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.     

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.     

Proteomics-based identification of α1-antitrypsin and haptoglobin precursors as novel serum markers in infiltrating ductal breast carcinomas

Background

The identification of pathological markers of breast cancer for either diagnosis, treatment response or for survival is of critical importance.

Methods

Serum protein profiling using 2-DE separations coupled to matrix-assisted laser desorption ionization mass spectrometry has been used to explore protein alterations in patients with infiltrating ductal breast carcinomas (IDCA). Sera from 39 breast cancer patients and 40 healthy controls were selected for screening study using 2-DE combined with MS. The protein expression patterns obtained after the depletion of high abundance proteins was determined by coomassie blue G-250 stain after 2-DE electrophoresis.

Results

Six proteins that expressed differentially in the IDCA group were found. The expression levels of four isoforms corresponding to haptoglobin precursor and two isoforms of α1-antitrypsin precursor (α1-AT) were upregulated in sera from breast cancer patients. There was an increased expression of both proteins in the sera of patients with various tumor stages (I, II, III) in comparison to healthy women. Applying immunohistochemistry, we further validated α1-AT immunoreactivity in 51 formalin-fixed paraffin-embedded sections of breast tumors. Enhanced expression of α1-AT like activity has been found in IDCA breast tumors, as well as, in different histological types of breast cancer. No significant association has been found with lymph node occurrence, while in high tumor categories a tendency to an increased expression of α1-AT has been found, thereby suggesting a possible role of this protein in tumor growth.

Conclusions

These proteins may constitute new and useful markers of breast cancer that offer a clue to a better understanding of inflammatory pathways and carcinogenesis events linked to breast cancer progression.     

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.     

IV. Über die Luxatio carpo-metacarpea

Zusammenfassung Unter Berücksichtigung eines eigenen Falles von isolierter Subluxation des Metacarpus 5 werden die bisher in dem Schrifttum beobachteten F?lle von Luxatio carpometacarpea cr?rtert. Mit Darlegung der Anatomie der Carpometacarpalgelenke werden die verschiedenen hierher geh?renden Luxationsformen besonders nach ihrem Entstehungsmechanismus besprochen. In der eigenen Beobachtung wird die Spielart der Subluxation als „seitliche“ erl?utert.     

The Inhibitory Effects of Prednisone, 16-Methylen-Prednisolone, and Acth on Con-A Induced Lymphokines (Interferon-Y) as Measured by the Chemiluminescence-Activity of Blood Monocytes

When lymphocytes are stimulated with mitogens or antigens they are enhanced via a cascade of lymphokines to produce interferon-y (IFN-y). IFN-y augments the H₂O₂secretion of human monocytes which indirectly can be measured by chemiluminescence. We tested prednisone, 16-methylen. prednisolone and ACTH for their effect to inhibit the Con-A induced stimulation of the chemiluminescence-activity. All three hormones inhibited significantly the stimulation: prednisone up to 52.5 % (concentration = 150 m;g/ml, p=0.000005), 16-methylen-prednisolone up to 22.5 % (concentration = 2.5 & m g/ml, p=0.006) and ACTH up to 33 % (concentration = 10 m g/ml, p=0.0036).     

Stimulation of human cytotoxic T cells with HIV-1-derived peptides presented by recombinant HLA-A2 peptide complexes

HLA-A2 heavy chain and beta 2-microglobulin were expressed in Escherichia coli, and refolded in the presence of peptides derived from HIV-1 RT and gag proteins. When recombinant HLA-A2 molecules were attached to cells lacking HLA-A2, the cells became susceptible to lysis by HLA-A2-restricted cytotoxic T lymphocyte (CTL) clones specific for peptides derived from RT and gag proteins. Limiting dilution analyses of peripheral blood mononuclear cells from HIV-1-infected individuals showed that the recombinant HLA-A2 peptide complexes covalently immobilized on microspheres stimulated the development of HLA-A2 peptide-specific CTL. Preformed HLA-peptide complexes may provide an alternative to immunization procedures that depend upon intracellular processing of antigen to elicit T cell responses.