MTT Heterogeneity in Perfusion CT Imaging as a Predictor of Outcome after Aneurysmal SAH.

BACKGROUND AND PURPOSE: Impairment of tissue oxygenation caused by inhomogeneous microscopic blood flow distribution, the so-called capillary transit time heterogeneity, is thought to contribute to delayed cerebral ischemia after aneurysmal SAH but has so far not been systematically evaluated in patients. We hypothesized that heterogeneity of the MTT, derived from CTP parameters, would give insight into the clinical course of patients with aneurysmal SAH and may identify patients at risk of poor outcome. MATERIALS AND METHODS: We retrospectively analyzed the heterogeneity of the MTT using the coefficient of variation in CTP scans from 132 patients. A multivariable logistic regression model was used to model the dichotomized mRS outcome. Linear regression was used to eliminate variables with high linear dependence. T tests were used to compare the means of 2 groups. Furthermore, the time of the maximum coefficient of variation for MTT after bleeding was evaluated for correlation with the mRS after 6 months. RESULTS: On average, each patient underwent 5.3 CTP scans during his or her stay. Patients with high coefficient of variation for MTT presented more often with higher modified Fisher (P = .011) and World Federation of Neurosurgical Societies grades (P = .014). A high coefficient of variation for MTT at days 3-21 after aneurysmal SAH correlated significantly with a worse mRS score after 6 months (P = .016). We found no correlation between the time of the maximum coefficient of variation for MTT after bleeding and the patients' outcomes after 6 months (P = .203). CONCLUSIONS: Heterogeneity of MTT in CTP after aneurysmal SAH correlates with the patients' outcomes. Because the findings are in line with the pathophysiologic concept of the capillary transit time heterogeneity, future studies should seek to verify the coefficient of variation for MTT as a potential imaging biomarker for outcome.

Is there A Relationship between route of delivery, perinatal characteristics, and neonatal outcome in preterm birth?

BACKGROUND: Preterm birth is one of the most challenging problems in obstetric care and it is closely related to perinatal mortality and morbidity. The aim of the current study was to document our experience with preterm births and to analyze the association between perinatal variables and clinical outcomes. METHODOLOGY: In this retrospective study, data were derived from the medical records of 785 singleton preterm births delivered in the obstetrics and gynecology department of our institution. Variables under investigation were maternal and gestational ages, fetal gender, route of delivery (vaginal vs. cesarean section [C/S]), causes of preterm birth, birth weight, placental weight, umbilical cord length, and Apgar scores at the 1st and 5th min. RESULTS: Pregnant women with advanced age (≥35 years) were more likely to undergo C/S (P < 0.001). Apgar score at the 1st and 5th min was influenced significantly by gestational age (P < 0.001), newborn birth weight (P < 0.001), placental weight (P < 0.001), and umbilical cord length (P < 0.001). Infants delivered due to antepartum fetal distress indication had remarkably lower Apgar scores at the 1st min and the birth weight seemed to be positively correlated with Apgar scores at both 1st (P < 0.001) and 5th min (P < 0.001). Apgar scores both at the 1st and 5th min were positively correlated with placental weight (R: 0.239 and 0.231, respectively, and P < 0.001 for both) and length of umbilical cord (R:0.228 and 0.211, respectively, and P < 0.001 for both). CONCLUSION: Advanced age pregnancies have higher C/S rates, but Apgar scores are significantly correlated with infant characteristics. Umbilical cord length and placental weight might be the new add-on predictors of postpartum well-being in premature infants.

Obstetric outcomes of recurrent pregnancy loss patients diagnosed with inherited thrombophilia.

BACKGROUND: Recurrent pregnancy loss (RPL) is defined by two or more failed pregnancies. The relation between RPL and inherited thrombophilia requires anticoagulant therapy during pregnancy. However the obstetric outcomes have not been well defined in these RPL patients diagnosed with inherited thrombophilia, who have been given anticoagulant therapy. AIM: To investigate the obstetric outcomes in pregnant women with RPL who are given low molecular weight heparin (LMWH) and low-dose aspirin due to diagnosis of inherited thrombophilia. METHODS: A hundred and eight RPL women were diagnosed with inherited thrombophilia, and 98 women were diagnosed with unexplained RPL. The patients with inherited thrombophilia were given LMWH and low-dose aspirin. Unexplained RPL patients were not given any medicine. The obstetric outcomes of participants were noted. RESULTS: In thrombophilic group, the live-birth levels were significantly higher [90 (83%) vs 67 (68%) p < 0.05], and the miscarriage levels were significantly lower than that in the control group [14 (13%) vs 27 (28%) p < 0.01]. The number of patients with preeclampsia was significantly higher in the thrombophilic group [16 (15%) vs 6 (6%) p < 0.05]. The number of preterm births was significantly higher than that of the controls [25 (23%) vs 10 (10%) p < 0.05]. The median gestation age of delivery was 35 weeks for thrombophilic patients and 38 weeks for controls (p < 0.05). CONCLUSION: The RPL patients diagnosed with inherited thrombophilia and who were given LMWH with low-dose aspirin had higher live-birth rates and lower miscarriage rates than those in the unexplained RPL patients. Increased risk of preeclampsia is seen in RPL patients with inherited thrombophilia despite thrombophilia prophylaxis.

Analysis of the anti-allodynic effects of combination of a synthetic cannabinoid and a selective noradrenaline re-uptake inhibitor in nerve injury-induced neuropathic mice.

BACKGROUND: Combining drugs not only reduces specific adverse effects of each of the drug at a higher dose but also may lead to enhanced efficacy. Tapentadol is a recently discovered analgesic possessing µ-opioid receptor agonism and noradrenaline re-uptake inhibition in a single molecule. Taking into consideration, the pharmacological similarities between opioids and cannabinoids, we assumed that combination of cannabinoids with noradrenaline re-uptake inhibitors might also be effective. We therefore aimed to determine whether combining 1:1, 1:3 and 3:1 fixed ratios of the synthetic cannabinoid WIN 55,212-2 and the selective noradrenaline re-uptake inhibitor maprotiline exert anti-allodynic synergy on nerve-injured neuropathic mice. METHODS: Partial tight ligation of the sciatic nerve was made in mice; on pre-operative and post-operative 15 days basal mechanical allodynia, cold allodynia and motor function were assessed using von Frey filaments, hot/cold plate and rota rod apparatus. RESULTS: Mechanical and cold allodynia developed in all groups on post-operative 15 days. Development of cold allodynia was statistically significant in all groups (p < 0.05); therefore, cold allodynia was used in combination studies. As shown by isobolographic analysis, interactions of 1:1 and 3:1 ratios of WIN 55,212-2:maprotiline combinations were supra-additive, whereas 1:3 ratio was sub-additive. CONCLUSIONS: Overall, our data suggest that combination of a cannabinoid with a selective noradrenaline re-uptake inhibitor may offer a beneficial treatment option for neuropathic pain.

Lack of effect of ceftriaxone, a GLT-1 transporter activator, on spatial memory in mice.

In the central nervous system, glutamate appears to be the principal excitatory amino acid neurotransmitter. Recent findings show that beta-lactam antibiotics, by stimulating glutamate transporter (GLT-1) expression, offer neuroprotection. The purpose of our study is to observe the effect of ceftriaxone, a beta-lactam antibiotic, on spatial memory in mice. Male Balb-c mice, weighing 20-25 g, were trained in Morris water maze (n=12 for each group) task. Animals were given 4 trials per day for 7 consecutive days to locate a hidden platform (acquisition phase). On the eighth day, the platform is removed and the animals were swum for one session of 60 s (retention phase). Learning and memory functions of the animals were evaluated based on their performances in these tests. Ceftriaxone was given for 9 days at different doses (50, 100, and 200 mg/kg, i.p.); additionally, its acute effect was evaluated in one group (200 mg/kg, i.p.). Our immunohistochemistry findings indicate that ceftriaxone increases GLT-1 expression in CA1, CA3 and DG regions of hippocampus, especially with the dose of 200 mg/kg. Evaluation of the acquisition parameters, such as time to reach platform, distance moved, and mean distance to platform indicates that chronic ceftriaxone has no effect on learning curves of the animals. When retention phase parameters (e.g. time to reach target quadrant, swim duration in target quadrant, and mean distance to platform area) are evaluated, it was found that both chronic and acute ceftriaxone did not affect memory at any dose used. In contrast to the contribution of GLT-1 expression to various central nervous system diseases, such as chronic pain, amyotrophic lateral sclerosis, Parkinson's disease and seizures, our findings suggest that ceftriaxone has no effect on spatial memory function in mice.

Ethical dilemmas in disaster medicine.

BACKGROUND: Disasters may lead to ethical challenges that are different from usual medical practices. In addition, disaster situations are related with public health ethics more than medical ethics, and accordingly may require stronger effort to achieve a balance between individual and collective rights. This paper aims to review some ethical dilemmas that arise in disasters and mainly focuses on health services. Disasters vary considerably with respect to their time, place and extent; therefore, ethical questions may not always have `one-size-fits-all` answers. On the other hand, embedding ethical values and principles in every aspect of health-care is of vital importance. Reviewing legal and organizational regulations, developing health-care related guidelines, and disaster recovery plans, establishing on-call ethics committees as well as adequate in-service training of health-care workers for ethical competence are among the most critical steps. It is only by making efforts before disasters, that ethical challenges can be minimized in disaster responses.

Evaluation of iloprost to prevent vasospasm in coronary artery bypass grafts.

This study assessed the efficacy of iloprost in relieving vasospasm in coronary artery bypass grafts. Radial artery (RA), left internal thoracic artery (LITA) and saphenous vein (SV) grafts were taken from 20 patients (13 men and seven women, mean age 63.8 years [range 48-74 years]) scheduled to undergo coronary artery bypass grafting. Ten 3 mm vascular rings were cut from each graft and kept under tension for at least 60 min. They were kept alive with 37 degrees C oxygenated Krebs solution. Smooth muscle contraction was achieved with phenylephrine before iloprost was administered every 2 min, starting at a concentration of 10(-9) mol/l and increasing in logarithmic increments to a concentration of 10(-5) mol/l. The vasodilation response to iloprost started in all samples at a concentration of 10(-9) mol/l and increased with each incremental increase in iloprost concentration up to 10(-5) mol/l. These data suggest that local administration of iloprost has a role in relieving graft vasospasm during harvesting and preparation for coronary artery bypass grafting.

Virtual bronchoscopy as a dynamic modality in the diagnosis and treatment of suspected foreign body aspiration.

AIM: Rigid bronchoscopy (RB) is an invasive procedure and has its own risks. The place of virtual bronchoscopy (VB) in the treatment of patients with a clinical and radiological suspicion of foreign body aspiration was evaluated to see whether its usage can prevent rigid bronchoscopy. PATIENTS AND METHODS: The study was performed between December 2005 and May 2007 in 60 patients (35 M and 25 F) aged between 4 months and 7 years with clinical and radiographical suspicion of foreign body aspiration. Patients with radio-opaque foreign body aspiration were excluded from the study and treated directly by RB. VB was performed using 16 detector multislice computerized tomography (MDCT). If VB or clinical follow-up supported the diagnosis of foreign body, RB was performed for diagnosis and treatment. The results of RB were compared with the results of VB. RESULTS: All patients underwent VB. In 40 patients there was a suspicion of foreign body with VB. Two patients improved without RB: one had spontaneous discharge of the foreign body with coughing, and one experienced spontaneous clinical improvement. The remaining 38 patients underwent RB and a foreign body was found in the reported localization in 33. No foreign body was found with RB in 5 patients showing foreign body in VB. But we found bronchial vegetations in 2, obstructing mucus plug in 2 and external bronchial compression by neuroenteric cyst in one. In 20 patients there was no suspicion of foreign body with VB. Of these, 7 patients with presenting symptoms for more than one month underwent RB, but no foreign body was found. The 13 remaining patients were followed up clinically with improvement of symptoms. CONCLUSION: MDCT devices still require further investigation when used in pediatric surgical pathologies. Reconstructed images of VB can reveal images close to the real anatomy. In patients with a suspicion of foreign body ingestion, initial VB may help to determine the presence and exact localization of the foreign body and if negative, may reduce the number of unnecessary rigid bronchoscopies. None of the patients with negative VB had foreign bodies. Positive VB may help to shorten the operative time by providing information about the localization and size of the foreign body.

Asymmetric dimethylarginine levels in thyroid diseases.

Thyroid diseases may lead to endothelial dysfunction; however, the mechanism underlying the endothelial dysfunction in thyroid disease is not clear yet. Asymmetric dimethylarginine (ADMA), a novel inhibitor of endothelial nitric oxide synthase (eNOS), blocks nitric oxide (NO) synthesis from L-arginine. Symmetric dimethylarginine (SDMA) is the structural isomer of the eNOS inhibitor ADMA. SDMA does not directly inhibit eNOS but is a competitive inhibitor of arginine transport. Increased plasma ADMA, SDMA concentrations, and low L-arginine/ADMA ratio were considered as possible contributing factors for endothelial dysfunction in hyperthyroid patients. On the other hand, plasma ADMA, SDMA levels and L-arginine/ADMA ratio in the hypothyroid group were unexpectedly found to be similar to those of the control subjects. The aim of this study is to evaluate and compare the plasma ADMA levels in hyperthyroid, hypothyroid and healthy subjects. Plasma ADMA, SDMA, and L-arginine levels were measured by high performance liquid chromatography. Plasma ADMA levels were significantly higher in both patients with hyperthyroidism and hypothyroidism than in the control group. SDMA concentrations were significantly increased in hypothyroid patients compared to control subjects. Patients with hyperthyroidism and hypothyroidism had significantly higher plasma L-arginine levels compared with healthy controls. L-arginine/ADMA ratio, which shows NO bioavailability, was significantly lower in hyperthyroid patients than in both hypothyroid and control subjects. In hyperthyroidism, plasma ADMA levels were related to age, L-arginine, and SDMA levels. SDMA was associated with age and L-arginine. L-arginine/ADMA ratio was negatively associated with freeT4 levels. There was a relationship between ADMA and L-arginine in hypothyroid patients. SDMA was significantly related to L-arginine, total cholesterol, and LDL. In conclusion, not only hyperthyroidism but also hypothyroidism was associated with alterations of ADMA and SDMA metabolism.

Congenital lobar emphysema: a clinicopathologic evaluation of 14 cases.

Controversy still exists concerning the diagnosis and treatment of congenital lobar emphysema (CLE). Although surgical removal of the affected lobe is the most commonly accepted form of treatment, detection of milder or even asymptomatic cases is usually followed by a more conservative management of patients, i. e. non-surgical treatment and follow-up. We therefore decided to evaluate our patients with CLE, placing special emphasis on treatment and diagnostic techniques. We also evaluated quantitative analyses of alveolar diameters. Fourteen children with CLE were analysed retrospectively, including age, sex, clinical picture, localisation, diagnostic and surgical modalities and histopathologic diagnosis. The alveolar diameters of affected lobes were compared with those of the lobectomised patients with other non-obstructive respiratory diseases. All children but one had severe respiratory distress as an initial symptom. All patients, except newborns, had a history of pulmonary infection. All cases underwent thoracic CT examination as the main radiologic method. In all of the patients, only one lobe was affected. We found an obvious mediastinal shift and atelectasis of adjacent lobes due to compression of the affected lobe. The affected lobe was therefore surgically removed in all of the children. In one case, we had to carry out a partial lobectomy to reduce the duration of the operation, due to an intraoperative fall of oxygen saturation. All of the children had an uneventful clinical course postoperatively. The alveolar diameters of the cases with CLE were significantly greater than those of the control patients. We think that the majority of cases with CLE have too severe respiratory distress to avoid surgical removal of affected lobe. Conservative management should be reserved only for patients with milder symptoms or no distress at all.

Involvement of NMDA receptors and nitric oxide in the thermoregulatory effect of morphine in mice.

Morphine has long been known to have potent effects on body temperature. It has been suggested that both N-methyl-D-aspartate (NMDA) receptors and nitric oxide (NO) pathway are involved in thermoregulation and also known to play important roles in some of morphine effects. The aim of this study was therefore to investigate the contribution of NMDA receptors and NO to the thermoregulatory effect of morphine. Morphine produced a hypothermic effect, especially at the dose of 10mg/kg. Ketamine (5-40mg/kg, i.p.) and N(G)-nitro-L-arginine-methyl ester (L-NAME, 1-100mg/kg, i.p.) also produced hypothermic effects with their higher doses. At doses which themselves produced no effect on colonic temperature in mice, both ketamine (10mg/kg, i.p.) and L-NAME (10mg/kg, i.p.) enhanced the hypothermic effect of morphine (10mg/kg, i.p.). These results further support the relationship between NO and NMDA receptors and suggest a possible role of NMDA-NO pathway in the thermoregulatory effect of morphine.

Compound 48/80, a histamine-depleting agent, blocks the protective effect of morphine against electroconvulsive shock in mice.

We have shown that morphine has an anticonvulsive effect against maximal electroconvulsive shock (MES) in mice, and this effect is antagonized by histamine H1-receptor antagonists. Brain histamine is localized both in neurons and in mast cells, and morphine is known to enhance the turnover of neuronal histamine and to release histamine from mast cells. In the present experiments, compound 48/80 was injected chronically (0.5 mg/kg on day 1, 1 mg/kg on day 2, 2 mg/kg on day 3, 3 mg/kg on day 4, and 4 mg/kg on day 5, twice daily, ip) to deplete mast cell contents. Morphine (0.001-10 mg/kg, ip; N = 20) produced a dose-dependent anticonvulsive effect against MES seizure in mice with non-depleted mast cells, whereas it did not exert any anticonvulsive effect in mice with depleted mast cells. These results indicate that morphine produces its anticonvulsive effect against maximal electroconvulsive shock in mice by liberating histamine from mast cells.

The role of histamine H1-receptors in the anticonvulsive effect of morphine against maximal electroconvulsive shock in mice.

Morphine is known to release histamine from mast cells. It is also known that histamine receptors mediate some of morphine's effects on the central nervous system. The contribution of H1- and H2-receptors to the effect of morphine on maximal electroconvulsive shock in mice was investigated in the present experiments. Morphine showed a dose-dependent anticonvulsive effect, but produced spontaneous clonic convulsions at higher doses (100 mg/kg, i.p.). The anticonvulsive effect of morphine (1 mg/kg, i.p.) was antagonized by histamine H1-receptor antagonists, dimethindene (0.1 mg/kg, i.p.) promethazine (0.4 mg/kg, i.p.) and pheniramine (30 mg/kg, i.p.), and naloxone (10 mg/kg, i.p.), but not by the H2-receptor antagonist ranitidine (10-50 micrograms, i.c.v.). These results show that morphine has an anticonvulsive effect via histamine H1-receptors against maximal electroconvulsive shock in mice.