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Biomedical subjects

M Winter

Publications and source records attributed to M Winter.

At least 55 records · Page 3Linked to original sources

Two-dimensional database of mouse liver proteins: changes in hepatic protein levels following treatment with acetaminophen or its nontoxic regioisomer 3-acetamidophenol.

Overdose of acetaminophen (APAP) causes acute hepatotoxicity in rodents and man. The mechanism underlying APAP-induced liver injury remains unclear, but experimental evidence strongly suggests that activation of APAP and subsequent formation of protein adducts are involved in hepatotoxicity. Using proteomics technologies, we constructed a two-dimensional protein database for mouse liver, comprising 256 different gene products and investigated the proteins affected after APAP-induced hepatotoxicity. Adult male mice received a single dose of APAP (100 or 300 mg/kg) or its nontoxic regioisomer 3-acetamidophenol (AMAP, 300 mg/kg). The extent of liver damage was assessed 8 h after administration by increased liver enzyme release and histopathology. Changes in the protein level were studied by comparison of the intensities of the corresponding spots on two-dimensional (2-D) gels. The expression level of about 35 of the identified proteins was modified due to treatment with APAP or AMAP. The observed changes were usually in the order of 10-50% of the control value and were more marked in the high- than in the low-dose of APAP-treated animals. Most of the changes caused by AMAP occurred in a subset of the proteins modified by APAP. Many of the proteins showing changed expression levels are either known targets for covalent modification by N-acetyl-p-benzoquinoneimine (NAPQI) or involved in the regulation of mechanisms that are believed to drive APAP-induced hepatotoxicity.

Acetaminophen↗

[Inverted papilloma of the nose and paranasal sinuses. Long-term outcome of endoscopic endonasal resection].

There is still some skepticism about endoscopic endonasal resection of inverted papillomas. We conducted a long-term retrospective study and examined 104 patients (82 male, 22 female) with inverted papilloma who were operated at the ENT-Department of the University of Erlangen between 1974 and 1997. The endoscopic approach was chosen in each case, either alone or in combination with external approaches. In 64.4% (67 cases), tumors of all T-classes were resected by endoscopic approach alone (T1:17.9%, T2:23.9%, T3:41.8%, T4:16.4%). For the rest of the patients an additional transoral and transfacial approach was necessary due to difficult tumor localization (T2:24.3%, T3:29.7%, T4:45.9%). The mean age of the patients was 55 years. The recurrence rate after primary endoscopic endonasal sinus surgery was 22.4% (15/67) and after combined endoscopic and external surgery 16.2% (6/37). Second salvage surgery after endoscopic sinus surgery was performed again endonasally in 46% (7/15) and externally in 53.3% (8/15). The recurrence rate after the endonasal approach was now 57.1% (4/7) and 50% (4/8) after external surgery. Third salvage surgery was performed again endoscopically in four cases and externally in four cases. The recurrence rate in both groups was 50% each, so that up to six operations, either endoscopically or externally, were necessary for complete tumor resection. The longest period for a tumor recurrence was 3.4 years after endoscopic sinus surgery and 9 years after combined endoscopic and external surgery. A tumor recurrence after endoscopic endonasal sinus surgery that could not be managed endoscopically again occurred in 12%. Tumor localization is the limiting factor for endoscopic endonasal sinus surgery of inverted papilloma. However, in 64.4% of cases, endoscopic endonasal sinus surgery alone was performed successfully without any loss of one patient. Long-term follow-up is necessary since the recurrence of tumor can happen after a long time. Endoscopic endonasal sinus surgery of inverted papilloma is safe and should be preferred due to its minimal invasive character.

Adolescent↗

Reduced factor XII levels in patients with the antiphospholipid syndrome are associated with antibodies to factor XII.

Antibodies to factor XII (FXII) have previously been identified in some patients who were lupus anti-coagulant-positive. The relationship between these antibodies and FXII levels appeared to be variable. The aim of the present study was to confirm the presence of antibodies to FXII in patients with well characterized antiphospholipid syndrome (APS) and to establish their potential effect on levels of FXII. Forty-two patients with APS were studied; 21 patients were found to have either immunoglobulin (Ig)G or IgM antibodies to FXII by enzyme-linked immunosorbent assay (ELISA) using a highly purified preparation of FXII (> 99% pure). Levels of FXII were statistically significantly lower (P = 0.02) in patients with antibodies to FXII when compared with patients without antibodies to FXII (median = 91 micro/dl, s.d. = 39.1, median = 122 micro/dl, s.d. = 41.1 respectively). Four of the 21 patients with antibodies to FXII were found to have FXII levels below the laboratory normal range. Antibodies to FXII are present in significant numbers of patients with APS and may lead to acquired FXII deficiency.

Adult↗

The importance of locally derived reference ranges and standardized calculation of dilute Russell's viper venom time results in screening for lupus anticoagulant.

Three commercial dilute Russell's viper venom time (DRVVT) kits were evaluated at four UK centres experienced at performing lupus anticoagulant (LA) tests. Each centre established a normal reference range for the DRVVT ratio calculated against local pooled normal plasma from 20 healthy normal subjects. Plasma from LA-positive patients and LA-negative thrombophilia patients was also tested. DRVVT ratios and the degree of correction were assessed in a variety of ways to reflect not only the UK national Guidelines, but also the manufacturers' recommendations. The reference range data showed a normal distribution in each case, but considerable variation in the mean and SD between the centres and reagents, with the mean +2SD value ranging from 1.06 to 1.19. The use of an arbitrary DRVVT ratio of < 1.1 as the cut-off value for normality, which is applied in many laboratories, is therefore inappropriate. Although no single kit had a clear overall advantage in terms of sensitivity and specificity, the way in which the screen and confirmation data were analysed had a major impact on the interpretation of the results. A data analysis method employing a mean plus two standard deviations (SDs) cut-off for normality, and judgement regarding confirmation of LA based on a percentage correction of DRVVT ratio, was the simplest and most consistent, with overall sensitivity and specificity values of 81% and 94%, respectively, for uncomplicated LA-positive and LA-negative thrombophilia samples. We conclude that the 1991 BSCH Guidelines are in need of revision, each laboratory should establish its own normal reference range for the DRVVT ratio and a common method should be used for calculating the degree of correction with confirmation reagents, so that LA results can be correctly interpreted between laboratories. Standardizing DRVVT interpretation in this way should improve the consistency of LA detection.

Humans↗

Effects of recent 0.08% legal blood alcohol limits on fatal crash involvement.

OBJECTIVES: This study assessed whether states that lowered legal blood alcohol limits from 0.10% to 0.08% in 1993 and 1994 experienced post-law reductions in alcohol related fatal crashes. METHODS: Six states that adopted 0.08% as the legal blood alcohol limit in 1993 and 1994 were paired with six nearby states that retained a 0.10% legal standard. Within each pair, comparisons were made for the maximum equal available number of pre-law and post-law years. RESULTS: States adopting 0.08% laws experienced a 6% greater post-law decline in the proportion of drivers in fatal crashes with blood alcohol levels at 0.10% or higher and a 5% greater decline in the proportion of fatal crashes that were alcohol related at 0.10% or higher. CONCLUSIONS: If all states adopted the 0.08% legal blood alcohol level, 400-500 fewer traffic fatalities would occur annually.

Accidents, Traffic↗

Histamine alters endothelial barrier function at cell-cell and cell-matrix sites.

To determine how histamine regulates endothelial barrier function through an integrative cytoskeletal network, we mathematically modeled the resistance across an endothelial cell-covered electrode as a function of cell-cell, cell-matrix, and transcellular resistances. Based on this approach, histamine initiated a rapid decrease in transendothelial resistance predominantly through decreases in cell-cell resistance in confluent cultured human umbilical vein endothelial cells (HUVECs). Restoration of resistance was characterized by initially increasing cell-matrix resistance, with later increases in cell-cell resistance. Thus histamine disrupts barrier function by specifically disrupting cell-cell adhesion and restores barrier function in part through direct effects on cell-matrix adhesion. To validate the precision of our technique, histamine increased the resistance in subconfluent HUVECs in which there was no cell-cell contact. Exposure of confluent monolayers to an antibody against cadherin-5 caused a predominant decrease in cell-cell resistance, whereas the resistance was unaffected by the antibody to cadherin-5 in subconfluent cells. Furthermore, we observed an increase predominantly in cell-cell resistance in ECV304 cells that were transfected with a plasmid containing a glucocorticoid-inducible promoter controlling expression of E-cadherin. Transmission electron microscopy confirmed tens of nanometer displacements between adjacent cells at a time point in which histamine maximally decreased cell-cell resistance.

Cadherins↗

Failure of potassium siphoning by Müller cells: a new hypothesis of perfluorocarbon liquid-induced retinopathy.

PURPOSE: To determine the effect of perfluorocarbon liquid (PFCL)-induced abolition of potassium siphoning by the vitreal end feet of Miller cells. METHODS: Porcine eyecups were filled with stained balanced salt solution and PFCLs (perfluorodecalin, perfluorooctane, perfluoroperhydrophenanthrene or the semifluorocarbon perfluorohexylhexane). With optical coherence tomography, the distance between PFCL and retina was determined, and the size of the aqueous space covering the retinal surface was estimated. The data were used to calculate the retinal potassium siphoning into small aqueous volumes. RESULTS: The distance between PFCL and retinal surface was found to be less than 5 to 10 microm with any PFCL tested. The resultant volume of the aqueous space was too small to act as a sufficient sink for K+ ion siphoning. CONCLUSIONS: A certain threshold volume of vitreal fluid seems to be necessary for efficient buffering of intraretinal increases of K+ and perhaps other (e.g., H+) ions through the Müller cells. When the aqueous fluid is replaced by a PFCL (or by silicone oil) for longer periods, the outer retina becomes subject to long-lasting K+ accumulation, and consequent neurodegeneration and reactive gliosis occurs. The authors propose to search for new vitreous-substituting fluids with the capability to dissolve ions.

Animals↗

[Prospective investigations on the spontaneous healing of intraoperative lesions of the mucosa of the nasal septum].

Mucosal lesions of the nasal septum during septal surgery are frequent, but there is scarce information in the literature about their outcome. In 283 operations of the nasal septum, 92 (32.5%) mucosal lesions occurred, 67 of these could be documented and classified 1, 3 and 6 months postoperatively. Although there was no therapy in 93% (74 cases) of the one-sided lesions, no permanent septal perforation was seen. A total of 7% (six cases) were treated by suture or lyophilised dura combined with tissue adhesive. On the other hand, double-sided and correspondent lesions (12 cases: six without therapy, four sutures, one lyophilised fascia, one tissue adhesive) showed a perforation in five cases without any symptoms. This represents 1.7% of all operations of the nasal septum and 7.4% of all recorded mucosal lesions of the nasal septum. Although the number of examinations are still few, it might be justifiable to conclude that one-sided lesions of the nasal septum need no specific therapy. All bilateral corresponding lesions, even those smaller than 5 mm, should be treated by one-sided suture in the anterior septum and with tissue adhesive in the posterior septum. The use of cartilage, bone or fascia alone is insufficient. Large defects of the mucosa should be treated by maximal therapy, i.e. covering with lyophilised fascia or dura, underlaying of cartilage or bone and using tissue adhesive.

Adult↗

Quantification of intraocular retained perfluorodecalin after macroscopic complete removal.

BACKGROUND: A study was performed to determine the amount of intraocular retained perfluorodecalin after macroscopic complete removal. MATERIAL AND METHODS: Freshly enucleated pig eyes had the anterior segment removed, vitrectomy was carried out, and the eye cups were placed in 0.9% buffered saline solution. One millilitre of perfluorodecalin was instilled for 30 min, followed by a fluid-air exchange. Perfluorodecalin was macroscopically removed. The retina was rinsed twice with 0.9% buffered saline solution. In a second group no rinsing was done, while in a third group no fluid-air exchange was performed. Finally all eye cups were filled with 2.0 ml of the perfluoropolyether Hostinert 130 to dissolve retained perfluorodecalin. The quantity of perfluorodecalin in perfluoropolyether was determined by gas chromatography. RESULTS: Retained perfluorodecalin was detected in all experiments. The smallest portion of perfluorodecalin retained (range 0.04-0.08, mean 0.058%, SD +/- 0.015%) was observed without fluid-air exchange. After fluid-air exchange the portion with rinsing was 0.11-0.27% (mean 0.21%, SD +/- 0.059%) and that without rinsing was 0.51-0.69% (mean 0.60%, SD +/- 0.065%). CONCLUSIONS: Even after macroscopic complete removal of perfluorodecalin a thin layer remains on the retina. If intraoperative fluid-gas exchange is necessary, multiple rinsing with 0.9% buffered saline solution should be performed to reduce the amount of perfluorocarbon liquid retained.

Animals↗

The "Boston model" of managed care and spinal cord injury: a cross-sectional study of the outcomes of risk-based, prepaid, managed care.

OBJECTIVE: To present preliminary data on the health-related consequences for people with spinal cord injury (SCI) of participation in a prepaid, risk-based, managed care plan. DESIGN: Baseline data from a longitudinal interview survey. SETTING: Massachusetts. PARTICIPANTS: Subjects were 114 independently living adults with SCI recruited from 6 independent living centers and 2 managed care plans; 45 received care from a risk-based prepaid managed care plan and 69 from other sources. MAIN OUTCOMES: Self-reports of use of health services; self-assessments of health, health at interview versus 12 months earlier; hospital admissions; numbers of secondary conditions, and experiences of specific secondary conditions (eg, pressure ulcers, depression, fatigue, and chronic pain). RESULTS: Persons in the managed care plan do not differ from their counterparts in terms of age, gender, education, level of SCI, number of comorbid conditions, activity of daily living profiles, household composition, and reliance upon health maintenance programs and routines (eg, bowel and bladder care). In terms of processes of care, they appear generally better-served. There also are a few differences in outcome that are statistically significant, or approach significance, and generally favor the managed care plan. CONCLUSION: Preliminary data suggest that thoughtfully and sensitively designed and implemented risk-based managed care may improve both access and outcomes.

Activities of Daily Living↗

Longitudinal evaluation of growth, puberty, and bone maturation in children with Williams syndrome.

OBJECTIVES: To establish syndrome-specific growth curves and growth rate (GR) curves for Williams syndrome (WS) and define the pattern of bone maturation and pubertal development. METHODS: In a prospective longitudinal study between 1990 and 1997, the growth data of 244 children with WS were collected: 295 values for GR were calculated for 74 girls and 331 values for 89 boys. RESULTS: Mean GR of children with WS was below normal by 1 to 2 cm/y in the first few years of life. One group of girls (n = 20) experienced an early pubertal growth spurt at age 9 years (maximal GR, 7.8 +/- 2.1 cm/y; menarcheal age, 10.4 +/- 1.4 years). A second group (n = 5) showed the growth spurt at age 11 years (7.5 +/- 1.1 cm/y; menarcheal age, 12.6 +/- 1.3 years). In boys, peak height velocity (8.7 +/- 2.3 cm/y) occurred at age 11 to 12 years. Bone age was delayed in both sexes during childhood and accelerated markedly during puberty. Final height was 152.4 +/- 5.7 cm in girls (n = 38) and 165.2 +/- 10. 9 cm in boys (n = 43). CONCLUSIONS: The syndrome-specific GR curves for WS showed a premature and abbreviated pubertal growth spurt in both sexes. This growth spurt was directly related to bone age acceleration during puberty. The data from this longitudinal study provide an overview of both the dynamics of growth and its course in children with WS.

Body Height↗

Amplification for infants: selection and verification.

Hearing aid fittings for children under the age of 1 year provide many challenges to the audiologist. This article offers guidelines for assessment, hearing aid selection, verification, and follow-up for infants with hearing loss. The importance of early intervention and the consideration of new technologies are emphasized in this article. Case studies illustrate various aspects of infant hearing aid fittings.

Correction of Hearing Impairment↗

Household nutrition and health in Poland.

Data from 600 households in the province of Lublin, Poland, are used to assess the relationships among self-rated household health, change in health status, sociodemographic characteristics, food purchasing behavior changes, and health care seeking behaviors. High ratings of health are enjoyed by rural families headed by comparatively young individuals with high education. Average household health is also a function of household changes in food purchasing behavior over the past 5 years and per capita consumption of starch-based foods. Families consuming greater proportions of bread and potatoes and purchasing foods of reduced quality, quantity, and price experience lower average levels of subjective physical health than other families. Reduction or postponement of medical or dental care over the past 5 years did not affect health status in this model.

Cohort Studies↗

Decrease of antigastric autoantibodies in Helicobacter pylori gastritis after cure of infection.

H. pylori infection leads to the formation of autoantibodies against canalicular structures with human parietal cells in about 30% of all patients. This type of autoreactivity is associated with gastric mucosa atrophy. This study aimed to analyse the effect of cure of infection on anticanalicular autoantibodies. H. pylori infection was cured in 34 patients. Sera of these patients were screened for anticanalicular autoantibodies using an immunohistochemical method before, 10 weeks after and one year after cure of infection. Prevalence of anticanalicular autoantibodies significantly decreased from 26% before treatment to 9% after one year. The data presented in this study add new information to the possible reversibility of gastric mucosa atrophy.

Adult↗

Effect of folding on the multifocal silicone intraocular lens: scanning electron microscopic study.

PURPOSE: To evaluate whether the surface of the refractive zonal multifocal silicone intraocular lens (IOL) is altered by different folding and implantation instruments and is more sensitive to manipulation during folding than the surface of a monofocal IOL. SETTING: Department of Ophthalmology, University Hospital, Kiel, Germany. METHODS: Evaluated were the refractive multifocal silicone IOL (SA-40N, Array) and an otherwise identical monofocal IOL (SI-40NB) from the same manufacturer (Allergan Inc.). Different folding devices (folding blocks, folding and implantation forceps, and an injector system) were used. The IOLs were kept folded for 60 seconds; 24 hours later, scanning electron microscopy (SEM) was performed. In addition, the cartridges of the injector system were examined by SEM. RESULTS: Overall, regardless of the folding and implantation instruments used, both the multifocal and monofocal IOLs had discrete surface alterations. The cartridges of the injector system had a rough surface at the tip, while the proximal portion appeared smooth. CONCLUSION: There were no signs of lesions particularly affecting the surface of multifocal IOLs.

Elasticity↗

Increased bleeding associated with protease inhibitor therapy in HIV-positive patients with bleeding disorders.

The use of protease inhibitor (PI) drugs in treatment regimens for HIV-infected patients with hereditary bleeding disorders has been associated with an increased bleeding tendency. To characterize the nature of this bleeding tendency, a retrospective case record analysis was performed on 67 HIV-positive patients with hereditary bleeding disorders who had been treated with PI therapy. 34 patients (51%) developed an increased bleeding tendency on PI therapy, usually within the first few weeks of treatment. As well as an increase in usual joint bleeds, patients developed spontaneous atypical small joint, soft tissue and muscle bleeds. Haematuria was also common. Bleeding episodes tended to respond suboptimally to factor concentrate replacement. Ritonavir was most likely to be associated with bleeding. Nine patients switched first-line PI therapy as a direct consequence of bleeding and seven had no further bleeding problem on their second PI. Factor concentrate usage was significantly increased during the first 6 months of PI therapy compared to the 6 months preceeding treatment. PI therapy is frequently associated with increased bleeding in patients with hereditary bleeding disorders. The mechanism of the bleeding tendency remains to be elucidated.

Adolescent↗

[Modified moisture chamber].

BACKGROUND: Moisture chambers can protect the eye in corneal lubrication or eyelid closure disorders. However, in cases with protrusio bulbi or pronounced chemosis conjunctivae direct damaging contact of the cornea or conjunctiva on the one hand and the inside of the moisture-chamber-bandage on the other hand are possible. Since commercial moisture-chamber-bandages are not available with different internal radii, new methods are necessary to increase the distance between the bandage and the eye. MATERIAL AND METHODS: A special pressure relieving foam dressing used in the therapy and prophylaxis of decubitus was prepared in such a way that a periocular attachment was enabled and an opening for the eye was left blank. This central opening was covered with a commercial moisture-chamber-bandage. Five test persons and two ventilated patients with protrusio bulbi and manifest lagophthalmus were treated with the modified moisture chamber. The relative humidity within the bandage was measured. RESULTS: The modified moisture chamber allows an individual adaptation to the periocular shape of the face and rises the level of the monoculus for about 7 mm. The internal relative humidity was for eight hours at 98% in both test persons and patients. All test persons felt more comfortable with the modified moisture chamber on their skin. CONCLUSIONS: The presented modified moisture chamber is a derivative of the commercial monoculus bandage for patients with sensitive protrusio bulbi.

Adult↗