Cluster Headache in One Year Old Infant?

SYNOPSIS
Cluster headache is a type of essential headache affecting young or middle-age patients, whereas it is highly rare in children.
The case we are reporting here concerns a child who since the very first days after his birth appeared to suffer from severe attacks of agitation and sudden fits of weeping twice a day on average. When 21 months old, while in the hospital, he was found during the fits of weeping to complain of severe pain in the forehead, right temple and around the right eye. The examination carried out on him revealed no lesions of any type. The characteristics of 213 attacks were recorded up to the age of 27 months, when the crises disappeared spontaneously. The nature, duration and location of pain and the associated phenomena, as well as their regular occurrence every day make this type of headache affecting this patient fall within the category of cluster headache. The possibility of this type of headache appearing at such an early age seems to bear out the hypothesis that it may derive from a congenital biochemical disorder.     

Doppler echocardiographic assessment of left ventricular diastolic function in patients with primary lung cancer treated with doxorubicin

Eighteen patients were examined by Doppler echocardiography before and after treatment with doxorubicin (DXR). Early left ventricular filling rate decreased from 66 +/- 15 to 51 +/- 10 cm/sec whereas late filling rate increased from 48 +/- 12 to 61 +/- 9 cm/sec (p less than 0.05) with inversion of the E/A ratio suggesting an impairment of left ventricular diastolic function; conversely no significant changes were found in systolic function indexes. These results suggest that follow-up of patients treated with DXR must include left ventricular diastolic function studies. Doppler echocardiography can be successfully used to detect the presence of diastolic abnormalities.     

Comparison of 2 techniques of anesthesia induction in modern closed-circuit anesthesia]

The application of low flow anesthesia goes back already for more than 65 years when Ralph Waters introduced and applied cyclopropane with a very simple canister technique. The guide-lines for the clinical use of the closed circuit anesthesia were published in Chicago and Los Angeles by Professor Lin and Professor Lowe 15 years ago. We examined and followed these procedures on a modern anesthesia machine and easily achieved a good clinical performance. Our results were consistent with the modern anesthesia standard in closed circuit t.i.: economical benefits, environment savage of waste gases, heat production and humidification and last but not least in both techniques a quick anesthesia plane on 10-12 minutes that was consistent with theoretical considerations.     

Reduction of LDL production rate in ileal bypassed rabbits treated with lovastatin

The effect of lovastatin on the low density lipoprotein metabolism in bypassed rabbits was investigated. Partial ileal bypass effectively reduced total and low density lipoprotein (LDL) cholesterol by 44 and 48% respectively. The LDL drop was due to an increased fractional catabolic rate (FCR) of apolipoprotein B (apo B) from 0.74 to 1.27 pools per day with no effect on the apo B absolute catabolic rate and an increased expression of liver LDL receptors (+71%). Association of lovastatin with PIB resulted in a further decrease of total and LDL cholesterol (56 and 75% respectively) as compared to bypassed animals, without effects on the LDL FCR (1.27 +/- 0.11 versus 1.42 +/- 0.13 pools/day) or the expression of LDL receptors by the liver. The reduction of LDL was due to a decrease of the apolipoprotein B absolute synthetic rate (8.5 +/- 1.7 versus 13.6 +/- 1.7 mg/day). From these data we conclude that in bypassed rabbits lovastatin lowers total and LDL cholesterol mainly by reducing apolipoprotein B production rate.     

Breath analysis by API/MS—human exposure to volatile organic solvents

Summary The expired breath of subjects, exposed for periods of ca. 90 min to atmospheres artificially contaminated with low levels of methanol, (ca. 100 ppm) toluene (ca. 50 ppm) or tetrachloroethylene, (ca. 50 ppm) was monitored during and after the exposure period using an atmospheric pressure ionization mass spectrometer, fitted with a direct breath analysis system. The retention of solvent by the subjects, estimated from steady state levels in the expired breath, averaged 82% of the inspired level for methanol, 83% for toluene and 87% for tetrachloroethylene. The elimination of unchanged solvent via respiration during the post exposure period followed first order kinetics with mean half life values of 24 min for methanol, 27 min for toluene and 79 min for tetrachloroethylene.     

Severity of mitral regurgitation assessed by echocardiography. Reliability and limitations

To assess whether echocardiography may represent a useful mean to evaluate the degree mitral regurgitation (DR), left ventricular diastolic internal dimension (LVIDd), left atrial dimension (LAD), and velocity of circumferential fiber shortening (Vcf) were compared to DR assessed by left ventriculography in 48 patients with primary (n = 21) and cardiomyopathic (n = 27) valvular incompetence. In patients with good left ventricular contractility, i.e. with Vcf values above 1.02, a significant positive linear correlation was found between LVIDd and DR (LVIDd = 5.38 + 0.45DR; r = 0.72; p less than 0.001). In contrast, in patients with depressed left ventricular function, i.e. with Vcf values below 1.02, LVIDd did not correlate to DR. In either group LAD and Vcf did not correlate to DR. Thus, echocardiography may provide useful semiquantitative information concerning DR only in patients with preserved left ventricular performance.     

Glutamergic transmission and cardiovascular apparatus in normotensive rats

The cardiovascular effects induced by L-glutamic acid (G) on the cardiovascular apparatus of normotensive ethyl urethane-anaesthetized rats have been evaluated. (a) When administered i.v. (1 to 100 mg/kg) G induced a transitory and dose-dependent increase of arterial pressure (AP) with very moderate sinus bradycardia. It was antagonized by L-glutamic acid diethyl ester (GDEE, 0.1 to 100 mg/kg i.v.). (b) The intracerebroventricular (i.c.v.) administration of G (third ventricle, right lateral ventricle, posterior hypothalamus and striatum) at a dose of 0.1 to 10 mg/an induced a transitory and dose-dependent increase of AP, abolished by i.c.v. GDEE (1 to 10 mcg/an). (c) G hypertension was reduced by several procedures, i.e. catecholamine depletion, alpha 1, alpha 1 and alpha 2 or beta adrenergic blocks, alpha 2 central adrenergic stimulation, Ca2+ transmembrane or gangliary block, surrenectomy, and spinal transection at C7. (d) Atropine, bilateral vagotomy and sinus carotidal denervation increased G hypertension. (e) Therefore the bradycardia does seem to be due to a reflex-mediated effect via sinus carotid and aortic baroreceptors. (f) These data show that glutamergic transmission also participates through a central mechanism in the regulation of cardiovascular function in rats, via an increase in central sympathetic efferent activity.     

Combining targeted therapies and drugs with multiple targets in the treatment of NSCLC

The first generation of clinical trials of targeted agents in non-small cell lung cancer (NSCLC) treatment has concluded. To date, only a few of these new agents can offer hope of a substantial impact on the natural history of the disease. Nevertheless, clinically meaningful advances have already been achieved. In chemotherapy-refractory advanced NSCLC patients, gefitinib and erlotinib, two epidermal growth factor receptor tyrosine kinase inhibitors, represent a further chance for tumor control and symptom palliation. In chemotherapy-naive, advanced, nonsquamous NSCLC patients, the combination of the anti-vascular endothelial growth factor monoclonal antibody bevacizumab with chemotherapy was demonstrated to produce better survival outcomes than with chemotherapy alone. The relative failure of first-generation targeted therapies in lung cancer may be a result of multilevel cross-stimulation among the targets of the new biological agents. Thus, blocking only one of these pathways allows others to act as salvage or escape mechanisms for cancer cells. Preclinical evidence of the synergistic antitumor activity achievable by combining targeted agents that block multiple signaling pathways has recently been emerging. Clinical trials of multitargeted therapy may represent the second generation of studies in this field, and some of these are already ongoing. In a recent phase I/II trial, the combination of erlotinib and bevacizumab demonstrated very promising activity in the treatment of advanced NSCLC pretreated with chemotherapy. Whether the multitargeted approach is best performed using combinations of selective agents or agents that intrinsically target various targets is a matter of debate.     

Intracerebral diffusion of paramagnetic cationic liposomes containing Gd(DTPA)2- followed by MRI spectroscopy: assessment of pattern diffusion and time steadiness of a non-viral vector model

Cationic liposomes are generally considered as the non-viral counterparts of the more common viral vectors used in several gene therapy protocols, but their use as delivery vehicles is limited by their efficiency even if they display a lower toxicity. However, cationic liposomes are promising delivery systems in cell biology due to their ability to incorporate small molecules into their inner aqueous spheres and to deliver them into cells. Additionally, on the external surface they can bind therapeutic molecules such as nucleic acids, oligonucleotides, plasmids, etc. through electrostatic interactions. The aim of this work was to study the diffusion properties of such vehicles in vivo with a non-invasive technique and to monitor their tissue migration in order to collect information to be further used in gene therapy procedures. For this purpose, cationic liposomes containing the paramagnetic contrast agent Gd(DTPA)2- (Gd(III)-diethylenetriamine-N,N,N',N",N"-pentaacetic acid) were investigated because of their extended paramagnetic persistency in vivo, compared to the use of the contrast agent alone, and they were used to monitor the diffusion of such vehicles in an animal model (rat model). In particular, these vectors were injected into the rat brain through a stereotactic frame in a preformed cavity mimicking the lesion which had originated after surgical removal of the primary tumor. For the purpose of comparison, the same injection procedure was also applied to a control series of animals without a preformed brain lesion. Pattern diffusion and steadiness of the reported paramagnetic cationic liposomes were studied by means of Magnetic Resonance Imaging (MRI) which allowed us to monitor their diffusion and assess their intracerebral time availability up to 24 hours.     

3alpha-6alpha-Dihydroxy-7alpha-fluoro-5beta-cholanoate (UPF-680), physicochemical and physiological properties of a new fluorinated bile acid that prevents 17alpha-ethynyl-estradiol-induced cholestasis in rats

3alpha-6alpha-Dihydroxy-7alpha-fluoro-5beta-cholanoate (UPF-680), the 7alpha-fluorine analog of hyodeoxycholic acid (HDCA), was synthesized to improve bioavailability and stability of ursodeoxycholic acid (UDCA). Acute rat biliary fistula and chronic cholestasis induced by 17alpha-ethynyl-estradiol (17EE) models were used to study and compare the effects of UPF-680 (dose range 0.6-6.0 micromol/kg min) with UDCA on bile flow, biliary bicarbonate (HCO(3)(-)), lipid output, biliary bile acid composition, hepatic enzymes and organic anion pumps. In acute infusion, UPF-680 increased bile flow in a dose-related manner, by up to 40.9%. Biliary HCO(3)(-) output was similarly increased. Changes were observed in phospholipid secretion only at the highest doses. Treatment with UDCA and UPF-680 reversed chronic cholestasis induced by 17EE; in this model, UDCA had no effect on bile flow in contrast to UPF-680, which significantly increased bile flow. With acute administration of UPF-680, the biliary bile acid pool became enriched with unconjugated and conjugated UPF-680 (71.7%) at the expense of endogenous cholic acid and muricholic isomers. With chronic administration of UPF-680 or UDCA, the main biliary bile acids were tauro conjugates, but modification of biliary bile acid pool was greater with UPF-680. UPF-680 increased the mRNA for cytochrome P450 7A1 (CYP7A1) and cytochrome P450 8B (CYP8B). Both UDCA and UPF-680 increased the mRNA for Na(+) taurocholate co-transporting polypeptide (NCTP). In conclusion, UPF-680 prevented 17EE-induced cholestasis and enriched the biliary bile acid pool with less detergent and cytotoxic bile acids. This novel fluorinated bile acid may have potential in the treatment of cholestatic liver disease.