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Ustekinumab is a fully human anti-p40 monoclonal antibody which neutralizes interleukin (IL)-12 and IL-23, thereby interfering with T-helper (Th)1/Th17 pathways and keratinocyte activation, and is highly effective in the treatment of psoriasis. During ustekinumab treatment, some of our patients noticed reduced koebnerization of noninvolved skin and less new plaque formation.To determine whether ustekinumab improves psoriasis-related gene expression and tape-strip responses in noninvolved skin.Before and 4 weeks after ustekinumab treatment, noninvolved skin was tape-stripped. After 5 h, biopsies were taken from untouched and tape-stripped skin. The mRNA expression of psoriasis-related markers such as NGF, GATA3 and IL-22RA1, and several antimicrobial peptides (AMP) was quantified. Leucocyte counts and a broad range of inflammatory serum proteins were analysed to gain insight into the systemic alterations.Four weeks following a single ustekinumab injection, NGF showed a significant decrease, whereas GATA3 and IL-22RA1 expression increased, indicative of reduced responsiveness to epidermal triggering. This was accompanied by an increase of the inflammation-related serum proteins GPNMB, MST1 and TRADD. The baseline and tape-strip-induced mRNA expression of the AMP human β-defensin-2 (hBD-2), S100A7 and LL-37 remained unaltered. Clinically, after 4 weeks, eight out of 11 patients showed a 50% psoriasis area and severity index (PASI) improvement, which was accompanied by a significant reduction in serum hBD-2 levels. No changes were noted in total leucocytes, C-reactive protein and erythrocyte sedimentation rate.These findings indicate that ustekinumab reduces psoriasis-related gene expression in noninvolved psoriatic skin, making it more resistant to exogenous triggering, without disturbing its antimicrobial response. In parallel, ustekinumab modulates important circulating inflammation-related proteins.

To investigate the effects of replacing a portion of endurance training by strength training on exercise performance, 14 competitive cyclists were divided into an experimental (E; n=6) and a control (C; n=8) group. Both groups received a training program of 9 weeks. The total training volume for both groups was the same [E: 8.8 (1.1) h/week; C: 8.9 (1.7) h/week], but 37% of training for E consisted of explosive-type strength training, whilst C received endurance training only. Simulated time trial performance (TT), short-term performance (STP), maximal workload (\(\dot W_{{\rm max}} \)) and gross (GE) and delta efficiency (DE) were measured before, after 4 weeks and at the end of the training program (9 weeks). No significant group-by-training effects for the markers of endurance performance (TT and \(\dot W_{{\rm max}} \) ) were found after 9 weeks, although after 4 weeks, these markers had only increased (P

Objective: This study was undertaken to assess frequencies of the methylenetetrahydrofolate reductase gene mutations cytosine-to-thymine substitution at base 677 (C677T) and adenine-to-cytosine substitution at base 1298 (A1298C) and their interactions with homocysteine and vitamin levels among Dutch women with preeclampsia. Study Design: Mutations were studied in the following 5 groups: 47 consecutive women with preeclampsia, 49 women with preeclampsia and with hyperhomocysteinemia, 36 women with preeclampsia but without hyperhomocysteinemia, 127 women with familial preeclampsia (typed for C677T mutations only), and 120 control subjects. Plasma levels of homocysteine, folate, and vitamin B 12 were measured. Results: Although 10.6% of the consecutive women with preeclampsia had strictly defined hyperhomocysteinemia (values >97.5th percentile), neither mutation was found in excess relative to the control group. Women with preeclampsia who had mild hyperhomocysteinemia (values >75th percentile) had a significant excess of the TT genotype (homozygosity for C677T mutation) relative to the women with preeclampsia who did not have hyperhomocysteinemia (odds ratio, 8.2; 95% confidence interval, 1.8-39). They also had significantly lower vitamin levels. Conclusion: Hyperhomocysteinemia in women with preeclampsia was associated with mutations in the gene for methylenetetrahydrofolate reductase, but the high frequency of hyperhomocysteinemia itself cannot be explained by these mutations alone. (Am J Obstet Gynecol 2001;184:394-402.)

The present study was undertaken to determine whether there were any differences in the distribution of hepatitis B virus-(HBV) associated serologic markers among hepatitis B surface antigen-(HBsAg) positive first-time and repeat blood donors. The markers examined in samples from 412 newly identified HBsAg-positive donors (254 first-time and 158 repeat) included HBsAg titer and subtype, HBeAg/anti-HBe, and anti-HBc. Repeat donors were more frequently HBeAg-positive (25.9%) than were first-time donors (17.7%). Anti-HBc and anti-HBe were observed more often among first-time (99.6 and 76%) than repeat (91.8 and 60.8%) donors. No differences were found in the mean HBsAg titer nor in the subtype distribution in the two populations. The frequency of HBeAg positivity and the mean HBsAg titer in blood were significantly lower among first-time donors aged 30 or older as compared to those younger than 30. Such age-related tendencies did not occur among the repeat donors. The profiles of HBV makers suggest that the HBsAg-positive first-time donor group consists predominantly of long-term HBsAg carriers who may have acquired HBV at an early age, while the HBsAg-positive repeat donors have newly acquired infections.

From January 1975 to December 1978, 19,140,169 units of blood were collected by the American Red Cross at 57 regional locations. Each unit was tested for hepatitis B surface antigen (HBsAg) by a single commercial radioimmunoassay test system. A total of 15,954 donations were reported reactive, representing a rate of HBsAg reactivity of 0.83/1,000 units tested. The rate during 1975 was 0.94/1,000 units tested, decreasing to 0.71/1,000 units tested in 1978 (p0.005). The prevalence of HBsAg among first-time donors was 2.08/1,000 during 1977 and 1978, 2.7 times higher than that calculated for repeat donors (0.77/1,000 donors). Substantial geographic variation in the prevalence and rate of detection of HBsAg was observed.

Traumatizing events and traumatizing conflicts may lead to defense mechanisms which in the course of time become part of character formation. In psychosomatic medicine much attention has been paid in the past to the so-called psychosomatic character profiles. Though discussions about psychosomatic specificity have remained controversial, it still seems advisable to take into account the power of induction of specific defense strategies. In this paper special attention is paid to the fact that asthmatics, patients suffering from hypertension or coronary heart disease, as well as patients suffering from other psychosomatic syndromes, and even patients suffering from carcinoma may induce their own defense strategies in interviewers and therapists, who usually are not sufficiently aware of the fact of such transference phenomena. A distortion of the normal psychotherapeutic process is more often a result of induction processes than has been thought of.

A new antigenic specificity for HBsAg is described, and its usefulness as an epidemiological marker is discussed. This specificity, l, was found in specimens from all geographic areas studied (United States, Latin America, South Africa, the Solomon Islands, and New Guinea). In these areas, l was strongly associated with HBsAg/ay; y-positive, l-negative samples were observed only among specimens from United States volunteer blood donors. This determinant allowed a distinction of HBsAg/ad classes. Thus, the l determinant was detected in 51.4% of HBsAg/adw4, 44.1% of HBsAg/adw(non-w4), and 50% of HBsAg/adr. The association of l and other HBsAg determinants with HBeAg or anti-HBe was also investigated. HBeAg was found to be associated with the presence of the l determinant and with the r determinant. Anti-HBe was associated with the presence of the d and w determinants and with the absence of the l specificity.

During the year 1978 this laboratory evaluated the specificity of all samples found reactive for hepatitis B surface antigen (HBsAg) by 44 of 57 regions of the American Red Cross Blood Services. Radioimmunoassay detected a total of 1.921 HBsAg-reactive sampled among more than three million donor units tested. A vast majority (96%) of the samples had high level of HBsAg (greater than or equal to 20 ng/ml). Only about 50% of the samples with low level of HBsAg (less than 20 ng/ml) were reactive in reversed passive hemagglutination. There were 13 samples that were repeatable for HBsAg but were considered nonspecific as they were nonneutralizable in radioimmunoassay, 2 donors who showed nonspecific reactivity were further tested and it was found that the reactivity in radioimmunoassay persisted for more than 9 months, and this reactivity was also detectable by a second commercial kit for HBsAg. Antibodies to core and surface antigen were not found in any of the nine samples that were tested. The explanation of this nonspecific reactivity is unclear, but the data suggest that the nonspecific factor(s) may be an inherent property of the sample rather than a deficiency of the test reagents.

The American Red Cross collects blood from a number of defined subsets of the donor population and teh proportion of blood collected from each subset varies widely from center to center. A large part of the variation in prevalence of HBsAg may be related to variations in the proportion of blood collected from plants and factories, military units and schools or colleges. We have derived a regression equation, significant at the p less than 0.001 level, which links HBsAg prevalence with these collection parameters. Using this equation, we were able to predict the prevelance of HBsAg among first-time donors in 6 of the 9 geographic divisions of the United States with an accuracy exceeding 10%. The predictions for the remaining division were within 35% of the actual value. Correlation studies were supported by measurements of true donor prevalence in three blood centers.

Microanalysis of the first interview is a technique developed by the author for the subtle translation of the verbal aspects of the doctor-patient contact. Every bit of information, derived from the patient, is translated in the traditional historical dimension, e.g., when did the complaint start, and in the here and now dimension, e.g., in how far does the information imply a cry for help and understanding. Psychosomatic patients, who are usually well adapted, suppress or repress their problems and emotions so much that they are hardly able to express these quite openly. Psychosomatic symptoms reflect the effort of the patient not to behave in a hysterical way. This means that the overt cry for help and attention, which is so characteristic for hysterical patients, is warded off. Especially the microanalytic translation of this hidden cry may be used by the interviewer to detect what the basic problems of the patient are and how the optimal climate for an efficient therapeutic contact can be established. In the Leyden Department of Psychiatry the technique is used to facilitate the training in interview technique. In the paper models will be given for the understanding of the interrelationship of psychiatric and psychosomatic symptoms.