Detection and evaluation of initial cartilage pathology in man: A comparison between MRT,arthroscopy and near-infrared spectroscopy (NIR) in their relation to initial knee pain

Background and aims: MRI and arthroscopy are important methods in the evaluation of cartilage pathology. But frequently initial changes of cartilage in combination with chronic knee pain cannot be detected by employing these two methods. Better diagnostic tools for the detection of the early stages of osteoarthritis (OA) are required. The objective of this study was to show that near-infrared spectroscopy (NIRS) can be incorporated into routine arthroscopy to improve detection and assessment of the initial cartilage pathology. Furthermore correlations between findings in MRI, arthroscopy and NIRS in patients with initial symptoms of OA have studied. Methods: Patients (n = 21, 12 women, 9 men, age: 15–59 years, mean 34.19 years) with knee pain lasting for at least half a year without any trauma of the knee in their history were interviewed (body weight, smoking behaviour) and clinically evaluated using the Knee Injury and Osteoarthritis Outcome Score (KOOS). Also serum parameters (cholesterol, lipids) were analysed, conventional X-rays in three directions (evaluated according to Kellgren and Lawrence) and MRI (evaluation of cartilage damage according to the ICRS-score) were performed preoperatively in all patients. During subsequent arthroscopy cartilage damage was evaluated according to the ICRS-score. In addition the spectral reflection of cartilage was investigated in all knees using a special micro-glass-fiber probe in the near-infrared light region (spectral range between 1150 and 1475 nm). To characterize relations between the investigated parameters the Spearman's rank correlation coefficient was used. Inter-observer variance was calculated employing the Cohens–Kappa-test. Results: MRI demonstrated a strong inter-observer variance with no significant correlations to other parameters. The same was observed for arthroscopic findings. Only NIRS showed significant correlations with three out of five KOOS subscores. Within the general parameters only smoking behaviour showed a significant correlation with two of the KOOS-scores. NIRS therefore seemed to be a sensitive diagnostic tool in detection of initial pathology in human cartilage. The additional necessary time for the spectroscopic investigation as part of the routine arthroscopy ranged between 3 and 7 min (mean: 4 min 18 s). Conclusion: Particularly for early-stage cartilage lesions (ICRS 0/I) MRI and arthroscopy have rather low predictive value. The inter-observer variance is very high (Cohens–Kappa < 0.4). Correlations found between NIRS and KOOS suggest that NIRS potentially can be used for detection of initial cartilage pathology and may be helpful in the evaluation of the benefit of different medical or surgical interventions at early-stage of articular cartilage damage.     

Ultrastructural changes in hepatocytes of precision-cut rat liver slices after incubation for 24 and 48 hours

Hepatocytes of precision-cut rat liver slices were studied by means of transmission electron microscopy after long-term incubation (24–48 h) in comparison with freshly prepared slices, indicating reversible and irreversible intracellular alterations of the cells. After 24 h incubation the morphological image in transversal sections of slices is characterised by a central zone of damaged and necrotic cells flanked by two to several superficial layers of viable cells. This is typical of a diffusion gradient of oxygen tension and nutrient content from the surface to the centre of the slices. In adapted cells on the surface of the slices we observed an organelle-free layer of fine granular material in the apical cytoplasm followed by parallel oriented stacks of rough endoplasmic reticulum near by. Mitochondria of essentially normal appearance in adapted cells did not contain flocculent densities, which were observed in damaged cells only. The cytoplasm of parenchymal cells consisted of defined areas of clear cytoplasmic material containing numerous branching tubular profiles of smooth endoplasmic reticulum, presumably in the regions with depleted glycogen aggregates. Subcellular signs of necrosis are destroyed mitochondria, dilated endoplasmic reticulum free of ribosomes and clumping of chromatin in the nucleus of hepatocytes. No appreciable differences of the cell organelles were observed between 24 and 48 h of incubation, but the incidence and intensity of signs of necrosis increased with the duration of incubation and the thickness of the slices. The process of these changes may reflect the phenomenon of cellular adaptation and of hypoxic cellular injury in the periphery and the centre of the slices, respectively.     

Mycoplasma gallisepticum invades chicken erythrocytes during infection

Recently, it was demonstrated using in vitro assays that the avian pathogen Mycoplasma gallisepticum is able to invade nonphagocytic cells. It was also shown that this mycoplasma can survive and multiply intracellularly for at least 48 h and that this cell invasion capacity contributes to the systemic spread of M. gallisepticum from the respiratory tract to the inner organs. Using the gentamicin invasion assay and a differential immunofluorescence technique combined with confocal laser scanning microscopy, we were able to demonstrate in in vitro experiments that M. gallisepticum is also capable of invading sheep and chicken erythrocytes. The frequencies of invasion of three well-defined M. gallisepticum strains were examined over a period of 24 h, and a significant increase in invasiveness occurred after 8 h of infection. In addition, blood samples derived from chickens experimentally infected via the aerosol route with the virulent strain M. gallisepticum R_low were analyzed. Surprisingly, M. gallisepticum R_low was detected in the bloodstream of infected chickens by nested PCR, as well as by differential immunofluorescence and interference contrast microscopy that showed that mycoplasmas were not only on the surface but also inside chicken erythrocytes. This finding provides novel insight into the pathomechanism of M. gallisepticum and may have implications for the development of preventive strategies.     

Cardiac and skeletal muscle adaptations to training in systemic hypertension and effect of beta blockade (metoprolol or propranolol)

Cardiovascular and peripheral adaptations to an aerobic conditioning program were studied in 30 hypertensive adults taking either placebo, beta 1-selective beta-adrenergic blocker (metoprolol) or beta 1-nonselective beta-adrenergic blocker (propranolol). The placebo group increased aerobic capacity (VO2max) 24% (p less than 0.002), largely explained by an increased peripheral arteriovenous (AV) oxygen difference with minimal changes in cardiac size and function. Resting blood pressure and total systemic resistance also decreased. The group taking a beta 1-selective beta blocker increased VO2max 8% (p less than 0.05), reduced resting blood pressure but had no significant change of AV oxygen difference or cardiac size or function. The group taking the beta 1-nonselective beta blocker propranolol had no increase in VO2max, no decrease in resting blood pressure and no cardiovascular or peripheral adaptations to the exercise program. Thus, beta 1-selective and beta 1-nonselective beta blockers attenuate conditioning in hypertensive patients to differing degrees, in each case by blocking peripheral mechanisms of conditioning.     

Intracranial Aneurysms Treated by Flow-Diverting Stents: Long-Term Follow-Up with Contrast-Enhanced Magnetic Resonance Angiography

Purpose

Long-term data on aneurysm treatment with flow-diverting stents are still sparse, and follow-up protocols differ widely between institutions. We present long-term results, with a focus on the usefulness of contrast-enhanced MR angiography (ceMRA).

Materials and Methods

Interventions and follow-up imaging of patients with aneurysms treated by flow-diverting stents (“Pipeline,” “Silk” and “FRED” models) without additional coiling were analyzed. All MRI scans included dedicated two-phase ceMRA. Aneurysm occlusion rates, size of the aneurysmal sac and complications were evaluated on MRI and digital subtraction angiography (DSA), where available. The ability of ceMRA to depict aneurysm occlusion and stent patency was graded on a three-point scale.

Results

Twenty-five patients with 102 MRI scans were included. The median duration of follow-up was 830 days. Aneurysm occlusion rates were 52% at 3 months (10 of 19 patients), 72% at 6 months (18/25) and 84% overall (21/25). Shrinkage of the aneurysmal sac was found in 19 patients (76%) and in 12 cases to <50% of the original size (48%). CeMRA assessability of aneurysmal occlusion was graded as good in all cases. When compared to DSA (18 cases), ceMRA had a sensitivity of 100% and specificity of 91% regarding aneurysm remnant detection. Assessability of the stent lumen varied and was limited in most cases.

Conclusions

Flow-diverter treatment achieves high occlusion rates and can cause major aneurysm shrinkage. CeMRA is highly valuable regarding imaging of the aneurysmal sac. There are limitations regarding the assessability of the stent lumen on ceMRA.

Level of Evidence

Level 4, Case Series.

     

Concanavalin A Derivatives with Altered Biological Activities

Chemical derivatization of tetrameric concanavalin A (Con A) with succinic anhydride or acetic anhydride converts the protein to a dimeric molecule without altering its carbohydrate-binding specificity. At low concentrations, the dose-response curves for the mitogenic stimulation of mouse spleen cells by native Con A and succinyl-Con A are similar. Above lectin concentrations of 10 mug/ml, however, the response to Con A is diminished, while that for succinyl-Con A does not decrease until much higher doses are reached. We have attributed this difference mainly to the higher rate of cell death induced by the native Con A molecule. Con A also shows a greater capacity than succinyl-Con A to agglutinate sheep erythrocytes and to inhibit cap formation by immunoglobulin receptors on spleen cells. Moreover, at low concentrations, Con A induced its glycoprotein receptors to form caps, but succinyl-Con A did not induce cap formation. Addition of antibodies directed against Con A to succinyl-Con A bound on cells restored the properties of agglutination, inhibition of immunoglobulin receptor cap formation, and induction of cap formation by Con A receptors. Similar results have been obtained for acetyl-Con A. These data suggest that the altered biological activities of succinyl-Con A and acetyl-Con A are attributable to their reduced valence.     

A Physiological Mechanism for Hebb''s Postulate of Learning

Hebb's postulate of learning envisages that activation or inactivation of extant synaptic contacts in plastic neural networks depends on the synchronous impulse activity of pre- and postsynaptic nerve cells. The physiological mechanism proposed here for this process posits that at synapses acting according to Hebb's postulate, the receptors for the neurotransmitter are eliminated from the postsynaptic membrane by the transient reversals of the sign of membrane polarization that occur during action potential impulses in the postsynaptic cell. But, since the release of neurotransmitter drives the membrane potential of the synaptic zone towards a level about half-way between the negative-inside resting potential and the positive-inside action potential, it would follow that the membrane patches surrounding the receptors of a synapse whose activity has contributed to setting off the postsynaptic impulse would be spared the full extent of the noxious polarity reversal. This mechanism can account for a neurophysiologically documented example of the operation of Hebb's postulate, namely the plasticity of the connections between fourth- and fifth-order neurons in the visual cortex of cats.     

Therapy of coronary vasoconstriction in patients with coronary artery disease

Patients with obstructive coronary artery disease and stable, exertional angina respond to the alpha adrenergic stimulus of the cold pressor test with an inappropriate increase in coronary vascular resistance. The clinical significance of this abnormal response and its possible role in the pathogenesis of ischemic heart disease are discussed. Comparison of the anti-anginal agents currently in use of undergoing investigation suggests that the calcium antagonists may be the most effective therapy for coronary vasoconstriction. Nifedipine, 10 mg buccally, successfully prevented the increase in coronary vascular resistance during the cold pressor test in 10 of 10 patients, whereas the response in placebo-treated patients was unaltered. This dose of nifedipine was without effect on systemic hemodynamics or myocardial oxygen consumption, suggesting a selective antivasoconstrictor effect on the coronary vasculature.     

The Eurotransplant Study on Twin Lung Transplants (ESOTWIN): 90 paired single-lung transplants from the same donor

BACKGROUND: Despite its reduced benefit for a single recipient, the transplantation of two single-lung allografts as opposed to one bilateral lung transplant has the indisputable advantage of maximizing the number of patients that benefit from a single donor. METHODS: In the period 1997 to 1999, 90 paired single-lung transplants (SLTx) from 45 donors were performed in 16 lung centers in Eurotransplant, with a complete follow-up of 1 year. RESULTS: No significant differences between left- and right-lung allograft recipients were observed regarding age, sex, primary disease, number of human leukocyte antigen mismatches, cold ischemic time, and donor-to-recipient cytomegalovirus match. Early posttransplant outcome, as assessed by oxygenation index at 12, 24, and 48 hr, also did not differ significantly, and there were no differences in time to extubation and time spent in the intensive care unit. In the first month, six left- and three right-lung allograft recipients died. Bronchiolitis obliterans syndrome developed in 5 of 39 left-lung and 10 of 42 right-lung allograft recipients. If the retrieval team was different from the transplanting team, a significantly worse 1-year posttransplant survival rate was seen in patients who underwent left SLTx compared with those who underwent right SLTx (62% vs. 92%, respectively; P=0.04). CONCLUSIONS: More fatal posttransplant complications occur in patients undergoing left SLTx compared with right SLTx. A less optimistic assessment of the left lung by the not-implanting retrieval team is warranted.     

Probleme und Ansätze zur Anlage und Bewertung von Therapiestudien bei Kopfschmerzpatienten

A review of studies on migraine therapy shows a large heterogeneity in the clinical evaluation of different drugs and behavioral approaches. The percentages of efficacy of beta-blockers or behavior therapy (relaxation, biofeedback) range from 30% to 80%. Methodological differences from one author to another in the design and conduct of the studies might be causes of this variation. For both clinical practice and empirical research (e.g. replication of treatment studies) an uniformity in the application of different methodological techniques should be sought. This paper discusses the influence of methodological aspects on the success rates of treatment for chronic headaches, especially migraine. We question the present practice of applying traditional group experiments in headache research. Double-blind and placebo-controlled studies are often required, but this demand often cannot be niet in empirical reality because of the individuality of the patient or the heterogeneity of the symptoms. We discuss some alternative approaches that could be used in empirical research on headache therapy. The application of single-case experiments as well as methods of time-series analysis are described as a more appropriate approach to the evaluation of studies on chronic headaches.