Postamputation Pain and Sensory Changes in Treatment-naive Patients: Characteristics and Responses to Treatment with Tramadol, Amitriptyline, and Placebo

Background: Pain after amputation is common but difficult to treat, and few controlled treatment studies exist.

Methods: In the current study, 94 treatment-naive posttraumatic limb amputees with phantom pain (intensity: mean visual analog scale score [0-100], 40 [95% confidence interval, 38-41]) were randomly assigned to receive individually titrated doses of tramadol, placebo (double-blind comparison), or amitriptyline (open comparison) for 1 month. Nonresponders were crossed over to the alternative active treatment.

Results: After 1 month, phantom pain intensity was 1 (0-2) in the 48 tramadol responders (mean dose, 448 mg [95% confidence interval, 391-505 mg]), 0 (0-0) in the 40 amitriptyline responders (55 [50-59] mg), and 0 (0-0) in the 2 placebo responders, with similar effects on stump pain. Cytochrome P-450 2D6 slow metabolizers derived greater analgesia from tramadol and less from amitriptyline compared with fast metabolizers in the first treatment week (P < 0.01). Electrical pain thresholds increased and pain during suprathreshold stimulation decreased markedly on the stump and, to a lesser extent, on the contralateral limb after 1 month of treatment with amitriptyline or tramadol. Adverse effects were minor in all groups, but more common with tramadol.     

Avoidance of Nitrous Oxide for Patients Undergoing Major Surgery: A Randomized Controlled Trial

Background: Nitrous oxide is widely used in anesthesia, often administered at an inspired concentration around 70%. Although nitrous oxide interferes with vitamin B12, folate metabolism, and deoxyribonucleic acid synthesis and prevents the use of high inspired oxygen concentrations, the consequences of these effects are unclear.

Methods: Patients having major surgery expected to last at least 2 h were randomly assigned to nitrous oxide-free (80% oxygen, 20% nitrogen) or nitrous oxide-based (70% N2O, 30% oxygen) anesthesia. Patients and observers were blind to group identity. The primary endpoint was duration of hospital stay. Secondary endpoints included duration of intensive care stay and postoperative complications; the latter included severe nausea and vomiting, and the following major complications: pneumonia, pneumothorax, pulmonary embolism, wound infection, myocardial infarction, venous thromboembolism, stroke, awareness, and death within 30 days of surgery.

Results: Of 3,187 eligible patients, 2,050 consenting patients were recruited. Patients in the nitrous oxide-free group had significantly lower rates of major complications (odds ratio, 0.71; 95% confidence interval, 0.56-0.89; P = 0.003) and severe nausea and vomiting (odds ratio, 0.40; 95% confidence interval, 0.31-0.51; P < 0.001), but median duration of hospital stay did not differ substantially between groups (7.0 vs. 7.1 days; P = 0.06). Among patients admitted to the intensive care unit postoperatively, those in the nitrous oxide-free group were more likely to be discharged from the unit on any given day than those in the nitrous oxide group (hazard ratio, 1.35; 95% confidence interval, 1.05-1.73; P = 0.02).     

Systemic Antiinflammatory Corticosteroid Reduces Mechanical Pain Behavior, Sympathetic Sprouting, and Elevation of Proinflammatory Cytokines in a Rat Model of Neuropathic Pain

Background: Chronic pain models are commonly defined as either nerve-injury or inflammation models, but recent work suggests inflammatory processes are important in nerve injury-induced pain.

Methods: In the rat spinal nerve ligation model, the authors examined effects of systemic corticosteroid triamcinolone acetonide (TA) on the cytokine protein profile and sympathetic sprouting in the axotomized sensory ganglia, excitability of sensory neurons, and mechanical sensitivity.

Results: By postoperative day 3, marked increases (5- to 16-fold) in monocyte chemoattractant protein-1, growth-related oncogene (GRO/KC or CXCL1), and interleukin (IL)-6 were observed, whereas IL-4 and IL-2 levels fell more than fourfold. The increased cytokines and number of sympathetic basket formations in the sensory ganglia were reduced toward normal values by TA given starting at the time of injury. Interleukin-4 and IL-2 levels were not restored by TA. Systemic TA also reduced the firing rate and incidence of bursting activity, but not the overall incidence of spontaneous activity, in large- and medium-sized neurons. Mechanical hypersensitivity on postoperative day 3 was reduced by TA, and some effect could still be observed 4 days after cessation of TA. However, starting TA at day 7 was ineffective.     

Generation of platelet activating factor (PAF) by a human lung epithelial cell line

A human lung epithelial cell line (ATC-CCL-185) was cultured in nutrient Ham-F12 medium. Cells in monolayers were stimulated with either ionophore A23187 (1 microM) or phorbol myristate acetate (PMA, 0.2 microM) for various periods of time. Samples were analysed by HPLC and the presence of platelet activating factor (PAF) was detected by bioassay of the release of [3H]serotonin from rabbit platelets undergoing aggregation. The ATC-CCL 185 cells were found to synthesize PAF following activation with either PMA or ionophore. Ionophore at 1 microM was found to be more potent than PMA at 0.2 microM in the induction of PAF synthesis (congruent to 80 ng/mg protein). The synthesis of PAF through ionophore stimulation reached a maximum at 5 min, whereas PMA stimulation peaked at 15-20 min. PMA induced approximately one third the level of PAF synthesis by the ionophore. The PAF synthesized by these CCL185 cells was found to be mainly associated with the cell membrane with less than 10% released into the medium. Release of PAF into cell supernatant was dependent on the presence of bovine serum albumin (BSA). In the absence of BSA, a large portion (approximately 90%) of PAF was found to be cell associated, and only 60% when BSA concentration reached greater than or equal to 0.2%. These results demonstrate the ability of this lung epithelial cell line to synthesis PAF thus, suggesting that epithelial cells might participate in the process of inflammatory lung diseases, through the generation of this important mediator.     

Randomized Evaluation of an Inflatable Femoral Artery Compression Device After Cardiac Catheterization

Mechanical femoral artery compression devices have several limitations. We compared a novel disposable beltheld pneumatic compression device to manual compression alone in 213 patients randomized into two equal groups. Both were comparable for age, gender, current therapy with aspirin (ASA) and warfarin, diameter of the arterial sheath, previous procedures via the same artery, procedure duration, and blood pressure. Manual compression time was 12 ± 3 minutes. Pneumatic compression was reduced during 60 minutes. Patient discomfort was assessed as none (82% vs 88%), mild (13% vs 8%), moderate (3% vs 4%), or severe (2% vs 0%) for the manual versus pneumatic group, respectively. Bleeding and hematoma occurred in 7.5% of patients with no difference between the treatment groups. However, manual compression was significantly more effective in the higher range of systolic blood pressure, and pneumatic in the lower range, with a cut point of approximately 170 mmHg. Predictors for bleeding were systolic blood pressure and dose of ASA. Among 113 patients with systolic blood pressure < 160 mmHg and low dose (75 mg) or no ASA, only / patient (0.9%) experienced bleeding while 31% of 16 patients with both elevated systolic blood pressure and high dose ASA (150–330 mg) bled. We conclude that pneumatic femoral artery compression does not reduce bleeding and hematoma compared with manual compression. The use of low dose (75 mg) or no ASA, as well as giving special attention to patients with elevated systolic blood pressure, may reduce the risk of bleeding after cardiac catheterization .     

High molecular weight aggregate from cataractous and normal human lenses: characterization by antisera to lens crystallins

High molecular weight and low molecular weight fractions were obtained from total soluble proteins of human cataractous and normal lens nuclei. These fractions were analyzed using a solid phase radioimmunoassay that employed monospecific antisera to alpha, beta and gamma crystallins. Relative to the high molecular weight fraction from normal lens nuclei, the high molecular weight fraction from cataractous lens nuclei showed decreased binding to antisera specific for beta and gamma crystallins. These results demonstrate that the polypeptides of the high molecular weight fraction comprise a special class of polypeptides that have preferentially undergone covalent and/or structural changes during the process of human cataractogenesis.     

B-cell and T-regulatory cell dysfunction in six Chinese children with hypogammaglobulinaemia

We report six Chinese boys with hypogammaglobulinaemia. All but one had very low or undetectable circulating B-lymphocytes, two had reversed CD4/CD8 ratios (in one of whom this later became normal), one had reduced lymphocyte proliferative responses to concanavalin A and pokeweed mitogen and three had deficient responses to OKT3. Generation of antibody-secreting cells in response to pokeweed mitogen was markedly defective in all patients. Co-cultures of purified lymphocyte subsets from the patients with those of normal donors revealed that in addition to B-cell deficiency seen in all patients, two had T-helper cell deficiency and two had T-suppressor cell hyperactivity. One of the latter patients was treated with cimetidine in an attempt to ablate histamine type 2 receptor-bearing suppressor cells: the absolute number of such cells was temporarily reduced but there was no concurrent correction of the functional hyperactivity. These studies point to the variable nature of T-regulatory cell deficiencies in hypogammaglobulinaemia.     

Social networks of residents in supportive housing

One goal of supportive housing is to enlarge and improve the functioning of the social support networks of residents. The networks of a convenience sample of 42 residents were assessed using scales developed by Barrera. The size of the networks (11.5) was no larger than that reported for similar clients living in other types of community settings but the composition differed. Staff and co-residents appear to partially replace rather than add to family and friends. This is of concern because friends are uniquely important determinants of satisfaction. An association between perceived need for support and network size was also found. These findings suggest some positive influences but also raise questions about unintended negative consequences of living in artificially constructed social environments.When this project was undertaken, Dr. Goering, Janet Durbin, Bill Lancee and Taras Babiak were all members of the Social and Community Psychiatry Section, Clarke Institute. Robert Foster was Executive Director of Regeneration House, Inc., where Susan Boyles is Assistant Executive Director.