The Presence of HLA-A Bw4-80I KIR Ligands Could Predict "Difficult-to-Treat" Psoriasis and Poor Response to Etanercept.

BACKGROUND: Psoriasis is an immune-mediated dermatosis with a wide genetic predisposition. The immunogenetic background, specifically interactions between human leukocyte antigen (HLA) class I ligands and killer-cell immunoglobulin-like receptor (KIRs), have functional significance in modulating natural killer (NK) cells and can influence susceptibility and response to biological therapy. OBJECTIVE: The main aim of this study was to correlate HLA-A and -B KIR ligands with response to biological therapy in patients with psoriasis. METHODS: HLA-A and -B polymorphisms were determined in 48 patients (35 males and 13 females), with a mean of 22 years of disease (range 8-55). All patients were treated with biological therapy (adalimumab, etanercept, infliximab, or ustekinumab) for at least 6 months. RESULTS: This study identifies, with statistical significance, the presence of at least one ligand HLA-A Bw4-80I in the "poor-responder" population (patients who needed two or more biologics) compared with the "responder" population (patients with good response after a single biological drug) (47.62 vs. 11.11%; p = 0.006) as well as in "non-responders to etanercept" compared with "responders to etanercept" (52.63 vs. 5%; p = 0.001). CONCLUSION: Our preliminary results suggest that at least one ligand HLA-A Bw4-80I could be associated with "difficult-to-treat" psoriasis and that this ligand may reduce the probability of response to etanercept, producing more tumor necrosis factor (TNF)-α and neutralizing NK activity through a predominance of activating KIR. The ab initio identification of genetic markers of response to biologic therapy could improve the efficacy and economic impact of these agents.

Population-based enrolment of adolescents in a long-term follow-up trial of human papillomavirus vaccine efficacy.

We evaluated a study setting for assessment of the long-term vaccine efficacy (VE) of human papillomavirus (HPV) virus-like-particle (VLP) vaccine against cervical carcinoma. A total of 22,412 16- to 17-year old adolescent women from seven cities in Finland were invited by letter to participate in a phase III study of a quadrivalent HPV (types 6, 11, 16, 18) VLP vaccine, between September 2002 and March 2003. A total of 30,947 18-year old women were invited to participate as unvaccinated controls. These women were asked about their willingness to participate in an HPV vaccination trial and to fill a health questionnaire. These three population-based cohorts of adolescent women, including women vaccinated with HPV vaccine or placebo vaccine and unvaccinated control women, are systematically followed over time. The study cohort database will be linked with the Finnish Cancer Registry using cervical carcinoma in situ (CIS) and invasive cervical carcinoma (ICC) as endpoints. Assuming that the cumulative incidence of CIS and ICC over 15 years is 0.45%, and that there is no loss to follow-up, and power of 80%, the determination of 70% total VE will require 3357 HPV vaccine recipients, 3357 placebo vaccine recipients, and 6714 unvaccinated controls. At the baseline, 2632 (12%) of the invited adolescents volunteered to the phase III vaccination trial, and 6790 (22%) responded to the questionnaire study. During a recruitment period of 10 months, 874 HPV vaccine recipients, 875 placebo recipients and 1919 unvaccinated controls were enrolled. Population-based enrollment of large cohorts of vaccinated and unvaccinated adolescents for passive registry-based follow-up with cervical carcinoma as the end-point is feasible and currently going on in Finland.

[Episodic headache, diminished performance and depressive mood]. / Episoden von Kopfschmerzen, Leistungsabfall und depressiver Verstimmung.

By the example of two case reports, typical signs of caffeine withdrawal like headache, increased irritability, decreased performance and disturbed concentration are described. These symptoms occurred two times within one week in two healthy nonsmoking individuals volunteering in a scientific study including periods of 24 hours with standardized caffeine-free-diet. The two volunteers were used to a regular coffee consumption of eight cups per day (about 600 mg/day). Since caffeine obviously represents the most common psycho-stimulant worldwide and since even moderate coffee consumption may lead to dependence, withdrawal symptoms induced by sudden reduction of consumption or withdrawal of caffeine may occur more often than usually assumed.

Positron emission tomography in clinical practice.

Positron emission tomography (PET) has been considered a research tool; however, advances in hardware and software, along with availability of small medical cyclotrons, make clinical metabolic imaging feasible. There is accumulating data, especially in the areas of neurology and cardiology, to support its use in the appropriate clinical setting and patient population.

[Five years experience with infra-inguinal arterial reconstruction: a comparison of venous with PTFE bypass]. / Fünf Jahre Erfahrung mit infrainguinaler Arterienrekonstruktion: Ein Vergleich des Venen- mit dem PTFE-Bypass.

Since January 1983 one surgeon of our team has performed 200 infrainguinal arterial reconstructions. Our patients had a mean age of 72 years and suffered from multiple concomitant diseases (coronary heart disease 35%, cerebro-vascular insufficiency 15%, hypertension 49% and diabetes mellitus 34%). The indication for arterial reconstruction was a chronic critical ischemia in every case. 154 autologous veins and 46 PTFE prosthesis had to be implanted. The former consisted in 64% in a femoropopliteal and in 35% femorodistal bypass graft; respective values of the latter group were 80% and 20%. The cumulative survival rates of two collectives were nearly identical. More than 50% of our patients died in the 4 years observation period. The life table patency rates differed statistically significant (p less than 0.001). The cumulative 5 year patency amounted to 85% in case of a vein graft and to 43% if a PTFE prosthesis was inserted. Extremely poor results were achieved in case of a PTFE prosthesis with a distal anastomosis to a single crural artery; just one out of 6 procedures was successful after two years.

Activity of ciprofloxacin against Mycobacteria in vitro: comparison of BACTEC and macrobroth dilution methods.

Various clinical isolates of mycobacteria were tested for susceptibility to ciprofloxacin by a standard macrobroth dilution test and the radiometric BACTEC method. Agreement between the two test systems was species dependent: Mycobacterium tuberculosis (80%), M. kansasii with M. scrofulaceum (30%), M. avium-intracellulare (20%), and 0% for the rapidly growing mycobacteria. Most mycobacterial strains other than M. tuberculosis were susceptible to the breakpoint ciprofloxacin concentration of 2 mg/l as determined by BACTEC MICs, whereas none were susceptible by macrobroth testing. Seven of nine M. tuberculosis isolates were susceptible by either method. Ciprofloxacin merits further study as a potential antimycobacterial agent.

Activity of amikacin against Mycobacteria in vitro and in murine tuberculosis.

Amikacin was found to be a potent inhibitor of clinical isolates of Mycobacterium tuberculosis in vitro. The drug was also active against some, but not all, strains of M. intracellulare, M. kansasii and rapidly growing mycobacteria in concentrations that may be attained clinically. Activity was independent of susceptibility or resistance of the isolates to commonly used antituberculosis agents. Groups of mice were infected intravenously with M. tuberculosis H37Rv and then treated daily with amikacin, streptomycin, isoniazid or kanamycin. One third of the mice in each group were killed 30, 60 and 90 days after infection. Extent of pulmonary disease was recorded and tubercle bacilli were enumerated in lungs. Isoniazid eradicated tubercle bacilli from the lungs within 90 days. The remaining drugs were suppressive. Amikacin was more efficacious than streptomycin or kanamycin given in equivalent or greater dosages. Because of its potent activity in vitro, efficacy in experimental tuberculosis and activity against drug resistant mycobacteria, amikacin merits further study as a potential therapeutic agent for tuberculosis and other mycobacterial infections.

Susceptibility of organisms in the Mycobacterium fortuitum complex to antituberculous and other antimicrobial agents.

Of 21 antimicrobial agents tested in vitro, amikacin was the most predictably active against clinical isolates belonging to the Mycobacterium fortuitum complex; however, only 50% of strains studied were susceptible to clinically attainable concentrations of the drug.