Cell plasticity in lung injury and repair: report from an NHLBI workshop, April 19-20, 2010

In April 2010, a NIH workshop was convened to discuss the current state of understanding of lung cell plasticity, including the responses of epithelial cells to injury, with the objectives of summarizing what is known, what the field needs to know, and how to get there. The proximal stimulus for this workshop is the body of recent evidence suggesting that plasticity is a prominent but incompletely characterized property of lung epithelial cells, and that a focus on understanding this aspect of epithelial cell biology in particular, may be an important window into disease pathobiology and pathogenesis. In addition to their many vital functions in maintaining tissue homeostasis, epithelial cells have emerged as both a central target of disease initiation and an active contributor to disease progression, making a workshop to investigate the role of cell plasticity in lung injury and repair timely. The workshop was organized around four major themes: lung epithelial cell plasticity, signaling control of plasticity, fibroblast plasticity and crosstalk, and translation to human disease. Although this breakdown was recognized to be somewhat artificial, it was felt that this approach would promote cross-fertilization among groups that ordinarily do not communicate and lend itself to the generation of new approaches. The summary reports of individual group discussions below are followed by consensus priorities and recommendations of the workshop participants.     

The role of thyroid FNA cytology in pediatric malignant lesions: An overview of the literature

When one is dealing with pediatric thyroid lesions, fine‐needle aspiration is the first diagnostic tool for the correct characterization of these nodules. Despite the apparent infrequency of thyroid cancers in children, recent data from the National Cancer Institute prove that the incidence has been increasing, especially in adolescents. With the same data, a higher prevalence of well‐differentiated cancers can be estimated, with 90% diagnosed as papillary thyroid cancer. Nonetheless, some publications have demonstrated that some specific malignant variants are more frequent in children and have a more aggressive behavior that justifies the increased number of surgical procedures. For this reason, the American Thyroid Association recommends the performance of neck ultrasonography and fine‐needle aspiration cytology (FNAC) for the evaluation of pediatric thyroid nodules. Accordingly, as reported in adult thyroid series, several authors have documented the high sensitivity and diagnostic accuracy of FNAC in pediatric series; they have also shared the same problematic issues encountered in adult populations, mostly in the diagnosis of indeterminate lesions. To provide precise clinical and/or surgical management, the correct cytological identification of specific malignant histotypes/entities should be mandatory because lymph nodes, distant metastases, and extrathyroidal infiltration are more frequent within specific histotypes. A perusal of the literature shows that their identification has not been extensively studied and investigated in cytological samples. This review focuses on the analysis of data from the literature on the evaluation of malignancies and specific morphological features in pediatric thyroid lesions. Cancer Cytopathol 2017;125:594‐603 . © 2017 American Cancer Society.     

Cytologic diagnosis of metastatic melanoma by FNA: A practical review

Malignant melanoma (MM) is a highly aggressive neoplasm with a growing worldwide incidence. It is not uncommon that the disease is already metastatic at the time of the first diagnosis. Regional lymph nodes and skin are the first and most common metastatic sites, followed by distant visceral sites (lungs, liver, and central nervous system) and bone. In this clinical setting, fine-needle aspiration (FNA) often represents the first diagnostic approach. FNA is a useful tool to obtain a rapid and accurate diagnosis, in conjunction with ancillary techniques and molecular analysis, as recommended by recent guidelines. The aim of this review was to describe the cytomorphology, immunocytochemical tools, and molecular tools used for the diagnosis of MM metastases on FNA.     

Ten-year follow-up for male twins divided into high- or low-risk groups for ischemic heart disease based on risk factors measured 25 years previously

PURPOSE: To undertake medical follow-up in white males in the National Heart, Lung, and Blood Institute (NHLBI) twin study, previously divided on the basis of cardiovascular disease risk factors. METHODS: Tree structured survival analysis (TSSA) used at a mean age of 63 years to classify twins into high and low risk subgroups for ischemic heart disease (IHD) found that subjects at a mean age of 48 years were at highest risk with high systolic blood pressures and low high density lipoprotein cholesterol levels. Low risk subjects had lower blood pressures, better pulmonary function tests, and a negative family history for IHD or low post load plasma glucose levels. Medical record review was performed ten years later at the 4th Examination of the NHLBI twin cohort conducted in 1995-1997. RESULTS: The percentage of men in the NHLBI twin study who died nearly tripled (from 9.3% to 25.8%) in the ten-year period between the ages of 63 and 73 years. Deaths have tended to remain higher in DZ than MZ twins (27.8% versus 23.7%). At Exam 4, the relative risk of IHD (fatal or non-fatal) was 5.24 times higher for those in the high risk group than those in the low risk class (95% confidence limit 2.72-10.07, p < 0.0001 and 5.86 for any cardiovascular disease (95% confidence limit 3.03-11.33). The proportion of deaths from IHD in subjects with a high risk profile at entry was 51.7%, and 70.0% had died from all cardiovascular related disease. CONCLUSION: The present results indicate TSSA remained effective in classifying subjects into subgroups with greater risk of morbidity and mortality related to cardiovascular disease after ten additional years.     

Nateglinide and glibenclamide metabolic effects in naïve type 2 diabetic patients treated with metformin

Background and objective: Most antidiabetic agents target only one of several underlying causes of diabetes. The complementary actions of the glinides and the biguanides may give optimal glycemic control in patients with type 2 diabetes mellitus. The aim of the present study was to compare the effects of nateglinide plus metformin with glibenclamide plus metformin on glucose and lipid metabolism, and haemodynamic parameters in patients with type 2 diabetes mellitus. Methods: We enrolled 248 type 2 diabetic patients. Patients were randomly assigned to receive nateglinide (n = 124) or glibenclamide (n = 124), after 6 months of run‐in, in which we titrated nateglinide (starting dose 180 mg/day), glibenclamide (starting dose 7·5 mg/day), and metformin (starting dose 1500 mg/day). The final doses were (mean ± standard deviation), 300 ± 60, 12·5 ± 2·5, and 2500 ± 500 mg/day, respectively. We followed these patients for 1 year after titration. We assessed body mass index (BMI), fasting (FPG) and post‐prandial (PPG) plasma glucose, glycosylated haemoglobin (HbA_1c), fasting (FPI) and post‐prandial (PPI) plasma insulin, homeostasis model assessment (HOMA) index, and lipid profile [total cholesterol (TC), low density lipoprotein‐cholesterol (LDL‐C), high density lipoprotein‐cholesterol (HDL‐C), triglycerides (Tg), apolipoprotein A‐I (Apo A‐I), and apolipoprotein B (Apo B)], systolic blood pressure (SBP), and diastolic blood pressure (DBP). All variables were evaluated at baseline and after 3 and 6 months in the run‐in period, and at baseline, and after 3, 6, 9 and 12 months for both treatment groups. Results and discussion: Body mass index did not show any significant change during the study. We observed a significant improvement from baseline to 1 year on HbA_1c (P < 0·01 vs. baseline and vs. glibenclamide group, respectively), FPG (P < 0·01 vs. baseline), PPG (P < 0·01 vs. baseline), and on HOMA index (P < 0·05 vs. baseline) in the nateglinide group. In the glibenclamide group, we found significant changes in HbA_1c (P < 0·05 vs. baseline), FPG (P < 0·01 vs. baseline), PPG (P < 0·05 vs. baseline), and HOMA index (P < 0·05 vs. baseline). No significant change was observed in TC, LDL‐C, HDL‐C, Tg, Apo A‐I, Apo B, SBP, DBP and HR in either group after 3, 6, 9 and 12 months. These effects of nateglinide and glibenclamide on insulin‐resistance parameters are in agreement with previous reports. Contrarily to previous reports, we did not observe any significant BP change in patients treated with glibenclamide. Although both nateglinide and glibenclamide attenuated PPG and HOMA index, they did not have significant effects on lipid metabolism, as already shown in subjects with type 2 diabetes and good glycemic control. Conclusion: Nateglinide improved glycemic control better than glibenclamide in combination with metformin.     

Distribution and regulation of galanin-like peptide (GALP) in the hypothalamus of the mouse.

Galanin-like peptide (GALP) is a newly discovered molecule whose expression in the brain is confined to the arcuate nucleus and median eminence. In the rat, cellular levels of GALP mRNA are reduced by fasting and reversed by peripheral administration of leptin. The purpose of this investigation was 1) to clone and map the distribution of GALP mRNA in the brain of the mouse; 2) to compare the pattern and magnitude of GALP mRNA expression in the leptin-deficient obese (ob/ob) mouse with that of wild-type controls; and 3) to examine the effects of leptin delivered into the brain on the expression of GALP mRNA in the ob/ob mouse. We report the sequence of a mouse GALP cDNA and show that GALP mRNA is expressed in the arcuate nucleus, median eminence, infundibular stalk, and the neurohypophysis of this species. The expression of GALP mRNA in the brain was markedly reduced in the ob/ob mice, compared with wild-type animals. Intracerebroventricular infusion of leptin to ob/ob mice increased both the number of GALP mRNA-expressing neurons and their content of GALP mRNA, compared with vehicle-treated controls. These observations demonstrate that GALP mRNA is induced by leptin through a direct action on the brain.     

Squamous cell carcinomatous meningitis

A case of leptomeningeal carcinomatosis due to a poorly differentiated malignancy is presented. Immunohistochemistry was used to characterize it as a squamous cell carcinoma. Squamous cell carcinomas rarely invade the meninges. There are few well-founded guidelines for managing patients with this condition. Prognosis is generally poor. A literature review of this entity is provided.     

Control beliefs of orthopaedic nurses in relation to knowledge and prevalence of pressure ulcers

Data are reported from a larger study of perceptions of locus of control and value of pressure ulcer prevention to show the position of orthopaedic nurse control beliefs, their departmental knowledge level, and their value of pressure ulcer prevention relative to that of staff in other specialties. The survey population consisted of trained and assistant nursing staff in both hospital and community settings of a rural Health Service Trust. Overall results showed that key personnel, such as sisters, were significantly associated with prevalence, in that the more they believed they controlled pressure sore prevention, rather than the patient, the higher the prevalence. This has been explained using locus of control typology. The more it was thought that fate controls pressure sore prevention, the lower the departmental prevalence. Further, beliefs about specific conditions (e.g. pressure ulcer prevention) may be less important than generalized beliefs about control in terms of reducing prevalence.It is suggested that the study is replicated and refined, and that the value of pressure sore prevention needs raising. Certain types of attitudes amongst staff may be unhelpful in a broader range of conditions and outcomes. There may be a need to change control expectations of groups of personnel in order to protect patients.