Defining tympanostomy tube plugs

OBJECTIVES: To define the composition of tympanostomy tube plugs because selecting or developing effective solvents depends on such knowledge. STUDY DESIGN: Prospective, in vitro laboratory study. METHODS: Luminal contents of 105 plugged, microscopically removed tympanostomy tubes were expressed, pooled, acid hydrolyzed, and passed through a high-performance liquid chromatography column. Retention times were compared with high-performance liquid chromatography standards to develop free amino acid and monosaccharide profiles. Cerumen, blood, and chronic mucoid effusion (collected during myringotomy) were pooled and subjected to the same analysis. The elution profiles of each substance were compared to determine which substance most closely matched the plugs. RESULTS: High-performance liquid chromatography amino acid and monosaccharide analysis demonstrated greatest similarity between tympanostomy tube plugs and mucoid effusion. CONCLUSIONS: Tympanostomy tube plug composition is more similar to mucoid effusion than to blood or cerumen. Solvents to open plugged tympanostomy tubes should be directed against the components of mucoid effusion.     

Older adult multiorgan donors and misdiagnosed tumor

BACKGROUND: In these last years, the increase in organ donations is mostly due to old patients died of primary vascular cerebral diseases. In this kind of patients some undiagnosed cancers can be present and can be transmitted to the receiver. Aim of this study is to carry out a research in order to identify any undiagnosed cancer which can be present during the period of encephalic death. METHODS: Perspective study: hospitals type II and type III. Polyvalent intensive care. From January 1999 to July 2000 encephalic death has been ascertained in 16 patients. The research of tumor markers has been carried out on these patients. Further diagnostic researches have been carried out on patients who had anomalous values. RESULTS: The organ donations have not been made by eight patients: five for family refusal, one for medical contraindications, two for the presence of undiagnosed tumor (PSA 1100 ng/ml and CEA 129.5 ng/ml) confirmed by prostatic and abdominal US imaging. A patient with CA 19-9 89.5 ng/ml has not been examined, because of the family refusal to donation. A patient with PSA of 135 ng/ml had a negative response from the anal scanner, and so the prosecution of the donation has not been interrupted. A blood sample has been taken and a biopsy of the prostate has been made to confirm the absence of neoplasm. CONCLUSIONS: It is necessary to make a careful examination of the organ donor to check if some cancers are present. Tumor markers cannot be used to make a diagnosis of a cancer, but they can be used as guide for further researches. In spite of all the diagnostic efforts, the objective evaluation of the surgeon is still the most important factor like the biopsy of all the suspected lesions during an operation and the autopsy.     

Mycobacterium tuberculosis may escape helper T cell recognition by infecting human fibroblasts

The host immune response can limit Mycobacterium tuberculosis (Mtb) spreading in primary tuberculosis (TB) without eradicating all bacilli, which can persist causing latent TB infection and are responsible for reactivation TB. Persistent Mtb is confined to granulomas within phagocytes, but it is also found in other non-immune cells. We focused on fibroblasts since these cells participate to the granuloma formation and were shown to be infected in latent TB infections.     

Abnormal hyperventilation in patients with hepatic cirrhosis: Role of enhanced chemosensitivity to carbon dioxide

Background

Patients with hepatic cirrhosis frequently show idiopathic hyperventilation at rest, despite no concomitant cardiopulmonary disease. The aim of the study was to determine whether altered chemosensitivity either to hypoxia or hypercapnia could underlie inappropriate hyperventilation in cirrhotic patients.

Methods

We consecutively recruited 30 biopsy proven cirrhotic patients equally distributed in the three Child's classes A, B and C (age 54 ± 8 years, mean ± SD). All patients underwent evaluation of chemosensitivity to hypoxia and to hypercapnia and blood sampling for brain natriuretic peptide, norepinephrine and progesterone, besides full clinical characterization. We also recruited 10 age- and gender-matched healthy controls (age 55 ± 7 years).

Results

Overall, 18 patients (60%) showed an increased chemosensitivity to carbon dioxide (CO₂), while 8 patients (27%) showed enhanced chemosensitivity to hypoxia. Child's class C patients had lower arterial partial pressure of CO₂ (PaCO₂), higher rest ventilation, increased chemosensitivity to hypercapnia, plasma level of norepinephrine and serum progesterone levels when compared to class A patients and controls (all p < 0.05). Rest ventilation was positively related to pH (R = 0.41, p = 0.023), chemosensitivity to hypercapnia (R = 0.54, p = 0.002), and progesterone (R = 0.53, p = 0.016) and negatively to PaCO₂ (R = 0.61, p < 0.001), but not to hemoglobin level and chemosensitivity to hypoxia. Chemosensitivity to hypercapnia was positively related to PaCO₂ (R = 0.74, p < 0.001), serum progesterone (R = 0.50, p = 0.016), and to plasma norepinephrine (R = 0.57, p = 0.004).

Conclusions

Enhanced chemosensitivity to hypercapnia was found in more decompensated cirrhotic patients and was associated with sympathetic overactivity and elevated serum progesterone, likely representing a key mechanism underlying the “unexplained” hyperventilation observed in such patients.     

5-Fluorouracil resistant colon cancer cells are addicted to OXPHOS to survive and enhance stem-like traits

Despite marked tumor shrinkage after 5-FU treatment, the frequency of colon cancer relapse indicates that a fraction of tumor cells survives treatment causing tumor recurrence. The majority of cancer cells divert metabolites into anabolic pathways through Warburg behavior giving an advantage in terms of tumor growth. Here, we report that treatment of colon cancer cell with 5-FU selects for cells with mesenchymal stem-like properties that undergo a metabolic reprogramming resulting in addiction to OXPHOS to meet energy demands. 5-FU treatment-resistant cells show a de novo expression of pyruvate kinase M1 (PKM1) and repression of PKM2, correlating with repression of the pentose phosphate pathway, decrease in NADPH level and in antioxidant defenses, promoting PKM2 oxidation and acquisition of stem-like phenotype. Response to 5-FU in a xenotransplantation model of human colon cancer confirms activation of mitochondrial function. Combined treatment with 5-FU and a pharmacological inhibitor of OXPHOS abolished the spherogenic potential of colon cancer cells and diminished the expression of stem-like markers. These findings suggest that inhibition of OXPHOS in combination with 5-FU is a rational combination strategy to achieve durable treatment response in colon cancer.     

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.