PubMed Health⌕ Search

Biomedical subjects

Errol D Crook

Publications and source records attributed to Errol D Crook.

At least 37 records · Page 2Linked to original sources
PubMed2003

Potential role of increased iron stores in diabetes.

Diabetes mellitus (DM) is an important risk factor for the development of cardiovascular disease. Extensive clinical, epidemiologic, and basic studies suggest that excessive tissue iron stores may contribute to the occurrence and complications of DM. Secondary diabetes occurs in inherited pathologic iron overload syndromes of European- and African-derived populations and is an established complication of transfusional iron overload. Epidemiologic studies have repeatedly shown positive correlation between levels of serum ferritin and those of fasting glucose, insulin, and glycosylated hemoglobin. Iron reduction therapy in hereditary hemochromatosis and transfusional iron overload is associated with improved glucose tolerance and reduced incidence of secondary diabetes. Trials of iron reduction therapy in diabetes mellitus, although limited and inconclusive, have shown clinical improvement in some patients. The current article reviews evidence suggesting that tissue iron contributes to DM and its complications and presents preliminary data that emphasize the potential importance of iron overload in DM of African Americans.

Black or African American↗
PubMed2003

Lipid abnormalities and renal disease: is dyslipidemia a predictor of progression of renal disease?

Dyslipidemia is a cardiovascular disease (CVD) risk factor that is associated with enhanced atherosclerosis and plaque instability. Renal insufficiency is associated with abnormalities in lipoprotein metabolism in both the early and the advanced stages of chronic renal failure. These include alterations in apolipoprotein A (apo A)- and B- containing lipoproteins, high-density lipoproteins, and triglycerides. In animal models, these alterations in lipid metabolism and action lead to macrophage activation and infiltration in the kidney with resultant tubulointerstitial and endothelial cell injury. Limited data in humans suggest that, in addition to contributing to CVD, dyslipidemia may be a risk factor for the progression of renal disease. The effects of dyslipidemia on the kidney are mainly observed in those with other risk factors for renal disease progression such as hypertension, diabetes, and proteinuria. Renal disease is a strong risk factor for CVD and African Americans have high rates of renal disease. Therefore, examining the effects of dyslipidemia on the development or progression or renal disease will be an important question for the Jackson Heart Study and is the topic of this review.

Black or African American↗
PubMed2003

Angiotensin-converting enzyme genotype in blacks with diabetic nephropathy: effects on risk of diabetes and its complications.

OBJECTIVE: Among blacks, we have observed that diabetic nephropathy (DN) is a more frequent primary cause of end-stage renal disease (ESRD) in women (approximately 50%) than in men (< 20%). In this study, we consider the role of the angiotensin-converting enzyme (ACE) polymorphism in determining this gender discrepancy and its role in the course of DN. METHODS: ACE genotype (I = insertion, D = deletion) was determined in consecutive consenting patients with type 2 diabetes mellitus and DN. Charts were subsequently reviewed for renal survival and its determinants (end point: time to ESRD from first clinic visit). RESULTS: Fifty-four patients (46 blacks) who had DN and were pre-ESRD consented: II = 6, ID = 31, and DD = 17. The allele frequency for D was approximately . 61 versus .39 for the I allele and did not differ by gender. Renal disease at presentation to the renal clinic was significantly worse in II. Twenty-one patients reached ESRD (II = 4, ID = 13, DD = 4; chi2 not significant), but ACE genotype had no significant effect on renal survival. Initial serum creatinine and blood pressure over follow-up independently predicted renal survival. Among blacks reaching ESRD, the presence of the D allele was associated with higher blood pressures. Patients without a family history of diabetes (chi2, p = .01) or diabetic retinopathy (chi2, p = .02) were more likely to have the DD genotype. CONCLUSIONS: The gender discrepancy observed in rates of ESRD owing to DN in blacks is not likely dependent on ACE genotype. The effects of ACE genotype on renal disease progression were not significant; however, patients with diabetic nephropathy and DD genotype were less likely to have traditional risk factors for diabetes or diabetic nephropathy.

Adult↗
PubMed2003

Overexpression of the complementary DNA for human glutamine:fructose-6-phosphate amidotransferase in mesangial cells enhances glucose-induced fibronectin synthesis and transcription factor cyclic adenosine monophosphate-responsive element binding phosphorylation.

Hyperglycemia-induced alterations in mesangial cell function and extracellular matrix protein (ECM) accumulation are seen in diabetic glomerulopathy. The hexosamine biosynthesis pathway (HBP) is implicated in mediating several metabolic effects of high glucose (HG) in cells. This pathway converts fructose-6-phosphate to glucosamine (GlcN)-6-phosphate by the rate-limiting enzyme glutamine:fructose-6-phosphate amidotransferase (GFA). We have previously shown that metabolism of glucose through the HBP regulates the effects of glucose on ECM (fibronectin) synthesis and transcription factor (cyclic adenosine monophosphate-responsive element binding [CREB]) phosphorylation in SV-40-transformed rat kidney mesangial cells. UDP-N-acetyl-GlcN is the end product of the HBP and serves as a precursor for O-linked serine/threonine glycosylation of cytoplasmic and nuclear proteins. Here we show that culturing mesangial cells in HG and GlcN increases the level of O-N-acetylglucosamine in several cytoplasmic and nuclear proteins. Inhibition of O-glycosylation by benzyl-2-acetamido-2-deoxy-alpha-D-galactopyranoside blocks both HG and GlcN-induced fibronectin synthesis and CREB phosphorylation. To further support the hypothesis that the HBP mediates HG-induced ECM synthesis, a complementary deoxyribonucleic acid (DNA) for human GFA was stably expressed in mesangial cells. Mesangial and GFA-overexpressing cells were cultured in 5 to 25 mM glucose for 48 hours. GFA-overexpressing cells were more sensitive to glucose as they demonstrated increases in fibronectin and CREB phosphorylation at lower glucose concentrations than seen In control cells. In addition, the response to 25 mM glucose for both proteins was increased in GFA when compared with controls. There is no difference in DNA synthesis and cellular adenosine triphosphate levels between the two cell lines. These results suggest that the HBP is a glucose sensor and mediator of the effects of hyperglycemia in the diabetic mesangium.

Animals↗
PubMed2003

Advanced diabetic nephropathy disproportionately affects African-American females: cross-sectional analysis and determinants of renal survival in an academic renal clinic.

OBJECTIVE: The aims of this study were to study further the previously observed 2-fold higher prevalence of endstage renal disease (ESRD) due to diabetic nephropathy (DN) in African-American (AA) women, when compared to AA men, and to identify factors predictive of renal survival in this population. DESIGN: Cross-sectional analysis of DN in an academic renal clinic. METHODS: We identified and retrospectively studied all patients with diabetic nephropathy enrolled in our renal clinic in 1996. Charts were reviewed for basic demographic factors, medications, and renal function. RESULTS: Of approximately 600 total patients, 141 were diagnosed with DN, and sufficient data was available on 119 (98 AA) of these, with a mean followup of 105 weeks. Patients were hypertensive, had advanced renal disease at presentation (creatinine [Cr]=3.97 mg/dL), and had been diabetic for 16.7 years. The AAs were disproportionately represented by females (69 vs 29). Seventy patients reached ESRD at the time of analysis (April 2000) with a mean time to dialysis of 79.3 weeks. Significant determinants for longer time to ESRD (TTE) were: lower presenting Cr, female gender, and AA race. A MAP<100 mm Hg over the course of followup was adversely related to TTE. Among AAs, taking an angiotensin converting enzyme (ACE) inhibitor, or a calcium channel blocker, was associated with better renal survival. Changes in renal function at 1 and 2 years were associated with age, urine protein at presentation, and MAP over the course of followup. CONCLUSIONS: In Mississippi, DN is more much more prevalent in AA females, compared to AA males. In those with advanced DN, MAP<100 mm Hg may lessen the chances for renal survival.

Academic Medical Centers↗
PubMed2002

Caring for adolescent family members of physician colleagues.

It is recommended that physicians do not care for their family members. However, there are also many concerning issues when physicians care for the family members of their colleagues. This can be particularly challenging when the patient is an adolescent. We present the case of Dr. B who is asked to see the teenage daughter of her colleague Dr. A, and discuss the issues of caring for an adolescent family member of a physician colleague. Patient confidentiality, autonomy, and maintenance of the patient-physician relationship are core principles that must be adhered to in this situation. The roles of the treating physician and the parental physician are discussed.

Adolescent↗
PubMed2002

Diabetic renal disease in African Americans.

Diabetic nephropathy (DN) is the No. 1 cause of end-stage renal disease in the United States and is highly prevalent in African Americans. Almost all DN in African Americans is caused by type 2 diabetes. Glycemic control and control of blood pressure are essential to prolong renal survival and to protect against cardiovascular events. Among African Americans, diabetic nephropathy seems to affect women more than men, which may be related to increased rates of obesity and diabetes in African American women. In addition to gender, the development of albuminuria, family history, and possibly birth weight are factors that predict progression of renal disease in African Americans with DN. The impact of glycemic control, appropriate antihypertensives, and the optimal level of blood pressure control in African Americans with advanced DN require further study. This article will review the clinical characteristics, risk factors, predictors of disease progression, and treatment of diabetic nephropathy in African Americans.

Black or African American↗
PubMed2002

Obesity, physical inactivity, and risk for cardiovascular disease.

Despite considerable progress in understanding disease mechanisms and risk factors, improved treatments, and public education efforts, cardiovascular disease (CVD) remains the leading cause of death in the United States. Obesity and physical inactivity, 2 important lifestyle-related risk factors for CVD, are prevalent in the southeastern United States and are becoming more prevalent in all racial groups and areas of the country. In reviewing these risk factors, we explored topics including prevalence and trends in population data; associated psychosocial and environmental factors; and some of the mechanisms through which these risk factors are thought to contribute to CVD. We identified significant, but as yet poorly understood, racial disparities in prevalence of obesity, low levels of physical activity, and correlates of these risk factors and examined important differences in the complex relationship between obesity, diabetes, and cardiovascular disease risk between African American and European American women. The Jackson Heart Study will provide important and unique information relevant to many unanswered questions about obesity, physical inactivity, and obesity in African Americans.

Behavior↗
PubMed2002

Mechanisms of obesity-associated cardiovascular and renal disease.

Obesity is the most common nutritional disorder in the United States. Growing evidence suggests that obesity initiates a cascade of disorders including hypertension, diabetes, atherosclerosis, and chronic renal disease, many of which are interdependent. Abnormal kidney function, caused by increased renal tubular reabsorption, initiates volume expansion and increased blood pressure during excess weight gain, and the hypertension and metabolic abnormalities associated with obesity, in turn, contribute to chronic renal disease. Obesity causes cardiac and vascular disease through well-known mediators such as hypertension, type II diabetes, and dyslipidemia, but there is evidence for less well-characterized mediators such as chronic inflammation and hypercoagulation. Although obesity is increasingly recognized as a serious health problem, there are still many unanswered questions about how the multiple disorders associated with excess weight gain interact to cause cardiovascular and renal disease. Also, there are few studies that have examined whether sustained weight loss in obese subjects can reverse these changes. In view of the "epidemic" of obesity in our country and the excess burden of cardiovascular and renal disease in minority populations, addressing these issues is of paramount importance for the Jackson Heart Study, as well as for other national health initiatives.

Animals↗
PubMed2002

Primary renal disease as a cardiovascular risk factor.

Cardiovascular disease (CVD) is the No. 1 cause of death in patients with end-stage renal disease (ESRD) and is approximately 3 to 5 times that of non-uremic control subjects. Moreover, higher rates of CVD are seen in patients with moderate and even mild renal dysfunction, particularly if the patient has hypertension or diabetes. Recent studies have indicated that even modest elevations in serum creatinine and urinary albumin excretion are associated with increased CVD risk, not only in persons with diabetes or hypertension but also in the general population. In addition, recent studies have suggested that targeting the kidney and/or kidney specific endpoints (via the renin-angiotensin-aldosterone-kinin system) in the treatment of hypertension, diabetes, and heart failure slows progression of renal disease and reduces the risk of extra-renal micro- and macrovascular complications. We conclude that it is important to screen for renal disease in those with hypertension, diabetes, and other CVD risk factors because it predicts those who are at high risk for major CVD events.

Adult↗
PubMed2002

Ethical issues in transplantation: living related donation in the setting of severe neurological damage without brain death.

The waiting list for renal transplantation has grown at an alarming rate over the last 2 decades, resulting in increased waiting times and deaths on the waiting list. To increase the number of available organs for transplantation, aggressive public education programs have been developed. The federal government has strengthened hospital regulations ensuring referral of all potential donors to organ recovery agencies, and living donor programs no longer limit donation to genetically related donors and recipients. We present a case that illustrates the complex ethical issues that are integral to the field of transplantation and the allocation of a scarce resource: a 50-year-old man who has a daughter with end-stage renal disease has suffered a severe cerebral vascular accident but is neither brain-dead nor a candidate for "non-heart-beating" donation. Given his poor prognosis, should the father be able to donate his kidney to the daughter in his compromised condition?

Adult↗
PubMed2002

The genetics of human hypertension.

Human hypertension is a common and complex disease and is associated with diabetes, cardiovascular, and renal disease. Therefore, it is important to understand the genetic basis of this disease. Specific genetic mutations leading to monogenic forms of hypertension have been identified in Liddle's syndrome and glucocorticoid-remediable hypertension and in some syndromes in which blood pressure is lowered. Because essential hypertension is a polygenic disease, elucidating a genotype that is causally related to essential hypertension will be difficult. To date, no genotype has been conclusively linked to essential hypertension except in certain populations. However, there has been progress in finding genetic variations that are associated with hypertension in patients with components of the metabolic syndrome (or Syndrome X). Future discoveries in this area should enhance our ability to intervene earlier and more effectively and therefore lessen the complications of this common disease.

Diabetes Complications↗
PubMed2002

Kidney disease in African Americans: genetic considerations.

African Americans shoulder a disproportionately high burden of kidney disease when compared with white Americans. While environmental factors such as poverty and poor health habits, and the high prevalence of risk factors such as obesity, contribute to the high rate of kidney disease in this population, genetic factors may also contribute. Studies of polymorphisms in genes encoding the proteins of the renin-angiotensin-aldosterone system have identified alleles that are associated with kidney disease or changes in renal function in some populations. A higher prevalence of such alleles in African Americans may contribute to the increased prevalence of kidney disease. Diabetes mellitus and hypertension, the main causes of end-stage renal disease in the United States, are more prevalent in African Americans. However, no direct links between diabetic or hypertensive kidney disease and any genetic polymorphisms seen in African Americans have been identified. Further research is thus required to elucidate the genetic components that contribute to the high prevalence of kidney disease in African Americans.

Black or African American↗
PubMed2002

Screening and prevention of chronic kidney disease.

The burden of kidney disease is disproportionately high in African Americans, and the condition often remains undiagnosed until late-stage disease. In order to reduce this burden, strategies must be implemented to improve the detection of kidney disease, and preventative measures must be targeted at those at greatest risk of disease. Important risk factors among African Americans in the US include hypertension, diabetes, and obesity. In this review, we discuss screening strategies that will allow earlier detection of kidney disease. The sensitivity of serum creatinine, proteinuria, and microalbuminuria as markers of disease are discussed, as is the importance of calculating glomerular filtration rates in individual patients. Implementation of community-based programs, such as the Kidney Early Evaluation Program developed by the National Kidney Foundation, can offer screening for kidney disease and its risk factors, and can educate and protect African Americans at risk of this prevalent disease.

Chronic Disease↗
PubMed2002

Addressing cardiovascular disease in patients with renal disease.

It is well-established that patients with renal disease are at increased risk of cardiovascular disease (CVD) death. Despite better understanding of CVD in endstage renal disease (ESRD) patients and more rigid guidelines addressing the major risk factors for CVD in this population, CVD continues to be the number one cause of death in patients with ESRD. Moreover, higher rates of CVD are seen in patients with moderate, and even mild, renal dysfunction and in patients with albuminuria (micro and macroscopic). Few studies with CVD endpoints have included patients with renal disease. There is sufficient evidence to support appropriate blood pressure reduction as having a beneficial effect on CVD morbidity and mortality in patients with renal disease (especially for patients with diabetes). Data supporting the benefit of modification of other CVD risk factors is not as strong, but current recommendations do stress aggressive control of lipids, smoking cessation, and maintenance of adequate nutritional status. Inclusion of patients with renal disease in studies with CVD endpoints is necessary. Until then, it is generally recommended that CVD risk stratification and modification strategies be applied to this high-risk population.

Albuminuria↗
PubMed2002

Therapeutic controversies in hypertension management: angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers for diabetic nephropathy? A case for ACE inhibitors.

Diabetic nephropathy is the number one cause of endstage renal disease in the United States. Blockade of the renin angiotensin system (RAS) is important in the treatment of diabetic nephropathy. With the reports of recently completed trials examining the role of angiotensin receptor blockers (ARBs) in type 2 diabetic nephropathy, the question has arisen as to which agents are best to block the RAS in type 2 diabetes. ACE inhibitors have been to preserve renal function in type 1 diabetics with nephropathy in large, randomized, placebo controlled trials, but such data is lacking in type 2 diabetes. Neverthelesss, ACE inhibitors have been recommended for use in type 2 diabetic nephropathy for some time. In type 2 diabetics, ACE inhibitors may have a role in preventing development of nephropathy, and, importantly, ACE inhibitors have been shown to reduce cardiovascular disease in diabetics with and without nephropathy. In addition, ACE inhibitors have beneficial effects on other diabetic complications such as retinopathy and neuropathy. Until better comparative data between ACE inhibitors and ARBs on nephropathy and cardiovascular outcomes is available, ACE inhibitors should remain an important consideration for treatment of diabetic nephropathy.

Angiotensin Receptor Antagonists↗