Prediction of late complications of femoral neck fractures by scintigraphy

Summary A prospective study was undertaken to determine the value of scintigraphy in predicting nonunion or necrosis of the femoral head following femoral neck fractures. Scintigraphy was carried out in 49 patients before operation and in 37 one week after operation; in 18 it was done before and after operation. The uptake of isotope was estimated visually as either normal or reduced compared to the opposite side. All the patients were followed up for at least 2 years. The results indicate that pre-operative bone scintigraphy is useful in elderly patients to predict nonunion and necrosis, and therefore is recommended to select those patients who will benefit from primary arthroplasty instead of fixation of the fracture.

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Résumé Etude prospective de la valeur de la scintigraphie dans la prévision des complications tardives après fracture du col du fémur. Une scintigraphie a été réalisée avant l'intervention chez 49 patients et une semaine après chez 37 autres; dans 18 cas elle a été faite avant et après l'opération. La concentration d'isotopes a été évaluée visuellement et considérée comme normale ou comme diminuée par comparaison avec la hanche opposée. Tous les patients ont été suivis deux ans au moins. Les résultats permettent de penser que la scintigraphie pré-opératoire est un examen utile chez les sujets âgés présentant une fracture du col avec déplacement pour prédire pseudarthrose et nécrose de la tête fémorale. Elle permet de choisir les patients pour lesquels l'arthroplastie est préférable à l'ostéosynthèse.

     

Linoleic acid and dihomogammalinolenic acid inhibit leukotriene B4 formation and stimulate the formation of their 15-lipoxygenase products by human neutrophilsin vitro. Evidence of formation of antiinflammatory compounds

Enzymatic transformation of then-6 polyunsaturated fatty acid (PUFA) arachidonic acid (AA) by the 5-lipoxygenase (LO) enzyme results in the formation of leukotrienes (LTs) including leukotriene B₄ (LTB₄), which is a potent mediator of inflammation. The purpose of the present study was to determine the effect of othern-6 fatty acids on the formation of LTB₄ by human neutrophils and to determine if thesen-6 fatty acids themselves may be transformed into products with antiinflammatory capacity. Purified neutrophils isolated from heparinized human venous blood were incubated with A23187 (5 M) and different concentrations (0–100 M) of then-6 fatty acids linoleic acid (LA) and dihomo-gammalinolenic acid (DGLA). LO products were determined by use of quantitative reversed-phase high performance liquid chromatography (RP-HPLC) and mass spectrometry. The formation of LTB₄ was dose dependently inhibited by both LA (IC₅₀=45 M) and DGLA (IC₅₀=40M). This inhibition of LTB₄ formation was associated with a dose dependent increase in the formation of the respective 15-LO products of LA (13-hydroxy-octadecadienoic acid; 13-HODE) and DGLA (15-hydroxy-eicosatrienoic acid; 15-HETrE). To determine whether these 15-LO products themselves might inhibit LTB₄ formation, neutrophils were incubated with 13-HODE and 15-HETrE. Both 15-LO products lead to a dose-dependent inhibition of LTB₄ formation (IC₅₀=7.5 M and IC₅₀=0.2 M). For comparison the 15-LO product of AA, 15-hydroxy-eicosatetraenoic acid (15-HETE), also inhibited LTB₄ formation (IC₅₀=0.75 M). The results show that the addition of LA and DGLA to neutrophils results in an inhibition of LTB₄ formation and simultaneously to the formation of 13-HODE and 15-HETrE, that also inhibits LTB₄ formation. Therefore, dietary supplementation or topical application of LA and DGLA or preferentially their respective 15-LO products, may have a therapeutic effect in inflammatroy diseases in which LTs are suspected to play a pathogenic role.     

Stem cell therapy for neurodegenerative diseases: the issue of transdifferentiation

In the past few years research on stem cells has exploded as a tool to develop potential therapies to treat incurable neurodegenerative diseases. Stem cell transplantation has been effective in several animal models, but the underlying restorative mechanisms are still unknown. Several events such as cell fusion, neurotrophic factor release, endogenous stem cell proliferation, and transdifferentiation (adult cell acquisition of new unexpected identities) may explain therapeutic success, in addition to replacement of lost cells. This issue needs to be clarified further to maximize the potential for effective therapies. Preliminary stem transplantation trials have already been performed for some neurodegenerative diseases. There is no effective pharmacological treatment for amyotrophic lateral sclerosis, but recent preliminary data both in experimental and clinical settings have targeted it as an ideal candidate disease for the development of stem cell therapy in humans. This review summarizes recent advances gained in stem cell research applied to neurodegenerative diseases with a special emphasis to the criticisms put forward.     

Pharmacological manipulation of cardiovascular responses to lower body negative pressure

To evaluate influences on blood volume distribution, atrial natriuretic peptide concentrations (ANP) and thoracic and leg electrical impedance at 2.5 (TI_2.5 and LI_2.5, respectively) and 100 kHz (TI₁₀₀ and LI₁₀₀, respectively) were monitored during administration of ketanserin, noradrenaline and trimetaphan combined with lower body negative pressure (LBNP) in 12 subjects. Administration of clinically relevant doses of ketanserin alone did not induce changes in mean arterial pressure (MAP) or in the central blood volume, as electrical impedance and ANP concentrations did not change. During continued infusion of ketanserin an increase in MAP from a mean of 90 (range 83–108) to 113 (range 98–138) mmHg was induced by noradrenaline, but TI_2.5 [mean 45.6 (range 39.3–54.2)] and TI₁₀₀ [mean 33.8 (range 27.5–38.5) ] remainded stable until ganglionic blockade and LBNP were applied, when they increased by a mean of 3.1 (range 2.0–6.1) and 2.7 (range 1.1–4.2) , respectively (P < 0.05). Conversely, LI_2.5 [mean 79.6 (range 74.1–89.4)] and LI₁₀₀ [mean 56.7 (range 52.4–63.3) ] decreased by a mean of 3.2 (range 1.2–8.0) and 2.3 (range 0.9–3.9) ANP from a mean of 27.7 (range 10.2–62.7) to 12.7 (range 7.1–27.5) pmol· 1^–1 and MAP fell to a mean of 62 (range 42–70) mmHg (P < 0.05). The heart rate was a mean of 75 (range 69–77) beats -min-' and did not change until LBNP, when it increased to a mean of 102 (range 78–104) beats · min^–1, as presyncopal symptoms appeared. The data indicated that serotonergic blockade by ketanserin and -sympathetic stimulation by noradrenaline did not affect blood volume distribution in normal humans, but that ganglionic blockade combined with LBNP reduced the central blood volume as leg volume increased; during central hypovolaemia tachycardia induced by ganglionic blockade did not prevent the fall in MAP, and thereby the appearance of presyncopal symptoms.     

Human pancreatic adenocarcinoma line Capan-1 in tissue culture and the nude mouse: morphologic, biologic, and biochemical characteristics

Human pancreatic ductal adenocarcinoma line Capan-1 was studied in tissue culture and the nude mouse. In tissue culture, the neoplastic cells grew as large epithelial-like mucin-producing cells. Subcutaneous and intraperitoneal transplantation of neoplastic cells into nude mice resulted in tumor formation characterized by marked invasiveness and distant metastases. Histologically, the tumor appeared as a well-differentiated mucin-producing adenocarcinoma morphologically resembling the tumor of origin. Chromosomal analysis showed a human karyotype with a chromosome number between 51-61. Lactate dehydrogenase and beta 2-microglobulin used as tumor markers were present in both tissue culture and the serum of tumor-bearing mice. The neoplasm, which was characterized by an increased level of cAMP, had lost completely the ability to respond to secretin stimulation. The tumor grown in the nude mouse was resistant to treatment with 5-fluorouracil, behavior identical to that of the original tumor. Diphtheria toxin resulted in complete tumor destruction. Because Capan-1 tumor grown in the nude mouse shows morphologic, biologic, and biochemical characteristics similar to the tumor of origin, it may be an invaluable tool in furthering understanding of the biology of human pancreatic cancer.     

Sensitivity of FL cells to polio- and adenoviruses

Summary Poliovirus plaque counts on the FL strain of human amnion cells were almost double the counts on rhesus monkey kidney for the same virus preparation, repeatedly assayed over more than six months. FL cells gave more consistent results in virus assay than monkey kidney cells. Plaque counts obtained with FL cells were 2 1/2 to 5 times higher than those obtained with HeLa, Chang's conjunctiva and Detroit-6 cells.Using the chick embryo-adapted MEF-1 strain of poliovirus, FL cells and primary human amnion cells reacted similarly in respect to plaque count and morphology, while no distinct plaques were seen on monkey kidney or HeLa monolayers under comparable conditions. For infectivity assays of adenovirus suspensions based on cytopathogenic effect, FL cells were found suitable, although no plaque formation was obtained.Aided by American Cancer Society Grant E-82 and a grant from the National Foundation.     

Quantitation of Passive Cutaneous Anaphylaxis (PGA) by Using Radiolabelled Antigen

The major problem of detecting reaginic antibody by passive cutaneous anaphylaxis IPCA) is the quantitation of the dye reaction. Radiolabelled antigen was used in an attempt to quantitate the PCA reaction (Radio-PCA). Antisera containing reaginic antibody against human serum albumin (HSA) were produced in rabbits. These antisera were injected into normal rabbit skin in different dilutions. Twenty-four hours later BSA was injected intravenously either with Evans Blue or as 125-1-HSA. Radioactivity found in antibody-containing skin was significantly higher than in control specimens containing saline or normal rabbit serum, as low as antiserum dilutions of 1:1,000. Compared with the Evans Blue technique Radio-PCA was able to distinguish quantitatively between different antiserum dilutions at a higher level of statistical significance.     

A Stochastic Nonlinear Autoregressive Algorithm Reflects Nonlinear Dynamics of Heart-Rate Fluctuations

Current methods for detecting nonlinear determinism in a time series require long and stationary data records, as most of them assume that the observed dynamics arise only from the internal, deterministic workings of the system, and the stochastic portion of the signal (the noise component) is assumed to be negligible. To explicitly account for the stochastic portion of the data we recently developed a method based on a stochastic nonlinear autoregressive (SNAR) algorithm. The method iteratively estimates nonlinear autoregressive models for both the deterministic and stochastic portions of the signal. Subsequently, the Lyapunov exponents (LE) are calculated for the estimated models in order to examine if nonlinear determinism is present in the deterministic portion of the fitted model. To determine if nonlinear dynamic analysis of heart-rate fluctuations can be used to assess arrhythmia susceptibility by predicting the outcome of invasive cardiac electrophysiologic study (EPS), we applied the SNAR algorithm to noninvasively measured resting sinus-rhythm heart-rate signals obtained from 16 patients. Our analysis revealed that a positive LE was highly correlated to a patient with a positive outcome of EPS. We found that the statistical accuracy of the SNAR algorithm in predicting the outcome of EPS was 88% (sensitivity=100%, specificity=75%, positive predictive value=80%, negative predictive value=100%, p=0.0019). Our results suggest that the SNAR algorithm may serve as a noninvasive probe for screening high-risk populations for malignant cardiac arrhythmias. © 2002 Biomedical Engineering Society. PAC2002: 8719Hh, 0545Tp, 8710+e