[Vaccination in adults]. / Impfungen bei Erwachsenen.

The vaccination programme for adults in Germany is based on the comprehensive immunization acquired during childhood and adolescence. The goal of these vaccinations given at regular intervals is to achieve effective immunization coverage lasting into old age. The public health authorities in Germany recommend, according to the Standing Vaccination Commission (STIKO) standards, that adults should receive at least a decennial booster vaccination against diphtheria and tetanus as well as a pertussis booster if the last pertussis vaccine was administered more than 10 years earlier. Individuals above the age of 60 additionally benefit from vaccinations against pneumococcal diseases and annual vaccinations against seasonal influenza. In special life situations, e.g. during pregnancy, vaccination against influenza is also recommended for younger people. The current amendments to the recommendations of the STIKO are aimed at definitive control of measles and eradication of rubella embryopathy. A periodic check-up of the individual vaccination status, and if appropriate completion of missing vaccinations is an important duty of every practising physician. Supporting the creation of herd immunity contributes to the protection of individuals as well as the whole population.

Functional interactions of T cells with endothelial cells: the role of CD40L-CD40-mediated signals.

CD40 is expressed on a variety of cells, including B cells, monocytes, dendritic cells, and fibroblasts. CD40 interacts with CD40L, a 30-33-kD activation-induced CD4+ T cell surface molecule. CD40L-CD40 interactions are known to play key roles in B cell activation and differentiation in vitro and in vivo. We now report that normal human endothelial cells also express CD40 in situ, and CD40L-CD40 interactions induce endothelial cell activation in vitro. Frozen sections from normal spleen, thyroid, skin, muscle, kidney, lung, or umbilical cord were studied for CD40 expression by immunohistochemistry. Endothelial cells from all tissues studied express CD40 in situ. Moreover, human umbilical vein endothelial cells (HUVEC) express CD40 in vitro, and recombinant interferon gamma induces HUVEC CD40 upregulation. CD40 expression on HUVEC is functionally significant because CD40L+ Jurkat T cells or CD40L+ 293 kidney cell transfectants, but not control cells, upregulate HUVEC CD54 (intercellular adhesion molecule-1), CD62E (E-selectin), and CD106 (vascular cell adhesion molecule-1) expression in vitro. Moreover, the kinetics of CD40L-, interleukin 1-, or tumor necrosis factor alpha-induced CD54, CD62E, and CD106 upregulation on HUVEC are similar. Finally, CD40L-CD40 interactions do not induce CD80, CD86, or major histocompatibility complex class II expression on HUVEC in vitro. These results demonstrate that CD40L-CD40 interactions induce endothelial cell activation in vitro. Moreover, they suggest a mechanism by which activated CD4+ T cells may augment inflammatory responses in vivo by upregulating the expression of endothelial cell surface adhesion molecules.

Targeted killing of TNFR2-expressing tumor cells and Tregs by TNFR2 antagonistic antibodies in advanced Sézary syndrome.

Sézary syndrome (SS) is a rare form of cutaneous T-cell lymphoma often refractory to treatment. SS is defined as adenopathy, erythroderma with high numbers of atypical T cells. This offers an opportunity for new interventions and perhaps antibody-based therapeutic by virtue of its high expression of the TNFR2 oncogene on the tumor cells and on T-regulatory cells (Tregs). Potent human-directed TNFR2 antagonistic antibodies have been created that preferentially target the TNFR2 oncogene and tumor-infiltrating TNFR2+ Tregs. Here we test the therapeutic potential of TNFR2 antagonists on freshly isolated lymphocytes from patients with Stage IVA SS and from healthy controls. SS patients were on a variety of end-stage multi-drug therapies. Baseline burden Treg/T effector (Teff) ratios and the responsiveness of tumor and infiltrating Tregs to TNFR2 antibody killing was studied. We show dose-escalating concentrations of a dominant TNFR2 antagonistic antibody killed TNFR2+ SS tumor cells and thus restored CD26- subpopulations of lymphocyte cell numbers to normal. The abundant TNFR2+ Tregs of SS subjects are also killed with TNFR2 antagonism. Beneficial and rapid expansion of Teff was observed. The combination of Treg inhibition and Teff expansion brought the high Treg/Teff ratio to normal. Our findings suggest a marked responsiveness of SS tumor cells and Tregs, to targeting with TNFR2 antagonistic antibodies. These results show TNFR2 antibodies are potent and efficacious in vitro.

Plant development: Genetic clues to petal evolution.

A recent study of the expression of floral organ identity genes in buttercups, poppies and their relatives has shed light on the evolutionary origin of petals.

Long-term complications of platinum-based chemotherapy in testicular cancer survivors.

The purpose of this study was to describe the rates of cardiovascular and other medical complications related to the use of platinum-based chemotherapy in American testicular cancer survivors. The study sample consisted of 143 eligible long-term testicular cancer survivors. Participants were interviewed, their medical records were reviewed, and blood was obtained for cholesterol measurement during their follow-up visit. The mean follow-up time was 8.4 yr, and their mean age at follow-up was 41.2 yr; 72.7% had had non-seminoma, and 82.5% had received platinum-based chemotherapy. Hypertension rates in the platinum-treated group increased significantly from baseline to follow-up; however, once adjusted for blood pressure measurement (undiagnosed hypertension), no such increase was seen, and hypertension rates were already higher than national estimates at baseline in all groups. At the follow-up visit, the rates of hyperlipidemia (adjusted for measured cholesterol level) in both platinum- and non-platinum-treated groups (28.4% and 37.5%, respectively) were higher than national estimates (16.9%). Rates of coronary artery disease were higher in those who had received platinum and radiation (11.1%) than in those who had received platinum alone (4.3%), but this difference was not statistically significant. As suggested by previous studies, platinum-based chemotherapy may be associated with hypertension, hyperlipidemia, and coronary artery disease. However, our data suggest that undiagnosed hypertension and hyperlipidemia may be significant confounders, and we also observed a trend toward lower testosterone levels in participants who experienced cardiovascular complications.

The evolution of plant development.

There has been much recent interest in the evolution of plant development and especially in trying to understand the developmental genetic basis of morphological evolution. Significant progress has been made in understanding the evolution of floral organization and the mechanisms that might underlie the evolution of compound leaves and inflorescence morphology. These advances are reinforcing the idea that phenotypic evolution can proceed via changes at few loci of large effect and that promoter evolution may be an important and frequent mechanism.

Ligation of CD40 on fibroblasts induces CD54 (ICAM-1) and CD106 (VCAM-1) up-regulation and IL-6 production and proliferation.

CD40 was originally described as a functionally significant B cell surface molecule. However, CD40 is also expressed on monocytes, dendritic cells, epithelial cells, and basophils. We now report that synovial membrane (SM) or dermal fibroblasts also express cell surface CD40 in vitro. Fibroblast CD40 expression declines with increasing time in culture and recombinant interferon-gamma (rINF-gamma) induces fibroblast CD40 up-regulation. This effect of rINF-gamma is augmented by recombinant interleukin-1 alpha or recombinant tumor necrosis factor-alpha. CD40 expression on fibroblasts is functionally significant because CD40L-CD40 interactions induce SM fibroblast CD54 (intercellular adhesion molecule-1) and CD106 (vascular cell adhesion molecule-1) up-regulation. Moreover, ligation of CD40 augments IL-6 production by SM fibroblasts and induces fibroblasts to proliferate. In addition, rINF-gamma enhances the effect of CD40L-CD40 interactions on fibroblast proliferation. Taken together, these studies show that fibroblasts can express CD40, cytokines can regulate fibroblast CD40 expression, and CD40 ligation induces fibroblast activation and proliferation.

Beta adrenergic receptor dysfunction in hypoxic inhibition of insulin release.

Insulin secretory responses were measured in air-breathing puppies given epinephrine, and compared with insulin responses during acute hypoxia. In puppies with oxygen deficiency, insulin levels declined, whereas during epinephrine infusion, they remained stable or increased slightly. When glucose was given during phentolamine administration, insulin levels rose more in the epinephrine-treated animals than in the hypoxic animals, despite similar blood glucose levels. Theophylline-induced insulin release was increased by epinephrine, but inhibited by hypoxia. When the beta adrenergic blocking agent, propranolol, was given with the epinephrine, the insulin response to theophylline was markedly reduced and similar to that observed during hypoxia. Control studies with propranolol showed no effect of this agent on glucose-induced insulin release. Isoproterenol infusion caused elevated insulin levels during air ventilation but this response was suppressed by hypoxia. From these data, we have concluded that the difference between hypoxia and epinephrine can be explained by a reduced ability of catecholamines to stimulate the beta adrenergic receptor during hypoxia. We hypothesize that this effect leads to an unmodulated alpha adrenergic inhibition of insulin release.

Phylogenetic overdispersion in Floridian oak communities.

Closely related species that occur together in communities and experience similar environmental conditions are likely to share phenotypic traits because of the process of environmental filtering. At the same time, species that are too similar are unlikely to co-occur because of competitive exclusion. In an effort to explain the coexistence of 17 oak species within forest communities in North Central Florida, we examined correlations between the phylogenetic relatedness of oak species, their degree of co-occurrence within communities and niche overlap across environmental gradients, and their similarity in ecophysiological and life-history traits. We show that the oaks are phylogenetically overdispersed because co-occurring species are more distantly related than expected by chance, and oaks within the same clade show less niche overlap than expected. Hence, communities are more likely to include members of both the red oak and the white + live oak clades than only members of one clade. This pattern of phylogenetic overdispersion arises because traits important for habitat specialization show evolutionary convergence. We hypothesize further that certain conserved traits permit coexistence of distantly related congeners. These results provide an explanation for how oak diversity is maintained at the community level in North Central Florida.

Adrenal cortical adenoma in the spinal canal of an 8-year-old girl.

An ectopic adrenal cortical adenoma containing high levels of androstenedione but without clinically detectable virilizing effects was found in the spinal intradural space of an 8-year-old girl. The tumor, which was located at the L2 level, manifested itself clinically by a short history of bilateral leg pain. It was well encapsulated; therefore, total surgical removal was accomplished. The light microscopic appearance of the tumor was typical of adenomatous adrenal cortical tissue. Ultrastructurally, it also showed characteristic features of steroid-producing tumors, including very abundant smooth endoplasmic reticulum and giant mitochondria with tubulovesicular and circular cristae. Frozen tissue analyzed by radioimmunoassay was found to contain almost 20 times the normal tissue level of androstenedione. There was no elevation of cortisol or aldosterone levels in the tumor. Postoperative magnetic resonance imaging (MRI) scan of the retroperitoneum showed no abnormalities in the patient's adrenal glands. Serum androstenedione levels were normal. We postulate that the adenoma developed from congenital ectopic rests of intraspinal adrenal tissue. Although ectopic occurrence of adrenal cortical tissue has been recorded in other areas, neither such rests nor tumors developing from them have been previously reported within the spinal canal.

Pediatric heart transplantation at Stanford: results of a 15-year experience.

The long-term results of pediatric heart transplantation were evaluated in 53 patients, aged 0.25 to 18.94 years, who received transplants at Stanford University Medical Center between 1974 and 1989. Indications for transplantation were idiopathic cardiomyopathy (68%), congenital heart disease (21%), endocardial fibroelastosis (8%), and doxorubicin cardiomyopathy (3%). Immunosuppression was achieved with combinations of cyclosporine, prednisone, and azathioprine. Thirty-seven of 42 recipients leaving the hospital after transplantation were alive and in New York Heart Association class I at study's end. Cumulative survival was 79% at 1 year, 76% at 3 years, and 69% at 5 years. Fourteen recipients have survived more than 5 years (5.1 to 12.4 years). Hospital readmission for illness has been infrequent, decreasing from 6.8 days to 0.9 days per year over 5 years. Eleven patients have required no rehospitalization. Posttransplant deaths were due to infection (19%), rejection (4%), pulmonary hypertension (4%), coronary artery disease (2%), and lymphoproliferative disease (2%). Retransplantation was required for intractable rejection in 4 patients and advanced coronary artery disease in 2. Hypertension and elevated blood urea nitrogen and creatinine levels were common in individuals receiving cyclosporine. Growth was often impaired in prepubertal children receiving daily prednisone. Based on this 15-year experience, it is concluded that heart transplantation represents a reasonable alternative for selected young patients with end-stage cardiac disease.

Growth and tissue abnormalities in young people with cyanotic congenital heart disease receiving systemic-pulmonary artery shunts.

The effects of systemic-pulmonary artery shunts on growth, body composition, and adipose tissue were studied in 29 children, aged 2 to 16 years, with cyanotic congenital heart disease. Of these, 16 received surgical shunts and 13 were unoperated. Postoperatively, all patients who received shunts were better oxygenated (systemic oxygen saturation 69 +/- 11% preoperatively and 84 +/- 4% postoperatively; mean +/- standard error of the mean) and were symptomatically improved. However, the groups were not significantly different in height, weight, lean body mass, total body fat, lean/fat ratio, cellular lipid content, or total number of lipid-containing fat cells. Age at operation did not seem to influence the effects of surgery. These observations suggest that growth and certain measurements of tissue development were unaffected by surgical systemic-pulmonary artery shunts despite increased oxygenation and symptomatic improvement after operation.

Echocardiographic findings in Uhl's anomaly. Demonstration of diastolic pulmonary valve opening.

The echocardiographic findings in a case of Uhl's anomaly, or congenital hypoplasia of the right ventricular myocardium, are reported. Diastolic opening of the pulmonary valve is described. Comparison is made with echocardiograms in Ebstein's disease of the tricuspid valve, and it is suggested that echocardiography can help in differentiating these two entities. In addition to the pulmonary valve finding, increased right ventricular dimension, delayed tricuspid closure and abnormality (prolapse) of the mitral valve were noted. The echocardiographic findings are compared with cardiac catheterization data.

Results of intraventricular baffle procedure for ventricular septal defect and double outlet right ventricle or d-transposition of the great arteries.

Thirty patients with ventricular septal defect and d-transposition of the great arteries or double outlet right ventricle underwent placement of an intraventricular baffle to achieve physiologic correction. Eighteen of these patients also required an external conduit to establish continuity between the right ventricle and the pulmonary artery. There was an overall 22 percent early mortality rate, although the rate was 63 percent in patients who weighed less than 10 kg. There was an additional 20 percent late mortality rate, primarily related to conduction disturbances and pulmonary vascular obstructive disease, problems that have not occurred in patients operated on since 1974. Of the survivors, all are asymptomatic and as a group have achieved a significant weight gain. Many have residual hemodynamic abnormalities that required cardiac catheterization for precise assessment. Four patients have been reoperated on, with no additional mortality.

Serial examination of 20,248 newborn fetuses and infants: correlations between drug exposure and major malformations.

Maternal medication during the first trimester of pregnancy has been discussed as a risk factor for development of birth defects. The correlation between maternal drug use and major malformations was investigated in a population-based case-control study in Mainz. Over a period of 5 years (1990-1994), 20,248 livebirths, stillbirths, and abortions underwent physical and sonographic examination, and anamnestic data were collected. A total of 1,472 births with congenital anomalies (cases) and 9,682 births without major and minor malformations (controls) were analyzed. We distinguished between 30 different drug categories, which were divided into medication taken continuously (before and during pregnancy; CM) and acute medication (drugs given within the first 3 months of gravidity; AM). Statistically highly-significant results [CM: Odds Ratios (OR) 1.2, Confidence Intervals (CI) 1.1-1.4, P = 0.008; AM: OR 1.2, CI 1.1-1.3, P = 0.008] were established for maternal drug use in correlation to birth defects. For the majority of combinations between drugs and specific malformations no teratogenic risks were found. However, statistically significant associations were recorded for antiallergics and heart anomalies (CM, AM) as well as musculoskeletal anomalies (AM); for bronchodilators and heart anomalies (CM, AM); for antiepileptics and anomalies of the internal urogenital system (CM), as well as cleft palate/cleft lips (AM); for thyroid hormones and anomalies of the nervous system (CM, AM), as well as anomalies of the external urogenital system (CM, AM); for insulin and anomalies of the musculoskeletal system (CM); for digitalis and anomalies of the musculoskeletal system (AM).

Current approach to hypoplastic left heart syndrome. Palliation, transplantation, or both?

Over the past 3 years, 35 newborn infants have been referred for surgical management of hypoplastic left heart syndrome. Surgical palliation (first-stage Norwood) or cardiac transplantation was offered. Twenty-four families (68%) chose palliation and 11 families (32%) chose cardiac transplantation. Of the 11 infants listed for cardiac transplantation, five underwent transplantation. Because of a lack of donors after an average wait of 25 days (19 to 31), the remaining six infants underwent palliation, with no perioperative deaths. Of the 30 infants undergoing palliation, including crossovers, 20 (67%) survived the first operative stage. Among the last 19 infants undergoing palliation in 1990, the early survival was 84%. Risk factors determined for poor outcome were year of operation (p less than 0.001) and circulatory arrest time greater than 50 minutes (p less than 0.001). Among the 13 infants undergoing palliation with a circulatory arrest time of less than 50 minutes, there were 12 survivors (92%); among 12 having a circulatory arrest time of more than 50 minutes, there were four survivors (33%). At intermediate follow-up, six infants have undergone second-stage procedures (Glenn), with five survivors. There were eight late deaths, four caused by respiratory infections and four caused by cardiac problems, including a thrombosed shunt in one infant. Three of five infants are alive and doing well after cardiac transplantation. Size of aorta, tricuspid regurgitation, and ventricular wall thickness did not prove to be risk factors. Given the existing data, we believe these infants should be managed selectively on the basis of donor availability and family wishes.

T-cell lymphoma in a child after heart transplantation.

Lymphoproliferative disease remains a small but worrisome problem after organ transplantation. This disorder is often a B-cell proliferation associated with Epstein-Barr virus. This article describes the unusual association of Epstein-Barr virus with a T-cell lymphoma in a child after heart transplantation and ultimately an atypical rejection episode with an increased number of eosinophils.

Stress hyperglycemia and the adrenergic regulation of pancreatic hormones in hypoxia.

Stress hyperglycemia occurs in normal and chronically hypoxemic dogs when PaO2's are acutely lowered below 30 torr. Several factors are thought to contribute to the rise in blood glucose. The initial fall in PaO2 activates the sympathetic nervous system, stimulating alpha and beta adrenergic receptors. Because of reduced beta receptor function, alpha receptor effects predominate, promoting glucagon and inhibiting insulin release. The changes in pancreatic hormones in conjunction with the direct effects of hypoxemia and alpha receptor stimulation increase hepatic glycogenolysis. Meanwhile, glucose clearance is decreased because of elevated circulating levels of catecholamines and low insulin concentrations. This combination of events plays a major role in the development of hyperglycemia. Since high blood glucose levels seems to protect the brain and other vital organs at low oxygen tensions, the development of hyperglycemia may represent an important protective mechanism in severely hypoxemic animals, including humans.

Heart, heart-lung, and lung transplantation in the first year of life.

Seventeen infants less than 1 year of age have undergone heart (12), heart-lung (3), and lung (2) transplantation for end-stage cardiopulmonary disease. The infants undergoing heart transplantation had a mean age of 4.5 months (range, 19 days to 12 months) with the diagnosis of cardiomyopathy in 4 and congenital heart disease in 8. Four of the 8 patients (50%) had hypoplastic left heart syndrome. Actuarial survival at 1 and 2 years was 74% and compared favorably with the survival of older children at 1 and 2 years of 82% and 69%. The linearized rejection rate was less in infants as compared with children more than 1 year of age (0.61 versus 1.48 episodes per 100 patient days). In intermediate follow-up, no graft atherosclerosis has been noted. Immunosuppression has included a three-drug protocol of cyclosporine, azathioprine, and prednisone. A steroid taper to alternate day steroids or off completely by 6 months has been the goal and has been accomplished in 6 of 12 infants. Heart-lung and lung transplantation has been performed in 5 infants. One infant in each group died: 1 infant secondary to airway complications and sepsis and another due to pulmonary sepsis. A pulmonary lobe from a larger and older donor was transplanted into a 4-week-old infant as a single-lung transplant with good outcome. The 3 surviving infants are well 24, 18, and 2 months after transplantation. Obliterative bronchiolitis has not been clinically apparent in this group. These data support the clinical efficacy of heart, heart-lung, and lung transplantation in the first year of life.

Nursing frequency and the energy intake from breast milk and supplementary food in a rural Thai population: a longitudinal study.

A group of 60 infants representative of a rural Thai population were studied longitudinally over the first year of life. Their breast milk intake, supplementary food intake and nursing patterns were measured for 2 consecutive days at about 15, 45, 90, 180, 270 and 360 days of age. For the sample as a whole, the estimated peak value for energy intake from breast milk was 529 kcal (2213 kJ) and occurred at 34 days post-partum. Thereafter milk intake declined, with 40% of infants fully weaned by the end of the first year. Supplements were introduced early, with 15% of infants supplemented by 2 weeks and 68% by 6 weeks. Higher levels of supplementation were associated with lower breast milk intake. In addition there was an independent positive effect of nursing patterns (number of breast feeds per day). Interaction terms show that both supplementary feeding and number of feeds have quantitatively different effects at different ages: breast milk intake varies more with level of supplementation in younger infants than in older infants, and varies more with number of feeds in older infants than in younger infants. Higher peak levels of breast milk intake were followed by a steeper decline, and infants who took more breast milk at 15 days were more likely to be fully weaned by their first birthday.