Surgical versus endovascular treatment of acute thoracic aortic rupture: a single-center experience

BACKGROUND: Surgical management of acute thoracic aortic ruptures is controversial, especially in patients with preexisting comorbidities; associated mortality and paraplegia rates remain high. It was our objective to evaluate whether treating these patients acutely with endovascular stent grafts would improve their outcome. METHODS: From November 1999 to February 2002 a total of 54 patients, age 28 to 83 years, were admitted to our institution with an acute rupture of the thoracic aorta (24 ruptured aneurysms, 14 perforated type B dissections, 16 traumatic ruptures). Twenty-eight patients were managed surgically using cardiopulmonary bypass (group 1), and 26 patients were treated acutely with an endovascular stent graft (group 2). The resuscitation protocol and interval from onset of symptoms to treatment was comparable in both groups. Medical records were reviewed for prehospitalization and emergency department data, operative findings, and outcomes. RESULTS: There were 5 of 28 deaths (17.8%) in the surgical group and 1 of 26 deaths (3.8%) in the endovascular group. In the surgical group 1 of 28 patients (3.6%) exhibited paraplegia; there were no cases of paraplegia in the endovascular group. There were 4 of 28 cases (14.3%) of renal failure in group 1 and 1 of 26 (3.8%) in group 2. In group 1, 8 patients (28.6%) required mechanical ventilation for more than 48 hours; there were 2 of 26 patients (7.7%) in group 2 with this ventilatory requirement. Three patients required a repeat thoracotomy for hemorrhage in the surgical group. There were two access failures in the endovascular group. CONCLUSIONS: In the treatment of acute ruptures of the thoracic aorta, the immediate outcome of patients treated with endovascular stent grafts appears to be better than with management by conventional surgical repair.     

Alcohol promotes dopamine release in the human nucleus accumbens

Microdialysis experiments in rodents indicate that ethanol promotes dopamine release predominantly in the nucleus accumbens, a phenomenon that is implicated in the reinforcing effects of drugs of abuse. The aim of the present study was to test the hypothesis in humans that an oral dose of ethanol would lead to dopamine release in the ventral striatum, including the nucleus accumbens. Six healthy subjects underwent two [(11)C]raclopride PET scans following either alcohol (1 ml/kg) in orange juice or orange juice alone. Subjective mood changes, heart rate, and blood-alcohol levels were monitored throughout the procedure. Personality traits were evaluated using the tridimensional personality questionnaire. PET images were co-registered with MRI and transformed into stereotaxic space. Statistical parametric maps of [(11)C]raclopride binding potential change were generated. There was a significant reduction in [(11)C]raclopride binding potential bilaterally in the ventral striatum/nucleus accumbens in the alcohol condition compared to the orange juice condition, indicative of increased extracellular dopamine. Moreover, the magnitude of the change in [(11)C]raclopride binding correlated with the alcohol-induced increase in heart rate, which is thought to be a marker of the psychostimulant effects of the drug, and with the personality dimension of impulsiveness. The present study is the first report that, in humans, alcohol promotes dopamine release in the brain, with a preferential effect in the ventral striatum. These findings support the hypothesis that mesolimbic dopamine activation is a common property of abused substances, possibly mediating their reinforcing effects.     

Long-term socio-economic impact of vestibular schwannoma for patients under observation and after surgery

This study describes and compares the long-term socio-economic impact for patients diagnosed with a vestibular schwannoma and either operated on or observed. A consecutive sample of patients diagnosed with vestibular schwannoma in Denmark and either operated on (748 patients) or observed by the wait-and-re-scan policy (272 patients) during the period 1976-2000 were studied retrospectively. The consequences of operation/diagnosis (and observation) on vocational status, ability to handle daily chores and some psycho-social aspects were studied by means of a prospective postal questionnaire. Ninety-six per cent of the operated and 83 per cent of the observed patients answered the questionnaire. Overall, 34 per cent of operated patients resumed their daily activities within one to two months, and 76 per cent within four to six months. Patients operated on for a large tumour resumed their daily activities later than patients with a small tumour. Regardless of tumour size, employment was unchanged for the majority of observed and operated patients. The vocational consequences were significantly worse for operated patients with a large tumour, than for observed patients. However, no difference existed between the observed group and operated patients with a tumour below 20 mm in size. A change in vocational status was most frequent for assisting spouses, unskilled manual workers and the self-employed. The majority of both observed and operated patients experienced no change in their ability to handle daily chores. The changed ability of operated patients was worse than that of observed patients. Among various changes in their psycho-social well-being, decrease in social ability was the most frequent complaint in both groups, followed by increased fatigue, decreased concentration, increased irritability, depression and headache, decreased intellect and libido. Regardless of tumour size, the change in social ability, concentration and fatigue was worse for operated patients. Concerning headache, patients operated on for a large tumour were better off than observed patients and patients operated on for a small tumour. There was no difference between the operated and observed groups concerning irritability, intellect and libido. Deterioration of vocational status, ability to handle daily chores and several aspects of psycho-social well-being are reported both by patients operated on and observed for vestibular schwannoma. However, the negative changes were more frequent among the operated patients, although the differences were surprisingly modest, especially when comparing observed patients with patients operated on for a small tumour.     

Pathogenesis of sinus cholesteatoma

The aim of the present study was to provide evidence for the establishment of sinus cholesteatoma, defined as postero-superior pars tensa retraction extending into the posterior tympanum and tympanic sinuses. Background: There is clinical evidence for formation of a retraction, but there is a lack of explanation for the transition from a retraction pocket to an active and expanding sinus cholesteatoma. Epidemiological studies on incidence of postero-superior retractions of pars tensa and follow-up studies on patients with similar pars tensa retractions were performed. Additionally, expression of proliferation marker and analysis of basement membrane were studied in samples of sinus cholesteatoma. The prevalence of pars tensa pathology was between 9.2 and 24% of investigated ears. In children with manifest secretory otitis there were some sinus cholesteatomas and 5–6% severe retractions, some of those became pre-cholesteatomas, requiring treatment and controls. Immunohistochemistry of sinus cholesteatomas showed that proliferating keratinocytes were very often found within epithelial cones growing towards the underlying stroma. These growth cones exhibit focal discontinuities of the basement membrane especially in areas of intense subepithelial inflammation. As a possible explanation based on clinical and immunohistochemical findings, we propose a four-step concept for pathogenesis of sinus cholesteatoma combining the retraction and proliferation theory: (1) The retraction pocket stage. (2) The proliferation stage of the retraction pocket, subdivided in (a) Cone formation, (b) Cone fusion. (3) Expansion stage of attic cholesteatoma. (4) Bone resorption.     

The post-winter prevalence rate of middle ear effusion in four-year-old children,judged by tympanometry

Tympanometry and otologic examinations were performed in 373 four-year-old children randomly selected from the Central National Register at the end of February, 1979. A close interaural correlation of the middle ear pressures of a child was found and therefore the tympanometric results represent related as well as independent data. Consequently, the post-winter prevalence rates of type B tympanograms were calculated according to different sampling units: per all ears 13.7%; per right ears 12.9%; per left ears 14.5%; per ears selected at random 13.9%. Additionally, the prevalence rate was estimated per child at 20.4% type B in at least one ear and at 7% type B in both ears. Based upon the literature the validity of the tympanometric method in detecting middle ear effusion is described. The predictive values of positive and negative tests mostly depend on the degree of the cutoff point (pass—fail point) which has been chosen. In this study the cutoff point was the presence of a type B tympanogram. The advantage and disadvantage of applying ‘one ear’ or ‘one child’ as the sampling unit is discussed from a statistical as well as a clinical point of view. When calculating either per ear or per child no sex differences in the prevalence rates could be proved.     

Frequency of secretory otitis and histology of the normal middle ear mucosa

Repetitive tympanometric screenings of healthy 1-year-old and 2-year-old children showed that 36% of all healthy children had a type B tympanogram, indicating middle ear effusion or secretory otitis, at least once during the first 2 years of life. Another 29% of children had a middle ear pressure of -200 to -350 mm H2O. It was rendered probable that at least 75% of all healthy children have secretory otitis in the course of the first 8 years of life. This high frequency of secretory otitis is correlated to the histology of the normal middle ear mucosa. The many conflicting opinions that prevail in the literature concerning the compostion of the normal middle ear mucosa, especially concerning the demonstration of mucous glands, probably arise from the fact that the middle ear mucosa of most healthy adults has been exposed to metaplastic changes in childhood but has normalized except for minor sequelae. These are often misinterpreted as constituting components of the normal mucosa.     

Functional genetic evaluation of DNA house-cleaning enzymes in the malaria parasite: dUTPase and Ap4AH are essential in Plasmodium berghei but ITPase and NDH are dispensable

Background: Cellular metabolism generates reactive oxygen species. The oxidation and deamination of the deoxynucleoside triphosphate (dNTP) pool results in the formation of non-canonical, toxic dNTPs that can cause mutations, genome instability, and cell death. House-cleaning or sanitation enzymes that break down and detoxify non-canonical nucleotides play major protective roles in nucleotide metabolism and constitute key drug targets for cancer and various pathogens. We hypothesized that owing to their protective roles in nucleotide metabolism, these house-cleaning enzymes are key drug targets in the malaria parasite.

Methods: Using the rodent malaria parasite Plasmodium berghei we evaluate here, by gene targeting, a group of conserved proteins with a putative function in the detoxification of non-canonical nucleotides as potential antimalarial drug targets: they are inosine triphosphate pyrophosphatase (ITPase), deoxyuridine triphosphate pyrophosphatase (dUTPase) and two NuDiX hydroxylases, the diadenosine tetraphosphate (Ap4A) hydrolase and the nucleoside triphosphate hydrolase (NDH).

Results: While all four proteins are expressed constitutively across the intraerythrocytic developmental cycle, neither ITPase nor NDH are required for parasite viability. dutpase and ap4ah null mutants, on the other hand, are not viable suggesting an essential function for these proteins for the malaria parasite.

Conclusions: Plasmodium dUTPase and Ap4A could be drug targets in the malaria parasite.     

Nutrition and lifestyle in relation to bone health and body weight in Croatian postmenopausal women

The objective was to investigate the association of nutrients and lifestyle modifiers with bone mineral density (BMD) and weight and/or body mass index (BMI) in 120 healthy Croatian postmenopausal women. The hip and spine BMD was assessed by Lunar Prodigy (GE Medical Systems). Nutrient assessment from 3-day records was analyzed using the US Department of Agriculture Food Composition Tables and the Croatian National Institute of Public Health database. Subjects were asked to record the consumption of alcohol, coffee, tea and mineral waters, the amount of salt added to foods and smoking habits, as well as involvement in recreational activities, walking and heavy housework. Spot urine samples were analyzed for calcium, magnesium, sodium, potassium and zinc and were normalized by creatinine. Alcohol showed statistically significant positive association with femur and spine BMD and its consumption was higher in subjects without osteoporosis. Urinary sodium/creatinine was significantly positively associated with femoral neck and trochanter BMD, while urinary calcium/creatinine was significantly negatively associated with trochanter, total femur and spine BMD. Consumption of mineral waters was inversely associated with weight/BMI and so were dietary fiber and magnesium. In conclusion, moderate alcohol consumption and urinary sodium were positively associated while urinary calcium was negatively associated with either hip and/or spine BMD. Mineral waters, higher fiber and magnesium intake were beneficial for weight/BMI in this population of apparently healthy Croatian women.     

3H-noradrenaline release from mouse iris–ciliary body: role of presynaptic muscarinic heteroreceptors

Sympathetic neurotransmitter release and its modulation by presynaptic muscarinic heteroreceptors were studied in mouse iris–ciliary bodies. Tissue preparations were preincubated with ³H-noradrenaline and then superfused and stimulated electrically. Firstly, experimental conditions were defined, allowing study of presynaptic sympathetic inhibition in mouse iris–ciliary body. If tissue was stimulated four times with 36 pulses/3 Hz, tritium overflow peaks were reliably and reproducibly measured. As expected, these stimulation conditions led to marked ₂-autoinhibition as indicated by the release-enhancing effect of the ₂-antagonists phentolamine and rauwolscine. To ensure autoinhibition-free ³H-noradrenaline release, which is optimal for studying presynaptic sympathetic inhibition, ₂-receptors were blocked in all subsequent experiments. Under these conditions, evoked tritium overflow was almost completely abolished in the presence of the sodium channel blocker tetrodotoxin, indicating a neuronal origin of ³H-noradrenaline release. Secondly, muscarinic inhibition of ³H-noradrenaline release was characterized using the conditions described above (36 pulses/3 Hz; phentolamine 1 M and rauwolscine 1 M throughout). The muscarinic receptor agonist oxotremorine M decreased evoked tritium overflow in a concentration-dependent manner with an IC₅₀ of 0.33 M and maximal inhibition of 51%. The concentration–response curve of oxotremorine M was shifted to the right by the muscarinic antagonists ipratropium and methoctramine, whereas pirenzepine was ineffective. The observed rank order of antagonist potencies, ipratropium > methoctramine > pirenzepine, which is typical for the M₂ subtype, indicates that presynaptic muscarinic receptors on sympathetic axons of mouse iris–ciliary bodies are predominantly M₂. Finally, inhibition of ³H-noradrenaline release by endogenously secreted acetylcholine was investigated. Longer pulse trains, 120 pulses/3 Hz and 600 pulses/5 Hz, were used and the cholinesterase inhibitor physostigmine was added to the superfusion medium to increase synaptic levels of endogenous acetylcholine. Under these conditions, ipratropium approximately doubled the evoked overflow of tritium, indicating that endogenously released acetylcholine can activate presynaptic muscarinic heteroreceptors. In conclusion, the present experiments establish measurement of the electrically induced release of ³H-noradrenaline from mouse iris–ciliary bodies. As in other species, noradrenaline release in this preparation was subject to presynaptic muscarinic inhibition. Our results also indicate that the presynaptic muscarinic receptors on sympathetic axons in mouse iris–ciliary body are predominantly M₂. Moreover, these receptors can be activated by both exogenous agonists and endogenously released acetylcholine and, hence, may operate physiologically in the interplay between the parasympathetic and sympathetic nervous system.