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A Kurz

Publications and source records attributed to A Kurz.

At least 91 records · Page 5Linked to original sources
PubMed1999

[Inheritable causes and risk factors of Alzheimer's disease].

A multifactorial etiology underlies the majority of cases of Alzheimer's disease (AD). Both ill-defined environmental and genetic factors contribute to the development of the disease. Allele epsilon 4 of ApoE is a genetic risk factor. Its presence increases the risk of developing AD. However, presence of e4 is neither necessary nor sufficient for the disease to arise. Apart from the common multifactorial forms of the disease, there are rare variants which are inherited as Mendelian traits. To date three genes are known that can be mutated in these rare forms of AD. Of these, mutations in the gene presenilin 1 on chromosome 14 are most frequent. In addition, mutations in the gene presenilin 2 on chromosome 1 and in the amyloid precursor protein gene (APP on chromosome 21) occur in autosomal dominant AD. This article reviews our present knowledge of the genetics of AD and discusses its relevance for patients with AD and their relatives.

Alzheimer Disease↗
PubMed1999

[Effect pf anti-dementia drugs on the daily routine and attitude of dementia patients].

The introduction of acetylcholinesterase inhibitors has greatly improved therapeutic opportunities for patients with dementia, in particular with Alzheimer's disease. The most likely outcome of treatment with these compounds is a maintenance of cognitive ability and/or activities of daily living over at least 6 months. Regarding the progressive nature of the underlying neurodegenerative process a temporary stabilization of symptoms is a clear treatment success. Approximately 25 per cent of patients experience a significant improvement in cognitive ability. They show more attentiveness, interest, activity, orientation, communicative ability, as well as better memory. In addition, the new medications can ameliorate non-cognitive symptoms including apathy, agitation, delusions, hallucinations, and disinhibition. Open-label long-term studies have demonstrated that patients receiving treatment with an acetylcholinesterase inhibitor cross their baseline cognitive ability at week 40 to 50 and continue to decline thereafter. In spite of this slow deterioration treated patients perform better than untreated individuals. Since ethical reasons do not permit to include placebo control groups in long-term trials it is not known presently how long the benefit from treatment lasts.

Activities of Daily Living↗
PubMed1999

Clinical features of Alzheimer's disease.

The preclinical stage of Alzheimer's disease is inconspicuous and there are - almost by definition - no reliable and valid symptoms and signs which would allow a very early diagnosis before the manifestation of irreversible deficits. For a clinical diagnosis of dementia, cognitive impairment has to be severe enough to compromise the activities of daily living. In the mild dementia stage, difficulties with declarative memory are usually prominent; depressive symptoms are not infrequent, but the patient usually manages to live alone. Supervision is needed in the moderate dementia stage, when other cognitive domains are affected in a more obvious manner and non-cognitive disturbances of thought, perception, affect, and behavior put increasing stress on the caregivers. Complete dependence of the patients, who frequently develop neurological disturbances, is typical of the late stage of illness. The life expectancy of patients with a clinical diagnosis of Alzheimer's disease is significantly reduced, but to date there is hope that the period of relative well-being and not of suffering can be prolonged with modern symptomatic treatment interventions.

Activities of Daily Living↗
PubMed1999

DNA and 2'-deoxyguanosine damage in the horseradish-peroxidase-catalyzed autoxidation of aldehydes: the search for the oxidizing species.

The horseradish-peroxidase(HRP)-catalyzed aerobic oxidation of aldehydes, in particular isobutanal, was used for the oxidative damage of DNA. In isolated calf-thymus DNA, the enzymatic oxidation of isobutanal led to 7,8-dihydro-8-oxoguanine (8-oxoGua) in up to 1.3% yield and appreciable single-strand breaks in supercoiled pBR 322 DNA. For the nucleoside dG, significant amounts of the guanidine-releasing products oxazolone and oxoimidazolidine have been detected, but 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxodG) was not obtained. Only enolizable aldehydes are effective, molecular oxygen is essential, and radical scavengers inhibit efficiently the oxidation. Comparative experiments with 3,3,4,4-tetramethyl-1,2-dioxetane (TMD) revealed that triplet-excited acetone does not play a significant role in this enzymatic DNA oxidation. 2-Hydroperoxy-2-methylpropanal, an intermediate in the HRP-catalyzed aerobic oxidation of isobutanal, does not contribute directly in the observed dG conversion. However, the peroxyl radical derived from the 2-hydroperoxy-2-methylpropanal appears to be active as oxidant because model studies with a structurally related peroxyl radical, produced by HRP-catalyzed one-electron oxidation of 3-hydroperoxy-3-methyl-2-butanone, causes both dG conversion and DNA strand breaks, but to a moderate extent. The active oxidant, as established by control experiments, is the peroxyisobutyric acid, that is efficiently formed through the HRP-catalyzed autoxidation of isobutanal. Still more effective is the acylperoxyl radical, conveniently generated from the peracid by one-electron oxidation by HRP.

Aerobiosis↗
PubMed1999

Onset time, recovery duration, and drug cost with four different methods of inducing general anesthesia.

UNLABELLED: We compared two conventional induction techniques (thiopental and propofol), an inhaled induction with sevoflurane using a circle system, and a rebreathing method. Fentanyl 1 microg/kg was given to women undergoing 10- to 20-min procedures. Anesthesia was induced (n = 20 each) with one of the following: 1) sevoflurane and N2O from a rebreathing bag (Sevo/Bag). A 5-L bag was prefilled with a mixture of sevoflurane 7% and N2O 60% in oxygen. The bag was connected between the normal circle system, separated by a spring-loaded valve; 2) sevoflurane 8% and N2O 60% from a circle system on a conventional anesthesia machine with a total fresh gas flow of 6 L/min (Sevo/Circle); 3) propofol 3 mg/kg as an i.v. bolus; 4) thiopental sodium 5 mg/kg as an i.v. bolus. Postoperative nausea and vomiting was treated with ondansetron. Induction times were comparable with each method. Recovery duration was shortest with sevoflurane, intermediate with propofol, and longest with thiopental. Induction drug costs were lowest with Sevo/Bag and thiopental, intermediate with Sevo/Circle, and highest with propofol. However, sevoflurane (by either method) caused considerable nausea and vomiting that required treatment. Consequently, total drug cost was least with thiopental, intermediate with Sevo/Bag and propofol, and greatest with Sevo/Circle. Thus, no single technique was clearly superior. IMPLICATIONS: Anesthetic induction techniques influence awakening time, recovery duration, and drug costs. We tested two i.v. methods and two inhaled techniques. However, none of the four tested methods was clearly superior to the others.

Adult↗
PubMed1999

Shivering and shivering-like tremor during labor with and without epidural analgesia.

BACKGROUND: Effective treatment and prevention of hyperthermia and shivering-like tremor during labor is hindered by a poor understanding of their causes. The authors sought to identify the incidence of nonthermoregulatory shivering-like tremor and the factors associated with this activity. METHODS: The authors studied women in spontaneous full-term labor who chose epidural analgesia (n = 21) or opioid sedation (n = 31). Shivering-like tremor and sweating were evaluated by observation. Core temperature was recorded in the external auditory canal using a compensated infrared thermometer. Arteriovenous shunt tone was evaluated with forearm minus fingertip skin temperature gradients; gradients less than 0 were considered evidence of vasodilation. Tremor was considered nonthermoregulatory when core temperature exceeded 37 degrees C and the arms were vasodilated. Pain was evaluated using a visual analog scale. RESULTS: Shivering-like tremor was observed in 18% of 290, 30-min data-acquisition epochs before delivery. The patients were both normothermic and vasodilated during 15% of these epochs. Shivering was observed in 16% of 116 postdelivery epochs and was nonthermoregulatory in 28%. Sweating was observed in 30% of predelivery epochs, and the patients were both hypothermic and vasoconstricted during 12%. The mean core temperature in patients given epidural analgesia was approximately 0.2 degrees C greater than in those given sedation. Hyperthermia was observed during 10 epochs (38.4+/-0.3 degrees C) during epidural analgesia and during 10 epochs (38.4+/-0.3 degrees C) with sedation. The patients were vasoconstricted in more than 50% of these epochs in each group. Multivariate mixed-effects modeling identified high pain scores and vasoconstriction as significant predictors of shivering. There were no predictors for shivering epochs in patients who were simultaneously normothermic and vasodilated. Significant predictors of sweating were time before delivery, high pain scores, hypothermia with vasoconstriction, high thermal comfort, and low mean skin temperature. There were no predictors for sweating epochs in patients who were simultaneously hypothermic and vasoconstricted. CONCLUSIONS: This study confirms the clinical impression that some peripartum shivering-like tremor is nonthermoregulatory. The authors also identified nonthermoregulatory sweating. These data indicate that shivering-like tremor and sweating in the peripartum period is multifactorial.

Adult↗
PubMed1999

Comparable postoperative pulmonary atelectasis in patients given 30% or 80% oxygen during and 2 hours after colon resection.

BACKGROUND: High concentrations of inspired oxygen are associated with pulmonary atelectasis but also provide recognized advantages. Consequently, the appropriate inspired oxygen concentration for general surgical use remains controversial. The authors tested the hypothesis that atelectasis and pulmonary dysfunction on the first postoperative day are comparable in patients given 30% or 80% perioperative oxygen. METHODS: Thirty patients aged 18-65 yr were anesthetized with isoflurane and randomly assigned to 30% or 80% oxygen during and for 2 h after colon resection. Chest radiographs and pulmonary function tests (forced vital capacity and forced expiratory volume) were obtained preoperatively and on the first postoperative day. Arterial blood gas measurements were obtained intraoperatively, after 2 h of recovery, and on the first postoperative day. Computed tomography scans of the chest were also obtained on the first postoperative day. RESULTS: Postoperative pulmonary mechanical function was significantly reduced compared with preoperative values, but there was no difference between the groups at either time. Arterial gas partial pressures and the alveolar-arterial oxygen difference were also comparable in the two groups. All preoperative chest radiographs were normal. Postoperative radiographs showed atelectasis in 36% of the patients in the 30%-oxygen group and in 44% of those in the 80%-oxygen group. Relatively small amounts of pulmonary atelectasis (expressed as a percentage of total lung volume) were observed on the computed tomography scans, and the percentages (mean +/- SD) did not differ significantly in the patients given 30% oxygen (2.5% +/- 3.2%) or 80% oxygen (3.0% +/- 1.8%). These data provided a 99% chance of detecting a 2% difference in atelectasis volume at an alpha level of 0.05. CONCLUSIONS: Lung volumes, the incidence and severity of atelectasis, and alveolar gas exchange were comparable in patients given 30% and 80% perioperative oxygen. The authors conclude that administration of 80% oxygen in the perioperative period does not worsen lung function. Therefore, patients who may benefit from generous oxygen partial pressures should not be denied supplemental perioperative oxygen for fear of causing atelectasis.

Adult↗
PubMed1998

The therapeutic potential of tacrine.

Tacrine, a non-competitive inhibitor of acetylcholine esterase, has been approved for the treatment of patients with mild to moderate Alzheimer's disease in 1995. The available evidence suggests that in a substantial proportion of patients tacrine has the potential to improve cognitive functions, to ameliorate behavioural problems, and to delay the time to significant clinical endpoints. Thus, tacrine meets realistic expectations from symptomatic treatment. The major safety concern about tacrine is the probability of liver enzyme elevations and the high frequency of adverse events, particularly gastrointestinal. Findings are presented from an open-label multicentre study showing that tacrine is a safe and manageable compound in private practice.

Activities of Daily Living↗
PubMed1998

[Tau protein. A potential biological indicator for early detection of Alzheimer disease].

In 40 patients with Alzheimer's disease (AD), in 5 patients with non-AD dementia and in 36 cognitively normal controls the concentration of protein tau was determined in the cerebrospinal fluid (CSF). Of the AD patients, 19 were very mildly demented (MMSE score from 25 to 28). Even in these patients, CSF tau was significantly more elevated than in controls. In the non-AD patients protein tau was less increased. Among the AD patients there was no association between CSF tau and severity of cognitive impairment or deficit in cerebral blood flow, determined by SPECT. Our findings suggest that CSF tau may be elevated even at the predementia stage of AD and be useful as a biological marker for the early recognition of the disease.

Adult↗
PubMed1998

Paternal age is a risk factor for Alzheimer disease in the absence of a major gene.

We compared the parental age at birth of patients with Alzheimer disease (AD) with that of cognitively healthy control subjects. Within 206 carefully diagnosed AD patients, two groups were distinguished according to the likelihood of carrying a major gene for AD (MGAD). This likelihood was calculated by applying a Bayesian approach which incorporates data on aggregation of the disease, age at onset, and "censoring" ages within the family. All AD patients were ranked by MGAD probability. According to the sample's quartiles, two subgroups were defined representing the 52 individuals with the lowest and the 52 with the highest MGAD probability. Age at onset of dementia, education, and apolipoprotein E epsilon4 allele frequencies were not statistically different between the two groups. Fathers of patients with a low MGAD probability were significantly older (35.7+/-8.1 years) than fathers of both other groups (high MGAD probability 31.3+/-6.9 years, P=0.004; controls 32.6+/-6.8 years, P=0.04, n=50). The differences for mothers were less pronounced and not statistically significant. These findings suggest that increased paternal age is a risk factor for AD in the absence of a major gene, whereas increased maternal age and AD are associated only weakly and independently of genetic disposition.

Adult↗
PubMed1998

Local radiant heating increases subcutaneous oxygen tension.

BACKGROUND: We evaluated a novel bandage that incorporates a thermostatically controlled radiant heater. We first determined optimal bandage temperature, based on increases in subcutaneous oxygen tension, a measure correlating well with resistance to infection and wound strength. We then tested the hypothesis that prolonged radiant heating would increase collagen deposition in experimental thigh wounds. METHODS: The experimental bandages were positioned on the anterior thigh of 8 volunteers, and heated for 2 hours at 38 degrees C, 42 degrees C, or 46 degrees C, in a random order. Subcutaneous oxygen tension under the bandage was recorded from an electrode positioned within a subcutaneous tonometer. We studied 10 volunteers in the second protocol. For 1 week, the experimental bandage was continuously applied to one thigh, and heated to 38 degrees C using a 2-hour on/off cycle. On the alternate week, a standard gauze bandage was applied to the contralateral thigh. Treatment order was randomly assigned. Wound collagen deposition under each bandage was evaluated with subcutaneous polytetrafluoroethylene tubes, which were removed and assayed for hydroxyproline on the eighth day. Data are presented as means +/- SDs. RESULTS: Skin temperature during heating ranged from 36 degrees C to 37.5 degrees C. Oxygen tension increased approximately 50% during heating, but the increase was comparable at the three tested temperatures. Even after heating was discontinued, subcutaneous oxygen tension remained elevated for the remaining 3 study hours. Collagen deposition after 1 week of active heating was 3.4 +/- 1.0 microg/ cm. After 1 week of control treatment, collagen deposition was 3.2 +/- 1.1 microg/cm (P = not significant). CONCLUSIONS: Our data suggest that radiant heating at 38 degrees C significantly increases subcutaneous oxygen tension, and presumably resistance to infection. However, prolonged heating at this temperature does not increase wound collagen deposition.

Adult↗
PubMed1998

Poikilothermia syndrome.

Poikilothermia syndrome is a rare cause of intrinsic thermoregulatory failure. Patients with this syndrome regulate body temperature poorly, if at all. Recently, a patient was referred to us who had clinical evidence of poikilothermia syndrome, as well as long-standing multiple sclerosis. Computerized tomography and magnetic resonance scanning failed to identify a hypothalamic lesion. The patient was gradually warmed to sweating, and then cooled to vasoconstriction and shivering. The core-temperature thresholds triggering each defence were calculated, after compensating for the changes in skin temperature. The calculated sweating threshold was 38.3 degrees C (normal: 37.0 +/- 0.3 degrees C). The vasoconstriction threshold was 34.4 degrees C (normal: 36.4 +/- 0.3 degrees C). The sweating-to-vasoconstriction interthreshold range was thus approximately 4 degrees C, which is between 10 and 20 times the normal value. The shivering threshold was 31.8 degrees C (normal: 35.6 +/- 0.3 degrees C). The vasoconstriction-to-shivering range was thus approximately 2.5 degrees C which is more than twice the normal value. The pattern of thermoregulatory failure in this patient resembled that resulting from general anaesthesia.

Body Temperature↗
PubMed1998

Desflurane reduces the febrile response to administration of interleukin-2.

BACKGROUND: Intraoperative fever is relatively rare considering how often pyrogenic causes are likely to be present and how common fever is postoperatively. This low incidence suggests that general anesthesia per se inhibits the normal response to pyrogenic stimulation. The authors therefore tested the hypothesis that desflurane-induced anesthesia produces a dose-dependent inhibition of the febrile response. METHODS: Eight volunteers were studied, each on 3 study days. Each was given an intravenous injection of 50,000 IU/ kg of interleukin-2 (elapsed time, 0 h), followed 2 h later by 100,000 IU/kg. One hour after the second dose, the volunteers were assigned randomly to three doses of desflurane to induce anesthesia: (1) 0.0 minimum alveolar concentration (MAC; control), (2) 0.6 MAC, and (3) 1.0 MAC. Anesthesia continued for 5 h. Core temperatures were recorded from the tympanic membrane. Thermoregulatory vasoconstriction was evaluated using forearm-minus-fingertip skin temperature gradients; shivering was evaluated with electromyography. Integrated and peak temperatures during anesthesia were compared with repeated-measures analysis of variance and Scheffé's F tests. RESULTS: Values are presented as mean +/- SD. Desflurane reduced the integrated (area under the curve) febrile response to pyrogen, from 7.7 +/- 2.0 degrees C x h on the control day to 2.1 +/- 2.3 degrees C x h during 0.6 MAC and to -1.4 +/- 3.1 degrees C x h during 1.0 MAC desflurane-induced anesthesia. Peak core temperature (elapsed time, 5-8 h) decreased in a dose-dependent fashion: 38.6 +/- 0.5 degrees C on the control day, 37.7 +/- 0.7 degrees C during 0.6 MAC and 37.2 +/- 1.0 degrees C during 1.0 MAC desflurane anesthesia. Rising core temperature was always associated with fingertip vasoconstriction and often with shivering. CONCLUSIONS: Desflurane-induced anesthesia produced a dose-dependent decrease in integrated and peak core temperatures after administration of pyrogen, with 1.0 MAC essentially obliterating fever. Anesthetic-induced inhibition of the pyrogenic response is therefore one reason that fever is an inconsistent clinical response to inflammation during surgery.

Adult↗
PubMed1998

Tissue heat content and distribution during and after cardiopulmonary bypass at 31 degrees C and 27 degrees C.

BACKGROUND: Afterdrop following cardiopulmonary bypass results from redistribution of body heat to inadequately warmed peripheral tissues. However, the distribution of heat between the thermal compartments and the extent to which core-to-peripheral redistribution contributes to post-bypass hypothermia remains unknown. METHODS: Patients were cooled during cardiopulmonary bypass to nasopharyngeal temperatures near 31 degrees C (n=8) or 27 degrees C (n=8) and subsequently rewarmed by the bypass heat exchanger to approximately 37.5 degrees C. A nasopharyngeal probe evaluated core (trunk and head) temperature and heat content. Peripheral compartment (arm and leg) temperature and heat content were estimated using fourth-order regressions and integration over volume from 19 intramuscular needle thermocouples, 10 skin temperatures, and "deep" foot temperature. RESULTS: In the 31 degrees C group, the average peripheral tissue temperature decreased to 31.9+/-1.4 degrees C (means+/-SD) and subsequently increased to 34+/-1.4 degrees C at the end of bypass. The core-to-peripheral tissue temperature gradient was 3.5+/-1.8 degrees C at the end of rewarming, and the afterdrop was 1.5+/-0.4 degrees C. Total body heat content decreased 231+/-93 kcal. During pump rewarming, the peripheral heat content increased to 7+/-27 kcal below precooling values, whereas the core heat content increased to 94+/-33 kcal above precooling values. Body heat content at the end of rewarming was thus 87+/-42 kcal more than at the onset of cooling. In the 27 degrees C group, the average peripheral tissue temperature decreased to a minimum of 29.8 +/-1.7 degrees C and subsequently increased to 32.8+/-2.1 degrees C at the end of bypass. The core-to-peripheral tissue temperature gradient was 4.6+/-1.9 degrees C at the end of rewarming, and the afterdrop was 2.3+/-0.9 degrees C. Total body heat content decreased 419+/-49 kcal. During pump rewarming, core heat content increased to 66+/-23 kcal above precooling values, whereas peripheral heat content remained 70+/-42 kcal below precooling values. Body heat content at the end of rewarming was thus 4+/-52 kcal less than at the onset of cooling. CONCLUSIONS: Peripheral tissues failed to fully rewarm by the end of bypass in the patients in the 27 degrees C group, and the afterdrop was 2.3+/-0.9 degrees C. Peripheral tissues rewarmed better in the patients in the 31 degrees C group, and the afterdrop was only 1.5+/-0.4 degrees C.

Adult↗
PubMed1998

Paralysis only slightly reduces the febrile response to interleukin-2 during isoflurane anesthesia.

BACKGROUND: Fever sometimes occurs during anesthesia. However, it is rare considering how often pyrogenic causes are likely to be present and how common fever is after surgery. This low incidence results in part from dose-dependent inhibition of fever by volatile anesthetics. Paralysis, however, may contribute by preventing shivering and the associated increase in metabolic heat production. Therefore the authors tested the hypothesis that paralysis during anesthesia decreases the febrile response to pyrogen administration. METHODS: Seven volunteers each participated on two study days. They were given 30 IU/g intravenous interleukin-2, followed 90 min later by an additional 70 IU/g dose. Anesthesia was induced 30 min after the second dose and maintained for 6 h with 0.6 minimum alveolar concentration isoflurane. The volunteers were randomly assigned to (1) paralysis with vecuronium or (2) no muscle relaxants. Body heat content and distribution were determined from measured tissue and skin temperatures. Data are presented as mean +/- SD; P < 0.05 was considered significant. RESULTS: There was no clinically important difference in peak core (tympanic membrane) temperatures on the unparalyzed (37.6+/-0.9 degrees C) and paralyzed (37.2+/-0.6 degrees C) days. Core heat content increased 1.2+/-0.7 kcal/kg over the last 5 h of anesthesia on the unparalyzed day, but only by 0.9+/-0.4 kcal/kg when the volunteers were paralyzed. Peripheral tissue heat content increased 0.1+/-1.1 kcal/kg on the unparalyzed day but decreased 1.1+/-0.7 kcal/kg when the volunteers were paralyzed. Consequently, body heat content increased 1.3+/-1.3 kcal/kg on the unparalyzed day but decreased significantly by 0.2+/-0.8 kcal/kg when the volunteers were paralyzed. CONCLUSIONS: Paralysis prevented shivering from increasing the metabolic rate. Consequently, body heat content decreased during paralysis, whereas otherwise it increased. Thermoregulatory vasoconstriction was nonetheless able to maintain similar peak and integrated core temperatures on each study day. Administration of muscle relaxants thus is not the primary explanation for the relative paucity of intraoperative fever.

Anesthesia↗
PubMed1998

Tau protein in cerebrospinal fluid is significantly increased at the earliest clinical stage of Alzheimer disease.

The concentration of tau protein in cerebrospinal fluid (CSF) was determined in 40 patients with clinically diagnosed probable Alzheimer disease (AD) and in 36 cognitively healthy controls. A significant increase of CSF tau was found in the AD patients, even in 19 subjects with very mild dementia as defined by a Mini-Mental State Examination score of 25 and above. Using a cutoff value of 260 pg/mL the sensitivity of elevated tau was 0.89, the specificity was 0.97, and the proportion of correctly allocated cases was 95%. In the AD groups there were no significant associations between CSF tau level and age, age at onset, duration of illness, apolipoprotein E genotype, severity of cognitive impairment, or deficit in regional cerebral blood flow as measured using 99Tm-ethyl cystein dimer single photon emission computed tomography. The findings demonstrate that CSF tau is significantly increased at the earliest clinical stage of AD and shows only minimal overlap with age-matched cognitively healthy controls. This finding suggests that CSF tau could be a biological marker of AD even before dementia has developed.

Adult↗