bluuebunny/crossref_metadata_2025 huggingface dataset:
Modulation of Mouse Brain Cortex Adrenoceptor in Old Mice by Supplementation of Zinc and Thymomodulin
Authors: Viticchi Claudio , Moresi Raffaella , Piantanelli Lucio
Published: April 2003

Background: Previous experiments have shown that the age-related decrease of mouse brain cortex adrenoceptor density can be recovered by grafting a neonatal thymus into old recipients. The question arises whether similar results can also be obtained in the presence of a single thymic factor such as thymomodulin (TMD). It is worth noting that the activity of some thymic factors is strictly zinc (Zn) dependent and that their age-related decreased production is recovered in old mice supplemented with Zn. Objective: The above-mentioned evidences prompted us to verify whether Zn and TMD, either alone or combined, are able to induce some corrective effects on age-dependent alterations of adrenoceptor characteristics of the mouse brain cortex. Methods: Thus, we performed experiments on four groups of Balb/c mice treated with saline, Zn, TMD, or both Zn and TMD. Treatments started when animals were 18 months old and ran for 6 months. The α1- and β-Adrenoceptor characteristics were assayed by steady state binding analysis using labelled prazosine and iodocyanopindolol, respectively. Data were analyzed using one-way analysis of variance, followed, when appropriate, by multiple-comparison analysis. Results: Results show an increase of β-adrenoceptor density and a decrease of α1-adrenoceptor density in both Zn- and Zn+TMD-treated animals when compared to saline-treated controls, while receptor affinities did not change significantly. Conclusions: The lack of action of TMD suggests that this type of treatment cannot mimic the effects of grafting the whole gland; it cannot be excluded that different time-dose schedule could be more effective. Zn treatment, on the other hand, does modulate adrenoceptors; however, it shows a corrective action on the age-related decreased density of β-adrenoceptors, but further decreases that of α1-adrenoceptors. This differential action could be due to their differential physiological role.
Mitochondrial Genome Lesions in the Pathogenesis of Sporadic Alzheimer’s Disease
Authors: Meier-Ruge W.A. , Bertoni-Freddari C.
Published: April 2003

Background: The recent, magnificent results of molecular biology concerning β-amyloid (βA) metabolism in early onset Alzheimer’s disease (AD) have generated a series of new findings and, in turn, a new etiological concept. Attention on the early events in the pathogenesis of AD has been shifted from the chromosomal abnormalities in the nucleus of nerve cells onto genetic changes in the mitochondrial genome. This offers a new pathogenetic approach which also opens new pharmacological challenges particularly for the episodic forms of AD. Objective: Alterations occurring at the mitochondrial genome result in major consequences of oxidative phosphorylation and, if a specific threshold is exceeded, they may constitute important causative events in the apoptosis of selected nerve cells. The fact that the main source of mitochondrial metabolism is its glucose turnover allows monitoring brain changes in glucose metabolism by 18F-2 deoxyglucose positron emission tomography. In the demented brain, a low glucose turnover causes a cholinergic deficit by decreasing the synthetic rate of acetyl coenzyme A (AcCoA). AcCoA represents the key substrate for the acetylation of choline to acetylcholine by choline acetyltransferase. The consistent energy need for AcCoA synthesis appears obvious when considering that 1 molecule of glucose generates just 2 molecules of AcCoA, but 38 molecules of ATP. In the brain, AcCoA is exclusively synthesized in the glycolitic pathway. Generation of βA is increased if the synthetic rate of ATP drops below a critical threshold: under these conditions, the βA precursor protein (βAPP) is inserted only in part into synaptic membranes which have the highest βAPP turnover. In conditions of short ATP supply, βAPP is not split at the β region by an ATP-activated protease and this results in a substantial increase in uncleaved βA molecules. Conclusion: Peroxidative alterations in mitochondrial DNA are of importance in degenerative diseases of postmitotic tissues, particularly in degenerative diseases. This offers a new pharmacological approach for the treatment of AD. Neurotrophic factors and estrogen seem to be the first pharmacological leads.
Changing Presentation of Seizures with Aging: Clinical and Etiological Factors
Authors: DeToledo John C.
Published: April 2003

Background: The historically higher incidence of seizures in children has changed, the elderly now have a higher incidence than any age-group, 2–3 times of that found in children. Classical teachings on etiologies, clinical presentation and progression of seizures are based on observations of a younger population and need to be revised in view of features unique to this age-group. The findings of two large VA cooperative studies show that even in sophisticated medical environments, up to 30% of patients 60 years and older with recurrent partial seizures go undiagnosed for more than 1 year of seizure onset. Objective: (a) To characterize the manifestations of auras, seizures and postictal states in the elderly and the relevance of various etiologies to these presentations. (b) To identify and discuss factors that contribute to the difficulties in the diagnosis of seizures in this population. Methods: A review of our experience in treating a large population of elderly patients in a university epilepsy center and a review of the literature relating to the problem. Conclusions: Seizures in the elderly are both overdiagnosed and underdiagnosed: either situation can have serious adverse consequences. Diversity of etiologies and atypical presentations make recognition of seizures difficult. Histories are frequently inadequate: complaints of multiple physical symptoms confuse the picture, unwillingness of elderly patients to admit to problems they believe are physiological in nature by the fear others may think they are ‘losing their mind’ and high staff turnover result in erratic identification of problems. The significant morbidity and mortality associated with poorly controlled seizures in this population are in large part preventable since excellent response to treatment can be achieved in more than 80% of individuals. The correct diagnosis of seizures is more likely if both physician and patients are familiar with the nuances of epilepsy in the elderly.
Evolutionary Theories of Aging
Authors: Keller Laurent , Genoud Michel
Published: April 2003

Background: In a Forum article Le Bourg (1998) criticized recent tests of evolutionary theories of aging and suggested alternative explanations for the long lifespan of ant queens and the positive relationship between body size and lifespan in mammals. Moreover, he attempts to criticize evolutionary theories of aging by showing that explanations other than evolutionary theories of aging probably account for the variation in human lifespan across countries. Objective: Here we show that the arguments of Le Bourg suffer several problems. First, many of the arguments reveal a misunderstanding of the process of natural selection. Second, some of the arguments reflect a lack of knowledge of evolutionary theories of aging (e.g. pre-reproductive mortality is not predicted to influence lifespan of organisms contrary to what is claimed). Finally, his final example on lifespan in humans simply is a straw-man because serious evolutionary biologists are well aware of the importance of confounding variables and would certainly not make the type of conclusion suggested by Le Bourg. Conclusion: Although a critical discussion of evolutionary theories of aging is welcome, we believe that the alternative explanations proposed by Le Bourg are implausible and reflect a misunderstanding of the process of natural selection.
Challenges to Understanding Age-Related Memory Loss in Late Adulthood: An Introduction
Authors: Luszcz Mary , Bryan Janet
Published: April 2003

Background: In the first 1999 issue of Gerontology several current hypotheses of age-related memory loss were canvassed. Objective: In hopes of fostering debate and further consideration of factors implicated in memory loss in late adulthood, commentaries were sought from a number of prominent cognitive ageing researchers on this review. Methods: Four commentaries were received and are briefly distilled in this preamble to them. Results: The papers elaborate on several themes raised in the original review, articulate assumptions implicit in the review, question the techniques used to assess mediational hypotheses, and suggest factors omitted from the review that need also to be considered. Conclusion: Despite an extensive literature on memory ageing, we are still a long way from understanding the mechanisms responsible for it. While considerable progress has already been made, over-reliance on between-person analyses, ambiguity in underlying constructs, and omission from consideration of key situation-specific characteristics of a memory episode may all contribute to a less than definitive understanding of memory ageing.
Timing, Instructions, and Inhibitory Control: Some Missing Factors in the Age and Memory Debate
Authors: Hasher Lynn , Zacks Rose T. , Rahhal Tamara A.
Published: April 2003

In response to Luszcz and Bryan, we point to three omitted factors that have been found to influence the presence and size of age differences in memory tasks and that, as such, have important implications for resolving theoretical questions about aging and memory. These include: (1) age differences in circadian rhythms and testing time effects that are associated with such differences; (2) instructions that may have a particularly disruptive effect on older adults, and (3) inhibitory control differences that have an age-related impact on both estimates of working memory span and on performance in multitask studies.
The Roots of Geriatric Medicine: Care of the Aged in Byzantine Times (324–1453 AD)
Authors: Lascaratos J. , Poulacou-Rebelacou Effie
Published: April 2003

Background: The search for the roots of geriatric medicine, which has been considered a relatively new branch. Objective: The purpose of the study is the research of the original Byzantine medical texts and the contemporary historical sources so as to bring to light knowledge about ancient medical care. Methods: The medical texts of Byzantine physicians were studied and analysed, as well as the Histories and Chronicles of their contemporary writers, so as to locate the extracts in the texts concerning geriatric care from the scientific point of view and that of the ‘vox populi’ which the historians and chroniclers express. Results: The problems of old age occupied physicians from earliest Byzantine times. They had dealt with the characteristics, symptoms and accompanying diseases of the aged and endeavoured to confront all the medical problems faced by the elderly, providing a special healthy regimen for the third age and taking steps for the prevention of diseases of this age group and their treatment. Parallel to this, the research of contemporary historical texts proves the concern of all society for the special problems of the aged and the significant impact of scientific geriatric medicine on the population. Conclusion: The study and analysis of the original medical and historical texts of the Byzantine period (324–1453 AD), written in Greek language, prove that the roots of medical care of old age could be traced from ancient Greek and Byzantine medicine.
Plasma Leptin Concentrations in Relation to Sick Euthyroid Syndrome in Elderly Patients with Nonthyroidal Illnesses
Authors: Corsonello Andrea , Buemi Michele , Artemisia Antonio , Giorgianni Grazia , Mauro Vittorio Nicita , Corica Francesco
Published: April 2003

Background: Leptin, the ob gene product, seems to be involved in regulating energy expenditure in humans, but its role in the pathophysiology of the energy imbalance in chronically ill patients is largely unknown. Objective: To evaluate plasma leptin concentrations and thyroid function in elderly patients with nonthyroidal illnesses (NTI). Methods: Sixty-four NTI elderly patients (75.0 ± 6.3 years, 27 males and 37 females) and 21 age- and sex-matched healthy controls (73.0 ± 5.5 years, 9 males and 12 females) were enrolled in the study. In all subjects tri-iodothyronine (T3), thyroxine (T4), reverse T3 (rT3), free T3 (fT3), free T4 (fT4), TSH, and plasma leptin concentrations were measured. Nutritional status was also evaluated in all subjects studied by the measurement of body mass index (BMI), lymphocytes, serum iron, hemoglobin, plasma albumin, transferrin and total cholesterol. Results: The data on thyroid hormones enabled us to identify three groups: group A, subjects (15 patients) with T3 and fT3 levels comparable to those of controls; group B, subjects (25 patients) with T3 and fT3 levels lower than controls and rT3 levels comparable to those of controls; group C, subjects (24 patients) with T3 and fT3 levels lower than those of controls and high rT3 levels. The patients of group C showed lower plasma leptin levels than the controls, 6.6 (5.5–14.2) and 16.3 (7.2–23.7) ng/ml (median with interquartile range in parentheses, p < 0.05), respectively. Females also showed higher plasma leptin levels than males in the controls, group A and group B, but not in group C. Moreover, plasma leptin concentrations were directly correlated to BMI in all the groups studied, while a negative correlation between leptin and rT3 was detectable in group C (r = –0.44, p < 0.05), also after adjusting for BMI and sex. Conclusions: The concurrence of modifications in plasma leptin and thyroid hormones concentrations found in elderly NTI patients with a sick euthyroid syndrome could reflect a particular neuroendocrine status, leading to a reduction in the catabolic processes in the course of chronic diseases.
A Critical Point for the Onset of Falls in the Elderly
Authors: Eke-Okoro Sunday T.
Published: April 2003

Background: Falls in the elderly during walking often result in very serious injuries. Gait analysts have meticulously explored the causes of these falls and reported age-related changes in gait parameters. It has not been possible to determine the level of derangement of gait parameters that is critical for falls in this population. There is the need to identify age-related interaction patterns of gait parameters. Such an interaction pattern could at least provide a mirror image of how the neural system adjusts to the age-related derangement. Objective: The purpose of this study was to utilize the interaction of gait parameters in the velocity field diagram (VFD) to explore the causes of falls in the elderly during walking. The VFD is a graph of the numerical values of gait parameters versus speed numbers derived by serially numbering the five speeds of walking from very slow to very fast. Methods: The gaits of healthy elderly persons (fallers and nonfallers) were recorded with those of healthy younger controls. The subjects walked along a 5-meter walkway in their shoes, but without walking aids. The subject walked from very slow to very fast according to what he/she considered to represent the respective speeds. Strides were counted, and the time taken to walk the distance was noted with a stopwatch. Numerical values of velocity (m/s), stride length (m), and stride frequency (strides/s) were used to construct the VFD. Results: The x-axis value of the equality point (E1) of the numerical values of velocity and stride frequency of the three study groups differed significantly (Anova α = 0.05, F = 22.94, p = 0.001). The E1 was formed in relation to gait efficiency. The x-axis value of the E1 was least in controls and greatest in fallers, while the reverse was the case for gait efficiency. The E1 of nonfallers defined a critical point for the precipitation of falls in the elderly. The value on the x-axis of the VFD of the critical point for the precipitation of a fall was 3.5 velots. A vertical line passing through E1 and abutting on the x-axis at 3.5 velots was described as fall precipitation line. Conclusion: Since the x-axis value of the critical point for the precipitation of a fall was 3.5 velots, it was suggested that elderly persons who equalize the numerical values of velocity and stride frequency at 3.5 velots should be provided with adequate preventive measures against falls.
Aged Mice Exhibit Greater Mortality Concomitant to Increased Brain and Plasma TNF-α Levels following Intracerebroventricular Injection of Lipopolysaccharide
Authors: Kalehua† A.N. , Taub D.D. , Baskar P.V. , Hengemihle J. , Muñoz J. , Trambadia M. , Speer D.L. , De Simoni M.-G. , Ingram D.K.
Published: April 2003

Background: Age-related defects in the development of peripheral inflammatory responses have been observed in rodents and humans. Objective: We examined the effects of age on a centrally injected endotoxin-induced cytokine production and cellular activation in mice. Methods: Male C57BL/6J (B6) mice, C3H/HeN mice, and C3H/HeJ mice received an intracerebroventricular injection of lipopolysaccharide (LPS) and were sacrificed at various times (2, 4, 8 h) thereafter. ELISA for IL-1β, IL-6, IL-12, and TNF-α were conducted on forebrain tissue homogenates as well as plasma samples, and lectin staining to detect activated microglia was prepared for selected brain slices. Results: Intracerebroventricular injection of LPS in B6 mice produced an age-associated increase in mortality which was paralleled with a significant increase in brain and plasma levels of TNF-α. AntiTNF-α- and IL-6-immunoreactive cells possessed macrophagelike morphologies and were observed along the LPS injection tract and scattered throughout the hilus of the dorsal hippocampus and cerebral cortices. This LPS-mediated response was found to be specific in that the LPS-hyporesponsive mouse strain (C3H/HeJ) failed to demonstrate significant brain or plasma levels of TNF-α after LPS administration compared to C3H/HeN mice. Conclusion: These results suggest that the age-related increases in TNF-α production and mortality following the intracerebroventricular administration of LPS may be due to an increased endotoxin hypersensitivity of brain microglia/macrophages within aged animals.
Use of In-Patient Hospital Beds by People Living in Residential Care
Authors: Finucane Paul , Wundke Rachel , Whitehead Craig , Williamson Lou , Baggoley Christopher
Published: April 2003

Background: There is concern that people living in residential care in Australia make significant and often inappropriate use of acute in-patient hospital services. To date, no factual information has been collected in Australia and its absence may allow myths and negative stereotypes to proliferate. Objective: To determine how and why people living in residential care in Australia use in-patient hospital beds. To determine the outcome of hospitalisation and functional status at 3 months following discharge. Methods: Prospective study of 184 consecutive admissions to hospital following Emergency Department (ED) attendance involving people aged over 65 years and living in residential care in southern Adelaide, South Australia. Information was obtained from the facilities’ transfer letters, and where these were inadequate or absent, telephone interviews were held with residential care staff. Results: 153 people accounted for the 184 admissions. They had a mean age of 84 years and 69% were female. 61% came from hostels and 35% from nursing homes. They had a wide range of clinical problems and twice as many were admitted to medical than to surgical units. Their mean length of hospital stay was 7.9 days, 2.3 days higher than for non-same-day patients and was higher for hostel than for nursing home residents. All but two admissions were considered unavoidable though the provision of specialised care within residential care could have prevented a further 19 (10%) admissions. 96% of admissions resulted in survival to leave hospital and in 74%, people returned directly to their place of origin. At 3 months follow-up, a further 20% of the group had died while 5% were in hospital. In all, 14% of the original group were in a different long-term care facility while 56% were living at their former residence. Conclusions: People living in residential care are often hospitalised because of acute illness. In the vast majority of cases hospitalisation is both appropriate and unavoidable. Most did not require prolonged hospitalisation and were discharged alive, usually to their original residence. However, within 3 months many had died or had functionally declined. Strategies that prevent health breakdown in the residential care setting need to be developed and trialed.
Nutritional Status According to Mini Nutritional Assessment in an Institutionalized Elderly Population in Sweden
Authors: Saletti Anja , Lindgren Elinor Yifter , Johansson Lennarth , Cederholm Tommy
Published: April 2003

Background: In 1992, local municipalities in Sweden took over full responsibility for the long-term care of elderly. This has led to an increased care burden for the various assisted accommodation services run by the municipalities. Objective: Since ageing and chronic diseases are risk factors for protein-energy malnutrition, we evaluated the nutritional status of all individuals in assisted accommodation, i.e., service flats (SF), old people’s homes (OPH), group living for the demented (GLD), and nursing homes (NH), in three Swedish municipalities. Methods: Of 994 eligible subjects, 872 were examined; the average age was 84.5 ± 8 years, and 69% were female. The Mini Nutritional Assessment (MNA) scale (0–30 points) was used, consisting of 18 point-weighted questions in four categories, i.e., anthropometry, global and dietary issues, and self-assessment. Results: MNA <17, i.e., malnutrition, was noted in 36% of the study population. Divided according to accommodation type, the MNA scores were <17 in 21% of individuals in SF, 33% of those in OPH, 38% of those in GLD, and 71% of those in NH. The corresponding values for MNA scores 17–23.5 (risk for malnutrition) were 49, 51, 57, and 29%, respectively. Average body mass index (BMI) values were 24.2 ± 5 (SF), 23.6 ± 5 (OPH), 23.9 ± 4 (GLD), and 22.3 ± 4 (NH). BMI values ≤20 were found in 18% of those in SF, in 25% of those in OPH, in 19% of those in GLD, and in 33% of those in NH. Both MNA and BMI correlated with upper arm and calf circumference, with r values ranging from 0.4 to 0.7 (p < 0.001). MNA and BMI correlated significantly (r = 0.52, p < 0.001). Age correlated with MNA and BMI with r values of 0.1 (p < 0.01) and 0.14 (p < 0.001), respectively. Subjects with signficant help requirements during meals ate fewer whole meals per day than those who could feed themselves. Conclusions: Based on the MNA, one third of the study subjects living in assisted accommodation, and more than half of those living in NH, appeared to be malnourished. Further studies are necessary to assess to what extent these nutritional disturbances are reversible.
The Adherent Gastric Antral and Duodenal Mucus Gel Layer Thins with Advancing Age in Subjects Infected with Helicobacter pylori
Authors: Newton Julia L. , Jordan Nicola , Pearson Jeff , Williams Gareth V. , Allen Adrian , James Oliver F.W.
Published: April 2003

Background: Peptic ulceration and Helicobacter pylori infection increase with advancing age. In the upper gastro-intestinal tract the first line of mucosal defence is the adherent mucus gel layer. Objective: We have examined, using a novel histological fixation technique, the thickness of the adherent mucus gel layer (1) in the gastric antrum and (2) in the duodenum in relation to advancing age and H. pylori status. Methods: The subjects had macroscopically normal stomach and duodenum at endoscopy. Measurement of the gastric antral mucus thickness was carried out on four antral biopsy specimens from within 2 cm of the pylorus (H. pylori positive n = 25, negative n = 21). The duodenal mucus thickness (D1) was measured from two biopsy specimens (H. pylori positive n = 7, negative n = 13). All specimens were snap frozen and cryostat sections stained using a modified PAS/AB stain. Results: In all sections the mucus layer was continuous. In both duodenum and gastric antrum, the mucus thickness was not significantly different between H. pylori positive and H. pylori negative age-matched samples. In duodenum and gastric antrum from H. pylori negative subjects, there was no correlation between mucus thickness and age. However, in H. pylori positive subjects, there was a significant thinning of the adherent gastric antral mucus gel layer (p = 0.005, r = –0.54) and the duodenal mucus thickness (p < 0.001, r = –0.99) with advancing age. Conclusion: This study shows a significant thinning of the adherent mucus gel layer in H. pylori positive individuals, as stomach and duodenum age. In those without H. pylori, the mucus gel thickness is preserved in stomach and duodenum.
Pulmonary Embolism in the Elderly: Clinical, Instrumental and Laboratory Aspects
Authors: Masotti Luca , Ceccarelli Elena , Cappelli Roberto , Guerrini Maurizio , Forconi Sandro
Published: April 2003

Objective: To focus on diagnostic and therapeutic problems of pulmonary embolism in the elderly. Methods: Retrospective analysis of 5 years of clinical, instrumental, and laboratory data (collected at the time of hospital admission) for patients 65 years and older with pulmonary embolism proven by a high-probability scintigraphic lung scan or necropsy. Sixty-eight patients, 46 females and 22 males, 78.61 ± (SD) 7.71 years old, were enrolled in the study. Results: Dyspnea, chest pain, tachycardia, and tachypnea were the most common symptoms and signs; they were present alone or in combination in all patients. Bed rest over 4 days was found in 65% of the patients and deep vein thrombosis in the leg in 35%. Only 7 patients were on anticoagulant therapy which was likely to reduce the incidence of pulmonary embolism. The mortality was 29.5%. Major bleeding due to anticoagulant therapy was observed in 4.4% of the patients; 1 case was fatal. Sinus tachycardia, ST segment and T wave abnormalities in anterior leads, and incomplete bundle branch block were the most frequent electrocardiographic findings. Chest X-ray was normal in 19.5% of the patients and compatible with pulmonary embolism in 10%. A transthoracic two-dimensional echocardiogram was abnormal in 74% of the cases, with involvement of the right ventricle in the majority of them. Many patients had laboratory parameters within the normal range. The value of the latex agglutination D-dimer assay was less than the cutoff value of 500 µg/l in 16% of the patients. Hypoxemia and a high alveolar-arterial oxygen gradient were the most frequent aspects of the arterial blood gas analysis. Respiratory alkalosis was observed in only one third of the patients. Conclusions: Pulmonary embolism is often underdiagnosed in the elderly. Clinical, instrumental, and laboratory findings are nonspecific. Only acute suspicion can increase the number of diagnoses, reduce the time to diagnosis, and improve the prognosis.
Muscle Strength and Mass of Lower Extremities in Relation to Functional Abilities in Elderly Adults
Authors: Carmeli Eli , Reznick Abraham Z. , Coleman Raymond , Carmeli Varda
Published: April 2003

Background: Functional and physiological declines in advancing age may be significant limiting factors in reduced physical activity. Sarcopenia of aging, as a normative process or disease, cannot entirely explain reduced physical activity in the elderly. Objective: The purpose of the study was to investigate the relationship between muscle loss and reduction in functional abilities in elderly adults and also to determine whether an exercise program can improve functional performance and muscle quality. Methods: Anthropometric measurements and sensorimotor testing were conducted on 28 volunteers (12 men and 16 women, 82.7 ± 2.4 years of age) who were permanent residents in a skilled nursing facility. Twenty-nine elderly adults (79.3 ± 3.5 years of age) served as a control, nonexercising group. Anthropometric measurements included: weight, height, body fat, and thigh circumference. The muscle strength was tested with a medical isokinetic system. We assessed two sensorimotor functions including a ‘timed up-and-go’ test and a 3-min distance walking test. The institutionalized participants undertook an exercise training program lasting 12 weeks. Results: No significant changes were observed in thigh circumference, body weight, or percentage of body fat in either gender as a result of the exercise training. An improvement in muscle strength was noticed in 82% of the relatively younger group (79–83 years of age) under a slow voluntary contraction at 60°/s (p < 0.05). Post-training results showed a significant improvement in performance in the two sensorimotor tests (p < 0.05). The correlation coefficients between muscle strength and functional ability were weak: r = 0.60 and r = 0.57 for males and females, respectively. Conclusions: This study confirmed the positive effects of an exercise program on functional performance in older adults. The improvement in functional abilities did not correlate with muscle strength, body weight, or body fat.
Frauen und Schwerbehinderte ...
Authors: Dapunt O.
Published: April 2003

Berufungsverhandlungen sind Tabuthemen. Nach einem 27jährigen Ordinariat und 4jährigem Dekanat stelle ich mich einigen Fragen aus zugegeben subjektiver und eingeschränkt österreichischer Sicht: Wählen wir die Besten oder entscheiden oftmals Lobbies jenseits der persönlichen Verantwortlichkeit der Kommissionsmitglieder? Lässt deren grosse Zahl und ihre Kompetenz eine Leistungsbeurteilung zu? Steht der Impactfaktor oder die klinische Rundumerfahrung im Vordergrund? Besteht Chancengleichheit für Kollegen mit onkologischem oder geburtshilflichem Tiefgang? Hat die Einrichtung von Arbeitskreisen für Gleichbehandlungsfragen für Kandidatinnen etwas gebracht?
Entwicklungen in der operativen Gynäkologie
Authors: Dapunt O.
Published: April 2003

Im ausgearbeiteten Text der Abschiedsvorlesung wird die Entwicklung der operativen Gynäkologie anhand der Onkochirurgie, der Uterusexstirpation mit oder ohne Rekonstruktion des Beckenbodens sowie der Korrekturoperationen am Uterovaginalkanal abgehandelt. Es gibt keinen Zweifel, dass endoskopische Chirurgie insbesondere im Bereich der Adnexe und des Cavum uteri grosse Bedeutung gewonnen hat. Die Uterusexstirpation sollte weiterhin die Domäne des vaginalen Vorgehens bleiben. Die für den erfahrenen «Vaginalisten» fast immer überflüssige «laparoskopische Assistenz» sollte sich im Sinne einer Renaissance der vaginalen Technik auswirken. Starke Betonung muss von Seiten der Gynäkologie weiterhin auf die vaginale Rekonstruktion des lädierten Beckenbodens im Rahmen von Inkontinenzoperationen gelegt werden. Fehlbildungen des Uterus werden dank neuer diagnostischer Möglichkeiten häufiger entdeckt, eine Verfeinerung der Diagnostik erscheint unerlässlich, will man verhindern, dass hier ein weiteres Tummelfeld laparoskopischer Polypragmatik entsteht. Die nach Ansicht des Autors vor allem an Universitätskliniken stetig mehr im Argen liegende operative Ausbildung der Fachärzte wird diskutiert.
Rückblick, Gegenwart und Ausblick in der Geburtshilfe
Authors: Husslein Peter
Published: April 2003

Die eindrucksvollste Entwicklung der Geburtshilfe in den letzten 25 Jahren ist das Absinken der perinatalen Mortalität von rund 25 auf unter 6‰. Entgegen der seinerzeitigen Erwartung ist dies nicht durch Reduktion der Frühgeburtenrate, sondern durch besseren Umgang mit Frühgeborenen erzielt worden, insbesondere durch die Induktion der fetalen Organreife durch Kortikosteroidgabe und die antenatale Transferierung von Hochrisikoschwangeren an ein Perinatalzentrum. Auch eine schonendere Geburtsleitung und entsprechende Verbesserungen auf Neonatologieseite (z.B. Surfactantgabe, weniger invasive Beatmungsformen) haben einen entsprechenden Beitrag zum besseren Ergebnis geleistet. Andere Marksteine der geburtshilflichen Entwicklung waren die Einführung der Prostaglandine zur Fruchtausstossung, Geburtseinleitung und Behandlung der postpartalen Atonie. Neben diesen medizinischen Entwicklungen haben aber auch soziologische Trends die Geburtshilfe geprägt und werden sie in Zukunft noch weiter beeinflussen: Die Zunahme der Bedeutung des Patientenwillens, paramedizinische Gesichtspunkte in der Geburtshilfe und die erhöhte Klagebereitschaft bei vermeintlichem Schaden. Die nächsten Jahrzehnte in der Geburtshilfe werden einen unaufhaltsamen Anstieg der Sectiofrequenz zeigen, unter anderem durch die Erkenntnis, dass vaginale Geburten bisher zuwenig beachtete Schäden am Beckenboden verursachen. Wegen des erwarteten Absinkens der Geburtenzahlen, des Ansteigens der Ärzte- und Hebammendichte, der erhöhten Anspruchshaltung der Bevölkerung und der schonungslosen Klagebereitschaft vermeintlich zu Schaden gekommener Patientinnen wird das Umfeld für geburtshilflich tätige Ärzte in Zukunft schwieriger werden.
Recurrent Warfarin-Induced Skin Necrosis in Kindreds with Protein S Deficiency
Authors: Sallah Sabah , Abdallah Jorge M. , Gagnon Gregory A.
Published: April 2003

Warfarin-induced skin necrosis is a rare complication of anticoagulant treatment. The incidence of this complication is undetermined, but it has been estimated to occur between 1:100 and 1:10,000 of patients treated with anticoagulants. Coumarin skin necrosis occurs almost exclusively in patients with venous thrombosis between the 3rd and 10th day after beginning anticoagulation. Although protein C deficiency is the most common underlying hypercoagulable state reportedly associated with warfarin skin necrosis, very few cases have been linked to congenital protein S deficiency. This article addresses the association of hereditary protein S deficiency and warfarin skin necrosis, and provides suggestions for management.
Out-of-Hospital Treatment of Venous Thrombosis: Socioeconomic Aspects and Patients’ Quality of Life
Authors: Bossuyt P.M.M. , van den Belt A.G.M. , Prins M.H.
Published: April 2003

Low-molecular-weight heparin has been recommended as the initial treatment of choice for patients with venous thromboembolism who require anticoagulant therapy. In recent studies, outpatient management of these patients has been proposed to be as effective and safe as treatment given in the hospital. This paper outlines the results of these studies and considers the feasibility of home treatment and the consequences of such a strategy. It is concluded that home treatment with low-molecular-weight heparin in patients with venous thromboembolism leads to significant benefits in terms of increase in the quality of life of the patients and a reduction in the duration of hospital stay, thus improving healthcare efficiency.
Venous Thromboembolism in Malignancy and Malignancy in Venous Thromboembolism
Authors: Rickles Frederick R. , Levine Mark N.
Published: April 2003

The activation of coagulation in patients with cancer contributes significantly to morbidity and mortality rates and may play a fundamental role in the host response to growing tumours. Patients with cancer are clearly at high risk for the development of venous thromboembolism (VTE), particularly during chemotherapy and surgery. This situation is aggravated by the use of venous access catheters and possibly growth factors. Data derived from large, randomized, controlled trials have been used to determine the true incidence of this complication of cancer and its treatment. The incidence based on the analyses of these randomized controlled trials varies from 1% for limited stage patients with breast cancer treated with tamoxifen to 60% for patients with any type of cancer who are subjected to orthopaedic surgery and do not receive prophylactic therapy. In view of the morbidity and mortality attributable to VTE in cancer, widespread utilization of prophylactic anticoagulation therapy, which has proven safe and effective in a variety of situations, should be considered. While migratory thrombophlebitis is a clear indicator of an underlying neoplasm, the risk of cancer in patients with the more typical form of VTE has been the subject of intense debate over recent years. Some investigators have suggested that the relative risk of being diagnosed with an occult cancer within 6 months of an episode of VTE (particularly recurrent VTE) could be up to 10-fold. However, the cost-effectiveness of aggressive screening for cancer in patients with VTE has not yet been defined adequately.
Unfractionated Heparin and Low-Molecular-Weight Heparin for the Initial Treatment of Acute Venous Thromboembolism
Authors: Prandoni Paolo
Published: April 2003

Anticoagulant drugs represent the therapy of choice for the initial treatment of venous thromboembolism. Unfractionated heparin (UFH) in adjusted doses and low-molecular- weight heparin (LMWH) in fixed doses are equally as effective and safe. Proper use of UFH requires considerable expertise, can cause inconvenience and has limitations. The use of LMWHs has multiple advantages over UFH including a more predictable dose-response and fixed administration dose. These properties make the treatment of suitable patients feasible in an outpatient setting. In two major clinical trials addressing the treatment of deep vein thrombosis, outpatient management with LMWH was associated with a substantial cost reduction compared with inpatient treatment using UFH. Recent studies have also shown that LMWHs are at least as effective and safe as UFH for the treatment of non-critical patients with pulmonary embolism. Whether or not home treatment of pulmonary embolism is feasible and safe remains to be demonstrated.
Effects of Polysulfonate Derivative (GL 522-Y-1) on Coagulation in vitro and Thrombosis in vivo
Authors: Radziwon P. , Boczkowska-Radziwon B. , Giedrojc J. , Schenk J. , Wojtukiewicz M.Z. , Kloczko J. , Breddin H.K.
Published: April 2003

We have investigated the influence of a polysulfonate derivative – GL 522-Y-1 – on platelet-induced thrombin generation time, platelet adhesion to siliconized glass, platelet aggregation induced by collagen and ADP, on aPTT, PT and TT in vitro and studied its antithrombotic effect in an animal model of thrombosis in vivo. In vitro, GL 522-Y-1 caused inhibition of ADP- and collagen-induced aggregation. In a dose-dependent manner this compound inhibited PITT, aPTT, and PT. GL 522-Y-1 did not prolong thrombin time. GL 522-Y-1 inhibited in vivo the laser-induced thrombus formation after intravenous and oral administration. On the basis of its unique antithrombotic properties, GL 522-Y-1 seems to open a new pathway in the field of antithrombotics.
Epidemiology of Post-Stroke Dementia
Authors: Kooten Fop van , Koudstaal Peter J.
Published: April 2003

Twenty to 25% of stroke patients are demented after stroke, which makes stroke an important risk factor for dementia. However, the diagnosis of dementia is difficult and depends heavily on methodology. In this review, we describe pitfalls of diagnosis, the prevalence and incidence of dementia after stroke based on data from prospectively studied stroke cohorts, and the risk factors for post-stroke dementia that emerged from these studies. Finally, the course and prognosis of post-stroke dementia are described.
Role of Platelet Activation in Dementia
Authors: van Kooten Fop , Ciabattoni Giovanni , Patrono Carlo , Koudstaal Peter J.
Published: April 2003

Platelets play an important role in atherosclerosis, and increased platelet activation is associated with stroke. Stroke is an important risk factor for dementia, as approximately 25% of the patients are demented after stroke. In this review, we describe platelet activation studies in patients with stroke and with dementia. In addition, we review the few studies that have investigated the effect of antiplatelet medication such as aspirin and non-steroidal anti-inflammatory drugs on cognitive function and the occurrence of dementia. We conclude that further studies are needed to characterize the mechanisms and determinants of platelet activation in relation to the development of dementia. Furthermore, the efficacy and safety of antiplatelet intervention will have to be assessed in properly designed randomized trials.
Coagulation and Fibrinolysis Markers and Risk of Dementia
Authors: Bots Michiel L. , Breteler Monique M.B. , van Kooten Fop , Haverkate Frits , Meijer Piet , Koudstaal Peter J. , Grobbee Diederick E. , Kluft Cornelis
Published: April 2003

We performed a cross-sectional case-control study among 277 subjects with dementia and 298 control subjects drawn from participants of the Rotterdam Study, a population-based cohort study among subjects aged 55 years or over, and from participants of the Rotterdam Stroke Databank, a hospital-based stroke registry, with the objective to evaluate the association of indicators of coagulability, fibrinogen, prothrombin fragments 1+2, thrombin-antithrombin complex (TAT), and indicators of fibrinolysis, plasmin-inhibitor complex, D-dimer and tissue-type plasminogen activator (t-PA) with dementia. Increased levels of TAT, D-dimer and t-PA activity were associated with an increased risk of dementia. Additional stratified analyses indicated that an increased TAT level was the primary factor related to dementia. The present study provides evidence that predominantly increased thrombin generation is associated with dementia.
Specificity of Haemostasis Abnormalities for Vascular Phenotypes
Authors: Lowe Gordon D.O. , Haverkate Frits
Published: April 2003

Atherothrombosis is a systemic disease, hence it is difficult to prove the specificity of haemostasis abnormality for any single vascular phenotype. Associations between haemostatic variables and any given phenotype, e.g. (vascular) dementia, should be interpreted with caution, given the overlaps of vascular disease phenotypes, risk factors, and haemostatic variables.
Massive Intracranial Bleeding Requiring Emergency Splenectomy in a Patient with CMV-Associated Thrombocytopenia
Authors: Gural Alexander , Gillis Shmuel , Gafanovich Anna , Israel Zvi , Wolf Danna , Pomeranz Shlomo , Ben-Yehuda Dina
Published: April 2003

We describe a previously healthy male patient, with severe immune thrombocytopenic purpura (ITP) following CMV infection which was refractory to steroids and intravenous immunoglobulin, who developed massive intracranial bleeding. Despite an extremely low platelet count (2×109/liter) which was refractory to platelet transfusions, successful emergency splenectomy was performed, with rapid resolution of the thrombocytopenia. Bleeding complications are extremely rare in viral-associated ITP. Emergency splenectomy should be considered in the presence of life-threatening bleeding when other modalities fail to produce a rise in the platelet count. Infection with CMV should be ruled out in cases of severe, treatment-resistant ITP.
High-Dose Dexamethasone for Splenectomy in Patients with Idiopathic Thrombocytopenic Purpura
Authors: Bulvik Shlomo , Winder Asher , Ben-Tal Ofira , Szold Amir , Eldor Amiram
Published: April 2003

High-dose intravenous immune globulin (IV IgG) is currently the treatment of choice for patients with idiopathic thrombocytopenic purpura (ITP) who undergo splenectomy; however, this treatment is extremely expensive. We report on 13 ITP patients with severe thrombocytopenia (<20 × 109/l) who were prepared for laparoscopic splenectomy with a 4-day oral course of high-dose (40 mg/day) dexamethasone (DEX). Four patients had an excellent response with platelet counts that increased to above 150 × 109/l. Seven patients had a good response with a platelet count that increased to between 50 and 150 × 109/l (median 121 × 109/l). Two patients were resistant both to DEX and IV IgG. The operation was uneventful in all the patients, including the 2 who had resistant ITP and were operated on while their platelet count was very low (5 × 109/l). Thus, high-dose DEX, which is an easy, effective and inexpensive treatment, is recommended for the preparation of ITP patients prior to splenectomy.
Elevated Thrombotic Activity after Myocardial Infarction: A 2-Year Follow-Up Study
Authors: Martínez-Sales V. , Vila V. , Réganon E. , Goberna M.A. , Ferrando F. , Palencia M.A. , Aznar J.
Published: April 2003

This study examines the evolution of the thrombotic activity in patients with myocardial infarction (MI) treated with aspirin (200 mg/day) for 2 years after MI. Plasma samples of 10 patients were collected at 7, 30, 60, 90, 120, 150, 180, 360 and 720 days. In all the samples we measured fibrinogen (Fg), high molecular weight Fg (HMW-Fg), fibrinopeptide A (FPA), prothrombin fragment 1+2 (F1+2), β-thromboglobulin (β-TG), von Willebrand factor (vWF), tissue factor (TF) and TF pathway inhibitor (TFPI). The plasma Fg, HMW-Fg, FPA, F1+2, β-TG and vWF levels were significantly elevated in the patients at the beginning of the study as compared to the normal group. The 95% confidence intervals were Fg 277–333 mg/dl, HMW-Fg 200–244 mg/dl, FPA 5.3–16.5 ng/ml, F1+2 1.4–1.8 nmol/l, β-TG 110–118 IU/ml and vWF 139–195%. At thirty days Fg and HMW-Fg returned to normal levels, whereas the increase in FPA and F1+2 levels persisted throughout the study. At 120 and 150 days, respectively, β-TG and vWF returned to normal levels. The increase in thrombin generation and activity pointed to a persistent hypercoagulable state 2 years after MI. Plasma levels of TF and TFPI showed no statistically significant variations with respect to the normal values over the 2-year period studied. In conclusion, these results suggest a persistent generation and activity of thrombin and cellular activation in these patients after MI.
Four Cases of Bleeding Diathesis in Children due to Congenital Plasminogen Activator Inhibitor-1 Deficiency
Authors: Minowa Hideki , Takahashi Yukihiro , Tanaka Taeko , Naganuma Kuniaki , Ida Shinobu , Maki Ichiro , Yoshioka Akira
Published: April 2003

Congenital plasminogen activator inhibitor-1 (PAI-1) deficiency is an extremely rare disorder characterized by a bleeding diathesis that begins in childhood due to hyperfibrinolysis as a result of decreased PAI-1 activity. We now present 4 unrelated pediatric cases of congenital PAI-1 deficiency. All 4 patients had a history of recurrent episodes of subcutaneous bleeding beginning in early childhood. These episodes were characterized by abnormal prolonged bleeding after trauma, tooth extraction, and surgical procedures, as well as by rebleeding following initial hemostasis. The 2 female patients both had symptoms compatible with hypermenorrhea. The family history was positive in 2 of the 4 patients. Hemostatic screening studies in all 4 patients revealed no abnormalities. Testing for factor XIII antigen, von Willebrand factor antigen, ristocetin cofactor activity, α2-plasmin inhibitor (α2PI) activity, and plasminogen activity was normal. The euglobulin lysis times were shortened in all cases as compared with those in normal control subjects. None of the patients had elevated tissue plasminogen activator (tPA) antigen levels, but PAI activity was markedly decreased in all cases. Three of the patients also had reduced levels of PAI-1 antigen. There tended to be a reduction in tPA-PAI-1 complex in all cases. In addition, 2 patients had elevated PIC (plasmin-α2PI complex). Tourniquet tests were performed in 2 patients, with no appreciable rise in PAI-1 activity or PAI-1 antigen levels. The administration of tranexamic acid clearly improved hemorrhagic symptoms in these patients. We considered PAI-1 deficiency to be the likely etiology of the congenital bleeding diatheses in these 4 cases.