Severe progressive deformities after limb lengthening in type-II fibular hemimelia

Until recently the accepted treatment of choice for severe type-II fibular hemimelia has been Syme's or Boyd's amputation. The alternative of distraction lengthening using the Ilizarov technique is now available. We report three patients (four limbs) with type-II fibular hemimelia who were treated by the Ilizarov technique and followed up for two to six years. Severe progressive procurvatum and valgus deformity of the tibia and valgus deformity and lateral subluxation of the ankle were found in all four limbs. Multiple additional soft-tissue and bony surgery was necessary. In view of these problems we feel that reappraisal of the indications for lengthening in type-II fibular hemimelia is necessary.     

Genetic determinants of p53-induced apoptosis and growth arrest

Previous studies have suggested that expression of p53 in cancer cells can result in either growth arrest or apoptosis. Accordingly, expression of p53 in a series of colorectal cancer cell lines yielded growth arrest in some lines (A-lines) and apoptosis in others (D-lines). To investigate the basis of this difference, we evaluated the role of p21WAF1/Cip1, a known mediator of p53-induced growth arrest. Inactivation of p21 by homologous recombination converted an A-line to a D-line, suggesting that p21 could protect cells from apoptosis. However, examination of p53-induced p21 expression in naturally occurring D-lines and A-lines demonstrated that the induction of p21 could not account for the differential response to p53. Moreover, when a D-line was fused to an A-line, the resulting hybrid cells underwent apoptosis in response to p53, indicating that the apoptosis pathway was dominant over the growth arrest pathway. Therefore, the apoptotic response to p53 in colorectal cancer cells is modulated by at least two factors: p21-mediated growth arrest that can protect cells from apoptosis in A-cells, and trans-acting factors in D-cells that can overcome this protection, resulting in cell death.     

Sesquiterpenoids of the drimane class from a sponge of the genus Dysidea

Ten sesquiterpenoids, including seven new ones, have been isolated from an undescribed sponge of the genus Dysidea. Compounds 1-8 are sesquiterpenoids of the drimane class, while 9 and 10 are 12-norsesquiterpenoids of the same structural class. The structures of novel compounds have been determined by combined spectroscopic methods. These compounds exhibited moderate antimicrobial and enzyme inhibitory (Na+/K(+)-ATPase and PLA2) activities.     

Viral interleukin 10 (IL-10), the human herpes virus 4 cellular IL-10 homologue, induces local anergy to allogeneic and syngeneic tumors

After the cloning of murine cytokine synthesis inhibitory factor, it was recognized that a homologous open reading frame was encoded within the Epstein-Barr virus (human herpes virus 4). This viral protein has now been termed viral interleukin 10 (vIL-10) to reflect its protein sequence homology to "cellular" IL-10 (cIL-10, either murine or human IL-10). It is now widely accepted that vIL-10 shares many functions with cIL-10, principally, the ability to enhance survival of newly infected B cells and to diminish the production of IFN-gamma and IL-2 during ongoing immune reactions. The immunomodulatory effect of locally secreted vIL-10 and murine IL-10 (mIL-10) was examined in tumor models using CL8-1 (a BL6 melanoma cell line transfected with the H-2Kb class I gene) in syngeneic animals. Although parental BL6 tumor cells grow in immunocompetent syngeneic hosts, CL8-1 are rejected. To achieve local secretion of vIL-10, we generated vIL-10 retroviral vectors. While nontransduced CL8-1 cells (1 x 10(4)) failed to grow when injected intradermally in C57BL/6 mice, CL8-1 cells (1 x 10(4)) transduced with vIL-10 formed palpable tumors and eventually killed 80% of injected animals. Suppression of tumor rejection was also noted when CL8-1 tumors with or without vIL-10 transfection were admixed with syngeneic vIL-10-transfected fibroblasts and inoculated. Since the in vitro proliferation of the tumor was not altered after transduction with the vIL-10 gene and injection of vIL-10-transduced CL8-1 does not affect the rejection of nontransduced CL8-1 inoculated at a distant site, local vIL-10 secretion appears to suppress the process of immune rejection of the target cells in a dose-dependent manner. Similar results were observed for the H-2b MCA105 sarcoma tumor model in allogeneic BALB/c mice (H-2d). Although all animals that received nontransfected MCA105 rapidly rejected these tumors, MCA105 sarcomas transfected with vIL-10 remained palpable for up to 37 d. The local immunosuppressive effect of gene-delivered vIL-10 could be neutralized by anti-human IL-10 monoclonal antibody or could be reversed by the systemic administration of IL-2 or IL-12. In marked contrast, mIL-10 transfection of CL8-1 significantly suppressed tumor growth and frequently led to the rejection of tumor. Similar results were obtained for the murine tumor cell lines MCA102.(ABSTRACT TRUNCATED AT 400 WORDS)     

Evolution of the cranial computed tomography scan in child abuse

Computed tomography (CT) scans obtained at the time of clinical presentation have occasionally been reported to be normal in children with history and findings of significant abusive head injury. We have retrospectively observed abnormalities in "normal" scans of some similar children. We have also seen abnormalities develop on serial scanning. To determine how frequently these situations occur, we reviewed charts of 34 children with a final diagnosis of child abuse who also had cranial CT scans performed. Their CT scans were retrospectively reviewed by a pediatric radiologist. Eleven (11/34) CT scans had initially been interpreted as normal. Four (4/11) of these had been reinterpreted during the hospitalization as abnormal, affecting medical (1) and legal (3) outcome. Repeat scanning in three of the remaining seven resulted in surgical drainage of a subdural effusion (1) and affected legal outcome (2). Four of the seven initial scans felt normal throughout the hospitalizations were judged abnormal on retrospective review. This evaluation was confirmed in the two rescanned. Initial CT interpretation most often failed to appreciate changes in parenchymal density and small amounts of falcine or cortical subdural blood. Subsequent scans also showed evolving effusions and infarcts. Changes were noted in 1 1/2 to 5 days. The CT scan frequently shows subtle changes in the immediate posttrauma period. If the child does not recover promptly, subsequent scans frequently result in significant changes in clinical and legal management.     

Localization of atrial natriuretic peptide receptors in the rat tongue and hard palate

The effect of a naturally occurring plant phenolic constituent (the acylphloroglucinol derivative, jensenone, derived from Eucalyptus jensenii) on the food intake of two folivorous marsupials, the common ringtail (Pseudocheirus peregrinus) and the common brushtail possum (Trichosurus vulpecula) was studied. When fed diets containing varying concentrations of jensenone, both species regulated their intake of jensenone so as not to exceed a ceiling intake. This ceiling was about twice as high for common ringtails as for common brushtails from northern Australia. Southern populations of common ringtails showed greatly reduced capacities to tolerate jensenone. When common brushtails were injected (0.5 mg.kg-0.75 body mass) with ondansetron (a selective antagonist of serotonin 5HT3 receptors), they ate significantly more jensenone than animals injected with physiological saline. The same pattern was observed when common ringtails were fed diets containing both jensenone and ondansetron (0.0035 mg.g-1 wet mass of diet). Ondansetron injection had no effect on food intake when the food did not contain jensenone while the addition of higher doses of ondansetron to diets of common ringtails very slightly reduced food intakes of a non-jensenone diet. When common brushtails were given 50 mg of jensenone by gastric lavage, their average subsequent intake of dietary jensenone matched the difference between the daily threshold and the dose given, although the response of individuals was highly variable. Lavage with water alone had no effect on subsequent jensenone intake compared with the pre-dose period. We interpret these results as evidence that the antifeedant effects of jensenone and related compounds are partly mediated by serotonin action on 5HT3 receptors most likely via "nausea" to condition a food aversion.     

Sleep-induced breathing instability. University of Wisconsin-Madison Sleep and respiration Research Group

We present a view of the neuromechanical regulation of breathing and causes of breathing instability during sleep. First, we would expect transient increases in upper airway resistance to be a major cause of transient hypopnea. This occurs in sleep because a hypotonic upper airway is more susceptible to narrowing and because the immediate excitatory increase in respiratory motor output in response to increased loads is absent in non-REM sleep. Secondly, sleep predisposes to an increased occurrence of ventilatory "overshoots", in part because abruptly changing sleep states cause transient changes in upper airway resistance and in the gain of the respiratory controller. Following these ventilatory overshoots, breathing stability will be maintained if excitatory short-term potentiation is the prevailing influence. On the other hand, apnea and hypopnea will occur if inhibitory mechanisms dominate following the ventilatory overshoot. These inhibitory mechanisms include: a) hypocapnia-if transient, will inhibit carotid chemoreceptors and cause hypopnea, but if prolonged will inhibit medullary chemoreceptors and cause apnea; b) a persistent inhibitory effect from lung stretch; c) baroreceptor stimulation, from a transient rise in systemic blood pressure immediately following termination of apnea or hypopnea may partially suppress the accompanying hyperpnea; d) depression of central respiratory motor output via prolonged brain hypoxia. Once apneas are initiated, reinitiation of inspiration is delayed even though excitatory stimuli have risen well above their apneic thresholds, and these prolonged apneas are commonly accompanied by tonic EMG activation of expiratory muscles of the chest wall and upper airway.     

Sturcture and function of the mononuclear phagocytic system (MPS) in chronic rhinosinusitis. A light and electron microscopic investigation (author's transl)

Neither the concept of the Reticulo-Endothelial-System (RES) Aschoff's (1924) nor that of the Reticulo-Histiocyte-System (RHS) provides a satisfactory framework into which the present knowledge of the phagocytic mononuclear cells can be fitted. Current knowledge concerning morphology, histochemistry (peroxydase and esterase activity), immunology (specific surface antigens, receptors on the cell membranes), function (immune phagocytosis, pinocytosis), kinetics (3H-thymidine labelling) and culture makes it possible to place all highly phagocytic mononuclear cells and their precursors in one system, which is called the Mononuclear-Phagocytic-System (MPS) (Langevoort, Cohn, Hirsch, Humphrey, Spector, van Furth, 1969). Kinetic studies with labelled cells have shown, that mononuclear phagocytes originate from precursor cells in the bone marrow (stem cell leads to monoblasts leads to promonocytes), than are circulating in the peripheral blood as monocytes and are transformed to tissue macrophages entering tissues. The MPS comprises following cells in following organs: connective tissue (histiocytes resp. macrophages); liver (Kupffer-cells); lung (alveolar macrophages); lymph nodes (free and fixed macrophages); bone marrow (macrophages); serous cavities (pleural and peritoneal macrophages); bone tissue (osteoclasts?); nervous system (microglial cells) (SEE Table 1). The reticular cells, endothelial cells and fibroblasts (fibrocytes) can therefore not be included in the MPS. Besides differences in morphology, histochemistry and function, they derive from mesenchymal cells and not from the bone marrow as the MPS. The present investigation demonstrates the structure and significance of the MPS in various kinds of chronic-specific and non-specific rhinosinusitis. On semithin sections two kinds of macrophages can be distinguished light-microscopically: 1. Larger macrophages with many phagosomes (storage cells) (Fig. 1A), which can exhibit sometimes a ring-shape on sections embracing greater parts of the interstitium (Fig. 1B). Such forms are mainly found in chronic (maxillary) sinusitis and are interpretated as "scavenger" macrophages. 2. The second type consists of smaller macrophages with extremely ruffling of the cell surface, which is interpretated as an expression of highly (specific?) stimulated states. These later macrophages can be seen mainly in edematous nasal polyps, which might be caused by allergic reactions of the anaphylactic type. The fine structure of the phagocytes is to some extent dependent on the actual development and functional state: there are "immature" macrophages, which are practically indistinguishable from blood monocytes (Fig. 2A); some of them can be stimulated and can therefore show many surface foldings and projections (Fig. 2B). The "mature" macrophage shows a well developed Golgi-area and many secondary lysosomes (Fig. 3). The storage type of the macrophages, which can predominate in some cases of chronic maxillary sinusitis, is characterized by many electron-lucent vacuoles (Fig. 4)...