Transsynaptic degeneration of lateral geniculate bodies in blind children: in vivo MR demonstration.

PURPOSETo investigate signal alterations in the thalamic lateral geniculate bodies of blind patients compatible with transsynaptic degeneration of these nuclei caused by pregeniculate or postgeniculate interruption of the visual pathway.METHODSSix patients were selected from a group of blind children in our care. Four had cerebral palsy caused by periventricular leukomalacia, one had infantile neuroaxonal dystrophy, and one had Chiari I malformation and hydrocephalus, which was worsened by bilateral ischemic lesions of the occipital lobes. MR examinations (obtained at 0.5 T) were reviewed retrospectively by two neuroradiologists, with particular attention to the visual pathway.RESULTSSymmetric, focal areas of T2 prolongation were found at the precise site of the lateral geniculate bodies.CONCLUSIONAnterograde (pregeniculate) and retrograde (postgeniculate) transsynaptic degeneration of the second neurons of the visual pathway produce alterations in MR signal.     

Mechanism of the antihypertensive effect of FCE 22716, a new ergoline derivative, in the spontaneously hypertensive rat

Both acute and chronic oral administration (1-20 mg/kg) of FCE 22716, a new ergoline derivative, resulted in a dose-related fall of arterial blood pressure lasting for more than 6 h. Tachycardia was observed only at high dosages. Yohimbine, propranolol and indometacin did not modify its antihypertensive effect; on the other hand pretreatment with prazosin, a selective alpha 1-adrenoceptor antagonist and pithing, almost completely neutralized its antihypertensive effect. Haloperidol, a dopamine antagonist that crosses the blood-brain barrier, also antagonized FCE 22716 activity. The lack of effects of domperidone (DA2-receptor antagonist selectively acting on the periphery) together with the finding that norepinephrine and epinephrine levels were unchanged after treatment with FCE 22716, seem to rule out an involvement of peripheral DA2-receptors. Both in vitro (isolated organs) and in vivo the compound antagonized responses mediated by stimulation of alpha 1-adrenoceptors and S2-receptors. Radioligand binding studies in different cerebral regions are in line with the above reported in vitro and in vivo results. These data suggest that FCE 22716 is endowed with a multitarget mechanism of action, mainly involving blockade of alpha 1-adrenoceptors and S2-receptors.     

Efficacy and safety of ciprofloxacin in the treatment of UTIs and RTIs in patients affected by liver diseases

The clinical efficacy and the safety of ciprofloxacin was studied in 92 patients (aged 26 to 83 years; mean 57.5 years) affected by urinary tract infections (UTI) and respiratory tract infections (RTI) suffering also with various liver diseases. Ciprofloxacin was given orally at different dose regimens: 500 mg b.i.d. (22 cases), 250 mg b.i.d. (20 cases), 500 mg s.i.d. (20 cases) for the treatment of UTIs; 500 mg b.i.d. (ten cases) and 250 mg b.i.d. (20 cases) for the treatment of RTIs. The doses were not correlated to the severity of the infections. Patients were treated for five to 15 days. All the bacteria isolated from sputum or urine before treatment were sensitive to ciprofloxacin (MIC range 0.015 mg/1 to 8 mg/1). The clinical and bacteriological responses were favourable in a high percentage of patients both for RTIs and UTIs, irrespective of the dose. Side effects were infrequent (7%) and mild (nausea, gastralgia, oral candidosis), never requiring the interruption of the treatment. No change in the blood chemistry tests was observed at any dose.Die klinische Wirksamkeit und Sicherheit von Ciprofloxacin wurde bei 92 Patienten (Alter 26 bis 83 Jahre, im Mittel 57,5 Jahre), die an verschiedenen Leberkrankheiten litten, bei interkurrent aufgetretenen Harnwegs- und Atemwegsinfektionen geprüft. Ciprofloxacin wurde in verschiedenen Dosierungen oral verabreicht. Zur Behandlung von Harnwegsinfektionen wurden Dosierungen von 500 mg zweimal täglich (22 Fälle), 250 mg zweimal täglich (20 Fälle) oder 500 mg in einer täglichen Einzeldosis (20 Fälle) verabreicht. Atemwegsinfektionen wurden mit zweimal täglich 500 mg (10 Fälle) oder mit zweimal täglich 250 mg (20 Fälle) behandelt. Die Dosen wurden nicht nach dem Schweregrad der Erkrankung gewählt. Die Behandlungsdauer betrug fünf bis 15 Tage. Alle aus Sputum oder Urin vor der Therapie isolierten Bakterien waren für Ciprofloxacin empfindlich (MHK-Werte 0,015 mg/l bis 8 mg/l). Bei einem hohen Prozentsatz der Patienten mit Atemwegs- und Harnwegsinfektionen wurden unabhängig von der Dosierung günstige klinische und bakteriologische Ergebnisse erzielt. Nebenwirkungen traten selten auf (7%) und waren leicht (Übelkeit, Magenschmerzen, orale Candidiasis). Ein Therapieabbruch war in keinem Fall nötig. Bei keiner der angewandten Dosierungen waren Änderungen in den klinisch-chemischen Parametern festzustellen.     

Hormones and the immunological capacity. V. Modification of growth hormone-producing cells in the adenohypophysis of neonatally thymectomized germ-free mice: an electron microscopical study

An electron microscopical study has been carried out to evaluate the effect of neonatal thymectomy on the hypophysis of germ-free mice at different times after the operation. The results fully confirm the previous findings in neonatally thymectomized, conventional mice. Also neonatal thymectomy in germ-free mice results in degranulation of growth hormone-producing cells in the anterior pituitary gland. A large number of these cells show an enlarged endoplasmic reticulum with formation of cisternae and loss of hormone granuli. This alteration of growth hormone-producing cells is similar to that observed in other cells of the hypophysis after removal of other target glands such as thyroid or gonads. The changes in the growth hormone-producing cells in neonatally thymectomized germ-free mice occur even in the first days after birth, when the number of differentiated growth hormone-producing cells is still very low.

Some thymectomized germ-free mice showed symptoms of the wasting syndrome but the alterations in their hypophysis were not more pronounced than those observed in thymectomized germ-free but nonwasting mice. The data fit well our suggestion that the perinatal thymus is under hypophysial control and that immunological maturation depends on endocrine function.

     

Uncoupling of inflammatory chemokine receptors by IL-10: generation of functional decoys

As originally demonstrated for the interleukin 1 (IL-1) type II receptor, some primary proinflammatory cytokines from the IL-1 and tumor necrosis factor families are regulated by decoy receptors that are structurally incapable of signaling. Here we report that concomitant exposure to proinflammatory signals and IL-10 generates functional decoy receptors in the chemokine system. Inflammatory signals, which cause dendritic cell (DC) maturation and migration to lymphoid organs, induce a chemokine receptor switch, with down-regulation of inflammatory receptors (such as CCR1, CCR2, CCR5) and induction of CCR7. Concomitant exposure to lipopolysaccharide (LPS) and IL-10 blocks the chemokine receptor switch associated with DC maturation. LPS + IL-10-treated DCs showed low expression of CCR7 and high expression of CCR1, CCR2 and CCR5. These receptors were unable to elicit migration. We provide evidence that uncoupled receptors, expressed on LPS + IL-10-treated cells, sequester and scavenge inflammatory chemokines. Similar results were obtained for monocytes exposed to activating signals and IL-10. Thus, in an inflammatory environment, IL-10 generates functional decoy receptors on DC and monocytes, which act as molecular sinks and scavengers for inflammatory chemokines.     

Towards improved clinical characterization of Leber congenital amaurosis: neurological and systemic findings

Leber congenital amaurosis (LCA) is the most severe form of inherited retinal dystrophy that presents in infancy. LCA is both clinically and genetically heterogeneous. The aim of our study was to clarify the clinical aspects of LCA and to contribute to improved characterization of the disorder. We studied 40 children affected by LCA (mean age at first observation: 19 months, range: 8-50 months), who underwent a comprehensive evaluation that included: neurophthalmological evaluation, electroretinogram (ERG), and visual evoked potentials (VEPs), general and neurological examinations, developmental assessment using scales for visually impaired children, neuroradiological examinations, hepatic and renal function and metabolic investigations, brainstem auditory evoked potentials (BAEPs), EEG, and hand radiographs. Analyses of known LCA genes are ongoing. The subjects are still being followed up at 6-/12-month intervals. All the subjects fulfilled De Laey's criteria for LCA. The neurological examination was abnormal in 31 cases (hypotonia, ataxia with/without associated cerebellar signs). Cognitive development was normal in 24 cases, borderline in five, and subnormal in 11. Mild and nonspecific alterations on MRI were present in seven cases, and "molar tooth" sign in four; all the others had a normal neuroradiological picture. Among the subjects presenting with neurological signs, a subgroup (13 patients) emerged that was characterized by systemic (skin, kidney, liver) involvement. Our data confirm that LCA is a heterogeneous entity that can present as an isolated ocular manifestation, or in association with neurological and systemic abnormalities and support the need for a multidisciplinary approach to this entity and for genotype-phenotype studies.     

Critical ovarian hyperstimulation syndrome in a coasted in-vitro fertilization patient

We report an instance of critical ovarian hyperstimulation syndrome in a highly responsive in-vitro fertilization patient despite the preventive measure of a 4 day 'coast' interval during which no gonadotrophins were administered while gonadotrophin-releasing hormone agonist therapy continued until serum oestradiol concentrations fell below 3000 pg/ml.      

Antibodies to cardiac conducting tissue and abnormalities of cardiac conduction in rheumatoid arthritis.

The prevalence of antibodies to cardiac conducting tissue and cardiac conduction electrocardiographic abnormalities were studied in 60 patients with rheumatoid arthritis (RA). Complete or incomplete right bundle branch block (RBBB) was found in 21 patients (35%). Antibodies to cardiac conducting tissue were found in 16 (76%) of the 21 with RBBB and in eight (21%) of the 39 without RBBB. Cardiac conducting tissue antibodies (CCTA) were found only in one of 42 patients with RBBB unrelated to RA and in two out of 60 normal subjects. This newly documented immunological abnormality is thus correlated with disorder of conducting tissue.     

Ligand and cytokine dependence of the immunosuppressive pathway of tryptophan catabolism in plasmacytoid dendritic cells

Murine plasmacytoid dendritic cells (pDCs) have been credited with a unique ability to express indoleamine 2,3-dioxygenase (IDO) function and mediate immunosuppression in specific settings; yet, the conditions of spontaneous versus induced activity have remained unclear. We have used maneuvers known to up-regulate IDO in different cell types and have examined the relative efficacy and mechanisms of the induced activity in splenic pDCs, namely, after specific receptor engagement by CTLA-4-Ig, CD200-Ig or CD28-Ig, the latter in combination with silenced expression of the suppressor of cytokine signaling 3 (SOCS3) gene. We found that pDCs (CD11c+ mPDCA-1+ 120G8+) do not express IDO and are not tolerogenic under basal conditions. B7-1 engagement by CTLA-4-Ig, CD200R1 engagement by CD200-Ig and B7-1/B7-2 engagement by CD28-Ig in SOCS3-deficient pDCs were each capable of initiating IDO-dependent tolerance via different mechanisms. IFN-gamma was the major cytokine responsible for CTLA-4-Ig effects, and type I IFNs for those of CD200-Ig. Immunosuppression by CD28-Ig in the absence of SOCS3 required IFN-gamma induction and IFN-like actions of IL-6. Therefore, although pDCs do not mediate IDO-dependent tolerance constitutively, multiple ligands and cytokines will contribute to the expression of a tolerogenic phenotype by pDCs in the mouse.     

Mathematical model to analyse urea synthesis following alanine infusion in control subjects and in patients with liver cirrhosis

A three-compartment model was used to analyse the urea response to an alanine infusion in control subjects and patients with liver cirrhosis. Discriminant analysis showed a good separation between model coefficients of the two groups. A single parameter was derived, able to quantify the liver functional capacity. The method provides a useful diagnostic tool in patients with liver disease.