Chronic Pain Treatment With Cannabidiol in Kidney Transplant Patients in Uruguay.

BACKGROUND: Chronic pain is a major therapeutic problem in kidney transplant patients owing to nephrotoxicity associated with nonsteroidal antiiflammatory drugs. Benefits in chronic pain treatment with cannabidiol (CBD) have been reported. This study assesses the effect, safety, and possible drug interactions in kidney transplant patients treated with CBD for chronic pain. METHODS: We assessed patients who asked to receive CBD for pain treatment. Doses were increased from 50 to 150 mg twice a day for 3 weeks. Creatinine, blood count, liver function, liver enzymes, and drug levels were determined every 48 hours the first week and then once a week thereafter. RESULTS: We assessed 7 patients with a mean age of 64.5 years (range, 58-75 years). CBD initial dose was 100 mg/d, CBD dose reduction to 50 mg/d has been done on day 4 to patient 1 for persistent nausea. Tacrolimus dose reduction in patient 3 was undertaken on days 4, 7, and 21 owing to persisting elevated levels (even before CBD) and itching, and on day 21 in patient 5. Tacrolimus levels decreased in patient 2 but were normal in the control 1 week later. Patients on cyclosporine were stable. Adverse effects were nausea, dry mouth, dizziness, drowsiness, and intermittent episodes of heat. CBD dose decrease was required in 2 patients. Two patients had total pain improvement, 4 had a partial response in the first 15 days, and in 1 there was no change. CONCLUSIONS: During this follow-up, CBD was well-tolerated, and there were no severe adverse effects. Plasma levels of tacrolimus were variable. Therefore, longer follow-up is required.

Altered development, oxidative stress and DNA damage in Leptodactylus chaquensis (Anura: Leptodactylidae) larvae exposed to poultry litter.

Poultry litter (PL), which is usually used as organic fertilizer, is a source of nutrients, metals, veterinary pharmaceuticals and bacterial pathogens, which, through runoff, may end up in the nearest aquatic ecosystems. In this study, Leptodactylus chaquensis at different development stages (eggs, larval stages 28 and 31 here referred to as stages I, II and III respectively) were exposed to PL test sediments as follows: 6.25% (T1), 12.5% (T2); 25% (T3); 50% (T4); 75% (T5); 100% PL (T6) and to dechlorinated water as control. Larval survival, development endpoints (growth rate -GR-, development rate -DR-, abnormalities), antioxidant enzyme activities (Catalase -CAT- and Glutathione-S-Transferase -GST-), and genotoxic effect (DNA damage index by the Comet assay) were analyzed at different times. In stage I, no egg eclosion was observed in treatments T3-T6, and 50% of embryo mortality was recorded after 24h of exposure to T2. In stages II and III, mortality in treatments T3-T6 reached 100% between 24 and 48h. In the three development stages evaluated, the DR and GR were higher in controls than in PL treatments (T1, T2), except for those T1-treated larvae of stage II. Larvae of stage I showed five types of morphological abnormalities, being diamond body shape and lateral displacement of the intestine the most prevalent in T1, whereas larvae of stages II and III presented lower prevalence of abnormalities. In stage I, CAT activity was similar to that of control (p>0.05), whereas it was higher in T1- and T2- treated larvae of stages II and III than controls (p<0.05). In stages I and III, GST activity was similar to that of controls (p>0.05), whereas it was inhibited in T1-treated larvae of stage II (p<0.05). T1- and T2-treated larvae of stages II and III caused higher DNA damage respect to controls (p<0.05), varying from medium to severe damage (comet types II, III and IV). These results showed that PL treatments altered development and growth and induced oxidative stress and DNA damage, resulting ecotoxic for L. chaquensis larvae.

First 1500 Kidney Transplants at the Institute of Nephrology and Urology in Uruguay: Analysis of the Results.

BACKGROUND: The Institute of Nephrology and Urology (INU) has performed 75% of kidney transplantations (KT) in Uruguay during its 35 years of activity, with 90.6% from cadaveric donors. We investigated the risk factors (RF) for delayed graft function (DGF) and patient and graft survival (SV). METHODS: We analyzed retrospectively the characteristics and evolution of 1500 KT performed by INU until December 2014. The incidence of DGF and RF for patient and graft SV were analyzed in 4 eras, according to the year that KT was performed. RESULTS: The number of KT per year has progressively increased until reaching 40 KT per million population in 2006, with a decrease of the living donor KT (LDKT) rate. The age of the donors (D) and recipients (R) as well as the time on dialysis (TOD) have progressively increased over the different eras. Five hundred twenty-five R (35%) presented with DGF. The RF for DGF were the age of the R and the D, the TOD, the DDKT, and the warm ischemia time (WIT). In the DDKT group, the cold ischemia time and "died of stroke" were added factors. The death-censored graft SV at 1, 5, 10, and 15 years were 90%, 76%, 62%, and 49%, respectively. They improved as from era I, the patient SV being 92%, 83%, and 75% at 1, 5, and 10 years, in era I; 98%, 93%, and 86% in era II; 98%, 92%, and 83% in era III; and 95% and 90% at 1 and 5 years in era IV (P < .001). The graft SV over the same periods was 76%, 58%, and 40% in era I; 88%, 68%, and 52% in era II; 93%, 81%, and 70% in era III; and 93% and 85% at 1 and 5 years in era IV (P < .0001). The RF for patient SV were diabetes mellitus, era I, lower albuminemia, older age or TOD, and DGF. For kidney SV, the era, the age of the R, TOD, DGF, and D older than 60 years were RF associated with a worse evolution. In DDKT, the RF for the graft SV were the era, younger age of the R, and DGF. The group with the worst graft SV was the one made up of children and adolescents. CONCLUSIONS: Our results relating to patient and graft SV are acceptable and comparable to those mentioned on large records such as the OPNT/SRTR and the Collaborative Transplant Study. This has been the case, even though we have transplanted increasingly aged patients, with increasingly aged donors, or donors with associated pathology. The risk factors that we found both for DGF and SV have also been pointed out by other authors. The validity of some findings has the limitation of being from a retrospective analysis; hence, they should be corroborated by a prospective study.

Successful Pregnancies in Kidney Transplant Recipients: Experience of the National Kidney Transplant Program From Uruguay.

BACKGROUND: Renal transplantation increases the possibilities of pregnancy in women of reproductive age. The course of pregnancy was analyzed retrospectively in patients with kidney or kidney-pancreas transplant, surveying maternal-fetal or renal graft complications and the relation with pre-pregnancy renal function. METHODS: A cohort that includes all the kidney transplant recipients who went through pregnancy in Uruguay in a period of 28 years is described. Forty pregnancies in 32 patients were registered; the average time between the kidney transplant and the beginning of the gestation period was 47 months. From the total gestations, 10 abortions, 1 neonatal death, and 1 fetal demise were registered. From the remaining pregnancies, we highlight prematurity (18/29) and low birth weight (14/21). Twenty-nine in 30 pregnancies ended in cesarean section; in 8 of 30, pre-eclampsia diagnosis was performed. Acute rejection was diagnosed in 2 of 30 pregnancies, both undergoing their first post-transplant year. RESULTS: Two patients required dialysis throughout the pregnancy because of progress into severe renal insufficiency. Higher obstetric perinatal morbidity and renal function deterioration was related to lower pre-pregnancy glomerular filtration rate (GFR). CONCLUSIONS: A successful pregnancy is possible in transplant recipients, yet there are risks of prematurity, low birth weight, and abortion. A lower GFR before pregnancy was associated with poorer maternal and perinatal results as shown in the different series.

Development of the National Kidney Transplantation Program in Uruguay.

The first kidney transplantation (KT) in Uruguay was performed in 1969. We report the rates of KT and survival of patients and grafts up to December 2014. The country has a surface of 176,215 km(2) and a population of 3,286,314 inhabitants (18.6 inhabitants per km(2)). Till December 31, 2014, 1,940 KT have been performed in Uruguay (41.8 pmp that year); 90.4% of them were from cadaveric donors (CD). Median age of recipients (R) was 44 ± 14 years; R older than 55 years increased from 0 to 27% during the period. Our pre-emptive KT program started in 2007. Optimal donors (D) decreased from 65.2% to 35.5%, and D older than 45 years old increased from 9% to 37%. Trauma as cause of death decreased from 49% to 32% and stroke as cause of death increased from 25% to 39%. Patient survival rates at 1, 5, and 8 years were 93%, 87%, and 78%, respectively for KT performed between 1980 and 1989; they were 98%, 93%, and 89%, respectively, for KT performed between 1990 and1999; they were 97%, 91%, and 90%, respectively, for KT performed between 2000 and 2010. In December 2013, there were 1098 patients pmp in renal replacement therapy, 758 pmp in dialysis, and 340 pmp (30.9%) with a functioning graft. Our national KT program is mainly based (90.6%) on cadaveric donation. Epidemiological changes in the characteristics of R and D followed the changes in aging that occurred in the general population and the dialysis population. The survival rates from patients and kidneys are similar to those reported by the European and the American registries.

Preemptive kidney transplantation--a team experience in Uruguay.

Kidney transplantation is the best treatment for end-stage chronic renal disease. In Uruguay, the prevalence of patients on dialysis is 757 patients per millon inhabitants, plus 316 alive with a functioning renal graft. We install a preemptive renal transplantation program. Twenty-five patients received grafts without dialysis from 2004 to 2013, 5 receiving their 2nd transplantation and 17 from cadaveric donors, with 7.4 ± 7.7 months in the waiting list. At 24 months, patients' survival rate was 100% and the grafts' 97%, with a serum creatinine of 1.4 ± 0.6 mg%. The developed programs of dialysis and renal health care contributed install our preemptive kidney transplantation. Kidney transplantation should be proposed to selected patients with chronic renal failure as primary therapy of substitution of renal function.

Clinical spectrum of cutaneous manifestations in renal and renopancreatic recipients in two centers in Uruguay.

Uruguay, with a total population of 3,345,000 inhabitants, is the Latin American country with the second highest number of renal replacement therapies. Long-term immunosuppressant therapy is essential for graft survival but results in reduced immunosurveillance, leading to an increased risk of complications. A variety of dermatological manifestations and a large increase in nonmelanoma skin cancers have been reported in this population. The purpose of this study was to evaluate the frequency and clinical spectrum of cutaneous manifestations in renal and renopancreatic recipients in 2 reference centers in Uruguay. Two hundred and six renal or renopancreatic recipients between 21 and 77 years old were evaluated between September 2009 and September 2011. A total of 206 dermatoses were observed; 60% of the patients had at least 1 cutaneous manifestation. The most frequent dermatoses were cutaneous side effects due to immunosuppressive treatment (40.6%), followed by infections (26.1%), miscellaneous causes (18.9%), and malignant and premalignant lesions (14.4%). Transplant recipients represent a high-risk dermatological population. Physicians in transplant units should be aware of the importance of dermatological screening in order to promote early detection of skin cancer.

Cutaneous manifestations in 100 renal and reno-pancreatic recipients of Uruguay.

Uruguay is the second country of Latin America in prevalence of renal replacement therapies, including functioning kidney allografts. Long-term immunosuppressive therapy is essential for adequate graft function, but results in reduced immunosurveillance leading to an increased risk of complications such as infections and malignancies. A variety of cutaneous manifestations as well as an increase in non-melanoma skin cancers have been reported in this population. The objective of this study was to evaluate the frequency and clinical spectrum of cutaneous manifestations in renal and reno-pancreatic recipients in Uruguay. One hundred renal or reno-pancreatic recipients aged between 21- and 77-years-old were evaluated between September 2009 and September 2010. A total of 104 dermatoses were observed; 68% of the patients had at least one cutaneous manifestation. The most frequent dermatoses were cutaneous side effects due to immunosuppressive treatment (43.3%), followed by infections (27.9%), miscellaneous causes (22.1%), as well as malignant and premalignant lesions (6.7%). This is the first study evaluating dermatological complications in organ transplant recipients in our country. Most of the patients had at least one dermatological manifestation of immunosuppression, including a malignant or pre-malignant lesion, highlighting that this is a high-risk dermatological population. Cancer is one of the most important causes of death in recipients with functioning grafts. Its prevention is a major goal in the care of transplant recipients. Physicians in transplant units should be aware of the importance of dermatological screening and skin cancer surveillance.

Counting of lymphocyte subpopulations using standard versus low-dose antiCD3 monoclonal antibody treatment.

The monoclonal anti-CD3 antibody is used as part of prophylaxis and also in treatment of rejection. In the present article we analyzed changes in different lymphocyte subpopulations after anti-CD3 treatment. T lymphocytes were decreased under anti-CD3 antibody administration, with a simultaneous increase in B lymphocytes but no changes in natural killer (NK)cells. No differences were found between patients administered anti-CD3 antibody (Ab) at 5 versus 2.5 mg/d. It is uncertain whether these changes may be implicated in the lack of response or in the prophylactic effects of anti-CD3 Ab.

Cardiovascular disease and/or elderly donors in renal transplantation: the outcome of grafts and patients.

Kidney transplant programs nowadays increasingly use elderly, hypertensive and cardiac disease donors (expanded criteria donors). The impact of these donors on patient and graft outcome was investigated in our transplant population. Among 257 consecutive cadaveric kidney transplants, 56 were from expanded criteria donors. The frequency of anuria, delayed graft function, and the days of renal failure were higher using organs from the expanded criteria donor group. Serum creatinine was higher in this group, although the statistical significance disappeared at 36 months. There were no significant differences in graft or patient survival during the first 3 years. The use of expanded criteria donors should not be discouraged, but recipient selection and immunosuppression use should be adapted and cold ischemia minimized.

[Most frequent causes of constipación in our environment]. / Causas más frecuentes de constipación en nuestro medio.

At the Digestive Motility Department on gastroenterology floor of the "Hospital de Clinicas Jose de San Martin", 165 patients were evaluated due to chronic constipation, underlying the most frequent causes in our environment. The use of the present diagnostic methods is suggested following a suitable clinical orientation. The most frequent causes of constipation after this test were: chronic idiopathic constipation in 112 cases (67.87%) and with megarectum, megasigma and megacolon 32 cases (19.09%), rectocele in 9 cases (5.45%), rectal prolapse in 5 cases (3.03%), enf. De Hirschprung 5 cases (3.03%) and anal estenosis 2 cases (1.21%).

Causas más frecuentes de constipación en nuestro medio / More frequent causes of constipación in our means

At the Digestive Motility Department on gastroenterology floor of the Hospital de Clinicas Jose de San Martin, 165 patients were evaluated due to chronic constipation, underlying the most frequent causes in our environment. The use of the present diagnostic methods is suggested following a suitable clinical orientation. The most frequent causes of constipation after this test were: chronic idiopathic constipation in 112 cases (67.87 per cent) and with megarectum, megasigma and megacolon 32 cases (19.09 per cent), rectocele in 9 cases (5.45 per cent), rectal prolapse in 5 cases (3.03 per cent), enf. De Hirschprung 5 cases (3.03 per cent) and anal estenosis 2 cases (1.21 per cent).

Causas más frecuentes de constipación en nuestro medio / More frequent causes of constipación in our means

At the Digestive Motility Department on gastroenterology floor of the Hospital de Clinicas Jose de San Martin, 165 patients were evaluated due to chronic constipation, underlying the most frequent causes in our environment. The use of the present diagnostic methods is suggested following a suitable clinical orientation. The most frequent causes of constipation after this test were: chronic idiopathic constipation in 112 cases (67.87 per cent) and with megarectum, megasigma and megacolon 32 cases (19.09 per cent), rectocele in 9 cases (5.45 per cent), rectal prolapse in 5 cases (3.03 per cent), enf. De Hirschprung 5 cases (3.03 per cent) and anal estenosis 2 cases (1.21 per cent). (AU)

Causas más frecuentes de constipación en nuestro medio. / [Most frequent causes of constipación in our environment]

At the Digestive Motility Department on gastroenterology floor of the [quot ]Hospital de Clinicas Jose de San Martin[quot ], 165 patients were evaluated due to chronic constipation, underlying the most frequent causes in our environment. The use of the present diagnostic methods is suggested following a suitable clinical orientation. The most frequent causes of constipation after this test were: chronic idiopathic constipation in 112 cases (67.87

) and with megarectum, megasigma and megacolon 32 cases (19.09

), rectocele in 9 cases (5.45

), rectal prolapse in 5 cases (3.03

), enf. De Hirschprung 5 cases (3.03

) and anal estenosis 2 cases (1.21

).

[Diagnostic value of defecography]. / Valor diagnóstico de la defecografía.

The aim of this study was to assess the importance of defecatography in the diagnosis of lower chronic constipation (4) or rectal type (12), principally in those patients on whom other diagnostic methods had not produced supportive data. Over a 64 month period, 65 patients who had consulted because of chronic constipation, were studied; they were suffering from low bowel symptoms like difficulty in the evacuation of the rectum. The average age was 48 and mostly female. All of them were asked to prepare the same mixture for the defecatory study, using the same type of contrast material and study technique. In most of the cases correlated functional elements were found, while very few cases resulting from just organic causes were found, and only one without functional or organic reason was found. Our results were as follows. 1) Insufficient laxity of the pubo-rectal beam related to forward or backward rectocele or lowering of the increased pelvic floor, a fact that was found in 19 patients (29.23%). 2) Inadequate laxity of the pubo rectal beam in 12 patients (18.46%). 3) Paradoxical contraction of the pubo rectal beam related to forward rectocele or lowering of the increased pelvic floor, in 11 patients (16.92%). 4) Lowering of the increased pelvic floor, related to forward or backward rectocele in 8 patients (12.30%). 5) Paradoxical contraction of the pubo rectal beam in 7 patients (10.76%). 6) Forward or backward rectocele in 3 patients (4.61%). 7) Lowering of the increased pelvic floor in 2 patients (3.07%). 8) Rectal intususception in 1 patient (1.53%). 9) Average study in 1 patient (1.53%). Therefore, the defecatography is a very useful method of study to appraise constipation with anorectoperineal symptoms, as it allows us to diagnose organic and functional problems in the area (6). Likewise, the importance of pre and post surgical tests, both therapeutic and reconstructive must be underlined.

Valor diagnóstico de la defecografía / Diagnostic value of defecography

The aim of this study was to assess the importance of defecatography in the diagnosis of lower chronic constipation (4) or rectal type (12), principally in those patients on whom other diagnostic methods had not produced supportive data. Over a 64 month period, 65 patients who had consulted because of chronic constipation, were studied; they were suffering from low bowel symptoms like difficulty in the evacuation of the rectum. The average age was 48 and mostly female. All of them were asked to prepare the same mixture for the defecatory study, using the same type of contrast material and study technique. In most of the cases correlated functional elements were found, while very few cases resulting from just organic causes were found, and only one without functional or organic reason was found. Our results were as follows. 1) Insufficient laxity of the pubo-rectal beam related to forward or backward rectocele or lowering of the increased pelvic floor, a fact that was found in 19 patients (29.23 percent). 2) Inadequate laxity of the pubo rectal beam in 12 patients (18.46 percent ). 3) Paradoxical contraction of the pubo rectal beam related to forward rectocele or lowering of the increased pelvic floor, in 11 patients (16.92 percent). 4) Lowering of the increased pelvic floor, related to forward or backward rectocele in 8 patients (12.30 percent). 5) Paradoxical contraction of the pubo rectal beam in 7 patients (10.76 percent ). 6) Forward or backward rectocele in 3 patients (4.61 percent). 7) Lowering of the increased pelvic floor in 2 patients (3.07 percent ). 8) Rectal intususception in 1 patient (1.53 percent). 9) Average study in 1 patient (1.53 percent ). Therefore, the defecatography is a very useful method of study to appraise constipation with anorectoperineal symptoms, as it allows us to diagnose organic and functional problems in the area (6). Likewise, the importance of pre and post surgical tests, both therapeutic and reconstructive must be underlined.

Valor diagnóstico de la defecografía / Diagnostic value of defecography

The aim of this study was to assess the importance of defecatography in the diagnosis of lower chronic constipation (4) or rectal type (12), principally in those patients on whom other diagnostic methods had not produced supportive data. Over a 64 month period, 65 patients who had consulted because of chronic constipation, were studied; they were suffering from low bowel symptoms like difficulty in the evacuation of the rectum. The average age was 48 and mostly female. All of them were asked to prepare the same mixture for the defecatory study, using the same type of contrast material and study technique. In most of the cases correlated functional elements were found, while very few cases resulting from just organic causes were found, and only one without functional or organic reason was found. Our results were as follows. 1) Insufficient laxity of the pubo-rectal beam related to forward or backward rectocele or lowering of the increased pelvic floor, a fact that was found in 19 patients (29.23 percent). 2) Inadequate laxity of the pubo rectal beam in 12 patients (18.46 percent ). 3) Paradoxical contraction of the pubo rectal beam related to forward rectocele or lowering of the increased pelvic floor, in 11 patients (16.92 percent). 4) Lowering of the increased pelvic floor, related to forward or backward rectocele in 8 patients (12.30 percent). 5) Paradoxical contraction of the pubo rectal beam in 7 patients (10.76 percent ). 6) Forward or backward rectocele in 3 patients (4.61 percent). 7) Lowering of the increased pelvic floor in 2 patients (3.07 percent ). 8) Rectal intususception in 1 patient (1.53 percent). 9) Average study in 1 patient (1.53 percent ). Therefore, the defecatography is a very useful method of study to appraise constipation with anorectoperineal symptoms, as it allows us to diagnose organic and functional problems in the area (6). Likewise, the importance of pre and post surgical tests, both therapeutic and reconstructive must be underlined. (Au)

Valor diagnóstico de la defecografía. / [Diagnostic value of defecography]

The aim of this study was to assess the importance of defecatography in the diagnosis of lower chronic constipation (4) or rectal type (12), principally in those patients on whom other diagnostic methods had not produced supportive data. Over a 64 month period, 65 patients who had consulted because of chronic constipation, were studied; they were suffering from low bowel symptoms like difficulty in the evacuation of the rectum. The average age was 48 and mostly female. All of them were asked to prepare the same mixture for the defecatory study, using the same type of contrast material and study technique. In most of the cases correlated functional elements were found, while very few cases resulting from just organic causes were found, and only one without functional or organic reason was found. Our results were as follows. 1) Insufficient laxity of the pubo-rectal beam related to forward or backward rectocele or lowering of the increased pelvic floor, a fact that was found in 19 patients (29.23

). 2) Inadequate laxity of the pubo rectal beam in 12 patients (18.46

). 3) Paradoxical contraction of the pubo rectal beam related to forward rectocele or lowering of the increased pelvic floor, in 11 patients (16.92

). 4) Lowering of the increased pelvic floor, related to forward or backward rectocele in 8 patients (12.30

). 5) Paradoxical contraction of the pubo rectal beam in 7 patients (10.76

). 6) Forward or backward rectocele in 3 patients (4.61

). 7) Lowering of the increased pelvic floor in 2 patients (3.07

). 8) Rectal intususception in 1 patient (1.53

). 9) Average study in 1 patient (1.53

). Therefore, the defecatography is a very useful method of study to appraise constipation with anorectoperineal symptoms, as it allows us to diagnose organic and functional problems in the area (6). Likewise, the importance of pre and post surgical tests, both therapeutic and reconstructive must be underlined.

[Most frequent causes of fecal incontinence in our environment]. / Causas más frecuentes de incontinencia fecal en nuestro medio.

The objective of this piece of work was to assess the most frequent causes of fecal incontinence in our environment. 204 patients undergoing fecal incontinence of various types of severity were evaluated and later referred to "motilidad digestiva" department of Gastroenterology floor of Hospital de Clínicas José de San Martín, in an eight year span of time, 58 male (28.43%) and 146 female (71.56%) of an average age of 56 years. Every patient underwent a serious anamnesis, a proctologic examination, anoscopy, a rectosigmoid study, an anorectal manometry, and, a preventive electromyography was performed to those patients with a possible neurologic damage. The most frequent cause of incontinence was idiopathic 37.7%, followed by post surgery (19.6%) and rectal prolapse (13.7%), post menopause (11.2%), post delivery (9.8%), Neurogenic Incontinence (4.9%) and Traumatic Incontinence (2.9%). Doctor's performance may prevent some of the causes of incontinence.