AIM: To examine DNA methylation profiles in a longitudinal comparison of pre-diabetes mellitus(Pre-DM) subjects who transitioned to type 2 diabetes mellitus(T2DM).METHODS: We performed DNA methylation study in bisulph...AIM: To examine DNA methylation profiles in a longitudinal comparison of pre-diabetes mellitus(Pre-DM) subjects who transitioned to type 2 diabetes mellitus(T2DM).METHODS: We performed DNA methylation study in bisulphite converted DNA from Pre-DM(n = 11) at baseline and at their transition to T2 DM using Illumina Infinium Human Methylation27 Bead Chip, that enables the query of 27578 individual cytosines at Cp G loci throughout the genome, which are focused on the promoter regions of 14495 genes.RESULTS: There were 694 Cp G sites hypomethylated and 174 Cp G sites hypermethylated in progression from Pre-DM to T2 DM, representing putative genes involved in glucose and fructose metabolism, inflammation, oxidative and mitochondrial stress, and fatty acid metabolism. These results suggest that this high throughput platform is able to identify hundreds of prospective Cp G sites associated with diverse genes that may reflect differences in Pre-DM compared with T2 DM. In addition, there were Cp G hypomethylation changes associated with a number of genes that may be associated with development of complications of diabetes, such as nephropathy. These hypomethylation changes were observed in all of the subjects.CONCLUSION: These data suggest that some epigenomic changes that may be involved in the progression of diabetes and/or the development of complications may be apparent at the Pre-DM state or during the transition to diabetes. Hypomethylation of a number of genes related to kidney function may be an early marker for developing diabetic nephropathy.展开更多
The development of formulas estimating glomerular filtration rate(eG FR) from serum creatinine and cystatin C and accounting for certain variables affecting the production rate of these biomarkers, including ethnicity...The development of formulas estimating glomerular filtration rate(eG FR) from serum creatinine and cystatin C and accounting for certain variables affecting the production rate of these biomarkers, including ethnicity, gender and age, has led to the current scheme of diagnosing and staging chronic kidney disease(CKD),which is based on e GFR values and albuminuria.This scheme has been applied extensively in various populations and has led to the current estimates of prevalence of CKD. In addition, this scheme is applied in clinical studies evaluating the risks of CKD and the efficacy of various interventions directed towards improving its course. Disagreements between creatinine-based and cystatin-based e GFR values and between e GFR values and measured GFR have been reported in various cohorts. These disagreements are the consequence of variations in the rate of production and in factors, other than GFR, affecting the rate of removal of creatinine and cystatin C. The disagreements create limitations for all e GFR formulas developed so far. The main limitations are low sensitivity in detecting early CKD in several subjects, e.g., those with hyperfiltration, and poor prediction of the course of CKD. Research efforts in CKD are currently directed towards identification of biomarkers that are better indices of GFR than the current biomarkers and,particularly, biomarkers of early renal tissue injury.展开更多
Nephropathy secondary to BK virus, a member of the Papoviridae family of viruses, has been recognized for some time as an important cause of allograft dysfunction in renal transplant recipients. In recent times, BK ne...Nephropathy secondary to BK virus, a member of the Papoviridae family of viruses, has been recognized for some time as an important cause of allograft dysfunction in renal transplant recipients. In recent times, BK nephropathy(BKN) of the native kidneys has being increasingly recognized as a cause of chronic kidney disease in patients with solid organ transplants, bone marrow transplants and in patients with other clinical entities associated with immunosuppression. In such patients renal dysfunction is often attributed to other factors including nephrotoxicity of medications used to prevent rejection of the transplanted organs. Renal biopsy is required for the diagnosis of BKN. Quantitation of the BK viral load in blood and urine are surrogate diagnostic methods. The treatment of BKN is based on reduction of the immunosuppressive medications. Several compounds have shown antiviral activity, but have not consistently shown to have beneficial effects in BKN. In addition to BKN, BK viral infection can cause severe urinary bladder cystitis, ureteritis and urinary tract obstruction as well as manifestations in other organ systems including the central nervous system, the respiratory system, the gastrointestinal system and the hematopoietic system. BK viral infection has also been implicated in tumorigenesis. The spectrum of clinical manifestations from BK infection and infection from other members of the Papoviridae family is widening. Prevention and treatment of BK infection and infections from other Papovaviruses are subjects of intense research.展开更多
AIM:To study the protein C activation system in human liver myofibroblasts,and the effects of activated protein C(APC)on these cells.METHODS:Human liver myofibroblasts were obtained by outgrowth.Expression of protease...AIM:To study the protein C activation system in human liver myofibroblasts,and the effects of activated protein C(APC)on these cells.METHODS:Human liver myofibroblasts were obtained by outgrowth.Expression of protease activated receptor 1(PAR-1),endothelial protein C receptor(EPCR) and thrombomodulin(TM)was analyzed by flow cytometry.Extracellular signal-regulated kinase(ERK)1/2 activation was assessed by Western blotting using anti-phospho-ERK antibodies.Collagen synthesis was studied with real-time reverse transcription-polymerase chain reaction(RT-PCR).Activation of protein C was studied by incubating liver myofibroblasts with zymogen protein C in the presence of thrombin and detecting the generation of APC with a colorimetric assay using a peptide substrate. RESULTS:Primary cultures of human liver myofibroblasts expressed EPCR on their surface,together with PAR-1 and TM.This receptor system was functional since exposure of myofibroblasts to APC inducedERK1/2 phosphorylation in a dose-and time-dependent manner.Furthermore,APC significantly upregulated the expression of collagen mRNA,as shown by real-time RT-PCR.Collagen upregulation was controlled through the ERK pathway as it was inhibited when using the mitogen-activated protein/extracellular signal-regulated kinase kinase inhibitor PD98059.Finally,using a cell-based colorimetric assay,we showed that intact myofibroblasts converted protein C into APC in the presence of thrombin.CONCLUSION:These data suggest that APC is a new modulator of liver myofibroblast activity and contributes to the pathophysiology of chronic liver diseases.展开更多
Artificial intelligence(AI)is a combination of different technologies that enable machines to sense,comprehend,and learn with human-like levels of intelligence.AI technology will eventually enhance human capability,pr...Artificial intelligence(AI)is a combination of different technologies that enable machines to sense,comprehend,and learn with human-like levels of intelligence.AI technology will eventually enhance human capability,provide machines genuine autonomy,and reduce errors,and increase productivity and efficiency.AI seems promising,and the field is full of invention,novel applications;however,the limitation of machine learning suggests a cautious optimism as the right strategy.AI is also becoming incorporated into medicine to improve patient care by speeding up processes and achieving greater accuracy for optimal patient care.AI using deep learning technology has been used to identify,differentiate catalog images in several medical fields including gastrointestinal endoscopy.The gastrointestinal endoscopy field involves endoscopic diagnoses and prognostication of various digestive diseases using image analysis with the help of various gastrointestinal endoscopic device systems.AI-based endoscopic systems can reliably detect and provide crucial information on gastrointestinal pathology based on their training and validation.These systems can make gastroenterology practice easier,faster,more reliable,and reduce inter-observer variability in the coming years.However,the thought that these systems will replace human decision making replace gastrointestinal endoscopists does not seem plausible in the near future.In this review,we discuss AI and associated various technological terminologies,evolving role in gastrointestinal endoscopy,and future possibilities.展开更多
Introduction: The epidemic of atherosclerotic cardiovascular disease in the Western World accounts for the majority of morbidity and mortality in adults. This disease is on the increase, and previous recommendations u...Introduction: The epidemic of atherosclerotic cardiovascular disease in the Western World accounts for the majority of morbidity and mortality in adults. This disease is on the increase, and previous recommendations using “risk equations” to prescribe preventive treatment have not been successful in reducing the prevalence of cardiovascular disease. Furthermore, compliance with statin medication has been limited, with approximately 50% of individuals being non-compliant within five years. This situation is unacceptable since atherosclerosis is both preventable and reversible. Methods: The guidelines presented in this article utilize coronary artery calcium scanning as the basis for preventative therapeutic decisions and identifying the presence of asymptomatic cardiovascular disease. This radiographic technique is superior to “risk equations” in predicting future cardiovascular events. It provides a comprehensive assessment of the lifelong insults to the coronary artery vascular endothelium and the resulting inflammation. Coronary artery calcium scanning is widely available, inexpensive, safe, and reproducible. It has the major advantage of increasing treatment compliance in patients with positive coronary artery calcium scores. Results: All suggested guidelines are supported by published scientific data. Citations are provided to allow the reader to obtain further information. The authors are available for further consultation. Each guideline provides specific recommendations that the primary caregiver can discuss with the patient. Patient involvement in decision-making is strongly recommended. Both treatment costs and adverse effects are minimal. Conclusion: It is anticipated that the early identification of asymptomatic cardiovascular disease and its aggressive treatment will result in regression of subclinical atherosclerosis. Adoption of these guidelines will stop the epidemic of symptomatic heart disease and result in healthier and more satisfied patients.展开更多
Purpose: Cardiovascular disease is the number one cause of death in the Western world. The purpose of this manuscript is to compare the benefits and deficiencies of coronary artery calcium scanning versus compute...Purpose: Cardiovascular disease is the number one cause of death in the Western world. The purpose of this manuscript is to compare the benefits and deficiencies of coronary artery calcium scanning versus computer generated risk equations in identifying atherosclerotic cardiovascular disease. These two approaches provide significantly different cardiovascular risk assessments and often lead to therapeutic differences in recommendations from the physician to the patient. Methods: Pertinent medical literature is reviewed concerning both risk assessment approaches (i.e., coronary artery scanning and computer generated risk equations). The strengths and weaknesses of both approaches are discussed, and recommendations are provided based upon available data. Results: Cardiovascular risk equations are simple and readily obtained at no charge by physicians. However, their drawbacks are several, including non-applicability to specific populations, disagreements among different cardiovascular society risk equations, wide ranges of risk outputs (e.g., intermediate 10-year risk is between 5% and 20%), inability to definitively identify coronary artery plaques, and lack of definitive anatomical coronary disease. Alternatively, coronary artery calcium scanning costs approximately $100/scan (if not covered by insurance), requires time and effort by the patient, and exposes the patient to a minimal amount of radiation. However, coronary calcium scanning identifies specific atherosclerotic coronary disease and provides additional information about the anatomical location (i.e., coronary artery) of the atherosclerotic plaque. Conclusion: Based on the published literature, coronary artery calcium scanning is the preferred approach for identifying atherosclerotic cardiovascular disease. Although there are minor drawbacks, overall it provides superior clinical information compared with computer generated risk equations.展开更多
AIM To test whether muscle mass evaluated by creatinine excretion(EXCr) is maintained in patients with end-stage kidney disease(ESKD) treated by peritoneal dialysis(PD),we evaluated repeated measurements of EXCr in a ...AIM To test whether muscle mass evaluated by creatinine excretion(EXCr) is maintained in patients with end-stage kidney disease(ESKD) treated by peritoneal dialysis(PD),we evaluated repeated measurements of EXCr in a PD population.METHODS One hundred and sixty-six PD patients(94 male,72 female) receiving the same PD dose for the duration of the study(up to approximately 2.5 years) had repeated determinations of total(in urine plus spent dialysate) 24-h EXCr(EXCr T) to assess the adequacy of PD by creatinine clearance.All 166 patients had two EXCr T determinations,84 of the 166 patients had three EXCr T determinations and 44 of the 166 patients had four EXCr T measurements.EXCr T values were compared using the paired t test in the patients who had two studies and by repeated measures ANOVA in those who were studied three or four times.RESULTS In patients who were studied twice,with the first and second EXCr T measurements performed at 9.2 ± 15.2 mo and 17.4 ± 15.8 mo after onset of PD,respectively,EXCr T did not differ between the first and second study.In patients studied three times and whose final assessment occurred 24.7 ± 16.3 mo after initiating PD,EXCr T did not differ between the first and second study,but was significantly lower in the third study compared to the first study.In patients who were studied four times and whose fourth measurement was taken 31.9 ± 16.8 mo after onset of PD,EXCr T did not differ between any of the studies.The average EXCr T value did not change significantly,with the exception of the third study in the patients studied thrice.However,repeated determinations of EXCr T in individuals showed substantial variability,with approximately 50% of the repeated determinations being higher or lower than the first determination by 15% or more.CONCLUSION The average value of EXCr T remains relatively constant for up to 2.5 years of follow-up in PD patients who adhere to the same PD schedule.However,repeated individual EXCr T values vary considerably in a large proportion of the patients.Further studies are needed to evaluate the clinical significance of varying EXCr T values and the stability of EXCr T beyond 2.5 years of PD follow-up.展开更多
BACKGROUND Roux-en-Y gastric bypass(RYGB)is a widely recognized bariatric procedure that is particularly beneficial for patients with class III obesity.It aids in significant weight loss and improves obesity-related m...BACKGROUND Roux-en-Y gastric bypass(RYGB)is a widely recognized bariatric procedure that is particularly beneficial for patients with class III obesity.It aids in significant weight loss and improves obesity-related medical conditions.Despite its effectiveness,postoperative care still has challenges.Clinical evidence shows that venous thromboembolism(VTE)is a leading cause of 30-d morbidity and mortality after RYGB.Therefore,a clear unmet need exists for a tailored risk assessment tool for VTE in RYGB candidates.AIM To develop and internally validate a scoring system determining the individualized risk of 30-d VTE in patients undergoing RYGB.METHODS Using the 2016–2021 Metabolic and Bariatric Surgery Accreditation Quality Improvement Program,data from 6526 patients(body mass index≥40 kg/m2)who underwent RYGB were analyzed.A backward elimination multivariate analysis identified predictors of VTE characterized by pulmonary embolism and/or deep venous thrombosis within 30 d of RYGB.The resultant risk scores were derived from the coefficients of statistically significant variables.The performance of the model was evaluated using receiver operating curves through 5-fold cross-validation.RESULTS Of the 26 initial variables,six predictors were identified.These included a history of chronic obstructive pulmonary disease with a regression coefficient(Coef)of 2.54(P<0.001),length of stay(Coef 0.08,P<0.001),prior deep venous thrombosis(Coef 1.61,P<0.001),hemoglobin A1c>7%(Coef 1.19,P<0.001),venous stasis history(Coef 1.43,P<0.001),and preoperative anticoagulation use(Coef 1.24,P<0.001).These variables were weighted according to their regression coefficients in an algorithm that was generated for the model predicting 30-d VTE risk post-RYGB.The risk model's area under the curve(AUC)was 0.79[95%confidence interval(CI):0.63-0.81],showing good discriminatory power,achieving a sensitivity of 0.60 and a specificity of 0.91.Without training,the same model performed satisfactorily in patients with laparoscopic sleeve gastrectomy with an AUC of 0.63(95%CI:0.62-0.64)and endoscopic sleeve gastroplasty with an AUC of 0.76(95%CI:0.75-0.78).CONCLUSION This simple risk model uses only six variables to assist clinicians in the preoperative risk stratification of RYGB patients,offering insights into factors that heighten the risk of VTE events.展开更多
The regulation of body fluid balance is a key concern in health and disease and comprises three concepts. The first concept pertains to the relationship between total body water(TBW) and total effective solute and is ...The regulation of body fluid balance is a key concern in health and disease and comprises three concepts. The first concept pertains to the relationship between total body water(TBW) and total effective solute and is expressed in terms of the tonicity of the body fluids. Disturbances in tonicity are the main factor responsible for changes in cell volume, which can critically affect brain cell function and survival. Solutes distributed almost exclusively in the extracellular compartment(mainly sodium salts) and in the intracellular compartment(mainly potassium salts) contribute to tonicity, while solutes distributed in TBW have no effect on tonicity. The second body fluid balance concept relates to the regulation and measurement of abnormalities of sodium salt balance and extracellular volume. Estimation of extracellular volume is more complex and error prone than measurement of TBW. A key function of extracellular volume, which is defined as the effective arterial blood volume(EABV), is to ensure adequate perfusion of cells and organs. Other factors, including cardiac output, total and regional capacity of both arteries and veins, Starling forces in the capillaries, and gravity also affect the EABV. Collectively, these factors interact closely with extracellular volume and some of them undergo substantial changes in certain acute and chronic severe illnesses. Their changes result not only in extracellular volume expansion, but in the need for a larger extracellular volume compared with that of healthy individuals. Assessing extracellular volume in severe illness is challenging because the estimates of this volume by commonly used methods are prone to large errors in many illnesses. In addition, the optimal extracellular volume may vary from illness to illness, is only partially based on volume measurements by traditional methods, and has not been determined for each illness. Further research is needed to determine optimal extracellular volume levels in several illnesses. For these reasons, extracellular volume in severe illness merits a separate third concept of body fluid balance.展开更多
Background: Quantifying ten-year cardiovascular risk can be challenging. Different online risk calculators provide different risk estimates and online risk calculators use only one point in time. However, risk factors...Background: Quantifying ten-year cardiovascular risk can be challenging. Different online risk calculators provide different risk estimates and online risk calculators use only one point in time. However, risk factors occur over the lifetime of the individual. Purpose: This manuscript provides three solutions to improving ten-year cardiovascular risk assessment in individuals at intermediate risk. Methods: Measuring Lipoprotein(a)—Lp(a) is recommended for assessing cardiovascular risk in all individuals who are in the intermediate risk category by standard online risk calculators. Lp(a) is primarily determined by genetic inheritance. It has the undesirable properties of being proatherosclerotic, proinflammatory, and prothrombotic. Measuring apolipoprotein B (apo B) provides a good index of the number of atherosclerotic particles present. Studies have demonstrated that small, dense LDL cholesterol particles are more atherogenic than larger, less dense LDL cholesterol particles. Measuring high sensitivity C-reactive protein (hsCRP) provides a good estimation of the degree of inflammation in the vascular system. Inflammation is a critical component of heart attacks and strokes. It is increased in diabetes and obesity. Treatment to reduce inflammation results in a reduction of cardiovascular events, independent of lipid values. Results: The above three risk factors should be measured in all patients with an intermediate risk score. Routine assays are readily available at a reasonable cost. They are independent risk factors for cardiovascular disease. Their recommendation is based on the pathophysiology of atherosclerotic cardiovascular disease. Successful therapy will result in the decrease of each of these risk factors. Conclusion: The recommended approach will improve the assessment of cardiovascular risk and guide the physician and patient to the correct treatment recommendations.展开更多
Background: COVID-19 has had a major impact on all facets of life in the United States. Its devastating effects have resulted in the mobilization of major resources, both at the national, state, and individu...Background: COVID-19 has had a major impact on all facets of life in the United States. Its devastating effects have resulted in the mobilization of major resources, both at the national, state, and individual levels. This mobilization has resulted in vaccination, personal preventive measures, and new therapies to combat this illness. As a result, the rates of new infections, hospitalizations, and deaths have greatly diminished, minimizing the associated morbidity and mortality. Purpose: What has not been appreciated is that a more serious epidemic has continued unabated in the United States and the Western world. This article emphasizes the importance of a national effort to eradicate cardiovascular disease. Methods: Cardiovascular disease has caused more deaths than COVID-19 in almost all months since the COVID-19 epidemic was first recognized in December 2020. In fact, cardiovascular disease has caused more deaths than either all cancers combined or infections for the last two decades. The tragedy of this truth is that effective therapy is currently available for preventing and reversing cardiovascular disease at a very low cost. What is required is a concerted effort and commitment by all legislative and medical organizations to allocate the resources to abolish asymptomatic cardiovascular disease. Results: Recognition and mobilization of resources to combat this epidemic are much overdue with the resultant savings of lives and billions of dollars. It is past time for the medical establishment to support the national identification of asymptomatic cardiovascular disease and initiate treatment before patients become symptomatic with this deadly disease. Conclusion: The national experience with COVID-19 has demonstrated what can be accomplished when a national concerted effort is made to address a devastating medical epidemic. This commitment is not only feasible for cardiovascular disease, but is also necessary for the benefit of all people in the world.展开更多
The role of blood cholesterol levels in coronary heart disease(CHD) and the true effect of cholesterollowering statin drugs are debatable. In particular,whether statins actually decrease cardiac mortality and increase...The role of blood cholesterol levels in coronary heart disease(CHD) and the true effect of cholesterollowering statin drugs are debatable. In particular,whether statins actually decrease cardiac mortality and increase life expectancy is controversial. Concurrently,the Mediterranean diet model has been shown to prolong life and reduce the risk of diabetes,cancer,and CHD. We herein review current data related to both statins and the Mediterranean diet. We conclude that the expectation that CHD could be prevented or eliminated by simply reducing cholesterol appears unfounded. On the contrary,we should acknowledge the inconsistencies of the cholesterol theory and recognize the proven benefits of a healthy lifestyle incorporating a Mediterranean diet to prevent CHD.展开更多
Respiratory failure complicating the course of diabetic ketoacidosis(DKA)is a source of increased morbidity and mortality.Detection of respiratory failure in DKA requires focused clinical monitoring,careful interpreta...Respiratory failure complicating the course of diabetic ketoacidosis(DKA)is a source of increased morbidity and mortality.Detection of respiratory failure in DKA requires focused clinical monitoring,careful interpretation of arterial blood gases,and investigation for conditions that can affect adversely the respiration.Conditions that compromise respiratory function caused by DKA can be detected at presentation but are usually more prevalent during treatment.These conditions include deficits of potassium,magnesium and phosphate and hydrostatic or non-hydrostatic pulmonary edema.Conditions not caused by DKA that can worsen respiratory function under the added stress of DKA include infections of the respiratory system,pre-existing respiratory or neuromuscular disease and miscellaneous other conditions.Prompt recognition and management of the conditions that can lead to respiratory failure in DKA may prevent respiratory failure and improve mortality from DKA.展开更多
Purpose: To report a case of bilateral glaucoma related to pseudophacomorphic mechanism in one eye and pupillary block in the other eye after Visian Implantable Collamer Lens (ICL;STAAR Surgical) insertion. Methods: A...Purpose: To report a case of bilateral glaucoma related to pseudophacomorphic mechanism in one eye and pupillary block in the other eye after Visian Implantable Collamer Lens (ICL;STAAR Surgical) insertion. Methods: A 44-year-old female with high myopia underwent bilateral ICL implantation of MICL12.6 after sulcus diameter measurements were performed by Pentacam. Results: Pseudophacomorphic glaucoma-related angle closure occurred due to lens oversizing in the right eye. The mechanism was relieved via ICL explantation. In the left eye, pupillary block developed in a subacute manner after closure of the Peripheral Iridotomy (PI). The attack was ameliorated by reestablishing patency of the iridotomy. Conclusions: ICL-related glaucomatous attacks may result from improper sizing as well as from placement of a single PI. Identification of the proper mechanism is vital as treatments differ significantly. In pseudo phacomorphic glaucoma, explantation is needed. In pupillary block glaucoma, treatment involves establishment of a patent PI.展开更多
Hyperoxaluria can cause not only nephrolithiasis and nephrocalcinosis,but also renal parenchymal disease histologically characterized by deposition of calcium oxalate crystals throughout the renal parenchyma,profound ...Hyperoxaluria can cause not only nephrolithiasis and nephrocalcinosis,but also renal parenchymal disease histologically characterized by deposition of calcium oxalate crystals throughout the renal parenchyma,profound tubular damage and interstitial inflammation and fibrosis.Hyperoxaluric nephropathy presents clinically as acute or chronic renal failure that may progress to endstage renal disease(ESRD).This sequence of events,well recognized in the past in primary and enteric hyperoxalurias,has also been documented in a few cases of dietary hyperoxaluria.Estimates of oxalate intake in patients with chronic dietary hyperoxaluria who developed chronic kidney disease or ESRD were comparable to the reported average oxalate content of the diets of certain populations worldwide,thus raising the question whether dietary hyperoxaluria is a primary cause of ESRD in these regions.Studies addressing this question have the potential of improving population health and should be undertaken,alongside ongoing studies which are yielding fresh insights into the mechanisms of intestinal absorption and renal excretion of oxalate,and into the mechanisms of development of oxalate-induced renal parenchymal disease.Novel preventive and therapeutic strategies for treating all types of hyperoxaluria are expected to develop from these studies.展开更多
A man with past lithium use for more than 15 years, but off lithium for two years and not carrying the diagnosis of diabetes mellitus or nephrogenic diabetes insipidus(NDI), presented with coma and hyperglycemic hyper...A man with past lithium use for more than 15 years, but off lithium for two years and not carrying the diagnosis of diabetes mellitus or nephrogenic diabetes insipidus(NDI), presented with coma and hyperglycemic hyperosmolar state(HHS). Following correction of HHS, he developed persistent hypernatremia accompanied by large volumes of urine with low osmolality and no response to desmopressin injections. Urine osmolality remained < 300 m Osm/kg after injection of vasopressin. Improvement in serum sodium concentration followed the intake of large volumes of water plus administration of amiloride and hydrochlorothiazide. Severe hyperglycemia may trigger symptomatic lithium-induced NDI years after cessation of lithium therapy. Patients with newonset diabetes mellitus who had been on prolonged lithium therapy in the past require monitoring of their serum sodium concentration after hyperglycemic episodes regardless of whether they do or do not carry the diagnosis of NDI.展开更多
Importance: Cardiovascular disease is the number one cause of death in the adult population, greater than all cancers combined. When a heart attack or stroke occurs, many individuals have no advance warning, thus maki...Importance: Cardiovascular disease is the number one cause of death in the adult population, greater than all cancers combined. When a heart attack or stroke occurs, many individuals have no advance warning, thus making prevention difficult. Cardiovascular disease begins early, i.e., in the developing fetus, and progresses throughout childhood and adolescence, such that it is identifiable both radiographically and ultrasonographically in the adolescent. Observations: There are multiple lines of evidence that atherosclerosis is present in the pediatric population. This evidence is based on autopsy studies in accident victims, coronary artery calcium scoring and carotid intermedia thickness measurements, intravascular ultrasound studies of hearts transplanted from teenage accident victims, and wartime casualties in young males. Multiple studies of cardiovascular risk factors (e.g., hypertension, obesity, insulin resistance, glucose intolerance and hyperlipidemia) have emphasized their importance in contributing to the pathogenesis of atherosclerosis. With the recent increase of obesity in the pediatric population, these risk factors will assume increasing importance in the development of clinical cardiovascular disease in the adult population. Prevention of atherosclerosis will require measuring a lipid profile in adolescents and initiating intervention to reduce the triglyceride and LDLc concentration. Education of both the adolescent at risk and his/her family will be necessary. Lifestyle changes are paramount. Hyperlipidemic medication should be reserved for individuals with severe lipid abnormalities. Conclusion and Relevance:Atherosclerotic changes of arteries begin during gestation and progress throughout the pediatric years into adulthood. Pediatricians’ contribution to reducing the progression of atherosclerosis in their patients can have major effects in controlling this epidemic in adults. Education of adolescents and their parents concerning a healthy lifestyle is paramount to a successful cardiovascular disease prevention program.展开更多
Hypertonicity causes severe clinical manifestations and is associated with mortality and severe short-term and longterm neurological sequelae. The main clinical syndromes of hypertonicity are hypernatremia and hypergl...Hypertonicity causes severe clinical manifestations and is associated with mortality and severe short-term and longterm neurological sequelae. The main clinical syndromes of hypertonicity are hypernatremia and hyperglycemia.Hypernatremia results from relative excess of body sodium over body water. Loss of water in excess of intake,gain of sodium salts in excess of losses or a combination of the two are the main mechanisms of hypernatremia.Hypernatremia can be hypervolemic,euvolemic or hypovolemic. The management of hypernatremia addresses both a quantitative replacement of water and,if present,sodium deficit,and correction of the underlying pathophysiologic process that led to hypernatremia.Hypertonicity in hyperglycemia has two components,solute gain secondary to glucose accumulation in the extracellular compartment and water loss through hyperglycemic osmotic diuresis in excess of the losses of sodium and potassium. Differentiating between these two components of hypertonicity has major therapeutic implications because the first component will be reversed simply by normalization of serum glucose concentration while the second component will require hypotonic fluid replacement. An estimate of the magnitude of the relative water deficit secondary to osmotic diuresis is obtained by the corrected sodium concentration,which represents a calculated value of the serum sodium concentration that would result from reduction of the serum glucose concentration to a normal level.展开更多
基金Supported by The grants from the National Center for Research Resources,No.5P20RR016480-12The National Institute of General Medical Sciences of the NIH,No.8P20GM103451-12+2 种基金the partial support from the National Center for Advancing Translational Sciences of the National Institutes of Health,No.8UL1TR000041the University of New Mexico Clinical and Translational Science Centerthe cost for clinical phenotyping and payments to participants was supported under a UNM Health Sciences Center-based Cardiovascular and Metabolic Diseases Signature Program
文摘AIM: To examine DNA methylation profiles in a longitudinal comparison of pre-diabetes mellitus(Pre-DM) subjects who transitioned to type 2 diabetes mellitus(T2DM).METHODS: We performed DNA methylation study in bisulphite converted DNA from Pre-DM(n = 11) at baseline and at their transition to T2 DM using Illumina Infinium Human Methylation27 Bead Chip, that enables the query of 27578 individual cytosines at Cp G loci throughout the genome, which are focused on the promoter regions of 14495 genes.RESULTS: There were 694 Cp G sites hypomethylated and 174 Cp G sites hypermethylated in progression from Pre-DM to T2 DM, representing putative genes involved in glucose and fructose metabolism, inflammation, oxidative and mitochondrial stress, and fatty acid metabolism. These results suggest that this high throughput platform is able to identify hundreds of prospective Cp G sites associated with diverse genes that may reflect differences in Pre-DM compared with T2 DM. In addition, there were Cp G hypomethylation changes associated with a number of genes that may be associated with development of complications of diabetes, such as nephropathy. These hypomethylation changes were observed in all of the subjects.CONCLUSION: These data suggest that some epigenomic changes that may be involved in the progression of diabetes and/or the development of complications may be apparent at the Pre-DM state or during the transition to diabetes. Hypomethylation of a number of genes related to kidney function may be an early marker for developing diabetic nephropathy.
基金the Research Service of the Raymond G. Murphy VA Medical Center for its support of this work
文摘The development of formulas estimating glomerular filtration rate(eG FR) from serum creatinine and cystatin C and accounting for certain variables affecting the production rate of these biomarkers, including ethnicity, gender and age, has led to the current scheme of diagnosing and staging chronic kidney disease(CKD),which is based on e GFR values and albuminuria.This scheme has been applied extensively in various populations and has led to the current estimates of prevalence of CKD. In addition, this scheme is applied in clinical studies evaluating the risks of CKD and the efficacy of various interventions directed towards improving its course. Disagreements between creatinine-based and cystatin-based e GFR values and between e GFR values and measured GFR have been reported in various cohorts. These disagreements are the consequence of variations in the rate of production and in factors, other than GFR, affecting the rate of removal of creatinine and cystatin C. The disagreements create limitations for all e GFR formulas developed so far. The main limitations are low sensitivity in detecting early CKD in several subjects, e.g., those with hyperfiltration, and poor prediction of the course of CKD. Research efforts in CKD are currently directed towards identification of biomarkers that are better indices of GFR than the current biomarkers and,particularly, biomarkers of early renal tissue injury.
文摘Nephropathy secondary to BK virus, a member of the Papoviridae family of viruses, has been recognized for some time as an important cause of allograft dysfunction in renal transplant recipients. In recent times, BK nephropathy(BKN) of the native kidneys has being increasingly recognized as a cause of chronic kidney disease in patients with solid organ transplants, bone marrow transplants and in patients with other clinical entities associated with immunosuppression. In such patients renal dysfunction is often attributed to other factors including nephrotoxicity of medications used to prevent rejection of the transplanted organs. Renal biopsy is required for the diagnosis of BKN. Quantitation of the BK viral load in blood and urine are surrogate diagnostic methods. The treatment of BKN is based on reduction of the immunosuppressive medications. Several compounds have shown antiviral activity, but have not consistently shown to have beneficial effects in BKN. In addition to BKN, BK viral infection can cause severe urinary bladder cystitis, ureteritis and urinary tract obstruction as well as manifestations in other organ systems including the central nervous system, the respiratory system, the gastrointestinal system and the hematopoietic system. BK viral infection has also been implicated in tumorigenesis. The spectrum of clinical manifestations from BK infection and infection from other members of the Papoviridae family is widening. Prevention and treatment of BK infection and infections from other Papovaviruses are subjects of intense research.
文摘AIM:To study the protein C activation system in human liver myofibroblasts,and the effects of activated protein C(APC)on these cells.METHODS:Human liver myofibroblasts were obtained by outgrowth.Expression of protease activated receptor 1(PAR-1),endothelial protein C receptor(EPCR) and thrombomodulin(TM)was analyzed by flow cytometry.Extracellular signal-regulated kinase(ERK)1/2 activation was assessed by Western blotting using anti-phospho-ERK antibodies.Collagen synthesis was studied with real-time reverse transcription-polymerase chain reaction(RT-PCR).Activation of protein C was studied by incubating liver myofibroblasts with zymogen protein C in the presence of thrombin and detecting the generation of APC with a colorimetric assay using a peptide substrate. RESULTS:Primary cultures of human liver myofibroblasts expressed EPCR on their surface,together with PAR-1 and TM.This receptor system was functional since exposure of myofibroblasts to APC inducedERK1/2 phosphorylation in a dose-and time-dependent manner.Furthermore,APC significantly upregulated the expression of collagen mRNA,as shown by real-time RT-PCR.Collagen upregulation was controlled through the ERK pathway as it was inhibited when using the mitogen-activated protein/extracellular signal-regulated kinase kinase inhibitor PD98059.Finally,using a cell-based colorimetric assay,we showed that intact myofibroblasts converted protein C into APC in the presence of thrombin.CONCLUSION:These data suggest that APC is a new modulator of liver myofibroblast activity and contributes to the pathophysiology of chronic liver diseases.
文摘Artificial intelligence(AI)is a combination of different technologies that enable machines to sense,comprehend,and learn with human-like levels of intelligence.AI technology will eventually enhance human capability,provide machines genuine autonomy,and reduce errors,and increase productivity and efficiency.AI seems promising,and the field is full of invention,novel applications;however,the limitation of machine learning suggests a cautious optimism as the right strategy.AI is also becoming incorporated into medicine to improve patient care by speeding up processes and achieving greater accuracy for optimal patient care.AI using deep learning technology has been used to identify,differentiate catalog images in several medical fields including gastrointestinal endoscopy.The gastrointestinal endoscopy field involves endoscopic diagnoses and prognostication of various digestive diseases using image analysis with the help of various gastrointestinal endoscopic device systems.AI-based endoscopic systems can reliably detect and provide crucial information on gastrointestinal pathology based on their training and validation.These systems can make gastroenterology practice easier,faster,more reliable,and reduce inter-observer variability in the coming years.However,the thought that these systems will replace human decision making replace gastrointestinal endoscopists does not seem plausible in the near future.In this review,we discuss AI and associated various technological terminologies,evolving role in gastrointestinal endoscopy,and future possibilities.
文摘Introduction: The epidemic of atherosclerotic cardiovascular disease in the Western World accounts for the majority of morbidity and mortality in adults. This disease is on the increase, and previous recommendations using “risk equations” to prescribe preventive treatment have not been successful in reducing the prevalence of cardiovascular disease. Furthermore, compliance with statin medication has been limited, with approximately 50% of individuals being non-compliant within five years. This situation is unacceptable since atherosclerosis is both preventable and reversible. Methods: The guidelines presented in this article utilize coronary artery calcium scanning as the basis for preventative therapeutic decisions and identifying the presence of asymptomatic cardiovascular disease. This radiographic technique is superior to “risk equations” in predicting future cardiovascular events. It provides a comprehensive assessment of the lifelong insults to the coronary artery vascular endothelium and the resulting inflammation. Coronary artery calcium scanning is widely available, inexpensive, safe, and reproducible. It has the major advantage of increasing treatment compliance in patients with positive coronary artery calcium scores. Results: All suggested guidelines are supported by published scientific data. Citations are provided to allow the reader to obtain further information. The authors are available for further consultation. Each guideline provides specific recommendations that the primary caregiver can discuss with the patient. Patient involvement in decision-making is strongly recommended. Both treatment costs and adverse effects are minimal. Conclusion: It is anticipated that the early identification of asymptomatic cardiovascular disease and its aggressive treatment will result in regression of subclinical atherosclerosis. Adoption of these guidelines will stop the epidemic of symptomatic heart disease and result in healthier and more satisfied patients.
文摘Purpose: Cardiovascular disease is the number one cause of death in the Western world. The purpose of this manuscript is to compare the benefits and deficiencies of coronary artery calcium scanning versus computer generated risk equations in identifying atherosclerotic cardiovascular disease. These two approaches provide significantly different cardiovascular risk assessments and often lead to therapeutic differences in recommendations from the physician to the patient. Methods: Pertinent medical literature is reviewed concerning both risk assessment approaches (i.e., coronary artery scanning and computer generated risk equations). The strengths and weaknesses of both approaches are discussed, and recommendations are provided based upon available data. Results: Cardiovascular risk equations are simple and readily obtained at no charge by physicians. However, their drawbacks are several, including non-applicability to specific populations, disagreements among different cardiovascular society risk equations, wide ranges of risk outputs (e.g., intermediate 10-year risk is between 5% and 20%), inability to definitively identify coronary artery plaques, and lack of definitive anatomical coronary disease. Alternatively, coronary artery calcium scanning costs approximately $100/scan (if not covered by insurance), requires time and effort by the patient, and exposes the patient to a minimal amount of radiation. However, coronary calcium scanning identifies specific atherosclerotic coronary disease and provides additional information about the anatomical location (i.e., coronary artery) of the atherosclerotic plaque. Conclusion: Based on the published literature, coronary artery calcium scanning is the preferred approach for identifying atherosclerotic cardiovascular disease. Although there are minor drawbacks, overall it provides superior clinical information compared with computer generated risk equations.
文摘AIM To test whether muscle mass evaluated by creatinine excretion(EXCr) is maintained in patients with end-stage kidney disease(ESKD) treated by peritoneal dialysis(PD),we evaluated repeated measurements of EXCr in a PD population.METHODS One hundred and sixty-six PD patients(94 male,72 female) receiving the same PD dose for the duration of the study(up to approximately 2.5 years) had repeated determinations of total(in urine plus spent dialysate) 24-h EXCr(EXCr T) to assess the adequacy of PD by creatinine clearance.All 166 patients had two EXCr T determinations,84 of the 166 patients had three EXCr T determinations and 44 of the 166 patients had four EXCr T measurements.EXCr T values were compared using the paired t test in the patients who had two studies and by repeated measures ANOVA in those who were studied three or four times.RESULTS In patients who were studied twice,with the first and second EXCr T measurements performed at 9.2 ± 15.2 mo and 17.4 ± 15.8 mo after onset of PD,respectively,EXCr T did not differ between the first and second study.In patients studied three times and whose final assessment occurred 24.7 ± 16.3 mo after initiating PD,EXCr T did not differ between the first and second study,but was significantly lower in the third study compared to the first study.In patients who were studied four times and whose fourth measurement was taken 31.9 ± 16.8 mo after onset of PD,EXCr T did not differ between any of the studies.The average EXCr T value did not change significantly,with the exception of the third study in the patients studied thrice.However,repeated determinations of EXCr T in individuals showed substantial variability,with approximately 50% of the repeated determinations being higher or lower than the first determination by 15% or more.CONCLUSION The average value of EXCr T remains relatively constant for up to 2.5 years of follow-up in PD patients who adhere to the same PD schedule.However,repeated individual EXCr T values vary considerably in a large proportion of the patients.Further studies are needed to evaluate the clinical significance of varying EXCr T values and the stability of EXCr T beyond 2.5 years of PD follow-up.
文摘BACKGROUND Roux-en-Y gastric bypass(RYGB)is a widely recognized bariatric procedure that is particularly beneficial for patients with class III obesity.It aids in significant weight loss and improves obesity-related medical conditions.Despite its effectiveness,postoperative care still has challenges.Clinical evidence shows that venous thromboembolism(VTE)is a leading cause of 30-d morbidity and mortality after RYGB.Therefore,a clear unmet need exists for a tailored risk assessment tool for VTE in RYGB candidates.AIM To develop and internally validate a scoring system determining the individualized risk of 30-d VTE in patients undergoing RYGB.METHODS Using the 2016–2021 Metabolic and Bariatric Surgery Accreditation Quality Improvement Program,data from 6526 patients(body mass index≥40 kg/m2)who underwent RYGB were analyzed.A backward elimination multivariate analysis identified predictors of VTE characterized by pulmonary embolism and/or deep venous thrombosis within 30 d of RYGB.The resultant risk scores were derived from the coefficients of statistically significant variables.The performance of the model was evaluated using receiver operating curves through 5-fold cross-validation.RESULTS Of the 26 initial variables,six predictors were identified.These included a history of chronic obstructive pulmonary disease with a regression coefficient(Coef)of 2.54(P<0.001),length of stay(Coef 0.08,P<0.001),prior deep venous thrombosis(Coef 1.61,P<0.001),hemoglobin A1c>7%(Coef 1.19,P<0.001),venous stasis history(Coef 1.43,P<0.001),and preoperative anticoagulation use(Coef 1.24,P<0.001).These variables were weighted according to their regression coefficients in an algorithm that was generated for the model predicting 30-d VTE risk post-RYGB.The risk model's area under the curve(AUC)was 0.79[95%confidence interval(CI):0.63-0.81],showing good discriminatory power,achieving a sensitivity of 0.60 and a specificity of 0.91.Without training,the same model performed satisfactorily in patients with laparoscopic sleeve gastrectomy with an AUC of 0.63(95%CI:0.62-0.64)and endoscopic sleeve gastroplasty with an AUC of 0.76(95%CI:0.75-0.78).CONCLUSION This simple risk model uses only six variables to assist clinicians in the preoperative risk stratification of RYGB patients,offering insights into factors that heighten the risk of VTE events.
文摘The regulation of body fluid balance is a key concern in health and disease and comprises three concepts. The first concept pertains to the relationship between total body water(TBW) and total effective solute and is expressed in terms of the tonicity of the body fluids. Disturbances in tonicity are the main factor responsible for changes in cell volume, which can critically affect brain cell function and survival. Solutes distributed almost exclusively in the extracellular compartment(mainly sodium salts) and in the intracellular compartment(mainly potassium salts) contribute to tonicity, while solutes distributed in TBW have no effect on tonicity. The second body fluid balance concept relates to the regulation and measurement of abnormalities of sodium salt balance and extracellular volume. Estimation of extracellular volume is more complex and error prone than measurement of TBW. A key function of extracellular volume, which is defined as the effective arterial blood volume(EABV), is to ensure adequate perfusion of cells and organs. Other factors, including cardiac output, total and regional capacity of both arteries and veins, Starling forces in the capillaries, and gravity also affect the EABV. Collectively, these factors interact closely with extracellular volume and some of them undergo substantial changes in certain acute and chronic severe illnesses. Their changes result not only in extracellular volume expansion, but in the need for a larger extracellular volume compared with that of healthy individuals. Assessing extracellular volume in severe illness is challenging because the estimates of this volume by commonly used methods are prone to large errors in many illnesses. In addition, the optimal extracellular volume may vary from illness to illness, is only partially based on volume measurements by traditional methods, and has not been determined for each illness. Further research is needed to determine optimal extracellular volume levels in several illnesses. For these reasons, extracellular volume in severe illness merits a separate third concept of body fluid balance.
文摘Background: Quantifying ten-year cardiovascular risk can be challenging. Different online risk calculators provide different risk estimates and online risk calculators use only one point in time. However, risk factors occur over the lifetime of the individual. Purpose: This manuscript provides three solutions to improving ten-year cardiovascular risk assessment in individuals at intermediate risk. Methods: Measuring Lipoprotein(a)—Lp(a) is recommended for assessing cardiovascular risk in all individuals who are in the intermediate risk category by standard online risk calculators. Lp(a) is primarily determined by genetic inheritance. It has the undesirable properties of being proatherosclerotic, proinflammatory, and prothrombotic. Measuring apolipoprotein B (apo B) provides a good index of the number of atherosclerotic particles present. Studies have demonstrated that small, dense LDL cholesterol particles are more atherogenic than larger, less dense LDL cholesterol particles. Measuring high sensitivity C-reactive protein (hsCRP) provides a good estimation of the degree of inflammation in the vascular system. Inflammation is a critical component of heart attacks and strokes. It is increased in diabetes and obesity. Treatment to reduce inflammation results in a reduction of cardiovascular events, independent of lipid values. Results: The above three risk factors should be measured in all patients with an intermediate risk score. Routine assays are readily available at a reasonable cost. They are independent risk factors for cardiovascular disease. Their recommendation is based on the pathophysiology of atherosclerotic cardiovascular disease. Successful therapy will result in the decrease of each of these risk factors. Conclusion: The recommended approach will improve the assessment of cardiovascular risk and guide the physician and patient to the correct treatment recommendations.
文摘Background: COVID-19 has had a major impact on all facets of life in the United States. Its devastating effects have resulted in the mobilization of major resources, both at the national, state, and individual levels. This mobilization has resulted in vaccination, personal preventive measures, and new therapies to combat this illness. As a result, the rates of new infections, hospitalizations, and deaths have greatly diminished, minimizing the associated morbidity and mortality. Purpose: What has not been appreciated is that a more serious epidemic has continued unabated in the United States and the Western world. This article emphasizes the importance of a national effort to eradicate cardiovascular disease. Methods: Cardiovascular disease has caused more deaths than COVID-19 in almost all months since the COVID-19 epidemic was first recognized in December 2020. In fact, cardiovascular disease has caused more deaths than either all cancers combined or infections for the last two decades. The tragedy of this truth is that effective therapy is currently available for preventing and reversing cardiovascular disease at a very low cost. What is required is a concerted effort and commitment by all legislative and medical organizations to allocate the resources to abolish asymptomatic cardiovascular disease. Results: Recognition and mobilization of resources to combat this epidemic are much overdue with the resultant savings of lives and billions of dollars. It is past time for the medical establishment to support the national identification of asymptomatic cardiovascular disease and initiate treatment before patients become symptomatic with this deadly disease. Conclusion: The national experience with COVID-19 has demonstrated what can be accomplished when a national concerted effort is made to address a devastating medical epidemic. This commitment is not only feasible for cardiovascular disease, but is also necessary for the benefit of all people in the world.
文摘The role of blood cholesterol levels in coronary heart disease(CHD) and the true effect of cholesterollowering statin drugs are debatable. In particular,whether statins actually decrease cardiac mortality and increase life expectancy is controversial. Concurrently,the Mediterranean diet model has been shown to prolong life and reduce the risk of diabetes,cancer,and CHD. We herein review current data related to both statins and the Mediterranean diet. We conclude that the expectation that CHD could be prevented or eliminated by simply reducing cholesterol appears unfounded. On the contrary,we should acknowledge the inconsistencies of the cholesterol theory and recognize the proven benefits of a healthy lifestyle incorporating a Mediterranean diet to prevent CHD.
文摘Respiratory failure complicating the course of diabetic ketoacidosis(DKA)is a source of increased morbidity and mortality.Detection of respiratory failure in DKA requires focused clinical monitoring,careful interpretation of arterial blood gases,and investigation for conditions that can affect adversely the respiration.Conditions that compromise respiratory function caused by DKA can be detected at presentation but are usually more prevalent during treatment.These conditions include deficits of potassium,magnesium and phosphate and hydrostatic or non-hydrostatic pulmonary edema.Conditions not caused by DKA that can worsen respiratory function under the added stress of DKA include infections of the respiratory system,pre-existing respiratory or neuromuscular disease and miscellaneous other conditions.Prompt recognition and management of the conditions that can lead to respiratory failure in DKA may prevent respiratory failure and improve mortality from DKA.
文摘Purpose: To report a case of bilateral glaucoma related to pseudophacomorphic mechanism in one eye and pupillary block in the other eye after Visian Implantable Collamer Lens (ICL;STAAR Surgical) insertion. Methods: A 44-year-old female with high myopia underwent bilateral ICL implantation of MICL12.6 after sulcus diameter measurements were performed by Pentacam. Results: Pseudophacomorphic glaucoma-related angle closure occurred due to lens oversizing in the right eye. The mechanism was relieved via ICL explantation. In the left eye, pupillary block developed in a subacute manner after closure of the Peripheral Iridotomy (PI). The attack was ameliorated by reestablishing patency of the iridotomy. Conclusions: ICL-related glaucomatous attacks may result from improper sizing as well as from placement of a single PI. Identification of the proper mechanism is vital as treatments differ significantly. In pseudo phacomorphic glaucoma, explantation is needed. In pupillary block glaucoma, treatment involves establishment of a patent PI.
文摘Hyperoxaluria can cause not only nephrolithiasis and nephrocalcinosis,but also renal parenchymal disease histologically characterized by deposition of calcium oxalate crystals throughout the renal parenchyma,profound tubular damage and interstitial inflammation and fibrosis.Hyperoxaluric nephropathy presents clinically as acute or chronic renal failure that may progress to endstage renal disease(ESRD).This sequence of events,well recognized in the past in primary and enteric hyperoxalurias,has also been documented in a few cases of dietary hyperoxaluria.Estimates of oxalate intake in patients with chronic dietary hyperoxaluria who developed chronic kidney disease or ESRD were comparable to the reported average oxalate content of the diets of certain populations worldwide,thus raising the question whether dietary hyperoxaluria is a primary cause of ESRD in these regions.Studies addressing this question have the potential of improving population health and should be undertaken,alongside ongoing studies which are yielding fresh insights into the mechanisms of intestinal absorption and renal excretion of oxalate,and into the mechanisms of development of oxalate-induced renal parenchymal disease.Novel preventive and therapeutic strategies for treating all types of hyperoxaluria are expected to develop from these studies.
文摘A man with past lithium use for more than 15 years, but off lithium for two years and not carrying the diagnosis of diabetes mellitus or nephrogenic diabetes insipidus(NDI), presented with coma and hyperglycemic hyperosmolar state(HHS). Following correction of HHS, he developed persistent hypernatremia accompanied by large volumes of urine with low osmolality and no response to desmopressin injections. Urine osmolality remained < 300 m Osm/kg after injection of vasopressin. Improvement in serum sodium concentration followed the intake of large volumes of water plus administration of amiloride and hydrochlorothiazide. Severe hyperglycemia may trigger symptomatic lithium-induced NDI years after cessation of lithium therapy. Patients with newonset diabetes mellitus who had been on prolonged lithium therapy in the past require monitoring of their serum sodium concentration after hyperglycemic episodes regardless of whether they do or do not carry the diagnosis of NDI.
文摘Importance: Cardiovascular disease is the number one cause of death in the adult population, greater than all cancers combined. When a heart attack or stroke occurs, many individuals have no advance warning, thus making prevention difficult. Cardiovascular disease begins early, i.e., in the developing fetus, and progresses throughout childhood and adolescence, such that it is identifiable both radiographically and ultrasonographically in the adolescent. Observations: There are multiple lines of evidence that atherosclerosis is present in the pediatric population. This evidence is based on autopsy studies in accident victims, coronary artery calcium scoring and carotid intermedia thickness measurements, intravascular ultrasound studies of hearts transplanted from teenage accident victims, and wartime casualties in young males. Multiple studies of cardiovascular risk factors (e.g., hypertension, obesity, insulin resistance, glucose intolerance and hyperlipidemia) have emphasized their importance in contributing to the pathogenesis of atherosclerosis. With the recent increase of obesity in the pediatric population, these risk factors will assume increasing importance in the development of clinical cardiovascular disease in the adult population. Prevention of atherosclerosis will require measuring a lipid profile in adolescents and initiating intervention to reduce the triglyceride and LDLc concentration. Education of both the adolescent at risk and his/her family will be necessary. Lifestyle changes are paramount. Hyperlipidemic medication should be reserved for individuals with severe lipid abnormalities. Conclusion and Relevance:Atherosclerotic changes of arteries begin during gestation and progress throughout the pediatric years into adulthood. Pediatricians’ contribution to reducing the progression of atherosclerosis in their patients can have major effects in controlling this epidemic in adults. Education of adolescents and their parents concerning a healthy lifestyle is paramount to a successful cardiovascular disease prevention program.
文摘Hypertonicity causes severe clinical manifestations and is associated with mortality and severe short-term and longterm neurological sequelae. The main clinical syndromes of hypertonicity are hypernatremia and hyperglycemia.Hypernatremia results from relative excess of body sodium over body water. Loss of water in excess of intake,gain of sodium salts in excess of losses or a combination of the two are the main mechanisms of hypernatremia.Hypernatremia can be hypervolemic,euvolemic or hypovolemic. The management of hypernatremia addresses both a quantitative replacement of water and,if present,sodium deficit,and correction of the underlying pathophysiologic process that led to hypernatremia.Hypertonicity in hyperglycemia has two components,solute gain secondary to glucose accumulation in the extracellular compartment and water loss through hyperglycemic osmotic diuresis in excess of the losses of sodium and potassium. Differentiating between these two components of hypertonicity has major therapeutic implications because the first component will be reversed simply by normalization of serum glucose concentration while the second component will require hypotonic fluid replacement. An estimate of the magnitude of the relative water deficit secondary to osmotic diuresis is obtained by the corrected sodium concentration,which represents a calculated value of the serum sodium concentration that would result from reduction of the serum glucose concentration to a normal level.
