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Biomedical subjects

M Kuilman

Publications and source records attributed to M Kuilman.

10 recordsLinked to original sources

Chronic mitochondrial inhibition induces selective motoneuron death in vitro: a new model for amyotrophic lateral sclerosis.

Evidence is increasing that mitochondrial dysfunction is involved in amyotrophic lateral sclerosis, a neurodegenerative disease characterized by selective motoneuron death. To study the role of mitochondrial dysfunction in the pathways leading to motoneuron death, we developed an in vitro model of chronic motoneuron toxicity, based on malonate-induced inhibition of complex II in the mitochondrial electron transport chain. Treatment with malonate resulted in a dose-dependent decrease in cellular ATP levels. We observed that motoneurons were significantly more vulnerable to mitochondrial inhibition than control neurons in the dorsal horn. We could reproduce this dose-dependent phenomenon with the complex IV inhibitor sodium azide. The free radical scavenger alpha-phenyl-N-tert-butylnitrone, the AMPA/kainate receptor blocker 6-cyano-7-nitroquinoxaline-2,3-dione, and riluzole, a drug that is currently used for the treatment of amyotrophic lateral sclerosis, were protective against malonate-induced motoneuron death. Furthermore, the caspase inhibitors N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone and z-Asp-Glu-Val-Asp-fluoromethyl ketone were both protective against malonate toxicity. Our model shows that chronic mitochondrial inhibition leads to selective motoneuron death, which is most likely apoptotic.

Adenosine Triphosphate↗

Long-term survival after out-of-hospital cardiac arrest: an 8-year follow-up.

Between 1988 and 1994, 441 patients were successfully resuscitated outside hospital in the city of Rotterdam, of whom 276 (63%) were discharged from hospital alive. Long-term survival was studied amongst those who were discharged alive. The duration of follow-up averaged 6.71 years. A survival rate of 88% after 1 year, 81% after 3 years, 77% after 5 years and 73% after 7 years was found. After multivariate analysis, age, diagnosis and gender were found to be independent and significant predictors of survival. No significant difference in survival was found in patients who had been resuscitated by emergency personnel, physicians and bystanders. Patients who were still alive were sent a EuroQol-questionnaire. No differences in outcomes between the four groups were found. Since long-term prognosis after out-of-hospital resuscitation is satisfactory, learning programmes for resuscitation should be continued.

Cardiopulmonary Resuscitation↗

Prospective study of the prevalence of Alzheimer-type dementia in institutionalized individuals with Down syndrome.

Institutionalized patients with Down syndrome (n = 307) were monitored for 5 to 10 years prospectively to determine prevalence of Alzheimer-type dementia. Clinical signs, cognitive functioning, and EEGs were assessed. When possible, postmortem neuropathological examinations were conducted. Progressive mental and physical deterioration was found for 56 of the residents. Mean age at onset of dementia was 56 years. Prevalence increased from 11% between ages 40 and 49 to 77% between 60 and 69. All patients 70 and over had dementia. Neuropathological findings were consistent with clinical diagnosis. Use of a dementia checklist, cognitive skills inventory, and EEG reliably detected Alzheimer-type dementia at an early stage.

Adult↗

Comparison of effect of cafetière and filtered coffee on serum concentrations of liver aminotransferases and lipids: six month randomised controlled trial.

OBJECTIVE: To study the effects of prolonged intake of cafetière coffee, which is rich in the diterpenes cafestol and kahweol, on serum aminotransferase and lipid concentrations. DESIGN: Randomised parallel controlled trial. SUBJECTS: 46 healthy men and women aged 19 to 69. INTERVENTION: Consumption of five to six strong cups (0.9 litres) a day of either cafetière (22 subjects) or filtered coffee (24 subjects) for 24 weeks. MAIN OUTCOME MEASURES: Mean changes in serum aminotransferase and lipid concentrations. RESULTS: Cafetière coffee raised alanine aminotransferase concentration by up to 80% above baseline values relative to filtered coffee. After 24 weeks the rise was still 45% (9 U/l (95% confidence interval 3 to 15 U/l), P = 0.007). Alanine aminotransferase concentration exceeded the upper limit of normal in eight of the 22 subjects drinking cafetière coffee, being twice the upper limit of normal in three of them. Cafetière coffee raised low density lipoprotein cholesterol concentrations by 9-14%. After 24 weeks the rise was 0.26 mmol/l (0.04 to 0.47 mmol/l) (P = 0.03) relative to filtered coffee. Triglyceride concentrations initially rose by 26% with cafetière coffee but returned close to baseline values within six months. All increases were reversible after the intervention was stopped. CONCLUSIONS: Daily consumption of five to six cups of strong cafetière coffee affects the integrity of liver cells as suggested by small increases in serum alanine aminotransferase concentration. The effect does not subside with prolonged intake. High intakes of coffee brews rich in cafestol and kahweol may thus be responsible for unexplained increases in this enzyme activity in apparently healthy subjects. Cafetière coffee also raises low density lipoprotein cholesterol concentration and thus the risk of coronary heart disease.

Adult↗

Use of electroencephalography to detect Alzheimer's disease in Down's syndrome.

We studied the role of electroencephalography (EEG) in the diagnosis of Alzheimer-type dementia in patients with Down's syndrome. 197 patients with Down's syndrome were monitored for 5 to 8 years. Aspects of cognitive functioning were assessed twice yearly. EEGs were scored in a blind fashion, and changes in the EEG were compared to changes in cognitive functioning. When possible, a neuropathological post-mortem examination was performed. Cognitive functioning was drastically reduced in 29 patients. The dominant occipital rhythm became slower at the onset of the cognitive deterioration, and eventually disappeared. In 11 of these patients neuropathological examination showed a severe form of Alzheimer's disease. Changes in the frequency of the dominant occipital rhythm could distinguish between Alzheimer's disease or other causes as underlying the cognitive decline. Slowing of the dominant occipital rhythm seems to be related to Alzheimer's disease in patients with Down's syndrome, and the frequency of the dominant occipital activity decreases at the onset of cognitive deterioration. The EEG is thus an important tool in the clinical diagnosis of Alzheimer-type dementia in patients with Down's syndrome.

Adult↗

[Dementia symptoms in Down's syndrome in a residentially treated group of mentally handicapped].

In a controlled retrospective study of 27 Down patients the occurrence of the neuropathological signs of Alzheimer's disease was investigated. The patients were divided into two groups: group I with neuropathologically proven Alzheimer and group II without Alzheimer's disease. All patients of group I had been older than 54 years at death, while all patients of group II were younger. All patients of group I suffered from severe dementia, none of group II did. The early clinical symptoms, changes in social competence and EEG alterations were combined in a dementia detection method suitable for mentally deficient patients.

Activities of Daily Living↗

A retrospective and explorative study of hypokalemia in psychiatric disorders: a beta 2-receptor related phenomenon.

Since the serum potassium level is under beta 2-adrenergic influence, we studied serum potassium values on admission in psychiatric patients. Data are reported on 683 patients from nine major diagnostic groups. Among these nine groups significant differences were found concerning the mean serum potassium level and incidence of hypokalemia. Significant differences existed between the alcohol withdrawal and attempted suicide groups compared to the dysthymic, bipolar manic, schizophrenic and nonschizophrenic psychosis groups. Like alcohol withdrawal, attempted suicide is assumed to be a hyper-adrenergic state. Although the relative contribution of factors like nutritional state, aldosterone, insulin, and beta 2-receptor density or sensitivity is unclear, the catecholamine-potassium relationship deserves further study.

Bipolar Disorder↗