Uso y prescripción de cannabis medicinal por reumatólogos en Argentina / Use and prescription of medical cannabis by rheumatologists in Argentina

El uso y prescripción del cannabis y sus derivados en Reumatología está aún en discusión. La ley de cannabis fue sancionada hace casi 3 años, aunque la reglamentación recién está comenzando. El objetivo de este estudio fue conocer la forma en que el reumatólogo se posiciona frente al uso de cannabis en el marco de su práctica médica. A través de una encuesta realizada durante el Congreso Argentino de Reumatología 2019 se recabó la opinión de 314 médicos que respondieron preguntas acerca del uso, recomendaciones y posturas respecto a la indicación y uso de cannabinoides en su práctica diaria. El 78,3% (246) conocían la existencia de una ley nacional. El 51,6% (162) se mostró en desacuerdo con el uso de cannabinoides en sus pacientes, mientras que el 36,6% (115) respondió estar de acuerdo, el 3,2% (10) refirió estar muy de acuerdo, y 8,6% (27) estaba muy en desacuerdo. Para pacientes con enfermedades reumáticas autoinmunes, el 94,6% (297) refirió que nunca indica cannabinoides, el 4,1% (13) que los indican pocas veces, y el 1,3% (4) algunas veces. Para las enfermedades reumáticas degenerativas, el 90,4% (284) nunca indica cannabinoides, el 6,7% (21) lo hace pocas veces, y el 2,9% (9) lo hace algunas veces. Para la fibromialgia, el 84,4% (265) nunca indica cannabinoides, el 8,3% (26) los indica pocas veces, el 6,4% (20) los indica algunas veces. El principal obstáculo para la prescripción (permitido más de una respuesta) fue no disponer de la suficiente información científica para prescribir (50,3%, 158), el 47,5% (149) contestó que no conoce los componentes de la preparación, el 47,1% (148) no conoce las dosis o la posología, el 41,4% (130) no le resultan confiables los productores, el 38,9% (122) respondió que no le convencen los estudios clínicos en la especialidad. No hubo diferencias significativas entre las variables edad, género, años en la especialidad o lugar de ejercicio y las respuestas descriptas. Conclusión: El uso de cannabis en Reumatología de acuerdo a los especialistas que ejercen en Argentina requiere de un mayor sustento científico y farmacéutico para poder prescribirlo en un marco seguro.

The use and prescription of cannabis and its derivatives in Rheumatology is still under discussion. The cannabis law was enacted near 3 years ago, although the regulation is just beginning. The objective of this study was to know how rheumatologists positions themselves about the use of cannabis in the framework of his medical practice. Through a survey conducted during the 2019 Argentine Congress of Rheumatology, 314 doctors answered questions about the use, recommendations and opinions regarding the indication and use of cannabinoids in their daily practice. 78.3% (246) knew of the existence of a national law. 51.6% (162) disagreed with the use of cannabinoids by their patients, while 36.6% (115) agreed, 3.2% (10) reported to strongly agree, and 8.6% (27) strongly disagreed. For patients with autoimmune rheumatic diseases, 94.6% (297) reported that they never prescribed cannabinoids, 4.1% (13) prescribed them rarely, and 1.3% (4) sometimes. For degenerative rheumatic diseases, 90.4% (284) never prescribed cannabinoids, 6.7% (21) did it rarely, and 2.9% (9) did so sometimes. For fibromyalgia, 84.4% (265) never prescribed cannabinoids, 8.3% (26) prescribed them rarely, 6.4% (20) sometimes. The main obstacle to prescribing (more than one answer allowed) was not having enough scientific information (50.3%, 158), 47.5% (149) were uncertain about the cannabis preparation, 47.1% (148) had no knowledge about doses or posology, 41.4% (130) didn´t trust the producers, 38.9% (122) were no convince by the trials in the field. There were no significant differences between the variables age, gender, years in the specialty or workplace and the responses described. Conclusion: According to specialists in Argentina, the use of cannabis in rheumatology requires more scientific and pharmaceutical data to prescribe cannabinoids in a safer framework.

[Long-term survival metastatic ovarian cancer elderly patient]. / Paziente anziana con carcinoma ovarico metastatico lungo-sopravvivente.

Ovarian cancer is the sixth diagnosed cancer among women worldwide, it has a high mortality and in most cases it's diagnosed in advanced stage (stage III-IV). Combination platinum-paclitaxel chemotherapy administered every 3 weeks is considered the gold standard for first-line treatment of patients with advanced ovarian cancer. Elderly patients with ovarian cancer represents a subgroup with poor prognosis because they are often treated less radically for comorbidities and age. In the present article, we report a case of a 85 year old woman who was diagnosed with stage IV ovarian carcinoma for the presence of peritoneal carcinomatosis ab initio, not radically debulked and then treated with weekly schedule platinum-based and paclitaxel. Despite not being able to complete the chemotherapy, the patient achieved excellent results and represents a case of long survival.

Altered neuronal activity and differential sensitivity to acute antidepressants of locus coeruleus and dorsal raphe nucleus in Wistar Kyoto rats: a comparative study with Sprague Dawley and Wistar rats.

The Wistar Kyoto rat (WKY) has been proposed as an animal model of depression. The noradrenergic nucleus, locus coeruleus (LC) and the serotonergic nucleus, dorsal raphe (DRN) have been widely implicated in the ethiopathology of this disease. Thus, the goal of the present study was to investigate in vivo the electrophysiological properties of LC and DRN neurons from WKY rats, using single-unit extracellular techniques. Wistar (Wis) and Sprague Dawley (SD) rats were used as control strains. In the LC from WKY rats the basal firing rate was higher than that obtained in the Wis and SD strain, and burst firing activity also was greater compared to that in Wis strain but not in SD. The sensitivity of LC neurons to the inhibitory effect of the α2-adrenoceptor agonist, clonidine and the antidepressant reboxetine was lower in WKY rats compared to Wis, but not SD. Regarding DRN neurons, in WKY rats burst activity was lower than that obtained in Wis and SD rats, although no differences were observed in other firing parameters. Interestingly, while the sensitivity of DRN neurons to the inhibitory effect of the 5-HT1A receptor agonist, 8-OH-DPAT was lower in the WKY strain, the antidepressant fluoxetine had a greater inhibitory potency in this rat strain compared to that recorded in the Wis group. Overall, these results point out important electrophysiological differences regarding noradrenergic and serotonergic systems between Wis and WKY rats, supporting the utility of the WKY rat as an important tool in the research of cellular basis of depression.

Prospects for efficient detectors for fast neutron imaging.

A physical model describing in detail the process of fast neutron imaging in luminescent screens is presented. The detection quantum efficiency, luminosity and inherent spatial resolution of the screen were calculated using this model. Properties of transparent and disperse screens were compared. Two imaging systems were suggested to improve the detection efficiency and spatial resolution. A stack consisting of alternating neutron converters and image plates can help in obtaining both high spatial resolution and efficiency. A system containing a screen of special form and a diaphragm can be of use especially in the case of the fan beam.

Near-field artifact reduction in planar coded aperture imaging.

Coded apertures for imaging problems are typically based on arrays having perfect cross-correlation properties. These arrays, however, guarantee a perfect point-spread function in far-field applications only. When these arrays are used in the near-field, artifacts arise. We present a mathematical derivation capable of predicting the shape of such artifacts. The theory shows that methods used in the past to compensate for the effects of background nonuniformities in far-field problems are also effective in reducing near-field artifacts. The case study of a nuclear medicine problem is presented to show good agreement of simulation and experimental results with mathematical predictions.

Extension of cell life-span and telomere length in animals cloned from senescent somatic cells.

The potential of cloning depends in part on whether the procedure can reverse cellular aging and restore somatic cells to a phenotypically youthful state. Here, we report the birth of six healthy cloned calves derived from populations of senescent donor somatic cells. Nuclear transfer extended the replicative life-span of senescent cells (zero to four population doublings remaining) to greater than 90 population doublings. Early population doubling level complementary DNA-1 (EPC-1, an age-dependent gene) expression in cells from the cloned animals was 3.5- to 5-fold higher than that in cells from age-matched (5 to 10 months old) controls. Southern blot and flow cytometric analyses indicated that the telomeres were also extended beyond those of newborn (<2 weeks old) and age-matched control animals. The ability to regenerate animals and cells may have important implications for medicine and the study of mammalian aging.

Cloning of an endangered species (Bos gaurus) using interspecies nuclear transfer.

Approximately 100 species become extinct a day. Despite increasing interest in using cloning to rescue endangered species, successful interspecies nuclear transfer has not been previously described, and only a few reports of in vitro embryo formation exist. Here we show that interspecies nuclear transfer can be used to clone an endangered species with normal karyotypic and phenotypic development through implantation and the late stages of fetal growth. Somatic cells from a gaur bull (Bos gaurus), a large wild ox on the verge of extinction, (Species Survival Plan < 100 animals) were electrofused with enucleated oocytes from domestic cows. Twelve percent of the reconstructed oocytes developed to the blastocyst stage, and 18% of these embryos developed to the fetal stage when transferred to surrogate mothers. Three of the fetuses were electively removed at days 46 to 54 of gestation, and two continued gestation longer than 180 (ongoing) and 200 days, respectively. Microsatellite marker and cytogenetic analyses confirmed that the nuclear genome of the cloned animals was gaurus in origin. The gaur nuclei were shown to direct normal fetal development, with differentiation into complex tissue and organs, even though the mitochondrial DNA (mtDNA) within all the tissue types evaluated was derived exclusively from the recipient bovine oocytes. These results suggest that somatic cell cloning methods could be used to restore endangered, or even extinct, species and populations.

Prospects for the use of nuclear transfer in human transplantation.

The successful application of nuclear transfer techniques to a range of mammalian species has brought the possibility of human therapeutic cloning significantly closer. The objective of therapeutic cloning is to produce pluripotent stem cells that carry the nuclear genome of the patient and then induce them to differentiate into replacement cells, such as cardiomyocytes to replace damaged heart tissue or insulin-producing beta cells for patients with diabetes. Although cloning would eliminate the critical problem of immune incompatibility, there is also the task of reconstituting the cells into more complex tissues and organs in vitro. In the review, we discuss recent progress that has been made in this field as well as the inherent dangers and scientific challenges that remain before these techniques can be used to harness genetically matched cells and tissues for human transplantation.

Human therapeutic cloning.

Somatic cell nuclear 'reprogramming' in livestock species is now routine in many laboratories. Here, Robert Lanza, Jose Cibelli and Michael West discuss how these techniques may soon be used to clone genetically matched cells and tissues for transplantation into patients suffering from a wide range of disorders that result from tissue loss or dysfunction.

Xenotransplantation of cells using biodegradable microcapsules.

BACKGROUND: The use of immunoisolation to protect transplanted cells from the immune system of the host has broad application to the treatment of major diseases such as diabetes and a wide range of other disorders resulting from functional defects of native cell systems. In most cases, limitations in functional cell longevity will necessitate periodic replenishment of the cells. We describe a hydrogel-based microcapsule that breaks down at a rate that can be adjusted to correspond to the functional longevity of the encapsulated cells. These injectable capsules can be engineered to degrade over several weeks to months for short-term drug delivery, or to remain intact and immunoprotective for more extended periods. When the supply of cells needs to be replenished, no surgery will be required to localize and remove the old capsules. METHODS: Porcine and bovine islets were immobilized in "composite" microcapsules fabricated from alginate and low-relative molecular mass (Mr) poly (L-lysine[PLL]) (Mr exclusion <120 Kd) and implanted into the peritoneum of normal and streptozotocin-induced diabetic rats. In addition to demonstrating long-term islet viability and function, a series of in vitro studies were carried out to determine the permeability and biodegradability of the microcapsules used in the present system. RESULTS: Xenogeneic islets implanted in nonimmunosuppressed rats remained in excellent condition indefinitely (>40 weeks)(viability was comparable to that of preimplant control specimens). In contrast, no islets survived in uncoated alginate spheres after 2 weeks postimplantation. By changing the concentration of the alginate, it was possible to vary the rate of capsule breakdown in rats from mechanically unstable (outer matrix <0.5-0.75% alginate) to stable for >1 year (> or =1.5% alginate). In addition to in vivo breakdown studies, the biodegradability of the capsular components was verified in vitro using a mixture of tritosomes (enzymes isolated from animal cells). CONCLUSIONS: We have designed a microcapsule system with controllable biodegradability which allows breakdown and absorption of implants when the cells die or become functionally inactive. These results may have application to other alginate-PLL encapsulation systems. The ability to cross species lines using these biodegradable microcapsules has the potential to expand dramatically the number of patients and the scope of diseases that can be successfully treated with cellular therapy.

Shoulder pain in wheelchair users with tetraplegia and paraplegia.

OBJECTIVE: To compare the prevalence and intensity of shoulder pain experienced during daily functional activities in individuals with tetraplegia and individuals with paraplegia who use manual wheelchairs. DESIGN: Self-report survey. SETTING: General community. PARTICIPANTS: Fifty-five women and 140 men, 92 subjects with tetraplegia and 103 subjects with paraplegia who met inclusion criteria of 3 hours per week of manual wheelchair use and at least 1 year since onset of spinal cord injury. MAIN OUTCOME MEASURES: Respondents completed a demographic and medical history questionnaire and the Wheelchair User's Shoulder Pain Index (WUSPI), a measure of pain during typical daily activities. RESULTS: More than two thirds of the sample reported shoulder pain since beginning wheelchair use, with 59% of the subjects with tetraplegia and 42% of the subjects with paraplegia reporting current pain. Performance-corrected WUSPI scores were significantly higher in subjects with tetraplegia than in subjects with paraplegia. CONCLUSIONS: Both the prevalence and intensity of shoulder pain was significantly higher in subjects with tetraplegia than in subjects with paraplegia. Efforts to monitor and prevent shoulder pain should continue after rehabilitation.

Transplantation of islets using microencapsulation: studies in diabetic rodents and dogs.

Studies involving the transplantation of human islets in Type I diabetics have been of significant value both in documenting the potential importance of islet transplantation as a therapeutic modality, and in defining some of the problems which must be overcome before this approach can be used in large numbers of patients. The currently limited supply of adult human pancreatic glands, and the fact that chronic immunosuppression is required to successfully transplant islets into patients, indicate that techniques must be further developed and refined for allo- and xenografting of isolated islets from human and animal sources to diabetic patients. An increasing body of evidence using microencapsulation techniques strongly suggests that this will be achieved during the next few years. Data from our laboratory in rodents and dogs indicate that these systems can function for extended periods of time. In one study, insulin independence was achieved in spontaneously diabetic dogs by islet microencapsulation inside uncoated alginate gel spheres (Mr exclusion >600 kD). No synthetic materials or membrane coatings were employed in this study. Spheres containing canine islets were implanted into the peritoneum of 4 diabetic dogs. The animals received low-dose CsA (levels below readable limits by HPLC at 3 weeks). Implantation of these spheres completely supplanted exogenous insulin therapy in the dogs for 60 to >175 days. Blood glucose concentration averaged 122+/-4 mg/dl for these animals during the first 2 months. The glycosylated hemoglobin (HbAIC) levels during this period dropped from 6.7+/-0.5% to 4.2+/-0.2% (P<0.001). IVGTT K-values at 1 and 2 months postimplantation were 1.6+/-0.1 (P<0.002) and 1.9+/-0.1 (P<0.001), respectively compared with 0.71+/-0.3 before implantation. In a second group of studies, bovine islets were immobilized inside a new type of selectively permeable "microreactor" (Mr exclusion <150 kD) and implanted into the peritoneum of 33 STZ-induced diabetic rats without any immunosuppression. Diabetes was promptly reversed, and normoglycemia maintained for periods of several weeks to months. Immunohistochemical staining of microreactors recovered from these animals revealed well-granulated beta-cells consistent with functionally active insulin synthesis and secretion. To test further the secretory function of the islets, some of the explanted microreactors were incubated in media containing either basal or stimulatory concentrations of glucose. The islets responded with an approximately 3- to 5-fold average increase above basal insulin secretion. These results are encouraging, and may have important implications in assessing the potential role of these microencapsulation systems as therapy for human insulin-dependent diabetes.