Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

African-American (AA) women with breast cancer have higher mortality rates than Caucasian woman, and some studies have suggested that this disparity may be partly explained by unequal access to medical care. The purpose of this study was to analyze racial differences in patterns and costs of care and survival among women treated for invasive breast cancer at a large academic medical center. Subjects included 331 AA and 257 Caucasian women diagnosed with stage I-III breast cancer between 1994 and 1997. Clinical, socio-demographic, and cost data were obtained from the medical record, cancer registry, and hospital financial database. Data were collected on the use of cancer directed treatments (surgery, radiation, chemo and hormonal therapy) up to 1-year post-diagnosis. Survival analyses compared disease-free and overall survival by race adjusting for age, stage, nodal involvement, ER/PR status and a diagnosis of hypertension, diabetes, heart disease and cerebral vascular accident. There were no significant racial differences in treatment utilization and costs. The mean total 1-year treatment costs were US 16,348 dollars for AAs and US 15,120 dollars for Caucasians. While AAs had a significantly higher unadjusted relative risk (RR) of recurrence 2.09 (95% CI: 1.41-3.10) and death 1.56 (95% CI: 1.09-2.25), the multivariate adjusted analyses resulted in no significant differences in recurrence 1.38 (95% CI: 0.85-2.26) or death 1.06 (95% CI: 0.64-1.75). There was no obvious racial disparity in treatment and costs noted. Our findings support the theory that equal treatments produce equal outcomes. Improvement in screening may have an important impact on survival among minority women with breast cancer.
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PMID:Racial disparities in treatment and survival of women with stage I-III breast cancer at a large academic medical center in metropolitan Detroit. 1595 57

The establishment of human embryonic stem (ES) cells has opened possibilities for cell replacement therapy to treat diseases such as diabetes, Parkinson's disease and cardiac myopathies. Self-renewal is one of the essential defining characteristics of stem cells. If stem cells are to have widespread therapeutic applications, it is essential to identify the extrinsic and intrinsic factors maintaining self-renewal, particularly in culture. Insight into the regulation of known self-renewal transcription factors and cross-talk between their upstream signalling pathways is important for a better understanding of how stem cell self-renewal and differentiation are related to downstream target genes. This may lead to the establishment of protocols for obtaining a large supply of ES cells. Here, we review the role that TGFbeta superfamily members are thought to play in self-renewal and differentiation of human and mouse ES cells. We focus on the prototype TGFbeta, TGFbeta1, activin A, nodal and bone morphogenetic proteins and their expression, activity and function in embryonic stem cells.
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PMID:Functions of the TGFbeta superfamily in human embryonic stem cells. 1648 Apr 49

Despite documented superiority of positron emission tomography over other investigative modalities in the preoperative staging of non-small cell lung cancer, a proportion of patients will have an inaccurate staging of their mediastinal nodes. The aim of this retrospective review is to analyse the clinicopathological factors responsible for inaccurate nodal staging by integrated PET-CT. A total of 100 consecutive patients with histologically proven non-small cell lung cancer underwent staging with PET-CT prior to lung resection. Thirty-three patients, inaccurately staged by PET-CT, were analysed. Univariate analysis identified the following as significant in causing inaccurate nodal staging: history of tuberculosis (P=0.039) and non-insulin dependant diabetes (P=0.014). In multivariate analysis, we have identified the following as independent factors in causing inaccurate staging of mediastinal lymph nodes: rheumatoid arthritis, non-insulin dependent diabetes, history of tuberculosis, presence of atypical adenomatous hyperplasia and pneumonia (P<0.05). The highest rate of inaccuracy in mediastinal nodal staging was in nodal station 4 (11%, P=0.01) followed by station 7 (10%, P=0.02) and station 9 (3.5%, P=0.01). Interpretation of PET-CT staging of the mediastinum in patients with a history of the above should be with caution, as the incidence of false upstaging and down staging in these subgroups is high. Vigilance of such factors may improve the accuracy of PET-CT in staging mediastinal lymph nodes. Histological confirmation should always be sought.
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PMID:Factors causing inaccurate staging of mediastinal nodal involvement in non-small cell lung cancer patients staged by positron emission tomography. 1766 63

Diabetic polyneuropathy (DPN) is the most common late complication of diabetes mellitus. The underlying pathogenesis is multifaceted, with partly interrelated mechanisms that display a dynamic course. The mechanisms underlying DPN in type 1 and type 2 diabetes mellitus show overlaps or may differ. The differences are mainly due to insulin deficiency in type 1 diabetes which exacerbates the abnormalities caused by hyperglycaemia. Experimental DPN in rat models have identified early metabolic abnormalities with consequences for nerve conduction velocities and endoneurial blood flow. When corrected, the early functional deficits are usually normalised. On the other hand, if not corrected, they lead to abnormalities in lipid peroxidation and expression of neurotrophic factors which in turn result in axonal, nodal and paranodal degenerative changes with worsening of nerve function. As the structural changes progress, they become increasingly less amendable to metabolic interventions. In the past several years, experimental drugs--such as aldose reductase inhibitors, antioxidants and protein kinase C inhibitors--have undergone clinical trials, with disappointing outcomes. These drugs, targeting a single underlying pathogenetic factor, have in most cases been initiated at the advanced stage of DPN. In contrast, substitution of acetyl-L-carnitine (ALC) or C-peptide in type 1 DPN target a multitude of underlying mechanisms and are therefore more likely to be effective on a broader spectrum of the underlying pathogenesis. Clinical trials utilising ALC have shown beneficial effects on nerve conduction slowing, neuropathic pain, axonal degenerative changes and nerve fibre regeneration, despite relatively late initiation in the natural history of DPN. Owing to the good safety profile of ALC, early initiation of ALC therapy would be justified, with potentially greater benefits.
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PMID:Acetyl-L-carnitine in diabetic polyneuropathy: experimental and clinical data. 1769 89

The present study was undertaken to evaluate the role of Na(+)/K(+) pump dysfunction in the development of diabetic neuropathy (DN). Nerve excitability techniques, which provide information about membrane potential and axonal ion channel function, were undertaken in 15 patients with established DN and in 10 patients with diabetes who had no evidence of neuropathy (DWN). Excitability parameters were recorded at baseline, and then before and after 1 min of maximal voluntary contraction (MVC) of abductor pollicis brevis. Compared to controls, CMAP amplitude was significantly decreased in DN patients with associated reductions in strength-duration time constant and refractoriness, consistent with a reduction in nodal Na(+) conductances. Following MVC for 1 min, there was an increase in normalized threshold in all diabetic patients and controls, consistent with axonal hyperpolarization. When compared to control values, the increase in threshold following MVC was significantly less in DN patients (DN group 13.1 +/- 2.2%; controls 20.4 +/- 1.9%; P < 0.05) and the rate of recovery was slower (P < 0.01). In DWN patients, CMAP amplitude was preserved, and excitability values following MVC were not significantly different to control values. The reduced threshold change and slower recovery in DN patients following MVC are likely to be secondary to Na(+)/K(+) pump dysfunction. Alteration in Na(+)/K(+) pump function, coupled with reductions in nodal Na(+) currents, may be sufficient to trigger conduction failure in DN patients and are likely to contribute to the clinical symptoms of weakness and fatigue.
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PMID:Activity-dependent excitability changes suggest Na+/K+ pump dysfunction in diabetic neuropathy. 1836 98

Diabetic polyneuropathy (DPN) occurs more frequently in type 1 diabetes resulting in a more severe DPN. The differences in DPN between the two types of diabetes are due to differences in the availability of insulin and C-peptide. Insulin and C-peptide provide gene regulatory effects on neurotrophic factors with effects on axonal cytoskeletal proteins and nerve fiber integrity. A significant abnormality in type 1 DPN is nodal degeneration. In the type 1 BB/Wor-rat, C-peptide replacement corrects metabolic abnormalities ameliorating the acute nerve conduction defect. It corrects abnormalities of neurotrophic factors and the expression of neuroskeletal proteins with improvements of axonal size and function. C-peptide corrects the expression of nodal adhesive molecules with prevention and repair of the functionally significant nodal degeneration. Cognitive dysfunction is a recognized complication of type 1 diabetes, and is associated with impaired neurotrophic support and apoptotic neuronal loss. C-peptide prevents hippocampal apoptosis and cognitive deficits. It is therefore clear that substitution of C-peptide in type 1 diabetes has a multitude of effects on DPN and cognitive dysfunction. Here the effects of C-peptide replenishment will be extensively described as they pertain to DPN and diabetic encephalopathy, underpinning its beneficial effects on neurological complications in type 1 diabetes.
Exp Diabetes Res 2008
PMID:The effects of C-peptide on type 1 diabetic polyneuropathies and encephalopathy in the BB/Wor-rat. 1843 23

The aim of this paper is to report an atypical presentation of MEN2A, in a patient carrying the C634R mutation of the RET-protooncogene. A 41-year-old Tunisian woman was admitted to our department with newly diagnosed hyperglycemia. She had a history of bilateral urinary stone recurrence, managed successfully on two occasions. On physical examination a thyroid node of 1cm on the left side was found. Laboratory evaluation and imaging findings confirmed the diagnosis of primary hyperparathyroidism. During cervicotomy, the parathyroid adenoma was resected and the thyroid node was suspected to be a carcinoma. Total thyroidectomy, with appropriate neck nodal resection, was performed. Histological examination confirmed the diagnosis of parathyroid adenoma and revealed a multifocal and bilateral medullary carcinoma. These findings led to the diagnosis of multiple endocrine neoplasia. DNA-analysis demonstrated a germline Cys634Arg mutation in the RET-protooncogene. During the postoperative follow-up, blood pressure as well as the level of urinary methoxylated metabolites increased progressively. Imaging findings were compatible with the diagnosis of bilateral pheochromocytoma. In conclusion, this case report of MEN 2A linked to a 634 RET mutation was peculiar by its revelation mode (1) hyperparathyroidism moreover linked to an adenoma and (2) associated with diabetes, mechanisms of which are probably multifactorial (familial type 2 diabetes, hypercalcemia, catecholamines excess).
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PMID:Unusual presentation of multiple endocrine neoplasia type 2A in a patient with the C634R mutation of the RET-protooncogene. 1875 92

One of the most significant interactions between Schwann cells and neurons is myelin sheath formation. Myelination is a vertebrate adaptation that enables rapid conduction of action potentials without a commensurate increase in axon diameter. In vitro neuronal systems provide a unique modality to study both factors influencing myelination and diseases associated with myelination. Currently, no in vitro system for motoneuron myelination by Schwann cells has been demonstrated. This work details the myelination of motoneuron axons by Schwann cells, with complete Node of Ranvier formation, in a defined in vitro culture system. This defined system utilizes a novel serum-free medium in combination with the non-biological substrate, N-1[3 (trimethoxysilyl) propyl] diethylenetriamine (DETA). The myelinated segments and nodal proteins were visualized and quantified using confocal microscopy. This defined system provides a highly controlled, reproducible model for studying Schwann cell interactions with motoneurons as well as the myelination process and its effect on neuronal plasticity. Furthermore, an in vitro system that would allow studies of motoneuron myelination would be beneficial for understanding peripheral demyelinating neuropathies such as diabetes induced peripheral neuropathy and could lead to a better understanding of CNS demyelinating diseases like multiple sclerosis, as well as neuromuscular junction maturation and maintenance.
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PMID:Node of Ranvier formation on motoneurons in vitro. 1936 59

The management of pancreatic cancer is complex and prognosis is poor. The etiopathogenesis of pancreatic cancer has been related to several factors, such as diabetes mellitus, smoking and alcohol use, the presence of pancreatic cystic lesions and distinct genetic syndromes. Among the diagnostic options, endoscopic ultrasound (EUS) continues to be developed, with the use of elastography, contrast agents and EUS-guided aspiration and the application of technical improvements that increase diagnostic efficacy (such as the use of specific stains, new aspiration needles, etc.). New biomarkers are also being sought that would help in differential diagnosis, such as M2PK, adiponectin, and Reg4. Among prognostic factors, the importance of nodal involvement and study of surgical resection margins has been confirmed. The role of individual predisposition in determining response to specific treatments continues to be investigated. Research also continues into the development of EUS-guided injection of therapeutic substances and the role of oncological treatment, with new data on the utility of gemcitabine and of statins as mediators of angiogenic suppression or of high-dose vitamin C with cytotoxic effects. Notable in the field of palliative treatment is the development of new biliary stents that aim to reduce obstruction rates. The development of EUS and EUS-guided fine-needle aspiration has been crucial in cystic pancreatic tumors, especially in distinguishing benign from malignant lesions or those with potential for malignant transformation (presence of mural modules, dilatation of the main pancreatic duct, the presence of masses, CEA levels, etc.). The characteristics of these tumors must be determined to evaluate whether surgery or conservative management is the best therapeutic option.
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PMID:[Pancreatic tumors]. 1943 73

The present study was conducted to evaluate whether experimentally induced type 1 diabetes results in alterations to atrioventricular nodal (AVN) electrophysiology at the cellular level. Spontaneous action potentials (APs) and ionic currents were recorded from AVN myocytes isolated from the hearts of control rats and from those with streptozotocin-induced diabetes. Perforated patch-clamp recordings were used to assess changes in cellular AP parameters and in ionic currents. Type 1 diabetes significantly increased AP duration, whilst reducing AP firing rate, upstroke velocity and rate of diastolic depolarization. The diabetes-induced changes in AP parameters were accompanied by a significant leftward shift in the zero current potential under voltage clamp, a reduction in peak L-type Ca(2+) current density and reduced amplitude of delayed rectifier and hyperpolarization-activated currents. These findings demonstrate that experimentally induced type 1 diabetes can lead to remodelling of AVN cellular electrophysiology.
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PMID:Streptozotocin-induced diabetes modulates action potentials and ion channel currents from the rat atrioventricular node. 1994 31


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