Safety and immunogenicity of a combined hepatitis B virus-Haemophilus influenzae type B vaccine comprising a synthetic antigen in healthy adults

The combined HB-Hib vaccine candidate Hebervac HB-Hib (CIGB, La Habana), comprising recombinant HBsAg and tetanus toxoid conjugate synthetic PRP antigens has shown to be highly immunogenic in animal models. A phase I open, controlled, randomized clinical trial was carried out to assess the safety and immunogenicity profile of this bivalent vaccine in 25 healthy adults who were positive for antibody to HBsAg (anti-HBs). The trial was performed according to Good Clinical Practices and Guidelines. Volunteers were randomly allocated to receive the combined vaccine or simultaneous administration of HB vaccine Heberbiovac-HB and Hib vaccine QuimiHib (CIGB, La Habana). All individuals were intramuscularly immunized with a unique dose of 10 microg HBsAg plus 10 microg conjugated synthetic PRP. Adverse events were actively recorded after vaccine administration. Total anti-HBs and IgG anti-PRP antibody titers were evaluated using commercial ELISA kits at baseline and 30 days post-vaccination. The combined vaccine candidate was safe and well tolerated. The most common adverse reactions were local pain, febricula, fever and local erythema. These reactions were all mild in intensity and resolved without medical treatment. Adverse events were mostly reported during the first 6-72 hours post-vaccination. There were no serious adverse events during the study. No severe or unexpected events were either recorded during the trial. The combined vaccine elicited an anti-HBs and anti-PRP booster response in 100% of subjects at day 30 of the immunization schedule. Anti-HBs and anti-PRP antibody levels had at least a two-fold increase compared to baseline sera. Even more, anti-HBs antibody titer showed a four-fold increase in 100% of volunteers in the study group. The results indicate that the combined HB-Hib vaccine produces increased antibody levels in healthy adults who have previously been exposed to these two antigens. To our knowledge, this is the first demonstration of safety and immunogenicity for a combined vaccine comprising recombinant HBV and synthetic Hib antigens. The present results support phase I-II clinical trial in the target population, two months old healthy infants.     

Cirugía de rescate en el cáncer colorrectal metastásico

El objetivo del estudio es el análisis de la supervivencia en el cáncer colorrectal metastásico tras la cirugía de rescate. Entre 1991 y 1998 se diagnosticaron 498 pacientes con cáncer colorrectal. En 10 pacientes se realizó cirugía de rescate de metástasis metacrónicas hepáticas o pulmonares. Se analizaron las características clínicas, el tratamiento realizado y la supervivencia. Siete fueron hombres y 3 mujeres con edades comprendidas entre 36–75 años (mediana: 61 años). La localización más frecuente fue recto seguida de sigma. Sólo 3 pacientes tenían afectación ganglionar. La localización más frecuente de las metástasis fue hepática, seguida de pulmonar. El nÚmero de metástasis fue 3 en un paciente, 2 en 3 pacientes y en el resto fue Única. El tamaño osciló entre 2 y 6,5 cm. La mediana del intervalo libre de enfermedad hasta el diagnóstico de la metástasis fue de 17 meses (rango: 8–48). El intervalo libre de enfermedad tras metastasectomía fue de 15,5 meses de mediana (rango: 3–72). La mediana del tiempo de seguimiento fue 47 meses (rango: 19–97). La cirugía de rescate de las metástasis hepáticas y pulmonares del cáncer colorrectal puede ofrecerun aumento de la supervivencia en pacientes seleccionados.     

Maternal corticosterone effects on hypothalamus-pituitary-adrenal axis regulation and behavior of the offspring in rodents

The behavioral and physiological traits of an individual are strongly influenced by early life events. One of the major systems implicated in the responses to environmental manipulations and stress is the hypothalamus-pituitary-adrenal (HPA) axis. Glucocorticoid hormones (cortisol in humans and corticosterone in rodents) represent the final step in the activation of the HPA system and play an important role in the effects induced by the perinatal environment. We demonstrated, in rats with some differences between males and females, that mothers whose drinking water was supplemented with moderate doses of corticosterone throughout the lactation period, give birth to offspring better able to meet the demands of the environment. The progeny of these mothers, as adults, show improved learning capabilities, reduced fearfulness in anxiogenic situations, lower metabotropic glutamate receptors and higher glucocorticoid receptors in the hippocampus with a persistent hyporeactivity of the HPA axis leading to a resistance to ischemic neuronal damage. Other studies performed in mice showed that low doses of corticosterone in the maternal drinking water, which, as in our rat model, may reflect a form of mild environmental stimulation, enhanced the offspring's ability to cope with different situations, while elevated doses, comparable to those elicited by strong stressors, caused developmental disruption. Significantly, adult rats and mice that had been nursed by mothers with a mild hypercorticosteronemia provide an example of how a moderate corticosterone increase mediates the salutary effects of some events occurring early in life. Both maternal and infantile plasma levels of the hormone may play a role in these effects, the first influencing maternal behavior, the second acting directly on the central nervous system of the developing rat.     

Trimethoprim as Adjuvant Treatment in Schizophrenia: A Double-Blind,Randomized, Placebo-Controlled Clinical Trial

Various infectious agents, such as Toxoplasma gondii, have been hypothesized to be potentially relevant etiological factors in the onset of some cases of schizophrenia. We conducted a randomized, double-blind, placebo-controlled treatment trial in an attempt to explore the hypothesis that the symptoms of schizophrenia may be related to infection of the central nervous system with toxoplasma gondii. Systematically selected patients with ongoing and at least moderately severe schizophrenia from Butajira, in rural Ethiopia, were randomly allocated to trimethoprim or placebo, which were added on to participants'' regular antipsychotic treatments. Trial treatments were given for 6 months. The Positive and Negative Syndrome Scale (PANSS) was used to assess outcome. Ninety-one patients were included in the study, with 80 cases (87.9%) positive for T. gondii immunoglobulin G antibody. Seventy-nine subjects (87.0%) completed the trial. The mean age of subjects was 35.3 (SD = 8.0) years, with a mean duration of illness of 13.2 (SD = 6.7) years. Both treatment groups showed significant reduction in the overall PANSS score with no significant between-group difference. In this sample of patients with chronic schizophrenia, trimethoprim used as adjuvant treatment is not superior to placebo. However, it is not possible to draw firm conclusion regarding the etiological role of toxoplasmosis on schizophrenia based on this study because the timing and the postulated mechanisms through which toxoplasmosis produces schizophrenia are variable.     

IgM antibody response to antigens prepared from vegetative and coccoid forms of Helicobacter pylori

This report describes the utility of antigens prepared from different coccoid and spiral forms of Helicobacter pylori in a serological method. The presence of IgM antibody to H. pylori was determined in 22 human sera on antigens prepared from 24 strains of H. pylori. Antigens prepared from spiral form of certain strains of H. pylori detected IgM in all confirmed positive sera. Antigens obtained from the coccoid cells of the same strains could not completely detect IgM in the same sera. Testing sera on boosted antigens of the coccoid cells showed reduction in the number of false negative, indicating that the coccoid cells do not have one or more antigenic fractions essential for accurate detection of antibody. Our data suggest that H. pylori may lose CagA during the coccoid conversion process and regain it in the spiral form. In conclusion, we suggest that the antigen used for the detection of antibodies to H. pylori in serological methods should contain a broad spectrum of antigenic fractions and should be prepared from certain strains and culturable cells of H. pylori.     

Recurrent malignant otitis externa: management and outcome

Necrotizing (malignant) external otitis (NEO) is an infection involving the temporal and the adjacent bones. It is a rare type of external otitis that occurs primarily in immunocompromised persons. The present study aimed to evaluate its management and outcome in recurrent cases. Ten patients attending the ENT Department, Alexandria University were included. They had recurrence of otitis externa over a period of 6 months after-cure, as well as severe night otalgia and high ESR level. Peri-auricular soft tissue swelling, cranial nerve paralysis and trismus were the main persistent or developing presentations in recurrent cases. Extensive surgical intervention was performed in four patients with unsatisfactory outcome. On the other hand, satisfactory results were obtained with those treated with specific medical therapy after culture and sensitivity test and those who underwent minimal surgical intervention. In conclusion, NEO is an aggressive disease that necessitates conservative management and local debridement of sequestrated tissues. The ESR is a good indicator of treatment response. It is recommended to be meticulous in treatment of cases with recurrent NEO and extensive surgical interventions are discouraged.