A liquid hexavalent combined vaccine against diphtheria, tetanus, pertussis, poliomyelitis, Haemophilus influenzae type B and hepatitis B: review of immunogenicity and safety

To reduce the number of injections needed to comply with paediatric vaccination requirements, a liquid, hexavalent vaccine (DTaP-IPV-PRP-T-HBs; Hexavac; Aventis Pasteur MSD) has been developed for primary and booster vaccination of infants and toddlers. In extensive clinical studies, Hexavac has been shown to be highly immunogenic. Seroconversion or seroprotective titres of antibodies against all antigens were achieved in the majority of infants following a primary series of three doses administered at 1-2-month intervals from 2 months of age. Hexavac also induced immunologic memory, as evidenced by the anamnestic response to booster vaccination at 12-18 months of age. These responses were comparable with those seen following concomitant administration of Pentavac (DTaP-IPV//PRP-T) and monovalent hepatitis B vaccine (H-B-Vax II), and were also within the ranges observed for other relevant licensed vaccines. Clinical studies comparing the immunogenicity of Hexavac administered at either 2, 3 and 4 months or 2, 4 and 6 months demonstrated that it can be used by either vaccination schedule. A further study also supported the use of primary doses of Hexavac at 3 and 5 months with a booster at 12 months of age. Hexavac demonstrated a good reactogenicity and tolerability profile. The most frequently reported adverse events after both primary and booster doses were local reactions of redness and swelling/induration and a systemic response of mild fever, irrespective of the vaccine used for priming. Hexavac provided immunity against six important childhood diseases with a single injection at each visit.     

New evidence for the theory of the stork

Data from Berlin (Germany) show a significant correlation between the increase in the stork population around the city and the increase in deliveries outside city hospitals (out-of-hospital deliveries). However, there is no correlation between deliveries in hospital buildings (clinical deliveries) and the stork population. The decline in the number of pairs of storks in the German state of Lower Saxony between 1970 and 1985 correlated with the decrease of deliveries in that area. The nearly constant number of deliveries from 1985 to 1995 was associated with an unchanged stork population (no statistical significance). However, the relevance of the stork for the birth rate in that part of Germany remains unclear, because the number of out-of-hospital deliveries in this area is not well documented. A lack of statistical information on out-of-hospital deliveries in general is a severe handicap for further proof for the Theory of the Stork.     

Immune recovery of lymphocyte subsets 6 years after autologous peripheral blood stem cell transplantation (PBSCT) for lymphoproliferative diseases. A comparison between NHL, HD and MM in group of 149 patients

To evaluate the normalization of lymphocyte subsets several years after autologous peripheral blood stem cell transplantation (aPBSCT) and to detect any differences based on the underlying lymphoproliferative diseases, we analyzed the immunological recovery of 149 patients with Non Hodgkin's Lymphoma (NHL), Hodgkin's Disease (HD), Multiple Myeloma (MM). Lymphocyte recovery was assessed before the transplant, on days 15, 30, 60, 90, 120 and on years 1, 2, 4, 6. Analysis of a total of 709 lymphocytes, including total lymphocyte count, CD3 + , CD4 + , CD8 + , CD4 + /CD8 + ratio, CD19 + , CD3 + HLA-DR + , CD16 + 56 + , was performed. The normalization of total lymphocyte counts was achieved between days 14 to 22 following PBSCT. CD3 + cells count showed a normalization after 2 years in the HD and NHL groups and after 4 years in MM group. CD4 + subset achieved normalization during the sixth year in the 3 groups. The CD8 + and CD19 + lymphocytes subsets achieved normal values in the 3 groups at day 60 and at day 120 respectively. CD16 + 56 + and CD3 + /HLA-DR + lymphocytes showed median values above the normal range starting from day 30. Immunological recovery was similar in all 3 groups. Moreover, the recovery of all subsets evaluated was similarly demonstrated within 6 years after aPBSCT.     

Efficacy and safety of intravenous amiodarone for incessant tachycardias in infants

Amiodarone is an effective anti-arrhythmic agent for the treatment of supraventricular and ventricular tachycardias. The safety and efficacy of intravenous amiodarone has been described in adults and children but only to a limited extent in infants. The purpose of this study was to evaluate the safety and efficacy of intravenous amiodarone in infants. Between February 1994 and June 2001, 23 infants with a median age of 8 days (range 1–300 days) with life-threatening incessant tachycardias (17 supraventricular, 6 ventricular) were treated with intravenous amiodarone as single anti-arrhythmic agent. At presentation, 22 infants were haemodynamically unstable. Amiodarone was given as an intravenous loading dose of 5 mg/kg over 1 h followed by an intravenous maintenance dose of 5 µg/kg per min with stepwise increase up to 25 µg/kg per min until arrhythmia control or side-effects occurred. Amiodarone was effective in 19 infants, partially effective in three and ineffective in one infant. The median time until arrhythmia control was 24 h (range 1–96 h) and the median maintenance dosage 15 µg/kg per min (range 5–26 µg/kg per min). Electrophysiological side-effects necessitating dose reduction comprised of sinus bradycardia in two patients. Hypotension in one patient resolved after dose diminution. Neurological side-effects consisted of choreatic movements in one infant, which resolved over time. Amiodarone administration was stopped in one patient with elevated liver enzymes. Conclusion:intravenous amiodarone is a safe and effective therapy for life-threatening incessant tachycardias in infants.     

Urinary nucleosides as potential tumor markers evaluated by learning vector quantization

Modified nucleosides were recently presented as potential tumor markers for breast cancer. The patterns of the levels of urinary nucleosides are different for tumor bearing individuals and for healthy individuals. Thus, a powerful pattern recognition method is needed. Although backpropagation (BP) neural networks are becoming increasingly common in medical literature for pattern recognition, it has been shown that often-superior methods exist like learning vector quantization (LVQ) and support vector machines (SVM). The aim of this feasibility study is to get an indication of the performance of urinary nucleoside levels evaluated by LVQ in contrast to the evaluation the popular BP and SVM networks. Urine samples were collected from female breast cancer patients and from healthy females. Twelve different ribonucleosides were isolated and quantified by a high performance liquid chromatography (HPLC) procedure. LVQ, SVM and BP networks were trained and the performance was evaluated by the classification of the test sets into the categories "cancer" and "healthy". All methods showed a good classification with a sensitivity ranging from 58.8 to 70.6% at a specificity of 88.4-94.2% for the test patterns. Although the classification performance of all methods is comparable, the LVQ implementations are superior in terms of more qualitative features: the results of LVQ networks are more reproducible, as the initialization is deterministic. The LVQ networks can be trained by unbalanced sizes of the different classes. LVQ networks are fast during training, need only few parameters adjusted for training and can be retrained by patterns of "local individuals". As at least some of these features play an important role in an implementation into a medical decision support system, it is recommended to use LVQ for an extended study.     

Mutational spectrum of the CTNS gene in Italy

Classic nephropathic or infantile cystinosis (NC) is an autosomal recessive disorder; the gene coding for the integral membrane protein cystinosin, which is responsible for membrane transport of cystine (CTNS), was cloned. Mutation analysis of the CTNS gene of Caucasian patients revealed a common 57-kb deletion, and several other mutations spread throughout the entire gene. In the present study, we report the CTNS mutations identified in 42 of 46 Italian families with NC. The percentage of mutations characterized in this study is 86%. The mutational spectrum of the Italian population is different from that of populations of North European origin: the 57-kb deletion is present in a lower percentage, while the splicing mutations represent 30% of mutation detected in our sample. In all, six novel mutations have been identified, and the origin of one recurrent mutation has been traced.     

Viral origin of antiphospholipid antibodies: endothelial cell activation and thrombus enhancement by CMV peptide-induced APL antibodies

Our observations and those from others, give further support to our hypothesis that "autoimmune aPL" may be generated by immunization with products from bacteria or viruses after incidental exposure or infection. We also were able to generate APS-like syndrome in a strain of mice susceptible to autoimmunity, indicating that other factors such as genetics are likely to be involved in the development of APS. Furthermore, not all aPL antibodies generated by immunization with bacterial or viral products are pathogenic. Based on the clinical experience and on the numerous reports indicating presence of aPL in a large number of infectious diseases, it may be expected that not all aPL antibodies produced during infection will be pathogenic. We hypothesize that a limited number aPL antibodies induced by certain viral/bacterial products would be pathogenic in certain groups of predisposed individuals. Identification of these bacterial and/ or viral agents may help to find strategies for the prevention of production of aPL "pathogenic" antibodies. Alternatively, free peptides may be used to induce tolerance against aPL production.     

Prevalence of anti-human respiratory syncytial virus antibodies over three consecutive years in a healthy adult population

The titers of anti-human respiratory syncytial virus (HRSV) antibodies have been measured by enzyme-linked immunosorbent assay (ELISA) in a cohort of healthy adult volunteers over 3 consecutive years. Significant increases in the level of these antibodies were detected in a small percentage of individuals (3-3.3%), when paired serum samples taken from two consecutive seasons were compared. In these cases, a significant increase was generally noted in the level of antibodies directed against either the F or the G glycoproteins, and in the level of neutralizing antibodies. However, no correlation was found between the level of binding and neutralizing antibodies, when samples representative of the population under study were analyzed. These results indicate some level of infection by HRSV in the adult population. The implications of these results for the epidemiology of HRSV are discussed.