Chemokines and pro-inflammatory cytokines in Down's syndrome: an early marker for Alzheimer-type dementia?

BACKGROUND: People with Down's syndrome (DS) show early Alzheimer-like dementia. It has been suggested that the pro-inflammatory cytokine class plays a role in Alzheimer's disease (AD). The study aims at verifying whether pro-inflammatory cytokines in DS are correlated with age, affective symptoms and intellectual decline to a different degree than in subjects with non-DS learning disabilities. METHODS: Cases: 19 subjects with DS; controls: sex- and age-matched individuals with learning disabilities caused by perinatal ischaemic damage. The level of mental retardation was assessed according to DSM-IV; psychopathological symptoms were measured by the Assessment and Information Rating Profile. Serum levels of cytokines were determined with ELISA. RESULTS: DS patients showed higher levels of cytokines and chemokines, with the exception of RANTES; but the only significant difference detected was for MIP-1alpha. A correlation between the degree of mental retardation and IL-6, and between MIP-lalpha and age was found in patients with DS, but not in controls. CONCLUSIONS: The data obtained suggest a possible involvement of chemokines in the inflammatory and degenerative processes similar to AD in DS. Further longitudinal research is required to confirm these findings.     

The role of pulmonary CO2 flow in the control of the phase i ventilatory response to exercise in humans

To gain an insight into the origin of the phase I ventilatory response to exercise (ph I) in humans, pulmonary ventilation WE) and end-tidal partial pressures of oxygen and carbon dioxide (P _ETO₂ and P _ETCO₂, respectively) were measured breath-by-breath in six male subjects during constant-intensity exercise on the cycle ergometer at 50, 100 and 150 W, with eupnoeic normocapnia (N) or hyperpnoeic hypocapnia (H) established prior to the exercise test. Cardiac output (Q₂) was also determined beat-by-beat by impedance cardiography on eight subjects during moderate exercise (50 W), and the C0₂ flow to the lungs (Q₂·C_vCO₂ where C_vCO₂ is concentration of CO₂ in mixed veneous blood) was estimated with a time resolution of one breathing cycle. In N, the initial abrupt increase of PE during ph I (V_E approximately 18 l · min^–1 above rest) was followed by a transient fall. When P _ETCO₂ started to increase (and P _ETO₂ decreased) V_E increased again (phase II ventilatory response, ph II). In H, during ph I V_E was similar to that of N. By contrast, during ph II V_E kept gradually decreasing and started to increase only when P _ETCO₂ had returned to approximately 40 mmHg (5.3 kPa). Thus, as a result of the prevailing initial conditions (N or H) a temporal shift of the time-course of V_E during ph II became apparent. No correlation was found between C0₂ flow to the lungs and V_E during ph I. These results are interpreted as suggesting that an increased C0₂ flow to the lungs does not constitute an important factor for the initial hyperventilatory response to exercise. They are rather compatible with a neural origin of ph I, and would support the neurohumoral theory of ventilatory control during exercise.     

Peritoneal implantation of meningeal melanosis via ventriculoperitoneal shunt: A case report and review of the literature

Systemic spread of primary intracranial neoplasms is rare and may be due to ventriculoperitoneal shunt (VPS). The most common tumors to metastasize via VPS are germinoma of the pineal gland and medulloblastoma. We report a case of 16-yr-old girl with central nervous system malignant melanosis who developed subsequent peritoneal implants via VPS. To the best of our knowledge, this patient represents the third reported case of meningeal melanosis or melanoma which metastasized to the peritoneal cavity via VPS. The VPS should be considered as possible mode of systemic spread in patients with primary cranial malignancy. © 1995 Wiley-Liss, Inc.     

Antibiotic prophylaxys in pediatric surgery of genito-urinary abnormalities

Ninety-two patients in the age range of 2,5 and 16 years with hypospadias (28 cases), vescicorenal reflux (22 cases), hydronephrosis (16 cases) and a series of other congenital genitourinary abnormalities underwent one or more surgical interventions performed by an unique surgeon at the department of Pediatric Surgery, S. Bortolo Hospital, Vicenza. The more frequently performed interventions were the plastic of the urethra (28 pts, 30,4%), that of the pyeloureteral joint (15 pts, 16,3%) and the modelling and the reimplantation of the ureter/ureters (12 pts, 13%). The interventions were considered as clean-contaminated, because all patients had a temporary urinary derivation with vescical catheters, uretral or pyelovescical stents. An antimicrobial prophylaxis was undertaken in all cases in order to prevent postoperatory infections. Ceftriaxone at a mean dosage of 50 mg/kg was administered to all patient for a mean duration of 5,5 days, in 79 cases by the intravenous and in 13 cases by the intramuscular route. Three patients received also metronidazol because of a concomitant intestinal surgery. The objective of this retrospective trial is to evaluate the efficacy of an antibiotic prophylaxis in pediatric genitourinary surgery with temporary urinary drainage. Data analysis evidenced a very low incidence of postoperatory infections, that occurred only in 2 patient on 92. It can be therefore concluded that ceftriaxone is effective and well tolerated when administered for the prevention of postoperative infections in urological interventions.     

Central precocious puberty and abnormal chromosomal patterns

Central precocious puberty (PP) can be caused by chromosomal aberrations. We report three patients presenting with central PP in whom karyotype analysis demonstrated abnormal chromosomal patterns. The first patient was affected by the triple-X syndrome, commonly characterized by premature ovarian failure. The second patient, a girl with inv dup(15)(pter→q12::q12→pter), had a chromosomal aberration involving an imprinted region of the human genome, whose deletion is commonly associated with Prader-Willi syndrome (PWS) and hypogonadotrophic hypogonadism. The third patient was a boy carrying a rare chromosome abnormality, the duplication of chromosome 9 (q22→qter). All patients had mental retardation, which was mild in patient 1, moderate in patient 2, and severe in case 3. They underwent treatment with luteinizing hormone releasing hormone (LHRH) analogs, which were able to stop the progression of the sexual development. We confirm that chromosomal aberrations are an important cause of central PP, and that karyotype analysis in patients with PP and mental retardation, even if mild, is necessary because chromosomal abnormalities can be present.     

Distribution of cytoskeletal and contractile proteins in normal and tumour bearing salivary and lacrimal glands

Summary We have evaluated by means of immunocytochemistry the distribution of various cytoskeletal and contractile proteins (cytokeratins, vimentin, desmin and -smooth muscle actin) in 23 salivary or lacrimal gland primary tumours (15 pleomorphic adenomas and 8 carcinomas in pleomorphic adenoma), one third of which contained areas of normal gland. Normal epithelial luminal cells were stained by cytokeratin antibodies with a general specificity, while myoepithelial cells were selectively stained by a monoclonal antibody (SK2-27) reacting in immunoblots with cytokeratin polypeptides 14, 16 and 17, according to the classification of Moll et al. (1982) and by an antibody directed against -smooth muscle actin (Skalli et al. 1986). In pleomorphic adenomas, both epithelial and myoepithelial cells displayed typical topographic distributions; moreover, myoepithelial cells showed two distinct cytoskeletal phenotypes. These findings could account in part for the heterogeneity of aspects observed in this tumour. In carcinomas, malignant cells were always positive to cytokeratin antibodies with general specificity and myoepithelial cells were absent as judged by anticytokeratin SK2-27 and anti--smooth muscle actin immunostainings. However, interestingly, there was in all cases a strong positivity for -smooth muscle actin in stromal cells, similarly to what has previously been described for mammary carcinoma (Skalli et al. 1986). Our findings may be useful for the interpretation of the histogenesis of salivary and lacrimal tumour and stromal cells.     

The efficacy of enrofloxacin,alone or combined with metronidazole,in the therapy of canine leishmaniasis

We evaluated the efficacy of enrofloxacin, alone or combined with metronidazole, against Leishmania infantum. The in vitro activity of this fluoroquinolone was assessed using two different methods: a direct test aimed at assessing the drug activity on the parasite, and an indirect test aimed at evaluating the drug effect on macrophage killing, lymphomonocyte activation and nitric oxide production. An in vivo test was also performed on 36 dogs with leishmaniasis, subdivided into three groups, one treated with enrofloxacin, another with enrofloxacin plus metronidazole, and a control group with meglumine antimoniate. The direct test did not show any action of enrofloxacin on the parasite, while the indirect testing showed an enhancement of macrophage killing and an increase in nitric oxide production. These findings show that enrofloxacin does not exert a direct anti-leishmanial activity in vitro. However, on the basis of the positive immunostimulation results shown in vitro and the clinical improvement, particularly of the cutaneous lesions, obtained in several dogs in the in vivo trial, the use of enrofloxacin in association with a specific anti-leishmanial drug can be proposed in the therapeutic protocol of canine leishmaniasis.