St Bartholomew's Hospital

About: St Bartholomew's Hospital is a healthcare organization based out in London, United Kingdom. It is known for research contribution in the topics: Population & Cancer. The organization has 11054 authors who have published 13229 publications receiving 501102 citations. The organization is also known as: St. Bartholomew's Hospital & The Royal Hospital of St Bartholomew.

Randomized placebo‐controlled trial of the activity of the morphine glucuronides

Abstract: Background Morphine-6-glucuronide (M6G) is an active metabolite of morphine with potent analgesic activity. Morphine-3-glucuronide (M3G), the most prevalent metabolite, has minimal affinity for opioid receptors. It has been suggested from animal model data and by examination of metabolite ratios in humans that M3G may functionally antagonize the respiratory depressant and analgesic actions of morphine and M6G. Methods We performed a double-blind placebo-controlled trial with 10 healthy volunteers. The trial had 6 arms: (1) placebo, (2) 10 mg/70 kg of morphine, (3) 3.3 mg/70 kg of M6G, (4) 30.6 mg/70 kg of M3G, (5) 30.6 mg/70 kg of M3G with 10 mg/70 kg of morphine, and (6) 30.6 mg/70 kg of M3G with 3.3 mg/70 kg of M6G; all were give by slow intravenous bolus. Analgesia was assessed with the use of the submaximal ischemic pain model. The effects were quantified on numerical and visual analogue scales. Respiratory parameters and response to steady state 5% carbon dioxide challenge were assessed with spirometry, mass spectroscopy, and earlobe blood gas analysis. Results Morphine and M6G produced significant pain relief compared with placebo (morphine, P < .0001; M6G, P = .033). Pain relief after M6G was less than after morphine (P = .009) and M3G was no better than placebo (P = .26). Pain relief with morphine and M6G were not significantly altered by M3G (P = .59 and P = .28, respectively). Significant and similar dysphoria and sedation occurred with both morphine (P < .002) and M6G (P < .016) but were absent with both M3G and placebo. Respiratory parameters suggested that M6G produced less respiratory depression than morphine. Both morphine and M6G caused a significant reduction in respiratory drive compared with placebo (morphine, P = .002; M6G, P = .013); this effect was not reversed by M3G (P = .35 and P = .83, respectively). Conclusions M3G appears to be devoid of significant activity; in these circumstances and at these doses, it does not antagonize either the analgesic or respiratory depressant effects of M6G or morphine. (Clin Pharmacol Ther 2000;68:667-76.) Clinical Pharmacology & Therapeutics (2000) 68, 667–676; doi: 10.1067/mcp.2000.111934

Bortezomib, doxorubicin and dexamethasone (PAD) front-line treatment of multiple myeloma: updated results after long-term follow-up

Abstract: Bortezomib, doxorubicin and dexamethasone (PAD) was evaluated as induction before stem cell transplantation in newly diagnosed multiple myeloma (MM) patients, using bortezomib 1.3 mg/m(2) (PAD1, N = 21) or 1.0 mg/m(2) (PAD2, N = 20). Complete/very good partial response rates with PAD1/PAD2 were 62%/42% postinduction and 81%/53% post-transplant. Progression-free survival (29 vs. 24 months), time to re-treatment (36 vs. 29 months) and overall survival (1 year: 100% vs. 95%; 2 years: 95% vs. 73%) were statistically similar but favoured PAD1 versus PAD2. Toxicity was lower in PAD2; bortezomib dose reduction may help manage toxicities while retaining efficacy. PAD is highly active as front-line induction in MM.

Insulin autoantibodies in the pre-diabetic period: correlation with islet cell antibodies and development of diabetes.

Abstract: IgG and IgM class insulin autoantibodies were measured by an enzyme-linked immunosorbent assay in sera from members of the Barts-Windsor-Middlesex prospective family study for Type 1 (insulin-dependent) diabetes. One hundred and twelve individuals from 28 families were selected for study on the basis of a clearly defined islet cell antibody status. IgG insulin autoantibodies were found to be significantly associated with islet cell antibody positive (n=30) versus islet cell antibody negative (n= 57) first degree family relatives (p=0.002), with increased significance (p=0.0003) if complement-fixing (CF)-islet cell antibody individuals (n=20) only were considered. In addition, a significant association of IgG insulin autoantibodies with subsequent development of diabetes was observed within the CF-islet cell antibody positive group (p<0.0003). No such associations were found for IgM insulin autoantibodies, but a higher prevalence of these autoantibodies was observed in islet cell antibody negative first degree relatives (n=57) compared with a control group of 73 Blood Bank donors (p=0.00007), and they were significantly associated with siblings (n=48) rather than parents (n=39), (p=0.001). We conclude that the presence of IgG insulin autoantibodies and CF-islet cell antibodies confer more risk for future development of diabetes than the presence of either marker alone.