Use of antibiotic and analgesic drugs during lactation.

During lactation, multiple situations can arise that require maternal pharmacological treatment. Because of the many health advantages of human milk to infants, breast feeding should be interrupted only when the needed drug might be harmful to the nursing child and exposure via the breast milk will be sufficient to pose a risk. Since the majority of drugs have not been shown to cause adverse effects when used during lactation, and even temporary interruption of breast feeding can be difficult for the nursing dyad, decisions regarding maternal medication use during breast feeding should be based on accurate and up-to-date information. This article reviews available data on the most commonly used antibiotics and analgesics. The use of most antibiotics is considered compatible with breast feeding. Penicillins, aminopenicillins, clavulanic acid, cephalosporins, macrolides and metronidazole at dosages at the low end of the recommended dosage range are considered appropriate for use for lactating women. Fluoroquinolones should not be administered as first-line treatment, but if they are indicated, breast feeding should not be interrupted because the risk of adverse effects is low and the risks are justified. Paracetamol (acetaminophen), low-dose aspirin (acetylsalicylic acid) [up to 100 mg/day] and short-term treatment with NSAIDs, codeine, morphine and propoxyphene are considered compatible with breast feeding. Safer alternatives should be considered instead of dipyrone, aspirin at a dosage >100 mg/day and pethidine (meperidine). In the light of the many safe alternatives for pain control, breast-feeding mothers should not be allowed to experience pain or be made to feel that they must choose between analgesia and breast feeding.     

Interleukin 1 receptor antagonist (IL1RA) in acute leukaemia: IL1RA is both secreted spontaneously by myelogenous leukaemia blasts and is a part of the acute phase reaction in patients with chemotherapy- induced leucopenia

Abstract: Blast cells derived from peripheral blood of patients with acute myelogenous leukaemia (AML) were cultured in vitro and interleukin 1 receptor antagonist (IL1RA) concentrations determined in culture supernatants. AML blasts derived from patients classified as AML-M4 and AML-M5 subtype showed an increased release of IL1RA. IL1α and IL1β caused a similar increase in AML blast release of IL1RA, and addition of anti-ILl antibodies decreased IL1RA release. IL1RA release from AML blasts was also increased by stem cell factor, tumour necrosis factor α (TNFα), granulocyte-macrophage colony-stimulating factor and macrophage colony-stimulating factor, whereas interleukin 3, interleukin 6, leukaemia inhibitory factor and granulocyte colony- stimulating factor did not significantly alter IL1RA release. When investigating IL1RA serum levels, serum concentrations were decreased in acute leukaemia patients with chemotherapy-induced cytopenia compared with healthy controls. Serum levels of both IL1RA as well as IL1β and soluble TNFα receptors increased when the leucopenic patients developed complicating bacterial infections.     

Über funktionelle Unterschiede zwischen Dünn-und Dickdarm—dargestellt an den verschiedenen Reaktionen der Darmschleimhaut bei Angebot von Lösungen nicht penetrabler Solute und steigender Osmolarität

Zusammenfassung Bei Instillation von Mannitlösungen steigender Osmolarität in durchblutete, in situ belassene Jejunum- und Colonschlingen von Ratten reagieren beide Darmabschnitte unterschiedlich.Während die durch Enterosorption binnen 30 min in das Jejunum gelangte Flüssigkeitsmenge 250% des Instillats ausmacht, beträgt der analoge Wert beim Colon nur 100%. Die enterosorbierten Mengen an Na⁺, Cl^– und Urea sind im Jejunum wesentlich größer als im Colon, da nicht nur die enterosorbierte Flüssigkeitsmenge größer ist, sondern weil auch die intraintestinalen Konzentrationen höher liegen.Zwischen den Ca⁺⁺-Konzentrationen im Jejunum und Colon bestehen keine Unterschiede, die K⁺-Konzentration ist im Colon höher. Bei Berücksichtigung der Wasserbewegungen ist die enterosorbierte Ca⁺⁺-Menge im Jejunum, die K⁺-Menge dagegen im Colon größer.Während der Versuchszeit — 30 min — erfolgt im Jejunum ein osmolarer Konzentrationsausgleich aller Lösungen mit dem Plasma, deren Konzentration kleiner als die 1,66 fache Blutisotonie ist. Im Colon stellt sich dieser Ausgleich auch für eine Lösung von 1,33 facher Blutisotonie nicht mehr ein.Die Colonschleimhaut verhält sich demnach so, als ob hier die Exsorption von Wasser, Na⁺, Cl^–, Ca⁺⁺ und Urea wesentlich stärker behindert wäre als die durch die Schleimhaut des Jejunums.Instillation großer Volumina stark hypertoner (ca. 2000 mOsmol/l) Lösungen, deren Solute nur schwer absorbiert werden können, führen zu einem so großen Einstrom von Blut- und Körperflüssigkeit in den Intestinaltrakt, daß Ratten in schwerer Exsiccose sterben. Dabei steigt der Anteil von Zellen am Blutvolumen von 48% auf 68% der Wassergehalt der geprüften Gewebe — quergestreifte und Herzmuskulatur, Gehirn — sinkt ab.     

Unterschiedliche Flüssigkeits- und Substanzbewegungen durch die Mucosa der verschiedenen Abschnitte des Intestinaltraktes beim Kaninchen

Zusammenfassung Die Schleimhaut des Duodenums beim Kaninchen sezerniert eine blutisotone Flüssigkeit, deren Hauptcharakteristikum ihr HCO₃ ^–-Gehalt von fast 100 mMol/l ist. Auf die Instillation einer Lösung, die wie das duodenale Sekret zusammengesetzt ist, reagiert das Jejunum mit einer isotonen Absorption bei nur geringfügigen Konzentrationsänderungen der Konstituenten der Instillationslösung. Das Ileum reagiert analog dem Jejunum, nur sind die Absorptionsraten für Flüssigkeit und die geprüften Solute größer als im Jejunum. Im Colon kommt es zu einer Enterosorption von Flüssigkeit mit teilweise beträchtlichen Konzentrationserniedrigungen der in der Installationslösung enthaltenen Solute.Auf die Instillation einer blutisotonen NaCl-Lösung reagiert das Jejunum stets mit einer Absorption von Flüssigkeit. Na⁺ und Cl^– werden absorbiert, während HCO₃ ^–, K⁺ und Harnstoff netto sezerniert werden. Im Colon kommt es unter den Bedingungen des 30 min-Versuches zur enterosorption von Flüssigkeit, zur Absorption von osmotisch aktivem Material, Na⁺ und Cl^–, während HCO₃ ^–, K⁺ und Harnstoff sezerniert werden.Auf die Instillation reinen Wassers reagiert das Jejunum mit einer Absorption von Flüssigkeit sowie einer Enterosorption aller geprüften Solute in das Jejunum hinein, daß fast Konzentrationsgleichheit mit dem Plasma eingestellt wird. Im Colon kommt es im 30 min-Versuch teils zur Enterosorption, teils zur Absorption von Flüssigkeit. Nach 60 min wird in allen Fällen eine Absorption von Flüssigkeit beobachtet. Die Gleichgewichtskonzentrationen im Jejunum sind: Osmolarität 296,0 mOsmol/l, Na⁺ 78,6 mMol/l, Cl^– 24,6 mMol/l, HCO₃ ^– 54,8 mMol/l, K⁺ 2,2 mMol/l, Harnstoff 59,9 mg/100 ml. Die analogen Werte für das Colon lauten: Osmolarität 184,0 mOsmol/l, Na⁺ 11,6 mMol/l, Cl^– 12,9 mMol/l, HCO₃ ^– 25,9 mMol/l, K⁺ 16,4 mMol/l, Harnstoff 18,8 mg/100 ml.     

Novel autosomal recessive progressive hyperpigmentation syndrome

We present a family of Iraqui origin with three siblings affected by a novel type of progressive hyperpigmentation syndrome. The generalized initially diffuse, later disseminated hyperpigmentation started in early infancy and increased during childhood. It also affected palms and soles, and the face but spared the cheeks. Additional features were dry, itchy and sunlight sensitive skin, dystrophy of toe nails, hair loss, and myopia, but normal sweat glands. Light and electron microscopy showed signs of pigment incontinence and compound melanosomes as well as fibrillar bodies. The occurrence of this entity in affected siblings from a consanguineous mating suggests autosomal recessive inheritance. Extensive review of the literature showed no previous report with this distinct combination of clinical and microscopic findings.     

IFN-gamma-enhanced allergen penetration across respiratory epithelium augments allergic inflammation

BACKGROUND: Respiratory allergen contact is the critical event in the elicitation and boosting of allergen-specific immune responses, as well as in the induction of immediate and late inflammatory reactions. OBJECTIVE: We sought to investigate the influence of various factors of allergic inflammation on the integrity and barrier function of respiratory epithelium for allergens. METHODS: We cultured the human bronchial epithelial cell line 16HBE14o- in a transwell culture system as a surrogate of intact respiratory epithelium and used purified iodine 125-labeled recombinant major birch pollen allergen (rBet v 1) to study the extent, kinetics, and factors influencing transepithelial allergen penetration. RESULTS: Culture supernatants from activated allergen-specific T H 1 clones decreased transepithelial resistance. A screening of various factors (histamine, IFN-gamma, IL-1beta, IL-2, IL-3, IL-4, IL-5, IL-8, IL-12, and TNF-alpha) identified IFN-gamma as a potent factor capable of reducing epithelial barrier properties and enhancing transepithelial allergen penetration. Increased submucosal allergen concentrations caused by IFN-gamma-mediated reduction of epithelial barrier function provoked a more than 7-fold augmentation of histamine release from sensitized basophils. CONCLUSION: These results demonstrate that the T H 1 cell-derived cytokine IFN-gamma facilitates allergen penetration through the respiratory epithelium and thereby can aggravate allergic inflammation.     

Dynamics of the Murine Humoral Immune Response to Neisseria meningitidis Group B Capsular Polysaccharide

Immunization with Neisseria meningitidis group B capsular polysaccharide (CpsB) elicited responses in adult mice that showed the typical dynamic characteristics of the response to a thymus-independent antigen, in contrast to the thymus-dependent behavior of antibody responses to CpsC. The former had a short latent period and showed a rapid increase in serum antibodies that peaked at day 5, and immunoglobulin M (IgM) was the major isotype even though IgG (mainly IgG2a and IgG2b) was also detectable. This response was of short duration, and the specific antibodies were rapidly cleared from the circulation. The secondary responses were similar in magnitude, kinetics, IgM predominance, and IgG distribution. Nevertheless, a threefold IgG increase, a correlation between IgM and IgG levels, and dose-dependent secondary responses were observed. Hyperimmunization considerably reinforced these responses: 10-fold for IgM and 300-fold for IgG. This favored isotype switch was accompanied by a progressive change in the subclass distribution to IgG3 (62%) and IgG1 (28%), along with the possible generation of B-cell memory. The results indicate that CpsB is being strictly thymus independent and suggest that unresponsiveness to purified CpsB is due to tolerance.

The capsular polysaccharide (Cps) of Neisseria meningitidis group B (CpsB), the major cause of meningococcal disease in developed countries (38), is a linear homopolymer of α(2→8)-linked sialic acid on host sialogangliosides and sialoproteins (12, 16) causes immunological tolerance to sequential CpsB epitopes, with the anti-CpsB antibodies being mainly, if not solely, directed against conformational determinants preferably expressed by chains of eight or more residues (10). The conformational antigenic nature and metastable spatial structure of CpsB (10, 19), in combination with its neuraminidase sensitivity, tendency to internal lactonization, and intramolecular self-cleavage under mild acidic conditions (22, 29), were proposed to explain its poor immunogenicity (35). According to this hypothesis, the interaction of CpsB with B cells is transitory and therefore unable to elicit an antibody response (34). Alternatively, the high expression of longer sialic acid polymers (>12 residues), having the same α(2→8) linkage in polysialylated glycoproteins of vertebrate fetal tissues as well as limited areas of the adult neural system (21, 42), has been proposed to induce tolerance also to the conformational epitopes of CpsB (11). A feasible mechanism for inducing and maintaining tolerance, however, is not known. In any event, the poor immunogenicity of CpsB is associated with the α(2→8) linkage. Purified CpsC, a homopolymer of α(2→9)-linked sialic acid, has been shown to be immunogenic in mice (48).Bacterial Cps complexed to protein carriers induces long-lasting immunoglobulin G (IgG) antibody responses in young children and mice, which is indicative of the Cps conversion to a T-cell-dependent (TD) antigen (18). In contrast, CpsB conjugated to tetanus toxoid (3, 8, 20) or complexed with meningococcal outer membrane proteins (OMPs) (23, 24) is able to induce only low levels of CpsB-specific IgM. In these responses, however, CpsB-specific IgG was detectable (3, 8, 23). Since in simple terms protection from these infectious agents is due to the presence of circulating specific antibodies (13) and bearing in mind that an artificial IgG immune response may initiate an autoimmune process (11), we studied the evolution over time of the serum antibodies and changes in isotype distribution obtained by immunization with the native form of CpsB—namely, live N. meningitidis—in order to further explore the underlying mechanisms in the generation of the immune responses to this peculiar autoantigen which has both epitopes disseminated in the host and epitopes of ontogenetic and topologically restricted expression, a situation reproduced in the mouse model.     

Three new families with arterial tortuosity syndrome

Arterial tortuosity syndrome (ATS) is a rare condition with autosomal recessive inheritance characterized by connective tissue abnormalities. The most specific clinical findings are cardiovascular anomalies including tortuosity, lengthening, aneurysm, and stenosis formation of major arteries. Also ventricular hypertrophy is frequently present. Other anomalies are skin hyperextensibility and cutis laxa, joint laxity or contractures of the joints, and inguinal herniae. Histology shows disruption of elastic fibers of the media. These features suggest that ATS is a connective tissue disorder. A biochemical or molecular defect has not yet been identified. We describe here nine additional ATS patients from three consanguineous Moroccan families and review a total of 35 patients with this uncommon condition.     

Cloning, Expression, and Sequencing of a Cell Surface Antigen Containing a Leucine-Rich Repeat Motif from Bacteroides forsythus ATCC 43037

Bacteroides forsythus is a recently recognized human periodontopathogen associated with advanced, as well as recurrent, periodontitis. However, very little is known about the mechanism of pathogenesis of this organism. The present study was undertaken to identify the surface molecules of this bacterium that may play roles in its adherence to oral tissues or triggering of a host immune response(s). The gene (bspA) encoding a cell surface-associated protein of B. forsythus with an apparent molecular mass of 98 kDa was isolated by immunoscreening of a B. forsythus gene library constructed in a lambda ZAP II vector. The encoded 98-kDa protein (BspA) contains 14 complete repeats of 23 amino acid residues that show partial homology to leucine-rich repeat motifs. A recombinant protein containing the repeat region was expressed in Escherichia coli, purified, and utilized for antibody production, as well as in vitro binding studies. The purified recombinant protein bound strongly to fibronectin and fibrinogen in a dose-dependent manner and further inhibited the binding of B. forsythus cells to these extracellular matrix (ECM) components. In addition, adult patients with B. forsythus-associated periodontitis expressed specific antibodies against the BspA protein. We report here the cloning and expression of an immunogenic cell surface-associated protein (BspA) of B. forsythus and speculate that it mediates the binding of bacteria to ECM components and clotting factors (fibronectin and fibrinogen, respectively), which may be important in the colonization of the oral cavity by this bacterium and is also a target for the host immune response.