Objective: Increased inflammatory response may be associated with adverse clinical outcomes, especially in the neonatal period. The aims of this study were to determine whether N-acetyl-cysteine (NAC), an anti-inflammatory agent, attenuates the inflammatory response in young rats and to determine the most effective route of administration.
Methods: Four groups of Sprague-Dawley rats (in each group four rats) were studied at 30 days of age. One hour following intraperitoneal (IP) injection of lipopolysaccharide 50 µg/kg, the rats were randomized to subcutaneous (SC), per os (PO), or intraperitoneal (IP) injection of NAC 300 mg/kg, or saline. The control group received saline injection (IP). Three hours following the N-acetyl-cysteine injection the rats were sacrificed, then serum tumor necrosis factor-α (TNF-α) and IL-6 levels were determined by ELISA.
Results: Lipopolysaccharide significantly increased the neonatal serum IL-6 and TNF-α (2051.0±349 and 147.0±25.8 pg/mL, respectively; P<0.01) levels compared to 10 pg/mL in the controls. N-acetyl-cysteine administered one hour following lipopolysaccharide injection significantly attenuated the inflammatory response. Intraperitoneal administration of NAC decreased IL-6 and TNF-α concentration to 294.6 and 17.1 pg/mL, respectively, and was more effective than SC or PO administration.
Conclusions: N-acetyl-cysteine attenuated the inflammatory response in the neonatal rats, and IP was the most effective administration route.
Obstetric anal sphincter injuries (OASIs) following vaginal deliveries are the main reason for subsequent development of anal incontinence in women. The diagnosis of such tears is crucial for treating and preventing such a grave sequela. The reported rate of OASIs in Israel was between 0.1% and 0.6%, out of all vaginal births, which is 10-fold lower than that reported in Europe and the United States. Structured hands-on training in repair of OASIs in seven medical centers in Israel significantly increased the detection rate of third-degree perineal tears. The implementation of such programs is crucial for increasing awareness and detection rates of OASIs following vaginal deliveries.
Recent developments in diagnostic imaging herald a new approach to diagnosis and management of prostate cancer. Multimodality fusion that combines anatomic with functional imaging data has surpassed either of the two alone. This opens up the possibility to “find and fix” malignancy with greater accuracy than ever before. This is particularly important for prostate cancer because it is the most common male cancer in most developed countries. This article describes technical advances under investigation at our institution and others using multimodality image fusion of magnetic resonance imaging (MRI), transrectal ultrasound (TRUS), and PSMA PET/CT (defined as the combination of prostate-specific membrane antigen [PSMA], positron emission tomography [PET], and computed tomography [CT]) for personalized medicine in the diagnosis and focal therapy of prostate cancer with high-intensity focused ultrasound (HiFUS).
The evolution of medicine is quite remarkable and astounding. Modern medicine is successfully treating or providing long-term control of conditions which in the not-so-distant past were lethal or resulted in permanent disability. The strong emphasis on evidence-based medicine in today’s medical profession has led to a more organized approach toward evaluating the safety and efficacy of new medical treatments. Despite attempts to meet the complex needs of an ever-aging population, an almost cynical or inherent distrust of physicians in general and their medical claims is being increasingly noted. For many physicians this has led to an uncomfortable sense of professional frustration as doubt is cast on themselves or the medical profession in general when the expectations and goals of patients or their families are not achieved. The causes of this apparent malady of contemporary medicine are myriad and may be explored from various perspectives, depending on the particular issue. To understand better the issues and challenges involved, today’s medical practitioner needs to be aware of the complex mix of organizational, professional, ethical, and at times anthropological perspectives contributing to this dissonance between medical professionals and the public. Improving our insight into the forces at work in this dissonance will help medical professionals improve medical services to the public and contribute to the preservation of medicine’s admirable historical legacy.
Background: Studying the biological pathways involved in mammalian milk production during lactation could have many clinical implications. The mammary gland is unique in its requirement for transport of free glucose into the cell for the synthesis of lactose, the primary carbohydrate in milk.
Objective: To study GLUT1 trafficking and subcellular targeting in living mammary epithelial cells (MEC) in culture.
Methods: Immunocytochemistry was used to study GLUT1 hormonally regulated subcellular targeting in human MEC (HMEC). To study GLUT1 targeting and recycling in living mouse MEC (MMEC) in culture, we constructed fusion proteins of GLUT1 and green fluorescent protein (GFP) and expressed them in CIT3 MMEC. Cells were maintained in growth medium (GM), or exposed to secretion medium (SM), containing prolactin.
Results: GLUT1 in HMEC localized primarily to the plasma membrane in GM. After exposure to prolactin for 4 days, GLUT1 was targeted intracellularly and demonstrated a perinuclear distribution, co-localizing with lactose synthetase. The dynamic trafficking of GFP-GLUT1 fusion proteins in CIT3 MMEC suggested a basal constitutive GLUT1 recycling pathway between an intracellular pool and the cell surface that targets most GLUT1 to the plasma membrane in GM. Upon exposure to prolactin in SM, GLUT1 was specifically targeted intracellularly within 90–110 minutes.
Conclusions: Our studies suggest intracellular targeting of GLUT1 to the central vesicular transport system upon exposure to prolactin. The existence of a dynamic prolactin-induced sorting machinery for GLUT1 could be important for transport of free glucose into the Golgi for lactose synthesis during lactation.
Differentiated thyroid carcinoma (DTC) comprises over 90% of thyroid tumors and includes papillary and follicular carcinomas. Patients with DTC have an excellent prognosis, with a 10-year survival rate of over 90%. However, the risk of recurrent tumor ranges between 5% and 30% within 10 years of the initial diagnosis. Cervical lymph node disease accounts for the majority of recurrences and in most cases is detected during follow-up by ultrasound or elevated levels of serum thyroglobulin. Recurrent disease is accompanied by increased morbidity. The mainstay of treatment of nodal recurrence is surgical management. We provide an overview of the literature addressing surgical management of recurrent or persistent lymph node disease in patients with DTC.
Thyroid cancer is an increasingly common malignancy, with a rapidly rising prevalence worldwide. The social and economic ramifications of the increase in thyroid cancer are multiple. Though mortality from thyroid cancer is low, and most patients will do well, the risk of recurrence is not insignificant, up to 30%. Therefore, it is important to accurately identify those patients who are more or less likely to be burdened by their disease over years and tailor their treatment plan accordingly. The goal of risk stratification is to do just that. The risk stratification process generally starts post-operatively with histopathologic staging, based on AJCC/UICC staging system as well as others designed to predict mortality. These do not, however, accurately assess the risk of recurrence/persistence. Patients initially considered to be at high risk may ultimately do very well yet be burdened by frequent unnecessary monitoring. Conversely, patients initially thought to be low risk, may not respond to their initial treatment as expected and if left unmonitored, may have higher morbidity. The concept of risk-adaptive management has been adopted, with an understanding that risk stratification for differentiated thyroid cancer is dynamic and ongoing. A multitude of variables not included in AJCC/UICC staging are used initially to classify patients as low-, intermediate-, or high-risk for recurrence. Over the course of time, a response to therapy variable is incorporated and patients essentially undergo re-risk stratification. Additional tools such as biochemical markers, genetic mutations and molecular markers have been added to this complex risk stratification process such that this is essentially a continuum of risk. In recent years, additional considerations have been discussed with a suggestion of pre-operative risk stratification based on certain clinical and/or biologic characteristics. With the increasing prevalence of thyroid cancer but stable mortality, this risk stratification may identify those in whom the risk of conventional surgical treatment may outweigh the benefit. This review aims to outline the process of risk stratification and highlight the important concepts that are involved and those that are continuously evolving.
The treatment of differentiated thyroid carcinoma (DTC) is surgery followed in some cases by adjuvant treatment, mostly with radioactive iodine (RAI). External beam radiotherapy (EBRT) is less common and not a well-established treatment modality in DTC. The risk of recurrence depends on three major prognostic factors: extra-thyroid extension, patient’s age, and tumor with reduced iodine uptake. Increased risk for recurrence is a major factor in the decision whether to treat the patient with EBRT. Data about the use of EBRT in DTC are limited to small retrospective studies. Most series have demonstrated an increase in loco-regional control. The risk/benefit from giving EBRT requires careful patient selection. Different scoring systems have been proposed by different investigators and centers. The authors encourage clinicians treating DTC to become familiarized with those scoring systems and to use them in the management of different cases. The irradiated volume should include areas of risk for microscopic disease. Determining those areas in each case can be difficult and requires detailed knowledge of the surgery and pathological results, and also understanding of the disease-spreading pattern. Treatment with EBRT in DTC can be beneficial, and data support the use of EBRT in high-risk patients. Randomized controlled trials are needed for better confirmation of the role of EBRT.
Objectives: Thyroid cancer incidence is increasing worldwide, while mortality from thyroid cancer is stable or decreasing. Consequently, survival rates are rising. We describe time trends in the incidence, mortality, and 5-year survival of thyroid cancer in Israel in 1980–2012, in light of the global trends.
Methods: Israel National Cancer Registry database provided information regarding thyroid cancer incidence and vital status, which enabled computation of survival rates. The Central Bureau of Statistics database provided information on thyroid cancer mortality. Incidence and mortality rates were age-adjusted and presented by population group (Jews/Arabs) and gender. Relative 5-year survival rates which account for the general population survival in the corresponding time period were presented by population group and gender. Joinpoint analyses were used to assess incidence trends over time.
Results: In 1980–2012 significant increases in the incidence of thyroid cancer were observed, with an annual percent change (APC) range of 3.98–6.93, driven almost entirely by papillary carcinoma (APCs 5.75–8.86), while rates of other types of thyroid cancer remained stable or decreased. Furthermore, higher rates of early detection were noted. In 1980–2012, a modest reduction in thyroid cancer mortality was observed in Jewish women (APC –1.07) with no substantial change in Jewish men. The 5-year relative survival after thyroid cancer diagnosis has increased to ≥90% in both population groups and both genders.
Conclusions: The Israeli secular trends of thyroid cancer incidence (increasing), mortality (mostly stable), and survival (modestly increasing) closely follow reported global trends.
Jewish medical ethics is arguably the oldest recorded system of bioethics still in use. It should be of interest to practicing nephrologists because of its influence on the ethical systems of Christianity, Islam, and Western secular society; because of the extensive written documentation of rabbinical response in addressing a broad range of bioethical dilemmas; and in understanding the values of patients who choose to adhere to religious Jewish law. The goal of this review is to provide a brief overview of the basic principles underlying mainstream traditional Jewish medical ethics, apply them to common clinical scenarios experienced in nephrology practice, and contrast them with that of secular medical ethics.
