Osteosarcomatosis

A review of the 690 cases of osteosarcoma in the radiographic file of the Armed Forces Institute of Pathology revealed 29 cases of "osteosarcomatosis" (multiple skeletal sites of osteosarcoma). Fifteen of these patients were 18 years old and under and manifested rapidly appearing, usually symmetric, sclerotic metaphyseal lesions. The remaining 14 patients were more than 18 years old and had fewer, asymmetric sclerotic lesions. In most patients (28 of 29), a radiographically dominant skeletal tumor was seen. Pulmonary metastases occurred in the majority of patients and were detected at the same time as the bone lesions. These 29 patients were studied with regard to demographic data and skeletal distribution and radiographic appearance of their lesions. As a result of the findings, a metastatic origin from a primary dominant osteosarcoma is favored over a multifocal origin as the basis for osteosarcomatosis. Osteosarcomatosis is more commonly encountered in the mature skeleton than has been previously recognized.     

Traumatic rectal injuries

The authors review the cases of traumatic rectal injuries admitted to the Emergency Service of the "Hospital das Clínicas", University of S?o Paulo Medical School, during the period of July 1981 to July 1988. Forty-five patients (62.5%) had their injuries due to gunshot, 14 (19.4%) due to foreign bodies on the rectum, 10 (13.8%) due to blunt trauma and 3 (4.1%) due to stab wounds. The intraperitoneal rectum was injured in 32 patients (44.4%) and extraperitoneal portion of the rectum in 40 patients (55.5%). On the intraperitoneal injuries the management adopted were simple suture (14 patients), associated with a colostomy (17 patients) and in one patient the Hartmann procedure was adopted. On the extraperitoneal wounds the management adopted were rectal repair (when feasible), colostomy, distal washout and drainage. The complications rate was 27.8%, and from them, the majority (70%) were related to infectious nature. Seven patients died (9.7%), four of them as a consequence of sepsis. The morbidity and mortality of the rectal injuries were closed related to infectious complications as a consequence of late diagnosis. For this reason, the authors consider that all efforts should be employed to establish the prompt diagnosis.     

Legionella micdadei prosthetic valve endocarditis

Summary Legionella usually causes pneumonia, but occasionally is in the differential diagnosis of culture negative endocarditis which sometimes involves prosthetic heart valves.Legionella prosthetic valve endocarditis is nearly always due toLegionella pneumophila and its clinical presentation is indistinguishable from other causes of prosthetic valve endocarditis. Diagnosis ofLegionella prosthetic valve endocarditis is by recovery of the organism from the blood, demonstration or isolation of the organism from the prosthetic heart valve, or by persistently highLegionella titers which are extremely elevated in prosthetic valve endocarditis compared toLegionella pneumonia. We believe this is the first case reported of prosthetic valve endocarditis caused byLegionella micdadei, and the first case ofLegionella prosthetic valve endocarditis with microscopic hematuria.

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Klappenprothesenendokarditis durchLegionella micdadei

Zusammenfassung Gelegentlich muß der PneumonieerregerLegionella in der Differentialdiagnose der kulturnegativen Endokarditis berücksichtigt werden, die manchmal auch Klappenprothesen befällt. Die Klappenprothesenendokarditis wird bei Legionellenätiologie fast ausschließlich durchLegionella pneumophila verursacht; in ihrem klinischen Erscheinungsbild ist sie von Klappenprothesenendokarditiden anderer Genese nicht zu unterscheiden. Die Diagnose wird durch Erregernachweis im But, in der entfernten Klappe oder durch sehr hoheLegionella-Titer nachgewiesen, die im Vergleich zur Legionellenpneumonie extrem stark erhöht sind. Wir gehen davon aus, daß unsere Fallmitteilung die erste Publikation einer Klappenprothesenendokarditis durchLegionella micdadei und der erste Fall mit Mikrohämaturie ist.

     

The selection and use of cephalosporins: a review

Cephalosporins are among the most frequently prescribed antibiotics as a result of their broad spectrum of microbiologic activity, favorable pharmacokinetics, low incidence of adverse reactions, and proven clinical efficacy for a wide variety of infections. Cephalosporins differ in their gram-positive, gram-negative, and anaerobic spectra, serum half-lives, penetration of the cerebrospinal fluid, and resistance to beta-lactamases. The first-generation and some second-generation agents maintain excellent activity against streptococci and staphylococci, while the third-generation agents have expanded gram-negative coverage. Two third-generation cephalosporins, ceftazidime and cefoperazone, are active against Pseudomonas. Ceftizoxime has become the workhorse third-generation cephalosporin. The fourth-generation agent cefepime provides excellent activity against gram-positive and gram-negative pathogens, including antibiotic-resistant Enterobacteriaceae. A major dilemma facing the practitioner is how to select the "right" cephalosporin for a particular patient, as no one drug will satisfy all clinical needs. This review describes a practical approach to selecting an appropriate cephalosporin for common infectious disease problems.     

Facilitation by arachidonic acid of acetylcholine release from the rat hippocampus

We investigated the effect of arachidonic acid (AA) on the release of [3H]acetylcholine ([3H]ACh) from the rat hippocampus. AA (3-30 microM) increased the basal tritium outflow and the field-electrically evoked release of [3H]ACh from hippocampal slices in a concentration-dependent manner. AA (30 microM) produced a 69+/-7% facilitation of the evoked and a 36+/-3% facilitation of basal tritium outflow. The effect of AA (30 microM) on the evoked tritium release was prevented by bovine serum albumin (BSA, 1%), which quenches AA, and was unaffected by the cyclooxygenase inhibitor, indomethacin (100 microM), and the lipooxygenase inhibitor, nordihydroguaiaretic acid (50 microM). Phospholipase A2 (PLA2, 2 U/ml), an enzyme that releases AA from the sn-2 position of phospholipids, mimicked the facilitatory effect of AA on the evoked tritium release (86+/-14% facilitation), an effect prevented by BSA (1%). The PLA2 activator, melittin (1 microM), enhanced the evoked tritium release by 98+/-11%, an effect prevented by the PLA2 inhibitor, arachidonyl trifluromethylketone (AACOCF3, 20 microM), and by BSA (1%). AA (30 microM), but not arachidic acid (30 microM), also facilitated (72+/-9%) the veratridine (10 microM)-evoked [3H]ACh release from superfused hippocampal synaptosomes, whereas PLA2 (2 U/ml) and melittin (1 microM) caused a lower facilitation (46+/-1% and 38+/-5%, respectively). The present results show that both exogenously added and endogenously produced AA increase the evoked release of [3H]ACh from rat hippocampal nerve terminals. Since muscarinic activation triggers AA production and we now observed that AA enhances ACh release, it is proposed that AA may act as a facilitatory retrograde messenger in hippocampal cholinergic muscarinic transmission as it has been proposed to act in glutamatergic transmission.     

Kainate receptors coupled to G(i)/G(o) proteins in the rat hippocampus.

Kainate receptors are a subtype of ionotropic glutamate receptors, permeable to cations and thus expected to have an excitatory depolarizing action on neurons. However, kainate receptor activation inhibits gamma-aminobutyric acid release in the hippocampus through activation of protein kinase C in a pertussis toxin-dependent manner, suggesting a coupling of kainate receptors to G proteins. Thus, we directly investigated the G protein coupling of kainate receptors in the rat hippocampus by using a selective kainate receptor agonist, [(3)H](2S,4R)-4-methylglutamate ([(3)H]MGA). [(3)H]MGA bound to a single site to hippocampal membranes with a K(D) value of 32 nM and a B(max) value of 1024 fmol/mg protein. This binding likely represents kainate receptors because it was displaced by domoate (K(i) = 4 nM), kainate (K(i) = 11 nM), and 6-cyano-7-nitroquinoxaline-2,3-dione (K(i) = 1.4 microM), but not by alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (K(i) > 10 microM), (RS)-alpha-methyl-4-phosphonophenylglycine (K(i) > 10 microM), or (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (K(i) > 10 microM). Guanylylimidodiphosphate (30 microM), which uncouples all G protein-coupled receptors, shifted to the right the saturation curve of [(3)H]MGA (K(D) = 133 nM). This effect was mimicked by pretreatment of hippocampal membranes with modifiers of G(i)/G(o) proteins [30 microM N-ethylmaleimide (K(D) = 98 nM) or 25 microgram/ml pertussis toxin (K(D) = 95 nM)] but not by a modifier of G(s) proteins [50 microgram/ml cholera toxin (K(D) = 32 nM)]. Treatment of solubilized hippocampal membranes with pertussis toxin (25 microgram/ml) decreased [(3)H]MGA affinity (K(D) = 105-113 nM), which was recovered by reconstitution of these pretreated solubilized hippocampal membranes with G(i)/G(o) proteins (K(D) = 41-76 nM). These results indicate that hippocampal kainate receptors are coupled to G(i)/G(o) proteins.     

Pharmacological evaluation of ricinine, a central nervous system stimulant isolated from Ricinus communis.

The extract of the pericarp of castor bean (Ricinus communis) showed some typical central nervous system stimulant effects when administered to mice. The animals became exophthalmic, presented tremors and clonic seizures and died a few minutes after receiving larger doses of the extract. At lower doses the extract improved memory consolidation and showed some neuroleptic-like properties, such as a decrease in exploratory behavior and catalepsy. The memory-improving effect and the seizure-eliciting properties of the extract were also observed with the administration of ricinine, a neutral alkaloid isolated from the extract. However, the neuroleptic-like properties of the extract were not observed with ricinine. As the therapeutic index of ricinine is of the order of 200, the compound may be considered as a promising cognition-enhancing drug that may be used for the treatment of human amnesias.     

Evidence for high-affinity binding sites for the adenosine A2A receptor agonist [3H] CGS 21680 in the rat hippocampus and cerebral cortex that are different from striatal A2A receptors

The binding of the adenosine A_2A receptor selective agonist 2-[4-(2-p-carboxyethyl) phenylamino]-5-N-ethylcarboxamidoadenosine (CGS 21680) to the rat hippocampal and cerebral cortical membranes was studied and compared with that to striatal membranes. [³H] CGS 21680, in the concentration range tested (0.2–200 nM), bound to a single site with a K _d of 58 nM and a B _max of 353 fmol/mg protein in the hippocampus, and with a K _d of 58 nM and a B _max of 264 fmol/mg protein in the cortex; in the striatum, the single high-affinity [³H] CGS 21680 binding site had a K _d of 17 nM and a B _max of 419 fmol/mg protein. Both guanylylimidodiphosphate (100 M) and Na⁺ (100 mM) reduced the affinity of [³H] CGS 21680 binding in the striatum by half and virtually abolished [³H] CGS 21680 binding in the hippocampus and cortex. The displacement curves of [³H] CGS 21680 binding with 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), N ⁶-cyclohexyladenosine (CHA), 5-N-ethyl-carboxamidoadenosine (NECA) and 2-chloroadenosine (CADO) were biphasic in the hippocampus and cortex as well as in the striatum. The predominant [³H]CGS 21680 binding site in the striatum (80%) had a pharmacological profile compatible with A_2A receptors and was also present in the hippocampus and cortex, representing 10–25% of [³H]CGS 21680 binding. The predominant [³H]CGS 21680 binding site in the hippocampus and cortex had a pharmacological profile distinct from A_2A receptors: the relative potency order of adenosine antagonists DPCPX, 1,3-dipropyl8-{4-[(2-aminoethyl)amino]carbonylmethyloxyphenyl} xanthine (XAC), 8-(3-chlorostyryl) caffeine (CSC), and (E)-1,3-dipropyl-8-(3,4-dimethoxystyryl)-methylxanthine (KF 17,837) as displacers of [³H] CGS 21680 (5 nM) binding in the hippocampus and cerebral cortex was DPCPX > XAC CSC KF 17,837, and the relative potency order of adenosine agonists CHA, NECA, CADO, 2-[(2-aminoethylamino)carbonylethylphenylethylamino]-5-N-ethylcar-boxamidoadenosine (APEC), and 2-phenylaminoadenosine (CV 1808) was CHA NECA CADO > APEC CV1808 > CGS 21680. In the presence of DPCPX (20 nM), [³H] CGS 21680 (0.2-200 nM) bound to a site (A_2A-like) with a K _d of 20 nM and a B _max of 56 fmol/mg protein in the hippocampus and with a K _d of 22 nM and a B _max of 63 fmol/mg protein in the cortex. In the presence of CSC (200 nM), [³H]CGS 21680 (0.2–200 nM) bound to a second high-affinity site with a K _d of 97 nM and a B _max of 255 fmol/mg protein in the hippocampus and with a K _d of 112 nM and a B _max of 221 fmol/mg protein in the cortex. Two pharmacologically distinct [³H]CGS 21680 binding sites were found in synaptosomal membranes of the hippocampus and cortex and in the striatum, one corresponding to A_2A receptors and the other to the second high-affinity [³H]CGS 21680 binding site. In contrast, the pharmacology of [³H]CHA binding was similar in synaptosomal membranes of the three brain areas. The present results establish the existence of at least two high-affinity [³H]CGS 21680 binding sites in the CNS and demonstrate that the [³H]CGS 21680 binding site predominant in the hippocampus and cerebral cortex has different binding characteristics from the classic A_2A adenosine receptor, which predominates in the striatum.     

Role of mesenchymal-epithelial interactions in mammary gland development

The mammary gland is a hormone-target organ derived from epidermis and develops as a result of reciprocal mesenchymal-epithelial interactions. The induction of mammary differentiation from indifferent epidermal cells by mammary mesenchyme implies induction of the complement of hormone receptors characteristic of normal mammary epithelium in cells of the epidermis. Considering the facts that mammary epithelial differentiation is induced by mammary mesenchyme and that certain aspects of hormone response (androgen-induced mammary regression) are inextricably linked to mesenchymal-epithelial interactions, it is evident that the biology of the mammary gland arises from and is maintained via cell-cell interactions. As a corollary, perturbation of stromal-epithelial interactions in adulthood may play a role in mammary carcinogenesis and in turn may provide opportunities for differentiation therapy.