d-penicillamine: Chemistry and clinical use in rheumatic disease

The discovery of d-penicillamine and its uses in medicine are reviewed. Chemical-physical properties are discussed, and the molecular structure of d-penicillamine and several of its reaction products are illustrated. Examples of its three main types of biochemical reactions—sulfhydryl-disulfide exchange, thiazolidine formation, and metal chelation are included. Trials of d-penicillamine in RA patients are reviewed critically. The administration of the drug is discussed in detail, including dosages, clinical and laboratory responses, patterns of adverse side effects or toxicity, drug-induced autoimmune diseases, indications and contraindications, and the monitoring and management of patients.     

Using pedometers to increase physical activity in overweight and obese women: a pilot study

Background  

Most public health guidelines recommend that adults participate in 30 minutes of moderate intensity physical activity on most days of the week. Establishing new ways to achieve these targets in sedentary populations need to be explored. This research evaluated whether the daily use of pedometers could increase physical activity and improve health outcomes in sedentary overweight and obese women.     

Octreotide in refractory functional epigastric pain with nutritional impairment—an open study

AIM: To test the therapeutic efficacy of octreotide administered subcutaneously for the relief of chronic refractory epigastric pain severe enough to provoke nutritional impairment. SUBJECTS AND METHODS: Seventeen patients were enrolled in an open trial. Epigastric pain had lasted from 1 to 8 years (median: 5 years), following anti-reflux surgery in eight patients. Median weight loss was 10% (range 10-15). The initial dose of octreotide was 50 microgram b.d, adjusted during the follow-up visits which were scheduled for months 1, 3, 6, 8, 10, 12 and every 3 months. At each visit, overall symptomatic improvement, frequency and intensity of symptoms were checked on a 10-cm visual analogic scale. RESULTS: At month 1, a progressive improvement of pain intensity was reported in 15 of the 17 patients, while octreotide was a therapeutic failure in two. In four out of 15, the daily dose of octreotide was increased to 100 microgram b.d. In these 15 patients, median follow-up was 7 months (3-27). The symptomatic benefit was maintained in each patient at month 3, with a median weight gain of 3.5 kg.2-5 An attempt to stop octreotide led to recurrence of symptoms in 2-3 days which were as intense as before the treatment. The 11 patients followed-up for at least 6 months reported persistent improvement of symptoms with octreotide and a median weight gain of 4 kg.3-7 Four patients were followed up for more 11-27 months: octreotide was withdrawn gradually in two who remained asymptomatic. Six of the 17 patients experienced minor side-effects, but none developed biliary sludge. CONCLUSIONS: This open study suggests that octreotide could be a promising alternative treatment when all others fail in refractory chronic functional epigastric pain severe enough to limit food intake and to induce nutritional impairment. These results must be tested by a placebo-controlled study.     

Serum Free‐Light Chain Removal by High Cutoff Hemodialysis: Optimizing Removal and Supportive Care

In multiple myeloma the predominant cause of irreversible renal failure is cast nephropathy, secondary to excess κ or λ serum free light chains (FLCs). These molecules are efficiently cleared by hemodialysis (HD) using the Gambro HCO 1100 dialyzer. To optimize the removal of FLCs by this dialyzer we have studied the effect of dialyzers in series, dialyzer change, and hemodiafiltration in 14 patients with multiple myeloma and renal failure. The clearance rates of both κ FLCs and λ FLCs were significantly increased on two dialyzers from 19 (7.3–34)–15.3 (9–28) mL/min to 47 (17–79)–35.5 (20–57) mL/min, respectively. Clearance rates of both FLCs decreased over the course of the dialysis sessions (both P < 0.001). Changing the dialyzer during a HD session increased λ FLC clearance rates (22.5 [6–41] to 37.6 [9–52] mL/min; P < 0.001) and decreased κ FLC clearance rates (39.6 [9–72] to 19 [8–59] mL/min; P < 0.003). Ultrafiltration during HD increased the clearance rates of κ FLCs (R 0.52, P < 0.01) but not λ FLCs (R ?0.25; P < 0.076). Hemodiafiltration increased the clearance rates of both κ (19 [SD 6.8] to 32 [SD 9.8] mL/min) and λ FLCs (15 [SD 7.8] to 20 [SD 7.7] mL/min). Albumin replacement requirements for 8 h of HD increased from 12 g for a single dialyzer to 45 g for two dialyzers in series (P < 0.001). Different protocols are required to optimize the removal of κ and λ FLCs in patients with myeloma and renal failure.     

Persistent Depression of Contractility and Vasodilation with Propofol but Not with Sevoflurane or Desflurane in Rabbits

Background: Propofol, sevoflurane, and desflurane may cause hemodynamic compromise during anesthesia and critical care management. The aim of the study was to compare these anesthetics during increased dose and recovery to maintenance level.

Methods: Anesthetized, open-chest New Zealand White rabbits were used to acquire dose-response curves with sevoflurane, desflurane, and propofol, followed by reduction to baseline infusion. Simultaneous high-fidelity left ventricular pressure and volume data were acquired during caval occlusion with a dual-field conductance catheter inserted via an apical stab. The preload recruitable stroke work and the end-diastolic pressure-volume relationship were used as the primary measures of contractility and diastolic function.

Results: The time-matched controls were stable over time. Propofol and desflurane but not sevoflurane caused dose-dependent reductions in myocardial contractility, although sevoflurane reduced contractility more at 1 minimal alveolar concentration. All anesthetics reduced mean arterial pressure, and significant recovery occurred for sevoflurane and desflurane but not for propofol. The end-diastolic pressure-volume relationship was increased by sevoflurane. Ejection fraction decreased with sevoflurane only. All anesthetics caused dose-dependent vasodilation, with recovery for desflurane and sevoflurane but not propofol. Heart rate was decreased with propofol without significant recovery. Propofol plasma concentrations remained elevated after dose return to baseline infusion rate, suggestive of distribution compartment saturation.