Umbilical blood flow and placental pathology.

The aim of the study was to establish whether or not placental morphostructural damage correlates with umbilical artery Doppler waveform and neonatal condition. To this end, seriated ultrasonographic monitoring, flowmeter tests on the cord artery and computerized cardiotocography were carried out in a population of 93 pregnant women in the second half of pregnancy. After birth placentas were subjected to macroscopic and microscopic examination. The Resistance Index showed a good correlation with placental vascular lesions, characterized by a distinct reduction in terminal villi and muscular wall arterioles. Two types of intrauterine growth retardation were discernible, the first of genetic origin with a low-profile growth curve and therefore not amenable to treatment, but with a positive fet l-neonatal prognosis, and the second with a pathologic placental component, presenting a late flattening growth curve with evolution towards fetal distress and a negative fetal-neonatal prognosis.     

Does dexamethasone with preemptive analgesia improve pediatric tonsillectomy pain?

OBJECTIVE: The study goal was to determine whether the combination of dexamethasone with preemptive analgesia has an additive effect in further improving recovery. STUDY DESIGN: We conducted a prospective, randomized, double-blinded trial of 50 children undergoing tonsillectomy at a university ambulatory surgery center. One study group received 1 intravenous dose of dexamethasone, and another group received 1 dose of saline solution. All patients received tonsillar fossa injections of ropivacaine plus clonidine before tonsil excision. RESULTS: The 2 study groups were similar in main outcome measurements. Pain intensity and quality of life were not statistically different between the groups. There was a small trend to less trismus and less cumulative codeine use in the steroid group. Overall, there was a very low incidence of nausea and vomiting in both groups, which may have been due to the preemptive analgesia. CONCLUSION: Dexamethasone does not significantly improve the morbidity of pediatric tonsillectomy when preemptive analgesia with ropivacaine and clonidine is used concurrently.     

Intracranial Complications of Sinusitis

Intracranial suppurative complications of sinusitis remain a challenging and contemporary topic. To determine the prevalence of sinogenic sources in intracranial infectious complications, we reviewed the records at a large public hospital between 1985 and 1995. There were 203 patients with 212 suppurative intracranial infections. Sinogenic sources were identified in 12 patients with 19 infections. Most patients had ethmoid or frontal sinusitis. We discuss the presentation, microbiology, diagnosis, treatment, and clinical course of these 12 cases. The diagnosis of intracranial complications of sinusitis requires a high index of suspicion and radiographic imaging of the head and paranasal sinuses. The mean hospital stay was 31.4 days and all 12 patients survived, although three patients had significant neurologic sequelae.     

Inhibition of complement activity by humanized anti-C5 antibody and single-chain Fv

Activation of the complement system contributes significantly to the pathogenesis of numerous acute and chronic diseases. Recently, a monoclonal antibody (5G1.1) that recognizes the human complement protein C5, has been shown to effectively block C5 cleavage, thereby preventing the generation of the pro-inflammatory complement components C5a and C5b-9. Humanized 5G1.1 antibody, Fab and scFv molecules have been produced by grafting the complementarity determining regions of 5G1.1 on to human framework regions. Competitive ELISA analysis indicated that no framework changes were required in the humanized variable regions for retention of high affinity binding to C5, even at framework positions predicted by computer modeling to influence CDR canonical structure. The humanized Fab and scFv molecules blocked complement-mediated lysis of chicken erythrocytes and porcine aortic endothelial cells in a dose-dependent fashion, with complete complement inhibition occurring at a three-fold molar excess, relative to the human C5 concentration. In contrast to a previously characterized anti-C5 scFv molecule, the humanized h5G1.1 scFv also effectively blocked C5a generation. Finally, an intact humanized h5G1.1 antibody blocked human complement lytic activity at concentrations identical to the original murine monoclonal antibody. These results demonstrate that humanized h5G1.1 and its recombinant derivatives retain both the affinity and blocking functions of the murine 5G1.1 antibody, and suggest that these molecules may serve as potent inhibitors of complement-mediated pathology in human inflammatory diseases.     

Convergence defects in patients with temporomandibular disorders

The aim of this study is to show the presence of a correlation between ocular convergence defects (OCD) and temporomandibular disorders (TMD) among a group of adult subjects. The group studied was made up of 48 subjects (12 males and 36 females). The average age was 35 with a range of 19-45 years of age. The subjects presented with TMD and muscular pain and/or dysfunction. Forty-eight subjects with TMD for the case study were matched by gender and age to 48 control subjects seeking routine dental care (control group). All the subjects were examined by the same orthoptist who classified the ocular convergence degree using two tests. The first test evaluated the distances (in centimeters) of the convergence near point (3-4 cm: normal; 5-7 cm: sufficient; > 7 cm: insufficient). The second test assessed the fusional convergence using a Berens prism test (> 25 diopters: normal; between 18-25: sufficient; < 18 diopters: insufficient). In the TMD group, 36 subjects (75%) showed a compromise of convergence: 13 (36%) were classified in the 5-7 degree range and 23 (48%) in the > 7 cm degree range. The Berens test showed ten subjects (28%) in the group < 18D and 26 (72%) in the group 18-25D. The control-group presented ten (21%) subjects with compromise of convergence: three classified in the group < 18D and seven in the group 18-25D. The TMD subjects presented a higher statistical percentage (p < 0.0001) of ocular convergence defects. The TMD patients also reported a strong association referred to specific signs and symptoms, i.e., limited maximal opening or myofascial pain. There were some subjective reports also of headaches and torcicollis (neck stiffness) which appeared significantly more frequently in subjects with a compromise of convergence. The study showed a much higher prevalence of ocular convergence defects in patients with head, neck, and shoulder pain.     

Interleukin-4 inhibits cyclo-oxygenase-2 expression and prostaglandin E production by human mature dendritic cells

Interleukin-4 (IL-4) is considered the key cytokine for inducing T helper type 2 (Th2) cell differentiation, while interferon-gamma and IL-12 are pivotal cytokines for Th1 immune responses. Paradoxically, IL-4 has also been demonstrated to enhance IL-12 production by dendritic cells, suggesting an IL-4-dependent regulatory feedback of the Th1/Th2 system. In addition, prostaglandin E(2) (PGE(2)), a lipid mediator of inflammation, has been implicated in the enhancement of Th2-type responses acting directly on T and B lymphocytes. PGE(2) synthesis is dependent on the serial engagement of various enzymes, among which the inducible cyclo-oxygenase-2 (COX-2) exerts a critical role in monocytes and dendritic cells. In this study we demonstrate that IL-4 inhibits COX-2 gene expression and consequently prevents secretion of PGE(2) by mature human dendritic cells. We also show that PGE(2) does not regulate IL-12 and IL-10 production by dendritic cells in an autocrine fashion. Hence, we suggest that IL-4 may exploit an IL-12-independent regulatory feedback of the Th1/Th2 system through PGE(2) inhibition.     

Semiquantitative human cerebral perfusion assessment with ultrasound in brain space-occupying lesions: preliminary data.

OBJECTIVE: Transcranial Duplex ultrasound imaging with ultrasound contrast agents is an emerging technique for evaluating brain perfusion. The aim of this study was to evaluate cerebral perfusion with ultrasound in brain space-occupying lesions to identify different perfusion patterns. METHODS: Twenty patients with brain space-occupying lesions underwent ultrasound assessment of brain perfusion with a contrast pulse sequencing nonharmonic ultrasound technique and an ultrasound contrast agent bolus. Data were analyzed with software for semiquantitative analysis. RESULTS: Contrast pulse sequencing imaging with the semiquantitative analysis software allowed identification of qualitative and semiquantitative brain perfusion. Brain hemorrhages showed lower or absent perfusion compared with normal tissue. Meningiomas and glioblastomas without large necrotic areas showed higher perfusion compared with normal tissue. Glioblastomas with large necrotic areas showed overall reduced perfusion compared with normal tissue but higher than that of brain hemorrhages. In glioblastomas with large necrotic areas, it was possible to distinguish between solid and necrotic tissue. CONCLUSIONS: This bedside ultrasound technique, if validated by larger-scale studies, may add helpful information in noninvasive staging of brain tumors. Further potential applications may be in follow-up imaging to evaluate postoperative tumor recurrence or the presence of radionecrosis.     

Population pharmacokinetic study of gentamicin in a large cohort of premature and term neonates

AimThis study aims to investigate the clinical and demographic factors influencing gentamicin pharmacokinetics in a large cohort of unselected premature and term newborns and to evaluate optimal regimens in this population.MethodsAll gentamicin concentration data, along with clinical and demographic characteristics, were retrieved from medical charts in a Neonatal Intensive Care Unit over 5 years within the frame of a routine therapeutic drug monitoring programme. Data were described using non-linear mixed-effects regression analysis ( nonmem®).ResultsA total of 3039 gentamicin concentrations collected in 994 preterm and 455 term newborns were included in the analysis. A two compartment model best characterized gentamicin disposition. The average parameter estimates, for a median body weight of 2170 g, were clearance (CL) 0.089 l h⁻¹ (CV 28%), central volume of distribution (V_c) 0.908 l (CV 18%), intercompartmental clearance (Q) 0.157 l h⁻¹ and peripheral volume of distribution (V_p) 0.560 l. Body weight, gestational age and post-natal age positively influenced CL. Dopamine co-administration had a significant negative effect on CL, whereas the influence of indomethacin and furosemide was not significant. Both body weight and gestational age significantly influenced V_c. Model-based simulations confirmed that, compared with term neonates, preterm infants need higher doses, superior to 4 mg kg⁻¹, at extended intervals to achieve adequate concentrations.ConclusionsThis observational study conducted in a large cohort of newborns confirms the importance of body weight and gestational age for dosage adjustment. The model will serve to set up dosing recommendations and elaborate a Bayesian tool for dosage individualization based on concentration monitoring.