A feasibility study of perioperative vitamin D supplementation in patients undergoing colorectal cancer resection.

Background: Vitamin D supplementation improves colorectal cancer (CRC) survival outcomes in randomized trials. The aim of this study was to test the feasibility, safety and efficacy of vitamin D supplementation in the pre- and perioperative period in patients undergoing CRC surgery. Methods: Patients were given 3200IU oral cholecalciferol (D3) per day perioperatively. Serial serum 25-hydroxyvitamin (25OHD) was measured by liquid chromatography tandem mass spectrometry and compared to untreated CRC controls. 25OHD and C-reactive protein (CRP) levels were compared using adjusted generalized linear mixed-effects models. Results: A total of 122 patients underwent serial perioperative sampling, including 41 patients given high-dose perioperative supplementation. Supplementation was well-tolerated with no adverse or serious adverse events related to supplementation reported. Pre-operative supplementation increased 25OHD levels on the day of surgery (103.9 vs. 42.5 nmol/l, P = 8.2E-12). Supplementation increased 25OHD levels at all post-operative timepoints (P < 0.001) and attenuated the post-operative drop in 25OHD (46 vs. 24% drop, P = 3.0E-4). Rate of vitamin D peri-operative insufficiency was significantly less in those on supplementation (e.g., day 3-5, 14 vs. 84%, P = 1.41E-08), with multivariate modeling across all timepoints indicating a ∼59 nmol/l higher 25OHD compared to control patients (P = 3.7E-21). Post-operative CRP was lower in patients taking supplementation (e.g., day 3-5 timepoint; 129 vs. 81 mg/l, P = 0.04). Conclusion: High dose pre-operative vitamin D supplementation is associated with higher perioperative 25OHD levels, lower rates of vitamin D insufficiency and reduced early post-operative CRP. Alongside published evidence for a beneficial effect of vitamin D on CRC survival outcomes, these novel findings provide strong rationale for early initiation of vitamin D supplementation after a diagnosis of CRC.

Exploring the directionality in the relationship between descriptive and injunctive parental and peer norms and snacking behavior in a three-year-cross-lagged study.

BACKGROUND: People's eating behavior is assumed to be influenced by what other people do (perceived descriptive norms) and what others approve of (perceived injunctive norms). It has been suggested that adolescents are more susceptible to peer norms than parental norms, because they experience a strong need for group acceptance that leads to conforming to peer group norms. The current study examined changes in snacking behavior and four types of social norms (i.e., parental and peer descriptive and injunctive norms) that promoted fruit and vegetable intake among adolescents. This study was the first to examine whether snacking behavior also influenced norm perceptions by testing the directionality of these associations. METHODS: The study consisted of 819 participants (M [SD] age = 11.19 [1.36]; 46.1% boys), collected at three time points (T1 = 2016, T2 = 2017 and T3 = 2018) during the MyMovez project. Self-reported frequency of snack consumption, perceived parental and peer descriptive and injunctive norms were assessed. The primary analysis consisted of a series of cross-lagged autoregressive models specified in a structural equation modeling framework. RESULTS: Model comparisons testing the descriptive and injunctive norms in separate models and in an additional combined model revealed evidence for bi-directional associations between norms and snacking behavior. Descriptive peer and parent norms were not found to have an effect on subsequent snacking behaviors. Perceived injunctive parental norms were positively associated with healthy snack food intake and negatively associated with unhealthy snack intake (forward direction). Injunctive peer norms were negatively associated with healthy snack food intake. In addition, higher unhealthy snack food intake was negatively associated with the perception of descriptive and injunctive parental norms 1 year later (reversed direction). We did not find peer norms to be more closely associated with changes in snacking behaviors compared to parental norms. CONCLUSIONS: Parents expecting their children to snack healthy had a positive influence on healthy snacking behavior whereas only acting as a healthy role model did not. Future research should address the possible interaction between descriptive and injunctive norms. Research should also take into account the bi-directional relations between eating behaviors and normative perceptions.

Development and qualification of the parallel line model for the estimation of human influenza haemagglutinin content using the single radial immunodiffusion assay.

Infection with human influenza virus leads to serious respiratory disease. Vaccination is the most common and effective prophylactic measure to prevent influenza. Influenza vaccine manufacturing and release is controlled by the correct determination of the potency-defining haemagglutinin (HA) content. This determination is historically done by single radial immunodiffusion (SRID), which utilizes a statistical slope-ratio model to estimate the actual HA content. In this paper we describe the development and qualification of a parallel line model for analysis of HA quantification by SRID in cell culture-derived whole virus final monovalent and trivalent influenza vaccines. We evaluated plate layout, sample randomization, and validity of data and statistical model. The parallel line model was shown to be robust and reproducible. The precision studies for HA content demonstrated 3.8-5.0% repeatability and 3.8%-7.9% intermediate precision. Furthermore, system suitability criteria were developed to guarantee long-term stability of this assay in a regulated production environment. SRID is fraught with methodological and logistical difficulties and the determination of the HA content requires the acceptance of new and modern release assays, but until that moment, the described parallel line model represents a significant and robust update for the current global influenza vaccine release assay.

CD8+ cell-mediated immune responses: relation to disease resistance and susceptibility in lentivirus-infected primates.

Immune responses mediated by CD8+ lymphocytes have been correlated with protection from HIV infection and disease progression in humans and nonhuman primates. The CD8+ cell population is heterogeneous in terms of biological function and phenotype. We have undertaken a review of the current state of knowledge of subtypes of CD8+ cells and their role in immune responses directed to HIV and related primate lentiviruses. Differences in the pathogenesis of lentivirus infections in various primate hosts were examined and the possible roles of the various subpopulations of CD8+ lymphocytes in the resistance and/or susceptibility to lentivirus-related disease were compared.

Flow cytometric analysis on reactivity of human T lymphocyte-specific and cytokine-receptor-specific antibodies with peripheral blood mononuclear cells of chimpanzee (Pan troglodytes), rhesus macaque (Macaca mulatta), and squirrel monkey (Saimiri sciureus)

There are relatively few monoclonal antibodies (mAb) that have been characterized for their applicability in studies on the immune system of various nonhuman primates. In the present study, we identified a large number of mAb that can be used in future immunological studies in three different nonhuman primates, i.e., chimpanzees, rhesus macaques, and squirrel monkeys. The reactivity of 161 anti-human mAb to T-cell antigens and cytokine receptors were tested on peripheral blood mononuclear cells (PBMC) from the three primate species by flow cytometric analysis. A total of 105 (65%), 73 (45%), and 68 (42%) antibodies reacted with PBMC from chimpanzees, rhesus macaques, and squirrel monkeys, respectively. Out of the 161 mAb, 38 reacted with all three species and 112 reacted with one or two of the species. No specific reaction was observed with mAb to receptors to GM-CSF, 4-1BB, FLT3, FLX2, common beta-chain, IL-1 (type I receptor), and IL-8.

The effect of recombinant human interferon alpha B/D compared to interferon alpha 2b on SIV infection in rhesus macaques.

The model of simian immunodeficiency virus (SIV) infection in rhesus macaques was used to evaluate the effects of recombinant human interferon alpha, Hu IFN-alpha 2b and Hu IFN-gamma B,D, at two doses. Administration began 1 day prior to infection and was continued for 90 days postinfection. Both interferons suppressed SIV antigenemia during the treatment period. Following treatment animals were monitored for 4 years for rate of disease progression. Neither IFN prolonged the asymptomatic period or survival.

Immune strategies utilized by lentivirus infected chimpanzees to resist progression to AIDS.

HIV-1 infected chimpanzees are relatively resistant to the development of AIDS despite their close genetic relatedness to humans and their susceptibility to HIV-1 infection. We have systematically studied possible reasons for their relative ability to maintain T helper (Th) cell numbers and immune competence in the presence of chronic HIV-1 infection. Factors which may alone or together cause the loss in T-cell dependent immunity include: (i) the loss of Th cell function; (ii) the loss of Th cells; and (iii) the loss of capacity for Th cell renewal. Differences in the in vivo and in vitro responses of T lymphocytes from chimpanzees and humans were compared for evidence of HIV-1 related T-cell dysfunction. In contrast to HIV infected individuals, HIV-1 infected chimpanzees maintained strong Th cell proliferative and cytokine responses after receiving tetanus toxoid boosts. In addition there was no abnormal Th1 to Th2 shift as is suggested to occur in AIDS patients. There was no evidence of Th cell dysfunction such as increased level of programmed cell death (PCD) or immune activation in HIV-1 infected chimpanzees in contrast to HIV-1 infected asymptomatic humans. Anergy could be induced with HIV-1 gp120 in human but not chimpanzee Th lymphocytes. We then asked if there was a direct loss of chimpanzee CD4+ cells due to HIV-1 infection in vitro. Infection of chimpanzee CD4+ lymphocyte cultures with HIV-1 in the absence of CD8+ cells resulted in marked cytopathic effect with complete lysis and loss of cells within 3 weeks. We concluded that most chronic HIV-1 infected chimpanzees were able to maintain relatively stable CD4+ lymphocyte numbers despite CD4+ lymphocyte destruction due to direct effects of the virus. Furthermore, there was no evidence of indirect Th cell loss, since neither increased levels of anergy nor apoptosis were observed. Lymph node biopsies from HIV-1 infected chimpanzees revealed that MHC class II rich regions of lymph nodes remained intact, in contrast to the involution of these regions in infected humans. This suggested that chimpanzees may maintain the capacity for Th cell renewal by preserving this MHC class II lymphoid environment. The data presented in this paper suggests that chimpanzees may preserve this critical MHC class II-Th cell environment by dramatically suppressing extra-cellular virus load and that this may be in part mediated by soluble lentivirus suppressing factors.

The role of CD8 cells in HIV infection.

Recently much has been elucidated about the role of CD8 cells in HIV infection. Different mechanisms by which CD8 cells are able to control HIV infection have been observed. These mechanisms may be able to positively influence the duration of the asymptomatic period of HIV infection. The implications of studies on CD8 cells in HIV infected individuals as well as clinical applications of these findings are discussed.

Hyaline-vascular type Castleman's disease with concomitant malignant B-cell lymphoma.

This case report describes a patient with localized hyaline-vascular (H-V) type Castleman's disease with concomitant malignant B-cell lymphoma. Malignant lymphoma has been described in association with multicentric type Castleman's disease, but not in association with the localized H-V type. Evidence for a relation between the two lesions in this patient by means of histologic, flow-cytometric, cytogenetic and gene rearrangement studies was not found.

[Treatment of AIDS patients with zidovudine]. / Behandeling van patiënten met AIDS met zidovudine.

During 20 months 49 AIDS patients treated with zidovudine were followed prospectively. The 12-month cumulative probability of survival was 73% and the 18-month probability of survival was 51%. The probability of survival was significantly higher when, at the start of therapy, the Karnofsky score was 70 or higher (p less than 0.001) or the CD4 cell count was 0.05 x 10(9)/l or higher (p less than 0.05). The general condition, Karnofsky score, body weight, number of CD4 positive cells and the lymphocyte stimulation in vitro improved during therapy, but the beneficial effects lasted only 6-9 months. Anaemia (Hb less than 6 mmol/l) developed in 21 (43%) of the patients. (Pan)cytopenia prompted dose reduction in 14 patients, in 5 patients with pancytopenia therapy was withdrawn. The length of stay in hospital was 885 days for the whole group of patients, equivalent to 20 days per patient year.