Impact of Time on Thrombolysis in Cerebral Infarction Score Results.

PURPOSE: Extended thrombolysis in cerebral infarction (eTICI) score results of 2b or higher are known to be predictors for favorable outcome after acute stroke. Additionally, time is a major factor influencing outcome after ischemic stroke. Until today only little is known about the impact of time on angiographic results regarding the outcome after mechanical thrombectomy; however, this impact might be of interest if an initially unfavorable angiographic result has to be improved. METHODS: Retrospective study of 164 patients with large vessel occlusion of the anterior circulation treated by mechanical thrombectomy. Multiple logistic regression analysis of relevant periprocedural and procedural times in respect to the probability of achieving functional independence at 90 days in respect to different eTICI results was performed to build a time and TICI score-dependent model for outcome prediction in which the influence of time was assumed to be steady among the TICI grades. RESULTS: The probability of achieving a favorable outcome is significantly different between eTICI2b-50, 67, TICI2c and TICI3 results (p < 0.001). The odds for achieving a favorable outcome decrease over time and differ for each TICI category and time point. The individual odds for each patient, time point and TICI grade can be calculated based on this model. CONCLUSION: The impact of periprocedural and procedural times and eTICI reperfusion results adds a new dimension to the decision-making process in patients with primary unfavorable angiographic results.

Evaluation of carbapenem-resistant Enterobacteriaceae in an Italian setting: report from the trench.

The spread of carbapenem resistant Enterobacteriaceae (CRE) has recently become a matter of concern in public health, mainly due to the wide distribution of carbapenemase genes. Italy is a country considered endemic for the spread of blaKPC Klebsiella pneumoniae (KP). The aim of this study was to depict the epidemiological trend of CRE in one Italian hospital over a long period (3 years surveillance, from May 2011 to April 2014). Based on defined MIC cut-off for specific carbapenems, 164 strains isolated from 146 different patients were analyzed both phenotypically and genotypically to establish the resistance genes. Molecular typing was performed using the RAPD technique. 77 strains were demonstrated to harbor the blaKPC gene (73 KP, 4 Escherichia coli - EC), 51 strains the blaVIM gene (44 KP, 3 EC, 2 Enterobacter cloacae and 2 Klebsiella oxytoca), 8 the blaNDM gene (3 KP, 4 EC and one Providencia stuartii), 3 the blaOXA-48 gene (2 KP, 1 EC), whereas 25 out of the 164 isolates (of different genera and species) had a negative multiplex-PCR amplification for all the targets tested. 39 out of the 164 strains analyzed (23.8%) revealed discrepancies between the MICs obtained with automated instrument and gradient MICs of more than two logs of difference; the broth microdilution provided a better agreement with the results obtained with the gradient MIC. The use of RAPD allowed to distinguish different clusters, closely related, both for blaKPC and for blaVIM KP.

Abnormal renal responses to calcium entry blockade in normotensive offspring of hypertensive parents.

In nine young normotensive subjects with no family history of hypertension and nine age-matched normotensive subjects with one parent with essential hypertension, effective renal plasma flow (p-aminohippuric acid clearance), glomerular filtration rate (inulin clearance), and excretion of sodium and exogenously administered lithium were measured for 90 minutes before and after administration of a single 20-mg oral dose of the calcium entry blocker nifedipine. Segmental tubular handling of fluid and sodium was estimated using lithium clearance as a marker of proximal tubular reabsorption. Nifedipine did not cause any change in subjects with no family history of hypertension, but in those with one hypertensive parent there was a marked increase in effective renal plasma flow (from 644 +/- 39 to 847 +/- 42 [SEM] ml/min x 1.73 m2; p less than 0.001) and a decrease in filtration fraction (from 17.6 +/- 1.0 to 12.6 +/- 0.4%; p less than 0.001), while the glomerular filtration rate was unchanged, thus suggesting a prevailing efferent vasodilation. Sodium excretion rate (p less than 0.02) and fractional sodium excretion (p less than 0.025) increased slightly but significantly in subjects with one hypertensive parent, but not in normotensive subjects with no family history of hypertension. Lithium clearance also rose (from 29.0 +/- 2.0 to 32.8 +/- 1.9 ml/min, p less than 0.001), and the derived value of fractional proximal reabsorption diminished (from 75.8 +/- 1.0 to 71.3 +/- 1.2%, p less than 0.001). Estimated distal delivery of sodium and absolute distal sodium reabsorption both increased significantly (p less than 0.005), while fractional distal sodium reabsorption was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Opioid modulation of the gamma-aminobutyric acid-controlled inhibition of exercise-stimulated growth hormone and prolactin secretion in normal men.

The possible involvement of endogenous opioids in the gamma-aminobutyric acid-controlled (GABAergic) inhibition of growth hormone (GH) and prolactin (PRL) during physical exercise was evaluated in normal men. After fasting overnight, seven subjects were tested on four mornings at least 1 week apart. Exercise was performed on a bicycle ergometer. The workload was gradually increased at 3-min intervals until exhaustion and lasted about 15 min in all subjects. Tests were carried out under administration of placebo, the opioid antagonist naloxone (10 mg as an iv bolus injection), the GABAergic agonist sodium valproate (600 mg in three divided doses orally) or naloxone plus sodium valproate. During exercise, plasma GH and PRL levels rose 5.5- and 1.9-fold, respectively. The administration of naloxone did not modify, whereas sodium valproate significantly reduced the plasma GH and PRL rise during exercise. In the presence of sodium valproate, GH and PRL levels rose 3- and 1.5-fold, respectively, in response to exercise. When naloxone was given together with sodium valproate, both GH and PRL responses to exercise were abolished completely. These data suggest the involvement of a GABAergic mechanism in the regulation of GH and PRL responses to physical exercise in men. Furthermore, the data argue against a role of naloxone-sensitive endogenous opioids in the control of these hormonal responses to exercise, whereas they suggest a modulation by opioids of the GABAergic inhibitory action.

Dopaminergic modulation of acute renal effects of nicardipine.

In order to investigate whether dopamine receptors are involved in the acute natriuretic effects of calcium channel blockade, experiments were carried out in humans with uncomplicated essential hypertension. In 8 hypertensives 5 mg intravenous nicardipine produced a large decrease in blood pressure and renal vascular resistance, a slight but significant increase in glomerular filtration rate (GFR) and marked natriuresis. When a second identical experiment was performed in the same subjects with the addition of 10 mg metoclopramide as dopamine blocker, changes in sodium excretion and vascular resistance were the same, but GFR did not increase during nicardipine. In a second set of experiments (n = 5) the same design was used, but nicardipine was infused at a dose of 0.01 mg/kg, ie, seven times less than in previous experiments. Under these conditions, blood pressure, renal vascular resistance and GFR did not change, but significant natriuresis occurred. Natriuresis was almost completely prevented by metoclopramide. In 5 additional hypertensives, metoclopramide alone was infused and 0.01 mg/kg nicardipine was added to the infusion. No change in any parameter was observed. Our findings suggest that the dopaminergic system participates in maintaining or increasing GFR during blood pressure reduction by calcium antagonists, although renal vasodilation and natriuresis are largely independent of dopamine receptor activity. In addition, when low doses of calcium antagonists produce natriuresis in the absence of renal or systemic hemodynamic changes (direct tubular effect), dopamine blockade is able to blunt this effect. This indicates a modulation by dopaminergic receptors of the direct tubular action of calcium antagonists.

Different effects of naloxone on the growth hormone response to melatonin and pyridostigmine in normal men.

The effect of melatonin (MEL) (12 mg orally), pyridostigmine (60 mg orally), the combination of MEL and pyridostigmine, or placebo on growth hormone (GH) secretion was tested in seven normal men. In addition, MEL tests and pyridostigmine tests were repeated after pretreatment with naloxone (1.2-mg bolus followed by intravenous [i.v.] infusion of 1.6 mg/h for 3 hours). Serum GH levels increased fivefold after MEL and sixfold after pyridostigmine administration. The concomitant administration of MEL did not change the GH response to pyridostigmine. In the presence of naloxone, the GH response to MEL was completely abolished, whereas naloxone did not modify the pyridostigmine-induced GH increase. These data suggest that MEL and pyridostigmine stimulate GH secretion through a common mechanism, which is probably represented by the inhibition of somatostatin activity. However, in contrast to pyridostigmine, the action of MEL appears to be exerted through a naloxone-sensitive opioid mediation.

Different effects of pyridostigmine on the thyrotropin response to thyrotropin-releasing hormone in endogenous depression and subclinical thyrotoxicosis.

Primary organic disorders of the thyroid gland must be excluded in interpreting the thyrotropin (TSH)-releasing hormone (TRH) test in affective disease. Both endogenous depression and subclinical thyrotoxicosis are frequently associated with low basal TSH levels and a blunted (<5 mIU/L) TSH response to TRH despite thyroid hormone levels within the normal range. The present study was performed to establish whether a reduction of the hypothalamic somatostatinergic tone by treatment with the acetylcholinesterase inhibitor pyridostigmine before TRH might be useful to distinguish endocrine from affective diseases. Twelve male depressed patients (aged 41.4 +/- 3.1 years) and 12 men (aged 43.4 +/- 4.1 years) with subclinical thyrotoxicosis because of autonomous thyroid nodules were selected according to the presence of a low basal TSH level and a blunted TSH response to 200 microg TRH intravenously (IV) (TSH increment was <5 mIU/L at 30 minutes [peak] after TRH) but thyroid hormone levels within the normal range. All patients were tested again with TRH 60 minutes after treatment with 180 mg pyridostigmine orally. Eleven normal men served as controls. Basal TSH levels were 0.2 +/- 0.2 mIU/L (mean +/- SE) in depression and 0.1 +/- 0.2 in subclinical thyrotoxicosis (normal controls, 1.4 +/- 0.3). In both groups, the mean peak response to TRH was significantly higher than baseline; however, according to selection, the TSH increase was less than 5 mIU/L. Pyridostigmine did not change basal TSH levels in any group, but significantly enhanced the TRH-induced TSH increase in normal controls and in depressed subjects (TSH increment became >7 mIU/L in all depressed subjects). In contrast, no significant change in the TSH response to TRH was observed in subclinical thyrotoxicosis after pyridostigmine treatment. Basal and TRH- and pyridostigmine + TRH-induced TSH levels were significantly higher in the normal controls than in the other groups. These data show a cholinergic involvement in the blunted TSH response to TRH in patients with endogenous depression, but not in subjects with subclinical thyrotoxicosis, suggesting that these diseases could be separated on the basis of the pyridostigmine + TRH-induced TSH response test.

Influence of thyroid status on the paradoxical growth hormone response to thyrotropin-releasing hormone in human obesity.

Thyrotropin-releasing hormone (TRH) tests were performed in 38 age- and weight-matched obese but otherwise healthy men. In all subjects, total thyroxine (T4) and triiodothyronine (T3) concentrations were in the normal range. According to basal and TRH-stimulated serum thyrotropin (TSH) levels, subjects were divided into the following three groups: group I (n = 14), euthyroid subjects; group II (n = 11), euthyroid subjects with normal basal but abnormally elevated TSH responses to TRH; group III (n = 13), subjects with elevated basal and TRH-induced TSH levels (subclinical hypothyroidism). Basal TSH levels were 1.8 +/- 0.4 mU/L in group I, 1.7 +/- 0.3 in group II, and 6.0 +/- 0.7 in group III. In both groups II and III, TRH-induced TSH increments were above the normal range (maximal increment > 14 mU/L) and were significantly higher than in group I. The definition of euthyroidism for groups I and II and of subclinical hypothyroidism for group III according to the basal levels of TSH was confirmed by clinical (Billewicz index), hormonal (serum free-T4 levels), and metabolic (serum apoprotein [apo] AI levels) parameters. Basal concentrations of growth hormone (GH) were similar in all groups. When GH levels after TRH stimulation were measured, significant increments (peak minus baseline > 5 micrograms/L) were observed in nine of 13 hypothyroid obese men. The overall mean peak GH increase in group III was 4.5 times higher than baseline and was observed at 45 minutes. None of the euthyroid obese subjects of groups I and II showed any significant change in GH levels in response to TRH.(ABSTRACT TRUNCATED AT 250 WORDS)

Luteinizing hormone response to an intravenous infusion of substance P in normal men.

The effect of synthetic substance P (SP), infused intravenously in doses of 0.5, 1.0, or 1.5 pmol/kg-1/min-1 for 60 minutes, on gonadotropin secretion was evaluated in seven healthy men. SP tests and a control test with normal saline were randomly performed at weekly intervals. During the tests, SP infusion did not produce untoward side effects or changes in blood pressure. Plasma testosterone concentrations were normal in all subjects and remained unmodified during all tests, regardless of the infused dose of SP. Plasma luteinizing hormone (LH) levels were not modified when either normal saline or the lowest dose of SP were infused, whereas they were significantly increased in a dose-dependent fashion when larger amounts of SP were administered. In contrast, plasma follicle-stimulating hormone (FSH) concentrations did not change significantly during any test. These data demonstrate for the first time in normal men that the systemic infusion of SP stimulates LH release, without modifications of FSH secretion.

Intravenously infused substance P enhances basal and growth hormone (GH) releasing hormone-stimulated GH secretion in normal men.

The effect of synthetic substance P (SP), infused intravenously (IV) in doses of 0.5, 1, or 1.5 pmol/kg-1/min-1 over 60 min, on GH secretion was evaluated in seven healthy men. Substance P tests and a control test with normal saline were randomly performed at weekly intervals. No untoward side effects or changes in blood pressure were observed during SP infusions. Serum GH concentrations did not change when normal saline, the lowest dose, or the middle dose of SP were infused. In contrast, GH levels rose significantly when the highest dose of SP was given, with a mean peak two times higher than baseline. Further studies were performed to test the possible influence of SP on the GH response to GH-RH. For this purpose, seven other healthy men were tested with GH-RH (1 micrograms/kg body weight in an IV bolus) during saline or SP (1.5 pmol/Kg-1/min-1 x 60 min) infusion. The GH-RH induced a significant GH rise, with a mean peak seven times higher than baseline. When subjects were infused with SP, the GH response to GH-RH was greatly enhanced, with a mean peak 12 times higher than baseline. These results demonstrate for the first time in humans that the systemic infusion of SP stimulates GH secretion, and suggest that SP might interact with GH-RH in the stimulation of GH secretion.