Efficacy and Toxicity Profile of Methotrexate Chloroquine Combination in Treatment of Active Rheumatoid Arthritis

Background

The present study was conducted to study the efficacy and toxicity profile of methotrexate chloroquine combination in treatment of active rheumatoid arthritis.

Methods

24 patients of rheumatoid arthritis confirming to revised American Rheumatism Association (ARA) criteria were studied prospectively for twenty months. Clinical evaluation was made every 3 months. Clinical disease variables measured at each visit were number of joints with swelling, number of joints with tenderness and pain, duration of morning stiffness and physician and patient assessment of disease activity. Blood counts, liver function tests and other adverse effects due to drugs were monitored every 2 months.

Results

10 patients demonstrated more than 50% improvement. 4 patients withdrew from study, 2 because of excessive nausea and vomiting and 2 because of noncompliance. Other side effects noted were hyperpigmentation, photosensitivity, skin rashes, raised transaminases and stomatitis.

Conclusion

Methotrexate chloroquine combination has good efficacy and toxicity profile. Gastrointestinal side effects are most common and usually responsible for the discontinuation of the drugs.Key Words: Rheumatoid arthritis, Methotrexate, Chloroquine, Efficacy, Toxicity     

Ethics roundtable debate: Child with severe brain damage and an underlying brain tumour

A young person presents with a highly malignant brain tumour with hemiparesis and limited prognosis after resection. She then suffers an iatrogenic cardiac and respiratory arrest that results in profound anoxic encephalopathy. A difference in opinion between the treatment team and the parent is based on a question of futile therapy. Opinions from five intensivists from around the world explore the differences in ethical and legal issues. A Physician-ethicist comments on the various approaches.     

The endocytotic pathway is required for increased A beta 42 secretion during apoptosis

Secretion and progressive cerebral accumulation of beta-amyloid peptides (A beta), which derive by endoproteolytic ('amyloidogenic') processing of beta-amyloid precursor protein (APP), are felt to represent collectively an early and necessary event in the pathogenesis of Alzheimer's disease. APP amyloidogenic processing can occur via secretory or endocytotic pathways, but the relative contribution of these pathways to A beta secretion remains to be established. The effect of apoptosis on amyloidogenic processing and A beta secretion similarly is incompletely understood. We tested the hypothesis that APP processing by the endocytotic pathway represents a stress-related neural cell response, by comparing A beta secretion after induction of apoptosis in PC12 cells transfected either for endocytosis-competent or -deficient APP. Newly prepared adenoviral vectors encompassing targeted mutagenesis of the cytoplasmic tail YENP tetrapeptide sequence, which serves as the principal APP internalization signal, were used to express endocytosis-deficient holoprotein. We report that the endocytotic pathway is required for the generation and secretion of A beta 42, and that secretion of this neurotoxic peptide increases significantly during apoptosis. We demonstrate additionally that more A beta 40 apparently is generated in secretory compartments during apoptosis when APP processing by the endocytotic pathway is impaired.     

Modulatory role of thymosin-alpha-1 in normal bone-marrow haematopoiesis and its effect on myelosuppression in T-cell lymphoma bearing mice

In continuation with the earlier and ongoing studies on Thymosin-alpha-1 (Talpha1) exerting its immunomodulatory effects on various components of the immune system including T-cells, NK-cells, blood lymphocytes and macrophages, the role of Talpha1 in normal bone-marrow haematopoiesis has been investigated in the present study. The haematopoietic alterations associated with the growth of murine T-cell lymphoma, Dalton's Lymphoma (DL) and subsequently its restoration by Talpha1 was also investigated. It is observed that the non-adherent bone-marrow cells from normal mice (N-BMCs) exhibited enhanced proliferation on in vitro treatment with Talpha1 (dose range of 1-100 ng/ml) with maximal response at 100 ng/ml of Talpha1. In vitro stimulation with 100 ng/ml of Talpha1 also resulted in increased myeloid colony formation, as manifested by the rise in total number of colonies, frequency of the individual colony types and their size. This response was further upregulated in the presence of various colony stimulating factors (CSFs) like MCSF, GMCSF, GCSF and IL-3. Similarly, in vivo administration of Talpha1 (a single intraperitoneal injection of 10 microg per mouse) to normal mice also resulted in enhanced proliferation and colony formation by BMCs as compared with BMCs obtained from untreated mice. On the contrary, the progressive growth of T-cell lymphoma in mice led to suppressed myelogenesis, with marked reduction in the total colony numbers and their size. The BMCs from DL-bearing mice (DL-BMCs) displayed a preferential lineage-restricted differentiation towards the granulocytic-type colonies with maximum numbers of CFU-Gs and CFU-GMs, followed by CFU-Ms. However, incubation of DL-BMCs with 100 ng/ml of Talpha1, in vitro restored their suppressed proliferation and colony forming ability (CFA) with significantly enhanced total number of colonies and individual colony types, which further increased in the presence of CSFs. In vivo studies with BMCs from DL-bearing mice treated with single intraperitoneal injection of 10 microg Talpha1/mouse also resulted in significant enhancement in their proliferative as well as colony forming ability in comparison to that of untreated DL-mice. The present observations suggest that Talpha1 can positively modulate the haematopoietic functions of normal murine BMCs, in addition to its myelorestorative role in tumour-bearing mice showing suppressed myelopoiesis.     

Assessment of the effect upon maternal knowledge of an information leaflet about pain relief in labour

Pregnant women were randomly assigned to receive, at booking, the usual written information pack either with or without the Obstetric Anaesthetists' Association's (OAA's) leaflet 'Pain Relief in Labour'. At 36 weeks' gestation, a structured interview was conducted at which we assessed the sources of information the women had used and their knowledge of specific aspects of obstetric analgesia and anaesthesia described in the OAA leaflet. The most useful sources of information overall were friends, family, midwives, books and information leaflets (no significant difference between the groups); 72% of all women felt they had received adequate information although 70% said they would have liked to have discussed methods of analgesia with an anaesthetist before delivery. Parturients allocated to receive the leaflet (n = 37) were more knowledgeable than those who received only standard booking information (n = 39) about all analgesic and anaesthetic techniques except for systemic pethidine, although this difference in knowledge only reached statistical significance for extending epidural analgesia for emergency Caesarean section. We conclude that the OAA leaflet improves women's knowledge of analgesic techniques and suggest that all information of this type be formally assessed in this manner; furthermore given the practical difficulties in conducting studies of this type, the latter should be adequately resourced, perhaps by the bodies that issue such leaflets.