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Biomedical subjects

J Kessler

Publications and source records attributed to J Kessler.

At least 91 records · Page 5Linked to original sources

Regional cerebral glucose metabolism and postmortem pathology in Alzheimer's disease.

In four patients with an antemortem diagnosis of probable Alzheimer's disease (AD) regional cerebral glucose metabolism (rCMRGl) was studied prospectively by positron emission tomography (PET) and compared with postmortem semiquantitative neuropathology. The interval between the last PET study and autopsy was 1.3 +/- 0.8 years. In comparison with age-matched controls, the AD patients showed predominant temporoparietal hypometabolism spreading to other cortical and subcortical regions during serial PET scans. All patients had neuropathological findings typical for AD. There was a significant relationship between rCMRGl and density of senile plaques (SP) in one patient (tau b = -0.86, P < 0.05). SP were distributed quite homogeneously in all regions examined. Neurofibrillary tangles (NFT) were concentrated focally in the hippocampus-amygdala-entorhinal complex. In the context of widespread developing cortical hypometabolism, the predilection of NFT for involvement in limbic areas suggests a disruption of projection neurons as the pathogenetic process of cortical dysfunction.

Aged↗

Written numeral transcoding in patients with Alzheimer's disease.

Transcoding verbal numerals into Arabic numerals and vice versa was studied in 21 patients with probable Alzheimer's disease and 22 healthy subjects. Transcoding errors were analyzed according to the classification schemes by Deloche and Seron (1982a, 1982b) and Seron and Deloche (1983). In the control group, errors occurred only 2% of the time in transcoding Arabic numerals into verbal numerals, and in 1.4% for the reverse order. In AD patients, more than one error frequently occurred in the same item. In 672 transcriptions from Arabic numerals into verbal numerals 479 errors occurred in 312 items. In the reverse order 672 transcriptions were performed and 290 errors occurred in 238 items. One kind of error was striking in both transcoding directions, not reported in aphasic or other brain damaged patients: elements of the source code reappeared in the target code, e.g. 3436--> 3tausendvierhundert36 (3 thousand four hundred 36), or zweihundertelf (211)-->2hindert11 (2hundred11). It is concluded that this error type is the result of a cognitive system which has multiple impairments and in which control mechanisms are temporarily failing.

Aged↗

[Etomidate versus propofol for anesthesia in ambulatory cardioversion].

OBJECTIVE: This study compared the two short-acting intravenous anaesthetic agents, etomidate in lipid emulsion and propofol, for anaesthesia during elective outpatient cardioversion. METHODS: After institutional approval and informed consent, 40 patients (ASA II/III) scheduled for cardioversion were studied. Patients with a left ventricular ejection fraction < 30% were excluded. The anti-arrhythmic medication was not discontinued, and no patient was given pharmacological premedication. Anaesthesia was induced either with etomidate (in lipid emulsion) 0.25 mg/kg or propofol 1.5 mg/kg. Both agents were administered over 30 seconds. Subsequent increments were given until the patients no longer followed verbal commands and the lid reflex was absent. Patients were allowed to breathe 40% oxygen via face mask. Artificial ventilation was performed if a patient became apnoeic for more than 20 seconds. The blood pressure was monitored continuously with the Finapres noninvasive blood pressure monitor, and the heart rate was recorded simultaneously. All data were collected electronically. The duration of anaesthesia was taken as the period from the start of induction until the opening of the eyes on command. For assessment of recovery from anaesthesia, patients were asked to perform a series of psychomotor tests. RESULTS: The two groups were similar in their demographic and haemodynamic baseline data. In both groups, a significant decrease in blood pressure occurred 120 seconds after anaesthesia induction, which was due to the performance of the cardioversion. Five minutes after induction, the blood pressure returned to baseline in the etomidate group, while it remained below baseline in the propofol group. Propofol caused a significant decrease in heart rate. Significantly more patients needed artificial ventilation after propofol administration because of apnoea. Involuntary muscle movements occurred only in patients receiving etomidate. The immediate emergence from anaesthesia was faster after propofol. However, 15 minutes after awakening there was no difference in psychomotor skills between the two groups. No residual psychomotor impairment was evident 60 minutes after anaesthesia in any patient. All patients were discharged four hours after the cardioversion. CONCLUSIONS: Because the recovery characteristics were similar in both groups, the occurrence of side effects may be a major factor when choosing between etomidate and propofol for outpatient cardioversion.

Adult↗

A review of problems of universal access to prenatal care.

Despite the preponderance of evidence that points to the advantages of prenatal care, the number of women who receive adequate prenatal care has remained at a plateau or actually decreased since 1980. Over the past decades, many demographic and structural barriers to receiving prenatal care have been identified; financial obstacles have been cited as the major barrier. The assumption has generally been made that if financial barriers to prenatal care were removed, problems with access to prenatal care would be solved. Recent appreciation of the significance of nonfinancial barriers to prenatal care has resulted in recognition that even if all financial barriers were removed, there would still be access problems.

Attitude to Health↗

Evidence for class-specific discrimination of a semiconserved base pair by tRNA synthetases.

Aminoacyl-tRNA synthetases have been divided into two classes based on the existence of two structurally distinct active sites. To date, few class-specific tRNA recognition features have been elucidated. High-resolution X-ray structures of representative class I and class II synthetases complexed to cognate tRNA substrates have been solved. In these structures, the class I enzyme approaches the end of the tRNA acceptor stem from the minor-groove side, while the class II synthetase approaches its cognate tRNA from the major-groove side. This distinction is reflected in the different initial sites (2'- or 3'-OH) of amino acid attachment. The role that the semiconserved G1.C72 terminal base pair plays in the aminoacylation of Escherichia coli tRNAs is probed in this in vitro study. We show here that class II alanyl-, prolyl-, and histidyl-tRNA synthetases are sensitive to changes at position 1 x 72. Previous work on class I synthetases and new data presented here with the valine-specific enzyme indicate that class I enzymes show little sensitivity to replacements of G1.C72. This work provides new evidence for class-specific differences in tRNA acceptor stem interactions that appear to be reflected not only in the initial site of aminoacylation but also in the mode of synthetase interaction with the semiconserved G1.C72 base pair proximal to the amino acid attachment site.

Alanine-tRNA Ligase↗

Heterotypic Fc gamma R clusters evoke a synergistic Ca2+ response in human neutrophils.

Both Fc gamma receptors on human neutrophils (Fc gamma RIIa and Fc gamma RIIIb) are capable of initiating signal transduction after multivalent cross-linking. However, immune complexes most likely activate neutrophils by a combined homotypic and heterotypic cross-linking of Fc gamma Rs. We have investigated the effect of homotypic and heterotypic Fc gamma R cluster formation on changes in the intracellular free Ca2+ concentration. Combined heterotypic and homotypic cluster formation resulted in a Ca2+ response that was strongly enhanced as compared to the sum of both individual Fc gamma R responses. This synergistic response was caused by the formation of heterotypic clusters of Fc gamma Rs and not by the simultaneous formation of homotypic clusters. This conclusion was supported by experiments with a bispecific antibody binding to both Fc gamma RIIa and Fc gamma RIIIb. The heterotypic Fc gamma R cross-linking results in efficient activation of Ca2+ influx, probably caused by a more pronounced depletion of intracellular Ca2+ stores. Stimulation with immune complexes also induced Ca2+ influx in normal neutrophils, but not in Fc gamma RIIIb-deficient neutrophils. The synergism between both Fc gamma Rs was also apparent in other responses of neutrophils, such as the activation of the respiratory burst. This study shows that the two different Fc gamma Rs on neutrophils complement each other in mediating an important cellular response.

Antibodies, Monoclonal↗

Molecular recognition of tRNA(Pro) by Escherichia coli proline tRNA synthetase in vitro.

In this study, we identify a subset of nucleotides that specify aminoacylation of tRNA(Pro) by Escherichia coli proline tRNA synthetase in vitro. Twenty-two tRNA(Pro) variants were prepared by in vitro transcription and their efficiency of aminoacylation with proline (kcat/KM) was measured. From this analysis, we conclude that recognition elements for tRNA(Pro) aminoacylation by ProRS are located in at least three domains of the tRNA molecule. The largest decreases in the kinetic parameters for aminoacylation resulted from single substitutions at position G72 of the acceptor stem and position G36 of the anticodon. Anticodon nucleotide G35 and position A73 in the acceptor stem were also identified as major recognition elements. Moreover, bases that are believed to be important for maintaining the tertiary structure of the tRNA (G15 and C48) appear to be important for efficient recognition of tRNA(Pro) by ProRS in vitro.

Amino Acyl-tRNA Synthetases↗

Long-term prognosis of poststroke aphasia studied with positron emission tomography.

OBJECTIVE: To evaluate positron emission tomography with the use of fludeoxyglucose F 18 as a predictor of the long-term outcome of poststroke aphasia. BACKGROUND: Positron emission tomography shows functional deficits after stroke even in morphologically intact brain regions. The regional metabolic impairment can be related to the clinical deficit. Little is known about whether regional hypometabolism early after stroke predicts the long-term prognosis of stroke sequelae. PATIENTS AND METHODS: Twenty-two patients with language disturbance caused by a single lesion in the territory of the left middle cerebral artery were studied with fludeoxyglucose positron emission tomography and with a neuropsychological test battery that included a test of receptive language (Token Test) and a test of word fluency (/f/, /a/, /s/ test). The neuropsychological test was readministered about 2 years after the initial test. RESULTS: Regional cerebral metabolic rates of glucose measured early after stroke showed a highly significant correlation with the results of the 2-year follow-up test. The receptive language disorder best correlated with cerebral metabolic rates of glucose in the left superior temporal cortex, and word fluency correlated with cerebral metabolic rates of glucose in the left prefrontal cortex. CONCLUSION: Cerebral metabolic rates of glucose in speech-relevant brain regions measured early after stroke are a predictor of the eventual outcome of aphasia.

Aged↗

Planum temporale and Brodmann's area 22. Magnetic resonance imaging and high-resolution positron emission tomography demonstrate functional left-right asymmetry.

OBJECTIVE: To describe the registered analysis of magnetic resonance imaging and glucose metabolic data acquired with positron emission tomography to determine the relationship between structure and function of temporal lobe cortical structures between the left and right hemispheres. BACKGROUND: The dominance of the left cerebral hemisphere is associated with a preponderance of the left planum temporale. SUBJECTS AND METHODS: Fifteen subjects without signs or symptoms of a neurological disorder. Three-dimensional-registered magnetic resonance imaging and positron emission tomography with the use of fludeoxyglucose F18 and a high-resolution positron emission tomography scanner. Analysis of regional metabolic activation during single-word repetition on matched parasagittal magnetic resonance imaging and positron emission tomography. RESULTS: The planum temporale was bilaterally activated without left-right asymmetry. The metabolic increase was asymmetric within the left Brodmann's area (BA) 22. The part of the left BA 22 that was buried in the superior temporal sulcus was significantly less activated than the part of BA 22 on the surface of the superior temporal gyrus. The metabolic activation in the sulcal part of the left BA 22 had a significant inverse correlation with the anatomical predominance of the left planum temporale (r = .71, P = .003) and a significant direct correlation with the metabolic activation in the surface aspects of the right BA 22 (r = .82, P < .001). CONCLUSION: Brodmann's area 22 is a critical feature of language dominance and is also important with regard to the exchange of information between the two hemispheres.

Adult↗

Neurological sequelae of cyanide intoxication--the patterns of clinical, magnetic resonance imaging, and positron emission tomography findings.

We report 2 patients with neurological sequelae of oral cyanide intoxication who were evaluated clinically and neuropsychologically, with high-resolution magnetic resonance imaging and one of them with positron emission tomography. The clinical syndrome was characterized by extrapyramidal motor and cerebellar symptoms such as bradykinesia, hypomimia, slowed speech, anteropulsion, and marked retropulsion, but little tremor. The sensory and pyramidal motor systems were normal or relatively spared. On neuropsychological testing the intellectual capacity and memory functions were normal, whereas the speed of motor reaction and verbal fluency were reduced. Magnetic resonance imaging showed damage of the globus pallidus, putamen, substantia nigra, subthalamic nucleus, and cerebellum in both patients, whereas the sensory-motor cortex and hippocampus were relatively spared. 18F-6-Fluoro-dopa positron emission tomography revealed a symmetrical reduction of striatal dopa uptake by 42% on average that was similar in the putamen and caudate. 18F-2-Fluoro-2-deoxyglucose positron emission tomography showed a regional reduction of the glucose metabolism in the posterior putamen and temporo-parieto-occipital and cerebellar cortex.

Adult↗

Cognitive impairment in Alzheimer's disease correlates with ventricular width and atrophy-corrected cortical glucose metabolism.

We compared the correlation of PET and MRI with neuropsychological tests in 26 patients with probable Alzheimer's disease (AD). The width of the temporal horns and the third ventricle, regional metabolic rates of glucose (rCMRGlu) and the proportion of cerebrospinal fluid space in mesial temporal and temporoparietal cortical regions were measured with three-dimensionally coregistered PET and MRI in two planes perpendicular to the Sylvian fissure. Highly significant correlations between rCMRGlu and neuropsychological tests were found mainly in the temporoparietal cortex, with and without correction for atrophy. Correlations of similar magnitude were seen also between most tests and the width of the temporal horns and third ventricle. Changes in the third ventricle and mesial temporal lobe were best seen with MRI, whereas PET most clearly depicted alterations in neocortical association areas. These two aspects of the disease correlated with the severity of dementia to a similar degree.

Aged↗

Impaired beta-cell function in the Chinese hamster CHIG/Han subline.

Plasma glucose and insulin levels were measured in the genetically diabetic CHIG/Han and the diabetes-resistant CHIA/Han subline of the Chinese hamster. At 31 +/- 8 wk of age, the CHIG hamsters were grouped into nondiabetic, mildly and severely diabetic, according to their levels of glycemia. Hyperinsulinemia, occurring in nondiabetic and mildly diabetic CHIG hamsters, was attenuated in severely diabetic animals. Light microscopy and immunohistochemistry revealed initial beta-cell hyperplasia, followed by extensive degranulation and loss of immunoreactive insulin in islets of severely diabetic animals. Staining intensity of glucagon-immunoreactive cells was unchanged in nondiabetic and mildly diabetic animals, but was increased in islets from the severely diabetic hamsters. A static incubation system was used to examine the insulin response of pancreatic islets isolated from the diabetic and nondiabetic CHIG hamsters, and the diabetes-resistant CHIA subline. Compared with the nondiabetic CHIG hamsters, islets from mildly and severely diabetic animals displayed increased basal insulin release at 1.5 mmol/l and a deficient response at 10 mmol/l glucose which was associated with 61 and 77% decreases (p < 0.01 and p < 0.001) in the islet insulin content. The addition of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) enhanced glucose-stimulated insulin release from islets of nondiabetic and mildly diabetic CHIG hamsters, although the response elicited was lower than from CHIA islets. However, IBMX failed to significantly increase the glucose-stimulated insulin response of islets from severely diabetic hamsters. A negative correlation (r = -0.73, p < 0.001, n = 48) was found between islet insulin content and plasma glucose levels. The data suggest that the reduced secretory capacity represents an early islet beta-cell dysfunction, and the decrease in the insulin content contributes to the islet abnormalities in the diabetes-susceptible CHIG hamsters.

1-Methyl-3-isobutylxanthine↗

Anaphylactoid reactions with intraperitoneal cisplatin.

OBJECTIVE: To report the occurrence of anaphylactoid reactions to intraperitoneal cisplatin in 3 patients. CASE SUMMARIES: While conducting a protocol evaluating the efficacy of intraperitoneal cisplatin and hyperthermia in the treatment of recurrent ovarian cancer, 3 patients were noted to exhibit anaphylactoid reactions. A 43-year-old woman received cisplatin 60 mg/m2 in 15 minutes during her sixth cycle of therapy. She developed pruritus, edema, and urticaria over both hands. The reaction subsided after treatment with diphenhydramine and dexamethasone. A 57-year-old woman received 400 mL (62.4 mg) of a cisplatin solution concentrated to deliver cisplatin 100 mg/m2 during her first attempted therapy. At this point, she developed whole body urticaria and pruritus with edema of the extremities. The reaction was aborted with diphenhydramine and dexamethasone. Despite premedication with dexamethasone prior to a second attempt at therapy, she again experienced similar symptoms after receiving 500 mL (78 mg) of cisplatin solution. A 55-year-old woman received 2 cycles of therapy with cisplatin 100 mg/m2 without difficulty. During her third cycle, she again received cisplatin 100 mg/m2 over 30 minutes and developed palmar pruritus, urticaria, and edema. Symptomatology resolved with diphenhydramine. Despite premedication with diphenhydramine and dexamethasone, she experienced generalized pruritus and urticaria, as well as headache and chest pain/tightness, after her next infusion. For both the second and third patients, symptomatology failed to resolve until the intraperitoneal cisplatin solution was withdrawn. DISCUSSION: Anaphylactoid reactions have been described previously with cisplatin administration. No dose-rate effect has been reported, however. We observed 5 reactions in 3 patients that appear to be related to a high dose-infusion time ratio, indicating that dose and rate of infusion may be important factors in precipitating anaphylactoid reactions with cisplatin. CONCLUSIONS: We conclude that a high dose combined with a short infusion time increases the risk of anaphylactoid reactions with the administration of intraperitoneal cisplatin. There was no indication that the increase in anaphylactoid reactions was associated with the use of hyperthermia.

Adult↗

Dysfunction of visual cortex contributes to disturbed processing of visual information in Alzheimer's disease.

The relation between visual impairment and regional cerebral metabolic rate of glucose (rCMRGl) was studied in 31 patients with probable Alzheimer's disease (AD) by using positron emission tomography with 18F-2-fluoro-2-deoxy-D-glucose. To exclude any precortical cause of visual dysfunction only patients were included who had amplitudes and latencies of visually evoked potentials (flash and pattern reversal) within the normal range. Visual information processing was evaluated psychometrically by a fragmented picture test (FPT), which is a combined perception (identification score) and memory (reidentification score) task and refers to Gollin's incomplete pictures. The identification and reidentification scores were significantly worse than in normals. Reductions of the rCMRGl in the primary visual fields, and in the secondary visual fields were found. A significant partial correlation with adjustment for age between the reidentification score of the FPT and the rCMRGl of the secondary visual fields (r = -.39, p < .05) in AD patients was found, indicating involvement of the secondary visual cortex in the pathological changes in AD.

Aged↗

[Premorbid intelligence diagnosis with the MWT-B(Multiple Choice Word Test-B) in patients with Alzheimer disease].

The usefulness of the multiple-choice word test (MWT-B) was tested as a measure for premorbid intelligence in 107 patients with probable Alzheimer's disease following the NINCDS-ADRDA criteria. The patients were allocated to three groups according to severity of dementia: mild (n = 40), moderate (n = 41) and severe (n = 26). Dementia severity was assessed with the Mini Mental State Test (MMST). The mean of the raw values of the MWT-B (maximum 37) in the group with mild dementia was 28.0 (SD = 5.57), in the group with moderate dementia 23.3 (SD = 8.01), and in the group with severe dementia 6.7 (SD = 8.44), indicating a parallel worsening with the other tests. The MWT-B value of the whole sample correlated with the MMST value (r = 0.70); a significant correlation still existed in patients with mild and moderate dementia. These results confirm that the MWT-B is relevant for dementia. The rate of cerebral glucose metabolism, measured with positron emission tomography (PET) and 18F-fluorodeoxy-glucose (FDG) correlated significantly with the MWT-B scores in the Alzheimer-sensitive temporoparietal region (r = 0.43; P = 0.001) and frontal brain region (r = 0.37; P < 0.05). Whether or not it can be used as a screening measure of dementia will have to be decided on the basis of its scales for sensitivity and specificity.

Aged↗

The amygdala's contribution to memory--a study on two patients with Urbach-Wiethe disease.

The consequences of primary amygdaloid damage on memory performance are described in terms of neuropsychological, CT, MRI and PET results of two patients, a brother and a sister. Both had circumscribed, bilaterally symmetrical damage confined to the amygdaloid region, while the hippocampal formation and other brain structures were intact. PET-imaging furthermore revealed an overall decrease in glucose metabolism which was particularly apparent at the cingular and thalamic levels. Although neither patient was amnesic, both showed memory impairments in selective tests. In one patient these impairments were more pronounced and they were accompanied by marked affective-emotional fluctuations. Our results suggest that the amygdaloid region is a bottle-neck structure that confers an affective flavour to memories, thereby enhancing the probability of their long term storage.

Adult↗

Discordant twins with Parkinson's disease: positron emission tomography and early signs of impaired cognitive circuits.

We evaluated 7 pairs of twins (2 monozygotic and 5 dizygotic) discordant for Parkinson's disease (PD), of whom the cotwins showed no signs of motor impairment on neurological examination. All subjects underwent positron emission tomographic measurements of cerebral glucose metabolism and dopaminergic, nigrostriatal function following injection of 2-[18F]fluoro-2-deoxy-D-glucose and L-6-[18F]fluorodopa ([18F]dopa), respectively, as well as testing for anterograde, verbal episodic, and semantic memory performance. Statistical analysis demonstrated significant reduction of striatal [18F]dopa uptake not only in the twin patients with PD but also in all of the cotwins, who showed significantly (p < 0.05) impaired [18F]dopa metabolism in at least one of the striatal measures including caudate, putaminal, and the rostrocaudal putaminal gradient of [18F]dopa uptake. Compared with age-matched controls, regional glucose metabolism was unchanged in all the twins. Neuropsychological testing showed significant (p < 0.05) impairment in verbal memory processing in the twin patients with PD and in 6 of the cotwins. Semantic memory skills were affected in 2 twin patients only. A significant correlation was found between scores obtained in Buschke's Selective Reminding Test and striatal [18F]dopa uptake, further substantiating the role of dopaminergic pathways in memory processing. The present study is the first to reveal not only significant disturbance of nigrostriatal dopaminergic function in verbal episodic memory that is known to be affected in PD. Larger studies with a longitudinal design will be necessary to answer the question of whether cognitive changes found in the cotwin group are signs of incipient PD.

Aged↗