Novel COL7A1 mutations in dystrophic forms of epidermolysis bullosa

OBJECTIVE: To characterize the use of the esophageal tracheal combitube (ETC) in trauma patients who fail orotracheal rapid sequence intubation (RSI). DESIGN: Prospective protocol design and retrospective chart review. MATERIALS AND METHODS: Flight nurses were trained in the use of the ETC by mannequin simulation, videotape review, and didactic sessions. ETC insertion was attempted after failure of two or more attempts at orotracheal RSI. Over a 12-month period, 12 patients had ETC insertion, and 10 cases qualified for review. Injuries, number of failed orotracheal RSI attempts, definitive airway, initial arterial blood gas results, and outcome were recorded. RESULTS: ETC insertion was successful in all 10 patients in whom it was attempted. Definitive airway control was achieved by conversion to orotracheal intubation in seven patients, emergency department cricothyroidotomy in one patient, and operative room tracheostomy in two patients. No patient died because of failure to control the airway. Seven patients requiring ETC had mandible fractures. CONCLUSION: ETC insertion is an effective method of airway control in trauma patients who fail orotracheal RSI. It may be particularly useful in the patient with maxillofacial trauma and offers a practical alternative to surgical cricothyroidotomy in difficult airway situations.     

Mitochondrial electron transport chain activity, but not ATP synthesis, is required for drug-induced apoptosis in human leukaemic cells: a possible novel mechanism of regulating drug resistance

There is increasing evidence for an association between mitochondrial function and susceptibility to apoptosis. It has been shown that the vinblastine-resistant leukaemic cell line CEM/VLB100 has a more active mitochondrial electron transport chain (ETC) than the parental CCRF-CEM cell line. Inhibition of mitochondrial DNA replication by ethidium bromide (EB) depleted the activity of the ETC and reduced cellular respiratory rate. Depletion of mitochondrial DNA was associated with increased resistance to vinblastine-induced apoptosis in both cell lines. In contrast, the highly specific inhibitor of the energy producing mitochondrial enzyme F1Fzero-ATPase, oligomycin, rendered CEM/VLB100 cells more sensitive to vinblastine by inhibiting the energy-dependent P-glycoprotein (Pgp) pump, suggesting that the effect of EB is independent of energy generation and ATPase activity. Both mitochondrial ETC depletion and ATPase inhibition decreased vinblastine-induced cell cycle changes in the CCRF-CEM cell line, suggesting that cell cycle changes are dependent on ATP generation. However, EB-induced ETC depletion in CEM/VLB100 cells inhibited apoptosis in response to high concentration of vinblastine, but not G2M arrest. We suggest that: (1) over-expression of Pgp by drug-resistant cells may up-regulate mitochondrial energy production; (2) mitochondrial ETC activity is required for DNA fragmentation in response to vinblastine, but the mechanism is independent of Pgp activity and ATP generation; (3) down-regulation of mitochondrial ETC activity may confer resistance to vinblastine-induced apoptosis; (4) the mitochondrial ETC is involved in vinblastine-induced apoptosis downstream of microtubule disruption and cell cycle changes.     

Analyzing Performance of ETC Plazas Using New Computer Software

This paper investigates the sensitivity of the peak hour plaza delay to market penetration of the electronic toll collection (ETC) system using the toll plaza simulation model developed by the Transportation Systems Institute at the University of Central Florida. This microscopic and stochastic computer software was applied to the busiest toll plaza in Orlando, Florida. The findings indicate that, for all plaza configurations simulated with the manual lanes operating over capacity, if only as little as 10% of the manual users switch to ETC lanes, then the total plaza delay (vehicle-hours) is cut in half, the average queuing delay per vehicle is reduced by more than 90 s, and the peak hour plaza throughput (vph) is increased by more than 20%. When the manual lanes operate under capacity, the increase in ETC usage has no impact on plaza delay or throughput. This study demonstrated that ETC vehicles' accessibility to the dedicated ETC lane(s) from the approach lanes could have a major impact on deciding the location of the dedicated ETC lane(s) within the toll plaza.     

Complement inhibition prevents gut ischemia and endothelial cell dysfunction after hemorrhage/resuscitation

BACKGROUND: Complement, a nonspecific immune response, is activated during hemorrhage/resuscitation (HEM/RES) and is involved in cellular damage. We hypothesized that activated complement injures endothelial cells (ETCs) and is responsible for intestinal microvascular hypoperfusion after HEM/RES. METHODS: Four groups of rats were studied by in vivo videomicroscopy of the intestine: SHAM, HEM/RES, HEM/RES + sCR1 (complement inhibitor, 15 mg/kg intravenously given before resuscitation), and SHAM + sCR1. Hemorrhage was to 50% of mean arterial pressure for 60 minutes followed by resuscitation with shed blood plus an equal volume of saline. ETC function was assessed by response to acetylcholine. RESULTS: Resuscitation restored central hemodynamics to baseline after hemorrhage. After resuscitation, inflow A1 and premucosal A3 arterioles progressively constricted (-24% and -29% change from baseline, respectively), mucosal blood flow was reduced, and ETC function was impaired. Complement inhibition prevented postresuscitation vasoconstriction and gut ischemia. This protective effect appeared to involve preservation of ETC function in the A3 vessels (SHAM 76% of maximal dilation, HEM/RES 61%, HEM/RES + sCR1 74%, P < .05). CONCLUSIONS: Complement inhibition preserved ETC function after HEM/RES and maintained gut perfusion. Inhibition of complement activation before resuscitation may be a useful adjunct in patients experiencing major hemorrhage and might prevent the sequelae of gut ischemia.     

Effects of endocrine state on sociosexual behavior of female rats tested in a complex environment.

Examined the influence of both natural and artificially induced endocrine states on the sociosexual behavior of female Long-Evans rats during 15-min behavioral observations in a complex testing apparatus that allowed Ss to control their contacts with sexually active and passive males and ovariectomized (OVX) females. Ss were either intact and in various stages of the estrous cycle or OVX and treated with estradiol benzoate (5–20 μg), estradiol plus progesterone (0.5 mg/kg), or vehicle. Factor analysis of the behavioral measures indicated separate loadings on a lordotic behavior factor, a factor for Ss' preference for proximity to OVX females or passive males; and a factor for Ss' locomotion between portions of the testing apparatus. Behavioral variables loading on these factors were influenced by endocrine state, but the nature of the relation between behaviors and endocrine state varied between factors. The utility of the present testing situation in investigations of the neuroendocrine substrates underlying the motivational aspects of feminine reproductive behavior is discussed. (22 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Mitochondrial electron transport can become a significant source of oxidative injury in cardiomyocytes

Ischemia/reperfusion causes oxidant injury in isolated cardiomyocytes without neutrophils or xanthine oxidase. Since these cells contain mitochondria, we hypothesized that the mitochondrial electron transport chain (ETC) causes this injury. To test this, we altered two conditions known to change within the mitochondria during ischemia/reperfusion-the extent of ETC redox-reduction and oxygen levels-and measured the resulting oxidant generation and injury. Specifically, we exposed cardiomyocytes for 1 h to the mitochondrial ETC inhibitors cyanide, antimycin, and rotenone and measured oxidant generation, using the intracellular fluorescent probe 2',7'-dichlorofluorescin (DCFH, sensitive to H2O2 and hydroxyl radicals). Inhibitors causing more extensive redox-reduction of the ETC (cyanide or antimycin) generated more oxidants than did partial ETC reduction with the inhibitor rotenone (10-fold v five-fold increases in DCFH oxidation). In addition, the DCFH oxidation caused by cyanide could be completely attenuated by the antioxidants 2-mercaptopropionylglycine (MPG) and 1,10 phenanthroline (PHEN). Finally, we tested the relevance of this oxidant generation on cell survival and contraction, with and without antioxidant interventions. Cell viability and contraction after 3-h recovery from cyanide exposure was significantly improved by either the addition of antioxidants, or by the "antioxidant" strategy of lowering O2 levels (i.e. from 150 to 3 tau) during the cyanide exposure (13.8% death with hypoxic cyanide v 48.6% cell death with normoxic cyanide). Collectively, these findings demonstrate that mitochondrial ETC carriers can cause significant oxidant injury, greatest when fully redox-reduced and exposed to oxygen, conditions known to occur in the transition from ischemia to reperfusion.     

Replacing the combitube by an endotracheal tube using a fibre-optic bronchoscope during spontaneous ventilation

We present a case of microlaryngoscopy in a patient with an unexpectedly difficult airway. The airway was managed by using an oesophageal-tracheal Combitube (Kendall-Sheridan, Argyle, NY) (ETC) and a fibre-optic bronchoscope (Pentax-Japan-5 mm).     

Modulatory effect of hyperthermia on hepatic microsomal cytochrome P450 in mice

It is widely known that the clearance of drugs is often compromised during episodes of infectious disease via a down-regulation of cytochrome P450 (P450) at a pre-translational step in enzyme synthesis. Etiocholanolone (ETC), a potent inflammatory agent, induces fever in humans and causes a decrease in the clearance of certain drugs that are metabolized by P450. On this basis it is widely believed that the fever per se rather than the immune modulation that occurs during infections may have a major role in depression of microsomal P450 enzymes during viral infections in humans. In the present study, we demonstrated that although ETC did not induce hyperthermia in mice, it still evoked a depression of the levels of P450 in hepatic microsomes. Ethoxyresorufin O-deethylase (EROD) was also inhibited significantly when hepatic microsomes were incubated with various concentrations of ETC in vitro. P450 levels and EROD activities remained unchanged following hyperthermia that was induced by a non-inflammatory procedure using 2,4-dinitrophenol. Provided the response in rodents is similar to humans, these results indicate that the depression of drug biotransformation by ETC in humans is more likely to be caused by the direct effects of this agent or other mechanisms rather than by the fever it produces. This may suggest that the loss of drug metabolism in humans during infections is due to the activation of host defence responses rather than to the febrile nature of the illness.     

Brain stem encephalitis in childhood

OBJECTIVE: To present two cases of post-infectious encephalitis of the brain stem (ETC) in infancy, which is very infrequent at this age. CLINICAL CASES: Two patients aged 4 months and 9 months respectively had a previous history of a catarrhal illness a few days before the onset of encephalitis. The clinical condition was of subacute onset and torpid course, characterized by ataxia, reduced level of consciousness, involvement of the pyramidal tracts and paralysis of the cranial nerves. No significant information for the diagnosis of either case was obtained from CT. MR showed lesions at the level of the pons. However, the MR image did not correspond in seventy to the clinical condition. The clinical courses of the two patients were different. One case recovered with no sequelae. In the other case the cranial nerves and gait did not return to normal. CONCLUSIONS: In our experience, ETC is rarely seen in infancy. A high degree of suspicion and early treatment of ETC caused by the herpes simplex virus is necessary, since there is usually a high mortality or serious neurological sequelae.     

Effect of treatment with the neuroactive peptide posatirelin on microanatomical changes of frontal cortex and hippocampus caused by lesions of the locus coeruleus

Recurrent pregnancy loss (RPL) is a frustrating problem for both the patient and the clinician. The causes of RPL are diverse and may be associated with genetic, anatomic, microbiologic, endocrine, or immunologic factors. When a couple is ready for an evaluation, the nurse practitioner needs to be able to discuss possible causes, aspects of diagnostic testing, and available options. Reassurance and clear information about prognosis are important and emotional support must be offered throughout the investigation and subsequent pregnancy.     

The functional organization of the adaptive and compensatory reactions of the endocrine glands

Current concepts of the systemic organization and interrelationship between adaptive and compensatory responses of the endocrine glands and hormone-producing cells are reviewed. Emphasis is made on the involvement of prolactin, insulin endorphins and other neuropeptides into stress responses. A problem of the multihormonal control of physiological functions and role of blood protein carriers and hormonal cytoreceptors in pathogenesis of various diseases are discussed. Special attention is paid to the importance of endocrine function reserves testing for diagnosis of premorbid states and for estimation of human psychophysiological and physical potentials.     

Chiasmal syndrome due to intrasellar abscess

A 43-year-old woman had diabetes insipidus and amenorrhea. There was panhypopituitarism on endocrine testing and visual field examination showed inexorably progressive loss to bitemporal hemianopsia. All radiographic findings were normal, but craniotomy disclosed the cause of this chiasmal syndrome to be an intrasellar abscess which, on culture, grew a Gram-positive anaerobe, Peptococcus. Intrasellar or pituitary abscess is rare, but it must always be considered in the differential diagnosis of the chiasmal syndrome, since loss of pituitary and visual function may occur much more rapidly than with the tumors most often responsible for this syndrome and since surgical cure is possible.     

Endocrine problems of adolescent pregnancy

A number of changes in renal and endocrine physiology occur during pregnancy that alter hormone levels and affect a number of disease processes. Increased glomerular filtration causes an increase in hormone and substrate clearance. Increased placental steroid production causes an increase in hormone-binding globulin production, insulin resistance, and prolactinoma growth. Production of peptide hormones may cause changes in normal physiology and alter dynamic hormone testing. Placental vasopressinase increases vasopressin clearance. A number of diseases of hormone overproduction and underproduction affect pregnancy outcome and must be treated promptly by therapeutic modalities that also may affect the fetus.     

Chronic pancreatitis: diagnosis

Chronic pancreatitis is a chronic, inflammatory process leading to destruction of the exocrine tissue, filorosis, and in some patients a loss of endocrine function. Because chronic pancreatitis results in a permanent destruction of pancreatic tissue, exocrine and/or endocrine pancreatic insufficiency may follow. However, owing to the tremendous reserve of pancreatic function, insufficiency may be subclinical at least in the beginning of the disease. The diagnosis of chronic pancreatitis is not difficult; it is based on a typical medical history, specific imaging procedures, and pancreatic function testing. The main differential diagnosis is to separate chronic pancreatitis form pancreatic carcinoma. In the present summary, the different imaging procedures and pancreatic function tests are discussed.     

Limited tumor involvement found at multiple endocrine neoplasia type I pancreatic exploration: can it be predicted by preoperative tumor localization?

Radiologically demonstrable pancreatic endocrine tumors are a frequent requirement for exploration in patients with multiple endocrine neoplasia type I (MEN-I). Such delayed intervention is accompanied by a 30% to 50% incidence of pancreatic endocrine metastases. This study explores biochemical tumor markers and operative findings in relation to preoperative pancreatic radiology in 25 MEN-I patients. They underwent pancreatic surgery with (n = 19) or without (n = 6) radiologic signs of primary tumor and absence of metastases upon conventional examination, including OctreoScan testing (n = 10). Biochemical diagnosis required an increasing elevation of at least two independent pancreatic tumor markers. Tumor diameters averaged 1.1 cm (0-5 cm) and 0.9 cm (0.2-1.5 cm) in the patients with and without positive preoperative radiology, respectively. These investigations never displayed more than one of the consistently multiple tumors, and the results were falsely positive in 26%. Preoperatively unidentified regional or hepatic metastases were found at surgical exploration in 26% of patients with radiologic localization and in none of the others. Limited pancreatic tumor involvement necessitated intraoperative absence of metastases and pancreatic lesions /= 7 mm in diameter. Conventional pancreatic imaging is insensitive and nonspecific for recognizing even substantial pancreatic tumors associated with MEN-I.     

Multiple pituitary hormone deficiencies in a patient with spinocerebellar ataxia: magnetic resonance imaging and hormonal studies

Degenerative spinocerebellar ataxia has a rare association with hypogonadotropic hypogonadism. In this report we present the results of the detailed endocrine evaluation and magnetic resonance imaging in one such patient. A 20-year-old male with progressive cerebellar ataxia, hypogonadism, and short stature was investigated. Basal testing revealed hypogonadotropic hypogonadism (LH < 5 mU/L, FSH < 5 mU/L, testosterone 2.5 nM/L). There was no rise in LH after stimulation with LHRH, peak LH level being < 5 mU/L. Insulin hypoglycemia testing was consistent with GH deficiency, with peak GH being 3.2 mU/L. On TRH stimulation, there was no significant rise in prolactin, though the TSH response was normal. Magnetic resonance imaging revealed cerebellar atrophy. The anterior pituitary was atrophic, with a height of 1.4 mm. The posterior pituitary and the pituitary stalk were normal in size and position. This patient with degenerative spinocerebellar ataxia had multiple pituitary hormone deficiencies. The results of our endocrine evaluation and MR imaging lead us to believe that these deficits may result from a lesion at the level of the pituitary gland.     

Oncological implications of RET gene mutations in Hirschsprung's disease

BACKGROUND: Germline mutations of the RET proto-oncogene identical to those found in the tumour predisposition syndrome multiple endocrine neoplasia type 2A (MEN2A), were detected in 2.5-5% of sporadic and familial cases of Hirschsprung's disease. Some patients with Hirschsprung's disease may therefore be exposed to a highly increased risk of tumours. AIMS: To define clinical use of RET gene testing in Hirschsprung's disease and related patient management from an oncological point of view. METHODS: Sixty patients with Hirschsprung's disease were screened for RET mutations. In three, MEN2A type RET mutations were detected. Case reports for these three patients are presented. RESULTS AND CONCLUSIONS: Only 22 families or sporadic patients with Hirschsprung's disease and MEN2A type RET mutations have been reported. Therefore, it is difficult to predict tumour risk for patients with familial or sporadic Hirschsprung's disease, and their relatives, who carry these mutations. For these mutation carriers, periodic screening for tumours as in MEN2A is advised, but prophylactic thyroidectomy is offered hesitantly. RET gene testing in familial or sporadic Hirschsprung's disease is not recommended at present outside a complete clinical research setting. In combined MEN2A/Hirschsprung's disease families RET gene testing, tumour screening, and prophylactic thyroidectomy are indicated as in MEN2A.     

Studies on the viability of the isolated vascularly perfused rat colon

The colon contains large numbers of endocrine cells. Insight into their physiological function is limited. This is due to the fact that no sufficient model of isolated endocrine colon cells is available. In the present study we introduce an isolated vascularly perfused colon model for in vitro studies. This model offers the advantage that it keeps the endocrine cells in their physiological orientation and environment. The gut mucosa is highly sensitive to ischemia. Therefore, a careful validation of its viability is crucial in gut organ preparations. This study demonstrates that, by utilizing an oxygenated vascular medium supplemented with 25% washed bovine erythrocytes, a perfusion of the colon is achieved for at least 1 h without obvious tissue injuries. During this time parameters such as perfusion pressure, venous lactate dehydrogenase release, glucose consumption, lactate output, oxygen consumption, perfusate loss by the preparation and morphology were analyzed. Dependent on stimulation, the endocrine L cells of the colon released glucagon-like peptide-I upon arterial perfusion of methacholine or gastrin-releasing peptide. In conclusion, a model for the isolated perfusion of the colon is introduced which is suitable for studies of endocrine colon cells.     

Diagnosis of thyroid dysfunction: present and future

Thyroid disorders represent the second most common endocrine disorder after diabetes mellitus. For this reason, investigation of thyroid function is frequently carried out, taking advantage of numerous tests currently available. It it the physicians's difficult task to select the most appropriate assay(s) in the different pathophysiological conditions from the bewildering array of thyroid function tests, in order to satisfy optimal diagnostic standards, but also to fulfill cost/benefit criteria. Aim of this paper is to provide a brief overview of advantages and disadvantages of main thyroid function tests, and to suggest a testing strategy for the diagnosis of suspected thyroid dysfunction.