Plasma changes in breast cancer patients during endocrine therapy — lipid measurements and nuclear magnetic resonance (NMR) spectroscopy

Summary Side-effects following long-term endocrine therapy might have clinical implications. The aim of this study was to study potential methods to detect effects on plasma induced by hormonal therapies. The composite methylene (chemical shift between 1.2-1.4 ppm) and methyl (0.8-0.9 ppm) aliphatic peaks of the¹H magnetic resonance spectrum (500 MHz) were analyzed in consecutive plasma samples of 23 cancer patients drawn before and during treatment with hormonally acting drugs. The aliphatic peaks were analyzed for line width at half-height and then averaged. In addition,¹³C magnetic resonance spectroscopy (125 MHz) analyses were done in selected patients. The blood samples were analyzed for triglyceride, cholesterol, apolipoprotein A1 (apo A1), and apolipoprotein B (apo B) levels.The methylene line width increased significantly after 9 weeks of tamoxifen (41.4 vs. 37.6 Hz). A trend of differences was observed in the saturated part of the¹³C magnetic resonance spectrum. A significant decrease in total cholesterol (mean decrease, 13%), increases in apo A1 (9%) and in the ratio of apo A1 to apo B (28%), but unchanged total triglycerides were found, indicating a decrease in LDL and increase in HDL lipoproteins in these patients following tamoxifen therapy. During dose escalation with the aromatase inhibitor exemestane, the methylene line width seemed to decrease (31.9 vs. 38.8 Hz, at 12 weeks and baseline, respectively). Significant decreases in total (13%) and HDL (32%) cholesterol, apo A1 (25%), and total triglyceride (16%) levels were found during the same interval. The apo A1/apo B ratio decreased by 25%. For patients on dexamethasone, the proton aliphatic line widths increased one day after the initiation of therapy. The changes in line shape observed during dexamethasone therapy indicated lower levels of triglyceride-rich relative to triglyceride-poor lipoproteins, consistent with results from the lipid analyses.In conclusion, nuclear magnetic resonance spectroscopy might have potential to detect effects on plasma induced by endocrine therapy. The lipid analyses in these patients were in support of the changes in lipid profile as evaluated by nuclear magnetic resonance spectroscopy.     

Influence of plasma estrogen levels on the length of the disease-free interval in postmenopausal women with breast cancer

Summary The influence of plasma estrogen levels on disease-free interval (time from primary treatment to first relapse, DFI) in breast cancer patients is not known. Any relation between plasma estrogens and the outcome in breast cancer patients may have implications considering use of hormone replacement therapy (HRT) in patients treated for breast cancer. We measured plasma estradiol (E₂), estrone (E₁), and estrone sulfate (E₁S) in 92 postmenopausal women with breast cancer relapse and correlated plasma estrogen levels to the length of their disease-free interval (DFI₁) and the length of the DFI in the subgroup of patients in whom this extended a time period of more than 2 years (DFI₂). The length of DFI₂ correlated negatively to plasma level of E₁S (p < 0.025) and E₂ (p < 0.05) and to the E₂/E₁ and E₁S/E₁ ratios (p < 0.05), while the length of DFI₁ correlated negatively to plasma level of E₁S (p < 0.025) and the E₁S/E₁ ratio (p < 0.005). We also analyzed for possible correlations between DFIs and plasma estrogen levels in subgroups based on tumor stage at diagnosis and previous therapy. In general, these subgroup analyses revealed negative correlations of statistical significance or borderline significance between the DFI₁ and DFI₂ and E₂ and the E₂/E₁ ratio and non-significant negative correlations between plasma levels of E₁S and DFI₁ and DFI₂. In particular, strong negative correlations between plasma estrogen levels and the length of DFI₁ and DFI₂ were found among patients responding to first line endocrine treatment for relapse and among patients with primar stage III tumors. Our findings suggest plasma E₂ and E₁S to stimulate the growth of micrometastases in patients treated for breast cancer.     

The effect of systematic care planning after acute stroke in general hospital medical wards

In a multidisciplinary study comprising 280 patients with acute cerebrovascular disease, the functional capacity was followed from the acute stage onwards with a test battery mainly measuring activities of daily living and motor capacity. Systematized care procedures with written care plans in accordance with the nursing process model, together with a booklet of guidelines in stroke care, were introduced during an experimental period in the care of 173 of the stroke victims. The remaining 107 patients received conventional care. The functional improvements were equal from a statistical standpoint in these two groups. However, in the group, which received special activities, there was a significant decrease in bed days, and a slightly larger number were able to return to their own homes. Compared with another stroke population from the same hospital, measured with the same functional instrument 7 years ago, the patients in this study seemed better off from a functional standpoint. For the individual severely-disabled patient, the care planning procedures seemed to be valuable and an effective way of promoting communication between different units. The difficulties in introducing new routines for documentation are discussed.     

High-performance liquid chromatography of Cladosporium herbarum. Identification of allergens with immunological techniques

High-performance liquid chromatography (HPLC) using a gel permeation column was applied to separate components in a crude extract of the mould Cladosporium herbarum. Allergenic activity as well as individual allergens in collected fractions were analyzed by direct radioallergosorbent test (RAST) and fused rocked radioimmunoelectrophoresis (FRRIE), respectively. Thus, information of the molecular weight as well as the importance of the individual allergens were obtained simultaneously in a system showing a high degree of resolution. The study demonstrated that the crude extract of C. herbarum contained allergens mainly in the molecular weight range between 10,000 and 300,000 daltons. The results demonstrated the importance of carrying out both RAST and FRRIE to detect all allergens.     

The Readiness for Return to Work Scale; Does it Help in Evaluation of Return to Work?

Journal of Occupational Rehabilitation - Purpose The Readiness for Return to Work (RRTW) scale is used to evaluate workers’ readiness to resume work after sick leave. Previous research has...     

Methodological approach for determining the Minimal Important Difference and Minimal Important Change scores for the European Organisation for Research and Treatment of Cancer Head and Neck Cancer Module (EORTC QLQ-HN43) exemplified by the Swallowing scale

Quality of Life Research - The aim of this study was to explore what methods should be used to determine the minimal important difference (MID) and minimal important change (MIC) in scores for the...     

Somatic mutations reveal complex metastatic seeding from multifocal primary prostate cancer

Primary prostate cancer shows a striking intraorgan molecular heterogeneity, with multiple spatially separated malignant foci in the majority of patients. Metastatic prostate cancer, however, typically reveals more homogenous molecular profiles, suggesting a monoclonal origin of the metastatic lesions. Longitudinal mutational spectra, comparing multiple primary lesions with metastases from the same patients remain poorly defined. We have here analyzed somatic mutations in multisampled, spatio-temporal biobanked lesions (38 samples from primary foci and 1 sample from each of 8 metastases from seven prostate cancer patients) applying a custom-designed panel targeting 68 prostate cancer relevant genes. The metastatic samples were taken at time of primary surgery and up to 7 years later, and sampling included circulating tumor DNA in plasma or solid metastatic tissue samples. A total of 282 somatic mutations were detected, with a range of 0 to 25 mutations per sample. Although seven samples had solely private mutations, the remaining 39 samples had both private and shared mutations. Seventy-four percent of mutations in metastases were not found in any primary samples, and vice versa, 96% of mutations in primary cancers were not found in any metastatic samples. However, for three patients, shared mutations were found suggesting the focus of origin, including mutations in AKT1, FOXA1, HOXB13, RB1 and TP53. In conclusion, the spatio-temporal heterogeneous nature of multifocal disease is emphasized in our study, and underlines the importance of testing a recent sample in genomics-based precision medicine for metastatic prostate cancer.     

Microstructure of inner surfaces on composite restorations related to filling procedure.

The inner surfaces of 40 Concise restorations placed in vivo on permanent molars have been studied by scanning electron microscopy. Only grinding traces could be seen on fillings from cavities which had not been etched, while the morphologic structure of the enamel and dentin was reflected on fillings from acid-etched cavities. Application of low-viscous non-composite resin in the cavities before filling with the composite resin did not influence the enamel pattern on the fillings, while the amount of processes of resin corresponding to the dentinal tubules in etched cavities was significantly increased. In the discussion the difference in surface structure of the fillings is correlated to marginal leakage along similar restorations.     

Deposits of immunoglobulins, complement, and immune complexes in inflamed human gingiva

Gingival biopsy specimens from 20 patients with moderate to advanced periodontitis were obtained from inflamed sites with pockets of 5 mm or more. Sections were studied by an immunofluorescence technique, using polyclonal rabbit or goat anti-IgG, anti-IgM, anti-C1q, anti-C3a, and anti-C3c and mouse monoclonal anti-C9. Prewashed ethanol-fixed and nonwashed ethanol-fixed or frozen specimens showed many plasma cells staining for IgG or C3a, suggesting the possible occurrence of a receptor for C3a in plasma cells. Plasma cells containing IgM were also seen. Deposits of IgG and IgM with C1q, C3a, and C3c, suggesting immune complexes, were demonstrated by a double staining technique, combining fluorescein (FITC) or rhodamine (TRITC)-labeled anti-immunoglobulins with TRITC- or FITC-conjugated antibody to C3a, C3c, and C1q. The complexes were located mainly within or around vessel walls. Deposits of C3a and C1q were found in vessel walls, in the basement membrane zone of oral gingival epithelium, or diffusely distributed in the tissues. Deposits of C3c were found to a lesser extent and only in vessel walls. Mouse monoclonal anti-C9, visualized with FITC-labeled rabbit anti-mouse and swine anti-rabbit antiserum, showed granular deposits of C9, mainly in the basement membrane zone of oral gingival epithelium. The study indicates the involvement of immune complex vasculitis in inflammatory periodontal lesions. Also, our observations of the occurrence of deposits of complement factors support the hypothesis that complement factors play an important role in the immunopathology of the periodontal lesion.     

Investigation into the accuracy and measurement methods of sequential 3D dental scan alignment

Objectives

Alignment procedures have yet to be standardised and may influence the measurement outcome. This investigation assessed the accuracy of commonly used alignment techniques and their impact on measurement metrics.