Middle ear schwannoma--case report

Schwannoma is one of the common benign middle ear space tumors. The tumors may present with facial nerve paresis or palsy, otologic symptoms and/or parotid mass middle ear schwannomas may originate from the nerves of the tympanic caviti or by extensions from outside the middle ear space. Schwannomas of the facial nerve can occur along any segment, but they frequently involve the geniculate ganglion and extend proximally or distally from there. MRI and CT imaging characteristics are similar to those of vestibular schwannomas. We present the clinical and radiologic features of a middle-space schwannoma originating from facial nerve. The patient underwent middle ear exploration and mastoidectomy. The tumor was of facial nerve origin and was separated from middle ear. The pathologic diagnosis was schwannoma.     

Melatonin-induced modulation of glucose metabolism in primary cultures of rabbit kidney-cortex tubules

The effect of melatonin on glucose metabolism in the presence and absence of insulin has been investigated in the primary cultures of renal tubules grown in a defined medium. In the absence of glucose in the medium containing 5 microg/mL of insulin and 2 mm alanine + 5 mm glycerol + 0.5 mm octanoate, 100 nm melatonin stimulated both glucose and lactate synthesis, while in the medium devoid of insulin melatonin action was negligible. Melatonin-induced increase in glucose and lactate synthesis was accompanied by an enhancement of alanine and glycerol consumption. In view of measurements of [U-14C]L-alanine and [U-14C]L-glycerol incorporation into glucose, it is likely that melatonin increased alanine utilization for glucose production, while accelerated lactate synthesis was because of an enhanced glycerol consumption. As (i) 10 nm luzindole attenuated the stimulatory action of melatonin on glucose formation and (ii) the indole induced a decrease in intracellular cAMP level, it seems likely that in renal tubules melatonin binds to ML1 membrane receptor subtype. In view of a decline of intracellular fructose-1,6-bisphosphate content accompanied by a significant rise in hexose-6-phosphate and glucose levels, melatonin might result in an acceleration of flux through fructose-1,6-bisphosphatase probably because of an increase in the active, dephosphorylated form of this enzyme. Thus, the administration of melatonin in combination with insulin might be beneficial for diabetic therapy because of protection against hypoglycemia.     

Quantitation in gated perfusion SPECT imaging: the Cedars-Sinai approach.

Cedars-Sinai's approach to the automation of gated perfusion single photon emission computed tomography (SPECT) imaging is based on the identification of key procedural steps (processing, quantitation, reporting), each of which is then implemented, in completely automated fashion, by use of mathematic algorithms and logical rules combined into expert systems. Our current suite of software applications has been designed to be platform- and operating system-independent, and every algorithm is based on the same 3-dimensional sampling scheme for the myocardium. The widespread acceptance of quantitative software by the nuclear cardiology community (QGS alone is used at over 20,000 locations) has provided the opportunity for extensive validation of quantitative measurements of myocardial perfusion and function, in our opinion, helping to make nuclear cardiology the most accurate and reproducible modality available for the assessment of the human heart.     

Arrhythmogenic right ventricular cardiomyopathy in two pairs of monozygotic twins

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inheritant disease with an autosomal dominant mode of transmission with incomplete penetrance and variable expression. Linkage analysis in affected families succeeds in identifying 9 loci determining 9 subtypes of the disease. Genotype phenotype correlation is unclear and the influence of various environmental factors is discussed. OBJECTIVES: Genotype phenotype correlation in 2 pairs of monozygotic twins with ARVC and the role of environmental factors are analyzed. PATIENTS AND METHODS: Among 40 pts with ARVC and their 195 relatives there were 2 pairs of monozygotic twins: brothers, age 47 y; and sisters, age 48 y. History, ECG, Holter monitoring, 2D and Doppler Echo, and MRI were analyzed. RESULTS: Twin brothers: ARVC was diagnosed in the proband after the episode of VT with LBBB morphology (enlarged right ventricle, focal hypokinesia of apex, MR evidence of adipose tissue in RV wall). Identical morphology of RV was seen in asymptomatic twin brother. The patient presenting arrhythmia has been rowing for 4 years. Twin sisters: diagnosis was done during family screening. Both were asymptomatic. RV morphology typical for ARVC was found discrete in one of them (bulges adipose tissue in the RV apex); the latter showed changes suggesting RV abnormality (mild segmental dilatation of infundibulum, adipose tissue in a free wall of the RV). No differences in previous viral infections and sports involvement were observed. CONCLUSIONS: 1. Clinical picture of ARVC in monozygotic twins is not identical. 2. Strenuous effort may be a factor triggering the arrhythmia in pts with ARVC.     

Cardiac status after childhood growth hormone treatment of Turner syndrome

CONTEXT: In Turner syndrome (TS), GH treatment is well established. Data on cardiac status after discontinuation of treatment are scarce. This study aimed to assess biventricular size and function in TS at least 6 months after discontinuation of GH treatment. METHODS: TS patients and healthy women prospectively underwent cardiac magnetic resonance imaging. Ventricular two-dimensional tomographic cine data were acquired to obtain biventricular volume, mass, and ejection fraction. Atrioventricular valve flow measurements were performed using a two-dimensional flow-sensitized sequence. Flow velocity curves were calculated and indices of biventricular diastolic filling were derived. RESULTS: Thirty-one patients [mean (sd) age 20 (2) yr, body surface area 1.75 (0.15) m(2), 5 (2) yr after GH discontinuation] and 23 normal control women [age 21 (2) yr, body surface area 1.80 (0.13) m(2)] were included. Compared with controls, patients had smaller mean end-diastolic volumes [right ventricle (RV), 84 (11) ml/m(2) vs. 79 (10), P = 0.02; left ventricle (LV), 81 (10) vs. 72 (9), P < 0.001], end-systolic volumes [RV 38 (7) ml/m(2) vs. 36 (6), P = 0.04; LV 34 (5) vs. 29 (4), P < 0.001], and stroke volumes [RV 46 (6) ml/m(2) vs. 43 (6), P = 0.03; LV, 47 (7) vs. 44 (4), P = 0.02]. Patients had a higher mean heart rate [79 (13) beats/min vs. 71 (10), P < 0.05]. Biventricular ejection fraction, mass, cardiac output, and diastolic filling pattern were comparable. CONCLUSION: After discontinuation of GH treatment TS patients showed no myocardial hypertrophy and well-preserved biventricular function. Ventricular volumes were smaller in Turner patients, compared with controls, whereas mean heart rate was higher. These last observations may be part of the natural development in TS and not linked to GH treatment, which at this point we consider safe.     

Towards potent but less toxic nanopharmaceuticals – lipoic acid bioconjugates of ultrasmall gold nanoparticles with an anticancer drug and addressing unit

Modification of ultrasmall gold nanoparticles (AuNPs) with the lipoic acid derivative of folic acid was found to enhance their accumulation in the cancer cell, as compared to AuNPs without addressing units. The application of lipoic acid enabled the control of the gold nanoparticle functionalities leading to enhanced solubility and allowing for attachment of both the folic acid and the cytotoxic drug, doxorubicin. More robust attachment of doxorubicin to the nanoparticle through the amide bond resulted in toxicity comparable with that of the drug alone, opening a new perspective for designing more potent, but less toxic nanopharmaceuticals. The increased uptake was accompanied by pronounced nuclear accumulation and observable cytotoxicity. Doxorubicin binding via covalent amide bonds enhanced stability of the whole drug vehicle and provided much better control over doxorubicin release in the cell environment, as compared to physical adsorption or pH sensitive bonding commonly used for anthracycline carriers. Confocal microscopy revealed that the bond was stable in the cytoplasm for 22 h. The ability to slow down the rate of drug release may be crucial for the application in sustained anticancer drug delivery. Biological analyses performed using MTT assay and confocal microscopy confirmed that the ultrasmall AuNPs with the lipoic acid derivative of folic acid exhibit relatively low cytotoxicity, however when loaded with a chemotherapeutic, they cause a significant reduction in the cell viability.

Modification of ultrasmall gold nanoparticles (AuNPs) with the lipoic acid derivative of folic acid was found to enhance their accumulation in the cancer cell, as compared to AuNPs without addressing units.     

New synthetic pathway leading to oxospirochlorins

In this work we propose a completely new approach for the synthesis of spirochlorin derivatives based on the use of an imino-keto intermediate formed in situ from 2-amino-5,10,15,20-tetraphenylporphyrins and inverse electron demand Diels–Alder (iEDDA) cycloaddition with 3,6-di-2-pyridyl-1,2,4,5-tetrazine. The mechanism of reaction was analyzed employing theoretical methods by comparing the difference in energy of Frontier Molecular Orbitals (FMO) for appropriate reagents. Ground-state molecular electrostatic (ESP) potential maps were employed as additional tools allowing explanation of the reactivity of substrates. The new class of spirochlorin compounds was fully characterized by means of mass spectrometry, IR, liquid and solid state NMR and X-ray crystallography. Correlation between molecular structure and optical properties for the obtained title compounds is discussed.

Oxospirochlorins – novel analogs of porphyrinoids were synthesized and characterized by various methods including X-ray, NMR spectroscopy and mass spectrometry.     

Non-invasive mechanical ventilation improves walking distance but not quadriceps strength in chronic respiratory failure

BACKGROUND: In patients with chronic respiratory failure (CRF) nocturnal mechanical ventilation (NMV) confers increased exercise tolerance. The hypothesis tested in the present study was that the increased exercise performance is associated with increased quadriceps strength. METHODS: In 28 patients with CRF due to chronic obstructive pulmonary disease and restrictive thoracic disease (post-tuberculosis-sequelae, scoliosis and obesity-hypoventilation) NMV was started. Before and after 2-month NMV the exercise tests, namely shuttle and 6-min walking distance, were performed. Furthermore, quadriceps strength was measured as the twitch tension elicited by magnetic stimulation the femoral nerve (TwQ) and the maximum voluntary contraction force (MVC). RESULTS: After 2 months therapy with NMV there was significant clinical and blood gas improvement. NMV significantly improved the walking distance by approximately 18% but there was no improvement in TwQ or MVC, the data could exclude a 15% improvement in TwQ with 82% confidence. CONCLUSION: The strength of quadriceps does not change after 2 months of effective NMV in patients with CRF despite a marked increase in endurance time. Factors other than quadriceps strength account for the improved performance.     

Elevated soluble intercellular adhesion molecule-1 levels in obesity: relationship to insulin resistance and tumor necrosis factor-alpha system activity.

Intercellular adhesion molecule-1 (ICAM-1) is 1 of the possible factors linking obesity and diabetes with cardiovascular disease, however, the mechanism of the increase in ICAM-1 concentration in obesity remains unclear. Therefore, the aim of the present study was to assess plasma soluble ICAM-1 (sICAM-1) levels in obese subjects with normal glucose tolerance and to evaluate whether those levels may be related to insulin resistance and tumor necrosis factor-alpha (TNFalpha) system activity. The study was performed in 8 lean and 15 obese subjects. Anthropometric and biochemical parameters were measured, and insulin sensitivity was evaluated using the euglycemic hyperinsulinemic clamp technique (insulin infusion, 50 mU x kg(-1) x h(-1)). Obese subjects were markedly more hyperinsulinemic and insulin resistant and had higher plasma soluble TNF receptor 2 (sTNFR2) and sICAM-1 levels. sICAM-1 was related positively to body mass index (BMI), waist-to-hip ratio (WHR), percent of body fat, glycated hemoglobin (HbA(1c)), plasma insulin and triglycerides (TG), TNFalpha, and sTNFR2 and negatively to insulin sensitivity. Multiple regression analysis showed that only sTNFR2 and insulin sensitivity were independent predictors of sICAM-1 concentrations and were responsible for 66% of sICAM-1 variability. We conclude that an increase in plasma sICAM-1 concentration in obesity is related to TNFalpha system activation and insulin resistance.