Otologic manifestations of petrous carotid aneurysms

BACKGROUND AND PURPOSE: The petrous and cavernous segments of the extradural internal carotid artery take a complex course through the skull base before entering the subarachnoid space distal to the cavernous sinus. Despite the protection from trauma afforded by the anatomy, the petrous and carotid internal carotid artery (ICA) segments of the vessel remains subject to disease, the most important of which are aneurysms. Aneurysms affecting the petrous portion of the vessel are extremely uncommon, and presentation with otologic symptoms is unusual. These symptoms include hearing loss, tinnitus, and life threatening hemorrhage. This article emphasizes the need for a high level of suspicion for aneurysm as a potential cause for otologic symptoms. We report and discuss three cases of petrous carotid aneurysms with otologic manifestations to increase the awareness and aid in the diagnosis and treatment of this uncommon disorder. METHODS: The medical records and imaging studies of three patients presenting to our institution with aneurysms involving the petrous internal carotid artery were reviewed. One presented with progressive bilateral sensorineural hearing loss. The next patient presented with pulsatile tinnitus. The last patient presented to the emergency room unresponsive with severe epistaxis. RESULTS: All three patients had imaging studies revealing petrous carotid aneurysms. Each patient had symptoms related to the aneurysms ranging from hearing loss, tinnitus, and life-threatening hemorrhage. CONCLUSION: Petrous carotid aneurysms are rare, and presentation with otologic symptoms is unusual. Awareness of these lesions as a cause of otologic symptoms, however, is highly important. These cases also illustrate the usefulness of endovascular treatments for aneurysms of the petrous portion of the internal carotid artery, which are extremely difficult to treat by using an open surgical approach.     

Ruptured ectopic pregnancy presenting as an irreducible inguinal hernia

An inguinal hernia that suddenly becomes irreducible may be secondary to a variety of other underlying conditions which can occasionally mislead the attending surgeon. Benign, inflammatory or neoplastic processes, as well as surgical emergencies such as intraperitoneal or retroperitoneal haemorrhage, have all been previously reported to mimic an inguinal hernia that suddenly becomes irreducible with or without clinical features of strangulation. We add an additional interesting presentation to this list in the form of a ruptured ectopic pregnancy, which is the first such case reported in the literature. A swelling in the groin may be much more complicated than it seems on superficial consideration and good clinical acumen is constantly required in managing such cases if a satisfactory outcome without any morbidity is to be expected.     

N-Acetylcysteine for Preventing Pump-Induced Oxidoinflammatory Response During Cardiopulmonary Bypass

Purpose To investigate the effect of N-acetylcysteine on preventing pump-induced oxidoinflammatory response during cardiopulmonary bypass (CPB).Methods Forty patients undergoing coronary artery bypass grafting (CABG) were randomly divided into a study group (n = 20), given 50mgkg^–1 N-acetylcysteine intravenously for 3 days, and a control group (n = 20) given saline. Serum samples were collected for measurement of myeloperoxidase (MPO), malondialdehyde (MDA), interleukin-6, ₁-acid glycoprotein (AAGP), and C-reactive protein (CRP) during surgery and postoperatively.Results The MPO and MDA values showed a similar pattern during and after CPB in the study group, with significantly less variance than in the control group. Interleukin-6 showed similar patterns in the two groups, but the data from 30min after the start of CPB and from 6h post-CPB were significantly different. The AAGP and CRP values were both elevated during CPB in the two groups without a significant difference, but 6 and 24h post-CPB, the values were significantly higher in the control group than in the study group.Conclusions N-Acetylcysteine decreased pump-induced oxidoinflammatory response during CPB, suggesting that it could be a novel therapy for assisting in the prevention of CBP-induced oxidoinflammatory damage.     

Association of Angiotensin-converting enzyme and angiotensinogen gene polymorphisms with preeclampsia

We tested the hypothesis that angiotensin-converting enzyme (ACE) and angiotensinogen gene polymorphism influence the incidence, development and outcome of preeclampsia. Subjects were recruited from 90 Korean patients with preeclampsia during pregnancy and 98 age-matched controls. After isolation of DNA, polymerase chain reactions (PCR) were carried out to detect polymorphism of the ACE and angiotensinogen. M235T and T174M genotypes of angiotensinogen were determined by digestion with restriction enzyme endonuclease Tth 111-I and NCo I, respectively. The frequency of DD genotype was significantly greater in preeclampsia (0.36) than in controls (0.14) (p<0.05). The frequency of D allele was 0.55 in preeclampsia and 0.40 in controls (p<0.05). There were no differences in the onset of preeclampsia and pregnancy outcomes according to the ACE genotypes. There was no difference in the frequency of a allele of angiotensinogen M235T between the groups (0.79:0.78 in preeclampsia : controls). The frequency of T allele of angiotensinogen T174M gene was slightly increased, but not significantly, in preeclampsia (0.11) than in controls (0.07). In a multivariate analysis, only ACE genotype was associated with the development of preeclampsia (beta=0.27, p=0.05). In conclusion, a molecular variant of ACE, but not angiotensinogen, gene is associated with preeclampsia in Korean women.     

Market share of the for-profit and not-for-profit sector from health insurance expenditures

AIM: The aim of the study is to analyze the market share of for-profit private and not-for-profit sector from the expenditures on medical services of the Hungarian National Health Insurance Fund (NHIF), to show its changes in the last years and to show on which field they can be found. DATA AND METHODS: The data derives from the financial database of the National Health Insurance Fund (NHIF) covering the period 1995-2002. The analysis includes the medical provisions (primary care, health visitors, dental care, out- and inpatient care, home care, kidney dialysis, CT-MRI). RESULTS: In 1995 only 6.91% (12.5 billions Ft) of total expenditure for medical services went to for-profit private providers. By 2002 the market share of private providers increased to 15.95% (78.5 billions Ft). During the same period we realized a dynamic increase in the market share of non-profit sector: from 1.04% in 1995 to 2.58% in 2002. The role of private providers is dominant in the case of general practitioners, dental care, transportation, kidney dialysis, CT/MRI and home care (home nursing). CONCLUSIONS: The financial data of the NHIF showed the dynamic increase of market share of for-profit private providers and non-profit sector in many field of health care, although they role in the two most important fields (out- and inpatient care) is still negligible.     

Role of cytochrome P4503A in cysteine S-conjugates sulfoxidation and the nephrotoxicity of the sevoflurane degradation product fluoromethyl-2,2-difluoro-1-(trifluoromethyl)vinyl ether (compound A) in rats

The volatile anesthetic sevoflurane is degraded to fluoromethyl-2,2-difluoro-1-(trifluoromethyl)vinyl ether (FDVE) in anesthesia machines. FDVE is nephrotoxic in rats. FDVE undergoes glutathione conjugation, subsequent conversion to cysteine and mercapturic acid conjugates, and cysteine conjugate metabolism by renal beta-lyase, which is a bioactivation pathway mediating nephrotoxicity in rats. Recent in vitro studies revealed cytochrome P4503A-catalyzed formation of novel sulfoxide metabolites of FDVE cysteine-S and mercapturic acid conjugates in rat liver and kidney microsomes. FDVE-mercapturic acid sulfoxides were more toxic than other FDVE conjugates to renal proximal tubular cells in culture. Nevertheless, the occurrence and toxicological significance of FDVE sulfoxides formation in vivo remain unknown. This investigation determined, in rats in vivo, the existence, role of P4503A, and nephrotoxic consequence of FDVE conjugates sulfoxidation. Rats were pretreated with dexamethasone, phenobarbital, troleandomycin, or nothing (controls) before FDVE, and then, nephrotoxicity, FDVE-mercapturate sulfoxide urinary excretion, and FDVE-mercapturate sulfoxidation by liver microsomes were assessed. The formation of FDVE-mercapturic acid sulfoxide metabolites in vivo and their urinary excretion were unambiguously established by mass spectrometry. Dexamethasone and phenobarbital increased, and troleandomycin decreased (i) liver microsomal FDVE-mercapturic acid sulfoxidation in vitro, (ii) FDVE-mercapturic acid sulfoxide urinary excretion in vivo, and (iii) FDVE nephrotoxicity in vivo assessed by renal histology, blood urea nitrogen concentrations, and urine volume and protein excretion. Urine 3,3,3-trifluoro-2-(fluoromethoxy)propanoic acid, reflecting beta-lyase-dependent FDVE-cysteine S-conjugates metabolism, was minimally affected by the pretreatments. These results demonstrate that FDVE S-conjugates undergo P4503A-catalyzed sulfoxidation in rats in vivo, and this sulfoxidation pathway contributes to nephrotoxicity. FDVE S-conjugates sulfoxidation constitutes a newly discovered mechanism of FDVE bioactivation and toxicification in rats, in addition to beta-lyase-catalyzed metabolism of FDVE-cysteine S-conjugates.     

Sulfoxidation of cysteine and mercapturic acid conjugates of the sevoflurane degradation product fluoromethyl-2,2-difluoro-1-(trifluoromethyl)vinyl ether (compound A)

The volatile anesthetic sevoflurane is degraded in anesthesia machines to the haloalkene fluoromethyl-2,2-difluoro-1-(trifluoromethyl)vinyl ether (FDVE), which can cause renal and hepatic toxicity in rats. FDVE is metabolized to S-[1,1-difluoro-2-fluoromethoxy-2-(trifluoromethyl)ethyl]-L-cysteine (DFEC) and (E) and (Z)-S-[1-fluoro-2-fluoromethoxy-2-(trifluoromethyl)vinyl]-L-cysteine [(E,Z)-FFVC], which are N-acetylated to N-Ac-DFEC and (E,Z)-N-Ac-FFVC S-conjugates. Some haloalkene S-conjugates undergo sulfoxidation. This investigation tested the hypothesis that FDVE S-conjugates can also undergo sulfoxidation, by evaluating sulfoxide formation by human and rat liver and kidney microsomes and expressed P450s and flavin monooxygenases. Rat, and at lower rates human, liver microsomes oxidized (Z)-N-Ac-FFVC and N-Ac-DFEC to the corresponding sulfoxides. Much lower rates of (Z)-N-Ac-FFVC, but not N-Ac-DFEC, sulfoxidation occurred with rat and human kidney microsomes. In human liver microsomes, the P450 inhibitor 1-aminobenzotriazole completely inhibited S-oxidation, while heating to inactivate FMO decreased (Z)-N-Ac-FFVC and N-Ac-DFEC sulfoxidation only 0 and 30%, respectively. Of the various cytochrome P450s examined, P450s 3A4 and 3A5 had the highest S-oxidase activity toward (Z)-N-Ac-FFVC; P450 3A4 was the predominant enzyme forming N-Ac-DFEC-SO. The P450 3A inhibitors troleandomycin and ketoconazole inhibited >95% of (Z)-N-Ac-FFVC sulfoxidation by P450 3A4 and 3A5 and 40-100% of (Z)-N-Ac-FFVC sulfoxidation by human liver microsomes and 15-85% of N-Ac-DFEC sulfoxidation by human liver microsomes. Sulfoxidation of DFEC was also examined in human liver microsomes. Substantial amounts of sulfoxide were observed, even in the absence of NADPH or protein, while enzymatic formation was comparatively minimal. These results show that FDVE S-conjugates undergo P450-catalyzed and nonenzymatic sulfoxidation and that enzymatic sulfoxidation of (Z)-N-Ac-FFVC and N-Ac-DFEC is catalyzed predominantly by P450 3A. The extent of FDVE sulfoxidation in vivo and the toxicologic significance of FDVE sulfoxides remain unknown and merit further investigation.     

Maternal deaths and their causes in Ankara, Turkey, 1982-2001

This study was carried out to determine the incidence and causes of maternal deaths about a 20-year period at the Zekai Tahir Burak Women's Health Education and Research Hospital (ZTBWHERH), Ankara, Turkey. All maternal deaths from January 1982 to July 2001 were reviewed and classified retrospectively. Using a computer-generated list, 348 patients admitted to the Labour Department of ZTBWHERH during 1982-2001 were selected as controls. Medical records were reviewed for demographic data, history of antenatal care, route of delivery, referral history, and perinatal mortality. Cases and controls were compared, and standard tests were used for calculating odds ratio (OR) and 95% confidence interval (CI) for the association of demographic and delivery characteristics. During this period, there were 174 maternal deaths and 430,559 livebirths, giving a maternal mortality ratio of 40.4/100,000 livebirths. The mortality rate declined from 85.1/100,000 in 1982 to 11.6/100,000 in 2001. One hundred thirty (74.7%) deaths were due to direct obstetric causes and 24 (13.7%) were abortion-related, while 20 (11.4%) were due to indirect obstetric causes. The most common cause of direct obstetric deaths was pre-eclampsia/eclampsia, followed by obstetric haemorrhage and embolism. Abortion-related sepsis and haemorrhage, anesthesia-related deaths, obstetric sepsis, acute fatty liver of pregnancy, and ectopic pregnancy accounted for other causes of deaths. Cardiovascular disease was the leading indirect cause of death. Referral, lack of antenatal care, and foetal death at admittance were associated with 8-, 3-, and 6-fold increased risk of maternal mortality respectively (OR 8.89, 95% CI 5.7-13.8; OR 3.74, 95% CI 2.5-5.5; OR 6.38, 95% CI 3.1-13.1). Although maternal mortality ratios have declined at the hospital, especially in the past five years, the rate is still high, and further improvements are needed. The problem of maternal mortality remains multifactorial. Short-term objectives should be focused on improving both medical and administrative practices. Improving the status of women will necessarily remain a long-term objective.