Prognostic value of the equivalents of transitory myocardial ischemia evaluated by exercise thallium-201 myocardial scintigraphy in an ambulatory population of 367 patients with a maximum 5-year follow-up

From 1-1-1981 to 3-31-1985, 367 subjects (227 males and 140 females) were examined by means of TL-201 myocardial scintigraphy for diagnostic purpose. A follow-up period, 5 years maximum, was run in order to assess the prognostic value of the three equivalents of transient myocardial ischemia which can be demonstrated by the test (angina, reversible hypoperfusion, and ST-T segment changes). The end points were myocardial infarction and/or sudden death. Three-hundred fifty-four patients complied (96%). During the observation period 9 severe ischemic events (SIE) occurred: 5 myocardial infarctions and 4 sudden deaths. As far as the predictivity of SIE is concerned, the "t" test for independent samples showed a statistically significant difference between the group of patients with no signs of ischemia and the group with positive scintiscan (p less than 0.05) and with the three equivalents of ischemia all together (p less than 0.05). Moreover, in the sub-group of patients with pathological scintigraphic results the probability for SIE to occur was statistically different in the patients with no hypoperfusion in the region supplied by the anterior descending coronary artery and in those with pathological scintigraphic findings in that region (p less than 0.05). In our opinion, the above data demonstrate the pathological signs noticeable with stress myocardial TL-201 scintiscan to have prognostic value.     

Different sympathovagal modulation of heart rate during social and nonsocial stress episodes in wild-type rats

The acute consequences of a social aversive stimulus (defeat) on the autonomic control upon the electrical activity of the heart were measured and compared to those observed in three nonsocial stress paradigms, namely restraint, shock-probe test, and swimming. Electrocardiograms were recorded from rats via radiotelemetry, and the autonomic neural control of the heart was evaluated via measures of heart rate and heart rate variability, such as the average R-R interval (RR), the standard deviation of RR (SD), the coefficient of variance (SD/RR), and the root-mean-square of successive R-R interval differences (r-MSSD). Although all stressors induced significant reductions of average R-R interval, the effect of defeat was significantly larger (p < 0.05). The social stimulus also determined a significant decrease in the variability indexes (p < 0.01 for all), whereas in the other stress conditions they were either unchanged or increased (SD/RR during restraint, p < 0.05; SD and SD/RR during swimming, p < 0.05 and p < 0.01). Cardiac arrhythmias (mostly ventricular premature beats, VPBs) were far more frequent during defeat than during the other challenging situations (p < 0.01), with an average of 33.5 +/- 6.5 VPBs per 15-min test recording. These data suggest that during defeat autonomic control was shifted toward a sympathetic dominance, whereas in rats exposed to nonsocial stressors, although significant heart rate accelerations were also found, sympathovagal balance was substantially maintained. These differences in autonomic stress responsivity explain the different susceptibility to ventricular arrhythmias and indicate that a social challenge can be far more detrimental for cardiac electrical stability than other nonsocial aversive stimuli.     

Tuberculosis: a rare and misleading etiology of tongue's ulcer

We report the case of a 43 year-old man, smoker, who used to live in Africa, consulting for a chronic ulcer of the mobile tongue. An initial biopsy did not show any carcinoma. A second biopsy highlighted an inflammation with numerous tuberculoid granulomas. However, the Ziehl-Neelsen stain was negative. Histoplasmosis of the tongue was then suspected as some round structures looking like yeasts and stained by the Gomori Grocott method were seen within the cytoplasm of giant cells. However, immunohistochemistry using anti-Histoplasma antibodies was negative. Polymerase chain reaction (PCR) assay performed on deparaffinized sections allowed the diagnosis of infection by Mycobacterium tuberculosis. A third biopsy confirmed the diagnosis of tuberculosis by showing some exceptional acid-fast bacilli. Culture was negative. Tuberculosis of the tongue is a very rare condition with different differential diagnosis including carcinoma in smoker population or histoplasmosis in endemic area.     

Activation of matrix metalloproteinase-2 from hepatic stellate cells requires interactions with hepatocytes.

Activation of matrix metalloproteinase (MMP)-2, the 72-kd collagenase IV/gelatinase A, is involved in extracellular matrix remodeling. It has been suggested that a membrane-type MMP (MT-MMP-1) and the tissue inhibitor of metalloproteinase (TIMP)-2 are involved in MMP-2 processing, but the exact mechanism(s) of its activation remains unclear. We have investigated the role of cell-cell cooperation in the activation of pro-MMP-2 in the liver, using pure cultures and co-cultures of hepatocytes and hepatic stellate cells (HSCs). Northern blot analysis and in situ hybridization showed that, in both pure and co-cultures, HSCs, but not hepatocytes, expressed MMP-2, TIMP-2, and MT-MMP-1 mRNA. Zymography analyses revealed the latent form of MMP-2 in medium from 2-day-old pure HSC cultures with higher amounts in medium from hepatocyte/HSC co-cultures. When hepatocytes were added to 10-day-old HSC cultures, the activated form of MMP-2 was detected, concomitantly with the deposition of an abundant extracellular matrix. Incubation of plasma membrane-enriched fractions from hepatocytes with conditioned medium from pure HSC cultures generated the activated species of MMP-2 (62 and 59 kd). Activation of pro-MMP-2 by hepatocyte membranes was inhibited by EDTA, heat, and trypsin but not by serine proteinase inhibitors. These data show that the co-expression of TIMP-2, MMP-2, and MT-MMP-1 by HSCs does not lead to secretion of the activated form of MMP-2. Hepatocytes, which do not express MMP-2, TIMP-2, or MT-MMP-1, induce MMP-2 activation through a plasma membrane-dependent mechanism(s), thus suggesting that cell-cell interactions are involved in this process in vivo.     

Morphine-induced TSH release in normal and hypothyroid subjects

The effects of morphine (10 mg i.v.), an opioid agonist, and of naloxone (10 mg i.v.), an opioid antagonist, on serum levels of TSH and PRL were studied in 7 hypothyroid patients and in 5 normal volunteers. Morphine administration induced a prompt, significant increase in serum TSH and PRL in all subjects. The degree of PRL release after morphine was similar in the two groups, while, as regards TSH, the increase was more evident in hypothyroid subjects. Pretreatment with naloxone (4 mg i.v. 5 min before morphine administration) blocked these effects in all subjects. In contrast, naloxone alone was not able to affect significantly TSH and PRL secretion. Moreover, in 5 other euthyroid volunteers, morphine significantly enhanced the response of TSH and PRL to TRH stimulation (200 micrograms i.v.). These data demonstrate that morphine exerts a stimulatory action on TSH and PRL secretion: the possible mode of action of this drug and the physiologic significance of these findings are discussed.     

Off-label thrombolysis versus full adherence to the current European Alteplase license: impact on early clinical outcomes after acute ischemic stroke

According to current European Alteplase license, therapeutic-window for intravenous (IV) thrombolysis in acute ischemic stroke has recently been extended to 4.5 h after symptoms onset. However, due to numerous contraindications, the portion of patients eligible for treatment still remains limited. Early neurological status after thrombolysis could identify more faithfully the impact of off-label Alteplase use that long-term functional outcome. We aimed to identify the impact of off-label thrombolysis and each off-label criterion on early clinical outcomes compared with the current European Alteplase license. We conducted an analysis on prospectively collected data of 500 consecutive thrombolysed patients. The primary outcome measures included major neurological improvement (NIHSS score decrease of ≤8 points from baseline or NIHSS score of 0) and neurological deterioration (NIHSS score increase of ≥4 points from baseline or death) at 24 h. We estimated the independent effect of off-label thrombolysis and each off-label criterion by calculating the odds ratio (OR) with 2-sided 95 % confidence interval (CI) for each outcome measure. As the reference, we used patients fully adhering to the current European Alteplase license. 237 (47.4 %) patients were treated with IV thrombolysis beyond the current European Alteplase license. We did not find significant differences between off- and on-label thrombolysis on early clinical outcomes. No off-label criteria were associated with decreased rate of major neurological improvement compared with on-label thrombolysis. History of stroke and concomitant diabetes was the only off-label criterion associated with increased rate of neurological deterioration (OR 5.84, 95 % CI 1.61–21.19; p = 0.024). Off-label thrombolysis may be less effective at 24 h than on-label Alteplase use in patients with previous stroke and concomitant diabetes. Instead, the impact of other off-label criteria on early clinical outcomes was not different compared with current European Alteplase license.     

Dengue Virus Type 3, South Pacific Islands, 2013

After an 18-year absence, dengue virus serotype 3 reemerged in the South Pacific Islands in 2013. Outbreaks in western (Solomon Islands) and eastern (French Polynesia) regions were caused by different genotypes. This finding suggested that immunity against dengue virus serotype, rather than virus genotype, was the principal determinant of reemergence.     

Lithium absorption prevented by sodium polystyrene sulfonate in volunteers.

STUDY OBJECTIVE: To determine if sodium polystyrene sulfonate prevents absorption of lithium in human beings. DESIGN: Prospective, crossover study. TYPE OF PARTICIPANTS: Healthy volunteers age 22 to 34 years (three women and three men). INTERVENTIONS: After an eight-hour fast, subjects ingested 0.5 mEq/kg (18.5 mg/kg) lithium carbonate. One hour later, they ingested either 857 mg/kg sodium polystyrene sulfonate in 4 mL water/g sodium polystyrene sulfonate (experimental) or an equal volume of water without sodium polystyrene sulfonate (control). MEASUREMENTS AND MAIN RESULTS: Serum lithium levels were drawn zero, one, two, three, four, six, eight, ten, 12, and 24 hours after lithium ingestion. The sodium polystyrene sulfonate group had a smaller mean area under the serum concentration curve (11.6 +/- 1.0 mEq/L.hr versus 13.6 +/- 1.5 mEq/L.hr, P < .001) and lower mean highest measured lithium level (0.85 +/- 0.11 mEq/L versus 1.05 +/- 0.10 mEq/L, P < .05) compared with the control group. There was no significant difference in 24-hour urine lithium excretion or in serum sodium and potassium levels. CONCLUSION: Sodium polystyrene sulfonate administration decreased absorption of lithium after a lithium carbonate overdose. Sodium polystyrene sulfonate may be useful clinically for gastric decontamination after lithium overdoses.