Bone Mass,Bone Microstructure and Biomechanics in Patients with Hand Osteoarthritis

The impact of primary hand osteoarthritis (HOA) on bone mass, microstructure, and biomechanics in the affected skeletal regions is largely unknown. HOA patients and healthy controls (HCs) underwent high-resolution peripheral quantitative computed tomography (HR-pQCT). We measured total, trabecular, and cortical volumetric bone mineral densities (vBMDs), microstructural attributes, and performed micro–finite element analysis for bone strength. Failure load and scaled multivariate outcome matrices from distal radius and second metacarpal (MCP2) head measurements were analyzed using multiple linear regression adjusting for age, sex, and functional status and reported as adjusted Z-score differences for total and direct effects. A total of 105 subjects were included (76 HC: 46 women, 30 men; 29 HOA: 23 women, six men). After adjustment, HOA was associated with significant changes in the multivariate outcome matrix from the MCP2 head (p < .001) (explained by an increase in cortical vBMD (Δz = 1.07, p = .02) and reduction in the trabecular vBMD (Δz = −0.07, p = .09). Distal radius analysis did not show an overall effect of HOA; however, there was a gender-study group interaction (p = .044) explained by reduced trabecular vBMD in males (Δz = −1.23, p = .02). HOA was associated with lower failure load (−514 N; 95%CI, −1018 to −9; p = 0.05) apparent in males after adjustment for functional status. HOA is associated with reduced trabecular and increased cortical vBMD in the MCP2 head and a reduction in radial trabecular vBMD and bone strength in males. Further investigations of gender-specific changes of bone architecture in HOA are warranted. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.     

Basic fibroblast growth factor mRNA, bFGF peptide and FGF receptor in epiretinal membranes of intraocular proliferative disorders (PVR and PDR)

Basic fibroblast growth factor (bFGF) has been shown to be involved in epiretinal membrane formation in proliferative vitreoretinal disorders. However, up to now, little knowledge exists, as to the actual cellular source of this potent mitogen.We examined 20 epiretinal membranes from patients with proliferative diabetic retinopathy (PDR) (n = 12) and proliferative vitreoretinopathy (PVR) (n = 8) for the presence of bFGF peptide, fibroblast growth factor receptor-1 (FGFR-1) and bFGF messenger ribonucleic acid (mRNA).Using a specific antibody, we detected bFGF peptide in most (8/10) examined PDR membranes and in all (8/8) PVR membranes. Moreover, we found positive staining for the corresponding receptor.Local production of bFGF in epiretinal membranes was confirmed by nonisotopic in situ hybridisation for bFGF mRNA in some (4/7) examined PDR membranes and some (3/4) examined PVR membranes. All membranes which contained bFGF mRNA were also positive for bFGF peptide.In conclusion, bFGF is produced and stored in epiretinal membranes. Together with the corresponding receptor, bFGF may play a role in the auto- and paracrine control of the proliferative processes at the vitroretinal interface.Abbreviations aFGF acidic fibroblast growth factor - bFGF basic fibroblast growth factor - FGFR-1 fibroblast growth factor receptor-1 - mRNA messenger ribonucleic acid     

Postinjection transmission scanning in myocardial 18F-FDG PET studies using both filtered backprojection and iterative reconstruction.

The aim of the present study was to evaluate the effect of postinjection transmission scanning (Post-Tx) on both the qualitative interpretation and the quantitative analysis of cardiac (18)F-FDG PET images. Furthermore, the accuracy of 2 different methods to correct for emission contamination was studied. An additional aim of this study was to compare images reconstructed with both standard filtered backprojection (FBP) and an iterative reconstruction algorithm (ordered-subset maximization expectation [OSEM]). METHODS: Sixteen patients underwent dynamic (18)F-FDG imaging. Both before injection of (18)F-FDG and after completing the emission scan, a 10-min transmission scan was performed (Pre-Tx and Post-Tx, respectively). Images were reconstructed using both FBP and OSEM. The emission study reconstructed with Pre-Tx was considered to be the gold standard. Emission studies were also reconstructed with Post-Tx, with and without correction for emission contamination. Correction for emission contamination was performed with either transmission image segmentation (TIS) or by estimating the emission bias from the last emission frame (dwell profile [DP] method). All images were then compared by calculating ratios of (18)F-FDG activity between corresponding myocardial segments in each patient. Furthermore, qualitative grading of (18)F-FDG uptake was compared between the studies. RESULTS: The mean ratio of (18)F-FDG activity between segments from FBP-Post and FBP-Pre was 0.78 +/- 0.08. When TIS and DP were used, the mean ratios were 0.80 +/- 0.07 and 0.94 +/- 0.06, respectively. The use of OSEM resulted in, on average, 2% lower values for (18)F-FDG activity as compared with FBP. The mean normalized (18)F-FDG uptake was higher in FBP-Post, especially in segments with decreased (18)F-FDG activity. Only in the case of DP were no significant differences observed as compared with FBP-Pre. In general, qualitative analysis of the images showed that the agreement between the reconstruction methods was comparable with the reproducibility of FBP-Pre. CONCLUSION: Post-Tx for attenuation correction in cardiac (18)F-FDG PET scans resulted in substantial underestimation of (18)F-FDG activity. More accurate results were obtained with correction for emission contamination using DP. Differences in visual assessment of (18)F-FDG images were small. Finally, iterative reconstruction could be used as an alternative to FBP in static (18)F-FDG imaging of the heart.     

Optimization of localized 19F magnetic resonance spectroscopy for the detection of fluorinated drugs in the human liver.

Fluorine MR spectroscopy ((19)F MRS) is an indispensable tool for assessing the pharmacokinetics of fluorinated drugs. Since the metabolism of 5-fluorouracil (5FU), a frequently used cytotoxic drug, is expected to be different in normal liver and in tumor tissue, spatial localization is required for detection by MRS. In this study, three independent signal-to-noise ratio (SNR) optimizations were combined to enable chemical shift imaging (CSI) as a localization method in the detection of 5FU and its metabolites in tumor tissue. First, the hardware was optimized by using circularly polarized coils together with integrated preamplifiers. Second, the optimal pulse angle (Ernst angle) was determined on the basis of T(1) relaxation time measurements of 5FU. Finally, averaging of CSI phase-encoding steps was optimized by using the applied Hamming filter as a weighting function. The combination of these three methods enables the in vivo detection of 5FU and alpha-fluoro-beta-alanine (FBAL) by (19)F MRS, localized in three dimensions in tumor and liver tissue at a time resolution of 4 min at 1.5 Tesla.     

Identification of cytotoxic principles from Fusarium avenaceum using bioassay-guided fractionation

The cytotoxicity of extracts from rice cultures of five Fusarium avenaceum strains against the porcine epithelial kidney cell-line PK-15 was investigated using the Alamar Blue™ assay. After the identification of known fungal metabolites, cytotoxic extracts were fractionated using semi-preparative reversed-phase HPLC and normal phase LC, and the fractions were tested for cytotoxicity. In this way, two different groups of metabolites were identified as the major cytotoxic principles of the extracts. High concentrations of enniatins, especially enniatins B and B1, inhibited the metabolic activity of PK-15 cells. Furthermore, an unidentified metabolite, produced in high amounts by a strain that produced relatively small amounts of enniatins, was also found to be cytotoxic to PK-15 cells. This study shows that enniatins, a group of cyclic depsipeptides, which have been ignored as significant contributors to the toxicity of fungal extracts, may account for most of the observed effect for F. avenaceum.     

Walking exercise in patients with intermittent claudication. Experience in routine clinical practice.

BACKGROUND: In patients with intermittent claudication, exercise in the form of walking is effective in reducing pain and maximising achievable walking distance. However, data are lacking on the implementation of walking exercise in these patients. AIMS: To explore the current behaviour and views of patients with intermittent claudication towards taking walking exercise. DESIGN OF STUDY: Postal questionnaire and focus group meetings. SETTING: Two academic general practice networks (Utrecht and Maastricht Universities) in The Netherlands. METHOD: Three hundred and seventy-five patients with intermittent claudication, selected from the files of general practitioners participating in two academic general practice networks, were sent a postal questionnaire; 216 (58%) were returned. Nine of these responders also attended a focus group meeting. RESULTS: Seventy per cent (151/216) of the patients reported having received advice about walking exercise. If specified, the advice given most often recommended walking in the local neighbourhood (56%, 84/151). Fifty-two per cent (113/216) of all patients actually performed walking exercise and only 32%of them received any kind of supervision. Among the barriers for taking walking exercise, 'comorbidity', 'lack of (specific) advice' and 'lack of supervision' were often mentioned. Among the stimuli to start and continue walking, 'following the doctor's advice', 'relief of complaints' and 'a better general condition' were often mentioned by patients. CONCLUSIONS: Walking exercise was not carried out by almost half of patients with intermittent claudication in this study. Lack of specific advice and supervision were found to be important barriers to taking walking exercise.     

Incidence and determinants of moderate COPD (GOLD II) in male smokers aged 40–65 years: 5-year follow up

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major health problem with an estimated prevalence of 10-15% among smokers. The incidence of moderate COPD, as defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD), is largely unknown. AIM: To determine the cumulative incidence of moderate COPD (forced expiratory volume in 1 second/forced vital capacity ratio [FEV1/FVC] <0.7 and FEV1 <80% predicted) and its association with patient characteristics in a cohort of male smokers. DESIGN: Prospective cohort study. SETTING: The city of IJsselstein, a small town in the Netherlands. METHOD: Smokers aged 40-65 years who were registered with local GPs, participated in a study to identify undetected COPD. Baseline measurements were taken in 1998 of 399 smokers with normal spirometry (n = 292) or mild COPD (FEV1/FVC <0.7 and FEV1 >or=80% predicted, n = 107) and follow-up measurements were conducted in 2003. RESULTS: After a mean follow-up of 5.2 years, 33 participants developed moderate COPD (GOLD II). This showed an estimated cumulative incidence of 8.3% (95% CI = 5.8 to 11.4) and a mean annual incidence of 1.6%. No participant developed severe airflow obstruction. The risk of developing moderate COPD in smokers with baseline mild COPD (GOLD I) was five times higher than in those with baseline normal spirometry (one in five versus one in 25). CONCLUSIONS: In a cohort of middle-aged male smokers, the estimated cumulative incidence of moderate COPD (GOLD II) over 5 years was relatively high (8.3%). Age, childhood smoking, cough, and one or more GP contacts for lower respiratory tract problems were independently associated with incident moderate COPD.     

Der Nachweis des frischen Herzinfarktes beim Menschen durch Bestimmung der Wasserstoffionenkonzentration im Herzmuskel mit Indicatorpapier

Zusammenfassung Bei 3 Patienten, die unmittelbar nach herzchirurgischen Eingriffen verstarben, konnte durch Bestimmung der Wasserstoffionenkonzentration [H⁺] mit Indicatorpapier am Gefrierschnitt des Herzens 1–2 Std nach dem Tod jeweils eine umschriebene ischämische Schädigung nachgewiesen und das Alter des frischen Herzinfarktes anhand der veränderten [H⁺] festgestellt werden. Innerhalb der ersten 1–2 Std nach Beginn der Herzmuskelischämie war die [H⁺] in dem ischämisch geschädigten Bereich erhöht (pH<6.0). Anschließend wies der Infarktbereich, im Randbereich beginnend, eine erniedrigte Wasserstoffionenkonzentration (pH 7.4–7.5) auf.Im Zusammenhang mit der erniedrigten [H⁺] ließ sich mit der Perjodsäure Schiff-(PAS-) Reaktion sogenanntes PAS-positives diastaseresistentes Material im Myokard nachweisen. Beim enzymhistochemischen Succinodehydrogenasenachweis fand sich in einem 7–8 Std alten Infarkt eine verstärkte Enzymreaktion.

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The demonstration of acute human cardiac infarction by determining the hydrogen ion concentration of the myocardium with indicator paper

Summary In three patients who died immediately after surgical procedures on the heart it was possible one—two hours after death to demonstrate with indicator paper on frozen sections of myocardium a circumscribed ischemic lesion and to determine the age of the infarction from the changed hydrogen ion concentration. Within the first one—two hours after the onset of ischemia the hydrogen ion concentration in the area of ischemic damage is increased (pH<6.0). Subsequently the infarcted area, beginning in the border zone, shows a decreased hydrogen ion concentration (pH appr. 7.4–7.5).As to the decreased hydrogen ion concentration, it was possible with the periodic-acid-Schiff (PAS) reaction to demonstrate so-called PAS-positive diastase-resistant material in the myocardium. The enzymhistochemical succinodehydrogenase test showed an increased enzyme reaction in an infarction which was 7–8 hours old.

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Mit Unterstützung der Deutschen Forschungsgemeinschaft.

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Vorgetragen auf der Thoraxchirurgischen Arbeitstagung, Februar 1970 in Bad Nauheim.     

M. Quadriceps femoris of Man,a muscle with an unusual enzyme activity pattern of energy supplying metabolism in mammals

1. The following enzyme activities were estimated in needle-biopsy samples of the lateral part of the human quadriceps femoris muscle: triosephosphate dehydrogenase (TPDH), lactate dehydrogenase (LDH), NAD : glycerol-3-phosphate dehydrogenase (GPDH), hexokinase (HK), NAD: malate dehydrogenase (MDH), citrate synthase (CS) and hydroxyacyl-CoA dehydrogenase. 2. Although the enzyme activities in muscles of women were lesser than in those of men, no difference was found in the calculated enzyme activity ratios. There is thus no sex-dependent metabolic type-differentiation in this muscle. 3. The human quadriceps femoris is a low-activity muscle, in comparison with muscles of homoiotherm laboratory animals. The enzyme activity ratio of TPDH to CS, characterizing the glycolytic pyruvate formation to aerobic oxidative capacities, shows this muscle to be of an intermediate type in this respect, similarly as the extensor digitorum longus of the rat. The relatively very high capacity of glucose phosphorylation (HK), the high aerobic regeneration of cytoplasmic dehydrogenated NAD (GPDH) and the very low anaerobic regeneration (LDH), show the unusually high proportion of carbohydrates (glucose) which can be broken down aerobically.