised patients as a result of HIV, cancer, and organ transplantation. In this article, we will review the indications, efficacy, and safety of the polyenes, imidazoles, triazoles, and other systemic antifungals in development that are used for systemic fungal infections.

Antifungal Agents↗
PubMed2004

Recent clinical experience with famciclovir--a "third generation" nucleoside prodrug.

The herpesviruses continue to produce considerable morbidity in man. Once infected with herpes simplex (HSV), the virus remains dormant within the nervous system and may reactivate if provoked by stress, trauma and/or other factors. To date, there is no cure, but antiviral medication can reduce duration and severity of symptoms and prophylaxis can suppress recurrent episodes of disease. The second-generation guanosine nucleosides, acyclovir and penciclovir, are effective inhibitors with low toxicity; both, however, have relatively low oral bioavailability. Subsequently, the orally bioavailable prodrugs valaciclovir and famciclovir have been introduced. These compounds offer high oral bioavailabilty and deliver acyclovir and penciclovir, respectively, to the target cells by means of more convenient dosing schedules. This short review points to recent experience with famciclovir in the management of HSV and varicella-zoster virus.

2-Aminopurine↗
PubMed2004

Emerging therapies for herpes viral infections (types 1 - 8).

There are eight members of the herpesviridae family: herpes simplex virus-1 (HSV-1), HSV-2, varicella-zoster virus, Epstein-Barr virus, cytomegalovirus, human herpes virus-6, human herpes virus-7 and human herpes virus-8. The diseases caused by viruses of the herpesviridae family are treated with and managed by systemic and topical antiviral therapies and immunomodulating drugs. Because these viruses establish a latent state in hosts, antiherpetic agents, such as nucleoside analogues, only control symptoms of disease or prevent outbreaks, and cannot cure the infections. There is a need for treatments that require less frequent dosing, can be taken even when lesions are more advanced than the first signs or symptoms, and can treat resistant strains of the viruses without the toxicities of existing therapies. Immunomodulating agents, such as resiquimod, can act on the viruses indirectly by inducing host production of cytokines, and can thereby reduce recurrences of herpes. The new helicase primase inhibitors, which are the first non-nucleoside antiviral compounds, are being investigated for treatment of HSV disease, including infections resistant to existing therapy.

Acyclovir↗
PubMed2003

A novel targeted T-cell modulator, efalizumab, for plaque psoriasis.

BACKGROUND: Interactions between leukocyte-function-associated antigen type 1 (LFA-1) and intercellular adhesion molecules are important in the pathogenesis of psoriasis. Efalizumab, a humanized monoclonal antibody, binds to the alpha subunit (CD11a) of LFA-1 and inhibits the activation of T cells. METHODS: In a phase 3, multicenter, randomized, placebo-controlled, double-blind study, we assign 597 subjects with psoriasis to receive subcutaneous efalizumab (1 or 2 mg per kilogram of body weight per week) or placebo for 12 weeks. Depending on the response after 12 weeks, subjects received an additional 12 weeks of treatment with efalizumab or placebo. Study treatments were discontinued at week 24, and subjects were followed for an additional 12 weeks. RESULTS: At week 12, there was an improvement of 75 percent or more in the psoriasis area-and-severity index in 22 percent of the subjects who had received 1 mg of efalizumab per kilogram per week and 28 percent of those who had received 2 mg of efalizumab per kilogram per week, as compared with 5 percent of the subjects in the placebo group (P<0.001 for both comparisons). Efalizumab-treated subjects had greater improvement than those in the placebo group as early as week 4 (P<0.001). Among the efalizumab-treated subjects who had an improvement of 75 percent or more at week 12, improvement was maintained through week 24 in 77 percent of those who continued to receive efalizumab, as compared with 20 percent of those who were switched to placebo (P<0.001 for both comparisons). After the discontinuation of efalizumab at week 24, an improvement of 50 percent or more in the psoriasis area-and-severity index was maintained in approximately 30 percent of subjects during the 12 weeks of follow-up. Efalizumab was well tolerated, and adverse events were generally mild to moderate. CONCLUSIONS: Efalizumab therapy resulted in significant improvements in plaque psoriasis in subjects with moderate-to-severe disease. Extending treatment from 12 to 24 weeks resulted in both maintenance and improvement of responses.

Adult↗
PubMed2003

Valacyclovir in the treatment of herpes simplex, herpes zoster, and other viral infections.

BACKGROUND: Genital herpes and herpes labialis are prevalent, physically and psychologically painful, and often disabling. Herpes zoster is often very painful and may result in months or years of postherpetic neuralgia (PHN). Over the past two decades, the treatment of these conditions has been transformed by guanosine nucleoside antivirals such as valacyclovir (Valtrex, a highly bioavailable prodrug of acyclovir (Zovirax, and famciclovir (Famvir), a highly bioavailable prodrug of penciclovir (Denavir). OBJECTIVE: We describe the pharmacology, pharmacokinetics, and clinical efficacy of valacyclovir for the treatment of herpes simplex, herpes zoster, and other viral infections. Valacyclovir is also compared with acyclovir and famciclovir. METHODS: All published literature containing the word "valacyclovir" was reviewed and summarized. RESULTS: Valacyclovir is the only oral antiviral agent approved for therapy of herpes labialis, the only antiviral drug approved for a 3-day course in the episodic treatment of recurrent genital herpes, as well as the only antiviral drug approved for once daily dosing for suppressive therapy. In herpes zoster, valacyclovir is more effective than acyclovir and equally effective as famciclovir at hastening the healing of zoster-associated pain and PHN. CONCLUSION: Valacyclovir is safe and effective in the therapy of patients with herpes simplex and herpes zoster and may be useful in other viral infections.

2-Aminopurine↗
PubMed2003

Differentiation-dependent expression of signal transducers and activators of transcription (STATs) might modify responses to growth factors in the cancers of the head and neck.

Overexpression of the epidermal growth factor receptor (EGFR) in the cancers of the head and neck is well demonstrated. In addition, copy numbers of the EGFR mRNA were significantly higher in poorly differentiated tumors than in tumors that had a differentiated phenotype. Studies by others also showed that the constitutively activated signal transducer and activator of transcription-3 (STAT3), but not STAT1, is required for EGFR-mediated cell growth. Our aim was to reveal if STAT expression is differentiation-dependent and thus, might respond to exogenous stimuli in a differentiation-dependent manner. Both reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry revealed that expression of STAT1 was high in well/moderately differentiated tumors in vivo. In contrast, STAT3 was expressed in poorly differentiated tumors. In vitro experiments showed that differentiated primary oral keratinocytes expressed higher levels of STAT1, but lower levels of STAT3 than did their undifferentiated counterparts. Epidermal growth factor treatment of oral keratinocytes with various degrees of differentiation showed the maximal induction of cyclin D1 in undifferentiated cells. Our findings suggest that the level of differentiation might modulate the outcome of EGFR signaling (i.e. cyclin D1 transcription), due to the differentiation-associated intracellular balance of transcriptional regulators (STAT1 versus STAT3).

Biopsy↗
PubMed2003

Expression of glutamate transporter, GABRA6, serine proteinase inhibitor 2 and low levels of glutamate and GABA in the brain of knock-out mouse for Canavan disease.

Canavan disease (CD) is an autosomal recessive leukodystrophy characterized by spongy degeneration of the brain. The clinical features of CD are hypotonia, megalencephaly, and mental retardation leading to early death. While aspartoacylase (ASPA) activity increases with age in the wild type mouse brain, there is no ASPA activity in the CD mouse brain. So far ASPA deficiency and elevated NAA have been ascribed with the CD. Other factors affecting the brain that result from ASPA deficiency may lead pathophysiology of CD. The NMR spectra and amino acid analysis showed lower levels of glutamate and gamma-aminobutyric acid in the CD mouse brain compared to the wild type. Microarray gene expression on CD mouse brain showed glutamate transporter-EAAT4 and gamma-aminobutyric acid-A receptor, subunit alpha6 (GABRA6) were lower 9.7- and 119.1-fold, respectively. Serine proteinase inhibitor 2 (Spi2) was 29.9-fold higher in the CD mouse brain compared to the wild type. The decrease of GABRA6 and high expression of Spi2 in CD mouse brain were also confirmed by real-time RT-PCR. This first report showing abnormal expression of EAAT4, GABRA6, Spi2 combined with lower levels of glutamate and GABA are likely to be associated with the pathophysiology of CD.

Amino Acid Transport System X-AG↗
PubMed2003

A functional interferon regulatory factor-1 (IRF-1)-binding site in the upstream regulatory region (URR) of human papillomavirus type 16.

We recently identified a new enhancer element (HIRE-1, HPV-Interferon Responsive Element-1) in the upstream regulatory region (URR) of human papillomavirus (HPV) type 16. HIRE-1 is located upstream from and in close proximity to the TATA box. HIRE-1 is 1 nt shorter in its 5' sequence in comparison to a consensus IRF-1 binding site (IRF-E). Gel shift analyses clearly demonstrated that HIRE-1 is capable of binding IRF-1 in response to interferon-gamma (IFN-gamma) treatment. In a reporter system, HIRE-1 stimulated transcription in response to IRF-1 or IFN gamma from both a heterologous or the homologous (p97) promoter in a dose-dependent manner. Mutations in the core binding sequence strongly decreased this enhancer activity. Interestingly, HIRE-1 stimulated transcription in the context of the full URR in a cell-type-specific manner, thereby suggesting the role of other cell-type-specific factors that might counteract with its function. Thus, our results may explain the inconsistent clinical and experimental results observed following IFN treatment of cervical lesions or cells. Also, this new enhancer may have an important function during inflammatory responses against HPV type 16.

5' Flanking Region↗
PubMed2003

Polymorphisms for chemical metabolizing genes and risk for cervical neoplasia.

Infection with high-risk human papillomavirus (HPV) plays a major role in the etiology of cervical cancer (CC). However, most infected women do not develop cancer. Therefore, exposure to other carcinogenic agents may be a contributing risk factor for CC. We investigated the hypothesis that environmental exposure to cigarette smoke and inheritance of polymorphic chemical metabolizing genes (CYP2E1, GSTM1, and mEH) significantly increase the risk for neoplasia. We selected 76 cases with high-grade cervical neoplasia or with invasive CC and 75 matched healthy controls. The collected data support the well-established observation that infection with high-risk HPV is the major risk factor for CC (OR = 75; 95% CI = 26-220). In addition, our data show that women who smoked more than 15 "pack-year" had a significant 6.9-fold increase in risk (95% CI = 1.2-40.3) after adjustment for HPV infection. The CYP2E1 variant genotype did not significantly increase the risk for neoplasia. A significant increase in risk for neoplasia was observed for the low-activity mEH 113 His allele after adjustment for smoking (OR = 3.0; 95% CI = 1.4-6.3). The GSTM1 null genotype was associated with a significant 3.3-fold increased risk for neoplasia (95% CI = 1.0-11.8) compared to women who were GSTM1-positive after adjustment for smoking and HPV infection. Our study suggests that genetic differences in the metabolism of cigarette smoke, particularly GSTM1, may confer susceptibility to CC. Further studies using larger populations will be needed to confirm our observations and to validate data for disease prevention.

Adolescent↗
PubMed2003

Acquired and genetic susceptibility to cervical cancer.

Infection with high-risk human papilloma virus (HPV) is a necessary risk factor for the development of cervical cancer (CC). However, there are many factors that contribute to the development of CC. We have been investigating the role of polymorphisms in chemical metabolizing genes and life-style factors in the development of CC between two countries with significantly different prevalence of CC. Our data confirm that infection with high-risk HPV is the most significant risk factor for CC in both Venezuela and US. In Venezuela, having multiple sex partners and early sexual activities are significant risk factors (OR=4.7, 95% CI=1.7-13.1; OR=6.7, 95% CI=2.3-20.1, respectively). On the other hand, cigarette smoking is the significant risk factor for women in the US (OR=6.4, 95% CI=1.8-23.2). Genotype analyses were conducted using specimens from the US population only. The GSTM1 null genotype was associated with a significant 3.4 fold increase in risk (95% CI=1.0-11.8) compared with those who were GSTM1 positive, after adjustment for smoking and HPV infection. Polymorphosis in CYP2E1 and mEH are associated with a non-significant increase in risk. Our study indicates that different acquired and genetic susceptibility factors can make significant contributions to the development of environmental disease such as cervical cancer.

Female↗
PubMed2003

Effect of epoxide hydrolase polymorphisms on chromosome aberrations and risk for lung cancer.

Microsomal epoxide hydrolase (mEH) gene is polymorphic and its enzyme is involved in the activation and subsequent detoxification of several tobacco carcinogens, for example polycyclic aromatic hydrocarbons. Therefore, we have investigated the association of two polymorphisms at exons 3 and 4 of the mEH gene with the development of lung cancer in 110 patients and 119 matched controls. In addition, we have investigated the relationship between the different mEH alleles and the frequency of chromosome aberrations (CA), as an approach to understand the role of genetic susceptibility on cancer risk. Our results show that only the homozygous exon 4 fast genotype is significantly associated with increased risk for lung cancer (odds ratio [OR]=6.26; 95% confidence interval [CI]=1.02-38.3). When the exons 3 and 4 polymorphisms are considered together, patients carrying the high enzyme activity genotype have a significantly increased risk for lung cancer (OR=2.46; 95% CI=1.06-5.68). More importantly, the increased risk for this group is confirmed by their having the highest frequency of CA compared to any other genotype groups. In addition, genotypes with higher risk had consistently more CA than those with lower risk. Our CA data also indicates that the low activity genotype may exert a protective role in cigarette smokers, as it was associated with a significant decrease in CA compared to the high and intermediate activity genotypes. In conclusion, the CA data provides evidence to support that susceptibility mEH alleles are significantly involved with the development of lung cancer from cigarette smoking.

Case-Control Studies↗
PubMed2003

Evidence for endogenous interleukin-10 during nociception.

Cytokines such as IL-1beta, IL-6 and tumor necrosis factor-alpha (TNF-alpha) have been shown to contribute directly to central and peripheral neuropathic pain. Recently, exogenous interleukin-10 (IL-10) was shown to impede development of dynorphin-induced allodynia presumably by inhibiting IL-1beta. We therefore wanted to determine whether endogenous IL-10 had a role in pain perception. By measuring the latency of the paw licking response, we show in IL-10 knockout mice and in normal mice treated with anti-IL-10 that latency times are increased, suggesting that endogenous IL-10 increases nociception. This does not appear to be directly correlated with IL-10's regulation of DREAM, a transcriptional regulator of prodynorphin synthesis.

Animals↗