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.     

Automated three-dimensional analysis of histological and autoradiographic rat brain sections: application to an activation study.

Besides the newly developed positron emission tomography scanners (microPET) dedicated to the in vivo functional study of small animals, autoradiography remains the reference technique widely used for functional brain imaging and the gold standard for the validation of in vivo results. The analysis of autoradiographic data is classically achieved in two dimensions (2D) using a section-by-section approach, is often limited to few sections and the delineation of the regions of interest to be analysed is directly performed on autoradiographic sections. In addition, such approach of analysis does not accommodate the possible anatomical shifts linked to dissymmetry associated with the sectioning process. This classic analysis is time-consuming, operator-dependent and can therefore lead to non-objective and non-reproducible results. In this paper, we have developed an automated and generic toolbox for processing of autoradiographic and corresponding histological rat brain sections based on a three-step approach, which involves: (1) an optimized digitization dealing with hundreds of autoradiographic and histological sections; (2) a robust reconstruction of the volumes based on a reliable registration method; and (3) an original 3D-geometry-based approach to analysis of anatomical and functional post-mortem data. The integration of the toolbox under a unified environment (in-house software BrainVISA, http://brainvisa.info) with a graphic interface enabled a robust and operator-independent exploitation of the overall anatomical and functional information. We illustrated the substantial qualitative and quantitative benefits obtained by applying our methodology to an activation study (rats, n=5, under unilateral visual stimulation).     

Intravenous Lidocaine Infusion Facilitates Acute Rehabilitation after Laparoscopic Colectomy

Background: Intravenous infusion of lidocaine decreases postoperative pain and speeds the return of bowel function. The authors therefore tested the hypothesis that perioperative lidocaine infusion facilitates acute rehabilitation protocol in patients undergoing laparoscopic colectomy.

Methods: Forty patients scheduled to undergo laparoscopic colectomy were randomly allocated to receive intravenous lidocaine (bolus injection of 1.5 mg/kg lidocaine at induction of anesthesia, then a continuous infusion of 2 mg [middle dot] kg-1 [middle dot] h-1 intraoperatively and 1.33 mg [middle dot] kg-1 [middle dot] h-1 for 24 h postoperatively) or an equal volume of saline. All patients received similar intensive postoperative rehabilitation. Postoperative pain scores, opioid consumption, and fatigue scores were measured. Times to first flatus, defecation, and hospital discharge were recorded. Postoperative endocrine (cortisol and catecholamines) and metabolic (leukocytes, C-reactive protein, and glucose) responses were measured for 48 h. Data (presented as median [25-75% interquartile range], lidocaine vs. saline groups) were analyzed using Mann-Whitney tests. P < 0.05 was considered statistically significant.

Results: Patient demographics were similar in the two groups. Times to first flatus (17 [11-24] vs. 28 [25-33] h; P < 0.001), defecation (28 [24-37] vs. 51 [41-70] h; P = 0.001), and hospital discharge (2 [2-3] vs. 3 [3-4] days; P = 0.001) were significantly shorter in patients who received lidocaine. Lidocaine significantly reduced opioid consumption (8 [5-18] vs. 22 [14-36] mg; P = 0.005) and postoperative pain and fatigue scores. In contrast, endocrine and metabolic responses were similar in the two groups.     

Optimising Hormone Therapy in Advanced Disease

Although most prostate cancer (PCa) patients nowadays are diagnosed at an early stage of disease, unfortunately still a significant number of patients will develop advanced PCa or will be diagnosed at an advanced (or metastatic) stage of disease. The group of patients showing the highest increase in incidence are those with rising prostate specific antigen (PSA) after radical therapy.In the last quarter of 2004, a Medline search has been performed targeting publications on patients diagnosed with advanced PCa, as well as with PSA relapse after previous radical therapy. This review aims at providing guidance to optimise hormone therapy in those selected groups of patients by addressing three pivotal questions; (i) who should receive hormonal treatment, (ii) what type of hormonal therapy should the patient be offered and (iii) what is the best timing of starting hormonal treatment.In patients relapsing after radical therapy, the PSA doubling time (PSA DT) has become a critical instrument to distinguish patients to have innocuous PSA evolution from patients at high risk for disease progression. A PSA DT of 3 months seems to be the cut-off point for identifying patients at risk. Therefore patients with a PSA DT of less than 3 months should be advised to initiate hormonal therapy. Antiandrogen monotherapy may be considered in this setting as it has been shown to delay progression; however, significant survival data are not yet available. Whether luteinising hormone releasing hormone (LHRH) agonists should be given continuously or intermittently (IHT) remains subject of debate.Surgical castration has been the standard of care in patients diagnosed with advanced PCa. Currently, LHRH agonists have become the preferred way of suppressing testosterone.Combination of an antiandrogen and a LHRH agonist (CAB) shows a modest benefit over LHRH agonist monotherapy. As CAB leads to increased side effects and costs, LHRH agonist monotherapy is preferred in the majority of patients.Conflicting data have been published concerning the optimal timing of LHRH agonist therapy. So it is not clear whether LHRH agonist therapy should be started immediately or deferred until appearance of symptoms. When initiating continuous hormone therapy, patients should be carefully monitored for the risk of long term androgen deprivation (anaemia, osteopenia and osteoporosis).     

Participation in patient self‐management programs

Objective

Participation in evidenced‐based arthritis self‐management programs (SMPs) has not been well documented. The purpose of this study was to investigate the participation rate and participant characteristics in a closed cohort of subjects in a geographic region where arthritis SMPs have been offered multiple times and continuously for 2 decades.

Methods

Data were from osteoarthritis (OA) and rheumatoid arthritis subjects participating in the Arthritis, Rheumatism, and Aging Medical Information System (ARAMIS) who resided in the San Francisco (SF) Bay area who had responded to questions about ever participating in an SMP. Differences between participants and nonparticipants were examined by t‐tests and chi‐square tests.

Results

Questions added to the Health Assessment Questionnaire were returned by 1,176 patients; 618 resided in the SF Bay area. Of the SF Bay area sample, 41.9% had participated in an SMP. Small group SMPs, which had been offered multiple times, in diverse settings, continuously over the past 2 decades, were attended by the highest proportion (28%) of participants. Characteristics of participants and nonparticipants in the SF Bay area were similar (～70 years old, 15 years of education, and the majority had OA [～72%]). However, a higher proportion of participants were white (88% versus 82%; P = 0.046) and female (82% versus 73%; P < 0.05).

Conclusion

When arthritis SMPs were offered multiple times in diverse settings and continuously over many years, >40% of the cohort was reached. More research is needed with larger samples and different geographic regions to identify participation rates in more diverse populations.     

Physiological pharmacokinetics of solutes in the isolated perfused rat hindlimb: Characterization of the physiology with changing perfusate flow,protein content,and temperature using statistical moment analysis

Distribution of Evans Blue (EB), sucrose, and water into the isolated perfused rat hindlimb was studied under various conditions using the multiple indicator dilution (MID) technique. Statistical moment analyses of the outflow profiles for the EB, sucrose, and water were used to define the vascular, extravascular, and total water spaces, respectively. The varied perfusion conditions included albumin content (2, 4.7, and 7%), temperature (25, 37, and 42 C), perfusate flow rate (2, 4, 8, and 12 ml/min) and the presence/absence of red blood cells. The range of studies undertaken were chosen to represent the variety of conditions used in the preparation of both isolated animal and human limbs, the latter being particularly important in cytotoxic therapy for recurrent malignant melanoma. The distribution volumes of EB, sucrose, and water were dependent on the flow rate and the albumin content of perfusate. The normalized variances (CV ² ) of the markers were of the following order: sucrose (2.18) > water (1.58) > EB (0.68), indicating that some disequilibrium occurs during the capillary exchange of water and sucrose. It is suggested that a Krebs-Henseleit buffer containing 2% BSA is a suitable perfusate for most studies of the isolated rat hindlimb perfusion. The effect of albumin concentration manifests itself only at higher flows.We acknowledge the support of the National Heart Foundation (Queensland) and the Mayne Bequest Foundation. This study was conducted while the investigator (Z.Y. Wu) was in receipt of a WHO Research Training Grant. Professor M. S. Roberts also acknowledges the support of the Queensland and Northern New South Wales Lions Kidney & Medical Research Foundation.     

Sexual behavior and attitudes of University students in Northern Ireland

Two surveys of a Northern Ireland student sample were conducted in 1987 and 1988. A total of 419 female and 201 male subjects completed self-administered anonymous questionnaires concerning their behavior, knowledge, and attitudes towards sex, AIDS, homosexuality, contraception, and relationships. Results indicated a relatively low level of sexual experience, and for those with experience, relatively few partners. The possible influences of gender and religiosity on sexual behavior and attitudes, in the context of Northern Ireland, are discussed. Subjects reported considerable variation in the amount of sex education, but the majority received little or none. This student sample held relatively conservative attitudes towards love, sex, and marriage and this was particularly true for females and for regular churchgoers. In addition, attitudes towards homosexuality were negative (particularly among regular churchgoers). Attitudes towards contraception were more positive than expected among Catholic subjects, and few indicated that they would refuse to use contraceptives on principle. Responses to items about AIDS were highly uniform, suggesting that much of the information made available to the public has been absorbed. However, the lack of uniformity of response to more general items about sex, relationships, and contraception may indicate that fundamental changes in sexual behavior are unlikely to be brought about by influencing a rather narrowly defined set of attitudes about AIDS.     

First analysis of the proteome in two nematomorph species, Paragordius tricuspidatus (Chordodidae) and Spinochordodes tellinii (Spinochordodidae).

The proteome of most parasite species is currently unknown. Hairworms (Nematomorpha), 300 species distributed around the world, are parasitic in arthropods (mainly terrestrial species) when juveniles, but they are free-living in aquatic environments when adult. Most aspects of their systematics and biology are currently unknown. The aim of this paper was (i) to report a novel and reproducible protocol for the analysis of the proteome of hairworms using two-dimensional gel electrophoresis (2-DGE) and mass spectrometry (matrix laser desorption ionization-time of flight mass spectrometry (MALDI-TOF)) and (ii) to determine the level of proteomic divergence between two sympatric but taxonomically unrelated nematomorph species in the adult stage, Paragordius tricuspidatus Dufour (Nematomorpha, Gordiidae) and Spinochordodes tellinii Camerano (Nematomorpha, Gordiidae). In total, 689 protein spots were observed for P. tricuspidatus, 575 for S. tellinii. Only 36.2% spots were shared between the two species. Quantitative analysis of the proteins which are common to both parasite species reveals substantial differences in the pattern of protein expression. These results suggest a rapid evolutionary divergence between these two nematomorph families. Also, to test the value of our MALDI-TOF protocol, we used Actin-2 (Act-2), a protein highly conserved in the course of evolution. Peptide mass fingerprint (PMF) data obtained for Act-2 of P. tricuspidatus and S. tellinii suggest a very high homology with Act-2 of different worms species belonging to the Bilateria phylum (Annelida and Nematoda) and more specifically to Lumbricus terrestris (Annelida, Lumbricidae) and Caenorhabditis elegans (Nematoda, Rhabditidae). We discuss our results in relationship with current ideas concerning the use of proteomics in systematics.