Brain tumor classification by proton MR spectroscopy: comparison of diagnostic accuracy at short and long TE

BACKGROUND AND PURPOSE: Different TE can be used for obtaining MR spectra of brain tumors. The purpose of this study was to determine the influence of the TE used in brain tumor classification by comparing the performance of spectra obtained at two different TE (30 ms and 136 ms). METHODS: One hundred fifty-one studies of patients with brain tumors (37 meningiomas, 12 low grade astrocytomas, 16 anaplastic astrocytomas, 54 glioblastomas, and 32 metastases) were retrospectively selected from a series of 378 consecutive examinations of brain masses. Single voxel proton MR spectroscopy at TE 30 ms and 136 ms was performed with point-resolved spectroscopy in all cases. Fitted areas of nine resonances of interest were normalized to water. Tumors were classified into four groups (meningioma, low grade astrocytoma, anaplastic astrocytoma, and glioblastoma-metastases) by means of linear discriminant analysis. The performance of linear discriminant analysis at each TE was assessed by using the leave-one-out method. RESULTS: Tumor classification was slightly better at short TE (123 [81%] of 151 cases correctly classified) than at long TE (118 [78%] of 151 cases correctly classified). Meningioma was the only group that showed higher sensitivity and specificity at long TE. Improved results were obtained when both TE were considered simultaneously: the suggested diagnosis was correct in 105 (94%) of 112 cases when both TE agreed, whereas the correct diagnosis was suggested by at least one TE in 136 (90%) of 151 cases. CONCLUSION: Short TE provides slightly better tumor classification, and results improve when both TE are considered simultaneously. Meningioma was the only tumor group in which long TE performed better than short TE.     

The KARTAN study: a postmarketing assessment of Irbesartan in patients with hypertension

BACKGROUND: An important purpose of postmarketing surveillance of drugs is to better characterize the safety profile of drug therapy in the clinical setting. Another goal is to confirm the effectiveness of these drugs in patients who are candidates for antihypertensive therapy and who may have been excluded from Phase III studies. Irbesartan is a long-acting angiotensin II-receptor blocker specific for the angiotensin 1-receptor subtype that, in clinical trials in patients with hypertension, reduces blood pressure. OBJECTIVES: The KARTAN (this word was derived from the first and last syllables of Karvea [trademark of Bristol-Myers Squibb Group, Madrid, Spain] and irbesartan) study was designed to confirm and extend the findings from previous clinical trials using data from a large number of patients with hypertension treated with irbesartan in routine clinical practice. The primary goal was to assess the types and incidences of adverse drug reactions (ADRs) occurring at a low frequency (<0.05%) with irbesartan. The secondary objectives were to study the effect of irbesartan as an antihypertensive agent, to assess the types and incidences of the most frequent ADRs (>/=0.05%) occurring in routine clinical practice, and to detect possible interactions between irbesartan and other drugs frequently used in the primary care setting. METHODS: This 6-month, observational, open-label, uncontrolled, national, longitudinal, prospective study was conducted by 852 primary care physicians across Spain. Men and women aged >/=18 years with mild to moderate hypertension who, in their physicians' opinion, should have been treated with irbesartan were included. Each patient was followed up for 6 months, attending visits at baseline (ie, the start of treatment) and 1, 3, and 6 months after the start of treatment. A sample size of 3219 patients was calculated for the detection of >/=1 low-incidence (<0.05%) ADR. After the baseline visit, therapy typically was begun with irbesartan 150 mg/d. The initial dose was titrated up, at 300-mg increments based on the patient's response, at each visit as needed to achieve the treatment goals (systolic blood pressure, <140 mm Hg; diastolic blood pressure, <90 mm Hg). Information regarding ADRs was collected on case-report forms designed for each visit and analyzed by the scientific committee of the study. All recruited patients were included in the tolerability analysis. RESULTS: A total of 4887 patients were enrolled (2165 men, 2 772 women; mean [SD] age, 61.1 [11.0] years [range, 19-94 years]; 23.3% of patients were aged >70 years); 4612 were assessable for efficacy. One hundred eight patients (2.2%) experienced ADRs over the 6-month treatment period; 3 of these patients (0.1%) experienced >1 ADR. Of the total number of clinical manifestations of ADRs, 24 occurred at an incidence <0.05%. Irbesartan produced reductions in blood pressure that were statistically significant from the first visit (all p < 0.001), and 39.9% of the patients achieved the treatment goal at the end of the follow-up period. CONCLUSION: In this postmarketing surveillance study of patients with hypertension treated in routine clinical practice, irbesartan showed a satisfactory tolerability profile that was consistent with that seen in randomized, controlled trials.     

Effect of glucomannan and the dosage form on ethinylestradiol oral absorption in rabbits

To the beneficial properties of dietary fiber in human health, several disadvantages can be added as the possible modification of the bioavailability of other drugs when administered by the oral route. In this study, the influence of glucomannan in the oral bioavailability of ethinyl estradiol (EE), when administered to female rabbits in two different dosage forms (enteric capsules and dispersed in water), was established. To carry out the study, three groups of six animals each were used. All animals received 1 mg kg(-1) oral EE, and rabbits in groups 2 and 3 received 1.5 g glucomannan dispersed in water or in enteric capsules, respectively, immediately before EE. When comparing the results obtained after the administration of EE/glucomannan dispersed in water with those obtained after the administration of this estrogen without fiber, we can see that Cmax is 1.4 times lower, AUC 1.9 times lower and that tmax is identical (10 min). However, after the administration of fiber in enteric capsules, AUC and Cmax are higher (4.1 and 7.8 times, respectively) than when the estrogen was administered alone, and also, there is a delay in tmax (20 min). After the administration of glucomannan in the enteric capsule, the fiber forms, as in the stomach, a highly viscous solution in the gut that would limit EE access to the mucosal surface delaying its absorption. However, this effect could be compensated by a reduction of EE metabolism in the intestinal wall, leading to a higher absorption of the estrogen.     

Community participation and social control in the health system

In Colombia, the 1991 Constitution established the obligation of promoting social participation. However, the discussion regarding the significance and scope of social participation is far from being over with the promulgation of the Constitution since social participation has a high political component, i.e., social participation requires the transfer of a part of power to sectors previously excluded from decision taking. As long as the State has conceived the market strategy as the best way to allocate resources and the receptors of social policy are considered as consumers, the challenge is to establish a balance between supply and demand in order to guarantee efficiency and efficacy in the application of resources and transparency in the public administration. Thus, the community of users has the mission of monitoring the correct allocation of State resources. Upon evaluating some of the results of the application of this strategy of social participation in health, three features can be highlighted: there are important advances in the promotion of social participation but not in social control; social control is dispersed and atomized, and participation as institutional policy is weak. Regarding the first aspect, it can be concluded that there has been a favorable response of the municipalities to the obligation of promoting the organizational forms of the community as far as health is concerned. When the actions carried out for social control are taken into account, the outlook varies. The convoking capacity of the institutions of the system to community organizations is considerably low, as well as the discussion of the reports presented by such organizations. On the other hand, the lack of communication between the different instances involved in both promotion of participation and social control became evident, situation which reflects the presence of relationships of bilateral nature, i.e., only the most direct interlocutor is known.     

Behavioral and molecular changes elicited by acute administration of SR141716 to Delta9-tetrahydrocannabinol-tolerant rats: an experimental model of cannabinoid abstinence

Whether chronic cannabinoid consumption produces a dependent state comparable to that occurring with other drugs (e.g. the appearance of withdrawal signs when consumption is interrupted), and whether chronic cannabinoid consumption increases the risk of consuming other drugs of greater addictive power, are probably the two questions relating to cannabinoid addiction that provoke the most controversy. The present study was designed to further explore these two questions in laboratory animals. Firstly, we examined the effects of an acute challenge with SR141716 (an antagonist for the cannabinoid CB(1) receptor) in Delta(9)-tetrahydrocannabinol (Delta(9)-THC)-tolerant rats. This antagonist has been reported to precipitate a cannabinoid withdrawal syndrome. Thus, the administration of SR141716 to Delta(9)-THC-tolerant rats reduced inactivity in the open-field test and enhanced responses as tremor, turning and retropulsion-these responses that were only slightly enhanced in control rats. The administration of SR141716 increased the plasma prolactin and the corticosterone concentration in controls, but these increases were much lesser in Delta(9)-THC-tolerant rats. In addition, CRF-mRNA levels in the paraventricular hypothalamic nucleus, while reduced in SR141716-treated controls, were significantly increased in Delta(9)-THC-tolerant rats. The analysis of endocannabinoids also revealed that the administration of SR141716, which was mostly inactive in control rats, was able to reverse the changes in anandamide or 2-arachidonoylglycerol concentrations found in Delta(9)-THC-tolerant rats, in the striatum, limbic forebrain, diencephalon, cerebellum and brainstem, but not in the midbrain and hippocampus. As a second objective, we evaluated whether Delta(9)-THC-tolerant rats were more vulnerable to morphine in a self-administration paradigm. The Delta(9)-THC-tolerant and control rats self-administered morphine to a similar extent, in concordance with the similar values of dopaminergic activity in limbic and motor regions. In summary, our data indicate that Delta(9)-THC-tolerant rats were not more vulnerable to the reinforcing properties of morphine. However, they responded to the blockade of CB(1) receptors by exhibiting slightly but possibly relevant differences in behavioral, endocrine and molecular parameters compared to the response in non-tolerant rats. This is indicative of the existence of a withdrawal syndrome in cannabinoid-tolerant rats that is mild compared with abstinence in opioid-dependent rats.     

Application of simple fertility awareness-based methods of family planning to breastfeeding women

OBJECTIVE: To determine the potential efficacy of two simple fertility awareness-based methods of family planning-the Standard Days Method and the TwoDay Method-among breastfeeding women. DESIGN: Analysis of pre-existing data set, collected in 1986-1990. SETTING: Pre-existing data from Australia, Britain, and Canada. PATIENT(S): Seventy-three breastfeeding women in Australia, Britain, and Canada, who were followed starting 42 days postpartum, until they had at least two potentially fertile cycles (defined as cycles with adequate levels of urinary estrogens (E) and pregnanediol glucuronide and a long enough luteal phase to support a pregnancy). We examine this existing data set. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Probability of pregnancy from intercourse on different days of the cycle relative to ovulation for breastfeeding women following the instructions of the Standard Days Method or the TwoDay Method. RESULT(S): These two methods may be appropriate for different groups of breastfeeding women at different times. The Standard Days Method may be appropriate after cycle regularity is established, whereas the TwoDay Method may be a more effective option earlier in the postpartum period. CONCLUSION: A need remains for a more appropriate simple fertility awareness-based method during this early period.     

Ultrastructural alterations induced by nifurtimox and another nitro derivative on epimastigotes of<Emphasis Type="Italic"> Trypanosoma cruzi</Emphasis>

We report the ultrastructural alterations induced on epimastigotes by nifurtimox and 5-nitro-2-thienyl-malononitrile (5NO2TM), a novel compound with anti-Trypanosoma cruzi activity. Parasites treated with concentrations of nifurtimox lower than usually employed for this kind of study showed vacuolisation, alterations of the mitochondria, the nucleus and the ribosomes. 5NO2TM caused the same kind of damage, but to a greater degree. This result correlates with the fact that cultures treated with this compound experienced a greater loss of viability.     

Proton MR spectroscopy in Wernicke encephalopathy

Wernicke encephalopathy is caused by thiamine deficiency. Although the clinical picture has been well established for some time, clinical diagnosis is attained in only 20% of the cases. MR imaging techniques contribute to early diagnosis of Wernicke encephalopathy. We herein report MR imaging and proton MR spectroscopic findings for a patient with clinical and biochemical features consistent with Wernicke encephalopathy. Increased lactate and typical MR imaging findings are discussed in the context of the known pathophysiology of Wernicke encephalopathy.     

The role of 5-HT1A/B autoreceptors in the antinociceptive effect of systemic administration of acetaminophen

BACKGROUND: It has been proposed that serotonin participates in the central antinociceptive effect of acetaminophen. The serotonin activity in the brainstem is primarily under the control of 5-HT1A somatodendritic receptors, although some data also suggest the involvement of 5-HT1B receptors. In the presence of serotonin, the blockade of 5-HT(1A/B) receptors at the level of the raphe nuclei leads to an increase in serotonin release in terminal areas, thus improving serotonin functions. This study examines the involvement of 5-HT(1A/B) receptors in the antinociceptive effect of acetaminophen in mice. METHODS: The effects of acetaminophen (600 mg/kg intraperitoneal) followed by different doses of antagonists (WAY 100635 [0.2-0.8 mg/kg subcutaneous] and SB 216641 [0.2-0.8 mg/kg subcutaneous]) or agonists (8-OH-DPAT [0.25-1 mg/kg subcutaneous] and CP 93129 [0.125-0.5 mg/kg subcutaneous]) of 5-HT1A and 5-HT1B receptors, respectively, were determined in the hot-plate test in mice. RESULTS: Acetaminophen (300-800 mg/kg) showed a dose-dependent antinociceptive effect in the hot-plate test in mice. WAY 100635 (0.2-0.8 mg/kg; 5-HT1A antagonist) induced an increase in the antinociceptive effect of 600 mg/kg acetaminophen, but this increase was not dose related. Conversely, 8-OH-DPAT (0.25-1 mg/kg; 5-HT1A agonist) decreased the antinociceptive effect of acetaminophen. SB 216641 (0.2-0.8 mg/kg; 5-HT1B antagonist) induced a dose-related increase in the antinociceptive effect of acetaminophen, and CP 93129 (0.25 mg/kg; 5-HT1B agonist) significantly decreased the antinociceptive effect of acetaminophen. CONCLUSIONS: These results suggest that the combination of acetaminophen with compounds having 5-HT1A and 5-HT1B antagonist properties could be a new strategy to improve the analgesia of acetaminophen, thanks to its mild serotonergic properties.