Erythema induratum of Bazin as a tuberculid: confirmation of Mycobacterium tuberculosis DNA polymerase chain reaction analysis.
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Biomedical subjects
Publications and source records attributed to S Tyring.
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OBJECTIVE: To determine the effect of acyclovir and prednisone treatment of herpes zoster on chronic pain and quality-of-life outcomes. DESIGN: Randomized, double-blind, placebo-controlled study with a 2 x 2 factorial design. SETTING: 15 university hospitals or affilliated clinics. PATIENTS: 208 immunocompetent patients older than 50 years of age who had localized herpes zoster that developed less than 72 hours before study enrollment. INTERVENTION: Acyclovir or a matched placebo was administered orally, 800 mg five times daily, for 21 days. Prednisone or a matched placebo was administered orally at 60 mg/d for the first 7 days, 30 mg/d for days 8 to 14, and 15 mg/d for days 15 to 21. The four treatments regimens given were acyclovir plus prednisone; acyclovir plus prednisone placebo; prednisone plus acyclovir placebo; and placebos for both acyclovir and prednisone. MEASUREMENTS: Patients were monitored daily for the first 28 days for lesion healing, resolution of pain, return to usual activity, and return to uninterrupted sleep. Monitoring was then done monthly for 6 months. Patients documented analgesic requirements each day, and adverse events and laboratory abnormalities were recorded at each clinical visit. An intention-to-treat analysis was used. RESULTS: Patients were randomly allocated to receive one of the four regimens. Demographic characteristics were similar for each group. Time to total crusting and healing was accelerated for patients receiving acyclovir plus prednisone compared with patients receiving two placebos; the risk ratios were 2.27 (95% Cl, 1.46 to 3.55) for total crusting and 2.07 (Cl, 1.26 to 3.38) for healing. Similarly, compared with the placebo group, patients receiving acyclovir plus prednisone had accelerated time to cessation of acute neuritis (risk ratio, 3.02 [Cl, 1.42 to 6.41]), time to return to uninterrupted sleep (risk ratio, 2.12 [Cl, 1.25 to 3.58]); time to return to usual daily activity (risk ratio, 3.22 [Cl, 1.92 to 5.40]); and time to cessation of analgesic therapy (risk ratio, 3.15 [Cl, 1.69 to 5.89]). In the acyclovir plus prednisone group, resolution of pain during the 6 months after disease onset did not statistically differ from that in the other groups. No important clinical or laboratory adverse events occurred in any group. CONCLUSIONS: In relatively healthy persons older than 50 years of age who have localized herpes zoster, combined acyclovir and prednisone therapy can improve quality of life.
OBJECTIVE: To document the effects of treatment with famciclovir on the acute signs and symptoms of herpes zoster and postherpetic neuralgia. DESIGN: A randomized, double-blind, placebo-controlled, multicenter trial. SETTING: 36 centers in the United States, Canada, and Australia. PATIENTS: 419 immunocompetent adults with uncomplicated herpes zoster. INTERVENTION: Patients were assigned within 72 hours of rash onset to famciclovir, 500 mg; famciclovir, 750 mg; or placebo, three times daily for 7 days. MEASUREMENTS: Lesions were assessed daily for as long as 14 days until full crusting occurred and then weekly until the lesions healed. Viral cultures were obtained daily while vesicles were present. Pain was assessed at each of the visits at which lesions were examined and then monthly for 5 months after the lesions healed. Safety was assessed throughout the study. RESULTS: Famciclovir was well tolerated, with a safety profile similar to that of placebo. Famciclovir accelerated lesion healing and reduced the duration of viral shedding. Most importantly, famciclovir recipients had faster resolution of postherpetic neuralgia (approximately twofold faster) than placebo recipients; differences between the placebo group and both the 500-mg famciclovir group (hazard ratio, 1.7 [95% CI, 1.1 to 2.7]) and the 750-mg famciclovir group (hazard ratio, 1.9 [CI, 1.2 to 2.9]) were statistically significant (P = 0.02 and 0.01, respectively). The median duration of postherpetic neuralgia was reduced by approximately 2 months. CONCLUSIONS: Oral famciclovir, 500 mg or 750 mg three times daily for 7 days, is an effective and well-tolerated therapy for herpes zoster that decreases the duration of the disease's most debilitating complication, postherpetic neuralgia.
Polymerase chain reaction (PCR) buffers were optimized for the specific detection of human papillomavirus (HPV) sequences. The effect of pH, potassium chloride concentration and magnesium chloride concentration of three different consensus primers were examined. Several phylogenetically distinct HPVs (HPV1, HPV2, HPV6, HPV8, HPV16, HPV18, and HPV20) were used to determine the optimal buffer components. Genital types were less sensitive to changes in pH than cutaneous types. Higher buffer pH, with a few exceptions, led to increased sensitivity and specificity of HPV detection.
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CMV-transformed cell lines demonstrated a greater level of H-ras RNA (7.5- to 9.5-fold) relative to the level for H-ras in parental cells. Nuclear run off assays showed that the RNA levels for the H-ras gene were regulated at the level of transcriptional initiation. The increased RNA levels for H-ras correlated with the level of p21rasVal-12 in transformed cells, while p21rasVal-12 was below the level of detection in nontransformed cells using Western blot analysis. In addition, an activating mutation was identified in both alleles of the first exon, codon 12 of H-ras resulting in a G:C to T:A transversion in all transformed cell lines examined in this study. These results suggest that the mutated H-ras may be one of the components by which an oncogenic phenotype is maintained in these CMV-transformed cells.
Immunohistochemical assays for human papillomavirus (HPV) L1 protein, using antiserum directed against the L1 major capsid protein of bovine papillomavirus (anti-BPV serum), were performed on 101 condylomata acuminata biopsy samples from 47 men (40 of whom had intact cell mediated immunity [CMI], and 7 with conditions known to cause CMI defects), and 54 women (48 with normal CMI, and 6 with CMI defects). L1 protein was detected in 28% of all biopsies, including 20.5% of samples from patients with normal CMI and 76.9% of patients with CMI defects (P = .00002). For both males and females, L1 protein was detected significantly more often in samples from patients with CMI defects than those with normal CMI. Immunohistochemical assays of HPV 11-infected human foreskin implants grown in athymic mice were performed to optimize the conditions of the assay. Three dilutions of anti-BPV serum or preimmune rabbit serum were used. A 1:500 dilution provided readily interpretable results, while preimmune serum at this dilution did not stain to any significant degree. However, at 1:10 and 1:100 dilution, both the anti-BPV serum and preimmune serum caused an unacceptable amount of nuclear staining, making results uninterpretable. Defects in CMI may allow active viral particle assembly at an increased rate, as judged by detection of L1 protein in condylomata acuminata from these patients.
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BACKGROUND AND DESIGN: Intralesional recombinant interferon alfa-2b has been shown to be effective in the treatment of actinic keratoses and basal cell carcinomas. This open-label study was designed to evaluate the effectiveness and cosmetic result of this therapy on actinically induced, primary cutaneous squamous cell carcinomas. Thirty-six squamous cell carcinomas (28 invasive lesions and 8 in situ lesions) ranging in size from 0.5 to 2.0 cm in the longest dimension were treated with interferon alfa-2b 1.5 million units injected intralesionally three times per week for 3 weeks. Eighteen weeks following therapy, the treatment sites were excised and examined for histologic evidence of remaining tumor. RESULTS: Thirty-three (97.1%) of 34 evaluable lesions revealed an absence of squamous cell carcinoma histologically after therapy, although three biopsy specimens (8.8%) obtained after treatment showed actinic keratoses, for an overall complete response rate of 88.2%. The lesion not eliminated after treatment was an invasive squamous cell carcinoma. The investigators and patients independently judged 93.9% of cases to have a very good or excellent cosmetic result. Adverse reactions were limited to those influenzalike symptoms well recognized to occur with interferon therapy and these were well tolerated. Only one patient discontinued therapy due to side effects. CONCLUSIONS: This trial demonstrates that intralesional interferon is effective in the treatment of small sun-induced squamous cell carcinomas with well-tolerated side effects and a highly acceptable cosmetic result.
A molecular form of soluble suppressor factor was identified in serum-free supernatant fluid of cultured peripheral blood mononuclear cells (PBMC) from patients with severe forms of papillomavirus infections (epidermodysplasia verruciformis and large treatment-resistant condyloma acuminatum). The papillomavirus-induced soluble suppressor factor (SSF-H) was highly purified by gel filtration, anion-exchange chromatography, chromatofocusing, hydrophobic chromatography, and nondissociating polyacrylamide gel electrophoresis (PAGE). The factor exhibited an apparent molecular weight of 67 kDa as determined by sodium dodecylsulfate-PAGE. The isoelectric point ranged from 4.8 to 5.2 as judged by chromatofocusing. The biologic activity of the SSF-H during purification and in subsequent characterization was examined by in vitro CTLL bioassay. Purified SSF-H was stable at 56 degrees C for 1 h and in the pH range of 4.0 to 8.0. Complete inactivation was observed at 80 degrees C. Trypsin and proteinase K treatment destroyed the biologic activity associated with purified SSF-H. This factor seems to be different in its molecular weight and other physicochemical properties from the known suppressor factors that affect lymphocyte functions.
A case of epithelioid hemangioendothelioma presenting as violaceous nodules on the skin of the thigh is described. On histologic examination the tumor exhibited a proliferation of vascular channels lined by plump cuboidal and atypical endothelial cells with an epithelioid appearance. Lesions of epithelioid hemangioendothelioma were subsequently discovered in the adjacent femur. These tumors were successfully treated with chemotherapy and irradiation followed by a limb salvage procedure. To our knowledge, cutaneous presentation of this rare tumor has not been reported previously.
In evaluating patients we have noted disparity between the locations of bound immunoreactants and the level of blistering in epidermolysis bullosa acquisita (EBA). We examined 10 consecutive EBA patients by routine histology, direct (DIF) and indirect (IIF; intact and NaCl-split skin) immunofluorescence, immunofluorescence mapping (IM), and/or direct immunoelectron microscopy (DIEM). DIF was positive in each. IIF was positive in 3/8 and 6/7 patients when intact and split skin were used as substrates. DIEM revealed immunoreactants within the lamina densa (LD) in 6/10, sub-LD in 1/10, and both LD and sub-LD in 3/10 patients. In contrast, by DIEM and IM, blister formation was noted within the lamina lucida (LL) in 7/9 and 8/10, sub-LD in 1/9 and 1/10, and within both LL and sub-LD in 1/9 and 1/10, respectively. In the presence of neutrophils within the upper dermis (n = 6), cleavage occurred within the LL in 5 specimens; in one additional specimen containing predominantly neutrophils, cleavage occurred within both LL and sub-LD. In the presence of mononuclear cells (n = 2), intra-LL cleavage occurred. In the presence of eosinophils, cleavage occurred within both LL and sub-LD. In the one specimen lacking any infiltrate, the cleavage plane was exclusively sub-LD. Intra-LL cleavage planes are more common than sub-LD ones in at least early cases of EBA. These findings likely represent the intra-LL-separating effect of leukocyte-derived proteolytic enzymes, when such cells are chemoattracted to the dermoepidermal junction by bound immuno-reactants.
STUDY OBJECTIVE: To determine the efficacy and toxicity of intralesionally administered interferons in the treatment of condyloma acuminatum. DESIGN: Randomized, double-blind, and placebo-controlled study. SETTING: Outpatient clinics at university medical centers. PATIENTS: Seventy-nine patients with biopsy-proved condyloma acuminatum that was refractory to conventional therapy were enrolled in the study. INTERVENTIONS: Alpha-2b, alpha-nl-, and beta-interferons were used. One wart on each patients was injected three times per week for 4 weeks with either 1 x 10(6) units of interferon or placebo. MEASUREMENTS AND MAIN RESULTS: Forty-seven percent of warts injected with interferon resolved completely, compared with 22% of placebo-injected warts (P = 0.009). In addition, more recipients of interferon had a complete resolution of uninjected lesions. No differences in rates of response were noted among the different interferon groups. Approximately one third of interferon-injected warts recurred, compared with none of four placebo-injected warts. Intralesionally administered interferon was nontoxic and well tolerated, although transient pain on injection was observed frequently. CONCLUSIONS: Intralesional administration of each of these three interferons appears to be useful in treating condyloma acuminatum. However, the frequent recurrence of disease and the failure of many lesions to resolve indicate that different regimens, such as longer courses of therapy or different routes of administration, should be evaluated to maximize beneficial effects of interferon for treating this common sexually transmitted disease.
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Mouse IFN gamma preparations purified 30-fold were found to have direct cytolytic activity against a number of tumor and normal cells. Cell killing was determined using a sensitive, rapid and accurate assay which employed very low numbers of cells and very small quantities of interferon. The cytolytic activity of IFN gamma on 11 murine tumor cell lines was investigated. A 20-fold difference was found between the most-sensitive cell type, P-388 lymphoma, versus the most resistant cell type, C127v leukemia. A number of normal mouse cells was also found to have low to intermediate sensitivity to the cytolytic action of IFN gamma. Human IFN gamma was also shown to have cytolytic activity which, like mouse IFN gamma, was relatively species-specific. Direct cytolysis was not found to be a characteristic of IFN-alpha/beta. Different mechanisms of action for the antiviral and cytolytic activities of IFN gamma are indicated because the cytolytic titer of IFN gamma did not parallel its antiviral titer on most cell types and increasing the cell number produced a decrease in the cytolytic titer and an increase in the anti-viral titer. High concentrations of IFN gamma (i.e., 2,900 units/ml) resulted in complete lysis of cells within 24 h, while lower concentrations (i.e., 700 units/ml) resulted in a reversible inhibition of cell growth during this time period. Evidence that the cytolytic substance in the IFN gamma preparation was IFN gamma include the following: (1) both antiviral and anticellular activities copurified through a 30-fold purification; and both activities were (2) relatively species-specific; (3) sensitive to heat; (4) inactivated by low pH and (5) neutralized by antibodies to IFN gamma. Therefore, we propose the possibility that direct cytolysis is yet another of IFN gamma's distinctive antivities.
The effects of ethanol alone or combined with pyrazole or disulfiram were studied in reference to interferon production. Saline, ethanol (2 g/kg), pyrazole (2 mg/kg), or disulfiram (2 mg/kg) were injected, intraperitoneally, 3 hr after poly I:C, an interferon inducer. Drugs were administered either by a single injection, or twice daily for 7 days, and the mice were sacrificed 6 hr after poly I:C. Sera from mice were pooled, dialyzed, and assayed for interferon by the microplaque reduction method. Administration of ethanol alone reduced interferon production 76% and 66% after the single and the multiple injections, respectively. A similar inhibition of interferon occurred after either pyrazole or disulfiram, with a greater potency for pyrazole. Treatment with pyrazole prior to ethanol reduced interferon production further, but only after the 7-day schedule. All drugs tested affected cellular immunity as measured by interferon production. Moreover, reduced interferon production by these agents was associated with a loss of splenic lymphoid tissue, suggesting that ethanol, pyrazole, and disulfiram could affect susceptibility to viral infection.
In a recently published study, the coexistence of HPV and MCV was demonstrated for the first time in the same molluscum contagiosum lesions from a single patient. Such a finding raises many questions in the understanding of both HPV and MCV. With this finding comes the potential of new treatments against dually infected MC lesions, which normally demonstrate high resistance to therapy. Furthermore, the finding of HPV and MCV coexistence raises questions on the effects of MCV immunosuppressive genes on HPV. For these reasons, further analysis was performed on a larger series of MC specimens for the rates of HPV and MCV coinfection within the same lesions. This study differed from the previous one on this subject in its use of cutaneous, rather than mucosal, lesions. The methods used in this study were identical to those which were previously employed; in situ hybridization was utilized using HPV probes, and was followed by histologic examination with hematoxylin-eosin stain. The results of this study did not identify coexistence of HPV and MCV in any of the collected MC specimens. These findings are in contrast to the previous study and suggest that, although HPV and MCV coexistence may occur, such coinfections are extremely rare in cutaneous tissue.