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BACKGROUND: Microbiologic screening of extrapulmonary TB (EPTB) patients could inform recommendations for aerosol precautions and close contact prophylaxis. However, this is currently not routinely recommended in India. Therefore, we estimated the proportion of Indian patients with EPTB with microbiologic evidence of pulmonary TB (PTB).METHODS: We characterized baseline clinical, radiological and sputum microbiologic data of 885 adult and pediatric TB patients in Chennai and Pune, India, between March 2014 and November 2018.RESULTS: Of 277 patients with EPTB, enhanced screening led to the identification of 124 (45%) with concomitant PTB, including 53 (19%) who reported a cough >2 weeks; 158 (63%) had an abnormal CXR and 51 (19%) had a positive sputum for TB. Of 70 participants with a normal CXR and without any cough, 14 (20%) had a positive sputum for TB. Overall, the incremental yield of enhanced screening of patients with EPTB to identify concomitant PTB disease was 14% (95% CI 12-16).CONCLUSIONS: A high proportion of patients classified as EPTB in India have concomitant PTB. Our results support the need for improved symptom and CXR screening, and recommends routine sputum TB microbiology screening of all Indian patients with EPTB.
Subject(s)
Tuberculosis, Pulmonary , Tuberculosis , Adult , Child , Cough , Humans , India/epidemiology , Sputum/microbiology , Tuberculosis/diagnosis , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/epidemiology , Tuberculosis, Pulmonary/microbiologyABSTRACT
INTRODUCTION: To analyse the results of Cauda Equina Syndrome (CES) operated by Percutaneous Transforaminal Endoscopic Lumbar Discectomy (PTELD). MATERIAL AND METHODS: The study is a retrospective series of 15 patients operated by PTELD. Bladder dysfunction was classified as incomplete CES (CESI) and complete CES retention (CESR). Bladder / motor recovery rate and its timing, Oswestry Disability Index (ODI), Visual Analogue Score (VAS), patient satisfaction index, and sexual dysfunction were used to measure the outcome objectively. Additionally, in CESR patients, post-void residual (PVR) urine was measured by sonography. Complications and technical problems were noted. RESULTS: There were ten patients of CESI and five patients of CESR. The average follow-up was 20.33(12.05) months. Bladder symptoms recovery was 100%, and motor recovery was 80%. VAS for back pain recovered to 0.53(0.52) from 8(2.39). VAS for leg pain recovered to 0.13(0.35) from 9.20(1.32). ODI improved to 6.07(2.85) from 77.52(13.20). The time to the recovery of bladder function was 1.47(1.55) days. All CESR patient's abnormal PVR urine was normalised at five weeks post-operative. No complications were reported. However, five technical executional problems occurred. CONCLUSION: PTELD can be considered for CES treatment due to its substantial and quick recovery advantages. However, more evidence support is needed to make it a practice recommendation.
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Subject(s)
Health Status , Tuberculosis, Pulmonary/drug therapy , Adolescent , Adult , Cohort Studies , Female , Follow-Up Studies , Humans , India , Male , Middle Aged , Recurrence , Surveys and Questionnaires , Treatment Outcome , Tuberculosis, Pulmonary/mortality , Tuberculosis, Pulmonary/physiopathology , Young AdultABSTRACT
SETTING: Pre-diabetes mellitus (pre-DM) and DM increase the risk of developing tuberculosis (TB). Screening contacts of TB patients for pre-DM/DM and linking them to care may mitigate the risk of developing TB and improve DM management. OBJECTIVE: To measure the prevalence of pre-DM/DM and associated factors among the adult household contacts (HHCs) of pulmonary TB patients. METHODS: Between August 2014 and May 2017, adult HHCs of newly diagnosed adult PTB patients in Pune and Chennai, India, had single blood samples tested for glycosylated haemoglobin (HbA1c) at enrolment. DM was defined as previously diagnosed, self-reported DM or HbA1c î¶6.5%, and pre-DM as HbA1c between 5.7% and 6.4%. Latent tuberculous infection (LTBI) was defined as a positive tuberculin skin test (î¶5 mm induration) or QuantiFERON® Gold In-Tube (î¶0.35 international units/ml). RESULTS: Of 652 adult HHCs, 175 (27%) had pre-DM and 64 (10%) had DM. Forty (64%) HHCs were newly diagnosed with DM and 48 (75%) had poor glycaemic control (HbA1c î¶7.0%). Sixty-eight (22%) pre-DM cases were aged 18-34 years. Age î¶35 years, body mass index î¶25 kg/m2, chronic disease and current tobacco smoking were significantly associated with DM among HHCs. CONCLUSIONS: Adult HHCs of TB patients in India have a high prevalence of undiagnosed DM, pre-DM and LTBI, putting them at high risk for developing TB. Routine DM screening should be considered among all adult HHCs of TB.
Subject(s)
Diabetes Mellitus/epidemiology , Mass Screening/methods , Prediabetic State/epidemiology , Tuberculosis/epidemiology , Adolescent , Adult , Contact Tracing/methods , Cross-Sectional Studies , Diabetes Mellitus/diagnosis , Female , Glycated Hemoglobin/analysis , Humans , India/epidemiology , Latent Tuberculosis/diagnosis , Latent Tuberculosis/epidemiology , Male , Middle Aged , Prediabetic State/diagnosis , Prevalence , Risk Factors , Tuberculosis/diagnosis , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/epidemiology , Young AdultABSTRACT
Hepatocellular adenomas (HCA) are benign tumours with potential for malignant transformation with no recommendations regarding management in the paediatric population. We report a case of an inflammatory adenoma with ß-catenin activated pathway in an obese, paediatric patient with nonalcoholic steatohepatitis (NASH). CASE REPORT: An 11-year-old female presented with a microlobulated liver lesion measuring >5 cm in magnetic resonance imaging (MRI) with inflammatory adenoma with ß-catenin activated pathology arising in a background of NASH, nonalcoholic fatty liver disease (NAFLD) activity score 5/8. Imaging follow-up demonstrated stable disease without progression for 3 years. DISCUSSION: Malignant transformation of Hepatocellular adenomas in a child is approximately 4.2%. It is unknown if hepatic steatosis increases this risk. Obese patients mainly develop inflammatory and ß-catenin activated (highest risk for malignant transformation) adenomas. Our patient had inflammatory and ß-catenin activation, which led to monitoring for malignant transformation. CONCLUSION: We report a ß-catenin activated inflammatory adenoma in a child with obesity and NASH with ongoing expectant management.
Subject(s)
Adenoma, Liver Cell/complications , Liver Neoplasms/pathology , Non-alcoholic Fatty Liver Disease/complications , Pediatric Obesity/complications , beta Catenin/metabolism , Adenoma, Liver Cell/metabolism , Cell Transformation, Neoplastic , Child , Female , Humans , Liver Neoplasms/metabolism , Magnetic Resonance ImagingABSTRACT
BACKGROUND: Non-alcoholic steatohepatitis (NASH) and resultant liver fibrosis is a major health problem without approved pharmacotherapy. Pre-clinical results of GR-MD-02, a galectin-3 inhibitor, suggested potential efficacy in NASH with advanced fibrosis/cirrhosis and prompted initiation of a clinical development programme in NASH with advanced fibrosis. AIM: To evaluate the safety, pharmacokinetics and exploratory pharmacodynamic markers of GR-MD-02 in subjects having NASH with bridging fibrosis. METHODS: The GT-020 study was a first-in-human, sequential dose-ranging, placebo controlled, double-blinded study with the primary objective to assess the safety, tolerability and dose limiting toxicity of GR-MD-02, in subjects with biopsy-proven NASH with advanced fibrosis (Brunt stage 3). The secondary objectives were to characterise first-dose and multiple-dose pharmacokinetic profiles and to evaluate changes in potential serum biomarkers and liver stiffness as assessed by FibroScan. RESULTS: GR-MD-02 single and three weekly repeated of 2, 4 and 8 mg/kg revealed no meaningful clinical differences in treatment emergent adverse events, vital signs, electrocardiographic findings or laboratory tests. Pharmokinetic parameters showed a dose-dependent relationship with evidence of drug accumulation following 8 mg/kg (~twofold). CONCLUSIONS: GR-MD-02 doses were in the upper range of the targeted therapeutic dose determined from pre-clinical data and were safe and well tolerated with evidence of a pharmacodynamic effect. These results provide support for a Phase 2 development programme in advanced fibrosis due to NASH.
Subject(s)
Galectin 3/antagonists & inhibitors , Liver Cirrhosis/drug therapy , Non-alcoholic Fatty Liver Disease/drug therapy , Pectins , Adult , Aged , Biomarkers/blood , Double-Blind Method , Female , Galectin 3/blood , Humans , Liver Cirrhosis/blood , Male , Middle Aged , Non-alcoholic Fatty Liver Disease/blood , Pectins/adverse effects , Pectins/blood , Pectins/pharmacokinetics , Pectins/pharmacologyABSTRACT
In eukaryotic DNA, cytosine can be enzymatically modified to yield up to four epigenetic base variants. DNA methyltransferases convert cytosine to 5-methylcytosine (mC), which plays critical roles in gene regulation during development. Ten-eleven translocation (TET) enzymes can sequentially oxidize mC to three products: 5-hydroxymethylcytosine (hmC), 5-formylcytosine (fC), and 5-carboxylcytosine (caC). These oxidized bases have been found in numerous mammalian cell types, where they potentially carry out independent epigenetic functions and aid in DNA demethylation. To gain insight into the mechanisms and functions of TET family enzymes, rigorous approaches are needed to quantify genomic cytosine modifications in cells and track TET enzyme activity in vitro. Here, we present tools developed by our lab and others to report on each of the five forms of cytosine (unmodified, mC, hmC, fC, and caC) with high specificity and sensitivity. We provide detailed protocols for qualitative and quantitative analysis of cytosine modifications in genomic DNA by dot blotting and LC-MS/MS. We then describe methods for generating synthetic oligonucleotide substrates for biochemical studies, provide optimized reaction conditions, and introduce several chemoenzymatic assays, as well as HPLC, mass spectrometry, and scintillation counting methods to quantify cytosine modifications in vitro. These approaches enable mechanistic studies of TET activity, which are key to understanding the role of these enzymes in epigenetic regulation.
Subject(s)
5-Methylcytosine/analysis , DNA-Binding Proteins/metabolism , DNA/chemistry , Enzyme Assays/methods , Mixed Function Oxygenases/metabolism , Proto-Oncogene Proteins/metabolism , 5-Methylcytosine/analogs & derivatives , 5-Methylcytosine/metabolism , Animals , Cell Line , Chromatography, High Pressure Liquid/methods , DNA/metabolism , DNA Methylation , Dioxygenases , Humans , Immunoblotting/methods , Insecta , Nucleosides/metabolism , Oligonucleotides/metabolism , Oxidation-Reduction , Recombinant Proteins/metabolism , Tandem Mass Spectrometry/methodsABSTRACT
Nonalcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of metabolic syndrome. The more clinically concerning form of the disease, nonalcoholic steatohepatitis (NASH), is characterized by steatosis, lobular inflammation, and ballooning degeneration. Here we describe a naturally occurring syndrome in the common marmoset that recapitulates the pathologic findings associated with NAFLD/NASH in humans. Hepatomegaly determined to result from NAFLD was observed in 33 of 183 marmosets. A comprehensive histopathologic assessment performed in 31 marmosets demonstrated that NAFLD was characterized by variably sized, Oil Red O staining cytoplasmic vacuoles and observed primarily in animals with evidence of obesity and insulin resistance. A subset of marmosets (16 of 31) also demonstrated evidence of NASH characterized by multifocal inflammation combined with ballooning hepatocellular degeneration. Marmosets with NASH demonstrated an increase in immunostaining with an antibody targeted against the human leukocyte antigens (HLA)-DP, HLA-DQ, and HLA-DR compared with marmosets without NASH (38.89 cells/10× field vs 12.05 cells/10× field, P = .05). In addition, marmosets with NASH demonstrated increased Ki-67 immunopositive cellular proliferation compared with those without (5.95 cells/10× field vs 1.53 cells/10× field, P = .0002). Finally, animals with NASH demonstrated significantly increased mean circulating serum iron levels (160.47 µg/dl, P = .008) and an increase in numbers of Prussian blue-positive Kupffer cells (9.28 cells/40× field, P = .005) relative to marmosets without NASH (97.75 µg/dl and 1.87 cells/40×, respectively). This study further characterizes the histopathology of NAFLD/NASH and suggests that the marmoset may be a valuable animal model with which to investigate the host and environmental factors contributing to the progression of NAFLD/ NASH.
Subject(s)
Callithrix , Disease Models, Animal , Fatty Liver/pathology , Non-alcoholic Fatty Liver Disease/pathology , Animals , Disease Progression , Female , Humans , Inflammation , Liver/pathology , Male , ObesityABSTRACT
Ninety-eight percent of the whole pancreas does not serve the purpose of pancreatic transplantation and it is a major cause of surgical complications. Up to 30% of pancreas transplant recipients experience surgical complications and require reoperation. Graft thrombosis and pancreatitis are the most common complications of pancreas transplantation (PT). Thus, different surgical techniques have been described to overcome the surgical hurdles and reduce surgical complications. In this study, for the first time, we report short- and long-term outcomes of PT with inferior vena cava (IVC) venous drainage. Forty-five PTs (22 simultaneous pancreas and kidney [SPK] transplantations and 23 pancreas after kidney [PAK] transplantations) were performed with this technique in our center. Sixty-eight percent of the donors were imported from outside of our area after they were declined by their local transplantation center. Patient and graft survival rates were 100% at 1 year. No graft thrombosis or pancreatitis occurred with this technique. Six patients (13.3%) required reoperation (3 bleeding, 2 anastomotic leak, and 1 small bowel perforation). No patient or graft loss occurred due to surgical complications. We conclude that this technique provides fast and easy dissection of the venous drainage of the PT without the need of complete occlusion of venous outflow. Surgical complication rates were lower with this technique compared with other reported techniques.
Subject(s)
Pancreas Transplantation/methods , Adult , Drainage/methods , Female , Graft Survival , Humans , Male , Middle Aged , Pancreas Transplantation/adverse effects , Postoperative Complications/prevention & control , Reoperation , Tissue Donors , Treatment Outcome , Vena Cava, Inferior/surgeryABSTRACT
BACKGROUND: Currently, the long-term advantages of having a pancreas transplantation (PT) are debated, particularly in patients receiving pancreas after kidney (PAK) allografts. The United Network for Organ Sharing (UNOS) requires that a transplant center perform a minimum number of PT per year to remain an active PT center. The long-term outcomes and challenges of PAK in small pancreas transplant centers are not well studied. METHODS: In this retrospective analysis, we report short- and long-term outcomes in a small center performing 2-9 PT annually. RESULTS: Forty-eight PT (25 simultaneous pancreas and kidney transplantation [SPK], 23 PAK) were performed in our center. Donor and recipient demographics were similar in both groups. All suitable local donors were used for SPK. All organs for PAK transplantation were imported from other UNOS regions. Mean follow-up was 61 ± 46 and 74 ± 46 months for SPK and PAK, respectively. Patient and graft survival rates were similar in SPK and PAK groups and better than the reported national average. Four patients (11%) died (1 due to trauma, 1 brain lymphoma, 1 ruptured aneurysm; and 1 unknown cause). Two patients (4%; 1 SPK, 1 PAK) lost their grafts because of thrombosis on postoperative days 3 and 5 in 2002. No graft thrombosis occurred since 2002. Seven patients (15%) required reoperation (4 for bleeding, 2 anastomotic leaks, 1 small bowel perforation). Two patients (4%) developed post-transplantation lymphoproliferative disease. Five patients (11%) experienced cytomegalovirus antigenemia which responded well to antiviral therapy. CONCLUSIONS: Compared with outcomes for diabetic patients on dialysis, current SPK and PAK short- and long-term results are favorable even in a small PT center. Therefore, unless there is a contraindication, PT should be offered to all type 1 diabetic patients with end-stage renal disease at the time of kidney transplantation or afterward.
Subject(s)
Graft Survival , Kidney Transplantation , Pancreas Transplantation , Adult , Antigens, Viral/blood , Cytomegalovirus/immunology , Cytomegalovirus Infections/complications , Female , Humans , Lymphoproliferative Disorders/epidemiology , Male , Middle Aged , Postoperative Complications , Reoperation/statistics & numerical data , Retrospective Studies , Thrombosis/epidemiology , United States/epidemiologyABSTRACT
The number of African Americans (AAs) on the kidney waiting list is increasing in the United States. Several studies showed that AAs are at higher risk for rejection and graft loss. Because of genetic polymorphisms, AAs may metabolize calcineurin inhibitors faster than Caucasian (C) individuals. The goal of this study is to evaluate the tacrolimus (TAC) dose required to reach therapeutic levels and to assess the impact of clotrimazole on TAC metabolism in AAs compared to C patients. One hundred forty-two AA renal transplant recipients (RTRs) were compared to 309 C RTRs. Demographics were similar in both groups. Induction therapy and maintenance immunosuppression were similar in both groups and included TAC, mycophenolate acid (MPA), and steroids. The goal in all RTRs was to maintain a 12-hour trough level of 10 to 15 ng/mL in the first 3 months, 8 to 10 ng/mL for the first year, and 5 to 8 ng/mL thereafter. To achieve these levels, AA RTRs require a significantly higher dosage of TAC compared to C patients (5.9 ± 2.9 vs 3.6 ± 2 mg/d, respectively, P < .0001). By multivariate analysis, TAC dose requirements were not affected by age, gender, MPA or prednisone dose, diabetes, and renal function. Adding clotrimazole (CTM) to the RTR regimen significantly reduced the TAC dose requirements in all RTRs. When CTM was used, the TAC dose requirement was not statistically significantly different between AA and C patients (2.6 ± 1.2 mg/d vs 1.8 ± 1.5 mg/d, P = .07). We conclude that AAs required a higher TAC dose to reach the desired trough level in RTRs compared to C RTRs. The use of CTM eliminates the need for higher doses of TAC in AA RTRs. Thus, CTM may aid AA RTRs in achieving therapeutic TAC levels while reducing drug costs.
Subject(s)
Anti-Infective Agents/administration & dosage , Black or African American , Clotrimazole/administration & dosage , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/pharmacokinetics , Kidney Transplantation , Tacrolimus/administration & dosage , Tacrolimus/pharmacokinetics , White People , Biotransformation , Chi-Square Distribution , Drug Dosage Calculations , Drug Interactions , Drug Monitoring , Drug Therapy, Combination , Humans , Immunosuppressive Agents/blood , Kaplan-Meier Estimate , Kidney Transplantation/adverse effects , Kidney Transplantation/mortality , Multivariate Analysis , Mycophenolic Acid/administration & dosage , Prednisone/administration & dosage , Proportional Hazards Models , Retrospective Studies , Tacrolimus/bloodABSTRACT
Adipose tissue distribution is an important determinant of obesity-related comorbidities. It is well established that central obesity (visceral adipose tissue accumulation) is a risk factor for many adverse health consequences such as dyslipidemia, insulin resistance and type-2-diabetes. We hypothesize that the metabolic dysregulation that occurs following high fat diet-induced increases in adiposity are due to alterations in visceral adipose tissue function which influence lipid flux to the liver via the portal vein. This metabolic pathology is not exclusively due to increases in visceral adipose tissue mass but also driven by intrinsic characteristics of this particular depot. In Experiment 1, high fat diet (HFD)-induced obese control (abdominal incision, but no fat manipulation) or autologous (excision and subsequent relocation of adipose tissue) subcutaneous tissue transplantation to the visceral cavity. In Experiment 2 mice received control surgery, subcutaneous fat removal or hetero-transplantation (tissue from obese donor) to the visceral cavity. Body composition analysis and glucose tolerance tests were performed 4 weeks post-surgery. Adipose mass and portal adipokines, cytokines, lipids and insulin were measured from samples collected at 5 weeks post-surgery. Auto- and hetero- transplantation in obese mice improved glucose tolerance, decreased systemic insulin concentration and reduced portal lipids and hepatic triglycerides compared with HFD controls. Hetero-transplantation of subcutaneous adipose tissue to the visceral cavity in obese mice restored hepatic insulin sensitivity and reduced insulin and leptin concentrations to chow control levels. Fat removal, however, as an independent procedure exacerbated obesity-induced increases in leptin and insulin concentrations. Overall subcutaneous adipose tissue protects against aspects of metabolic dysregulation in obese mice. Transplantation-induced improvements do not occur via enhanced storage of lipid in adipose tissue, however altered hepatic lipid regulation may play a contributory role.
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INTRODUCTION: Machine perfusion to preserve kidneys for transplantation has grown over the past decade with demonstrated diagnostic and therapeutic benefits. Flow and resistance patterns are used to predict delayed graft function (DGF) and posttransplant graft survival. Preimplantation biopsies obtained serve a similar role in evaluating kidneys especially if they meet expanded criteria. The reliability of available data is greater if there is a correlation among various forms of assessment. In this study we attempted to study serial pump parameters that might correlate with abnormal findings in preimplantation biopsies and subsequently in outcomes after transplantation. METHODS: Two hundred sixty-eight kidneys were assessed for changes in pump pressures in mm Hg, flow in mL/min, resistance in mm Hg/mL/min, and temperature in °C at 15-minute intervals. Allografts were separated into two groups on the basis of pathology; group 1 showed abnormal (AH) and group 2 normal histology (NH). AH was defined by the presence of glomerulosclerosis in ≥10% of sampled glomeruli or arteriosclerosis affecting at least 10% of the arterial lumens of sampled intrarenal arteries. We assessed discordance between frozen and permanent sections. Measured clinical outcomes included DGF, 1-year graft survival, 1-year serum creatinine and estimated glomerular filtration rate (eGFR). Statistical analysis was performed using a paired Student t test and chi-square analysis. RESULTS: Compared to NH kidneys, those with AH showed uniformly significant lower flow rates and higher resistances during the entire perfusion. Graft pathology did not predict DGF (70% versus 60%, P = .45). However, 1-year graft survival (96.2% versus 80%, P = .07) and eGFR (58 versus 48 mL/min, P = .19) were lower among kidneys with AH, though these matrics did not reach significance. CONCLUSION: Preimplantation biopsy findings correlated with flow and resistance to perfusion. If a discrepancy is evident upon evaluation of a donor kidney, a repeat biopsy is prudent prior to discarding or using the organ.
Subject(s)
Arteriosclerosis/physiopathology , Glomerulosclerosis, Focal Segmental/physiopathology , Kidney Transplantation , Humans , PerfusionABSTRACT
INTRODUCTION: Pulsatile pump perfusion of potential kidneys for transplantation is known to decrease the rate of delayed graft function (DGF) and improve their 1-year survival. Flow and resistance parameters are often used to determine the suitability of kidneys for transplantation. Kidneys with low flow rates are often subjected to higher pressures to improve flow. This study evaluated the effect of higher pump pressures on posttransplant renal function. METHODS: We performed a retrospective analysis of 73 deceased donor kidneys preserved using pump perfusion (LifePort) at our center between May 2006 and September 2009. We calculated the mean pump pressure (MP) for the duration of perfusion of each kidney, using systolic pressure (SP) and diastolic pressure (DP) readings with the following formula: (MP = DP + 1/3 (SP - DP). The kidneys were divided into a low (LP; n = 49) and a high-pressure group (HP; n = 24) based on a MP cutoff value of 23 mm Hg. The two groups were then compared for differences in perfusion dynamics and primary endpoints including DGF and 1-year graft survival. Statistical analysis was performed using paired Student t test and chi-square analysis. RESULTS: The two groups were comparable for donor age, extended criteria, sensitization, and cold ischemic times. They differed significantly in higher initial (0.65 ± 0.4 versus 0.4 ± 0.2, P = .01), average (0.25 ± 0.08 versus 0.18 ± 0.06, P = .0006), and terminal resistance (0.21 ± 0.07 versus 0.17 ± 0.06, P = .008) of HP versus LP kidneys. Flow rates were comparable between the two groups. DGF was higher in HP kidneys (75% versus 40%, P = .006) with similar 1-year graft survival (87.5% versus 89%, P = .7). CONCLUSIONS: Perfusate flow through a kidney can be improved by increasing pressure settings to overcome elevated resistance. This maneuver was not associated with a lower rate of DGF after transplantation. One-year graft survival remained unaffected.
Subject(s)
Kidney Transplantation , Tissue Donors , Perfusion , Pressure , Retrospective StudiesABSTRACT
UNLABELLED: Pulsatile pump perfusion of kidney transplants is known to decrease delayed graft function (DGF) and improve 1 year graft survival when compared to static cold preservation. Kidneys with better flow and resistance parameters on perfusion are likely to have a better post transplant function. These parameters are commonly used to evaluate kidneys being considered for transplantation. This study assesses the time frame for a kidney within which it reaches optimal perfusion parameters. All kidneys pumped between 5/2006 and 9/2009 on a Lifeport© kidney transporter at our local organ procurement agency were studied. 190 kidneys were evaluated and then divided into two groups based on whether terminal flows increased or declined after prolonged perfusion. All kidneys were assessed for changes in flow (F), resistance (R) and temperature at 15 minute intervals. Discards, DGF and one year graft survival were noted. The Student paired t test and Chi-square analysis were used to compare data. A multiple logistic regression analysis was performed to study independent predictors of DGF on pump perfusion. RESULTS: For all kidneys, the mean initial flow was 59 ± 35 mL/min which improved to an average flow of 128 ± 38 mL/min with continued perfusion. The maximal flow and terminal flows were 148 ± 51 and 135 ± 38 mL/min respectively. The flows at 2, 4, and 6 hours was 125 ± 41, 128 ± 42 and 130 ± 39 mL/min respectively. Kidneys that improved on continued perfusion had a significantly lower discard rate (20 vs 34% p < 0.05), but a higher incidence of DGF (64 vs 39%, P < .05). One year graft loss (death censored) was comparable in the two groups. (4/42 vs. 3/33, P = .94). Resistance at 2, 4, and 6 hours was predictive of DGF, as was donor anoxia and cerebrovascular accident (CVA) as the cause of death. CONCLUSIONS: Kidneys on pulsatile pump perfusion tend to show improved flows and decreased resistance over time. The average flow for a kidney is reached by 2 hours. Those kidneys that start with lower flow rates that improve after 2 hours with continued perfusion are less likely to be discarded but are still associated with a greater incidence of delayed graft function. Resistance at 2 hours predicts DGF while initial resistance predicts one year graft survival.
Subject(s)
Kidney Transplantation , Perfusion , Tissue Donors , Adult , Humans , Middle Aged , PrognosisABSTRACT
OBJECTIVE: This clinical study was designed to compare dentin hypersensitivity relief among subjects who brushed their teeth with a new toothpaste containing 8.0% arginine, calcium carbonate, and 1000 ppm fluoride as sodium monofluorophosphate (MFP) to subjects who brushed with a commercially available dentifrice containing 2% potassium ion as potassium nitrate over an eight-week period. METHODS: Adult male and female subjects from the New Delhi, India area were required to present two teeth that exhibited dentin hypersensitivity, both to tactile stimulation using the Yeaple Probe and to air blast stimulation delivered by a standard dental unit syringe. After an examination of the oral soft and hard tissues, qualifying subjects were randomly assigned one of the study dentifrices and a soft-bristled toothbrush, and were instructed to brush their teeth for one minute, twice daily (morning and evening), using only the toothbrush and dentifrice provided. No other oral hygiene practices were permitted over the course of the study. After two, four, and eight weeks of product use, subjects returned to the dental clinic for follow-up examinations of tactile and air blast sensitivity of the baseline-designated hypersensitive teeth. Examinations of the oral soft and hard tissues were also performed at these follow-up visits. RESULTS: Subjects who brushed with the new dentifrice containing 8.0% arginine, calcium carbonate, and 1000 ppm MFP exhibited statistically significant reductions (p < 0.05) in dentin hypersensitivity in response to tactile (36.2%, 33.1%, and 29.7%) and air blast (16.4%, 31.1%, 58.8%) stimuli when compared to the subjects who brushed with the 2% potassium ion as potassium nitrate dentifrice after two, four, and eight weeks, respectively. CONCLUSION: The use ofa new dentifrice containing 8.0% arginine, calcium carbonate, and 1000 ppm MFP provides greater efficacy in reducing dentin hypersensitivity when compared to a dentifrice containing 2% potassium ion, as potassium nitrate, after two, four, and eight weeks of product use.
Subject(s)
Arginine/therapeutic use , Calcium Carbonate/therapeutic use , Dentin Desensitizing Agents/therapeutic use , Dentin Sensitivity/drug therapy , Toothpastes/therapeutic use , Adolescent , Adult , Analysis of Variance , Double-Blind Method , Female , Fluorides/therapeutic use , Follow-Up Studies , Humans , Male , Middle Aged , Nitrates/therapeutic use , Phosphates/therapeutic use , Potassium Compounds/therapeutic use , Prospective Studies , Sodium Fluoride/therapeutic use , Toothpastes/chemistry , Treatment Outcome , Young AdultABSTRACT
OBJECTIVE: This clinical study evaluated relief from dentin hypersensitivity among subjects who brushed their teeth with a new dentifrice containing 8.0% arginine, calcium carbonate, and 1000 ppm fluoride as sodium monofluorophosphate (MFP) to subjects who brushed with a commercially available dentifrice containing 1000 ppm MFP over an eight-week period. METHODS: Adult subjects from the New Delhi, India area, with two teeth that exhibited dentin hypersensitivity, both to tactile stimulation using the Yeaple Probe and to stimulation using an air blast delivered by a standard dental unit syringe, were screened for study enrollment. Qualifying subjects were randomly assigned one of the study dentifrices and instructed to brush their teeth for one minute, twice daily (morning and evening) with the provided dentifrice. Follow-up examinations for dentin hypersensitivity were conducted after two, four, and eight weeks of product use. RESULTS: Subjects provided with the new dentifrice containing 8.0% arginine, calcium carbonate, and 1000 ppm MFP exhibited statistically significantly (p < 0.05) greater reductions in dentin hypersensitivity in response to tactile (81.9%, 90.5%, and 116.7%) and air blast (39.5%, 56.7%, and 76.7%) stimuli than subjects assigned the 1000 ppm MFP dentifrice after two, four, and eight weeks, respectively. CONCLUSION: The use of a new dentifrice containing 8.0% arginine, calcium carbonate, and 1000 ppm MFP provides superior efficacy in reducing dentin hypersensitivity (p < 0.05) than a control dentifrice containing 1000 ppm MFP alone after two, four, and eight weeks of use.
Subject(s)
Arginine/therapeutic use , Calcium Carbonate/therapeutic use , Dentin Desensitizing Agents/therapeutic use , Dentin Sensitivity/drug therapy , Toothpastes/therapeutic use , Adult , Analysis of Variance , Double-Blind Method , Female , Fluorides/therapeutic use , Follow-Up Studies , Humans , Male , Middle Aged , Phosphates/therapeutic use , Prospective Studies , Toothpastes/chemistry , Treatment OutcomeABSTRACT
Researchers have raised concerns that microbicide use during clinical trials would displace condom use. We sought to understand whether condom use changed for participants in a microbicide clinical trial in Pune, India, to understand whether condom shifts were a legitimate concern. We hypothesize that women participating in a microbicide clinical trial in Pune, India, were more likely, on average, to report condom use at follow-up. We further hypothesize that men, whose female partners participated in a microbicide clinical trial were more likely, on average, to report condom use at follow-up. The outcome measure for reported condom use was a dichotomous variable to indicate whether or not the participant had used a male or female condom with a sexual partner since 2 months before enrollment or since the last survey, depending on the visit. Data are from semi-structured interviews at baseline, 2 months, 4 months, and 6 months with HPTN 059 clinical trial participants (100 women and 57 male partners). We used generalized estimating equations with a logit link function, exchangeable correlation, and a binomial family to model condom use. The odds of condom use for clinical trial women increased from baseline to 6 months by a factor of 3.7 (95% CI: 1.84-7.63) and the change in odds of condom use for clinical trial men from baseline to 6 months increased by a factor of 2.58 (95% CI: 1.37-4.85). We found concerns about microbicide use displacing condom use were not merited in this study population. The percent of participants reporting condom use declined from 4 to 6 months, suggesting that increases in condom use may only be during active study participation. Information about clinical trial factors that enabled these men and women to enact this important HIV prevention behavior is needed to develop interventions.
Subject(s)
Adenine/analogs & derivatives , Anti-HIV Agents/administration & dosage , Condoms/statistics & numerical data , Counseling , HIV Infections/prevention & control , Organophosphonates/administration & dosage , Sexual Behavior/statistics & numerical data , Adenine/administration & dosage , Adult , Cohort Studies , Female , Follow-Up Studies , Gels , HIV Infections/epidemiology , Health Knowledge, Attitudes, Practice , Humans , India/epidemiology , Male , Middle Aged , Odds Ratio , Risk Factors , Risk Reduction Behavior , Sex Distribution , Sexual Partners , Surveys and Questionnaires , Tenofovir , Young AdultABSTRACT
Depression and sleep disorders are more frequent in patients on maintenance hemodialysis (HD) than the general population, and are associated with reduced quality of life and increased mortality risk. The purpose of this study was to assess the prevalence of depression, sleep apnea, insomnia in patients on HD as well as depression in their primary caregiver and to correlate these with the demographic profile. A cross-sectional study was conducted among 69 patients on maintenance HD for more than 3 months. There was high p revalence of depression (47.8%), insomnia (60.9%), increased risk of sleep apnea (24.6%) and depression in caregiver (31.9%). Depression was significantly more in patients with low monthly income (P=0.03), those on dialysis for more than 1 year (P=0.001) and the unemployed (P=0.009). High-risk patients for sleep apnea tended to be males with low monthly income (P=0.02). Insomnia was significantly higher in patients who were on dialysis for more than 1 year (P=0.003).