Decreased insulin requirement in relation to GFR in nephropathic Type 1 and insulin-treated Type 2 diabetic patients.

AIMS: In the presence of impaired renal function, patients require less insulin mainly because insulin clearance is prolonged. The aim of this study was to evaluate the insulin requirement related to glomerular filtration rate (GFR) in nephropathic Type 1 and Type 2 diabetic patients. METHODS: In a retrospective study we compared insulin requirement in 20 nephropathic Type 1 diabetic patients and 20 insulin-treated Type 2 diabetic patients from the onset of overt nephropathy until the final stage of renal disease. All patients had proteinuria > 0.5 g/24 h and creatinine clearance >/= 80 ml/min per 1.73 m2 at baseline. Creatinine clearance, urinary protein excretion, glycated haemoglobin and the required insulin doses were determined 3- to 6-monthly, basal C-peptide was measured at the beginning and the end of the observation period. The required insulin doses were evaluated at creatinine clearance rates of 80, 60, 40, 20 and 10 ml/min per 1.73 m2 (or at the initiation of dialysis treatment). RESULTS: The insulin requirement of patients with Type 1 diabetes was reduced from 0.72 +/- 0.16 IU/kg per day at a creatinine clearance rate of 80 ml/min, to 0.45 +/- 0.13 IU/kg per day at a creatinine clearance rate of 10 ml/min (decrement of 38%, P < 0.001). The insulin dose required by Type 2 diabetic patients was reduced from 0.68 +/- 0.28 IU/kg per day at a creatinine clearance rate of 80 ml/min to 0.33 +/- 0.19 IU/kg per day at a clearance rate of 10 ml/min (decrement 51%, P < 0.001). The fall in GFR, urinary protein excretion and glycated haemoglobin levels was similar in the two groups. In patients with Type 2 diabetes, C-peptide levels at the beginning and the end of renal function impairment were 2.2 (0.4-7.3) vs. 2.7 (0.1-4.9) ng/ml (NS). The reduction in insulin requirement was approximately the same in patients with an initial C-peptide level < 1.0 and in those >/= 1.0 ng/ml (decrement 57% vs. 46%). CONCLUSIONS: The reduction in insulin requirement in renal insufficiency is similar in Type 1 and insulin-treated Type 2 diabetic patients. In subjects with Type 2 diabetes, the residual insulin secretion has no impact on the reduction in insulin requirement dependent on the GFR.     

Alzheimer's disease: identical phenotype of familial and non-familial cases

Summary Ninety outpatients with Alzheimer's disease according to ICD-10 diagnostic draft criteria were studied to test the hypothesis that cases with a familial aggregation are different from cases without such an aggregation with respect to cognitive impairment. In all cases the diagnosis of Alzheimer's disease was confirmed by prospective observation within 12 months of initial evaluation. Patients were divided into two groups: one consisting of 23 patients with a familial aggregation, the other consisting of 67 patients without secondary cases among first-degree relatives. By means oft-tests differences in impairment of cognitive functions between the groups were calculated. The results did not yield statistically significant differences between the groups for any of the neuropsychologically investigated cognitive deficits. Thus the hypothesis that the presence of a familial aggregation may lead to a distinct phenotype in Alzheimer's disease was not confirmed.     

Intoxicating effects of lorazepam and barbital in rat lines selected for differential sensitivity to ethanol

The motor impairing effects and plasma concentrations of barbital and lorazepam were studied in the alcohol tolerant (AT) and alcohol non-tolerant (ANT) rat lines developed for low and high sensitivity to motor impairment from ethanol. The mixed (M) line, from which the AT and ANT rats were derived, was also included in the study. Like ethanol, barbital and lorazepam impaired the performance of the ANT rats more than that of the AT rats. The motor performance of the M rats was relatively more impaired after barbital than after lorazepam administration at the same dose used in the AT and ANT rats. At the two latter time points (2.5 and 3.5 h) the sensitive ANT rats had significantly higher serum barbital concentrations than the AT rats. The serum barbital concentrations of the AT and ANT rats did not differ, however, at the two first time points (0.5 and 1.5 h) of the tilting plane tests, although the ANT rats were significantly more intoxicated. The concentrations of lorazepam in plasma do not explain the differential motor impairment either, since the sensitive ANT rats had lower plasma concentrations than the insensitive AT rats. The results, thus, suggest that the selection involved in the development of the AT and ANT lines has not been specific for ethanol. The results also support the idea that ethanol, barbiturates and benzodiazepines have some modes of action in common.     

A longitudinal study of age-associated memory impairment

An 8-year longitudinal study of elderly people has provided data concerning age-associated impairment (AAMI). In 1985 a random sample of 146 persons aged 65 years or more, living in their own homes, were assessed using the Guild Memory Test the Mini–Mental State Examination (MMSE) and other ratings. After excluding 21% of the sample because they scored less than 24 on the MMSE, and another 34% who fulfilled other exclusion criteria, some 48% of the remainder (22% of the total sample) clearly fulfilled NIMH criteria for AAMI and a further 36% (16% of the total sample) were recorded as forgetful. The NIMH criteria are appropriate for certain research purposes but not in assessing prevalence of memory disorders. Follow–up interviews were conducted after 2, 4, 6 and 8 years. The mortality rate and development of dementia among those fulfilling criteria for AAMI appeared similar to the other non-demented groups of subjects; the mortality rate of those with MMSE scores below 24 was significantly higher. Guild test results at 2-yearly intervals showed considerable changes; half of those scoring least well who were retested showed improvement.     

An integrative psychophysiological approach to brain hemisphere functions in schizophrenia

The present paper proposes a new psychophysiological approach to the genesis of positive and negative schizophrenic symptoms. According to this approach, the initial factor in schizophrenic disorders is a functional insufficiency of the right hemisphere which can be determined by early emotional experience in combination with subtle brain damage. This functional insufficiency causes (a) the inability to grasp and select information before its realization; and (b) the inability to produce a polysemantic context which is crucial for creativity, psychological defense, and the restoration of search activity, all of which determine psychophysiological adaptation to the environment. Right hemisphere insufficiency causes left hemisphere hyperactivity as an ineffective attempt to compensate for this functional deficiency. As a result, normal search activity is replaced by artificial search activity which is represented by “positive” symptoms, and which uses the predisposition of the left hemisphere's catecholamine system for its increased activity. The suggestion is made that cognitive impairment in schizophrenia (the inability to use appropriate previous information in relation to current perceptual input) is related to the competition between information processing which requires left hemisphere activity, and the formation of positive symptoms, also based on left hemisphere activity.     

Disinhibition of somatosensory evoked potential recovery in alcoholics

The pathogenesis of cognitive impairment in alcoholics remains unclear. Previous studies suggested that diffuse white matter atrophy is associated with cognitive impairment in alcoholics. To elucidate this issue, the present study evaluated alcoholics with cognitive impairment using the somatosensory evoked potential (SEP) recovery method, which is suitable for detecting subtle dysfunction at the cortical level. Subjects comprised 12 alcoholics with mild cognitive impairment [Mild group: Mini Mental State Examination Score (MMSE), ≥24; mean, 27.9 ± 1.6], 12 alcoholics with moderate to severe cognitive impairment (Moderate group: MMSE score, < 24; mean, 21.0 ± 2.5) and 12 normal subjects (Control group). SEP was recorded from the hand sensory area contralateral to the median nerve stimulated at the wrist. Single-pulse or paired-pulse stimuli at various interstimulus intervals (10–300 ms) were administered. Recovery functions of N9 (a peripheral nerve component), N20, N20-P25 and P25-N33 (cortical components) were studied. N20 recovery curves of both alcoholic groups were less suppressive than those of Controls, and P25-N33 recovery curves of the Moderate group were more excitatory than those of the Mild or Control groups. A disinhibited recovery pattern of N20 indicates subcortical dysfunction, and a disinhibited pattern of P25-N33 would be induced by cortical dysfunction. Therefore, subcortical dysfunction indicated by an abnormal N20 recovery pattern may contribute to the early cognitive impairment of alcoholics, whilst the cortical dysfunction indicated by an abnormal P25-N33 recovery pattern may contribute to the later cognitive impairment of alcoholics.     

图片学习测验在识别老年人轻微认知功能损害中的作用

目的　分析图片学习测验在识别老年人轻微认知功能损害 (MCI)中的作用。方法　选择符合MCI诊断标准的老年人 4 8例与正常对照组 5 6名完成图片学习测验、简易智能状态检查、听觉词语学习测验及多种非记忆测验。结果　图片学习测验的 3个记忆指标 (图片短时记忆、延迟记忆和学习记忆 )在MCI与正常对照组之间有非常显著的差异。已经给出这三个图片记忆指标区分MCI与正常老年人的划界分、敏感性和特异性。结论　图片记忆操作简便、信度和效度好 ,可以作为临床医师筛选MCI的有效工具     

Neuropsychological changes during steady-state drug use,withdrawal and abstinence in primary benzodiazepine-dependent patients

Impairment on neuropsychological tests during steady-state drug use and withdrawal, and after discontinuation of benzodiazepines, was studied in primary benzodiazepine-dependent patients. One group of patients was tested before and the other group after the initiation of a gradual tapering-off of the drug, and both groups were tested approximately 1 year later. At the initial assessment, both groups of patients showed impairment on most of the tests of general intelligence and on several of the tests in the Halstead-Reitan battery, as well as on a test of nonverbal memory, in comparison with healthy controls. At follow-up the patient groups had reached the level of the control group. This study confirmed earlier observations of neuropsychological deficits in long-term benzodiazepine-using patients and demonstrated that these changes are at least partly reversible by discontinuing drug intake.