Waist circumference measurement in clinical practice

The obesity epidemic is a major public health problem worldwide. Adult obesity is associated with increased morbidity and mortality. Measurement of abdominal obesity is strongly associated with increased cardiometabolic risk, cardiovascular events, and mortality. Although waist circumference is a crude measurement, it correlates with obesity and visceral fat amount, and is a surrogate marker for insulin resistance. A normal waist circumference differs for specific ethnic groups due to different cardiometabolic risk. For example, Asians have increased cardiometabolic risk at lower body mass indexes and with lower waist circumferences than other populations. One criterion for the diagnosis of the metabolic syndrome, according to different study groups, includes measurement of abdominal obesity (waist circumference or waist-to-hip ratio) because visceral adipose tissue is a key component of the syndrome. The waist circumference measurement is a simple tool that should be widely implemented in clinical practice to improve cardiometabolic risk stratification.     

Melatonin attenuates tyrosine hydroxylase loss and hypolocomotion in MPTP-lesioned rats

Parkinson's disease is a chronic neurological disease characterized by dopaminergic neuron degeneration in the substantia nigra pars compacta. Melatonin is a powerful antioxidant agent secreted by the pineal gland which has numerous physiological functions and seems to exert an important neuroprotective effect. The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model has been used to understand the pathophysiology of the disease because of its capacity to mimic biochemical and histological features observed in Parkinson's disease. This study investigated the effect of pretreatment with melatonin (50 mg/kg) on MPTP-lesioned animals 24 h and 7 days after neurotoxin infusion using the open-field test, two-way avoidance task and immunohistochemistry. Twenty-four hours after lesioning, the MPTP+vehicle group exhibited hypolocomotion and significant loss of tyrosine hydroxylase-immunoreactive cells, whereas no differences in these parameters were observed in lesioned animals receiving melatonin. Seven days after surgery, the MPTP-lesioned rats did not show hypolocomotion compared to control animals, while there was a significant dopaminergic neuronal loss. In the two-way avoidance task, MPTP-treated animals presented a cognitive deficit compared to the control groups and melatonin administration did not repair this defect. The present results suggest that melatonin reduces neuronal loss in the MPTP animal model of Parkinson's disease.     

A pilot study of compositional analysis of the breast and estimation of breast mammographic density using three-dimensional T1-weighted magnetic resonance imaging

PURPOSE: A method and computer tool to estimate percentage magnetic resonance (MR) imaging (MRI) breast density using three-dimensional T(1)-weighted MRI is introduced, and compared with mammographic percentage density [X-ray mammography (XRM)]. MATERIALS AND METHODS: Ethical approval and informed consent were obtained. A method to assess MRI breast density as percentage volume occupied by water-containing tissue on three-dimensional T(1)-weighted MR images is described and applied in a pilot study to 138 subjects who were imaged by both MRI and XRM during the Magnetic Resonance Imaging in Breast Screening study. For comparison, percentage mammographic density was measured from matching XRMs as a ratio of dense to total projection areas scored visually using a 21-point score and measured by applying a two-dimensional interactive program (CUMULUS). The MRI and XRM percent methods were compared, including assessment of left-right and interreader consistency. RESULTS: Percent MRI density correlated strongly (r = 0.78; P < 0.0001) with percent mammographic density estimated using Cumulus. Comparison with visual assessment also showed a strong correlation. The mammographic methods overestimate density compared with MRI volumetric assessment by a factor approaching 2. DISCUSSION: MRI provides direct three-dimensional measurement of the proportion of water-based tissue in the breast. It correlates well with visual and computerized percent mammographic density measurements. This method may have direct application in women having breast cancer screening by breast MRI and may aid in determination of risk.     

Genetic polymorphisms involved in insulin-like growth factor (IGF) pathway in relation to mammographic breast density and IGF levels.

The insulin-like growth factor (IGF) pathway is believed to play a role in carcinogenesis of the mammary gland. Single nucleotide polymorphisms (SNPs) of IGF-I, IGF-binding protein-3 (IGFBP-3), IGF receptor 1, insulin receptor substrate 1, and phosphoinositide-3-kinase, catalytic, beta polypeptide genes, which are members of the IGF pathway, have been associated with risk of common cancers, breast density, and/or IGF levels but results remain inconclusive. Thus, we evaluated the association of 11 targeted IGF pathway SNPs with circulating IGF levels and mammographic breast density. Among 741 white premenopausal women, blood samples were collected at time of screening mammography, and plasma IGF-I and IGFBP-3 levels were measured by ELISA. Percent and absolute breast density were estimated using a computer-assisted method. Multivariate linear models were used to examine the associations. Women carrying increasing number of copies of the rare allele of IGF-I rs1520220 and rs6220 SNPs had increased percent breast density (P(trend) = 0.04 and 0.06, respectively). Carriers of increasing number of copies of the rare allele of phosphoinositide-3-kinase, catalytic, beta polypeptide rs361072 SNP had decreased percent (P(trend) = 0.04) and absolute (P(trend) = 0.02) breast density. An association of insulin receptor substrate 1 rs1801278 SNP with absolute density (P(trend) = 0.03) was also observed. All four IGFBP-3 SNPs (including rs2854744) were associated with IGF-I and IGFBP-3 levels. This study shows that several components of the IGF pathway are associated with breast density or IGF levels. Our findings provide additional support for the idea that several components of the IGF pathway may affect breast cancer risk and that this effect on breast cancer development may be mediated, at least in part, through its influence on the morphogenesis of breast tissue.     

Establishing a patient navigator program to reduce cancer disparities in the American Indian communities of Western South Dakota: initial observations and results

BACKGROUND: American Indians (AIs) in the Northern Plains region suffer disproportionately high cancer mortality rates compared with the general US population and with AIs from other regions in the United States. METHODS: The National Cancer Institute developed the Cancer Disparity Research Partnership to address these inequities. This initiative in Rapid City, South Dakota, attempts to lower cancer mortality rates for AIs by access to innovative clinical trials, behavioral research, and a genetic study. Patient navigation is a critical part of the program. Two navigation strategies are described: navigators at the cancer center and navigators on each reservation. A retrospective analysis was performed to determine if navigated patients (n = 42) undergoing potentially curative radiotherapy had fewer treatment interruptions compared with nonnavigated patients (n = 74). RESULTS: A total of 213 AIs with cancer have undergone patient navigation. For those undergoing cancer treatment, the median number of patient navigation interactions was 15 (range 1 to 95), whereas for those seen in follow-up after their cancer treatment, the median number of contacts was 4 (range 1 to 26). AIs who received navigation services during curative radiation treatment had on average 3 fewer days of treatment interruptions compared to AIs who did not receive navigation services during curative radiation treatment (P = .002, N = 116). CONCLUSIONS: Early findings suggest that patient navigation is a critical component in addressing cancer disparities in this population. The program has established trust with individual cancer patients, with the tribal councils, and with the general population on each of the three reservations of western South Dakota.     

Management of Narcolepsy

Narcolepsy is a chronic sleep disorder characterised by excessive daytime sleepiness, with or without cataplexy, sleep paralysis and hypnagogic hallucinations, with an estimated prevalence of 0.02 to 0.05% worldwide.The goal of managing narcolepsy is to keep patients as alert as possible during daytime hours and to minimise the incidence of cataplexy. A combination of nonpharmacological (lifestyle and behavioural modifications) and pharmacological treatments may be used to alleviate excessive daytime sleepiness. Stimulants such as amphetamines and methylphenidate have been the mainstay of pharmacological treatment, although a range of different agents have been used over several decades.Modafinil, a benzohydrylsulfinyl-acetamide derivative, has demonstrated good efficacy in the treatment of excessive daytime sleepiness, but has limited anticataplectic effects. In clinical studies modafinil 200 to 400 mg/day significantly improved subjective and objective measures of sleepiness and alertness compared with placebo. A long term study of up to 10 years’ duration showed modafinil to have good to excellent efficacy in 64% of patients. Use of modafinil does not appear to be associated with the development of tolerance or dependence, and it is considered to have limited potential for abuse. Modafinil is generally well tolerated with few adverse effects, the most common being headache, nausea, nervousness and anxiety. It may be coadministered with drugs for treating cataplexy. The efficacy and the cost effectiveness of modafinil in the treatment of narcolepsy have not been compared with other available agents. Conclusions: Modafinil provides a useful alternative to traditional stimulants for the treatment of excessive daytime sleepiness associated with narcolepsy. It is well tolerated, may be taken in combination with medications for cataplexy, and shows long term efficacy without development of tolerance.     

Expression of cd44 splice variants in human cutaneous melanoma and melanoma cell lines is related to tumor progression and metastatic potential

Expression of CD44, particularly of certain splice variants, has been linked to tumor progression and metastasis formation in a number of different animal and human cancers. Because human cutaneous melanoma is among the most aggressive human cancers, we explored expression of CD44 isoforms (CD44v) in lesions of melanocytic tumor progression. In addition, by RT-PCR and FACS analysis we assessed CD44v RNA species and cell surface expression of CD44v in cultured melanocytes isolated from human foreskin and in a panel of 2 non-, 2 sporadically and 2 highly metastatic human melanoma cell lines. We observed that all melanocytic lesions examined showed strong uniform expression of standard CD44 (CD44s) epitopes. We did not detect CD44v6 expression in the melanocytic lesions. However, CD44 isoforms containing v5 or v10 were differentially expressed. V5 was expressed in 16%, 0%, 20%, 67% and 58% of common nevi, atypical nevi, early primary melanomas (± 1.5 mm), advanced primary melanomas (> 1.5 mm) and metastases, respectively, and hence was related to tumor progression. In contrast, CD44vl0 was expressed in all common nevi, whereas part of the atypical nevi and most primary melanomas and metastases lacked v10. CD44v RNA patterns were closely similar in cultured melanocytes and all melanoma cell lines. Melanocytes expressed high levels of CD44s but no CD44v, whereas all melanoma cell lines expressed CD44v at the surface. Interestingly, expression of v5 was strongly increased in the highly metastatic cell lines. Our results suggest a role for CD44 variant domains, particularly v5 and v10, in human melanocytic tumor progression. © 1995 Wiley-Liss, Inc.     

A phase I/II study of high-dose cyclophosphamide,cisplatin, and thioTEPA followed by autologous bone marrow and granulocyte colony-stimulating factor-primed peripheral-blood progenitor cells in patients with advanced malignancies

 The purpose of the present study was to determine the maximally tolerated dose of thioTEPA given with fixed high-dose cyclophosphamide (CPA) and cisplatin (cDDP) followed by autologous bone marrow (ABM) with or without granulocyte colonystimulating factor (G-CSF)-primed peripheral-blood progenitor cells (PBPCs) in patients with advanced malignancies. Patients were required to have histologically documented malignancies and adequate renal, hepatic, pulmonary, and cardiac function. CPA was given at 1,875 mg/m² per day as a 1-h i.v. infusion for 3 consecutive days, and cDDP was given at 55 mg/m² per day as a 24-h continuous i.v. infusion over 3 days concurrently with CPA. ThioTEPA was given once as a 1-h i.v. infusion (300–900 mg/m²) either following (the first 13 patients) or prior to CPA and cDDP. In all, 31 patients received PBPCs. A total of 46 patients were treated. There were 6 deaths among the 15 patients who did not receive PBPCs (13 received thioTEPA following CPA and cDDP). Among the other 31 patients who received PBPCs (all of whom also received thioTEPA prior to CPA and cDDP), there were 4 deaths, all involving patients with refractory ovarian carcinoma. The main toxicities were mucositis, esophagitis, hepatotoxicity, and nephrotoxicity. The median time required to achieve an absolute neutrophil count of 500 μl was 10 days (range, 9–12 days) for those who received PBPCs and 15 days (range, 15–34 days) for those who did not receive PBPCs. Altogether, 47% of the major organ toxicities (grades 3 and 4 renal, hepatic, and cardiac toxicities) occurred among the 15 patients who did not receive PBPCs, although these patients received thioTEPA at the lowest 2 dose levels. There were 3 complete responses and 22 partial responses among 35 evaluable patients (overall response rate, 71%), with the median duration of response being 3.5 months (range, 2–17 months). The maximally tolerated dose of thioTEPA was 600 mg/m² given as a 1-h i.v. infusion on the day prior to CPA and cDDP administration. The combination of high-dose CPA, cDDP, and thioTEPA is a well-tolerated regimen when thioTEPA is given prior to CPA and cDDP and when the combination also includes PBPCs in addition to ABM. This regimen is active in a variety of malignancies. Received: 15 February 1995/Accepted: 22 May 1995     

Should Hemoglobin be Normalized in Patients with Chronic Kidney Disease?

In the last decade the nephrology community has learned much about the impact of anemia on patients with kidney disease. Therapy of anemia can correct many of the symptoms which seriously compromise patient function. Despite the obvious benefits, controversy continues regarding the optimal target hemoglobin concentration both in patients prior to dialysis and in dialysis populations. In this editorial we review the clinical data that contribute to this controversy and the physiologic concepts underlying the treatment of anemia. Furthermore, we discuss the need to individualize hemoglobin targets for specific patient populations and the importance of early identification and treatment of anemia in patients with kidney disease. The economic impact of normalizing hemoglobin with the use of erythropoietin and intravenous or oral iron has affected clinical practice over the last decade. Current guidelines published by Kidney Disease Outcomes and Quality Initiative (KDOQI), the European Working Group on Anemia Management, and the Canadian Society of Nephrology all recommend target hemoglobin concentrations and thresholds for initiation of therapy and also suggest the need for reevaluation of current targets in light of new evidence. This editorial supports those guidelines and challenges the reader to critically evaluate current practice in the context of the accumulating data and the physiologic principles discussed herein. The therapy of anemia in patients with chronic kidney disease (CKD) is becoming increasingly sophisticated and is an essential component of care in patients with CKD. However, the effects of therapy will be most impressive when accompanied by the optimal care of all hemodynamic and metabolic abnormalities that are associated with CKD.