Immunogenicity,safety and reactogenicity of ROTAVAC® in healthy infants aged 6–8 weeks in Vietnam

BackgroundROTAVAC® is derived from human 116E rotavirus (RV) neonatal strain. In this study, we evaluated the immunogenicity, safety and reactogenicity of ROTAVAC® in Vietnam.MethodWe conducted a phase IV clinical trial in healthy infants aged 6–8 weeks using the complete regimen of ROTAVAC® with three doses. Serum anti-RV IgA was measured by enzyme-linked immunosorbent assay to assess the geometric mean concentration in infants who received the complete regimen of the vaccine.ResultsA total of 360 participants were enrolled in this clinical trial. The mean age ± standard deviation at enrollment was 6.9 ± 0.6 weeks. The anti-RV IgA titer was 4.01 ± 3.74 mg/ml pre-vaccination and substantially increased to 29.27 ± 80.64 mg/ml post-vaccination. The value of logIgA significantly increased (p = 0.003) from 0.28 ± 0.79 to 1.03 ± 0.54. The proportion of participants with equal to and greater than 3-fold and 4-fold shifts in pre- to post-vaccination antibody titer (IgA) were 55.4% and 48.3%, respectively. No adverse events or serious adverse events were recorded immediately within 30 min after the administration of each dose. The most common adverse events within 14 days after each visit were fever, unusual crying and irritability. Other adverse events occurred at a low rate, and no case of intussusception was noted.ConclusionsThe complete regimen of ROTAVAC® demonstrated an immunological response with clinically acceptable safety profile. Post-completion of this study, ROTAVAC® is now a WHO-prequalified vaccine and available in Vietnam.     

Vascularisation des glandes surrénales

Résumé La glande surrénale de l'homme réunit deux structures initialement sans rapport physiologique. Cette dualité phyllogénique et embryologique se retrouve dans sa structure vasculaire de façon paradoxale. Les artères métamériques de l'organe phéochrome irriguent en priorité le cortex. L'axe veineux de l'ébauche mésenchymateuse draine le réseau des capillaires sinusoïdaux vers la médulla. Le réseau lymphatique est quasi inexistant au niveau de la médulla. Bien développé dans le cortex, il se draine presque exclusivement de façon centrifuge le long des axes artériels. A côté de son intérêt anatomo-chirurgical évident, l'étude de la vascularisation des glandes surrénales se doit de répondre aux besoins des investigations morphologiques vasculaires. La connaissance des variations artérielles et de leur fréquence, des territoires glandulaires de distribution, des voies anastomotiques de suppléance et des regroupements typologiques a retenu notre attention. Elle facilitera la lecture des artériographies globales toujours difficile dans le plan rétro-péritonéal. Elle guidera l'angiographie artérielle sélective. La phlébographie cave occlusive permet d'obtenir des opacifications remarquables des veines centrales, en particulier à gauche. Cette méthode est utile dans l'étude des tumeurs rétro-péritonéales et dans l'exploration des masses ganglionnaires lombo-aortiques susceptibles d'imprimer leur empreinte sur les structures veineuses. Elle a d'autant plus d'intérêt que la lymphographie pédieuse qui opacifie bien les chaînes latéro-aortiques gauche et latérocave à droite, ne permet pas, sauf reflux à contrecourant, une étude de l'important carrefour inter-aortico-cave sous-rénal. Des cathétérismes et des prélèvements électifs au niveau des différentes voies excrétrices de cette glande endocrine (veines et lymphatiques) peuvent aider à une meilleure connaissance de la physiologie et de la pathologie de l'organe. Les voies de dérivations veineuses des glandes surrénales ont été étudiées dans cet esprit.     

Elevated serum cytokines in patients with malignancy and weight-loss

Tumour necrosis factor (TNF) has been implicated in the pathogenesis of cachexia in neoplastic and infectious diseases. In our study, the relationship between TNF and other cytokines in patients with malignancy was studied by measuring the serum levels of TNF, Interleukin-I (IL-1), Interleukin-2 (IL-2), and Interleukin-6 (IL-6). Eight patients with cancer had weight loss >10% of their body weight prior to starting anticancer therapy, and their weight loss was not attributable to gastrointestinal disorder, or other medical conditions. Seven patients with malignancy and no weight loss, as well as three normal donors without malignancy were also tested as controls. TNF, IL-1, IL-2 and IL-6 serum levels were determined using a quantitative ELISA test. Elevated levels of TNF, IL-1, IL-2 and IL-6 were detected in 25%, 12.5%, 12.5% and 50% of patients, respectively. In contrast, TNF levels were elevated in 28.5% of seven patients with cancer and no weight loss. In these patients, IL-1, IL-2 and IL-6 levels were undetectable. No TNF, IL-1, IL-2 or IL-6 could be detected in the sera of normal controls. Elevated cytokines serum levels, and especially IL-6, are detected in patients with cancer-cachexia. The determination of such cytokines may have a prognostic value.     

A multinational investigation of the impact of subcutaneous sumatriptan. I: Design, methods and clinical findings

This report describes the design, methods and clinical results of a prospective sequential multinational (5 countries) study conducted to evaluate the effects of subcutaneous sumatriptan on health-related quality of life, workplace productivity, clinical parameters and patient satisfaction. Adult patients with moderate to severe migraine initially received customary therapy for migraine episodes for 12 weeks, followed by 24 weeks' treatment with self-administered subcutaneous sumatriptan 6 mg. Demographic, baseline, health-related quality of life and patient satisfaction rating data were collected during visits to the clinic. Data relating to migraine symptoms, migraine therapy, work productivity and non-work activity time were collected on diary cards filled out by the patients. 749 patients were recruited to the study and 637 received at least 1 dose of sumatriptan. Overall, 75.5% of migraines were successfully treated within 2 hours with sumatriptan compared with 31.9% with customary therapy; 36% of patients reported complete relief at 2 hours with sumatriptan treatment compared with 1% of patients receiving customary therapy. 69% of patients successfully treated 70% of their migraines with sumatriptan within 2 hours, compared with 12% of patients with customary therapy. No serious adverse events were reported; 50% of patients reported an adverse event during the 12-week customary therapy phase and 89% of patients during the 24-week sumatriptan phase. These clinical results, which are consistent with those reported in randomised blinded studies of subcutaneous sumatriptan, suggest that relief of migraine symptoms occurs more often, and in less time, in patients receiving subcutaneous sumatriptan rather than customary therapy as their primary medication.     

Conversion factor for comparison of data from Humphrey and Medmont automated perimeters

Background : Clinical experience has shown that the sensitivity indices reported by the Humphrey Field Analyser (HFA) are generally higher than those given by the Medmont Automated Perimeter (M600). It is the purpose of this paper to determine a conversion factor for the two perimeters and to confirm this prediction using clinical data. Theory predicted that HFA_sensitivity ? 5 dB = M600_sensitivity. Methods : Sensitivity versus eccentricity profiles were measured over the central visual field on 10 young subjects using both perimeters. Results : Both the HFA and the M600 operate within the realms of the Weber law and measure similar Weber fractions. The sensitivity profiles had similar slopes (about ?0.2 dB/degree) and were separated by about six decibels with the HFA reporting higher sensitivity values. This result confirmed the theoretical prediction. Conclusion : The difference in threshold sensitivities between the two perimeters is a result of differences in scaling factors and instrument luminances. A suggested clinical conversion factor is to subtract 5 dB from the HFA data to approximate those of the M600.     

Molecular analysis of lymphoid malignancies

Although lymphoid malignancies have been widely studied at the molecular level, no group has reported on the simultaneous investigation of t(14;18) chromosomal translocation, B-cell clonality and bcl2 gene expression. We have performed PCR analysis of t(14;18) translocation and B-cell clonality as well as semi-quantitation of bcl2 expression by Western blotting on a group of 41 patients treated at our institution for lymphoid malignancies. The t(14;18) translocation was observed in 10 out of 40 cases (25%) with a prevalence in the subgroup of centrofollicular lymphoma (9 out of 19, or 47%, which includes one patient in complete clinical remission). bcl2 was overexpressed in 84% of the patients (21/25) and B monoclonality was observed in 21 out of 37 B-cell neoplasia patients (57%) with or without a t(14;18) translocation. In 4 patients, bcl2 overexpression, which has been implicated in the sensitivity to a variety of cytotoxic drugs, was the only abnormality detected. Studies are currently underway to determine whether semi-quantitation of bcl2 expression provides improved prediction of a patient's response to chemotherapy.     

Ivermectin in human onchocerciasis: a clinical-pathological study of skin lesions before and three days after treatment.

Findings are presented from an histological study of 360 skin-snips (from iliac crests, calves, ankles) taken from 30 Ivory Coast onchocerciasis patients before and three days after an oral dose of ivermectin (200 micrograms/kg). This dose causes a nearly complete disappearance of the intralymphatic microfilariae and, surprisingly, of the "extra-vascular" ones. That shows the difficulty to localize the microfilariae on histological sections; these microfilariae are in fact inside the lymphatic pre-capillaries. There was no intensification of acute skin lesions after the treatment, thus showing that, contrary to diethylcarbamazine (DEC), ivermectin does not induce an exit of microfilariae into the extralymphatic connective tissue. Under the influence of ivermectin, paralyzed microfilariae may be carried passively towards the deep sub-cutaneous lymphatics, and then destroyed inside the regional lymph nodes, without producing major changes in the skin.     

Stable weight during lamotrigine therapy: a review of 32 studies

A side effect associated with the use of some antiepileptic drugs (AEDs) is change in body weight. To evaluate the effect of lamotrigine on body weight in adult patients with epilepsy, we conducted a retrospective review of data from 463 patients treated with lamotrigine in 32 clinical trials. Mean daily dose was 259 (+/-155) mg and duration of therapy was 318 (+/-87) days. The mean change in body weight was 0.5 (+/-5) kg. Lamotrigine was associated with stable body weight in patients with epilepsy.     

Renal abnormalities in sickle cell disease

Renal abnormalities in sickle cell disease. Sickle cell nephropathy is indicated by sickled erythrocytes, with the consequent effects of decreased medullary blood flow, ischemia, microinfarct and papillary necrosis. Impaired urinary concentrating ability, renal acidification, hematuria, and potassium secretion are also found. There may be a causal relationship between an increase in nitric oxide synthesis and experimental sickle cell nephropathy, and some studies have indicated that the progression of sickle cell nephropathy is hemodynamically mediated. Although there are many studies showing that proteinuria, nephrotic syndrome, chronic progressive renal failure, and acute renal failure syndromes are the outcome of this disease, the pathogenic mechanism(s) and potential therapies remain to be elucidated. Survival of patients with sickle cell nephropathy who progress to end-stage renal disease (ESRD) is equal to non-diabetic ESRD patients, and graft survival rates are also similar for those who undergo renal transplantation. This article presents a historical review of the glomerular and tubular disorders associated with sickle cell nephropathy, and reviews therapeutic indications to slow its progression. Further research is needed.     

Aberrant crypt focus promotion and glucose intolerance: correlation in the rat across diets differing in fat, n-3 fatty acids and energy

McKeown-Eyssen (Cancer Epidemiol. Biomarkers Prevent., 3, 687-695, 1994) and Giovannucci (Cancer Causes Control, 6, 164-179, 1995), noting the striking similarity in lifestyle risk factors for colorectal cancer and insulin resistance, proposed that the hyperinsulinemia, glycemia and hypertriglyceridemia associated with insulin resistance promotes colon cancer. To compare the effect of diet on colon cancer promotion and insulin resistance in the F344 rat, we assessed the effect of fat, n-3 fatty acids and energy in pairwise comparisons on average size of aberrant crypt foci (ACF) and on glucose intolerance in the same animals in a single experiment. Diets high in fat and energy increased and diets with increased n-3 fatty acids and calorie restriction decreased both ACF growth and glucose intolerance compared with control diets. The measures of promotion of colon cancer and insulin resistance were strongly correlated (n = 98, r = 0.67, P < 0.001). In addition, both were highly correlated with daily energy intake (r = 0.62 and 0.66) and were also correlated with basal (post-prandial) insulin, glucose and triglycerides (r = 0.31-0.53, P < 0.01). We concluded that ACF growth and glucose intolerance are correlated for a wide range of diets and that increased circulating energy (glucose and triglycerides) may lead to both colon cancer promotion and insulin resistance.