Mitogenic stimulation of hepatocellular proliferation in rodents following 1,4-dichlorobenzene administration.

1,4-Dichlorobenzene (DCB), a non-DNA-reactive compound, induced hepatocellular carcinomas at 600 mg/kg/day, but not 300 mg/kg/day in male and female B6C3F1 mice in a National Toxicology Program (NTP) bioassay. Cell proliferation studies were performed under conditions of the NTP bioassay to determine the mode of DCB-induced hepatocellular proliferation and whether this proliferative response may be related to the carcinogenic activity of DCB. The percentage of cells in S-phase (labeling index; LI) was measured using immunohistochemical detection of 5-bromo-2'-deoxyuridine. Time-course and dose-response studies revealed a sharp increase in LI 24 h after treatment in female mice and rats, and at 48 h in male mice with no increases in liver-associated plasma enzymes at up to twice the highest bioassay dose. During 13 weeks of DCB administration under bioassay conditions, a statistically significant transient peak of hepatocellular proliferation was observed during week 1 at 600 mg/kg/day, but not at 300 mg/kg/day, in male and female mice. Hepatocellular proliferation was also observed in female rats, which were reported as exhibiting no increased liver tumor incidence when compared to controls in the NTP bioassay. An increase in liver weight as a percentage of body weight compared to controls was observed in high dose male and female mice, and female rats at all time points. No significant elevations in liver-associated plasma enzymes were found at any time point, indicating a lack of overt hepatotoxicity. Histopathological evaluation revealed no evidence of hepatocellular necrosis in all groups. These data indicate an early mitogenic stimulation of cell proliferation, rather than regeneration secondary to cytolethality, in the livers of DCB-treated mice, which correlates with previously observed tumor formation in a dose-dependent manner. The mode by which a chemical induces cell proliferation is an important consideration in mechanistic studies and the risk assessment process. The demonstrated mitogenic activity of DCB raises the possibility that this early proliferative response may be sufficient for liver tumor formation in the B6C3F1 mouse, or that DCB may provide a selective growth advantage to preneoplastic cells in the mouse liver upon long-term treatment. The observed induction of cell proliferation by DCB in the rat in the absence of a tumorigenic response suggests important species differences and complexities in the relationship between cell proliferation and carcinogenesis, and indicates that caution be applied in equating cell proliferation to cancer.     

Long-term experience with implanted intrathecal drug administration systems for failed back syndrome and chronic mechanical low back pain

Background  

Continuous intrathecal drug delivery has been shown in open studies to improve pain and quality of life in those with intractable back pain who have had spinal surgery. There is limited data on long term effects and and even less for patients with mechanical back pain without prior spinal surgery.     

The mucosal immune system: from fundamental concepts to vaccine development.

Recent studies in experimental animals and humans have shown that the mucosal immune system, which is characterized by secretory IgA (S-IgA) antibodies as the major humoral defence factor, contains specialized lymphoid tissues where antigens are encountered from the environment, are taken up and induce B- and T-cell responses. This event is followed by an exodus of specific lymphocytes, which home to various effector sites such as the lamina propria regions and glands. These responses are regulated by T cells and cytokines and lead to plasma cell differentiation and subsequent production of S-IgA antibodies in external secretions. This knowledge has led to practical approaches for vaccine construction and delivery into mucosal inductive sites in an effort to elicit host protection at mucosal surfaces where the infection actually occurs.     

Good practice in statistical reporting for Family Practice

Good research depends not only on good ideas. The research mustalso be conducted, analysed and reported well. At Family Practice,we aim to publish high-quality reports of high-quality research.For publications based on quantitative studies, one importantelement of good reporting is reporting statistical aspects ofthe study correctly. In this editorial, we discuss a numberof important factors that lead to a report which we considerto be statistically sound. Guidance for reporting quantitative studies has mostly focusedon randomized controlled trials, for example, in the CONSORT(Consolidated Standards of Reporting Trials) statement,¹ andmore recently an extended statement for cluster randomized trials.²Randomized     

Evidence for a mature B cell subpopulation in Peyer''s patches of young adult xid mice

Peyer's patch (PP) and mesenteric lymph node (MLN) cell cultures from young adult X-linked immunodeficient (xid) CBA/N and (CBA/N X DBA/2) F1 male mice support primary anti-sheep erythrocyte (SRBC) plaque-forming cell (PFC) responses, which suggests that gut-associated lymphoreticular tissue (GALT) contains a normal B lymphocyte subpopulation. Further support for this was provided by the observation that PP cells from xid mice gave responses to both TI-1 and TI-2 antigens that were similar to the responses of PP cell cultures from normal mice. Spleen cell cultures from xid mice were unresponsive to SRBC and TI-2 antigens. Proof that GALT of xid mice contain mature B lymphocytes was provided by the demonstration of PP B cells that bear a low density of surface immunoglobulin M. When these cells were separated by flow cytometry and immunized with trinitrophenyl (TNP)- Ficoll in vitro, good anti-TNP PFC responses were observed. These results suggest that GALT of young adult xid mice contain mature B cells and may represent the origin for the mature B cell responses seen in aged xid mice.     

Beliefs and behavior of deceivers in a randomized, controlled trial of anti-smoking advice at a primary care clinic in Kelantan, Malaysia

Smoking deception is often ignored, but is important in health care. In this trial it was assessed at both study entry and outcome. At study entry, 1,044 males at a primary care clinic were asked smoking status and tested for breath carbon monoxide (CO). Of self-reported non-smokers, 57/402 (14%) were actually smokers, as were 59/251 (24%) of self-reported ex-smokers. The self-reported smokers (n=387) entered a randomized, controlled trial where the intervention comprised four questions on knowledge and beliefs about smoking, standardized verbal advice against smoking, and a leaflet. At follow-up, subjects were also questioned about beliefs. Follow-up was difficult, but 191/387 (49%) attended at three or six months. Of 27 who claimed to have quit, 6 (22%) were deceivers and 21 were confirmed quitters. Cessation did not differ between intervention and control groups. Overall confirmed cessation at six months was 16/387 (4.1 %). Confirmed quitters were significantly lighter smokers than deceivers and still smokers. There were non-significant trends between the outcome groups whereby deceivers had least knowledge and most lay beliefs, and quitters had most knowledge and fewest lay beliefs. The lay beliefs may prevent some smokers from quitting.