Therapeutic approach in blast injuries of the ear

Otic blast injury is caused by arrhythmic air blast wave. The perforation of the tympanic membrane is the commonet finding associated with lacerations of mucosa in the middle ear. Makki [6] published 34 cases of myringoplasty after war blast injuries. However, healing of such perforations is common; Kerr [7] noted a healing rate of 83% after the blast injury. The aim of the study was to evaluate different therapic procedures of otic blast injuries. There were 74 patients with bilateral otic blast injuries, who underwent otomycroscopic examination. The following parameters were noted: Integrity of tympanic membrane and size of perforation, presence of haemorrhagic exudate in the middle ear and median value of conductive deafness (Table 2). Main symptoms, presented in Table 1 were: pain, deafness and otohaematorrhoea. The first group of 19 patients received antibiotics by parenteral way during 7 days according to the bacterial finding in ear exudate. Healing rate was dependent on the size of tympanic membrane perforation, and rated from 71% in perforation of one third of tympanic membrane to 25% in total perforation of tympanic membrane. Data are presented in Table 3. The second group of 24 patients received the same therapy as the first treatment, plus otomycroscopic removal of haemorrhagic exudate, lacerated middle ear mucosa, and repair of tympanic membrane lacerations. Healing rate was significantly better than the one obtained in the first group (Table 4). Persistent tympanic perforation, as indicator of failed therapy, was present in 5 (35%) of all examined ears with two thirds of tympanic membrane perforation in the first group, while in the second group the rate was 3 (12%). The third group received the same therapy as the second treatment, including administration of amicacyn into the external auditory canal. The results were statistically compared by chi 2 test, and we found that the second therapy protocol was significantly better. There was no significant difference between the second and the third therapy protocols. We found blast ruptures of tympanic membrane and auditory ossicles chain discontinuity in 88% of examined ears. In our material the high incidence of total tympanic membrane ruptures and subtotal ruptures (48%) is quite different in comparison to other authors [5-7]. We consider it as the effect of high power blast wave. Loss of conductive hearing was present in 91% of blast injured patients, while 7.4% of patients had mixed, predominantly senzoneural deafness. Consequently, in addition to mechanic blast injuries acoustic trauma could profoundly damage the inner ear. Spontaneous healing of tympanic membrane occurred in 71% of injured persons and this was a better result than the results obtained by other authors [3, 4, 6]. The spontaneous healing of tympanic membrane failed if infection of the middle ear occurred or blast caused the total tympanic membrane perforation. In the second and third therapy protocols significantly higher healing of tympanic membrane ruptures was evident; it rated from 88% to 91%. Better results could be explained by the effect of optimal healing conditions, based on removal of exudate from the middle ear and necrotic parts of tympanic membrane, completed by fitting of lacerated parts of tympanic membrane and antibiotic prophylaxis. Healing of tympanic membrane without scars and adhesions was more frequent than in patients treated only with antibiotics. Incidence of undesired outcome of persistent perforation of tympanic membrane was reduced. To prevent posttraumatic complications in the middle ear, we recommend early cleaning of margins, reposition of lacerated fragments of tympanic membrane, and removal of haemorrhagic exudate. Myringoplasty should be performed if spontaneous healing of tympanic membrane did not occur after 6 months. CONCLUSION: Otic blast injury was frequently found in war induced trauma. (ABSTRACT TRUNCATED)     

Electrical heterogeneity in the ventricular wall--and the M cell

Contact dermatitis to cooling lubricants is commonly encountered in occupational dermatology, but it rarely induces pigmentary skin changes. It is sometimes difficult to differentiate between toxic leukoderma and postinflammatory hypopigmentation when examining a depigmentation. A differential diagnosis is described in the case of a 31-year-old metal worker, spending most of his time on a computer-numerically controlled machine, who presented with cumulative irritant hand dermatitis and secondary hypopigmentation. Patch tests gave negative reactions to the European standard series, the disinfection and preservative series, the base preparation and emollient series, the metal series, the mechanical worker series as well as to the cooling lubricant itself. Atopy screening was positive for a variety of pollens. Based on biopsy findings, toxic leukoderma could be diagnosed even though none of the known melanotoxic compounds could be identified in his work environment. The patient was advised to avoid further contact with the regular composed cooling lubricant and the contact eczema improved dramatically, whereas the condition of hypopigmentation got better slowly within weeks under PUVA therapy.     

Hypoglycemic activity of glyburide (glibenclamide) metabolites in humans

OBJECTIVE: To assess the hypoglycemic effect and the insulin-releasing effect of the main glyburide (glibenclamide) metabolites 4-trans-hydroxy-glibenclamide (M1) and 3-cis-hydroxy-glibenclamide (M2) in humans. RESEARCH DESIGN AND METHODS: Eight healthy subjects participated in a placebo-controlled, randomized, single-blind crossover study with five single-dose tests, 3 months apart: 3.5 mg glibenclamide (Gb) orally, 3.5 mg Gb intravenously, 3.5 mg M1 intravenously, 3.5 mg M2 intravenously, and placebo intravenously, each in the fasting state. Standardized meals were given 0.5 and 5.5 h after each medication. Blood glucose levels were measured by a glucose oxidase method, and serum insulin concentrations were analyzed by a specific immunoassay. RESULTS: Blood glucose levels during the first 5 h were significantly lowered not only by Gb but also by M1 and M2. The mean +/- SE blood glucose reductions (versus placebo) expressed as percent of area under the curve (AUC) (0-5 h) were 18.2 +/- 3.3% for M1, 12.5 +/- 2.3% for M2, 19.9 +/- 2.1% for intravenous Gb, and 23.8 +/- 1.2% for Gb orally. Serum insulin levels were significantly increased by Gb as well as by M1 and M2. and M2. CONCLUSIONS: The two main metabolites of glyburide (glibenclamide) have a hypoglycemic effect in humans, which is due to increased insulin secretion.     

Age-related changes in gastric mucosal repair and proliferative activities in rats exposed acutely to aspirin

OBJECTIVES: (1) To determine whether and how outcome measurements in the ECASS trial are influenced by a shorter time window (0-3 vs. 3-6 h) between onset of symptoms and start of thrombolytic therapy using recombinant tissue plasminogen activator (rt-PA) in acute ischemic stroke. (2) To discuss the results of the ECASS 0- to 3-hour cohort with the results of the National Institute of Neurological Disorders and Stroke Study (NINDSS). DESIGN AND ANALYSIS: Analysis of the 0- to 3-hour and the 3- to 6-hour cohort in accordance with the ECASS protocol. Comparative analysis of the ECASS and NINDSS results following the NINDSS protocol using dichotomized endpoints. MAIN OUTCOME MEASURES: Primary endpoints: modified Rankin Scale, Barthel Index; secondary endpoints: combined Barthel/Rankin, long-term Scandinavian Stroke Scale, National Institutes of Health Stroke Scale, mortality at 30 and 90 days, occurrence of intracranial hemorrhage. NINDS trial endpoint: favorable outcome as defined in the NINDS trial. RESULTS: In ECASS, 87 patients were randomized within 3 h of stroke onset. Differences in favor of rt-PA treatment can be found for all primary and secondary outcome measures in the ECASS 0- to 3-hour cohort, except for mortality at day 30, which is somewhat higher in the rt-pA-treated group. However, due to the small sample size, the differences do not reach statistical significance. Early infarct signs (as defined by the ECASS protocol) are found as early as 2 h after stroke onset. Parenchymal hemorrhages are found significantly more often among rt-PA-treated patients. The results in the ECASS 0- to 3-hour cohort fit well with the results in NINDSS. CONCLUSION: Data from the 3-hour ECASS cohort support the efficacy of early thrombolytic therapy in acute hemispheric stroke patients. Comparing bleeding complications between the ECASS and NINDSS is difficult because of differences in the definition and occurrence of hemorrhagic events.     

Growth and function of human parathyroid tissue transplanted to athymic mice

The morphology, cell proliferation and function of transplanted normal, hyperplastic and adenomatous human parathyroid tissue was studied after transplantation to athymic mice. The iPTH was evaluated in relation to morphology. Human parathyroid tissue collected during surgery for hyperparathyroidism was implanted subcutaneously into athymic mice (nu/nu-BALB/cA) and was analysed 1, 4, 7 and 12 weeks after transplantation. The transplants were examined by light and electron microscopy and by autoradiography after continuous infusion of 3H-thymidine. The relative amount of viable tissue was evaluated using a computer image analysing programme. Graft function was evaluated by measuring human iPTH in mouse serum. A transplant take ratio of 93% was observed. The proliferation rate in adenoma grafts at 12 weeks after transplantation was five and fifteen times that observed in normal and hyperplastic transplants, respectively. In normal and adenoma groups, a continuous increase in iPTH concentrations was observed, but in the hyperplastic group the iPTH remained on the same level. The secretion of iPTH in relation to the amount of transplanted tissue and the fraction of viable tissue was at the same level at 12 weeks in normal and adenomatous grafted animals. In conclusion, human parathyroid tissue was successfully transplanted and maintained its original structure. The growth potential, but not the iPTH secretion, was significantly higher in adenoma grafts compared to grafts from hyperplastic and normal glands.     

Probing the substrate alignment at the active site of 15-lipoxygenases by targeted substrate modification and site-directed mutagenesis. Evidence for an inverse substrate orientation

For oxygenation of polyenoic fatty acids by 12- and 15-lipoxygenases the methyl terminus of the substrate constitutes the signal for the initial hydrogen abstraction. In contrast, for 5-lipoxygenases an inverse head to tail substrate orientation has been proposed. However, recent structure-based sequence alignments suggested a conserved uniform substrate orientation for 5S- and 15S-lipoxygenation. Oxygenation of 15S-HETE derivatives by various wild-type and mutant lipoxygenases was investigated, and the evidence proved an inverse substrate orientation: (i) Substrate affinity and Vmax of 15S-HETE oxygenation by arachidonic acid 15-lipoxygenases are >1 order of magnitude lower than the corresponding data for polyenoic fatty acids. 5S,15S- and 14R, 15S-DiH(P)ETE were identified as major reaction products. (ii) Methylation of the carboxylate group of 15S-HETE augmented the reaction rate and shifted the reaction specificity strongly toward 5S-lipoxygenation. In contrast, methyl arachidonate was less effectively oxygenated than the free acid. Methylation of 15S-HETrE(8,11,14), which lacks the C5-C6 double bond, was without major impact on the oxygenation rate and on the product specificity. (iii) Introduction of a bulky glycerol moiety at the carboxylic group of 15S-HETE reversed the kinetic effects of methylation and led to a 14R-oxygenation of the substrate. (iv) When the product pattern of 15S-HETE oxygenation by the recombinant wild-type rabbit 15-lipoxygenase was compared with that formed by the Arg403Leu mutant, 5S- and 8S-lipoxygenations were augmented and 14R, 15S-DiH(P)ETE formation was impaired. (v) Phe353Leu or Ile418Ala mutation of the same enzyme, which favored 12S-HETE formation from arachidonic acid, strongly augmented 8S-lipoxygenation of 15S-HETE methyl ester. These kinetic data and the alterations in the product specificity are consistent with the concept of an inverse head to tail substrate orientation during the oxygenation of 15S-HETE methyl ester and/or of free 15S-HETE by 15-LOXs. For 5S- and 8S-lipoxygenation, 15-HETE may slide into the substrate binding pocket with its carboxy terminus approaching the doubly allylic methylenes C-7 or C-10 to the non-heme iron.     

Effect of various methods of treatment in chronic renal insufficiency on the quality of life in patients

Interest in measuring the quality of life (QL) in relation to health care has increased enormously in recent years. This is also true for end-stage renal failure where it is important not only to provide a better survival but also the quality of that survival. The aim of this study was to assess the relative influence of different kinds of treatment on end-stage renal disease after the patients' evaluation of their overall QL. We studied 167 patients receiving conservative treatment (45), haemodialysis (44), haemodialysis and erythropoieth (36), and continuous ambulatory peritoneal dialysis (42). The patients completed an original questionnaire consisting of 37 questions divided in five groups and generating 15 QL variables: personal data (name, gender, age, basic kidney disease); sociodemographic data influenced by the illness (family history, working ability, employment status); general health characteristics (fatigue, appetite, wound healing, sleep, resistance to cold); aspects of private life that are mostly influenced by the disease (social interaction, traveling, mood, sports, sexual life), and patients subjective assessment of their condition (self care and happiness). Patients on haemodialysis showed lower levels of QL than that on peritoneal dialysis related to fatigue (p < 0.01), working ability (p < 0.05), wound healing (p < 0.05), and appetite (p < 0.01) compared to the conservative treatment. Peritoneal dialysis had also a statistically significant positive influence on fatigue (p < 0.05) compared to conservative treatment. However, erythropoletin treatment showed better results with regard to traveling (p < 0.05), resistance to cold (p < 0.01), self care (p < 0.05) and mood (p < 0.05) compared to peritoneal dialysis, and working ability (p < 0.05), fatigue (p < 0.05) and mood (p < 0.05) compared to conservative treatment and haemodialysis.     

Vertical bridgman techniques to homogenize zinc composition of CdZnTe substrates

In order to improve the Zn homogeneity along the axial direction of CdZnTe boule, we have employed a modified Bridgman technique using a (Cd, Zn) alloy source in communication with the melt, whose temperature has been gradually changed from 800 to 840°C during growth. Electron probe microanalysis (EPMA) measurements of Zn composition in the boule shows an excellent homogeneity of Zn along the axis of the CdZnTe boule compared with results in a boule grown by using a fixed source temperature. We have performed a numerical simulation to obtain the approximate temperatures of additional heating and cooling needed to improve the radial Zn homogeneity. CdZnTe boule has been grown by seeded vertical Bridgman furnace with two zones of heater and cooler. Ultraviolet/visible spectroscopic measurements of Zn composition over the length of the boule indicate that the radial distribution of Zn composition is very homogeneous in the body region of the boule, where the radial variation of Zn composition is ±0.0005.