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Biomedical subjects

S K Tyring

Publications and source records attributed to S K Tyring.

At least 19 recordsLinked to original sources
PubMed2006

Large neutral amino acids in the treatment of phenylketonuria (PKU).

Large neutral amino acids (LNAAs) have been used on a limited number of patients with phenylketonuria (PKU) with the purpose of decreasing the influx of phenylalanine (Phe) to the brain. In earlier studies on mice with PKU (ENU(2)/ENU(2)), LNAAs were given and a surprising decline in blood Phe concentrations was observed. The formula used in the mouse experiment (PreKUnil) lacked lysine. Therefore, a new formulation of LNAAs (NeoPhe) was developed, introducing changes in the concentration of some amino acids and adding lysine, so that such a mixture could be used in humans. The new formula was found to be effective in reducing blood Phe concentration in mice by about 50% of the elevated levels. Patients with PKU were given LNAAs and blood Phe concentrations were determined in an open-label study. Three centers--in Russia, the Ukraine and the USA--took part in the study. NeoPhe was given at 0.5 g/kg per day in three divided doses to eight subjects with PKU and at 1.0 g/kg per day to three patients, for one week. The NeoPhe resulted in decrease of elevated blood Phe by 50% in both groups. The preliminary data from this study are encouraging and a double blind placebo-controlled trial will be required to show long-term efficacy and tolerance of LNAAs in the treatment of PKU.

Adolescent↗
PubMed2005

A rare case of disseminated cutaneous zoster in an immunocompetent patient.

BACKGROUND: Disseminated cutaneous herpes zoster in healthy persons is uncommon, though it has been described in immunocompromised patients. CASE PRESENTATION: We describe a case of disseminated cutaneous herpes zoster in an elderly man with no apparent immunosuppressive condition. The patient was treated successfully with intravenous Acyclovir. CONCLUSION: We suggest that disseminated zoster can occur in an immunocompetent host and should be promptly recognized and treated to prevent serious complications.

Acyclovir↗
PubMed2005

Thalidomide: dermatological indications, mechanisms of action and side-effects.

Thalidomide was first introduced in the 1950s as a sedative but was quickly removed from the market after it was linked to cases of severe birth defects. However, it has since made a remarkable comeback for the U.S. Food and Drug Administration-approved use in the treatment of erythema nodosum leprosum. Further, it has shown its effectiveness in unresponsive dermatological conditions such as actinic prurigo, adult Langerhans cell histiocytosis, aphthous stomatitis, Behçet's syndrome, graft-versus-host disease, cutaneous sarcoidosis, erythema multiforme, Jessner-Kanof lymphocytic infiltration of the skin, Kaposi sarcoma, lichen planus, lupus erythematosus, melanoma, prurigo nodularis, pyoderma gangrenosum and uraemic pruritus. This article reviews the history, pharmacology, mechanism of action, clinical uses and adverse effects of thalidomide.

Adult↗
PubMed2005

Valacyclovir for the management of herpes viral infections.

The Herpesviridae family (Types 1-8) continues to inflict considerable morbidity and social stigma upon humanity. Once infected with the herpes viruses, especially Types 1-3, they establish permanent residence within our nervous system and reactivate during periods of stress, trauma, and/or other precipitating factors. To date, there is no cure for herpes viral infections but antivirals can attenuate the symptoms and duration of episodic outbreaks. Prophylactic therapy can suppress recurrences. The first antiviral with selective activity against virus-infected cells is considered to be acyclovir. Our article will highlight the clinical indications of the current generation, valacyclovir, which is a prodrug of acyclovir. We consider valacyclovir as a second-generation antiviral, having taken into account the initial selectivity and safety profile of its progenitor, acyclovir.

Acyclovir↗
PubMed2004

Mental retardation and hypotonia seen in the knock out mouse for Canavan disease is not due to succinate semialdehyde dehydrogenase deficiency.

Canavan disease (CD) is an autosomal recessive disorder caused by aspartoacylase deficiency leading to accumulation of N-acetylaspartic acid and spongy degeneration of the brain. The mouse model for CD showed low levels of glutamate and gamma-aminobutyric acid (GABA) in the brain. Whether the low levels of glutamate and GABA observed in the CD mouse brain lead to abnormal production of glutamate-GABA associated enzymes and resulting succinate production is not obvious. While glutamate dehydrogenase and alpha-ketoglutarate dehydrogenase complex activities are lower in the cerebellum and brain stem of the CD mouse, alanine aminotransferase and succinate semialdehyde dehydrogenase (SSADH) activities and succinate level are similar to the levels observed in the wild type. Deficiency of SSADH has been suggested to be associated with mental retardation and hypotonia, similar to the clinical features of CD. The normal SSADH activity in the CD mouse brain suggests that mental retardation and hypotonia seen in the CD mouse is not due to SSADH activity and if documented also in patients with CD.

Aldehyde Oxidoreductases↗
PubMed2004

Treatment of postherpetic neuralgia.

Postherpetic neuralgia (PHN) is a serious complication of herpes zoster that has a predilection for older individuals. PHN is often associated with significant morbidity, and it can cause insomnia, fatigue, depression and interference with daily activities in affected individuals. Treatment for PHN is initiated with antivirals during the acute herpes zoster outbreak. Acyclovir (Zoviraxr, GlaxoSmithKline), valacyclovir (Valtrex, GlaxoSmithKline) or famciclovir (Famvir, Novartis) can be used to treat herpes zoster, and all three have been shown to reduce the duration of the herpetic rash and zoster-associated pain. These antivirals are most effective when used within the first 72 hours of the onset of the rash. Side-effects of these antivirals are low and include nausea, vomiting, abdominal pain and headache. Other treatment options for PHN include topical analgesics, opioid analgesics, tricyclic antidepressants and gabapentin. Because of the complexity of PHN, most patients require a combination of treatment modalities for adequate pain relief.

2-Aminopurine↗
PubMed2003

Clinical aspects of epidermodysplasia verruciformis.

Thirteen patients with epidermodysplasia verruciformis (EV) were studied over a period of 7 years. EV is a rare genodermatosis characterized by a generalized infection with a specific group of human papilloma virus (HPV) and a propensity for developing skin malignant tumours in 30%-50% of patients. The diagnosis of EV was confirmed by histopathological and immunohistochemical findings. Three of our patients had the benign form of EV, which is characterized by monomorphous lesions and no malignant changes, whereas 10 had the malignant form, which is characterized by polymorphic lesions and development of cutaneous malignant tumours. All EV patients with the malignant form developed multiple skin tumours (77%). They started to appear at age 20, predominantly on the forehead (50%). Most were squamous cell carcinoma, extremely aggressive and invasive, which provoked metastasis and death in two patients.

Adolescent↗
PubMed2001

Malonyl CoA decarboxylase deficiency: C to T transition in intron 2 of the MCD gene.

Malonyl CoA decarboxylase (MCD) is an enzyme involved in the metabolism of fatty acids synthesis. Based on reports of MCD deficiency, this enzyme is particular important in muscle and brain metabolism. Mutations in the MCD gene result in a deficiency of MCD activity, that lead to psychomotor retardation, cardiomyopathy and neonatal death. To date however, only a few patients have been reported with defects in MCD. We report here studies of a patient with MCD deficiency, who presented with hypotonia, cardiomyopathy and psychomotor retardation. DNA sequencing of MCD revealed a homozygous intronic mutation, specifically a -5 C to T transition near the acceptor site for exon 3. RT-PCR amplification of exons 2 and 3 revealed that although mRNA from a normal control sample yielded one major DNA band, the mutant mRNA sample resulted in two distinct DNA fragments. Sequencing of the patient's two RT-PCR products revealed that the larger molecular weight fragments contained exons 2 and 3 as well as the intervening intronic sequence. The smaller size band from the patient contained the properly spliced exons, similar to the normal control. Western blotting analysis of the expressed protein showed only a faint band in the patient sample in contrast to a robust band in the control. In addition, the enzyme activity of the mutant protein was lower than that of the control protein. The data indicate that homozygous mutation in intron 2 disrupt normal splicing of the gene, leading to lower expression of the MCD protein and MCD deficiency.

Base Sequence↗
PubMed2001

Human papillomavirus, smoking, and cancer.

BACKGROUND: The effect of smoking on human papillomavirus (HPV) activity and subsequent dysplasia and neoplasia remains controversial. OBJECTIVE: To determine any reported effects of smoking on either HPV activity or HPV-related dysplasia/cancer using retrospective analysis of the literature from 1966 through 1998 via Toxline and PubMed to search for "smoking," "papillomavirus," and "cancer." CONCLUSION: Several recent large studies demonstrated that smoking was associated with a greater incidence of cervical, vulvar, penile, anal, oral, and head and neck cancer in a dose-dependent fashion, while other studies did not show any correlation between smoking and cervical dysplasia after multivariate adjustment. Recent studies have also indicated that smoking may be more closely related to high-grade lesions of the cervix and vulva. These data provide evidence of an association between HPV, smoking, and cancer. Progression of dysplasia likewise seems to be associated with smoking. Several groups have attempted to discern whether the connection between smoking and cervical cancer is from local immunosuppression and/or from direct carcinogenic effects.

Anus Neoplasms↗
PubMed2001

Application of a topical immune response modifier, resiquimod gel, to modify the recurrence rate of recurrent genital herpes: a pilot study.

Resiquimod (R-848), a topically active immune response modifier, induced production of interferon-alpha and interleukin-12 in cultured blood mononuclear cells and decreased genital herpes recurrences in an animal model. In this study, 52 patients with frequently recurrent genital herpes applied topical resiquimod gel 0.01% (twice or thrice weekly) or 0.05% (once or twice weekly) or vehicle gel to herpes lesions for 3 weeks. During the 6-month observation period after treatment, median days to first recurrence in the pooled resiquimod group was 169 days, compared with 57 days for the vehicle group (P=.0058). In all, 32% of resiquimod-treated patients completed the observation period without a recurrence, compared with 6% of vehicle-treated patients (P=.039). Resiquimod 0.05% twice weekly produced dose-limiting inflammation at the lesion sites, but the other regimens were well tolerated. Application of resiquimod to genital herpes lesions appeared to reduce the frequency of recurrences.

Adult↗
PubMed2001

Molecular diagnosis of skin-associated infectious agents.

Molecular pathology is a relatively new division of laboratory medicine that detects, characterizes, and/or quantifies nucleic acids to assist in the diagnosis of human disease. Molecular assays augment classic areas of laboratory medicine by providing additional diagnostic data more quickly or by providing results that are not obtainable using standard methods. For these reasons, molecular pathology is the most rapidly growing area in laboratory medicine.

Genetic Markers↗
PubMed2001

Antiviral agents.

The potential severity of many viral infections and the lack of appropriate treatment for these diseases have been a source of endless frustration and helplessness for clinicians. The newly developed field of antiviral therapy is expanding at an astounding rate, with new discoveries each day. Although physicians are not yet able to cure many of the viral infections, such as HSV, HIV, and CMV, a means of controlling them is available. It is hoped that the research and investigations currently under way will lead to a future era of antiviral drugs that will be able to eradicate these diseases.

AIDS-Related Opportunistic Infections↗
PubMed2001

Advances in HIV treatment and treatment toxicities.

Among the different classes and complexities of antiretroviral regimens, maximal viral suppression, sustained durability, increased CD4 count, decreased evolving resistance, and fewer side effects combined with increased compliance resulting in decreased morbidity and mortality remain the goals of therapy. Serial viral load measurements help best guide the direction of therapy. According to the CDC 20% fewer people died of HIV in 1998 compared to 1997 in the United States. HAART, although expensive (sometimes exceeding $20,000 per year), is not readily available to 95% of the estimated 36 million HIV-infected people in the world. HAART therapy commonly consists of two NRTIs and a protease inhibitor, but other combination regimens exist. The disadvantage of HAART therapy is that antiretroviral agents are not virucidal, thus eradication with these drug cocktails cannot be achieved. When HAART therapy is stopped, viral loads return to pre-treatment levels. New drug classes under investigation may completely prevent fusion between the HIV virus and healthy cells. For now, the epidemic can only be controlled with good public awareness, such as education, condom use, or abstinence. Because a cure does not seem immediately foreseeable, an effective prophylactic vaccine may afford protection. Defined treatment regimens exist for occupational postexposure prophylaxis. Ultimately, an expert in the field should be involved in manipulating drug regimens; however, dermatologists remain an integral part of the health care team because most HIV patients experience cutaneous manifestations related either to their HIV or to their drug therapy.

Anti-HIV Agents↗
PubMed2001

Prophylactic and therapeutic vaccines for genital papillomavirus infection.

The development of potential therapeutic and prophylactic vaccines for human papillomavirus (HPV) infection is a very exciting area of HPV research. There are a number of features of HPV biology that makes the development of a vaccine particularly difficult, although there are several examples of vaccines that have had spectacular success in the prevention of other viral diseases. Our poor understanding of the immune response to HPV infection is the first problem. We do not understand the mechanism by which spontaneous clearing of warts is generated and therefore cannot particularly target this pathway in the development of a vaccine. Furthermore, there is no in vitro culture system nor an animal model for HPV. Another problem is that there is no ready source of live virus that might be exploited for a live attenuated viral vaccine, such as was used with poliovirus. Although most other viruses spend a portion of their life cycle in the systemic circulation where they are vulnerable to neutralizing antibodies, HPV remain exclusively in the epithelium and thus antibodies must transverse the basement membrane and reach the other layers of the skin or mucosa to be effective in preventing infection. Significant progress is being made in the development of potential vaccine candidates despite these and other confounding factors.

Animals↗