Challenges in accessing multidisciplinary pain treatment facilities in Canada

PURPOSE: The objective of this survey was to examine the services offered by multidisciplinary pain treatment facilities (MPTFs) across Canada and to compare access to care at these MPTFs. METHODS: A MPTF was defined as a clinic that advertised specialized multidisciplinary services for the diagnosis and management of patients with chronic pain, having a minimum of three different health care disciplines (including at least one medical speciality) available and integrated within the facility. The search method included approaching all hospital and rehabilitation centre administrators in Canada, the Insurance Bureau of Canada, the Workplace Safety and Insurance Board or similar body in each province. Designated investigators were responsible for confirming and supplementing MPTFs from the preliminary list for each province. Administrative leads at each eligible MPTF were asked to complete a detailed questionnaire regarding their MPTF infrastructure, clinical, research, teaching and administrative activities. RESULTS: Completed survey forms were received from 102 MPTFs (response rate 85%) with 80% concentrated in major cities, and none in Prince Edward Island and the Territories. The MPTFs offer a wide variety of treatments including non-pharmacological modalities such as interventional, physical and psychological therapy. The median wait time for a first appointment in public MPTFs is six months, which is approximately 12 times longer than non-public MPTFs. Eighteen pain fellowship programs exist in Canadian MPTFs and 64% engage in some form of research activities CONCLUSION: Canadian MPTFs are unable to meet clinical demands of patients suffering from chronic pain, both in terms of regional accessibility and reasonable wait time for patients' first appointment.     

Poly-l-aspartic acid protects cultured human proximal tubule cells against aminoglycoside-induced electrophysiological alterations

Cultured human proximal tubule cell monolayers maintained on permeable supports were treated simultaneously with the aminoglycoside antibiotic, gentamicin, and poly- -aspartic acid (PAA), an inhibitor of aminoglycoside nephrotoxicity. Following 4 days of exposure, cell monolayers were placed into Ussing chambers to allow monitoring of transepithelial electrical properties. For each of the three cell isolatation examined, aminoglycoside-induced alterations in electrogenic transport, reflected by changes in short-circuit current (Isc), as well as alterations in paracellular properties, indicated by changes in transepithelial electrical resistance (R_T), were diminished in the presence of PAA. Alterations resulting from selective basolateral exposure to gentamicin were unchanged in the case of apically applied PAA and attenuated only when PAA acid was added basolaterally. This is the first demonstration of PAA inhibition of aminoglycoside-induced cellular alterations involving human cells.     

Cell proliferation in human cerebral tumors. In vivo study of 45 cases by incorporation of 5-iododesoxyuridine

A method to study the proliferation of human brain tumors, is presented. Non radioactive 5-Iododeoxyuridine (2.4 gr) infused over a 24 hours period is detected in situ on histologic section by an immunological technique (peroxidase-anti-peroxidase) using a specific anti-Iododeoxyuridine antibody. This exploration utilised in 45 patients is easy, reliable and harmless. All cells which enter in S phase of cellular cycle during the infusion are labelled. So the cellular kinetics of all the brain tumor cells (malignant cells, inflammatory stroma reaction cells, reactive astrocytes, endothelial and muscular cells of the vessels) are detected on the same histological section, as well as all the others proliferative cells of the body (leukocytes, primitive tumor of the metastatic brain localisation...) if multiples biopsies are done. 8 of 9 gliomas of low histological malignancy (grade I and II) have a slow cellular kinetic. The 23 astrocytomas of different histological malignancy (grade III and IV) have variable proliferative speed (7 very fast, 8 fast and 8 slow). Only the large cells of the pinealoma are very proliferative, the lymphoid stroma is quiescent. The 5 metastasis have a slow to very fast kinetic without correlation with the cellular differentiation except in one case (important differentiation and slow cellular proliferation). The 5 lymphoma cells kinetics are well correlated with the histologic differentiation (3 large cells poor differentiated lymphomas and very fast kinetic, 2 better differentiated and slower proliferation). The 2 meningiomas proliferate slowly. The biochemical and histopathological grounds of the presented method and the limits of quantification are discussed. This method is compared with this using Bromodeoxyuridine. The correlation between proliferation and histologic malignancy is analysed. The use of cytokinetic results for therapeutic and prognosis need further statistical anatomoclinical studies.     

Acetylcholinesterase Adaptation to Voluntary Wheel Running is Proportional to the Volume of Activity in Fast, but not Slow, Rat Hindlimb Muscles

Chronic enhancement of neuromuscular activity by forced exercise training programmes results in selective adaptation of the G₄ acetylcholinesterase (AChE) molecular form in hindlimb fast muscles of the rat, with only minor and non-selective AChE changes in the soleus. In order to shed further light on the physiological significance of this G₄ adaptation to training, we turned to a voluntary exercise model. The impact of 5 days and 4 weeks of voluntary wheel cage running on AChE molecular forms was examined in four hindlimb fast muscles and the slow-twitch soleus from two rat strains. Inbred Fisher and Sprague– Dawley rats, placed in live-in wheel cages, exercised spontaneously for distances which progressively increased up to an average of ∼3 and 18 km/day, respectively, by the end of week 4. Fast muscles responded to this voluntary activity by massive G₄ increases (up to 420%) with almost no changes in A₁₂, so that by week 4 the tetramer became the main AChE component of these muscles. The additional G₄ was composed primarily of amphiphilic molecules, suggesting a membrane-bound state. The G₄ content of fast muscles was highly correlated with the distance covered by the rats during the 5 days before they were killed ( r = 0.850-0.879, P < 0.001 in three muscles). The soleus muscle, in turn, responded to wheel cage activity by a marked selective reduction of its asymmetric forms—up to 45% for A₁₂. This A₁₂ decline, already maximal by day 5 of wheel cage running, showed no relationship with the distance covered. The present results constitute strong new evidence suggesting that the role of AChE in neuromuscular transmission is not limited solely to the rapid inactivation of just-released acetylcholine.     

The S segment of the Germiston virus RNA genome can code for three proteins

The complete sequence of the S segment of Germiston bunyavirus has been determined from plasmids containing S cDNA inserts. The S segment is 980 nucleotides long with the first 15 bases at the 3' end complementary to the first 15 bases at the 5' end. Three overlapping open reading frames (ORF) were identified in the viral complementary RNA strand. The first ORF codes for a polypeptide of 233 amino acids (Mr 26,600) which is the nucleoprotein N. The second ORF codes for a polypeptide of 109 amino acids (Mr 11,800) which corresponds to the NSS protein, also called p12. Following this ORF, in the same frame, a third ORF which could encode a polypeptide of 75 amino acids was identified. Such a polypeptide has not yet been detected in infected cells. The N and NSS proteins of Germiston virus were compared with the corresponding proteins of La Crosse, snowshoe hare, and Aino viruses, and show a high extent of homology.     

Tetrahydrothiadiazoloisoquinolines: synthesis and inhibition of phenylethanolamine-N-methyltransferase

A series of 7,8-fused heterocyclic tetrahydroisoquinolines were synthesized and tested as inhibitors of rabbit adrenal phenylethanolamine-N-methyltransferase (PNMT). 6,7,8,9-Tetrahydro[1,2,3]thiadiazolo[5,4-h]isoquinoline 5 (SK&F 86607) was found to be a potent inhibitor of PNMT with an IC50 similar to that of 7,8-dichloro-1,2,3,4-tetrahydroisoquinoline (1, SK&F 64139). The isomeric tetrahydro[1,2,3]thiadiazolo[4,5-h]- and tetrahydro[1,2,5]thiadiazolo[3,4-h]isoquinolines, 13 and 20, were also potent PNMT inhibitors. However, substitution of Cl at position 5 (17) resulted in loss of potency similar to the loss observed in the 5-chloro analogue of 1. The 1,2,5 isomer 20 showed only a small drop in activity at 10(-6) M. All of the thiadiazoles were more potent than the 7,8-benzo-fused analogue 36. Fusion of other five-membered heterocyclic ring systems at the 7,8-position, e.g. triazole 22 and imidazoles 24 and 26, resulted in a decrease of PNMT inhibition. The alpha-adrenoreceptor affinities of 1 and 5 were also compared.     

A reusable, custom-made warming blanket prevents core hypothermia during major neonatal surgery

PURPOSE: To introduce a reusable model of neonatal forced air warming blanket for intraoperative use during major noncardiac neonatal surgery and to determine clinical efficacy of this reusable blanket compared with the commonly used disposable blankets. METHODS: Delivered air temperature and calorie uptake of standard thermal bodies within the reusable blankets, Bair Hugger(R) blanket model 530 and model 555 were studied. Also, an efficacy study was conducted in 90 neonatal patients scheduled for major noncardiac surgery comparing the reusable blanket, the Bair Hugger(R) blanket model 530 and passive heat conservation as a control. The covered reusable blanket was used as a rescue procedure if the core temperature was < 35.5 degrees C. RESULTS: Delivered air temperature and heat transfer from the covered reusable blanket did not differ significantly from those of the Bair Hugger(R) blanket model 530 and model 555 (despite 0.75 degrees C-1.2 degrees C of heat trapped under the sheet and 1.3 Kcal less energy transfer). Temperatures measured underneath patients (correlated to poorly perfused areas) were highest using the Bair Hugger(R) blanket model 555. The reusable blanket was efficacious in preventing intraoperative core hypothermia and not different from the Bair Hugger(R) blanket model 530. About 1/3 of the patients in the control group had presented a core temperature < 35.5 degrees C but were successfully rescued using the reusable blanket. No adverse events were associated with any of these warming methods. CONCLUSION: This study shows the clinical efficacy of our reusable blanket for the prevention of core hypothermia during major neonatal surgery, which is not different from commonly used disposable blankets.