Fine needle aspiration of the thyroid. Distinction between colloid nodules and follicular neoplasms using cell blocks and 21-gauge needles

Although fine needle aspiration (FNA) of the thyroid has been found to be useful in selecting patients for surgery in most cases, the cytologic differentiation of cellular colloid nodules from follicular neoplasms has not been possible because of the scanty amount of tissue obtained by this technique and because of the infrequent preparation of cell blocks, thus precluding appreciation of the tissue architecture. Review of the histology of nodular goiters and follicular neoplasms and comparison of their morphology in smears and cell blocks from FNA specimens with the histology of the surgically excised specimens in 74 cases revealed the presence of hyperplastic papillae and fragments of dilated follicles in the aspirates of most cases of colloid nodules. These two features appear to be specific for colloid nodules and are useful for distinguishing colloid nodules from follicular neoplasms. The merits of using a 21-gauge needle and of preparing cell blocks in thyroid studies are also discussed.     

Synthesis of protoporphyrin IX induced by 5-aminolevulinic acid in yeast cells in the presence of 2,2;-dipyridyl

5-Aminolevulinic acid (ALA), a precursor of porphyrin synthesis, increased the production of various porphyrin compounds in Candida guilliermondii cells. Metalloporphyrins and protoporphyrin IX (PPIX) were predominantly accumulated, respectively, at ALA concentrations of 0.2-0.4 mM and at those higher than 1.5 mM. 2,2;-Dipyridyl which complexed with bivalent metals significantly increased the content of endogenous PPIX even at ALA concentrations lower than 0.5 mM. Under these conditions, the yeast sensitivity to photodynamic effect of visible light (400-600 nm) dramatically increased due to photosensitization by endogenous PPIX.     

Oral Octreotide: A Review of Recent Clinical Trials and Practical Recommendations for Its Use in the Treatment of Patients With Acromegaly

ObjectiveAcromegaly is characterized by chronic growth hormone (GH) and insulin-like growth factor 1 (IGF-1) hypersecretion, often caused by a GH-secreting pituitary adenoma. Even though surgery remains the first line of treatment, medical therapy is essential if surgery is contraindicated, does not achieve remission, or does not prevent recurrence despite apparent surgical remission. Oral octreotide capsules (OOCs) that combine octreotide with a transient permeability enhancer technology are the first oral somatostatin receptor ligands (SRLs) approved in the United States for acromegaly.MethodsWe review the literature and clinical trial data on OOC therapy in patients with acromegaly and discuss the clinical assessment of OOC use, potential drug–drug interactions, drug initiation, dose titration, and monitoring of drug efficacy and tolerability.ResultsIn 4 pivotal clinical trials involving 238 patients with acromegaly treated with OOC, effective suppression of serum GH and IGF-1 levels, maintenance of disease control, decreased breakthrough symptoms and symptomatic improvement with non-inferiority of OOCs to injectable SRLs in maintaining biochemical response was seen. Additionally, the safety profile of OOC therapy is comparable to that of injectable SRLs. Most patients who completed the clinical trials of OOCs have also expressed preference for oral compared with injectable SRL administration.ConclusionOOCs are an effective treatment option for patients with acromegaly who previously responded to injectable SRLs, with the benefits of avoiding injection-related side effects. This article provides a review of the pharmacology, safety, and efficacy and offers practical recommendations on the use of OOCs to treat injectable SRL-responsive patients with acromegaly.     

High expression of COL5A2, a member of COL5 family,indicates the poor survival and facilitates cell migration in gastric cancer

Background: Gastric cancer (GC) metastasis determines the prognosis of patients, and exploring the molecular mechanism of GC metastasis is expected to provide a theoretical basis for clinical treatment. Recent studies have shown that extracellular matrix protein is closely related to GC metastasis. The present study aimed to explore the expression profile and role of COL5A2, as an extracellular matrix protein, in GC.Methods: The expression, overall survival, and progression-free survival data of COL5 family members were extracted from The Cancer Genome Atlas (TCGA) database, respectively. Weighted gene co-expression network analysis of the {"type":"entrez-geo","attrs":{"text":"GSE62229","term_id":"62229"}}GSE62229 database was performed out to identify modules and associated genes.Results: COL5A2 was selected as our research target in the TCGA database, and was also verified in the {"type":"entrez-geo","attrs":{"text":"GSE62229","term_id":"62229"}}GSE62229 and {"type":"entrez-geo","attrs":{"text":"GSE15459","term_id":"15459"}}GSE15459 datasets. COL5A2 was up-regulated in GC tissues by paraffin immunohistochemistry and RT-qPCR. The prognosis of patients with low COL5A2 expression was better than that of patients with high COL5A2 expression. Scratch and migration experiments showed that knockdown of COL5A2 decreased the migration ability of gastric cancer cells compared with the control group. In vivo, mice with tail vein injection COL5A2 knockdown had fewer and smaller metastatic nodules in liver. GSEA results showed that the TCGA and {"type":"entrez-geo","attrs":{"text":"GSE62229","term_id":"62229"}}GSE62229 samples were significantly enriched in several well-known cancer-related pathways, such as the TGF-β, MAPK, and JAK2 signaling pathways.Conclusion: COL5A2 was most closely related to advanced GC among COL5 family members. High COL5A2 expression is associated with a poor prognosis, and may be a novel therapeutic target for GC.     

An analysis of maternal deaths in British Columbia: 1963 to 1970

There were 132 maternal deaths in British Columbia in the years 1963 to 1970. The mean maternal mortality rate for these eight years was 0.317. Sixty of these deaths (45.5%) were due to direct obstetrical causes. Indirect and nonrelated deaths accounted for 21.2 and 33.3% of the total, respectively. The most common causes of direct obstetrical deaths were hemorrhage, infection and vascular accidents, in that order; pre-eclampsia ranked a distant fourth. Ninety-five percent of direct obstetrical deaths were probably avoidable. Approximately 27% of all direct obstetrical deaths were abortion-related. Hemorrhage continues to be a major problem, in particular among the native Indian women of the province.If further reduction in maternal mortality is to be achieved, obstetrical hemorrhage must be better managed and deaths due to abortions reduced. Future studies should reveal if the liberalized abortion laws will assist in the realization of the latter goal.     

Influence of Chilling on Electrolyte Permeability, Oxygen Uptake and 2,4-Binitrophenol Stimulated Oxygen Uptake in Leaf Discs of the Thermophilic Cucumis sativus

The effect of chilling was studied in leaf discs from the chilling-sensitive Cucumis sativus L. by measurement of the electrolyte leakage from the discs, by oxygen uptake and by uncoupling of respiration with 2,4 dinitrophenol. Short periods of chilling are characterized by minor significant increases of electrolyte permeability, of respiration and of preserved ability to be uncoupled by 2,4-dinilrophenol. A longer period of chilling resulted in a strongly increased electrolyte permeability, in reduced oxygen uptake and in disappearance of uncoupling by 2,4 dinitrophenol. In general the induced changes in permeability and respiration were reversible within 4 days of chilling, if the discs were placed at 25°C after chilling.     

Signaling and apoptosis differences between severe hypoxia and desferoxamine treatment of human epithelial cells

The mechanisms by which cells undergo proliferation arrest or cell death in response to hypoxia are still not completely understood. Originally, we showed that HeLa and Hep3B carcinoma cells undergo different proliferation responses in hypoxia. We now show that these 2 cell lines also have different cell death responses to severe hypoxia, with HeLa showing both cell cycle arrest and apoptosis (as early as 12 h after hypoxia treatment), and Hep3B showing resistance to both. Hypoxia-induced apoptosis in Hela was associated with decreases of both phospho-S473- and -T308-AKT and loss of AKT function, whereas Hep3B cells were resistant to hypoxia-induced apoptosis and did not lose phospho-AKT or AKT function. We then decided to test if our observations were confirmed using a hypoxia mimic, desferoxamine. Desferoxamine treatment yielded cell cycle arrest in HeLa and moderate arrest in Hep3B but, surprisingly, did not induce notable apoptosis of either cell line with up to 24 h of treatment. Hypoxia-treated normal human mammary epithelial cells also showed hypoxia-induced apoptosis. Interestingly, in these cell lines, there was a complete correlation between loss of phospho-AKT and (or) total AKT, and susceptibility to hypoxia-induced apoptosis. Our data suggests a model in which regulated loss of active AKT at a precise time point in hypoxia may be associated with apoptosis in susceptible cells.