Gold: an old drug still working in refractory pemphigus

BACKGROUND: The mainstay of treatment for pemphigus is systemic corticosteroids. Different adjuvants have been used to reduce side-effects of long-term corticotherapy. Gold is an anti-inflammatory drug used in autoimmune diseases, whose use has waned with the advent of new immunosuppressive agents. OBJECTIVE: To study the outcome of the use of intramuscular gold treatment of pemphigus vulgaris refractory to previous therapies. METHODS: Thirteen patients with pemphigus vulgaris who had failed to respond to several prior therapies were treated with aurothiomalate, as a steroid-sparing agent. Patients were monitored to assess disease activity and gold toxicity. RESULTS: Seven patients achieved complete remission. Four patients were able to taper prednisone doses, although pemphigus flared when prednisone was discontinued or reduced. Toxicity was observed in the other two patients. CONCLUSIONS: In 53.4% of the patients, the use of chrysotherapy resulted in the complete clearing of the disease, discontinuation of all systemic therapies and induced a long-term clinical remission. Prednisone doses were able to be reduced in the remaining 46.6%. Any side-effects were reversible with drug discontinuation. Gold therapy showed efficacy as a secondary line treatment in refractory pemphigus vulgaris.     

Folic acid in the treatment of acute watery diarrhoea in children: a double-blind, randomized, controlled trial

One-hundred and six male children aged 6-23 months with a history of acute watery diarrhoea of less than 72 h duration were randomized to receive either folic acid in a dose of 5 mg at 8-h intervals or placebo for 5 d. There were 54 children in the folic acid group and 52 in the placebo group. The admission characteristics were comparable between the two groups. No significant differences were observed in the intake of oral rehydration solution or stool output between the groups. The mean ± SD of total stool output (g kg⁻¹) was 532 ± 476 vs 479 ± 354 and the duration (h) of diarrhoea was 108 ± 68 vs 103 ± 53 in the folic acid vs placebo group, respectively. The findings, therefore, should have a positive influence on preventing the inappropriate use of folic acid in acute diarrhoea.     

Incidence and determinants of moderate COPD (GOLD II) in male smokers aged 40–65 years: 5-year follow up

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major health problem with an estimated prevalence of 10-15% among smokers. The incidence of moderate COPD, as defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD), is largely unknown. AIM: To determine the cumulative incidence of moderate COPD (forced expiratory volume in 1 second/forced vital capacity ratio [FEV1/FVC] <0.7 and FEV1 <80% predicted) and its association with patient characteristics in a cohort of male smokers. DESIGN: Prospective cohort study. SETTING: The city of IJsselstein, a small town in the Netherlands. METHOD: Smokers aged 40-65 years who were registered with local GPs, participated in a study to identify undetected COPD. Baseline measurements were taken in 1998 of 399 smokers with normal spirometry (n = 292) or mild COPD (FEV1/FVC <0.7 and FEV1 >or=80% predicted, n = 107) and follow-up measurements were conducted in 2003. RESULTS: After a mean follow-up of 5.2 years, 33 participants developed moderate COPD (GOLD II). This showed an estimated cumulative incidence of 8.3% (95% CI = 5.8 to 11.4) and a mean annual incidence of 1.6%. No participant developed severe airflow obstruction. The risk of developing moderate COPD in smokers with baseline mild COPD (GOLD I) was five times higher than in those with baseline normal spirometry (one in five versus one in 25). CONCLUSIONS: In a cohort of middle-aged male smokers, the estimated cumulative incidence of moderate COPD (GOLD II) over 5 years was relatively high (8.3%). Age, childhood smoking, cough, and one or more GP contacts for lower respiratory tract problems were independently associated with incident moderate COPD.     

Lipopolysaccharide (LPS) from Brucella abortus is less toxic than that from Escherichia coli, suggesting the possible use of B. abortus or LPS from B. abortus as a carrier in vaccines.

Brucella abortus may be useful as a component of vaccines. This is because it possesses several unique properties as a carrier that enable it to stimulate human B cells even in the relative absence of T cells. Human immunodeficiency virus type 1 proteins conjugated to B. abortus could induce neutralizing antibodies against human immunodeficiency virus type 1. Recently we showed that the characteristics of lipopolysaccharide (LPS) derived from B. abortus are similar to those of the whole bacterium in that the LPS acts as a T-independent type 1 carrier in mice. In this study we wanted to determine whether LPS derived from B. abortus is associated with the adverse effects seen with other bacterial endotoxins. LPS purified from B. abortus by butanol extraction was shown to have less than 2% (wt/wt) contamination by protein and less than 1% (wt/wt) contamination by nucleic acids and to contain 1% (wt/wt) ketodeoxyoctanic acid. Compared with LPS derived from Escherichia coli, B. abortus LPS was 10,000-fold less potent in eliciting fever in rabbits, 268-fold less potent in killing D-galactosamine-sensitized mice, and 1,400-fold and 400-fold less potent in inducing interleukin-1 beta and tumor necrosis factor alpha production, respectively. These results suggest that B. abortus LPS is much less likely than the LPS from E. coli to evoke endotoxic shock; therefore, it may be feasible to incorporate B. abortus as a component of vaccines.     

Progression and regression of cervical lesions: Review of smears from women followed without initial biopsy or treatment

Cervical smears were reviewed from patients in whom a cytological abnormality was followed, after an interval without interference, either by regression to `negative' or else by progression to invasive carcinoma. Twenty-eight cases were from a previously analysed series with positive smears and an interval of at least two years before investigation, resulting from refusal or failure to trace. Slides were also reviewed from 25 cases in which `positive' smears had regressed to negative without escaping from surveillance, and from 10 patients subsequently developing invasive carcinoma whose previous slides, taken several years earlier, showed abnormalities on review. None of these 63 patients had any biopsy or other surgical procedure to the cervix between the initial smear and the outcome.

Slides showing `superficial cell dyskaryosis' and/or well-differentiated `parabasal cell dyskaryosis' were found only among the groups with subsequent regression. Those showing dissociated poorly differentiated dyskaryotic parabasal cells regressed to negative in two cases and progressed to invasion in nine. This suggests that many examples of spontaneous regression correspond to mild dysplasias which are not precancerous, and overdiagnosis must often have resulted in unnecessary surgical procedures in the past.

`Regressing' and `progressing' groups both included cases in which the spatula had removed coherent pieces of undifferentiated epithelium. These are difficult to interpret cytologically. In nine of them (including four which regressed) the cytological picture was that of carcinoma in situ. The remainder (14 cases) were probably examples of reserve cell hyperplasia, and it is noteworthy that, of the 21 cases subsequently progressing to invasive carcinoma, five were preceded by appearances of this type. It is concluded that cell aggregates suggesting an unusual degree of reserve cell hyperplasia are a danger signal and require careful surveillance.

     

Murine splenic hematopoietic subpopulations: the enlarged undifferentiated subset in New Zealand black mice is multipotent stem cells.

We recently reported that a significant population of the murine splenic non-T, non-B "null" cell compartment consists of non-lineage-specific, undifferentiated cells which are in the G0 and G1 phases of the cell cycle and that their numbers are particularly high in the spleens of New Zealand Black mice. A highly enriched population of these non-lineage-specific cells obtained by successive elimination of differentiated cells was further purified to homogeneity by fluorescence-activated cell sorting. The morphologic, phenotypic, and histochemical characteristics of this purified population suggest that these cells may be primitive hematopoietic stem cells. The germ line configuration of the genomic DNA establishes that these are uncommitted stem cells. In vivo, these cells form day 12 colonies in the spleen and liver of lethally irradiated recipients and confer radioprotection. These cells also differentiate into T- and B-cell lineages and reconstitute the immunodeficiency in mice with severe combined immunodeficiency. In response to a combination of a very few early-acting lymphokines and/or stromal cell-conditioned medium in vitro, these cells differentiate into both myeloid and lymphoid cell types. More of these cells are obtained from the enlarged spleens of New Zealand Black mice than from those of BALB/c mice. The presence of a comparatively higher number of stem cells in the spleen than in the marrow or fetal liver provides an alternative, and possibly superior, source of uncommitted stem cells for a variety of experimental investigations or therapeutic manipulations.     

Hapten-specific B cell blockade of the immune response to a thymus-independent-1 antigen produced by concomitant administration of a thymus-independent-2 antigen.

CBA/N mice harbour an X-linked B cell defect which is transmitted by CBA/N female mice to their hybrid male progeny. These mice mount normal responses to thymus-dependent (TD) and some thymus-independent (TI-1) antigens, while the response to TI-2 antigens is absent. Hapten-specific plaque-forming cell (PFC) responses to TD antigens can be blockaded by concomitant exposure of these mice to TI-2 antigens bearing the same hapten. This paper investigates in defective mice the blockade of their response to TNP3-LPS (trinitrophenylated lipopolysaccharide, a TI-1 antigen), imposed by DNP59-Ficoll (dinitrophenylated Ficoll, a TI-2 antigen). The effectiveness of the blocking agent, DNP59-Ficoll, differed in various inbred mouse strains: CBA/N X C3H/HeN F1 male greater than CBA/N female greater than CBA/N X C3H/HeN F1 female. The role of T cells in the observed hapten-specific blockade phenomenon was investigated using athymic CBA/N nude mice and a B cell tolerogen. Our findings indicate that T cell participation is not essential for the blockade of CBA/N PFC responses and they suggest that direct blockade of TI- and TD-responsive B cell populations is likely to occur.